Section 2 Medical Aspects

*Neurological and Mental Disorders*

[82] Treasure J, Schmidt U. The cognitive-interpersonal maintenance model of anorexia nervosa revisited: A summary of the evidence for cognitive, socio-emotional and interpersonal predisposing and perpetuating factors. Journal of Eating Disorders. 2013;**1**:13

[83] Hudson JI, Hiripi E, Pope HG, Kessler RC. The prevalence and correlates of eating disorders in the national comorbidity survey replication. Biological Psychiatry.

[84] Bahji A, Mazhar MN, Hudson CC, Nadkarni P, MacNeil BA, Hawken E. Prevalence of substance use disorder comorbidity among individuals with eating disorders: A systematic review and meta-analysis. Psychiatry Reaserch.

2007;**61**(3):348-358

2019;**273**:58-66

**62**

**65**

curcumin, vitamin D3, donepezil

cognition and learning [1, 2].

**1. Introduction**

**Chapter 5**

**Abstract**

Neuroprotective Effects of

Scopolamine-Induced

Alzheimer's Disease

*Saima Khan and Kaneez Fatima Shad*

Curcumin and Vitamin D3 on

Learning-Impaired Rat Model of

The purpose of this study was to find out the beneficial effects of curcumin and vitamin D3 in rats treated with scopolamine as to generate animal model of tauopathies, i.e., neurodegenerative disorders, including Alzheimer's disease (AD). Abnormal phosphorylation of tau results in the transformation of normal adult tau into pairedhelical-filament (PHF) tau and neurofibrillary tangles (NFTs). Our results indicated that scopolamine-treated rats exhibit increased levels of hyperphosphorylated tau protein along with PHF, and curcumin and vitamin D3 lowered the levels of PHF better than donepezil. The effect of abnormal hyperphosphorylation of tau was also detected in the hematoxylin and eosin staining of brain tissues as well as in the western blot analyses in our experimental rat models of AD. This abnormal level of hyperphosphorylated tau probably causes cognitive and memory deficit as observed in different behavioral tests on exploratory groups. Hyperphosphorylated tau may have disrupted the microtubule network in experimental rats. Signs of temporal region dementia noted during behavioral studies may be linked to the neurodegeneration and abnormal hyperphosphorylation of tau observed in our experimental animal model of AD. The curcumin and vitamin D3-treated group presented lower levels of hyperphosphorylated tau and a better behavioral response. Thus, inhibition of abnormal hyperphosphorylation of tau offers a promising therapeutic target for AD and related tauopathies.

**Keywords:** Alzheimer's disease, memory impairment, inflammation, scopolamine,

Alzheimer's disease (AD) is a neurodegenerative disorder, which present mainly in the elderly patients. It is characterized by progressive loss of cognitive functions, amyloid β (Aβ) deposition, and formation of paired-helical-filament (PHF) tau and neurofibrillary tangles (NFTs) in the brain cells. NFTs are formed inside the cell bodies of the neurons. These NFTs cause shrinkage of neurons and resultant loss of

#### **Chapter 5**

## Neuroprotective Effects of Curcumin and Vitamin D3 on Scopolamine-Induced Learning-Impaired Rat Model of Alzheimer's Disease

*Saima Khan and Kaneez Fatima Shad*

### **Abstract**

The purpose of this study was to find out the beneficial effects of curcumin and vitamin D3 in rats treated with scopolamine as to generate animal model of tauopathies, i.e., neurodegenerative disorders, including Alzheimer's disease (AD). Abnormal phosphorylation of tau results in the transformation of normal adult tau into pairedhelical-filament (PHF) tau and neurofibrillary tangles (NFTs). Our results indicated that scopolamine-treated rats exhibit increased levels of hyperphosphorylated tau protein along with PHF, and curcumin and vitamin D3 lowered the levels of PHF better than donepezil. The effect of abnormal hyperphosphorylation of tau was also detected in the hematoxylin and eosin staining of brain tissues as well as in the western blot analyses in our experimental rat models of AD. This abnormal level of hyperphosphorylated tau probably causes cognitive and memory deficit as observed in different behavioral tests on exploratory groups. Hyperphosphorylated tau may have disrupted the microtubule network in experimental rats. Signs of temporal region dementia noted during behavioral studies may be linked to the neurodegeneration and abnormal hyperphosphorylation of tau observed in our experimental animal model of AD. The curcumin and vitamin D3-treated group presented lower levels of hyperphosphorylated tau and a better behavioral response. Thus, inhibition of abnormal hyperphosphorylation of tau offers a promising therapeutic target for AD and related tauopathies.

**Keywords:** Alzheimer's disease, memory impairment, inflammation, scopolamine, curcumin, vitamin D3, donepezil

#### **1. Introduction**

Alzheimer's disease (AD) is a neurodegenerative disorder, which present mainly in the elderly patients. It is characterized by progressive loss of cognitive functions, amyloid β (Aβ) deposition, and formation of paired-helical-filament (PHF) tau and neurofibrillary tangles (NFTs) in the brain cells. NFTs are formed inside the cell bodies of the neurons. These NFTs cause shrinkage of neurons and resultant loss of cognition and learning [1, 2].

Tau protein is a highly soluble microtubule-associated protein found abundantly in the neuronal cells of the central nervous system (CNS). Tau proteins are the product of alternative splicing from a single gene, designated for microtubule-associated protein tau (MAPT) in humans, located on chromosome 17. There are six isoforms of tau found in the human brain. They can be distinguished by their binding domains. Tau has 79 potential phosphorylation sites on the longest isoform [3]. Tau is the major microtubule-associated protein of a mature neuron. The other two neuronal MAPs are MAP1 and MAP2, which are involved in tubulin interaction and promotion of its assembly into microtubules and stabilization of the microtubule network [4].

Normal adult human brain contains 2–3 moles of phosphorylated tau protein. Hyperphosphorylation of tau decreases its normal function. In Alzheimer's disease, brain tau is approximately three- to fourfold more hyperphosphorylated than the normal adult brain. This hyperphosphorylated state polymerized into paired-helical-filament tau and when mixed with straight filaments (SF) formed neurofibrillary tangles (NFT). The hyperphosphorylated tau in AD brain has the ability to sequester normal tau, MAP1, and MAP2, to disrupt microtubules, and to self-assemble into PHF/SF. Abnormal hyperphosphorylated tau, in the cytosol, does not polymerized into PHF [5]. The cytosolic hyperphosphorylated tau is involved in tubulin assembly but inhibiting its normal assembly and disrupting microtubule [6]. In addition, with hyperphosphorylation of tau, conformational changes and abnormal cleavage of tau may contribute to the pathogenesis of AD [7, 8]. Tau hyperphosphorylation has been reported in AD and other tauopathies; thus, the inhibition of abnormal hyperphosphorylation of tau offers a promising therapeutic target for AD and related tauopathies [9].

Similarly, oxidative stress is also strongly linked to neuronal dysfunction and neuronal cell death [10]. It is suggested that oxidative stress plays a significant role in the pathological conditions of AD by enhancing Aβ deposition, tau phosphorylation, and loss of synapses and neurons [11].

Reactive oxygen species (ROS) are by-products of biochemical and physiological processes in the body and can cause oxidative damage to macromolecules in an uncontrolled manner that may lead to many chronic diseases. Thus, overproduction of ROS is a hallmark of neurodegenerative disorders and other diseases [12, 13].

Neuroinflammation also causes neurodegeneration in the vulnerable regions of the brain such as the hippocampus. Microglia and astrocytes play important roles in neuroinflammation and contribute to neurological disorders [14, 15].

Previous studies showed that curcumin acts as an antioxidant by activating macrophages to remove ROS-like, superoxide anions, H2O2, and nitrite radicals. Its anti-inflammatory properties were tested in vivo and in vitro on animals in acute and chronic inflammatory conditions [16]. Moreover, vitamin D also reported to play a part in the cerebral processes of detoxification by interacting with reactive oxygen and nitrogen species in the rat brain and by regulating the activity of glutamyl transpeptidase [17, 18], which is a key enzyme in the metabolism of glutathione. Vitamin D3 is the active form of vitamin D. This study investigated the effects of curcumin and vitamin D3 on memory and learning, by assessing the behavioral responses of scopolamine-induced learning-impaired rats through assays involving the locomotive and maze activities and histological and protein analysis in the rat brain tissues. The findings of this study show that inducing learning impairment in rats by using scopolamine followed by treatment with curcumin and vitamin D3 results in neuroprotection and attenuation of cognitive deficits as shown by reduced brain tissue damage in histoanalysis, decreased accumulation of abnormal proteins with immunoblot analysis and increased in the numbers of correct responses to behavioral stimuli during locomotive and maze tests.

**67**

disease patients [36].

*Neuroprotective Effects of Curcumin and Vitamin D3 on Scopolamine-Induced Learning…*

Aging is the primary risk factor for AD development. Aged population is prone to oxidative stress that results in the degeneration of their brains [19, 20]. Diets containing saturated fat and less intake of vitamin E and C are linked with the risk of AD [20]. AD patients suffer from memory impairment along with other cognitive deficits such as language, visuospatial skills, insight, and apraxia. Most patients may suffer from other symptoms such as depression, hallucination, apathy, and delusions at later stages of AD [21]. Numerous studies have indicated that accumulation of amyloid beta proteins (A*β*) and phosphorylated tau (p-tau) are the key pathological hallmarks of AD [22]. Similarly, oxidative stress changes ionic homeostasis and other biochemical parameters, which ultimately causes neuronal dysfunction and cell death leading to progressive dementia associated with extensive Aβ and tau pathology [23]. Tau is a neuronal microtubule-associated protein that is responsible for maintaining the microtubule dynamics and its function of transportation by axons and neurite outgrowth [24]. Animal models have demonstrated that loss of synaptic plasticity is one of the key components in the neurodegenerative process of AD, and tau is one of the contributing factors for neurodegeneration [25]. Literature indicated that the oxidative stress plays a significant role in the pathology of AD by enhancing Aβ deposition, tau phos-

Vitamin D is a group of fat-soluble secosteroids that helps to absorb calcium, magnesium, phosphate, iron, and zinc. Vitamin D protects the brain from the degenerative processes of AD by binding itself with vitamin D receptors [27]. Vitamin D deficiency has been associated with neurological and psychiatric disorders. Previous studies revealed that it controls Ca2+ homeostasis in the hippocampus by regulating intracellular Ca2+. It also controls neurotrophic agents and protects the brain from Aβ-42 accumulation by stimulating phagocytosis. It also protects acetylcholine deficiency by increasing the activity of choline acetyltransferase in the brain. Due to its multiple biological targets, vitamin D can be used as an aide with the standard anti-dementia treatment. Among vitamin Ds, the most important compound is vitamin D3, also known as cholecalciferol. Increasing evidence highlights the impact of vitamin D deficiency as an important factor in various central or peripheral neurological diseases, especially multiple sclerosis and other neurodegenerative diseases, such as amyotrophic lateral sclerosis, Parkinson's disease, and

Curcumin (*Curcuma longa* (Haldi)) was used as a treatment in the animal models of AD. It was observed that curcumin reduced the formation of NFTs, Aβ deposition, and Aβ oligomerization. Curcumin can cross the blood–brain barrier because of its lipophilic nature. It can also inhibit acetylcholinesterase (AChE) activities [29] and can bind with the plaques leading to the alleviation of behavioral impairment [30–31]. Curcumin also acts as an antioxidant by activating macrophages to remove

Donepezil is available with the trade name "Aricept" developed by Eisai Inc. in 1983. It is a reversible AChE inhibitor, used for the treatment of mild to moderate dementia in AD patients. It has a long plasma half-life of 70 h. It is a noncompetitive reversible inhibitor of AChE that improves the function of cholinergic transmission. It increases the concentration of acetylcholine by preventing its hydrolysis. Animal studies have shown its selectivity for brain tissues and inhibition of AChE activities in smooth, striated, cardiac muscles. It can also inhibit AChE in red blood cells similar to its effect at synapses in CNS. AChE inhibition in red blood cells has been used as an indicator of the clinical effectiveness of donepezil in Alzheimer's

ROS-like radicals, superoxide anions, H2O2, and nitrite radicals [32–35].

*DOI: http://dx.doi.org/10.5772/intechopen.92407*

phorylation, and loss of synapses and neurons [26].

**2. Literature review**

Alzheimer's disease [28].

*Neuroprotective Effects of Curcumin and Vitamin D3 on Scopolamine-Induced Learning… DOI: http://dx.doi.org/10.5772/intechopen.92407*

#### **2. Literature review**

*Neurological and Mental Disorders*

target for AD and related tauopathies [9].

tion, and loss of synapses and neurons [11].

Tau protein is a highly soluble microtubule-associated protein found abundantly in the neuronal cells of the central nervous system (CNS). Tau proteins are the product of alternative splicing from a single gene, designated for microtubule-associated protein tau (MAPT) in humans, located on chromosome 17. There are six isoforms of tau found in the human brain. They can be distinguished by their binding domains. Tau has 79 potential phosphorylation sites on the longest isoform [3]. Tau is the major microtubule-associated protein of a mature neuron. The other two neuronal MAPs are MAP1 and MAP2, which are involved in tubulin interaction and promotion of its assembly into microtubules and stabilization of the microtubule network [4].

Normal adult human brain contains 2–3 moles of phosphorylated tau protein. Hyperphosphorylation of tau decreases its normal function. In Alzheimer's disease, brain tau is approximately three- to fourfold more hyperphosphorylated than the normal adult brain. This hyperphosphorylated state polymerized into paired-helical-filament tau and when mixed with straight filaments (SF) formed neurofibrillary tangles (NFT). The hyperphosphorylated tau in AD brain has the ability to sequester normal tau, MAP1, and MAP2, to disrupt microtubules, and to self-assemble into PHF/SF. Abnormal hyperphosphorylated tau, in the cytosol, does not polymerized into PHF [5]. The cytosolic hyperphosphorylated tau is involved in tubulin assembly but inhibiting its normal assembly and disrupting microtubule [6]. In addition, with hyperphosphorylation of tau, conformational changes and abnormal cleavage of tau may contribute to the pathogenesis of AD [7, 8]. Tau hyperphosphorylation has been reported in AD and other tauopathies; thus, the inhibition of abnormal hyperphosphorylation of tau offers a promising therapeutic

Similarly, oxidative stress is also strongly linked to neuronal dysfunction and neuronal cell death [10]. It is suggested that oxidative stress plays a significant role in the pathological conditions of AD by enhancing Aβ deposition, tau phosphoryla-

Reactive oxygen species (ROS) are by-products of biochemical and physiological processes in the body and can cause oxidative damage to macromolecules in an uncontrolled manner that may lead to many chronic diseases. Thus, overproduction of ROS is a hallmark of neurodegenerative disorders and other diseases [12, 13]. Neuroinflammation also causes neurodegeneration in the vulnerable regions of the brain such as the hippocampus. Microglia and astrocytes play important roles in

Previous studies showed that curcumin acts as an antioxidant by activating macrophages to remove ROS-like, superoxide anions, H2O2, and nitrite radicals. Its anti-inflammatory properties were tested in vivo and in vitro on animals in acute and chronic inflammatory conditions [16]. Moreover, vitamin D also reported to play a part in the cerebral processes of detoxification by interacting with reactive oxygen and nitrogen species in the rat brain and by regulating the activity of glutamyl transpeptidase [17, 18], which is a key enzyme in the metabolism of glutathione. Vitamin D3 is the active form of vitamin D. This study investigated the effects of curcumin and vitamin D3 on memory and learning, by assessing the behavioral responses of scopolamine-induced learning-impaired rats through assays involving the locomotive and maze activities and histological and protein analysis in the rat brain tissues. The findings of this study show that inducing learning impairment in rats by using scopolamine followed by treatment with curcumin and vitamin D3 results in neuroprotection and attenuation of cognitive deficits as shown by reduced brain tissue damage in histoanalysis, decreased accumulation of abnormal proteins with immunoblot analysis and increased in the numbers of correct responses to behavioral stimuli during

neuroinflammation and contribute to neurological disorders [14, 15].

**66**

locomotive and maze tests.

Aging is the primary risk factor for AD development. Aged population is prone to oxidative stress that results in the degeneration of their brains [19, 20]. Diets containing saturated fat and less intake of vitamin E and C are linked with the risk of AD [20]. AD patients suffer from memory impairment along with other cognitive deficits such as language, visuospatial skills, insight, and apraxia. Most patients may suffer from other symptoms such as depression, hallucination, apathy, and delusions at later stages of AD [21]. Numerous studies have indicated that accumulation of amyloid beta proteins (A*β*) and phosphorylated tau (p-tau) are the key pathological hallmarks of AD [22]. Similarly, oxidative stress changes ionic homeostasis and other biochemical parameters, which ultimately causes neuronal dysfunction and cell death leading to progressive dementia associated with extensive Aβ and tau pathology [23]. Tau is a neuronal microtubule-associated protein that is responsible for maintaining the microtubule dynamics and its function of transportation by axons and neurite outgrowth [24]. Animal models have demonstrated that loss of synaptic plasticity is one of the key components in the neurodegenerative process of AD, and tau is one of the contributing factors for neurodegeneration [25]. Literature indicated that the oxidative stress plays a significant role in the pathology of AD by enhancing Aβ deposition, tau phosphorylation, and loss of synapses and neurons [26].

Vitamin D is a group of fat-soluble secosteroids that helps to absorb calcium, magnesium, phosphate, iron, and zinc. Vitamin D protects the brain from the degenerative processes of AD by binding itself with vitamin D receptors [27]. Vitamin D deficiency has been associated with neurological and psychiatric disorders. Previous studies revealed that it controls Ca2+ homeostasis in the hippocampus by regulating intracellular Ca2+. It also controls neurotrophic agents and protects the brain from Aβ-42 accumulation by stimulating phagocytosis. It also protects acetylcholine deficiency by increasing the activity of choline acetyltransferase in the brain. Due to its multiple biological targets, vitamin D can be used as an aide with the standard anti-dementia treatment. Among vitamin Ds, the most important compound is vitamin D3, also known as cholecalciferol. Increasing evidence highlights the impact of vitamin D deficiency as an important factor in various central or peripheral neurological diseases, especially multiple sclerosis and other neurodegenerative diseases, such as amyotrophic lateral sclerosis, Parkinson's disease, and Alzheimer's disease [28].

Curcumin (*Curcuma longa* (Haldi)) was used as a treatment in the animal models of AD. It was observed that curcumin reduced the formation of NFTs, Aβ deposition, and Aβ oligomerization. Curcumin can cross the blood–brain barrier because of its lipophilic nature. It can also inhibit acetylcholinesterase (AChE) activities [29] and can bind with the plaques leading to the alleviation of behavioral impairment [30–31]. Curcumin also acts as an antioxidant by activating macrophages to remove ROS-like radicals, superoxide anions, H2O2, and nitrite radicals [32–35].

Donepezil is available with the trade name "Aricept" developed by Eisai Inc. in 1983. It is a reversible AChE inhibitor, used for the treatment of mild to moderate dementia in AD patients. It has a long plasma half-life of 70 h. It is a noncompetitive reversible inhibitor of AChE that improves the function of cholinergic transmission. It increases the concentration of acetylcholine by preventing its hydrolysis. Animal studies have shown its selectivity for brain tissues and inhibition of AChE activities in smooth, striated, cardiac muscles. It can also inhibit AChE in red blood cells similar to its effect at synapses in CNS. AChE inhibition in red blood cells has been used as an indicator of the clinical effectiveness of donepezil in Alzheimer's disease patients [36].

Scopolamine is a tropane alkaloid that acts as a muscarinic receptor antagonist. Scopolamine is used to study memory and cognition in animal model of AD. Studies have shown that scopolamine provides a suitable pharmacological model of memory defect. Scopolamine administration characterizes cognitive deficits resulting in the impairment of verbal learning, spatial learning, and reaction time [37]. Scopolamine can also have an influence on other neurotransmitter systems due to the functional interaction of cholinergic neurons with other neurotransmitter systems [38]. Cholinergic transmission is blocked, resulting in cognitive impairment in a rat model of AD [39]. Histological studies of the brain of Alzheimer's patients have revealed the presence of activated microglia and reactive astrocytes around the Aβ plaques. The chronic activation of microglia secretes cytokines and some reactive substances that exacerbate Aβ pathology; thus, neuroglia plays an important part in the pathogenesis of AD [40]. Curcumin has a lipophilic property that is capable of passing through all cell membranes and thus exerts its intracellular effects. Curcumin has antiproliferative actions on microglia. A minimal dose of curcumin affects the neuroglial proliferation and differentiation. The overall effect of curcumin on neuroglial cells involves decreased astrocytes proliferation, improved myelogenesis, and increased activity and differentiation of oligodendrocytes [40].

#### **3. Aims and objectives of this study**

This study was conducted with the following objectives:


#### **4. Material and methods**

#### **4.1 Animals**

Male Sprague Dawley rats of 200 ± 25 g were obtained from the animal house (PAPRSB Institute of Health Sciences Animal Facility, University Brunei Darussalam). Thirty animals were divided into five groups of six animals per group and reared under a standard laboratory condition with free access to food and water. Rats were acclimatized in a laboratory condition for a minimum of 1 week before undergoing behavioral test. The food was restricted under a daily feeding regime to maintain the weight of the rats.

All experiments were performed during daylight for 27 days, and all groups except group I (saline control) received daily scopolamine injection (2.5 mg/kg) to induce excitotoxicity. Curcumin, vitamin D3, and donepezil were administered to rats orally (**Table 1**). All experiments were conducted in accordance with institutional ethics guidelines for animal care and use (**Table 2**).

**69**

**Figure 1.**

*Rectangular maze test.*

*Neuroprotective Effects of Curcumin and Vitamin D3 on Scopolamine-Induced Learning…*

Group 3 Scopolamine (2.5 mg/kg) injection and curcumin (80 mg/kg) oral Group 4 Scopolamine (2.5 mg/kg) injection and donepezil (2.5 mg/kg) oral Group 5 Scopolamine (2.5 mg/kg) injection and vitamin D3 (0.0179 mg/kg) oral

**Control Scopolamine Curcumin Vitamin D3 Donepezil**

Mean 17.42607 176.1054 27.29171 33.8713571 34.12914 SEM 1.261983 71.34413 14.49811 11.5630538 12.12356

*Data expressed as mean ± standard error of the mean (SEM), expressed as the mean of time taken by different* 

This test was used to investigate learning and memory. The maze consisted of a rectangular box with an entry and a reward chamber with food, which were placed at the opposite ends of the box (**Figure 1**). All groups were given training in rectangular maze 1 week before drug administration. Each animal was placed in the same spot, recording the time taken by the animal to reach the reward chamber (transfer latency). Five readings were taken for each animal, and the average was calculated

*DOI: http://dx.doi.org/10.5772/intechopen.92407*

**Group Treatment**

Group 1 Saline control (0.9% saline) Group 2 Scopolamine (2.5 mg/kg) injection

*List of treatments received by each of the five groups of rats.*

*groups to reach the reward chamber each alternate day for 27 days.*

**4.2 Experimental design**

*4.2.1 Behavioral tests*

**Table 1.**

**Table 2.**

*4.2.1.1 Rectangular maze*

as their learning score [41–43].

*Neuroprotective Effects of Curcumin and Vitamin D3 on Scopolamine-Induced Learning… DOI: http://dx.doi.org/10.5772/intechopen.92407*


#### **Table 1.**

*Neurological and Mental Disorders*

cytes [40].

**3. Aims and objectives of this study**

**4. Material and methods**

regime to maintain the weight of the rats.

tional ethics guidelines for animal care and use (**Table 2**).

**4.1 Animals**

This study was conducted with the following objectives:

rats with and without curcumin or vitamin D3 or donepezil.

1.To determine the effects of curcumin, vitamin D3, and donepezil on behavioral responses of scopolamine-induced memory and learning-impaired rats.

2.To examine the structure of brain tissues obtained from scopolamine-treated

3.To investigate the concentration of hyperphosphorylated tau protein in scopolamine-treated rat brain tissues with donepezil, curcumin, or vitamin D3.

Male Sprague Dawley rats of 200 ± 25 g were obtained from the animal house (PAPRSB Institute of Health Sciences Animal Facility, University Brunei Darussalam). Thirty animals were divided into five groups of six animals per group and reared under a standard laboratory condition with free access to food and water. Rats were acclimatized in a laboratory condition for a minimum of 1 week before undergoing behavioral test. The food was restricted under a daily feeding

All experiments were performed during daylight for 27 days, and all groups except group I (saline control) received daily scopolamine injection (2.5 mg/kg) to induce excitotoxicity. Curcumin, vitamin D3, and donepezil were administered to rats orally (**Table 1**). All experiments were conducted in accordance with institu-

Scopolamine is a tropane alkaloid that acts as a muscarinic receptor antagonist.

Scopolamine is used to study memory and cognition in animal model of AD. Studies have shown that scopolamine provides a suitable pharmacological model of memory defect. Scopolamine administration characterizes cognitive deficits resulting in the impairment of verbal learning, spatial learning, and reaction time [37]. Scopolamine can also have an influence on other neurotransmitter systems due to the functional interaction of cholinergic neurons with other neurotransmitter systems [38]. Cholinergic transmission is blocked, resulting in cognitive impairment in a rat model of AD [39]. Histological studies of the brain of Alzheimer's patients have revealed the presence of activated microglia and reactive astrocytes around the Aβ plaques. The chronic activation of microglia secretes cytokines and some reactive substances that exacerbate Aβ pathology; thus, neuroglia plays an important part in the pathogenesis of AD [40]. Curcumin has a lipophilic property that is capable of passing through all cell membranes and thus exerts its intracellular effects. Curcumin has antiproliferative actions on microglia. A minimal dose of curcumin affects the neuroglial proliferation and differentiation. The overall effect of curcumin on neuroglial cells involves decreased astrocytes proliferation, improved myelogenesis, and increased activity and differentiation of oligodendro-

**68**

*List of treatments received by each of the five groups of rats.*


#### **Table 2.**

*Data expressed as mean ± standard error of the mean (SEM), expressed as the mean of time taken by different groups to reach the reward chamber each alternate day for 27 days.*

#### **4.2 Experimental design**

#### *4.2.1 Behavioral tests*

#### *4.2.1.1 Rectangular maze*

This test was used to investigate learning and memory. The maze consisted of a rectangular box with an entry and a reward chamber with food, which were placed at the opposite ends of the box (**Figure 1**). All groups were given training in rectangular maze 1 week before drug administration. Each animal was placed in the same spot, recording the time taken by the animal to reach the reward chamber (transfer latency). Five readings were taken for each animal, and the average was calculated as their learning score [41–43].

**Figure 1.** *Rectangular maze test.*

#### *4.2.1.2 Locomotor activity*

Actophotometer was used to measure the locomotor activity (**Figure 2**). Each animal was treated with their respective compound, was placed in actophotometer, and was given 2 min in activity cage. When the beam of light falling on photocell was cut off due to the movement of the animal, an activity count was recorded. The increase or decrease in locomotor activity was then calculated [42, 43].

#### *4.2.2 Histology*

After the behavioral study was conducted, the animals were anesthetized, and their brains were removed and stored in 4% paraformaldehyde (**Figure 3**). The brains were embedded in paraffin and kept in the refrigerator. Paraffin sections (5 μm) were prepared using rotary microtome (**Figure 4**) and stained with hematoxylin and eosin [44]. Photographs were taken for each section.

#### *4.2.3 Estimation of protein concentration*

#### *4.2.3.1 Immunoblotting*

Curcumin, donepezil, and vitamin D3 reduce tau phosphorylation in the brains of a scopolamine-treated rat model of Alzheimer's disease.

The brain tissues were dissected from the coronal area with clean tools and put on ice as quickly as possible to prevent protein degradation by proteases. The tissues

**71**

*Neuroprotective Effects of Curcumin and Vitamin D3 on Scopolamine-Induced Learning…*

were placed in microcentrifuge tubes and immersed in liquid nitrogen to snapfreeze. They were homogenized on ice after adding 1× ice-cold lysis buffer, rinsed twice with the same buffer, and agitated on a shaker for 2 h at 4°C. After centrifugation for 20 min at 12,000 rpm at 4°C, the supernatant was transferred into a fresh tube kept on ice discarding the pellet. A small volume of lysate was sampled to

After boiling each cell lysate in Tris-buffered saline, 0.1% Tween 20 (TBST) at 100°C for 5 min, 50 μg of protein was loaded into the wells of the sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) gel for immunoblot analysis. After gel running for 1–2 h at 100 V, the proteins were then transferred onto the membrane and blocked for 1 h at room temperature. The membrane was then incubated with 1:1000 dilution of primary antibody in blocking buffer followed by washing three times with TBST for 5 min each wash. The membrane was incubated with the 1:1000 dilution of conjugated secondary antibody in blocking buffer at room temperature for 1 h and washed three times with TBST at 5 min each wash. Excess reagents were removed, and the membrane was covered with transparent plastic wrap. The image was acquired using the darkroom development techniques

Data were expressed as mean ± standard error of the mean (SEM). The analysis

of variance (ANOVA, single factor) was used to measure transfer latency with

*DOI: http://dx.doi.org/10.5772/intechopen.92407*

**Figure 3.**

**Figure 4.**

*Freshly dissected rat brains.*

perform a protein quantification assay.

*Paraffin embedding for immunohistochemistry.*

for chemiluminescence detection.

statistical significance set at p < 0.05.

**4.3 Statistical analysis**

**Figure 2.** *Actophotometer for locomotor activity.*

*Neuroprotective Effects of Curcumin and Vitamin D3 on Scopolamine-Induced Learning… DOI: http://dx.doi.org/10.5772/intechopen.92407*

**Figure 3.** *Freshly dissected rat brains.*

*Neurological and Mental Disorders*

Actophotometer was used to measure the locomotor activity (**Figure 2**). Each animal was treated with their respective compound, was placed in actophotometer, and was given 2 min in activity cage. When the beam of light falling on photocell was cut off due to the movement of the animal, an activity count was recorded. The

After the behavioral study was conducted, the animals were anesthetized, and their brains were removed and stored in 4% paraformaldehyde (**Figure 3**). The brains were embedded in paraffin and kept in the refrigerator. Paraffin sections (5 μm) were prepared using rotary microtome (**Figure 4**) and stained with hema-

Curcumin, donepezil, and vitamin D3 reduce tau phosphorylation in the brains

The brain tissues were dissected from the coronal area with clean tools and put on ice as quickly as possible to prevent protein degradation by proteases. The tissues

increase or decrease in locomotor activity was then calculated [42, 43].

toxylin and eosin [44]. Photographs were taken for each section.

of a scopolamine-treated rat model of Alzheimer's disease.

*4.2.3 Estimation of protein concentration*

*4.2.3.1 Immunoblotting*

*4.2.1.2 Locomotor activity*

*4.2.2 Histology*

**70**

**Figure 2.**

*Actophotometer for locomotor activity.*

**Figure 4.** *Paraffin embedding for immunohistochemistry.*

were placed in microcentrifuge tubes and immersed in liquid nitrogen to snapfreeze. They were homogenized on ice after adding 1× ice-cold lysis buffer, rinsed twice with the same buffer, and agitated on a shaker for 2 h at 4°C. After centrifugation for 20 min at 12,000 rpm at 4°C, the supernatant was transferred into a fresh tube kept on ice discarding the pellet. A small volume of lysate was sampled to perform a protein quantification assay.

After boiling each cell lysate in Tris-buffered saline, 0.1% Tween 20 (TBST) at 100°C for 5 min, 50 μg of protein was loaded into the wells of the sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) gel for immunoblot analysis. After gel running for 1–2 h at 100 V, the proteins were then transferred onto the membrane and blocked for 1 h at room temperature. The membrane was then incubated with 1:1000 dilution of primary antibody in blocking buffer followed by washing three times with TBST for 5 min each wash. The membrane was incubated with the 1:1000 dilution of conjugated secondary antibody in blocking buffer at room temperature for 1 h and washed three times with TBST at 5 min each wash. Excess reagents were removed, and the membrane was covered with transparent plastic wrap. The image was acquired using the darkroom development techniques for chemiluminescence detection.

#### **4.3 Statistical analysis**

Data were expressed as mean ± standard error of the mean (SEM). The analysis of variance (ANOVA, single factor) was used to measure transfer latency with statistical significance set at p < 0.05.

### **5. Results**

#### **5.1 Rectangular maze test**

The effects of curcumin and vitamin D3 on scopolamine-induced rats were investigated using the rectangular maze test comparing the results obtained with that of donepezil, a widely accepted AD standard drug. Rats that were injected with scopolamine showed significantly higher transfer latency, indicating the longer time for rats to reach the food (nearly 200 s). Also, there was no sign of improvement during the successive days (**Figure 5**). Rats treated with curcumin and vitamin D3 displayed significant reduction in transfer latency, which means that treated rats did not take a longer time to reach the food, less than 50 s as shown in **Figure 6**. Furthermore, there was a slight reduction in the latency time from day to day. The effect of these two compounds was also comparable to that of donepezil.

#### **5.2 Locomotor activity**

Actophotometer was used to measure locomotor activity by counting total photocell counts per rat for 2 min. Rat injected with scopolamine showed progressive decline in their locomotor activity (**Figure 7**), and average values were shown in **Table 3** and **Figure 8**. Rats treated with curcumin and vitamin D3 showed an initial increase in locomotor activities then slightly declined after 7 days followed by leveling off in the succeeding days. In contrast, rats treated with curcumin and vitamin D3 showed high locomotor activity compared with the non-treated control rats treated with donepezil that exhibited similar response as those treated with curcumin and vitamin D3, suggesting that these two compounds had triggered alertness and excitatory activities in scopolamine-treated rats.

#### **5.3 Histology**

Non-treated rats injected with scopolamine revealed prominent degeneration of cells and decrease number of nuclei in their brain tissues as compared to those treated with curcumin and vitamin D3. Moreover, treatment with curcumin, vitamin D3, and donepezil showed similar cell morphology similar to the control group demonstrating brain cells that appeared normal (**Figure 9**).

**Figure 5.**

*Effect of curcumin, vitamin D3, and donepezil on latency time compared with the disease control group (mean, n = 6). The histogram shows the mean of latency time in seconds.*

**73**

**Figure 8.**

*Neuroprotective Effects of Curcumin and Vitamin D3 on Scopolamine-Induced Learning…*

*Time taken to reach the reward chamber in the rectangular maze. Y-axis represents time in second. Data* 

*Effect of curcumin, vitamin D3, and donepezil on latency time compared to scopolamine-treated group (mean,* 

Mean 12.88686 6.161643 9.911429 11.77929 12.0664286 SEM 3.712271 6.766518 2.502838 3.992999 3.23978538

*Locomotor activities of all rats except scopolamine-treated rats in actophotometer showed no significant difference. Data expressed as mean of photocell count (mean ± SEM, n = 6) of animals on each alternate day for 27 days.*

*Data expressed as mean ± SEM for the total number of photocell counts for each group.*

**Control Scopolamine Curcumin Vitamin D3 Donepezil**

*DOI: http://dx.doi.org/10.5772/intechopen.92407*

**Figure 6.**

**Figure 7.**

**Table 3.**

*n = 6). Graph shows mean latency time in seconds.*

*expressed as mean ± SEM.*

*Neuroprotective Effects of Curcumin and Vitamin D3 on Scopolamine-Induced Learning… DOI: http://dx.doi.org/10.5772/intechopen.92407*

#### **Figure 6.**

*Neurological and Mental Disorders*

**5.1 Rectangular maze test**

**5. Results**

of donepezil.

**5.3 Histology**

**5.2 Locomotor activity**

**72**

**Figure 5.**

*Effect of curcumin, vitamin D3, and donepezil on latency time compared with the disease control group (mean,* 

The effects of curcumin and vitamin D3 on scopolamine-induced rats were investigated using the rectangular maze test comparing the results obtained with that of donepezil, a widely accepted AD standard drug. Rats that were injected with scopolamine showed significantly higher transfer latency, indicating the longer time for rats to reach the food (nearly 200 s). Also, there was no sign of improvement during the successive days (**Figure 5**). Rats treated with curcumin and vitamin D3 displayed significant reduction in transfer latency, which means that treated rats did not take a longer time to reach the food, less than 50 s as shown in **Figure 6**. Furthermore, there was a slight reduction in the latency time from day to day. The effect of these two compounds was also comparable to that

Actophotometer was used to measure locomotor activity by counting total photocell counts per rat for 2 min. Rat injected with scopolamine showed progressive decline in their locomotor activity (**Figure 7**), and average values were shown in **Table 3** and **Figure 8**. Rats treated with curcumin and vitamin D3 showed an initial increase in locomotor activities then slightly declined after 7 days followed by leveling off in the succeeding days. In contrast, rats treated with curcumin and vitamin D3 showed high locomotor activity compared with the non-treated control rats treated with donepezil that exhibited similar response as those treated with curcumin and vitamin D3, suggesting that these two compounds had triggered

Non-treated rats injected with scopolamine revealed prominent degeneration of cells and decrease number of nuclei in their brain tissues as compared to those treated with curcumin and vitamin D3. Moreover, treatment with curcumin, vitamin D3, and donepezil showed similar cell morphology similar to the control group

alertness and excitatory activities in scopolamine-treated rats.

demonstrating brain cells that appeared normal (**Figure 9**).

*n = 6). The histogram shows the mean of latency time in seconds.*

*Time taken to reach the reward chamber in the rectangular maze. Y-axis represents time in second. Data expressed as mean ± SEM.*

#### **Figure 7.**

*Effect of curcumin, vitamin D3, and donepezil on latency time compared to scopolamine-treated group (mean, n = 6). Graph shows mean latency time in seconds.*


#### **Table 3.**

*Data expressed as mean ± SEM for the total number of photocell counts for each group.*

#### **Figure 8.**

*Locomotor activities of all rats except scopolamine-treated rats in actophotometer showed no significant difference. Data expressed as mean of photocell count (mean ± SEM, n = 6) of animals on each alternate day for 27 days.*

#### **Figure 9.**

*Hematoxylin and eosin staining of rat brain tissues: A, control; B, scopolamine-induced; C, curcumin-treated; D, vitamin D3-treated; and E, donepezil. The images show no significant difference in the cellular histology of the hippocampal area (cornu ammonis) (CA3) in the experimental groups (curcumin, vitamin D3, and donepezil) as compared with those of scopolamine group, which showed less number of nuclei stained as revealed by H and E staining. Arrows in scopolamine slide B indicated the gaps around the neuronal cells of coronal sections (5 μm) at magnification 40×.*

#### *5.3.1 Immunoblotting*

#### See **Figure 10**.

#### **Figure 10.**

*Western blot analyses of scopolamine-treated and other treatments (curcumin and vitamin D3 and donepezil) groups showing difference in the levels of hyperphosphorylated tau in a rat model of AD. (a) Immunoblot of hippocampus homogenates from treated rats (scopolamine, vehicle, treated with curcumin and vitamin D3) using the PHF monoclonal antibodies and (b) normalized with β actin.*

**75**

**6. Discussion**

**Figure 11.**

*groups.*

*Neuroprotective Effects of Curcumin and Vitamin D3 on Scopolamine-Induced Learning…*

**S/No. Area Percent** 13690.4 17.975 22076.4 28.986 16481.8 21.641 10,292 13.513 13,621 17.884

*Densitometry data were obtained using image J software, exhibiting relative density of protein from all groups.*

*Densitometry data were obtained using image J software. Representing relative density of Tau protein for all* 

**S/No. Area Percent** 4240.34 23.631 3502.99 19.522 1857.51 10.352 4913.31 27.381 3429.87 19.114

This study investigated the effects of curcumin and vitamin D3 on learning and memory and locomotion. The first part of the study involved subjecting the rats to several behavioral tests and examining their memory competencies and locomotor responses. Histological studies were also done on rats' brains to observe the changes that have occurred in the brain tissues after various treatments. The results obtained from rats treated with curcumin and vitamin D3 were compared with

*Densitometry data obtained from image J software, presented as relative density of tau protein present in all* 

*DOI: http://dx.doi.org/10.5772/intechopen.92407*

**Table 4.**

**Table 5.**

*groups.*

#### *5.3.2 Vitamin D3 + scopolamine*

See **Tables 4**, **5** and **Figure 11**.

*Neuroprotective Effects of Curcumin and Vitamin D3 on Scopolamine-Induced Learning… DOI: http://dx.doi.org/10.5772/intechopen.92407*


**Table 4.**

*Neurological and Mental Disorders*

**Figure 9.**

*coronal sections (5 μm) at magnification 40×.*

*5.3.2 Vitamin D3 + scopolamine*

See **Tables 4**, **5** and **Figure 11**.

*using the PHF monoclonal antibodies and (b) normalized with β actin.*

*5.3.1 Immunoblotting*

See **Figure 10**.

*Hematoxylin and eosin staining of rat brain tissues: A, control; B, scopolamine-induced; C, curcumin-treated; D, vitamin D3-treated; and E, donepezil. The images show no significant difference in the cellular histology of the hippocampal area (cornu ammonis) (CA3) in the experimental groups (curcumin, vitamin D3, and donepezil) as compared with those of scopolamine group, which showed less number of nuclei stained as revealed by H and E staining. Arrows in scopolamine slide B indicated the gaps around the neuronal cells of* 

*Western blot analyses of scopolamine-treated and other treatments (curcumin and vitamin D3 and donepezil) groups showing difference in the levels of hyperphosphorylated tau in a rat model of AD. (a) Immunoblot of hippocampus homogenates from treated rats (scopolamine, vehicle, treated with curcumin and vitamin D3)* 

**74**

**Figure 10.**

*Densitometry data were obtained using image J software, exhibiting relative density of protein from all groups.*


#### **Table 5.**

*Densitometry data were obtained using image J software. Representing relative density of Tau protein for all groups.*

**Figure 11.**

*Densitometry data obtained from image J software, presented as relative density of tau protein present in all groups.*

#### **6. Discussion**

This study investigated the effects of curcumin and vitamin D3 on learning and memory and locomotion. The first part of the study involved subjecting the rats to several behavioral tests and examining their memory competencies and locomotor responses. Histological studies were also done on rats' brains to observe the changes that have occurred in the brain tissues after various treatments. The results obtained from rats treated with curcumin and vitamin D3 were compared with

donepezil-treated rats. Scopolamine (muscarinic cholinergic antagonist) was used to induce memory impairment in rats [45]. Curcumin was selected as the previous research showed that curcumin could be used to recover learning and memory abilities in rats in AD and other inflammatory conditions [46]. Literature also reported that curcumin facilitates learning and memory functions by diminishing or preventing lipid peroxidation in the brains of aged rats [47]. In general, curcumin is a well-known oxygen free radical scavenger [46].

Vitamin D plays an important role in the regulation of numerous neurotransmitters including acetylcholine, dopamine, serotonin, and gamma aminobutyric acid. Several studies have also been reported that vitamin D deficiency is associated with neurological dysfunction and that supplementation of vitamin D may induce a protective effect against neurological disorders [48]. Based on the results of this study, the rats that were injected with scopolamine only revealed a gradual increase in the latency time until day 9, indicating a longer time required for rats to reach the end of the maze where food as a source of attractive stimuli was placed. After the ninth day, the latency time remained high and was three times higher than that of curcumin, vitamin D3, and donepezil. Rats treated with curcumin and vitamin D3 exhibits reduced latency time. A slight increase in time was observed between days 1 and 7 and gradually decreased up to day 27. The daily decrease in the latency time represented the effects of these two compounds on long-term memory. When comparing between curcumin and vitamin D3, rats treated with curcumin had slightly lower latency time than vitamin D3, suggesting that curcumin was comparatively more effective than vitamin D3 and donepezil in improving learning and memory among rats. Rats treated with donepezil initially showed low latency time, but remained constant until the 27 days. The similarity of latency time values obtained among curcumin, vitamin D3, donepezil, and the control suggested that curcumin and vitamin D3 have comparable effects like that of donepezil and may reverse the memory impairment induced by scopolamine.

The locomotor activity of rats was investigated by placing each rat in an actophotometer for 2 min and then assessing their movement as compared with those treated with curcumin and vitamin D3. Furthermore, the results indicated a decline in daily activities suggesting signs of slowing down. Vitamin D3 showed an increase in locomotor activity, which was comparable with those of donepezil and the controls confirming previous studies on the role of vitamin D in motor activities [49].

Curcumin exhibited slightly less action when compared to vitamin D3, donepezil treated, and control rats but was still exhibiting higher movements than scopolamine only. After 9 days, the locomotor activity for each treatment except scopolamine became relatively stable throughout 27 days and did not show any signs of slowing down, indicating that rats treated with vitamin D3 and curcumin exhibited signs of alertness that continued for a longer time.

The effects of each treatment were also histologically examined in rat brains. Sections of the brain tissue from the region of hippocampus were stained to investigate histological appearance before and after the treatment with selected compound. The cells in the brain tissue treated only with scopolamine exhibited less number of nuclei that appeared to be shrunken and smaller than with those of the control group. Treatment with curcumin and vitamin D3 showed no difference as compared with those of the brain tissue treated with donepezil and control group, suggesting that the brain tissues seemed to have recovered after the rats were treated with curcumin and vitamin D3. The difference in the levels of tau protein was also assessed using immunoblotting. In scopolamine-induced group, phosphorylated tau proteins were relatively higher than other groups indicating a state of proliferation in the brain tissues. Previous studies reported that accumulation of phosphorylated tau protein is one of the hallmarks of AD [50].

**77**

*Neuroprotective Effects of Curcumin and Vitamin D3 on Scopolamine-Induced Learning…*

the rat brains, confirming the earlier studies (**Figures 10** and **11**) [51, 52].

Western blot images were also assessed visually by making comparisons between bands in different lanes (**Figure 10**). Densitometry data obtained from image J software presented as relative density of tau protein found in all groups (**Tables 4** and **5**). After the rats were treated with curcumin and vitamin D3, the levels of tau proteins were reduced suggesting an attenuation of phosphorylated tau proteins in

We concluded that Alzheimer's disease is a progressive neurodegenerative disorder characterized by gradual memory loss and shrinkage of neuronal cells particularly in the hippocampus and basal forebrain regions. Curcumin and vitamin D3 have biomedical qualities that protect the brain from degeneration associated with AD. In this study, the behavioral tasks involving rectangular maze test and locomotor activity were used to determine if curcumin and vitamin D3 could improve learning and memory among rats subjected to scopolamine-induced impaired cognition. With cognitive impairment, the correct response rate of animals during acquisition and retention period was significantly lower than that of the control group. However, treatment with curcumin and vitamin D3 has increased their correct response rate for both tasks that became equal with those of the control group (p < 0.05). Tissue analysis by H and E staining of the rat brain from the scopolamine group showed less number of cells, which was improved upon the treatment with curcumin and vitamin D3, resulting in significantly increase in the number of cells with no gap around them. This was accompanied by reduced level of abnormal tau proteins detected via immunoblot analysis. Together, these findings demonstrate that curcumin and vitamin D3 have the potential to reverse some cognitive deficits, correct memory impairment, and protect the brain from degeneration.

The animal model of AD has shown improvement in learning and memory after exposure to curcumin and vitamin D3 treatment, which slowed down the progress of AD pathologies delaying the onset of AD. With potential as a treatment for AD in future, the active structure and the target of both curcumin and vitamin D3 can be further investigated to elucidate the molecular mechanism by which their beneficial effects can be enhanced for the improvement of AD patients. Vitamin D due to its multiple biological targets can be used as an adjunct to standard anti-dementia treatment in AD. Curcumin has intensively been studied for the improvement of AD symptoms, and existing investigations on inhalable curcumin and ar-turmerone

on neural stem cells (NSCs) are currently under clinical trials.

*DOI: http://dx.doi.org/10.5772/intechopen.92407*

**7. Conclusion**

*Neuroprotective Effects of Curcumin and Vitamin D3 on Scopolamine-Induced Learning… DOI: http://dx.doi.org/10.5772/intechopen.92407*

Western blot images were also assessed visually by making comparisons between bands in different lanes (**Figure 10**). Densitometry data obtained from image J software presented as relative density of tau protein found in all groups (**Tables 4** and **5**). After the rats were treated with curcumin and vitamin D3, the levels of tau proteins were reduced suggesting an attenuation of phosphorylated tau proteins in the rat brains, confirming the earlier studies (**Figures 10** and **11**) [51, 52].

#### **7. Conclusion**

*Neurological and Mental Disorders*

is a well-known oxygen free radical scavenger [46].

memory impairment induced by scopolamine.

exhibited signs of alertness that continued for a longer time.

donepezil-treated rats. Scopolamine (muscarinic cholinergic antagonist) was used to induce memory impairment in rats [45]. Curcumin was selected as the previous research showed that curcumin could be used to recover learning and memory abilities in rats in AD and other inflammatory conditions [46]. Literature also reported that curcumin facilitates learning and memory functions by diminishing or preventing lipid peroxidation in the brains of aged rats [47]. In general, curcumin

Vitamin D plays an important role in the regulation of numerous neurotransmitters including acetylcholine, dopamine, serotonin, and gamma aminobutyric acid. Several studies have also been reported that vitamin D deficiency is associated with neurological dysfunction and that supplementation of vitamin D may induce a protective effect against neurological disorders [48]. Based on the results of this study, the rats that were injected with scopolamine only revealed a gradual increase in the latency time until day 9, indicating a longer time required for rats to reach the end of the maze where food as a source of attractive stimuli was placed. After the ninth day, the latency time remained high and was three times higher than that of curcumin, vitamin D3, and donepezil. Rats treated with curcumin and vitamin D3 exhibits reduced latency time. A slight increase in time was observed between days 1 and 7 and gradually decreased up to day 27. The daily decrease in the latency time represented the effects of these two compounds on long-term memory. When comparing between curcumin and vitamin D3, rats treated with curcumin had slightly lower latency time than vitamin D3, suggesting that curcumin was comparatively more effective than vitamin D3 and donepezil in improving learning and memory among rats. Rats treated with donepezil initially showed low latency time, but remained constant until the 27 days. The similarity of latency time values obtained among curcumin, vitamin D3, donepezil, and the control suggested that curcumin and vitamin D3 have comparable effects like that of donepezil and may reverse the

The locomotor activity of rats was investigated by placing each rat in an actophotometer for 2 min and then assessing their movement as compared with those treated with curcumin and vitamin D3. Furthermore, the results indicated a decline in daily activities suggesting signs of slowing down. Vitamin D3 showed an increase in locomotor activity, which was comparable with those of donepezil and the controls confirming previous studies on the role of vitamin D in motor activities [49].

Curcumin exhibited slightly less action when compared to vitamin D3, donepezil treated, and control rats but was still exhibiting higher movements than scopolamine only. After 9 days, the locomotor activity for each treatment except scopolamine became relatively stable throughout 27 days and did not show any signs of slowing down, indicating that rats treated with vitamin D3 and curcumin

The effects of each treatment were also histologically examined in rat brains.

Sections of the brain tissue from the region of hippocampus were stained to investigate histological appearance before and after the treatment with selected compound. The cells in the brain tissue treated only with scopolamine exhibited less number of nuclei that appeared to be shrunken and smaller than with those of the control group. Treatment with curcumin and vitamin D3 showed no difference as compared with those of the brain tissue treated with donepezil and control group, suggesting that the brain tissues seemed to have recovered after the rats were treated with curcumin and vitamin D3. The difference in the levels of tau protein was also assessed using immunoblotting. In scopolamine-induced group, phosphorylated tau proteins were relatively higher than other groups indicating a state of proliferation in the brain tissues. Previous studies reported that accumulation of phosphorylated tau protein is one of the hallmarks of AD [50].

**76**

We concluded that Alzheimer's disease is a progressive neurodegenerative disorder characterized by gradual memory loss and shrinkage of neuronal cells particularly in the hippocampus and basal forebrain regions. Curcumin and vitamin D3 have biomedical qualities that protect the brain from degeneration associated with AD. In this study, the behavioral tasks involving rectangular maze test and locomotor activity were used to determine if curcumin and vitamin D3 could improve learning and memory among rats subjected to scopolamine-induced impaired cognition. With cognitive impairment, the correct response rate of animals during acquisition and retention period was significantly lower than that of the control group. However, treatment with curcumin and vitamin D3 has increased their correct response rate for both tasks that became equal with those of the control group (p < 0.05). Tissue analysis by H and E staining of the rat brain from the scopolamine group showed less number of cells, which was improved upon the treatment with curcumin and vitamin D3, resulting in significantly increase in the number of cells with no gap around them. This was accompanied by reduced level of abnormal tau proteins detected via immunoblot analysis. Together, these findings demonstrate that curcumin and vitamin D3 have the potential to reverse some cognitive deficits, correct memory impairment, and protect the brain from degeneration.

The animal model of AD has shown improvement in learning and memory after exposure to curcumin and vitamin D3 treatment, which slowed down the progress of AD pathologies delaying the onset of AD. With potential as a treatment for AD in future, the active structure and the target of both curcumin and vitamin D3 can be further investigated to elucidate the molecular mechanism by which their beneficial effects can be enhanced for the improvement of AD patients. Vitamin D due to its multiple biological targets can be used as an adjunct to standard anti-dementia treatment in AD. Curcumin has intensively been studied for the improvement of AD symptoms, and existing investigations on inhalable curcumin and ar-turmerone on neural stem cells (NSCs) are currently under clinical trials.

*Neurological and Mental Disorders*

### **Author details**

Saima Khan1 and Kaneez Fatima Shad<sup>2</sup> \*

1 Institute of Health Sciences Universiti Brunei Darussalam, Gadong, BE, Brunei Darussalam

2 University of Technology, Sydney, Australia

\*Address all correspondence to: ftmshad@gmail.com

© 2020 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

**79**

*Neuroprotective Effects of Curcumin and Vitamin D3 on Scopolamine-Induced Learning…*

[9] Alonso A, Zaidi T, Novak M, Grundke-Iqbal I, Iqbal K. Hyperphosphorylation induces self-

[10] Nunomura A, Castellani RJ, Zhu X, Moreira PI, Perry G,

Smith MA. Involvement of oxidative stress in Alzheimer disease. Journal of Neuropathology & Experimental Neurology. 2006;**65**(7):631-641

[11] Chen Z, Zhong C. Oxidative stress in Alzheimer's disease. Neuroscience

[12] Moreira PI, Smith MA, Zhu X, Nunomura A, Castellani RJ, Perry G. Oxidative stress and neurodegeneration. Annals of the New York Academy of Sciences. 2005;**1043**(1):545-552

Bulletin. 2014;**30**(2):271-281

[13] Folli F, Corradi D, Fanti P, Davalli A, Paez A, Giaccari A, et al. The role of oxidative stress in the pathogenesis of type 2 diabetes mellitus micro-and macrovascular complications: Avenues for a mechanistic-based therapeutic approach. Current Diabetes Reviews.

[14] Lee Mosley R, Benner EJ, Kadiu I, Thomas M, Boska MD, Hasan K, et al. Neuroinflammation, oxidative stress, and the pathogenesis of Parkinson's disease. Clinical Neuroscience Research.

[15] Rohl C, Armbrust E, Herbst E, Jess A, Gulden M, Maser E, et al.

Mechanisms involved in the modulation of astroglial resistance to oxidative stress induced by activated microglia: Antioxidative systems, peroxide elimination, radical generation, lipid

2011;**7**(5):313-324

2006;**6**(5):261-281

assembly of tau into tangles of paired helical filaments/straight filaments. Proceedings of the National Academy of Sciences of the United States of America. 2001;**98**(12):6923-6928

*DOI: http://dx.doi.org/10.5772/intechopen.92407*

Grundke-Iqbal I. Curr Alzheimer Res.

Molecular, Cellular and Medical Aspects.

[1] Iqbal K, Liu F, Gong C-X,

[2] Brady S, Siegel G, Albers RW, Price D. Basic Neurochemistry:

[3] Billingsley ML, Kincaid RL. Regulated phosphorylation and dephosphorylation of tau protein: Effects on microtubule interaction, intracellular trafficking, and

Journal. 1997;**323**(3):577-591

Iqbal K. Role of abnormally

1986;**2**:421-426

501-511

[4] Kopke E, Tung YC, Shaikh S, Alonso AC, Iqbal K, Grundke-Iqbal I. Microtubule-associated protein tau. Abnormal phosphorylation of a non-paired helical filament pool in Alzheimer disease. Journal of Biological Chemistry. 1993;**268**:24374-24384

neurodegeneration. The Biochemical

[5] Alonso AD, Zaidi T, Grundke-Iqbal I,

phosphorylated tau in the breakdown of microtubules in Alzheimer disease. Proceedings of the National Academy of Sciences of the United States of America. 1994;**91**:5562-5566

[6] Iqbal K, Grundke-Iqbal I, Zaidi T, Merz PA, Wen GY, Shaikh SS, et al. Defective brain microtubule assembly in Alzheimer's disease. Lancet.

[7] Li B, Chohan MO, Grundke-Iqbal I, Iqbal K. Disruption of microtubule network by Alzheimer abnormally hyperphosphorylated tau. Acta Neuropathology (Berl). 2007;**113**:

[8] Wang JZ, Gong CX, Zaidi T, Grundke-Iqbal I, Iqbal K. Dephosphorylation of Alzheimer paired helical filaments by protein phosphatase-2A and -2B. The Journal of Biological Chemistry. 1995;**270**:4854-4860

**References**

2010;**7**(8):656-664

Academic Press; 2005

*Neuroprotective Effects of Curcumin and Vitamin D3 on Scopolamine-Induced Learning… DOI: http://dx.doi.org/10.5772/intechopen.92407*

#### **References**

*Neurological and Mental Disorders*

**78**

**Author details**

Brunei Darussalam

and Kaneez Fatima Shad<sup>2</sup>

\*Address all correspondence to: ftmshad@gmail.com

2 University of Technology, Sydney, Australia

provided the original work is properly cited.

\*

© 2020 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

1 Institute of Health Sciences Universiti Brunei Darussalam, Gadong, BE,

Saima Khan1

[1] Iqbal K, Liu F, Gong C-X, Grundke-Iqbal I. Curr Alzheimer Res. 2010;**7**(8):656-664

[2] Brady S, Siegel G, Albers RW, Price D. Basic Neurochemistry: Molecular, Cellular and Medical Aspects. Academic Press; 2005

[3] Billingsley ML, Kincaid RL. Regulated phosphorylation and dephosphorylation of tau protein: Effects on microtubule interaction, intracellular trafficking, and neurodegeneration. The Biochemical Journal. 1997;**323**(3):577-591

[4] Kopke E, Tung YC, Shaikh S, Alonso AC, Iqbal K, Grundke-Iqbal I. Microtubule-associated protein tau. Abnormal phosphorylation of a non-paired helical filament pool in Alzheimer disease. Journal of Biological Chemistry. 1993;**268**:24374-24384

[5] Alonso AD, Zaidi T, Grundke-Iqbal I, Iqbal K. Role of abnormally phosphorylated tau in the breakdown of microtubules in Alzheimer disease. Proceedings of the National Academy of Sciences of the United States of America. 1994;**91**:5562-5566

[6] Iqbal K, Grundke-Iqbal I, Zaidi T, Merz PA, Wen GY, Shaikh SS, et al. Defective brain microtubule assembly in Alzheimer's disease. Lancet. 1986;**2**:421-426

[7] Li B, Chohan MO, Grundke-Iqbal I, Iqbal K. Disruption of microtubule network by Alzheimer abnormally hyperphosphorylated tau. Acta Neuropathology (Berl). 2007;**113**: 501-511

[8] Wang JZ, Gong CX, Zaidi T, Grundke-Iqbal I, Iqbal K. Dephosphorylation of Alzheimer paired helical filaments by protein phosphatase-2A and -2B. The Journal of Biological Chemistry. 1995;**270**:4854-4860

[9] Alonso A, Zaidi T, Novak M, Grundke-Iqbal I, Iqbal K. Hyperphosphorylation induces selfassembly of tau into tangles of paired helical filaments/straight filaments. Proceedings of the National Academy of Sciences of the United States of America. 2001;**98**(12):6923-6928

[10] Nunomura A, Castellani RJ, Zhu X, Moreira PI, Perry G, Smith MA. Involvement of oxidative stress in Alzheimer disease. Journal of Neuropathology & Experimental Neurology. 2006;**65**(7):631-641

[11] Chen Z, Zhong C. Oxidative stress in Alzheimer's disease. Neuroscience Bulletin. 2014;**30**(2):271-281

[12] Moreira PI, Smith MA, Zhu X, Nunomura A, Castellani RJ, Perry G. Oxidative stress and neurodegeneration. Annals of the New York Academy of Sciences. 2005;**1043**(1):545-552

[13] Folli F, Corradi D, Fanti P, Davalli A, Paez A, Giaccari A, et al. The role of oxidative stress in the pathogenesis of type 2 diabetes mellitus micro-and macrovascular complications: Avenues for a mechanistic-based therapeutic approach. Current Diabetes Reviews. 2011;**7**(5):313-324

[14] Lee Mosley R, Benner EJ, Kadiu I, Thomas M, Boska MD, Hasan K, et al. Neuroinflammation, oxidative stress, and the pathogenesis of Parkinson's disease. Clinical Neuroscience Research. 2006;**6**(5):261-281

[15] Rohl C, Armbrust E, Herbst E, Jess A, Gulden M, Maser E, et al. Mechanisms involved in the modulation of astroglial resistance to oxidative stress induced by activated microglia: Antioxidative systems, peroxide elimination, radical generation, lipid

peroxidation. Neurotoxicity Research. 2010;**17**(4):317-331

[16] Kumar A, Dora J, Singh A. A review on spice of life *Curcuma longa* (turmeric). International Journal of Applied Biology and Pharmaceutical Technology. 2011;**2**(4):371-379

[17] Garcion E, Sindji L, Nataf S, Brachet P, Darcy F, Montero-Menei CN. Treatment of experimental autoimmune encephalomyelitis in rat by 1,25-dihydroxyvitamin D3 leads to early effects within the central nervous sys- tem. Acta Neuropathologica. 2003;**105**:438-448

[18] Garcion E, Wion-Barbot N, Montero-Menei CN, Berger F, Wion D. New clues about vitamin D functions in the nervous system. Trends in Endocrinology and Metabolism. 2002;**13**:100-105

[19] Coyle JT, Puttfarcken P. Oxidative stress, glutamate, and neurodegenerative disorders. Science. 1993;**262**(5134): 689-695

[20] Barnard ND, Bush AI, Ceccarelli A, Cooper J, de Jager CA, Erickson KI, et al. Dietary and lifestyle guidelines for the prevention of Alzheimer's disease. Neurobiology of Aging. 2014;**35**:S74-S78

[21] Murman DL, Colenda CC. The economic impact of neuropsychiatric symptoms in Alzheimer's disease. PharmacoEconomics. 2005;**23**(3): 227-242

[22] Selkoe DJ. Cell biology of protein misfolding: The examples of Alzheimer's and Parkinson's diseases. Nature Cell Biology. 2004;**6**(11):1054-1061

[23] Haass C, Selkoe DJ. Soluble protein oligomers in neurodegeneration: Lessons from the Alzheimer's amyloid β-peptide. Nature Reviews Molecular Cell Biology. 2007;**8**(2):101-112

[24] Johnson GV, Stoothoff WH. Tau phosphorylation in neuronal cell function and dysfunction. Journal of Cell Science. 2004;**117**(24):5721-5729

[25] Crimins JL, Pooler A, Polydoro M, Luebke JI, Spires-Jones TL. The intersection of amyloid beta and tau in glutamatergic synaptic dysfunction and collapse in Alzheimer's disease. Ageing Research Reviews. 2013;**12**(3):757-763

[26] Chen Z, Zhong C. Oxidative stress in Alzheimer's disease. Neuroscience Bulletin. 2014;**30**(2):271-281

[27] Gezen-Ak D, Atasoy IL, Candas E, Alaylioglu M, Yılmazer S, Dursun E. Vitamin D receptor regulates amyloid beta 1-42 production with protein disulfide isomerase A3. ACS Chemical Neuroscience. 2017;**8**(10):2335-2346

[28] Kalueff AV, Tuohimaa P. Neurosteroid hormone vitamin D and its utility in clinical nutrition. Current Opinion in Clinical Nutrition and Metabolic Care. 2007;**10**:12-19

[29] Ahmed T, Gilani A. Inhibitory effect of curcuminoids on acetylcholinesterase activity and attenuation of scopolamine induced amnesia may explain medicinal use of turmeric in Alzheimer's disease. Pharmacology Biochemistry and Behavior. 2009;**91**(4):554-559

[30] Ono K, Hasegawa K, Naiki H, Yamada M. Curcumin has potent anti-amyloidogenic effects for Alzheimer's β-amyloid fibrils in vitro. Journal of Neuroscience Research. 2004;**75**(6):742-750

[31] Yang F, Lim GP, Begum AN. Curcumin inhibits formation of amyloid β oligomers and fibrils, binds plaques, and reduces amyloid in vivo. Journal of Biological Chemistry. 2005;**280**(7):5892-5901

[32] Akinyemi AJ, Oboh G, Oyeleye SI, Ogunsuyi. Anti-amnestic effect

**81**

*Neuroprotective Effects of Curcumin and Vitamin D3 on Scopolamine-Induced Learning…*

International Journal of Alzheimer's Disease. 2012;**2012**(8). Article ID 974013.

[40] Mishra S, Palanivelu K. The effect of curcumin (turmeric) on Alzheimer's disease: An overview. Annals of Indian Academy of Neurology. 2008;**11**(1):13

DOI: 10.1155/2012/974013

[41] Indumathy S, Kavimani S, Raman KV. The role of angiotensin antagonists in memory enhancement. International Journal of Pharma and Bio

[42] Moghaddam AH, Zare M. Neuroprotective effect of hesperetin and nano-hesperetin on recognition memory impairment and the

elevated oxygen stress in rat model of Alzheimer's disease. Biomedicine & Pharmacotherapy. 2018;**97**:1096-1101

[43] Shahidi S, Zargooshnia S, Asl SS, Komaki A, Sarihi A. Influence of N-acetyl cysteine on beta-amyloidinduced Alzheimer's disease in a rat model: A behavioral and electrophysiological study. Brain Research Bulletin. 2017;**131**:142-149

[44] Jahanshahi M, Golalipour MJ, Afshar M. The effect of *Urtica dioica* extract on the number of astrocytes in the dentate gyrus of diabetic rats. Folia Morphologica. 2009;**68**(2):93-97

[45] Sunderland T, Tariot PN, Cohen RM, Weingartner H, Mueller EA, Murphy DL. Anticholinergic sensitivity in patients with dementia of the Alzheimer type and age-matched controls: A dose-response study. Archives of General Psychiatry.

[46] Pan R, Qiu S, Lu DX, Dong J. Curcumin improves learning and memory ability and its neuroprotective mechanism in mice. Chinese Medical

[47] Sun CY, Qi SS, Zhou P, Cui HR, Chen SX, Dai KY. Neurobiological and

Journal. 2008;**121**:832-839

1987;**44**(5):418-426

Sciences. 2010;**1**(3):1-4

*DOI: http://dx.doi.org/10.5772/intechopen.92407*

[33] Ma Q-L, Zuo X, Yang F. Curcumin suppresses soluble tau dimers and corrects molecular chaperone, synaptic, and behavioral deficits in aged human tau transgenic mice. The Journal of Biological Chemistry.

[34] Menon VP, Sudheer AR. Antioxidant and anti-inflammatory properties of curcumin. Advances in Experimental Medicine and Biology. 2007;**595**:105-125. DOI: 10.1007/978-0-387-46401-5\_3

of curcumin in combination with donepezil, an anticholinesterase drug: Involvement of cholinergic system. Neurotoxicity Research. 2017;**31**(4):

560-569. ISSN: 1476-3524

2013;**288**(6):4056-4065

[35] Ray B, Lahiri DK. Neuro-

curcumin. Current Opinion in Pharmacology. 2009;**9**(4):434-444

2014;**38**(2):371-377

1988;**2**(2):67-79

[36] Pakaski M, Feher A, Juhasz A, Drotos G, Fazekas OC, Kovacs J, et al. Serum adipokine levels modified by donepezil treatment in Alzheimer's disease. Journal of Alzheimer's Disease.

[37] Preston GC, Brazell C, Ward C, Broks P, Traub M, Stahl SM. The scopolamine model of dementia: Determination of central cholinomimetic effects of physostigmine on cognition and biochemical markers in man. Journal of Psychopharmacology.

[38] Flood JF, Cherkin A. Scopolamine effects on memory retentionin mice: A model of dementia? Behavioral and Neural Biology. 1986;**45**:169-184

[39] Goverdhan P, Sravanthi A, Mamatha T. Neuroprotective effects of meloxicam and selegiline in scopolamine-induced cognitive impairment and oxidative stress.

inflammation in Alzheimer's disease: Different molecular targets and potential therapeutic agents including *Neuroprotective Effects of Curcumin and Vitamin D3 on Scopolamine-Induced Learning… DOI: http://dx.doi.org/10.5772/intechopen.92407*

of curcumin in combination with donepezil, an anticholinesterase drug: Involvement of cholinergic system. Neurotoxicity Research. 2017;**31**(4): 560-569. ISSN: 1476-3524

*Neurological and Mental Disorders*

2010;**17**(4):317-331

2003;**105**:438-448

2002;**13**:100-105

689-695

227-242

peroxidation. Neurotoxicity Research.

[24] Johnson GV, Stoothoff WH. Tau phosphorylation in neuronal cell function and dysfunction. Journal of Cell Science. 2004;**117**(24):5721-5729

[25] Crimins JL, Pooler A, Polydoro M, Luebke JI, Spires-Jones TL. The intersection of amyloid beta and tau in glutamatergic synaptic dysfunction and collapse in Alzheimer's disease. Ageing Research Reviews. 2013;**12**(3):757-763

[26] Chen Z, Zhong C. Oxidative stress in Alzheimer's disease. Neuroscience

[27] Gezen-Ak D, Atasoy IL, Candas E, Alaylioglu M, Yılmazer S, Dursun E. Vitamin D receptor regulates amyloid beta 1-42 production with protein disulfide isomerase A3. ACS Chemical Neuroscience. 2017;**8**(10):2335-2346

Neurosteroid hormone vitamin D and its utility in clinical nutrition. Current Opinion in Clinical Nutrition and Metabolic Care. 2007;**10**:12-19

[29] Ahmed T, Gilani A. Inhibitory effect of curcuminoids on acetylcholinesterase activity and attenuation of scopolamine induced amnesia may explain medicinal use of turmeric in Alzheimer's disease. Pharmacology Biochemistry and Behavior. 2009;**91**(4):554-559

[30] Ono K, Hasegawa K, Naiki H, Yamada M. Curcumin has potent anti-amyloidogenic effects for

[31] Yang F, Lim GP, Begum AN.

β oligomers and fibrils, binds

2005;**280**(7):5892-5901

2004;**75**(6):742-750

Alzheimer's β-amyloid fibrils in vitro. Journal of Neuroscience Research.

Curcumin inhibits formation of amyloid

plaques, and reduces amyloid in vivo. Journal of Biological Chemistry.

[32] Akinyemi AJ, Oboh G, Oyeleye SI, Ogunsuyi. Anti-amnestic effect

Bulletin. 2014;**30**(2):271-281

[28] Kalueff AV, Tuohimaa P.

[16] Kumar A, Dora J, Singh A. A review on spice of life *Curcuma longa* (turmeric). International Journal of Applied Biology and Pharmaceutical Technology. 2011;**2**(4):371-379

[17] Garcion E, Sindji L, Nataf S,

[18] Garcion E, Wion-Barbot N, Montero-Menei CN, Berger F, Wion D. New clues about vitamin D functions in the nervous system. Trends in Endocrinology and Metabolism.

[19] Coyle JT, Puttfarcken P. Oxidative stress, glutamate, and neurodegenerative disorders. Science. 1993;**262**(5134):

[20] Barnard ND, Bush AI, Ceccarelli A, Cooper J, de Jager CA, Erickson KI, et al. Dietary and lifestyle guidelines for the prevention of Alzheimer's disease. Neurobiology of Aging. 2014;**35**:S74-S78

[21] Murman DL, Colenda CC. The economic impact of neuropsychiatric symptoms in Alzheimer's disease. PharmacoEconomics. 2005;**23**(3):

[22] Selkoe DJ. Cell biology of protein misfolding: The examples of Alzheimer's and Parkinson's diseases. Nature Cell Biology. 2004;**6**(11):1054-1061

[23] Haass C, Selkoe DJ. Soluble protein oligomers in neurodegeneration: Lessons from the Alzheimer's amyloid β-peptide. Nature Reviews Molecular Cell Biology. 2007;**8**(2):101-112

Brachet P, Darcy F, Montero-Menei CN. Treatment of experimental autoimmune encephalomyelitis in rat by 1,25-dihydroxyvitamin D3 leads to early effects within the central nervous sys- tem. Acta Neuropathologica.

**80**

[33] Ma Q-L, Zuo X, Yang F. Curcumin suppresses soluble tau dimers and corrects molecular chaperone, synaptic, and behavioral deficits in aged human tau transgenic mice. The Journal of Biological Chemistry. 2013;**288**(6):4056-4065

[34] Menon VP, Sudheer AR. Antioxidant and anti-inflammatory properties of curcumin. Advances in Experimental Medicine and Biology. 2007;**595**:105-125. DOI: 10.1007/978-0-387-46401-5\_3

[35] Ray B, Lahiri DK. Neuroinflammation in Alzheimer's disease: Different molecular targets and potential therapeutic agents including curcumin. Current Opinion in Pharmacology. 2009;**9**(4):434-444

[36] Pakaski M, Feher A, Juhasz A, Drotos G, Fazekas OC, Kovacs J, et al. Serum adipokine levels modified by donepezil treatment in Alzheimer's disease. Journal of Alzheimer's Disease. 2014;**38**(2):371-377

[37] Preston GC, Brazell C, Ward C, Broks P, Traub M, Stahl SM. The scopolamine model of dementia: Determination of central cholinomimetic effects of physostigmine on cognition and biochemical markers in man. Journal of Psychopharmacology. 1988;**2**(2):67-79

[38] Flood JF, Cherkin A. Scopolamine effects on memory retentionin mice: A model of dementia? Behavioral and Neural Biology. 1986;**45**:169-184

[39] Goverdhan P, Sravanthi A, Mamatha T. Neuroprotective effects of meloxicam and selegiline in scopolamine-induced cognitive impairment and oxidative stress.

International Journal of Alzheimer's Disease. 2012;**2012**(8). Article ID 974013. DOI: 10.1155/2012/974013

[40] Mishra S, Palanivelu K. The effect of curcumin (turmeric) on Alzheimer's disease: An overview. Annals of Indian Academy of Neurology. 2008;**11**(1):13

[41] Indumathy S, Kavimani S, Raman KV. The role of angiotensin antagonists in memory enhancement. International Journal of Pharma and Bio Sciences. 2010;**1**(3):1-4

[42] Moghaddam AH, Zare M. Neuroprotective effect of hesperetin and nano-hesperetin on recognition memory impairment and the elevated oxygen stress in rat model of Alzheimer's disease. Biomedicine & Pharmacotherapy. 2018;**97**:1096-1101

[43] Shahidi S, Zargooshnia S, Asl SS, Komaki A, Sarihi A. Influence of N-acetyl cysteine on beta-amyloidinduced Alzheimer's disease in a rat model: A behavioral and electrophysiological study. Brain Research Bulletin. 2017;**131**:142-149

[44] Jahanshahi M, Golalipour MJ, Afshar M. The effect of *Urtica dioica* extract on the number of astrocytes in the dentate gyrus of diabetic rats. Folia Morphologica. 2009;**68**(2):93-97

[45] Sunderland T, Tariot PN, Cohen RM, Weingartner H, Mueller EA, Murphy DL. Anticholinergic sensitivity in patients with dementia of the Alzheimer type and age-matched controls: A dose-response study. Archives of General Psychiatry. 1987;**44**(5):418-426

[46] Pan R, Qiu S, Lu DX, Dong J. Curcumin improves learning and memory ability and its neuroprotective mechanism in mice. Chinese Medical Journal. 2008;**121**:832-839

[47] Sun CY, Qi SS, Zhou P, Cui HR, Chen SX, Dai KY. Neurobiological and

#### *Neurological and Mental Disorders*

pharmacological validity of curcumin in ameliorating memory performance of senescence-accelerated mice. Pharmacology, Biochemistry, and Behavior. 2013;**105**:76-82

[48] Annweiler C, Karras SN, Anagnostis P, Beauchet O. Vitamin D supplements: A novel therapeutic approach for Alzheimer patients. Frontiers in Pharmacology. 2014;**5**:6

[49] Burne TH, Johnston AN, McGrath J, Mack-ay-Sim A. Swimming behavior and post-swimming activity in vitamin D receptor knockout mice. Brain Research Bulletin. 2006;**69**:74-78

[50] Harrison RS, Sharpe PC, Singh Y, Fairlie DP. Amyloid peptides and proteins in review. Reviews of Physiology, Biochemistry and Pharmacology. 2007;**159**:1-77

[51] Huang HC, Tang D, Xu K, Jiang ZF. Curcumin attenuates amyloidβ-induced tau hyperphosphorylation in human neuroblastoma SH-SY5Y cells involving PTEN/Akt/GSK-3β signaling pathway. Journal of Receptors and Signal Transduction. 2014;**34**(1):26-37

[52] Das TK, Jana P, Chakrabarti SK, Hamid A, Mas RW. Curcumin downregulates GSK3 and Cdk5 in scopolamine-induced Alzheimer's disease rats abrogating Aβ 40/42 and tau hyperphosphorylation. Journal of Alzheimer's disease reports. 2019;**3**(1):257-267

**83**

**Chapter 6**

**Abstract**

Disorder

*and Tinatin Kutubidze*

disorders, and other comorbidities.

ance of clinical picture in adulthood [1].

**1. Introduction**

Attention Deficit Hyperactivity

Attention deficit hyperactivity disorder (ADHD) is a mental disorder of the neurodevelopmental type. The disorder represents one of the common causes of referral for behavioral problems in children to medical and mental health doctors all around the world. The diagnosis can be done by DSM-V criteria. According to DSM-V, there are three main subtypes of ADHD: ADHD-inattentive type, ADHD-hyperactive-impulsive type, and ADHD-combined type. The etiology of ADHD is not definitively known. A genetic imbalance of catecholamine metabolism in the cerebral cortex appears to play a primary role. Various environmental factors may play a secondary role. Cognitive impairments in a variety of domains have been found in ADHD as well as impairment in overall intellectual function. A meta-analysis of children and adolescents with ADHD showed impairments in several aspects of executive functioning. The most important part of any intervention plan for a child with ADHD is the physical, behavioral and neuromotor/ neuropsychological examination. Medication should be started with one of the stimulants. Both d-amphetamine and methylphenidate have been shown to be effective for improvement of hyperactivity, concentration problems, learning

**Keywords:** ADHD, inattention, hyperactivity, impulsivity, behavioral therapy

Attention deficit hyperactivity disorder (ADHD) is a mental disorder of the neurodevelopmental type. It is characterized by difficulty paying attention, excessive activity and acting without regards to consequences, which are otherwise not appropriate for a person's age. The disorder represents one of the common causes of referral for behavioral problems in children to medical and mental health doctors all around the world. It is one of the most prevalent psychiatric conditions in children affecting 5% of children and adolescents worldwide. Symptoms which are specific for ADHD could decrease with age as almost 65% of children with ADHD have partial resolution of signs but 15% of ADHD children exhibit complete disappear-

A meta-analysis of 175 research studies worldwide on ADHD prevalence in

The number of children with ADHD can reach millions. According to data received in 2016 from USA almost 6.1 million of children have ADHD (9.4%). About

children aged 18 and under found an overall pooled estimate of 7.2% [2].

*Sophia Bakhtadze, Tinatin Tkemeladze* 

#### **Chapter 6**

*Neurological and Mental Disorders*

Behavior. 2013;**105**:76-82

[48] Annweiler C, Karras SN, Anagnostis P, Beauchet O. Vitamin D supplements: A novel therapeutic approach for Alzheimer patients. Frontiers in Pharmacology. 2014;**5**:6

pharmacological validity of curcumin in ameliorating memory performance of senescence-accelerated mice. Pharmacology, Biochemistry, and

[49] Burne TH, Johnston AN, McGrath J, Mack-ay-Sim A. Swimming behavior and post-swimming activity in vitamin D receptor knockout mice. Brain Research Bulletin. 2006;**69**:74-78

[50] Harrison RS, Sharpe PC, Singh Y, Fairlie DP. Amyloid peptides and proteins in review. Reviews of Physiology, Biochemistry and Pharmacology. 2007;**159**:1-77

Jiang ZF. Curcumin attenuates amyloidβ-induced tau hyperphosphorylation in human neuroblastoma SH-SY5Y cells involving PTEN/Akt/GSK-3β signaling pathway. Journal of Receptors and Signal Transduction. 2014;**34**(1):26-37

[52] Das TK, Jana P, Chakrabarti SK, Hamid A, Mas RW. Curcumin downregulates GSK3 and Cdk5 in scopolamine-induced Alzheimer's disease rats abrogating Aβ 40/42 and tau hyperphosphorylation. Journal of Alzheimer's disease reports.

2019;**3**(1):257-267

[51] Huang HC, Tang D, Xu K,

**82**

## Attention Deficit Hyperactivity Disorder

*Sophia Bakhtadze, Tinatin Tkemeladze and Tinatin Kutubidze*

#### **Abstract**

Attention deficit hyperactivity disorder (ADHD) is a mental disorder of the neurodevelopmental type. The disorder represents one of the common causes of referral for behavioral problems in children to medical and mental health doctors all around the world. The diagnosis can be done by DSM-V criteria. According to DSM-V, there are three main subtypes of ADHD: ADHD-inattentive type, ADHD-hyperactive-impulsive type, and ADHD-combined type. The etiology of ADHD is not definitively known. A genetic imbalance of catecholamine metabolism in the cerebral cortex appears to play a primary role. Various environmental factors may play a secondary role. Cognitive impairments in a variety of domains have been found in ADHD as well as impairment in overall intellectual function. A meta-analysis of children and adolescents with ADHD showed impairments in several aspects of executive functioning. The most important part of any intervention plan for a child with ADHD is the physical, behavioral and neuromotor/ neuropsychological examination. Medication should be started with one of the stimulants. Both d-amphetamine and methylphenidate have been shown to be effective for improvement of hyperactivity, concentration problems, learning disorders, and other comorbidities.

**Keywords:** ADHD, inattention, hyperactivity, impulsivity, behavioral therapy

#### **1. Introduction**

Attention deficit hyperactivity disorder (ADHD) is a mental disorder of the neurodevelopmental type. It is characterized by difficulty paying attention, excessive activity and acting without regards to consequences, which are otherwise not appropriate for a person's age. The disorder represents one of the common causes of referral for behavioral problems in children to medical and mental health doctors all around the world. It is one of the most prevalent psychiatric conditions in children affecting 5% of children and adolescents worldwide. Symptoms which are specific for ADHD could decrease with age as almost 65% of children with ADHD have partial resolution of signs but 15% of ADHD children exhibit complete disappearance of clinical picture in adulthood [1].

A meta-analysis of 175 research studies worldwide on ADHD prevalence in children aged 18 and under found an overall pooled estimate of 7.2% [2].

The number of children with ADHD can reach millions. According to data received in 2016 from USA almost 6.1 million of children have ADHD (9.4%). About 388,000 children are 2–5 years of age; 4 million children are 6–11 years; and 3 million children aged 12–17 years. Boys are more likely to be diagnosed with ADHD than girls [3]. The prevalence age for diagnosis is 2–17 years.

Centers for Disease Control and prevention (CDC) uses datasets from parent surveys and healthcare claims to understand diagnosis and treatment patterns for ADHD. Estimates for diagnosis and treatment can vary depending on the source [4]. The methods used for ADHD assessment are also different.

Coexisting disorders are common in children with ADHD. According to a national 2016 parent survey every 6 in 10 children with ADHD could have at least one other mental, emotional or behavioral disorder; almost half of the children with ADHD have coexisting behavioral and conduct disorders. One third of ADHD children could exhibit anxiety disorders as well. Depression, autism spectrum disorder and Tourette syndrome are also common disorders accompanying ADHD [2].

The first information about ADHD appeared in 1865 while German doctor Heinrich Hoffman described hyperactive child ("Fidgety Phil"). The enormous scientific contribution was done by George Still and Alfred Tregold who were the first authors to emphasize those clinical clues which still persist [5]. In 1922, the condition was called as "postencephalic behavior disorder", later in 1947, it was changed with "brain-injured child," then in 1963 it was renamed as "perceptually handicapped child" and ending with "minimal brain dysfunction" in 1966 [6]. Two years after in 1968 Diagnostic and Statistical Manual (DSM) recognized it as a syndrome under the term "hyperkinetic reaction of childhood or adolescence." In late 80s DSM-III recognized two subtypes of attention deficit disorder (*ADD) with hyperactivity and ADD without hyperactivity.* DSM-III revised the term ADD and changed it with "attention-deficit hyperactivity disorder (ADHD)." Finally DSM-IV identified three subtypes of the syndrome: ADHD-inattentive type, ADHD-hyperactive-impulsive type, and ADHD-combined type [7]. The DSM-V shared the same clinical forms of ADHD and identified strict diagnostic criteria for each [8].

#### **2. DSM-5 diagnostic criteria**

	- 1.**Inattention:** Six (or more) of the following symptoms have persisted for at least 6 months to a degree that is inconsistent with developmental level and that negatively impact directly on social and academic/occupational activities.

**Note:** The symptoms are not solely a manifestation of oppositional behavior, defiance, hostility or failure to understand tasks or instructions. For older adolescents and adults (age 17 and older) at least five symptoms are required.


**85**

up with).

*Attention Deficit Hyperactivity Disorder DOI: http://dx.doi.org/10.5772/intechopen.92334*

meet deadlines).

lengthy papers).

telephones).

appointments).

academic/occupational activities:

c.Often does not seem to listen when spoken to directly (e.g., mind seems

d.Often does not follow through on instructions and fails to finish schoolwork, chores, or duties in the workplace (e.g., starts tasks but quickly

e.Often has difficulty organizing tasks and activities (e.g., difficulty managing sequential tasks; difficulty keeping materials and belongings in order, messy, disorganized work; has poor time management; fails to

f. Often avoids, dislikes or is reluctant to engage in tasks that require sustained mental effort (e.g., schoolwork or homework; for older adolescents and adult, preparing reports, completing forms, reviewing

g.Often loses things necessary for tasks or activities (e.g., school materials, pencils, books, tools, wallets, keys, paperwork, eyeglasses, mobile

h.Is often easily distracted by extraneous stimuli (for older adolescents

i. Is often forgetful in daily activities (e.g., doing chores, running errands; for older adolescents and adults returning calls, paying bills, keeping

2.**Hyperactivity and impulsivity:** Six (or more) of the following symptoms have persisted for at least 6 months to a degree that is inconsistent with developmental level and that negatively impacts directly on social and

b.Often leaves seat in situations when remaining seated is expected (e.g., leaves his or her place in the classroom, in the office or other workplace

c.Often runs about or climbs in situations where it is inappropriate (Note:

e.Is often "on the go" acting as if "driven by a motor" (e.g., is unable to be or uncomfortable being still for extended time as in restaurants, meeting; may be experienced by others as being restless or difficult to keep

**Note:** The symptoms are not solely a manifestation of oppositional behavior, defiance, hostility or a failure to understand tasks or instructions. For older adoles-

a.Often fidgets with or taps hands or feet or squirms in a seat.

or in other situations that require remaining in place).

In adolescents or adults may be limited to feeling restless).

d.Often unable to play or engage in leisure activities quietly.

cents and adults (age 17 and older) at least five symptoms are required.

and adults may include unrelated thoughts).

elsewhere, even in the absence of any obvious distraction).

loses focus and is easily sidetracked).

*Neurological and Mental Disorders*

388,000 children are 2–5 years of age; 4 million children are 6–11 years; and 3 million children aged 12–17 years. Boys are more likely to be diagnosed with ADHD

Centers for Disease Control and prevention (CDC) uses datasets from parent surveys and healthcare claims to understand diagnosis and treatment patterns for ADHD. Estimates for diagnosis and treatment can vary depending on the source [4].

Coexisting disorders are common in children with ADHD. According to a national 2016 parent survey every 6 in 10 children with ADHD could have at least one other mental, emotional or behavioral disorder; almost half of the children with ADHD have coexisting behavioral and conduct disorders. One third of ADHD children could exhibit anxiety disorders as well. Depression, autism spectrum disorder and Tourette syndrome are also common disorders accompanying ADHD [2]. The first information about ADHD appeared in 1865 while German doctor Heinrich Hoffman described hyperactive child ("Fidgety Phil"). The enormous scientific contribution was done by George Still and Alfred Tregold who were the first authors to emphasize those clinical clues which still persist [5]. In 1922, the condition was called as "postencephalic behavior disorder", later in 1947, it was changed with "brain-injured child," then in 1963 it was renamed as "perceptually handicapped child" and ending with "minimal brain dysfunction" in 1966 [6]. Two years after in 1968 Diagnostic and Statistical Manual (DSM) recognized it as a syndrome under the term "hyperkinetic reaction of childhood or adolescence." In late 80s DSM-III recognized two subtypes of attention deficit disorder (*ADD) with hyperactivity and ADD without hyperactivity.* DSM-III revised the term ADD and changed it with "attention-deficit hyperactivity disorder (ADHD)." Finally DSM-IV identified three subtypes of the syndrome: ADHD-inattentive type, ADHD-hyperactive-impulsive type, and ADHD-combined type [7]. The DSM-V shared the same clinical forms of

than girls [3]. The prevalence age for diagnosis is 2–17 years.

The methods used for ADHD assessment are also different.

ADHD and identified strict diagnostic criteria for each [8].

**A. A persistent pattern of inattention and/or hyperactivity-impulsivity that interferes with functioning or development as characterized by (1) and/**

**Note:** The symptoms are not solely a manifestation of oppositional behavior, defiance, hostility or failure to understand tasks or instructions. For older adoles-

cents and adults (age 17 and older) at least five symptoms are required.

details, work is inaccurate).

lengthy reading).

1.**Inattention:** Six (or more) of the following symptoms have persisted for at least 6 months to a degree that is inconsistent with developmental level and that negatively impact directly on social and academic/occupational

a.Often fails to give close attention to details or make careless mistakes in schoolwork, at work or during other activities (e.g., overlooks or misses

b.Often has difficulty sustaining attention in tasks or play activities (e.g., has difficulty remaining focused during lectures, conversations or

**2. DSM-5 diagnostic criteria**

activities.

**or (2):**

**84**


**Note:** The symptoms are not solely a manifestation of oppositional behavior, defiance, hostility or a failure to understand tasks or instructions. For older adolescents and adults (age 17 and older) at least five symptoms are required.


**Specify** whether

**314.01 (F90.2) Combined presentation:** If both criterion A1 (inattention) and criterion A2 (hyperactivity-impulsivity) are met for the past 6 months.

**314.00 (F90.0) Predominantly inattentive presentation:** If criterion A1 (inattention) is met but criterion A2 (hyperactivity-impulsivity) is not met for the past 6 months.

**314.01 (F90.1) Predominantly hyperactive/impulsive presentation:** If criterion A2 (hyperactivity-impulsivity) is met but criterion A1 (inattention) is not mere over the past 6 months.

**Specify** if:

**In partial remission:** When full criteria were previously met, fewer than the full criteria have been met for the past 6 months and the symptoms still result in impairment in social, academic or occupational functioning.

**Specify** current severity:

**Mild:** Few if any symptoms in excess of those required to make the diagnosis are present and symptoms result it only minor functional impairments.

**Moderate:** Symptoms or functional impairment between "mild" and "severe" are present and symptoms result in only minor functional impairments.

**Severe:** Many symptoms in excess of those required to make the diagnosis or several symptoms that are particularly severe, are present or the symptoms result in marked impairment is social or occupational functioning.

**87**

study [4].

*2.1.5 Iron deficiency*

*Attention Deficit Hyperactivity Disorder DOI: http://dx.doi.org/10.5772/intechopen.92334*

The etiology of ADHD is not definitely known. A genetic imbalance of catecholamines in the cerebral cortex appears to play a primary role. A genetic contribution to the pathogenesis of ADHD is supported by the increased risk of ADHD in the first-degree relatives of patients with ADHD and twin studies from different countries that consistently provide heritability estimates of approximately 75% [1]. Various environmental factors may play a secondary role; the significance of environmental factors is controversial. Dietary influences, sleep deficiency, prenatal

The influence of diet on attention, hyperactivity, and behavior is controversial. Some children may demonstrate mild adverse behavioral effects of diets containing food additives, artificial colors, excess sugar, or reduced intake of essential fatty

Food additives were first suggested as potential cause of hyperactive behavior in the 1970. Systematic reviews and the meta-analyses of randomized trials with methodological limitations suggest that some children with ADHD respond favorably to elimination diets [9, 10]. However, this conclusion is not universally

Adverse behavior effects including hyperactivity are commonly attributed to excess sugar intake by parents and teachers. Parent of children with ADHD frequently note a worsening of hyperactivity after consuming high carbohydrate meal. There are proposed mechanisms: sensitivity to refined sugar and functional reactive hypoglycemia (which triggers release of stress hormones such as adrenaline) after ingesting sugar [11]. There is no evidence that sugar effects the behavior and/or cognitive performance [11]. Future studies are necessary to confirm the effect on even a small

Food allergy is proposed as a possible factor in the cause of ADHD. There are few well-designed trials evaluating the potential association between food sensitivity (allergy or intolerance) and behavior. Demonstration of such association requires removal of the suspect food(s) from child's diet (elimination diet). Followed by challenge with suspected food(s) versus placebo. The role of food sensitivity as a cause of ADHD is difficult to document, cooperation on neurologist, allergist and dietician being essential. The hypoallergic diet deserves further

The role of iron deficiency in the ADHD has not clearly defined. A comparison of clinical characteristics of children with the lowest serum ferritin

medications, prematurity, iron deficiency, iodine deficiency and etc.

**2.1 Etiology**

*2.1.1 Dietary influences*

acids and minerals.

*2.1.2 Food additives*

*2.1.3 Refined sugar*

subset of children.

*2.1.4 Food sensitivity*

accepted, and the issue remains controversial.

#### **2.1 Etiology**

*Neurological and Mental Disorders*

f. Often talks excessively

take over what others are doing).

conversation).

in line).

**to age 12 years.**

**other activities).**

**withdrawal).**

**Specify** whether

mere over the past 6 months.

**Specify** current severity:

6 months.

**Specify** if:

g.Often blurts out an answer before a question has been com-

h.Often has difficulty waiting his or her turn (e.g., while waiting

pleted (e.g., complete people's sentences; cannot wait for turn in

i. Often interrupts or intrudes on others (e.g., butts into conversations, games or activities; may start using other people's things without asking or receiving permission; for adolescents and adults, may intrude into or

**B. Several inattentive or hyperactive-impulsive symptoms were present prior** 

**C. Several inattentive or hyperactive-impulsive symptoms are present in two or more setting (e.g., at home, school or work; with friends or relatives; in** 

**D. There is clear evidence that the symptoms interfere with or reduce the** 

**E. The symptoms do not occur exclusively during the course of schizophrenia or another psychotic disorder and are not better explained by another mental disorder (e.g., mood disorder, anxiety disorder, dissociative disorder, personality disorder, substance intoxication or** 

**314.01 (F90.2) Combined presentation:** If both criterion A1 (inattention) and

**314.00 (F90.0) Predominantly inattentive presentation:** If criterion A1 (inattention) is met but criterion A2 (hyperactivity-impulsivity) is not met for the past

**314.01 (F90.1) Predominantly hyperactive/impulsive presentation:** If criterion A2 (hyperactivity-impulsivity) is met but criterion A1 (inattention) is not

**In partial remission:** When full criteria were previously met, fewer than the full criteria have been met for the past 6 months and the symptoms still result in

**Mild:** Few if any symptoms in excess of those required to make the diagnosis are

**Moderate:** Symptoms or functional impairment between "mild" and "severe"

**Severe:** Many symptoms in excess of those required to make the diagnosis or several symptoms that are particularly severe, are present or the symptoms result in

**quality of social, academic or occupational functioning.**

criterion A2 (hyperactivity-impulsivity) are met for the past 6 months.

impairment in social, academic or occupational functioning.

marked impairment is social or occupational functioning.

present and symptoms result it only minor functional impairments.

are present and symptoms result in only minor functional impairments.

**86**

The etiology of ADHD is not definitely known. A genetic imbalance of catecholamines in the cerebral cortex appears to play a primary role. A genetic contribution to the pathogenesis of ADHD is supported by the increased risk of ADHD in the first-degree relatives of patients with ADHD and twin studies from different countries that consistently provide heritability estimates of approximately 75% [1].

Various environmental factors may play a secondary role; the significance of environmental factors is controversial. Dietary influences, sleep deficiency, prenatal medications, prematurity, iron deficiency, iodine deficiency and etc.

#### *2.1.1 Dietary influences*

The influence of diet on attention, hyperactivity, and behavior is controversial. Some children may demonstrate mild adverse behavioral effects of diets containing food additives, artificial colors, excess sugar, or reduced intake of essential fatty acids and minerals.

#### *2.1.2 Food additives*

Food additives were first suggested as potential cause of hyperactive behavior in the 1970. Systematic reviews and the meta-analyses of randomized trials with methodological limitations suggest that some children with ADHD respond favorably to elimination diets [9, 10]. However, this conclusion is not universally accepted, and the issue remains controversial.

#### *2.1.3 Refined sugar*

Adverse behavior effects including hyperactivity are commonly attributed to excess sugar intake by parents and teachers. Parent of children with ADHD frequently note a worsening of hyperactivity after consuming high carbohydrate meal. There are proposed mechanisms: sensitivity to refined sugar and functional reactive hypoglycemia (which triggers release of stress hormones such as adrenaline) after ingesting sugar [11].

There is no evidence that sugar effects the behavior and/or cognitive performance [11]. Future studies are necessary to confirm the effect on even a small subset of children.

#### *2.1.4 Food sensitivity*

Food allergy is proposed as a possible factor in the cause of ADHD. There are few well-designed trials evaluating the potential association between food sensitivity (allergy or intolerance) and behavior. Demonstration of such association requires removal of the suspect food(s) from child's diet (elimination diet). Followed by challenge with suspected food(s) versus placebo. The role of food sensitivity as a cause of ADHD is difficult to document, cooperation on neurologist, allergist and dietician being essential. The hypoallergic diet deserves further study [4].

#### *2.1.5 Iron deficiency*

The role of iron deficiency in the ADHD has not clearly defined. A comparison of clinical characteristics of children with the lowest serum ferritin levels (20ng/ml) and those with highest serum ferritin levels (60ng/ml) show no significant difference in severity or frequency of ADHD and comorbid symptoms [4]. In addition, there appears to be an overlap between restless leg syndrome (which is associated with iron deficiency) and ADHD symptom in children [12].

#### *2.1.6 Zinc deficiency*

The role of zinc in ADHD is also controversial. Several studies have been conducted to find out the role of zinc in the etiology of ADHD. Study by Arnold and colleagues [13] did not show that the zinc alone could improve the ADHD symptoms. In another study zinc was a part of the treatment [14]. In conclusion, zinc is tolerated well in children with ADHD. However, further evidences are required to indicate whether zinc is effective for treating children with ADHD. It is recommended to replicate the randomized well-controlled trials [15].

#### *2.1.7 Prenatal exposure to tobacco smoke*

Prenatal exposure to tobacco smoke is consistently associated with development of ADHD in case-control and cohort studies [16]. Smoking during pregnancy increased the risk of offspring ADHD. The risk of ADHD was greater for children whose mothers were heavy smokers than for those mothers were light smokers. The authors suppose that there can be relationship between maternal smoking and ADHD in children but could not clarify if other confounding risk factors can affect on this causality. Thus it is necessary to perform more studies in order to detect association between maternal smoking and ADHD in offsprings.

#### *2.1.8 Iodine deficiency and children with ADHD*

Correlation of the Iodine deficiency and ADHD in children is of high interest. Thyroid hormones are necessary for the normal metabolic function and the Iodine is important element in the synthesis and regulation of thyroid hormones. It is well known that Iodine deficiency (ID) can lead to mental retardation although preventable and the most critical period for this is fetal development. Maternal thyroid function and Iodine concentration of infant are strongly correlated and the group of disorders due to disturbances in this correlation are called ID disorders. According to Hope Abel and colleagues [17] maternal ID during pregnancy has direct association with severe ADHD symptoms in offsprings at eight years of age. Although it is not recommended maternal iodine intake in order to avoid ADHD risk in child especially as it is known iodine supplementation in the first trimester is associated with an increased health risks

#### *2.1.9 Lead exposure and ADHD*

Lead (Pb) has as a neurotoxic effect leading to abnormal behavior in children. There are plenty of studies attempting to detect correlation between exposure to heavy metals and other harmful environmental factors in the pathogenesis of behavioral disorders. In 1991 recommended level of lead in children's blood (BLL) by CDC is set to 10 micrograms of lead per deciliter of blood (μg/dL) and it has not been changed since then. Donzelli et al. [18] performed systematic review of 17 studies assessing the correlation of lead level and ADHD. According to their results there is a direct correlation between low lead level of lead in ADHD children's blood

**89**

nontwin full siblings.

*Attention Deficit Hyperactivity Disorder DOI: http://dx.doi.org/10.5772/intechopen.92334*

studies to prove this relationship.

**2.2 Genetic factors**

and severity of ADHD symptoms. However, we need more high quality clinical

Although evidence shows that ADHD is a worth recognizing disorder many environmental risk factors such as exposure to heavy metals, dietary factors, environmental exposure to different substances could intensify or accelerate the progression of this disease. The efforts for early diagnosis of the disease is crucial, and identifying the contributing factors is of prime importance to prevent ADHD. Although evidence shows that ADHD is a worth recognizing disorder many environmental risk factors such as exposure to heavy metals, dietary factors, environmental exposure to different substances could intensify or accelerate the progression of this disease. The efforts for early diagnosis of the disease is crucial, and identifying the contributing factors is of prime importance to prevent ADHD.

It has been implicated that genetic factors play a critical role in the etiology of ADHD as well as its comorbidities. Based on multiple familial, twin, adoption and single epidemiological studies ADHD is considered as one of the psychiatric disorders which shows the strongest genetic basis. Several twin studies have revealed that concordance in monozygotic (MZ) twins is higher than in dizygotic (DZ) twins with heritability estimates of approximately 75–80%. Large numbers of linkage studies, genome wide association studies (GWAS) and meta-analyses have been conducted and numbers of susceptibility variants, genes and chromosomal regions have been reported to be associated with ADHD. Moreover, number of studies also shows that about one third of ADHD's heritability is due to a polygenic component encompassing many common variants, where each variant individually has small effect but their cumulative effect contributes to the development of the condition. Investigation of copy number variants (CNVs) has also shown that rare insertions or deletions contribute to the part of ADHD's heritability. Recent progress in identifying ADHD susceptibility genes underlines new biological pathways that may have

According to the literature the mean heritability across multiple twin studies of ADHD is 74–80% [19, 20] and it is similar in ADHD males and females [21]. According to one study, where 894 probands with ADHD and their 1135 siblings were studied, there was nine-fold increased risk of ADHD in siblings of ADHD probands compared with siblings of controls. Several adoption studies also indicate that ADHD is greater among the biological relatives of non-adopted ADHD children than adoptive relatives of adopted ADHD children and the risk for ADHD in adoptive relatives is similar to the risk in relatives of control children. Additionally, adoption studies suggest that the familial aggregation of ADHD is defined more by genetic factors rather than common environmental factors. Based on the largest longitudinal study to date on familial aggregation of ADHD, the closer was the relatedness of probands and their relatives the higher was the familial aggregation [20]. Consistently, among full siblings, the familial aggregation did not differ significantly by index person's sex. Moreover, it is expected that genetic factors play more important role in explaining familial aggregation than shared environmental factors [22], given that the familial aggregation is remarkably higher in MZ twins than in DZ twins and similar between DZ twins and

Genetic linkage was the first genome-wide method applied to ADHD. This method looks through the genome to find evidence that a segment of DNA is transmitted with a disorder within families. According to the literature there is no

implication for prevention and treatment development.

#### *Attention Deficit Hyperactivity Disorder DOI: http://dx.doi.org/10.5772/intechopen.92334*

and severity of ADHD symptoms. However, we need more high quality clinical studies to prove this relationship.

Although evidence shows that ADHD is a worth recognizing disorder many environmental risk factors such as exposure to heavy metals, dietary factors, environmental exposure to different substances could intensify or accelerate the progression of this disease. The efforts for early diagnosis of the disease is crucial, and identifying the contributing factors is of prime importance to prevent ADHD.

Although evidence shows that ADHD is a worth recognizing disorder many environmental risk factors such as exposure to heavy metals, dietary factors, environmental exposure to different substances could intensify or accelerate the progression of this disease. The efforts for early diagnosis of the disease is crucial, and identifying the contributing factors is of prime importance to prevent ADHD.

#### **2.2 Genetic factors**

*Neurological and Mental Disorders*

children [12].

*2.1.6 Zinc deficiency*

levels (20ng/ml) and those with highest serum ferritin levels (60ng/ml) show no significant difference in severity or frequency of ADHD and comorbid symptoms [4]. In addition, there appears to be an overlap between restless leg syndrome (which is associated with iron deficiency) and ADHD symptom in

The role of zinc in ADHD is also controversial. Several studies have been conducted to find out the role of zinc in the etiology of ADHD. Study by Arnold and colleagues [13] did not show that the zinc alone could improve the ADHD symptoms. In another study zinc was a part of the treatment [14]. In conclusion, zinc is tolerated well in children with ADHD. However, further evidences are required to indicate whether zinc is effective for treating children with ADHD. It is recom-

Prenatal exposure to tobacco smoke is consistently associated with development

Correlation of the Iodine deficiency and ADHD in children is of high interest. Thyroid hormones are necessary for the normal metabolic function and the Iodine is important element in the synthesis and regulation of thyroid hormones. It is well known that Iodine deficiency (ID) can lead to mental retardation although preventable and the most critical period for this is fetal development. Maternal thyroid function and Iodine concentration of infant are strongly correlated and the group of disorders due to disturbances in this correlation are called ID disorders. According to Hope Abel and colleagues [17] maternal ID during pregnancy has direct association with severe ADHD symptoms in offsprings at eight years of age. Although it is not recommended maternal iodine intake in order to avoid ADHD risk in child especially as it is known iodine supplementation in the first trimester is associated

Lead (Pb) has as a neurotoxic effect leading to abnormal behavior in children. There are plenty of studies attempting to detect correlation between exposure to heavy metals and other harmful environmental factors in the pathogenesis of behavioral disorders. In 1991 recommended level of lead in children's blood (BLL) by CDC is set to 10 micrograms of lead per deciliter of blood (μg/dL) and it has not been changed since then. Donzelli et al. [18] performed systematic review of 17 studies assessing the correlation of lead level and ADHD. According to their results there is a direct correlation between low lead level of lead in ADHD children's blood

of ADHD in case-control and cohort studies [16]. Smoking during pregnancy increased the risk of offspring ADHD. The risk of ADHD was greater for children whose mothers were heavy smokers than for those mothers were light smokers. The authors suppose that there can be relationship between maternal smoking and ADHD in children but could not clarify if other confounding risk factors can affect on this causality. Thus it is necessary to perform more studies in order to detect

mended to replicate the randomized well-controlled trials [15].

association between maternal smoking and ADHD in offsprings.

*2.1.7 Prenatal exposure to tobacco smoke*

*2.1.8 Iodine deficiency and children with ADHD*

with an increased health risks

*2.1.9 Lead exposure and ADHD*

**88**

It has been implicated that genetic factors play a critical role in the etiology of ADHD as well as its comorbidities. Based on multiple familial, twin, adoption and single epidemiological studies ADHD is considered as one of the psychiatric disorders which shows the strongest genetic basis. Several twin studies have revealed that concordance in monozygotic (MZ) twins is higher than in dizygotic (DZ) twins with heritability estimates of approximately 75–80%. Large numbers of linkage studies, genome wide association studies (GWAS) and meta-analyses have been conducted and numbers of susceptibility variants, genes and chromosomal regions have been reported to be associated with ADHD. Moreover, number of studies also shows that about one third of ADHD's heritability is due to a polygenic component encompassing many common variants, where each variant individually has small effect but their cumulative effect contributes to the development of the condition. Investigation of copy number variants (CNVs) has also shown that rare insertions or deletions contribute to the part of ADHD's heritability. Recent progress in identifying ADHD susceptibility genes underlines new biological pathways that may have implication for prevention and treatment development.

According to the literature the mean heritability across multiple twin studies of ADHD is 74–80% [19, 20] and it is similar in ADHD males and females [21]. According to one study, where 894 probands with ADHD and their 1135 siblings were studied, there was nine-fold increased risk of ADHD in siblings of ADHD probands compared with siblings of controls. Several adoption studies also indicate that ADHD is greater among the biological relatives of non-adopted ADHD children than adoptive relatives of adopted ADHD children and the risk for ADHD in adoptive relatives is similar to the risk in relatives of control children. Additionally, adoption studies suggest that the familial aggregation of ADHD is defined more by genetic factors rather than common environmental factors. Based on the largest longitudinal study to date on familial aggregation of ADHD, the closer was the relatedness of probands and their relatives the higher was the familial aggregation [20]. Consistently, among full siblings, the familial aggregation did not differ significantly by index person's sex. Moreover, it is expected that genetic factors play more important role in explaining familial aggregation than shared environmental factors [22], given that the familial aggregation is remarkably higher in MZ twins than in DZ twins and similar between DZ twins and nontwin full siblings.

Genetic linkage was the first genome-wide method applied to ADHD. This method looks through the genome to find evidence that a segment of DNA is transmitted with a disorder within families. According to the literature there is no clear-cut evidence about which chromosomal regions are linked to ADHD and so far none of the findings met genome-wide significance, suggesting that common DNA variants having a large effect on ADHD may not exist [23].

Genome-wide association studies (GWAS) scan the entire genome to detect common (frequency more than 1%) DNA variants that have very small etiologic effects. The early GWAS of ADHD did not discover any DNA variants that achieved genome-wide significance. However, recent studies have implicated contribution of some genes with relevant biological roles in ADHD. For example *USP6* is involved in regulation of dopamine levels in the synapses and regulates neurotransmitter homeostasis. Certain variants in *LINC00461* are associated with educational attainment and *ST3GAL3* and *MEF2C* are associated with ID and psychiatric disorders [24]. The GWAS analyses also showed that polygenic effects may also contribute to ADHD's heritability, where multiple common risk variants each with very small effects contribute to the development of the disease as a cumulative effect. The polygenic nature of ADHD was confirmed by evaluating polygenic risk scores and revealing that it predicted ADHD, in a dose-dependent manner. The discovery of a polygenic susceptibility to ADHD does not show which DNA variants comprise the susceptibility, however significant findings implicate that genes involved in biological processes such as synaptic plasticity, catecholamine metabolic processes, G-protein signaling pathways, cell adhesion, neuronal morphogenesis and neuron migration were over-represented in ADHD. Moreover, many of these genes show considerable interactions with genes identified as trending towards significance in GWAS [25].

It has been known for a long time that rare DNA variants can lead to ADHD. Because chromosomal deletions and duplications often delete or duplicate a large segment of DNA which may include part of a gene or even several genes, they often have clear implications for gene functioning. Several studies indicate that there is a greater burden of large, rare CNVs among ADHD patients compared with controls [26]. Despite the fact that deletions and duplications are equivalently overrepresented in ADHD individuals, statistical significance for ADHD is observed only for duplications, as well as in schizophrenia and ASDs [27] Several well-known syndromes and chromosomal abnormalities may be associated with multiple medical and psychiatric problems along with ADHD. Among these are Klinefelter syndrome, Turner syndrome, 22q11 deletion syndrome, fragile-X syndrome, tuberous sclerosis, neurofibromatosis, Williams syndrome, as well as translocations involving *SLC9A9*, duplication of 7p15.2-15.3 and deletion of 15q13. It is noteworthy to mention that such larger chromosomal rearrangements show increased incidence of ADHD along with global developmental delay (GDD), intellectual disability (ID) and ASD [28]. Beside chromosomal abnormalities there is increasing evidence of single-gene contribution to ADHD, including inactivating mutation in *TPH2*, duplication of *CHRNA7* and pathogenic changes in *PARK2*, *FBXO33* and *RNF122* [29]. New technologies like next generation sequencing (NGS) and whole exome sequencing (WES) revealed several novel rare variants in candidate genes, among them *TBC1D9*, *DAGLA*, *QARS*, *CSMD2*, *TRPM2*, and *WDR83*, *NT5DC1*, *SEC23IP*, *PSD*, *ZCCHC4*, and *BDNF* [30].

It is clear that certain DNA variants increase the risk for ADHD. It is not common that only a single genetic alteration may cause ADHD in the absence of other DNA variants. At the same time it is clear that there are no common DNA variants that are necessary and sufficient causes of ADHD. GWAS show that a genetic susceptibility to ADHD encompasses of many common DNA variants, but yet we do not know exactly which variants or how many of them contribute to the polygenic nature. The heritability that cannot be explained by main effects of rare or common variants is likely due to gene-gene and gene-environment interactions.

**91**

*Attention Deficit Hyperactivity Disorder DOI: http://dx.doi.org/10.5772/intechopen.92334*

**2.3 Biological basis**

**2.4 Neurobiology**

key contributor to behavioral adaptation.

The accumulating evidence for ADHD risk factors genes does not exclude the environmental etiological factors which likely work through epigenetic mechanisms, but these yet have barely been studied in ADHD. In the coming years, we can expect breakthroughs in the genetics of ADHD. Unraveling the genetics of ADHD will not be easy, but with rapid development of technologies and with wider application and better interpretation of whole exome and whole genome sequencing (WGS) data the knowledge and significance of various rare and common variants will increase dramatically. Such advances will enable us to understand the etiology of ADHD and

Attention problems manifested in ADHD are due to dysfunction of ventral catecholaminergic pathways projecting to prefrontal and frontal cortex. More than thirty structural and functional neuroimaging studies in ADHD brain have been reported. The main area in the brain implicating in ADHD is prefrontal cortex and its innervations of subcotrical regions such as caudate-putamen, nucleus accumbens, and amygdala. Reduced size of corpus callosum has been detected in some children with ADHD and typically larger corpus callosum in the human female brain may be protective against ADHD. Cerebellum has been implicated in cognition and emotion besides the well-known role in coordination and maintaining body posture, suggesting a possible role contributing to ADHD that is consistent with reports of disorders of fine motor movements in ADHD children. Hippocampus as an important site for memory is also can be considered as possible participant in pathogenesis of ADHD. Structural brain imaging could not confirm the structural abnormalities of hippocampus but functional imaging found reduced cerebral

glucose metabolism in hippocampus in adolescents with ADHD [31].

with severity of symptoms in children with this disorder [35].

The neurotransmitter dopamine has been recognized to play a role in attention and cognition especially executive functioning and reward processing [32]. It is a

**Dopamine** transporter is the most important molecule in the regulation of dopamine signaling in most areas of the brain-is the main target of stimulants like Methylphenidate and also dexamphetamine-drugs for ADHD treatment. These drugs block the dopamine transporter and lead to an increase in dopamine concentration particularly in the parts of the basal ganglia that are highest in the expression of the transporter, the striatum [33]. Positron emission tomography (PET) shows that people with ADHD have more dopamine transporter activity compared with healthy controls [34]. Besides genetic studies reveal that disorders in dopamine signaling could occur due to alteration in dopamine receptors which also has to be seen by PET**.** Meta analyses have shown significant involvement of dopamine transporter protein (DAT) and its gene- *DAT1* gene 3'-regulatory region in a larger group of patients with ADHD suggested association of this set of genes

**Norepinephrine** signaling is related with dopamine system as norepinephrine is a downstream product of metabolism of dopamine. Innervation of the prefrontal cortex by norepinephrine pathways is very important to understand ADHD. Norepinephrine and dopamine signaling are linked in prefrontal cortex thus influencing each other in organizing prefrontal cortex performance in cognitive tasks [36]. The role of norepinephrine can be explained by the fact that

set forth opportunities to diagnose and treat the disorder.

#### *Attention Deficit Hyperactivity Disorder DOI: http://dx.doi.org/10.5772/intechopen.92334*

The accumulating evidence for ADHD risk factors genes does not exclude the environmental etiological factors which likely work through epigenetic mechanisms, but these yet have barely been studied in ADHD. In the coming years, we can expect breakthroughs in the genetics of ADHD. Unraveling the genetics of ADHD will not be easy, but with rapid development of technologies and with wider application and better interpretation of whole exome and whole genome sequencing (WGS) data the knowledge and significance of various rare and common variants will increase dramatically. Such advances will enable us to understand the etiology of ADHD and set forth opportunities to diagnose and treat the disorder.

#### **2.3 Biological basis**

*Neurological and Mental Disorders*

clear-cut evidence about which chromosomal regions are linked to ADHD and so far none of the findings met genome-wide significance, suggesting that common

Genome-wide association studies (GWAS) scan the entire genome to detect common (frequency more than 1%) DNA variants that have very small etiologic effects. The early GWAS of ADHD did not discover any DNA variants that achieved genome-wide significance. However, recent studies have implicated contribution of some genes with relevant biological roles in ADHD. For example *USP6* is involved in regulation of dopamine levels in the synapses and regulates neurotransmitter homeostasis. Certain variants in *LINC00461* are associated with educational attainment and *ST3GAL3* and *MEF2C* are associated with ID and psychiatric disorders [24]. The GWAS analyses also showed that polygenic effects may also contribute to ADHD's heritability, where multiple common risk variants each with very small effects contribute to the development of the disease as a cumulative effect. The polygenic nature of ADHD was confirmed by evaluating polygenic risk scores and revealing that it predicted ADHD, in a dose-dependent manner. The discovery of a polygenic susceptibility to ADHD does not show which DNA variants comprise the susceptibility, however significant findings implicate that genes involved in biological processes such as synaptic plasticity, catecholamine metabolic processes, G-protein signaling pathways, cell adhesion, neuronal morphogenesis and neuron migration were over-represented in ADHD. Moreover, many of these genes show considerable interactions with genes identified as trending towards significance in GWAS [25]. It has been known for a long time that rare DNA variants can lead to ADHD. Because chromosomal deletions and duplications often delete or duplicate a large segment of DNA which may include part of a gene or even several genes, they often have clear implications for gene functioning. Several studies indicate that there is a greater burden of large, rare CNVs among ADHD patients compared with controls [26]. Despite the fact that deletions and duplications are equivalently overrepresented in ADHD individuals, statistical significance for ADHD is observed only for duplications, as well as in schizophrenia and ASDs [27] Several well-known syndromes and chromosomal abnormalities may be associated with multiple medical and psychiatric problems along with ADHD. Among these are Klinefelter syndrome, Turner syndrome, 22q11 deletion syndrome, fragile-X syndrome, tuberous sclerosis, neurofibromatosis, Williams syndrome, as well as translocations involving *SLC9A9*, duplication of 7p15.2-15.3 and deletion of 15q13. It is noteworthy to mention that such larger chromosomal rearrangements show increased incidence of ADHD along with global developmental delay (GDD), intellectual disability (ID) and ASD [28]. Beside chromosomal abnormalities there is increasing evidence of single-gene contribution to ADHD, including inactivating mutation in *TPH2*, duplication of *CHRNA7* and pathogenic changes in *PARK2*, *FBXO33* and *RNF122* [29]. New technologies like next generation sequencing (NGS) and whole exome sequencing (WES) revealed several novel rare variants in candidate genes, among them *TBC1D9*, *DAGLA*, *QARS*, *CSMD2*, *TRPM2*, and *WDR83*, *NT5DC1*, *SEC23IP*,

It is clear that certain DNA variants increase the risk for ADHD. It is not common that only a single genetic alteration may cause ADHD in the absence of other DNA variants. At the same time it is clear that there are no common DNA variants that are necessary and sufficient causes of ADHD. GWAS show that a genetic susceptibility to ADHD encompasses of many common DNA variants, but yet we do not know exactly which variants or how many of them contribute to the polygenic nature. The heritability that cannot be explained by main effects of rare or common variants is likely due to gene-gene and gene-environment interactions.

DNA variants having a large effect on ADHD may not exist [23].

**90**

*PSD*, *ZCCHC4*, and *BDNF* [30].

Attention problems manifested in ADHD are due to dysfunction of ventral catecholaminergic pathways projecting to prefrontal and frontal cortex. More than thirty structural and functional neuroimaging studies in ADHD brain have been reported. The main area in the brain implicating in ADHD is prefrontal cortex and its innervations of subcotrical regions such as caudate-putamen, nucleus accumbens, and amygdala. Reduced size of corpus callosum has been detected in some children with ADHD and typically larger corpus callosum in the human female brain may be protective against ADHD. Cerebellum has been implicated in cognition and emotion besides the well-known role in coordination and maintaining body posture, suggesting a possible role contributing to ADHD that is consistent with reports of disorders of fine motor movements in ADHD children. Hippocampus as an important site for memory is also can be considered as possible participant in pathogenesis of ADHD. Structural brain imaging could not confirm the structural abnormalities of hippocampus but functional imaging found reduced cerebral glucose metabolism in hippocampus in adolescents with ADHD [31].

#### **2.4 Neurobiology**

The neurotransmitter dopamine has been recognized to play a role in attention and cognition especially executive functioning and reward processing [32]. It is a key contributor to behavioral adaptation.

**Dopamine** transporter is the most important molecule in the regulation of dopamine signaling in most areas of the brain-is the main target of stimulants like Methylphenidate and also dexamphetamine-drugs for ADHD treatment. These drugs block the dopamine transporter and lead to an increase in dopamine concentration particularly in the parts of the basal ganglia that are highest in the expression of the transporter, the striatum [33]. Positron emission tomography (PET) shows that people with ADHD have more dopamine transporter activity compared with healthy controls [34]. Besides genetic studies reveal that disorders in dopamine signaling could occur due to alteration in dopamine receptors which also has to be seen by PET**.** Meta analyses have shown significant involvement of dopamine transporter protein (DAT) and its gene- *DAT1* gene 3'-regulatory region in a larger group of patients with ADHD suggested association of this set of genes with severity of symptoms in children with this disorder [35].

**Norepinephrine** signaling is related with dopamine system as norepinephrine is a downstream product of metabolism of dopamine. Innervation of the prefrontal cortex by norepinephrine pathways is very important to understand ADHD. Norepinephrine and dopamine signaling are linked in prefrontal cortex thus influencing each other in organizing prefrontal cortex performance in cognitive tasks [36]. The role of norepinephrine can be explained by the fact that

Methylphenidate and dexamphetamine inhibit the norepinephrine transporter together with DAT [36]. It is proved that altering norepinephrine signaling can improve ADHD symptoms but there is lack of evidence to link it with ADHD neurobiology [37].

**Serotonin** has been studied closely in animal models of ADHD. It was found that serotonin-potentiating agents can inhibit effects on motor hyperactivity [38]. Serotonin neurotransmission may modulate the severity of ADHD symptoms rather than being related to ADHD onset [39]. Other position means that it may be the comorbidity especially with conduct disorder, obsessive compulsive disorder and aggression and mood disorders rather than the core symptoms of ADHD which is influenced by serotonin [40]. Although serotonin receptor gene HTR1B and gene encoding the serotonin transporter (SLC6A4, 5-HTT, SERT) have been implicated in ADHD the effect of environment on ADHD symptoms may explain some of the observed inconsistency across studies especially the effect of stress on ADHD seems to be influences by genetic variation in the serotonin transporter gene [37]. In experimental models serotonin may be critically involved in mediating the behavior inhibiting effects of stimulants [41]. All these suggest that serotonin may play a role in pathogenesis in some circumstances but do not establish serotonin-enhancing drugs as useful treatment.

#### **2.5 Main cognitive finding associated with ADHD**

Cognitive impairments in a variety of domains have been found in ADHD as well as impairment in overall intellectual function. Deficit in executive function are common in children with ADHD. Executive functioning are the group of cognitive processes which are responsible for purposeful, goal-directed and problem solving behavior. A meta-analysis of children and adolescents with ADHD showed impairments in several aspects of executive functioning.

#### *2.5.1 Intellectual function*

Visuospatial abilities (block-design subtest) and general knowledge (vocabulary subtest) on the Wechsler Intelligence Scale for Children-III (WISC-III) have to be changed in children with ADHD compared with healthy controls. Children with predominantly inattention without hyperactivity have disorders of visuospatial abilities. In contrast, the ADHD group predominantly with hyperactivity have the same evidence in visuospatial abilities or vocabulary as their healthy teens [1].

#### *2.5.2 Language*

Language can be impaired in ADHD children. A meta-analysis of children with ADHD found impairments in verbal fluency especially in phenomic fluency compared with semantic fluency [42]. Sometimes in adolescents with ADHD the disorders with object naming also can be revealed [43].

#### *2.5.3 Learning and memory*

Working memory is considered to be the most central executive function. Working memory disorders are quite variable in ADHD children. Mainly working memory is impaired and becomes the core feature of ADHD with the strongest impairments reported for the spatial domain of working memory as opposed to the verbal or phonological domain [44]. Visuospatial working memory is provided

**93**

inhibition.

*Attention Deficit Hyperactivity Disorder DOI: http://dx.doi.org/10.5772/intechopen.92334*

impairments associated with ADHD [1].

predominantly by inferior and superior parietal areas together with dorsolateral prefrontal regions [45–48, 49], Cerebellum also can be activated during visuospatial working memory tasks [50, 51]. Learning disorders also can be seen in ADHD children. Children with learning disorders and ADHD have more severe learning problems than children who have only ADHD. Learning disorder and attention problems are on continuum, are interrelated and usually coexist [52]. Comorbidity with learning disorders is a modifying factor in the health related quality of life of children with ADHD [4]**.** It was found that 5% of children have ADHD without learning disorder, 5% have learning disorder without ADHD and 4% have both conditions. Boys are more likely those girls to have each diagnosis. In 2006 approximately 4.5 million school aged children have ever been diagnosed with ADHD and 4.6 million children with learning disorders [53, 54]. Thus ADHD associated learning and language disabilities are important comorbidities. Neurological assessment is recommended in children with learning disorder who fail to make academic progress despite appropriate educational intervention. The adolescents with ADHD experienced written expression impairment (17.2–22.4%) at a similar rate to reading impairment (17.0–24.3%) and at a slightly lower rate than mathematics impairment (24.7–36.3%) [4]. Dyslexia occurs in 5–10% of school children; it overlaps with ADHD and shows similar genetic characteristics but different brain localizations [4]. Another part of executive disorder is **impairment of response inhibition**. Response inhibition specifically is the ability to control oneself by suppressing or altering intended actions that are no longer required or appropriate. Thus normal response inhibition enables people to adapt properly to changes in the environment. Impaired response inhibition is central to theoretical models of ADHD [55]. According to Barkley [56] response inhibition is a central deficit of ADHD affecting top-down multiple executive functions including working memory, self-regulation, internalization of speech and reconstitution. A large community study showed that ADHD symptoms in children and adolescents are associated with worse response inhibition and slower response latency [57]. Response inhibition deficit in ADHD is proved by magnetic resonance imaging (MRI). Healthy children activate core network of brain regions involved in response inhibition including a frontal-striatal and frontal-parietal network. Children and adolescents with ADHD show decreased activation in frontal, medial and parietal regions during inhibition compared with healthy teens [58].

Willcut et al [59] found impairments in other domains of executive functioning like planning and vigilance in addition to response inhibition and working memory. They noted that while impairment in executive functioning are closely associated with ADHD such deficits do not explain all of the cognitive impairments observed in ADHD suggesting that executive dysfunction is only one part of the cognitive

Another frequently described comorbidity is disorder of **cognitive flexibility**. It is clear that ADHD children are more likely to respond with overlearned and automatic responses when faced with problem-solving situations or context that demand the thoughtful formation of strategies and the flexible shifting of thought [60]. Barkley et al [60] suggested that **behavioral or verbal creativity** can be impaired in children with ADHD as a consequence of their poor verbal

**Decision making** can be considered as important part of executive functioning. ADHD children and adolescents have specific decision making deficits. ADHD people have no impaired learning rate per se as it was suggested before [61]. ADHD individuals exhibit less comprehensive decision process and more frequent exploration activity compared with controls. This feature could occur due to impaired reward prediction processing in the medial prefrontal cortex which is considered as an integrative hub in the brain responsible for decision making and learning. The deficit

#### *Attention Deficit Hyperactivity Disorder DOI: http://dx.doi.org/10.5772/intechopen.92334*

*Neurological and Mental Disorders*

neurobiology [37].

drugs as useful treatment.

*2.5.1 Intellectual function*

teens [1].

*2.5.2 Language*

*2.5.3 Learning and memory*

**2.5 Main cognitive finding associated with ADHD**

ments in several aspects of executive functioning.

disorders with object naming also can be revealed [43].

Methylphenidate and dexamphetamine inhibit the norepinephrine transporter together with DAT [36]. It is proved that altering norepinephrine signaling can improve ADHD symptoms but there is lack of evidence to link it with ADHD

**Serotonin** has been studied closely in animal models of ADHD. It was found that serotonin-potentiating agents can inhibit effects on motor hyperactivity [38]. Serotonin neurotransmission may modulate the severity of ADHD symptoms rather than being related to ADHD onset [39]. Other position means that it may be the comorbidity especially with conduct disorder, obsessive compulsive disorder and aggression and mood disorders rather than the core symptoms of ADHD which is influenced by serotonin [40]. Although serotonin receptor gene HTR1B and gene encoding the serotonin transporter (SLC6A4, 5-HTT, SERT) have been implicated in ADHD the effect of environment on ADHD symptoms may explain some of the observed inconsistency across studies especially the effect of stress on ADHD seems to be influences by genetic variation in the serotonin transporter gene [37]. In experimental models serotonin may be critically involved in mediating the behavior inhibiting effects of stimulants [41]. All these suggest that serotonin may play a role in pathogenesis in some circumstances but do not establish serotonin-enhancing

Cognitive impairments in a variety of domains have been found in ADHD as well as impairment in overall intellectual function. Deficit in executive function are common in children with ADHD. Executive functioning are the group of cognitive processes which are responsible for purposeful, goal-directed and problem solving behavior. A meta-analysis of children and adolescents with ADHD showed impair-

Visuospatial abilities (block-design subtest) and general knowledge (vocabulary subtest) on the Wechsler Intelligence Scale for Children-III (WISC-III) have to be changed in children with ADHD compared with healthy controls. Children with predominantly inattention without hyperactivity have disorders of visuospatial abilities. In contrast, the ADHD group predominantly with hyperactivity have the same evidence in visuospatial abilities or vocabulary as their healthy

Language can be impaired in ADHD children. A meta-analysis of children with ADHD found impairments in verbal fluency especially in phenomic fluency compared with semantic fluency [42]. Sometimes in adolescents with ADHD the

Working memory is considered to be the most central executive function. Working memory disorders are quite variable in ADHD children. Mainly working memory is impaired and becomes the core feature of ADHD with the strongest impairments reported for the spatial domain of working memory as opposed to the verbal or phonological domain [44]. Visuospatial working memory is provided

**92**

predominantly by inferior and superior parietal areas together with dorsolateral prefrontal regions [45–48, 49], Cerebellum also can be activated during visuospatial working memory tasks [50, 51]. Learning disorders also can be seen in ADHD children. Children with learning disorders and ADHD have more severe learning problems than children who have only ADHD. Learning disorder and attention problems are on continuum, are interrelated and usually coexist [52]. Comorbidity with learning disorders is a modifying factor in the health related quality of life of children with ADHD [4]**.** It was found that 5% of children have ADHD without learning disorder, 5% have learning disorder without ADHD and 4% have both conditions. Boys are more likely those girls to have each diagnosis. In 2006 approximately 4.5 million school aged children have ever been diagnosed with ADHD and 4.6 million children with learning disorders [53, 54]. Thus ADHD associated learning and language disabilities are important comorbidities. Neurological assessment is recommended in children with learning disorder who fail to make academic progress despite appropriate educational intervention. The adolescents with ADHD experienced written expression impairment (17.2–22.4%) at a similar rate to reading impairment (17.0–24.3%) and at a slightly lower rate than mathematics impairment (24.7–36.3%) [4]. Dyslexia occurs in 5–10% of school children; it overlaps with ADHD and shows similar genetic characteristics but different brain localizations [4].

Another part of executive disorder is **impairment of response inhibition**. Response inhibition specifically is the ability to control oneself by suppressing or altering intended actions that are no longer required or appropriate. Thus normal response inhibition enables people to adapt properly to changes in the environment. Impaired response inhibition is central to theoretical models of ADHD [55]. According to Barkley [56] response inhibition is a central deficit of ADHD affecting top-down multiple executive functions including working memory, self-regulation, internalization of speech and reconstitution. A large community study showed that ADHD symptoms in children and adolescents are associated with worse response inhibition and slower response latency [57]. Response inhibition deficit in ADHD is proved by magnetic resonance imaging (MRI). Healthy children activate core network of brain regions involved in response inhibition including a frontal-striatal and frontal-parietal network. Children and adolescents with ADHD show decreased activation in frontal, medial and parietal regions during inhibition compared with healthy teens [58].

Willcut et al [59] found impairments in other domains of executive functioning like planning and vigilance in addition to response inhibition and working memory. They noted that while impairment in executive functioning are closely associated with ADHD such deficits do not explain all of the cognitive impairments observed in ADHD suggesting that executive dysfunction is only one part of the cognitive impairments associated with ADHD [1].

Another frequently described comorbidity is disorder of **cognitive flexibility**. It is clear that ADHD children are more likely to respond with overlearned and automatic responses when faced with problem-solving situations or context that demand the thoughtful formation of strategies and the flexible shifting of thought [60]. Barkley et al [60] suggested that **behavioral or verbal creativity** can be impaired in children with ADHD as a consequence of their poor verbal inhibition.

**Decision making** can be considered as important part of executive functioning. ADHD children and adolescents have specific decision making deficits. ADHD people have no impaired learning rate per se as it was suggested before [61]. ADHD individuals exhibit less comprehensive decision process and more frequent exploration activity compared with controls. This feature could occur due to impaired reward prediction processing in the medial prefrontal cortex which is considered as an integrative hub in the brain responsible for decision making and learning. The deficit

in decision making in adolescents and adults was similar in severity to the deficits in attention in individuals with ADHD [62].

**Reward sensitivity** is an evolutionary important part of executive functioning. Rewards are accompanied by positive feeling and they reinforce reward linked behavior [37]. This process of reinforcing behavior forms the basic principle of learning [63]. Individuals with highly sensitive to rewards shows maladaptive behavior like risky behavior and addictions [37]. Theoretical model of ADHD consider altered reward sensitivity as a main cognitive mechanism [64], Children and adolescents with ADHD are performing risky and suboptimal decisions. ADHD population with impaired reward processing and impulsivity show increased activations in the anterior cingulated and anterior frontal cortex as well as in orbitofrontal cortex and nucleus accumbens [65]. Other studies in ADHD adolescents have reported less triatal activation during reward compared with healthy teens [66].

Specific motor deficits may be found in children with ADHD but like other measures of neuropsychological functioning, such difficulties are not specific predictors of the presence of ADHD [67]. Commonly difficulties can be seen in coordination. When both attention and coordination deficits co occur in conjunction with perceptual problems the term "deficit in attention, motor control and perception (DAMP)" can be applied [68]. The concept of DAMP is fairly controversial and the label is more widely used in Scandinavian countries than in UK or USA.

#### *2.5.4 Treatment*

The most important part of any intervention plan for a child with ADHD is the physical, behavioral and neuromotor/neuropsychological examination followed by oral and written information of parents, child, teacher about the type of problems the child exhibits and their possible etiology.

Special education- many children with ADHD need special educational measures. In order to acquire some academic skill some children will need individualized education lasting for several hours every day [69].

The two most commonly used behavioral interventions are:

1.Creating and maintaining a well structured environment to compensate for poor stimulus control

#### 2.Parent training

It is very important to organize the school environment with minimal distractions and with seating that is somewhat isolated and close to the front of the classroom in front of the teacher. Common triggers that can easily distract child are instructional demand, withholding of a desired object or activity and withdrawal of parental attention.

Behavior therapy can be considered as the best method for treatment of ADHD children and youths regarding the improvement of behavior, self-control and selfesteem. It is recommended for parents of children younger than 12 years of age to start training in behavior therapy. For children less than 6 years of age it is better to start behavior therapy before prescribing ADHD medicine. Behavior therapy helps parents to learn skills and strategies to improve their children academic achievement at school, behavior at home and improve their social interaction. Although studying and practicing of behavioral therapy needs time and effort from parents the sequence benefit for the child and family could last for a long period of time.

**95**

*Attention Deficit Hyperactivity Disorder DOI: http://dx.doi.org/10.5772/intechopen.92334*

children with ADHD.

ADHD children

activity and to provide support

**3. What can parents expect?**

is needed to change strategy plans.

Parent training in behavior management is also known as parent behavior therapy**,** behavioral parent training or just parent training**.** If possible, families should look for a therapist who focuses on training parents. Some therapists will have training or certification in a parent training program that has been proven to work in young

The following are the main goals for therapist while working with parents:

• Parents need to be aware how to interact and communicate with their

• Therapists needs to teach parents practical skill how to work with their child

• Therapist needs to meet with family members to observe the progress in their

• Therapist needs to re-evaluate treatment strategy and method and in case if it

It is recommended for parents to attend eight or more session with a therapist who can work with groups of parents or only with one family. It is necessary to work on a regular basis in order to monitor progress of parents and to change the working strategy in case if it needed. Parents' role in treatment planning and implementing is extremely crucial as they can have greatest influence on their child's behavior. There are many treatment options for therapist for working with ADHD children. Play therapy and talk therapy could be considered as one of the best treatment option. Talk therapy uses verbal communication between ADHD child and therapist in order to improve child's emotional state. Although behavioral therapy needs

Successful treatment for ADHD means both behavior therapy and medication. For children 6 years of age and older, the American Academy of Pediatrics (AAP) recommends both behavior therapy and medication. For children under 6 years of

**Medication** should be start with one of the stimulants. Both d-amphetamine (10–40 mg/day given in 2–5 dosed with 3-hour intervals in order to last through the school day) and methylphenidate (20–80 mg/day given in the same fashion) have been shown to be effective for improvement of hyperactivity, concentration problems, learning disorders and other comorbidities. Both drugs have minimal side effects. "Long-acting," "slow-release" preparations of methylphenidate have also been shown to have good effects and they can sometimes be dosed (18–54 mg/ day or 10–60 mg/day depending on preparation) only once daily. Relatively common side effects are loss of appetite, a tendency to increase the likelihood of tics and stereotypies, reduced mimicry and hallucinations. They can easily stop with drug discontinuation. There are some evidence that long-term methylphenidate treatment should be as effective as the combination of methylphenidate and behavioral therapy and considerably more effective than behavioral therapy alone [72]. Combination of methylphenidate and behavioral therapy is the best choice for improving both ADHD

time and effort its effect could last for long period of time [70].

age behavior therapy is recommended as the first line of treatment [71].

• Parents need to know how to make positive reinforcement, how to construct and control child's behavior. Thus they need to acquire these skills and strategies.

#### *Attention Deficit Hyperactivity Disorder DOI: http://dx.doi.org/10.5772/intechopen.92334*

*Neurological and Mental Disorders*

teens [66].

*2.5.4 Treatment*

attention in individuals with ADHD [62].

the child exhibits and their possible etiology.

poor stimulus control

2.Parent training

parental attention.

ized education lasting for several hours every day [69].

The two most commonly used behavioral interventions are:

in decision making in adolescents and adults was similar in severity to the deficits in

Rewards are accompanied by positive feeling and they reinforce reward linked behavior [37]. This process of reinforcing behavior forms the basic principle of learning [63]. Individuals with highly sensitive to rewards shows maladaptive behavior like risky behavior and addictions [37]. Theoretical model of ADHD consider altered reward sensitivity as a main cognitive mechanism [64], Children and adolescents with ADHD are performing risky and suboptimal decisions. ADHD population with impaired reward processing and impulsivity show increased activations in the anterior cingulated and anterior frontal cortex as well as in orbitofrontal cortex and nucleus accumbens [65]. Other studies in ADHD adolescents have reported less triatal activation during reward compared with healthy

**Reward sensitivity** is an evolutionary important part of executive functioning.

Specific motor deficits may be found in children with ADHD but like other measures of neuropsychological functioning, such difficulties are not specific predictors of the presence of ADHD [67]. Commonly difficulties can be seen in coordination. When both attention and coordination deficits co occur in conjunction with perceptual problems the term "deficit in attention, motor control and perception (DAMP)" can be applied [68]. The concept of DAMP is fairly controversial and the

The most important part of any intervention plan for a child with ADHD is the physical, behavioral and neuromotor/neuropsychological examination followed by oral and written information of parents, child, teacher about the type of problems

Special education- many children with ADHD need special educational measures. In order to acquire some academic skill some children will need individual-

1.Creating and maintaining a well structured environment to compensate for

It is very important to organize the school environment with minimal distrac-

Behavior therapy can be considered as the best method for treatment of ADHD children and youths regarding the improvement of behavior, self-control and selfesteem. It is recommended for parents of children younger than 12 years of age to start training in behavior therapy. For children less than 6 years of age it is better to start behavior therapy before prescribing ADHD medicine. Behavior therapy helps parents to learn skills and strategies to improve their children academic achievement at school, behavior at home and improve their social interaction. Although studying and practicing of behavioral therapy needs time and effort from parents the sequence benefit for the child and family could last for a long period of time.

tions and with seating that is somewhat isolated and close to the front of the classroom in front of the teacher. Common triggers that can easily distract child are instructional demand, withholding of a desired object or activity and withdrawal of

label is more widely used in Scandinavian countries than in UK or USA.

**94**

Parent training in behavior management is also known as parent behavior therapy**,** behavioral parent training or just parent training**.** If possible, families should look for a therapist who focuses on training parents. Some therapists will have training or certification in a parent training program that has been proven to work in young children with ADHD.

The following are the main goals for therapist while working with parents:


#### **3. What can parents expect?**

It is recommended for parents to attend eight or more session with a therapist who can work with groups of parents or only with one family. It is necessary to work on a regular basis in order to monitor progress of parents and to change the working strategy in case if it needed. Parents' role in treatment planning and implementing is extremely crucial as they can have greatest influence on their child's behavior. There are many treatment options for therapist for working with ADHD children. Play therapy and talk therapy could be considered as one of the best treatment option. Talk therapy uses verbal communication between ADHD child and therapist in order to improve child's emotional state. Although behavioral therapy needs time and effort its effect could last for long period of time [70].

Successful treatment for ADHD means both behavior therapy and medication. For children 6 years of age and older, the American Academy of Pediatrics (AAP) recommends both behavior therapy and medication. For children under 6 years of age behavior therapy is recommended as the first line of treatment [71].

**Medication** should be start with one of the stimulants. Both d-amphetamine (10–40 mg/day given in 2–5 dosed with 3-hour intervals in order to last through the school day) and methylphenidate (20–80 mg/day given in the same fashion) have been shown to be effective for improvement of hyperactivity, concentration problems, learning disorders and other comorbidities. Both drugs have minimal side effects. "Long-acting," "slow-release" preparations of methylphenidate have also been shown to have good effects and they can sometimes be dosed (18–54 mg/ day or 10–60 mg/day depending on preparation) only once daily. Relatively common side effects are loss of appetite, a tendency to increase the likelihood of tics and stereotypies, reduced mimicry and hallucinations. They can easily stop with drug discontinuation. There are some evidence that long-term methylphenidate treatment should be as effective as the combination of methylphenidate and behavioral therapy and considerably more effective than behavioral therapy alone [72]. Combination of methylphenidate and behavioral therapy is the best choice for improving both ADHD

#### *Neurological and Mental Disorders*

and ADHD plus depression and anxiety. Doctor should be careful for monitoring the child's height, drug dependency while treating the child with stimulants for long term period although they appear rare compared with tricyclic antidepressants.

The noradrenergic reuptake inhibitor atomoxetine has also been shown to have beneficial effects on ADHD as a second line treatment in children with ADHD. Although clinical effects appear to be less effective than with methylphenidate but the advantage if this medication is that it can be used only once daily and it is not stimulant [69].

### **Author details**

Sophia Bakhtadze1 \*, Tinatin Tkemeladze2 and Tinatin Kutubidze3

1 Department of Paediatric Neurology, Tbilisi State Medical University, Tbilisi, Georgia

2 Department of Molecular and Medical Genetics, Tbilisi State Medical University, Tbilisi, Georgia

3 Department of Child and Adolescent Medicine, Tbilisi State Medical University, Tbilisi, Georgia

\*Address all correspondence to: sophiabakhtadze@yahoo.com

© 2020 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

**97**

*Attention Deficit Hyperactivity Disorder DOI: http://dx.doi.org/10.5772/intechopen.92334*

[1] Hedges D et al. The Brain at Risk. Springer Nature Switzerland AG: Springer International Publisher; 2019 [11] Wolraich M, Wilson D, White J. The effect of sugar on behavior or cognition in children. A meta-analysis. JAMA.

Lecendreux M, Arnulf I, Mouren MC, Darra F, et al. Restless legs syndrome and attention-deficit/hyperactivity disorder: A review of the literature.

[14] Akhondzadeh S, Mohammadi MR, Khademi M. Zinc sulfate as an adjunct to methylphenidate for the treatment of attention deficit hyperactivity disorder in children: A double blind and randomized trial. BMC Psychiatry.

[15] Ghanizadeh A, Berk M. Zinc for treating children and adolescents with attention-deficit hyperactivity disorder: A systematic review of randomized controlled clinical trials. European Journal of Clinical Nutrition.

[16] Huang L, Wang Y, Zhang L, et al. Maternal smoking and attentiondeficit/hyperactivity disorder in

offspring: A meta-analysis. Pediatrician.

[17] Hope Abel M, Ystrom E, et al. Maternal Iodine intake and offspring attention-deficit/hyperactivity disorder: Results for a large prospective cohort study. Nutrients. 2017;**9**(11):1239

1995;**274**(20):1617-1621

[12] Cortese S, Konofal E,

Sleep. 2005;**28**(8):1007

2004;**4**:9

2013;**67**:122-124

2018;**141**(1):piie20172465

[18] Gonzelli G, Carducci A, Llopis-Gonzalez A, Verani M,

[13] Arnold LE, Disilvestro RA, Bozzolo D, Bozzolo H, Crowl L, Fernandez S, et al. Zinc for attentiondeficit/hyperactivity disorder: Placebocontrolled double-blind pilot trial alone and combined with amphetamine. Journal of Child and Adolescent Psychopharmacology. 2011;**21**:1-19

[2] Danielson ML, Bitsko RH, Ghandour RM, et al. Prevalence of parent-reported ADHD diagnosis and associated treatment among US children and adolescents, 2016. Journal of Clinical Child and Adolescent Psychology. 2018;**47**(2):199-212

[3] Thomas R et al. Prevalence of

[4] Millichap G. Attention Deficit Hyperactivity Disorder Handbook: A Physician's Guide to ADHD. 2nd ed. New York: Springer-Verlag; 2010

[5] Still G. Some abnormal psychical conditions in children. Lancet. 1902;**1**:

[6] Stewart M. Hyperactive children. Scientific American. 1970;**222**:94-98

[7] Psychiatric Association (APA). Diagnostic American and Statistical Manual of Mental Disorders. 4th ed.

[8] Psychiatric Association (APA). Diagnostic American and Statistical Manual of Mental Disorders. 5th ed.

[9] Schab D, Trinh NH. Do artificial food colors promote hyperactivity in children with hyperactive syndromes? A meta-analysis of double-blind placebo-controlled trials. Journal of Developmental and Behavioral

Washington, DC: APA; 1994

Washington, DC: APA; 2013

Pediatrics. 2004;**25**(6):423

[10] Krummel DA, Seligson FH, Guthrie HA. Hyperactivity: is candy causal? Critical Revue of Food Science

and Nutrition. 1996;**36**(1-2):31

1008-1012

attention-deficit/hyperactivity disorder: A systematic review and meta-analysis. Pediatrics. 2015;**135**(4):e994-e1001

**References**

*Attention Deficit Hyperactivity Disorder DOI: http://dx.doi.org/10.5772/intechopen.92334*

#### **References**

*Neurological and Mental Disorders*

**96**

**Author details**

Sophia Bakhtadze1

Tbilisi, Georgia

Tbilisi, Georgia

Georgia

\*, Tinatin Tkemeladze2

\*Address all correspondence to: sophiabakhtadze@yahoo.com

provided the original work is properly cited.

1 Department of Paediatric Neurology, Tbilisi State Medical University, Tbilisi,

2 Department of Molecular and Medical Genetics, Tbilisi State Medical University,

and ADHD plus depression and anxiety. Doctor should be careful for monitoring the child's height, drug dependency while treating the child with stimulants for long term

The noradrenergic reuptake inhibitor atomoxetine has also been shown to have beneficial effects on ADHD as a second line treatment in children with ADHD. Although clinical effects appear to be less effective than with methylphenidate but the advantage if this medication is that it can be used only once daily and it is not stimulant [69].

period although they appear rare compared with tricyclic antidepressants.

3 Department of Child and Adolescent Medicine, Tbilisi State Medical University,

© 2020 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

and Tinatin Kutubidze3

[1] Hedges D et al. The Brain at Risk. Springer Nature Switzerland AG: Springer International Publisher; 2019

[2] Danielson ML, Bitsko RH, Ghandour RM, et al. Prevalence of parent-reported ADHD diagnosis and associated treatment among US children and adolescents, 2016. Journal of Clinical Child and Adolescent Psychology. 2018;**47**(2):199-212

[3] Thomas R et al. Prevalence of attention-deficit/hyperactivity disorder: A systematic review and meta-analysis. Pediatrics. 2015;**135**(4):e994-e1001

[4] Millichap G. Attention Deficit Hyperactivity Disorder Handbook: A Physician's Guide to ADHD. 2nd ed. New York: Springer-Verlag; 2010

[5] Still G. Some abnormal psychical conditions in children. Lancet. 1902;**1**: 1008-1012

[6] Stewart M. Hyperactive children. Scientific American. 1970;**222**:94-98

[7] Psychiatric Association (APA). Diagnostic American and Statistical Manual of Mental Disorders. 4th ed. Washington, DC: APA; 1994

[8] Psychiatric Association (APA). Diagnostic American and Statistical Manual of Mental Disorders. 5th ed. Washington, DC: APA; 2013

[9] Schab D, Trinh NH. Do artificial food colors promote hyperactivity in children with hyperactive syndromes? A meta-analysis of double-blind placebo-controlled trials. Journal of Developmental and Behavioral Pediatrics. 2004;**25**(6):423

[10] Krummel DA, Seligson FH, Guthrie HA. Hyperactivity: is candy causal? Critical Revue of Food Science and Nutrition. 1996;**36**(1-2):31

[11] Wolraich M, Wilson D, White J. The effect of sugar on behavior or cognition in children. A meta-analysis. JAMA. 1995;**274**(20):1617-1621

[12] Cortese S, Konofal E, Lecendreux M, Arnulf I, Mouren MC, Darra F, et al. Restless legs syndrome and attention-deficit/hyperactivity disorder: A review of the literature. Sleep. 2005;**28**(8):1007

[13] Arnold LE, Disilvestro RA, Bozzolo D, Bozzolo H, Crowl L, Fernandez S, et al. Zinc for attentiondeficit/hyperactivity disorder: Placebocontrolled double-blind pilot trial alone and combined with amphetamine. Journal of Child and Adolescent Psychopharmacology. 2011;**21**:1-19

[14] Akhondzadeh S, Mohammadi MR, Khademi M. Zinc sulfate as an adjunct to methylphenidate for the treatment of attention deficit hyperactivity disorder in children: A double blind and randomized trial. BMC Psychiatry. 2004;**4**:9

[15] Ghanizadeh A, Berk M. Zinc for treating children and adolescents with attention-deficit hyperactivity disorder: A systematic review of randomized controlled clinical trials. European Journal of Clinical Nutrition. 2013;**67**:122-124

[16] Huang L, Wang Y, Zhang L, et al. Maternal smoking and attentiondeficit/hyperactivity disorder in offspring: A meta-analysis. Pediatrician. 2018;**141**(1):piie20172465

[17] Hope Abel M, Ystrom E, et al. Maternal Iodine intake and offspring attention-deficit/hyperactivity disorder: Results for a large prospective cohort study. Nutrients. 2017;**9**(11):1239

[18] Gonzelli G, Carducci A, Llopis-Gonzalez A, Verani M, Llopis-Morales A, Cioni L, et al. The association between lead and attentiondeficit/hyperactivity disorder: A systematic review. Journal of Environmental Research and Public Health. 2019;**16**(3):piiE382

[19] Faraone S, Larsson H. Genetics of attention deficit hyperactivity disorder. Molecular Psychiatry. 2019;**24**(4): 562-575

[20] Chen Q, Brikell I, Lichtenstein P, Serlachius E, Kuja-Halkola R, Sandin S, et al. Familial aggregation of attentiondeficit/hyperactivity disorder. Journal of Child Psychology and Psychiatry. 2017;**58**:231-239

[21] Larsson H, Lichtenstein P, Larsson JO.Genetic contributions to the development of ADHD subtypes from childhood to adolescence. Journal of the American Academy of Child and Adolescent Psychiatry. 2006;**45**:973-981

[22] Lee SH, Ripke S, Neale BM, Faraone SV, Purcell SM, Perlis RH, et al. Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs. Nature Genetics. 2013;**45**:984-994

[23] Faraone SV, Mick E. Molecular genetics of attention deficit hyperactivity disorder. Psychiatry Clinics of North America. 2010;**33**:159-180

[24] Demontis D, Walters RK, Martin J, Mattheisen M, Als TD, Agerbo E, et al. Discovery of the first genome-wide significant risk loci for ADHD. Submitted for publication, bioRxiv. 2017;**14558**:1-43

[25] Groen-Blokhuis MM, Middeldorp CM, Kan KJ, Abdellaoui A, van Beijsterveldt CE, Ehli EA, et al. Attention-deficit/hyperactivity disorder polygenic risk scores predict attention problems in a population-based sample of children. Journal of the American

Academy of Child and Adolescent Psychiatry. 2014;**53**:1123-1129 e6

[26] Yang L, Neale BM, Liu L, Lee SH, Wray NR, Ji N, et al. Psychiatric GWAS Consortium: ADHD Subgroup. Polygenic transmission and complex neuro developmental network for attention deficit hyperactivity disorder: genome-wide association study of both common and rare variants. American Journal of Medical Genetics and Biological Neuropsychiatric Genetics. 2013;**162B**(5):419-430

[27] Thapar A, Martin J, Mick E, Arias Vasquez A, Langley K, Scherer SW, et al. Psychiatric gene discoveries shape evidence on ADHD's biology. Molecular Psychiatry. 2015;**21**:1202-1207

[28] Lo-Castro A, D'Agati E, Curatolo P. ADHD and genetic syndromes. Brain & Development. 2011;**33**(6):456-461

[29] Jarick I, Volckmar AL, Putter C, Pechlivanis S, Nguyen TT, Dauvermann MR, et al. Genome-wide analysis of rare copy number variations reveals PARK2 as a candidate gene for attention-deficit/hyperactivity disorder. Molecular Psychiatry. 2012;**19**:115-121

[30] Faraone SV, Larsson H. Genetics of attention deficit hyperactivity disorder. Molecular Psychiatry. 2019;**24**:562-575

[31] Taylor E. People with Hyperactivity: Understanding and Managing Their Problems. London: Mac Keith Press; 2007

[32] Nieoullon A. Dopamine and the regulation of cognition and attention. Progress in Neurobiology. 2002;**67**(1):53-83

[33] Kuczenski R, Segal DS. Stimulant actions in rodents: Implications for attention-deficit/hyperactivity disorder treatment and potential substance abuse. Biological Psychiatry. 2005;**57**(11):1391-1396

**99**

*Attention Deficit Hyperactivity Disorder DOI: http://dx.doi.org/10.5772/intechopen.92334*

[34] Fusar-Poli P, Rubia K, Rossi G, Sartori G, et al. Striatal dopamine transporter alterations in ADHD: pathophysiology or adaptation to psychostimulants? a meta-analysis. The American Journal of Psychiatry. [41] Gainetdinov RR, Wetsel WC, Jones SR, et al. Role of serotonin in the paradoxical calming effect of psychostimulants on hyperactivity.

Science. 1999;**283**:397-401

[42] Walshaw P, Alloy L, Sabb F. Executive function in pediatric bipolar

disorder and attention-deficit hyperactivity disorder: In search of distinct phenotypic profiles. Neuropsychological Reviews.

[43] Rucklidge J, Tannock R. Neuropsychological profiles of adolescents with ADHD: Effect of reading difficulties and gender. Journal of Child Psychology and Psychiatry.

[44] Martinussen R, Hayden J, Hogg-Johnson S, Tannock R. A meta-anaylsis of working memory impairements in children with attention-deficit/hyperactivity disorder. Journal of American Child and Adolescent Psychiatry.

[45] Awh E, Jonides J. Overlapping mechanisms of attention and spatial working memory. Trend in Cognitive

[46] Smith E, Jonides J, Koeppe R. Dissociating verbal and spatial working memory using PET. Cerebral Cortex.

[47] Thomas K, King S, Franzen P, Welsh T, Berkowitz A, Noll D, et al. A Developmental functional MRI study of spatial working memory. NeuroImage.

[48] Zurowski B, Gostomzyk J, Gron G, Weller R, Schirrmeister H, Neumeier B, et al. Dissociating a common working memory network from different neural substrates of phonological and spatial stimulus processing. NeuroImage.

Sceince. 2001;**5**(3):119-126

2010;**20**:103-120

2002;**43**:988-1003

2005;**44**(4):377-384

1996;**6**(1):11-20

1999;**10**(3 Pt):327-338

2002;**15**(1):45-57

Waldman I, et al. Candidate genetic pathways for attention-deficiti/ hyperactivity disorder (ADHD) show association to hyperactive/ impulsive symptoms in children with ADHD. Journal of American Academy of Child and Adolescent Psychiatry.

2012;**169**(3):264-272

[35] Bralten J, Franke B,

2013;**52**(11):1204-1212.e.l

LTDA; 2019

[36] Arnsten AF, Pliszka SR.

Catecholamine influences on prefrontal cortical function: relevance to treatment of attention deficit/hyperactivity disorder and related disorders. Pharmacology, Biochemistry, and Behavior. 2011;**99**(2):211-216

[37] Rohde LJ, Gerlach M, Buitelaar J. The World Federation of ADHD Guide. Santana, Sao Paulo: Artmed Editora

[38] Bishop C, Kamdar DP, Walker PD.

Waldman I, Rommelse N, Hartman C, Asherson P, et al. Candidate genetic pathways for attention-deficit/ hyperactivity disorder (ADHD) show association to hyperactive/ impulsive symptoms in children with ADHD. Journal of American Academy of Child and Adolescent Psychiatry.

[40] Banerjee E, Nandagopal K. Does serotonin deficit mediate susceptibility

Intrastiatal serotonin 5-HT2 receptors mediating dopamine D1-induced hyperlocomotion in 6-hydroxydopamine-lesioned rats.

Synapse. 2003;**50**:164-170

[39] Bralten J, Franke B,

2013;**52**(11):1204-1212.e1

to ADHD? Neurochemsitry International. 2015;**82**:52-68

#### *Attention Deficit Hyperactivity Disorder DOI: http://dx.doi.org/10.5772/intechopen.92334*

*Neurological and Mental Disorders*

deficit/hyperactivity disorder: A systematic review. Journal of Environmental Research and Public

Health. 2019;**16**(3):piiE382

562-575

2017;**58**:231-239

2013;**45**:984-994

2010;**33**:159-180

2017;**14558**:1-43

Llopis-Morales A, Cioni L, et al. The association between lead and attentionAcademy of Child and Adolescent Psychiatry. 2014;**53**:1123-1129 e6

Consortium: ADHD Subgroup. Polygenic transmission and complex neuro developmental network for attention deficit hyperactivity disorder: genome-wide association study of both common and rare variants. American Journal of Medical Genetics and Biological Neuropsychiatric Genetics.

2013;**162B**(5):419-430

[26] Yang L, Neale BM, Liu L, Lee SH, Wray NR, Ji N, et al. Psychiatric GWAS

[27] Thapar A, Martin J, Mick E, Arias Vasquez A, Langley K, Scherer SW, et al. Psychiatric gene discoveries shape evidence on ADHD's biology. Molecular

[28] Lo-Castro A, D'Agati E, Curatolo P. ADHD and genetic syndromes. Brain & Development. 2011;**33**(6):456-461

[29] Jarick I, Volckmar AL, Putter C,

Dauvermann MR, et al. Genome-wide analysis of rare copy number variations reveals PARK2 as a candidate gene for attention-deficit/hyperactivity disorder. Molecular Psychiatry. 2012;**19**:115-121

[30] Faraone SV, Larsson H. Genetics of attention deficit hyperactivity disorder. Molecular Psychiatry. 2019;**24**:562-575

[31] Taylor E. People with Hyperactivity: Understanding and Managing Their Problems. London: Mac Keith Press;

[32] Nieoullon A. Dopamine and the regulation of cognition and attention. Progress in Neurobiology.

[33] Kuczenski R, Segal DS. Stimulant actions in rodents: Implications for attention-deficit/hyperactivity disorder treatment and potential substance abuse. Biological Psychiatry.

Pechlivanis S, Nguyen TT,

2007

2002;**67**(1):53-83

2005;**57**(11):1391-1396

Psychiatry. 2015;**21**:1202-1207

[19] Faraone S, Larsson H. Genetics of attention deficit hyperactivity disorder. Molecular Psychiatry. 2019;**24**(4):

[20] Chen Q, Brikell I, Lichtenstein P, Serlachius E, Kuja-Halkola R, Sandin S, et al. Familial aggregation of attentiondeficit/hyperactivity disorder. Journal of Child Psychology and Psychiatry.

[21] Larsson H, Lichtenstein P,

[22] Lee SH, Ripke S, Neale BM, Faraone SV, Purcell SM, Perlis RH, et al. Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs. Nature Genetics.

[23] Faraone SV, Mick E. Molecular genetics of attention deficit hyperactivity disorder. Psychiatry

[24] Demontis D, Walters RK, Martin J, Mattheisen M, Als TD, Agerbo E, et al. Discovery of the first genome-wide significant risk loci for ADHD. Submitted for publication, bioRxiv.

Middeldorp CM, Kan KJ, Abdellaoui A, van Beijsterveldt CE, Ehli EA, et al. Attention-deficit/hyperactivity disorder polygenic risk scores predict attention problems in a population-based sample of children. Journal of the American

Clinics of North America.

[25] Groen-Blokhuis MM,

Larsson JO.Genetic contributions to the development of ADHD subtypes from childhood to adolescence. Journal of the American Academy of Child and Adolescent Psychiatry. 2006;**45**:973-981

**98**

[34] Fusar-Poli P, Rubia K, Rossi G, Sartori G, et al. Striatal dopamine transporter alterations in ADHD: pathophysiology or adaptation to psychostimulants? a meta-analysis. The American Journal of Psychiatry. 2012;**169**(3):264-272

[35] Bralten J, Franke B, Waldman I, et al. Candidate genetic pathways for attention-deficiti/ hyperactivity disorder (ADHD) show association to hyperactive/ impulsive symptoms in children with ADHD. Journal of American Academy of Child and Adolescent Psychiatry. 2013;**52**(11):1204-1212.e.l

[36] Arnsten AF, Pliszka SR. Catecholamine influences on prefrontal cortical function: relevance to treatment of attention deficit/hyperactivity disorder and related disorders. Pharmacology, Biochemistry, and Behavior. 2011;**99**(2):211-216

[37] Rohde LJ, Gerlach M, Buitelaar J. The World Federation of ADHD Guide. Santana, Sao Paulo: Artmed Editora LTDA; 2019

[38] Bishop C, Kamdar DP, Walker PD. Intrastiatal serotonin 5-HT2 receptors mediating dopamine D1-induced hyperlocomotion in 6-hydroxydopamine-lesioned rats. Synapse. 2003;**50**:164-170

[39] Bralten J, Franke B, Waldman I, Rommelse N, Hartman C, Asherson P, et al. Candidate genetic pathways for attention-deficit/ hyperactivity disorder (ADHD) show association to hyperactive/ impulsive symptoms in children with ADHD. Journal of American Academy of Child and Adolescent Psychiatry. 2013;**52**(11):1204-1212.e1

[40] Banerjee E, Nandagopal K. Does serotonin deficit mediate susceptibility to ADHD? Neurochemsitry International. 2015;**82**:52-68

[41] Gainetdinov RR, Wetsel WC, Jones SR, et al. Role of serotonin in the paradoxical calming effect of psychostimulants on hyperactivity. Science. 1999;**283**:397-401

[42] Walshaw P, Alloy L, Sabb F. Executive function in pediatric bipolar disorder and attention-deficit hyperactivity disorder: In search of distinct phenotypic profiles. Neuropsychological Reviews. 2010;**20**:103-120

[43] Rucklidge J, Tannock R. Neuropsychological profiles of adolescents with ADHD: Effect of reading difficulties and gender. Journal of Child Psychology and Psychiatry. 2002;**43**:988-1003

[44] Martinussen R, Hayden J, Hogg-Johnson S, Tannock R. A meta-anaylsis of working memory impairements in children with attention-deficit/hyperactivity disorder. Journal of American Child and Adolescent Psychiatry. 2005;**44**(4):377-384

[45] Awh E, Jonides J. Overlapping mechanisms of attention and spatial working memory. Trend in Cognitive Sceince. 2001;**5**(3):119-126

[46] Smith E, Jonides J, Koeppe R. Dissociating verbal and spatial working memory using PET. Cerebral Cortex. 1996;**6**(1):11-20

[47] Thomas K, King S, Franzen P, Welsh T, Berkowitz A, Noll D, et al. A Developmental functional MRI study of spatial working memory. NeuroImage. 1999;**10**(3 Pt):327-338

[48] Zurowski B, Gostomzyk J, Gron G, Weller R, Schirrmeister H, Neumeier B, et al. Dissociating a common working memory network from different neural substrates of phonological and spatial stimulus processing. NeuroImage. 2002;**15**(1):45-57

[49] Booth J, Burman D, Meyer J, Lei Z, Trommer B, Davenport N, et al. Larger deficits in brain networks for response inhibition than for visual selective attention in attention-deficit hyperactivity disorder (ADHD). Journal of Child Psychology and Psychiatry. 2005;**46**(1):94-111

[50] Leung H, Oh H, Ferri J, Yi Y. Load response functions in the human spatial working memory circuit during location memory updating. NeuroImage. 2007;**35**(1):368-377

[51] Middleton F, Strick P. Basal ganglia and cerebellar loops: motor and cognitive circuits. Brain Research Reviews. 2000;**31**(2-3):236-250

[52] Kasper L, Alderson R, Hudec K. Moderators of working memory deficits in children with attention-deficit/ hyperactivity disorder (ADHD): A meta-analytic review. Clinical Psychology Review. 2012;**32**:605-617

[53] Mayes S, Calhoun S, Crowel E. Learning disabilities and ADHD: overlapping spectrum disorders. Journal of Learning Disabilities. 2000;**33**: 417-424

[54] Bloom B, Cohen R. Summary health statistics for US children: National health Interview Survey. National Center for Health Statistics. Vital and Health Statistics. 2007;**10**(234)

[55] Molitor S, Joshua M, et al. The written expression abilities of adolescents with Attention-Deficit/ Hyperactivity Disorder. Research in Developmental Disabilities. 2016;**51-52**:49-59

[56] Oosterlaan J, Logan G, Sergeant J. Response inhibition in AD/HD, CD, comorbid AD/HD+CD, anxious, and control children: A meta-analysis of studies with stop task. Journal of Child Psychology and Psychiatry. 1998;**39**(3):411-425

[57] Barkley R. Behavioral inhibition, sustained attention, and executive functions: constructing a unifying theory of ADHD. Psychological Bulletin. 1997;**121**(1):7-12

[58] Crosbie J, Arnold P, Paterson A, Swanson J, Dupuis A, Li X, et al. Response inhibition and ADHD traits: correlates and heritability in a community sample. Journal of Abnormal Child Psychology. 2013;**41**(3):497-507

[59] Hart H, Radua J, Nakao T, Mataix-Cols D, Rubia K. Meta anaylisis of functional magnetic resonance imaging studies of inhibition and attention in attention-deficit/ hyperactivity disorder: exploring task-specific, stimulant medication and age effect. JAMA Psychiatry. 2013;**70**(2):185-198

[60] Willcut E, Doyle A, Nigg J, Faraone S, Pennington B. Validity of the executive function theory of attention – deficit/hyperactivity disorder: A metaanalytic review. Biological Psychiatry. 2005;**57**:1336-1346

[61] Barkley R. Attention -Deficit Hyperactivity Disorder. A handbook for diagnosis and treatment. 3rd ed. New York, London: The Guilford press; 2006

[62] Tobias U, Hauser P, Iannaccone M, et al. Role of the medial prefrontal cortex in impaired decision making in juvenile attention-deficit/hyperactivity disorder. JAMA Psychiatry. 2014;**71**(10):1165-1173. DOI: 10.1001/ jamapsychiatry.2014;1093

[63] Blaukopf C, DiGirolamo G. Reward, context and human behavior. The Scientific World Journal. 2007;**7**:626-640

[64] Luman M, Tripp G, Scheres A. Identifying the neurobiology of altered reinforcement sensitivity in ADHD:

**101**

*Attention Deficit Hyperactivity Disorder DOI: http://dx.doi.org/10.5772/intechopen.92334*

> Collaborative Multimodal Treatment Study of Children with ADHD (the MTA). Design challenges and choices. Archives of General Psychiatry. 1997;**54**:

865-870

a review and research agenda. Neuroscience and Behavior Review.

[65] Plichta M, Scheres A. Ventralstriatal responsiveness during reward anticipation in ADHD and its relation to trait impulsivity in the healthy population: A meta-analysis review of the fMRI literature. Neuroscience and Biobehavioral Reviews. 2014;**38**:125-134

[66] Paloyelis Y, Mehta M, Faraone S, Asherson P, Kuntsi J. Striatal sensitivity during reward processing in attention-

[67] Mowinckel A, Lund Pedersen M, Eilertsen E, Biele G. A meta-analysis of decision making and attention in adults with ADHD. Journal of Attention

[68] Kadesjo B, Gillberg C. Attention deficits and clumsiness in Swedish 7-year old children. Developmental Medicine and Child Neurology. 1988;**40**:

[69] Aicardi J. Diseases of the Nervous System in Childhood. 3rd ed. London:

[70] Centers for Disease Control and Prevention. 2019. Available from: https://www.cdc.gov/ncbddd/adhd/

deficit/hyperactivity disorder. Journal of American Academy of Child and Adolescent Psychiatry.

2012;**51**(7):722-732.e.9

Disorders. 2015;**19**:355-367

Mac Keith Press; 2009

behavior-therapy.html

aappublications.org/news

[72] Arnold L, Abikoff H, Cantwell D, et al. National Institute of Mental Health

[71] Wolraich M, Hagan J, et al. Clinical practice guideline for the diagnosis, evaluation and treatment of attention-deficit/hyperactivity disorder in children and adolescents. American Academy of Paediatrics. 2019;144(4)e20192528. DOI: 10.1542/ peds.2019-2528. Available from: www.

796-804

2010;**34**(5):744-754

*Attention Deficit Hyperactivity Disorder DOI: http://dx.doi.org/10.5772/intechopen.92334*

a review and research agenda. Neuroscience and Behavior Review. 2010;**34**(5):744-754

*Neurological and Mental Disorders*

2005;**46**(1):94-111

2007;**35**(1):368-377

[49] Booth J, Burman D, Meyer J, Lei Z, Trommer B, Davenport N, et al. Larger deficits in brain networks for response inhibition than for visual selective attention in attention-deficit hyperactivity disorder (ADHD). Journal of Child Psychology and Psychiatry.

[57] Barkley R. Behavioral inhibition, sustained attention, and executive functions: constructing a unifying theory of ADHD. Psychological Bulletin. 1997;**121**(1):7-12

[58] Crosbie J, Arnold P, Paterson A, Swanson J, Dupuis A, Li X, et al. Response inhibition and ADHD traits: correlates and heritability in a community sample. Journal of Abnormal Child Psychology.

2013;**41**(3):497-507

2013;**70**(2):185-198

2005;**57**:1336-1346

2006

[59] Hart H, Radua J, Nakao T,

[60] Willcut E, Doyle A, Nigg J,

[61] Barkley R. Attention -Deficit Hyperactivity Disorder. A handbook for diagnosis and treatment. 3rd ed. New York, London: The Guilford press;

[62] Tobias U, Hauser P, Iannaccone M, et al. Role of the medial prefrontal cortex in impaired decision making in juvenile attention-deficit/hyperactivity

2014;**71**(10):1165-1173. DOI: 10.1001/

disorder. JAMA Psychiatry.

jamapsychiatry.2014;1093

[63] Blaukopf C, DiGirolamo G. Reward, context and human behavior.

The Scientific World Journal.

[64] Luman M, Tripp G, Scheres A. Identifying the neurobiology of altered reinforcement sensitivity in ADHD:

2007;**7**:626-640

Faraone S, Pennington B. Validity of the executive function theory of attention – deficit/hyperactivity disorder: A metaanalytic review. Biological Psychiatry.

Mataix-Cols D, Rubia K. Meta anaylisis of functional magnetic resonance imaging studies of inhibition and attention in attention-deficit/ hyperactivity disorder: exploring task-specific, stimulant medication and age effect. JAMA Psychiatry.

[50] Leung H, Oh H, Ferri J, Yi Y. Load response functions in the human spatial working memory circuit during location

memory updating. NeuroImage.

[51] Middleton F, Strick P. Basal ganglia and cerebellar loops: motor and cognitive circuits. Brain Research Reviews. 2000;**31**(2-3):236-250

[52] Kasper L, Alderson R, Hudec K. Moderators of working memory deficits in children with attention-deficit/ hyperactivity disorder (ADHD): A meta-analytic review. Clinical Psychology Review. 2012;**32**:605-617

[53] Mayes S, Calhoun S, Crowel E. Learning disabilities and ADHD:

overlapping spectrum disorders. Journal of Learning Disabilities. 2000;**33**:

[54] Bloom B, Cohen R. Summary health statistics for US children: National health Interview Survey. National Center for Health Statistics. Vital and Health Statistics. 2007;**10**(234)

[55] Molitor S, Joshua M, et al. The written expression abilities of adolescents with Attention-Deficit/ Hyperactivity Disorder. Research in Developmental Disabilities.

[56] Oosterlaan J, Logan G, Sergeant J. Response inhibition in AD/HD, CD, comorbid AD/HD+CD, anxious, and control children: A meta-analysis of studies with stop task. Journal of Child Psychology and Psychiatry.

2016;**51-52**:49-59

1998;**39**(3):411-425

**100**

417-424

[65] Plichta M, Scheres A. Ventralstriatal responsiveness during reward anticipation in ADHD and its relation to trait impulsivity in the healthy population: A meta-analysis review of the fMRI literature. Neuroscience and Biobehavioral Reviews. 2014;**38**:125-134

[66] Paloyelis Y, Mehta M, Faraone S, Asherson P, Kuntsi J. Striatal sensitivity during reward processing in attentiondeficit/hyperactivity disorder. Journal of American Academy of Child and Adolescent Psychiatry. 2012;**51**(7):722-732.e.9

[67] Mowinckel A, Lund Pedersen M, Eilertsen E, Biele G. A meta-analysis of decision making and attention in adults with ADHD. Journal of Attention Disorders. 2015;**19**:355-367

[68] Kadesjo B, Gillberg C. Attention deficits and clumsiness in Swedish 7-year old children. Developmental Medicine and Child Neurology. 1988;**40**: 796-804

[69] Aicardi J. Diseases of the Nervous System in Childhood. 3rd ed. London: Mac Keith Press; 2009

[70] Centers for Disease Control and Prevention. 2019. Available from: https://www.cdc.gov/ncbddd/adhd/ behavior-therapy.html

[71] Wolraich M, Hagan J, et al. Clinical practice guideline for the diagnosis, evaluation and treatment of attention-deficit/hyperactivity disorder in children and adolescents. American Academy of Paediatrics. 2019;144(4)e20192528. DOI: 10.1542/ peds.2019-2528. Available from: www. aappublications.org/news

[72] Arnold L, Abikoff H, Cantwell D, et al. National Institute of Mental Health Collaborative Multimodal Treatment Study of Children with ADHD (the MTA). Design challenges and choices. Archives of General Psychiatry. 1997;**54**: 865-870

**103**

**Chapter 7**

Cases

**Abstract**

Suicide Attempts from Height and

Injury Patterns: An Analysis of 64

*Spyridon Galanakos, Konstantinos Kateros, Grigorios Leon,* 

Falls from height are a common cause of death and disability. A majority of free falls occur accidentally and only a minority result from suicidal behaviour. Adolescents in many countries show high rates of suicide attempts and their repetition is a common feature. We describe the demographic characteristics of these patients, their psychiatric diagnosis at the time of the attempt and the injury patterns. We present 64 patients who sustained injuries as a result of a fall from height. They were divided into those without mental disorders (n = 32, group I) and those with mental disorders (n = 32, group II). The mean height from which the fall occurred was 5.4 m (range, 3–25 m). The mean injury severity score was 19 (range, 6–58) for all fall victims. Upper extremity fractures were found in 37 patients, while pelvic and lower extremity fractures were found in 198 cases. Spinal fractures were noted in 32 patients. Head injuries were revealed by CT scan in 16 patients. Patients following a suicidal high fall mostly had lower limb fractures, pelvis fractures,

**Keywords:** attempted suicide, spinal cord injury (SCI), limb and spinal fractures

Falls from height cause significant death and disability worldwide, due to the severe traumatic load inflicted on their victims [1–4]. According to the WHO, the yearly mortality due to suicide worldwide is approximately 800,000 people. What is more important is the fact that it affects mainly young people, suicide being the primary cause of death in the age group of 25–34 years [5]. The mean incidence of suicides across Europe in 2013 was of 11.7 deaths per 100,000 people. Low rates, under 8 deaths per 100,000 inhabitants were recorded in Italy, Malta, Cyprus and the United Kingdom. The lowest incidence was observed in Greece (4.8 cases per 100,000 people) [6]. There was a lag between the beginning of the economic crisis in Europe, and the manifestation of its effects on the Greek population. These became evident 3 or 4 years later, in the form of a reduction of household income

*Stamatios A. Papadakis, Dimitrios Pallis,* 

*George Machairas and George Sapkas*

spinal fractures and head injuries.

and an increase in the rate of unemployment [7–9].

**1. Introduction**

#### **Chapter 7**

## Suicide Attempts from Height and Injury Patterns: An Analysis of 64 Cases

*Stamatios A. Papadakis, Dimitrios Pallis, Spyridon Galanakos, Konstantinos Kateros, Grigorios Leon, George Machairas and George Sapkas*

### **Abstract**

Falls from height are a common cause of death and disability. A majority of free falls occur accidentally and only a minority result from suicidal behaviour. Adolescents in many countries show high rates of suicide attempts and their repetition is a common feature. We describe the demographic characteristics of these patients, their psychiatric diagnosis at the time of the attempt and the injury patterns. We present 64 patients who sustained injuries as a result of a fall from height. They were divided into those without mental disorders (n = 32, group I) and those with mental disorders (n = 32, group II). The mean height from which the fall occurred was 5.4 m (range, 3–25 m). The mean injury severity score was 19 (range, 6–58) for all fall victims. Upper extremity fractures were found in 37 patients, while pelvic and lower extremity fractures were found in 198 cases. Spinal fractures were noted in 32 patients. Head injuries were revealed by CT scan in 16 patients. Patients following a suicidal high fall mostly had lower limb fractures, pelvis fractures, spinal fractures and head injuries.

**Keywords:** attempted suicide, spinal cord injury (SCI), limb and spinal fractures

#### **1. Introduction**

Falls from height cause significant death and disability worldwide, due to the severe traumatic load inflicted on their victims [1–4]. According to the WHO, the yearly mortality due to suicide worldwide is approximately 800,000 people. What is more important is the fact that it affects mainly young people, suicide being the primary cause of death in the age group of 25–34 years [5]. The mean incidence of suicides across Europe in 2013 was of 11.7 deaths per 100,000 people. Low rates, under 8 deaths per 100,000 inhabitants were recorded in Italy, Malta, Cyprus and the United Kingdom. The lowest incidence was observed in Greece (4.8 cases per 100,000 people) [6]. There was a lag between the beginning of the economic crisis in Europe, and the manifestation of its effects on the Greek population. These became evident 3 or 4 years later, in the form of a reduction of household income and an increase in the rate of unemployment [7–9].

Causes for this mechanism of injury include both accidental falls and deliberate suicide attempts [10]. The latter constitutes a major social problem, with implications for the entire society, but particularly for the affected family. The psychological profile of people committing suicide is complex and unique for each case [11]. Thus, identifying contributing factors that may lead to suicide and establishing strategies for the safekeeping of mental health in communities are of paramount importance.

The type of injuries incurred after a fall constitute a unique pattern of blunt trauma, with a characteristic distribution of damage (multiple lesions in a variety of body areas) [1, 12, 13]. The most common form of trauma are fractures, followed by other areas, such as the head, the thorax, the abdomen as well as the retroperitoneum, being injured by varied degrees [14]. The quantity and the quality of traumatic load absorbed depend on factors like the height from which the fall occurred, the part of the patient's body that had the first impact, the surface where the impact occurred and the victim's age, taking into account the associated comorbidity, and reduced physiologic reserve that advanced age implies [15–17]. Anticipation and prediction of the exact areas being injured are not possible, because of the multitude of factors involved, and the exact unpredictability of the fall's kinematic [18, 19].

As aforementioned, one can infer that the differential diagnosis of falls from height from other types of blunt trauma (for example, a road-traffic-collision with expulsion of the occupants from the vehicle) is difficult. Thus, a high index of suspicion must be maintained concerning the initial cause in cases of polytrauma in victims with an unknown history [20]. An array of papers have dealt with injuryrelated deaths in general, while others have differentiated between unintentional and intentional injury-related deaths [21–24]. There are few studies though that have looked into patients with intentional or unintentional injuries, due to a fall from height, at a single centre [13, 25].

As noted by research in the past, self-harm due to a fall is a rare phenomenon, being responsible for 4–7% of deaths from suicide in the developed world [26–29]. On the other hand, studies have shown that psychiatric disorders are a frequent finding in patients suffering trauma [30–32]. Nevertheless, the connection between mental disorders and specific injury patterns has not been adequately described. Furthermore, the elucidation of patterns of injury incurred after accidental falls and after intentional suicide jumps, might be of help to forensic pathologists while investigating the circumstances of a death after a fall from height.

#### **2. Materials and methods**

From January 1990 to October 2012, 64 patients (15 males and 49 females) were studied as a result of falls from height. Fall from height ≥ 3 m is classified as high energy trauma in accordance to ATLS guidelines [33]. The mean patient age was 34 years (range 16–65 years). These 64 cases comprised our series and, for comparison, were divided into those without mental disorders (n = 32, group I) and those with mental disorders (n = 32, group II). Group II cases were further stratified according to their psychiatric diagnosis.

The principles of Advanced Trauma Life Support were followed in the management of all patients. Basic laboratory screening included haemoglobin level, prothrombin time, type and crossmatch and arterial blood gas analysis. Data collected included age, gender, associated trauma, injury severity score (ISS), Glasgow Coma

**105**

**Table 1.**

**4. Socioeconomic factors**

*Suicide Attempts from Height and Injury Patterns: An Analysis of 64 Cases*

arrival), length of intensive care unit (ICU) and hospital stay.

19–45) and the mean ICU stay was 9 (range, 5–13) (**Table 1**).

Scale (GCS), haemodynamic status (systolic blood pressure less than 90 mm Hg on

Also, the following trauma variables were analysed: specific intracranial injuries (epidural, subdural and subarachnoid haemorrhage and brain contusion), spinal injuries (cervical, thoracic and lumbar spine), thoracic injuries, specific intraabdominal injuries (liver, spleen, kidney, and hollow viscus) and specific fractures (pelvis, femur and tibia). The diagnosis of mental disorder was ascertained by psychiatric specialists using the criteria of the International Classification of Disease

The mean height of fall was 5.4 m (range, 3–25 m). The patients were separated

Concerning their background psychiatric disorder in group II, the diagnosis was schizophrenia in 32 patients, depression in 12, drugs or alcohol abuse in 3, personality disorder in one, manic depression in one, another psychiatric condition in one and 14 cases without a specific diagnosis (generally marital or work related).

Patients due to suicide attempts from height comprised of 15 males and 49 females with a mean of age 35 years (range: 18–65 years). Of those, 16 were single, 14 were married and 2 were divorced. Thirty-three patients were employed, 6 were housewives, 7 were unemployed, 3 were students/pupils and 15 had various occupations. As far as religion was concerned, 48 were Christian Orthodox, one Roman

Regarding their family status: 20 had children, 6 had only their parents, 3 had only their spouse, 2 had a step family, 2 had parents who were divorced, 6 had parents and/or siblings, one had both parents and children and 24 had no family at all.

Catholic, one Jewish, one Muslim and 13 of other religions.

*Comparisons of demographic data of patients with suicide attempts from height.*

in two groups: group I, without mental disorders (n = 32), and group II, with mental disorders (n = 32). The demographic data, including age, gender, height of fall, ISS, GCS, initial shock (SBP <90 mm Hg), hospital stay (days), ICU stay (days) and deaths are summarized in **Table 1**. The mean hospital stay was 29 days (range

**Data Patients** Age 35 (18–65) Gender (M:F) 15:49 ISS 20 (12–58) GCS 9 (6–13) Haemodynamic status-SBP <90 mmHg 34 Hospital stay (days) 29 (19–45) ICU stay (days) 9 (5–13) Deaths 13

*DOI: http://dx.doi.org/10.5772/intechopen.89477*

Ninth Version Clinical Modification (ICD-9CM).

**3. Results**

#### *Suicide Attempts from Height and Injury Patterns: An Analysis of 64 Cases DOI: http://dx.doi.org/10.5772/intechopen.89477*

Scale (GCS), haemodynamic status (systolic blood pressure less than 90 mm Hg on arrival), length of intensive care unit (ICU) and hospital stay.

Also, the following trauma variables were analysed: specific intracranial injuries (epidural, subdural and subarachnoid haemorrhage and brain contusion), spinal injuries (cervical, thoracic and lumbar spine), thoracic injuries, specific intraabdominal injuries (liver, spleen, kidney, and hollow viscus) and specific fractures (pelvis, femur and tibia). The diagnosis of mental disorder was ascertained by psychiatric specialists using the criteria of the International Classification of Disease Ninth Version Clinical Modification (ICD-9CM).

#### **3. Results**

*Neurological and Mental Disorders*

dictability of the fall's kinematic [18, 19].

from height, at a single centre [13, 25].

importance.

Causes for this mechanism of injury include both accidental falls and deliberate suicide attempts [10]. The latter constitutes a major social problem, with implications for the entire society, but particularly for the affected family. The psychological profile of people committing suicide is complex and unique for each case [11]. Thus, identifying contributing factors that may lead to suicide and establishing strategies for the safekeeping of mental health in communities are of paramount

The type of injuries incurred after a fall constitute a unique pattern of blunt

As aforementioned, one can infer that the differential diagnosis of falls from height from other types of blunt trauma (for example, a road-traffic-collision with expulsion of the occupants from the vehicle) is difficult. Thus, a high index of suspicion must be maintained concerning the initial cause in cases of polytrauma in victims with an unknown history [20]. An array of papers have dealt with injuryrelated deaths in general, while others have differentiated between unintentional and intentional injury-related deaths [21–24]. There are few studies though that have looked into patients with intentional or unintentional injuries, due to a fall

As noted by research in the past, self-harm due to a fall is a rare phenomenon, being responsible for 4–7% of deaths from suicide in the developed world [26–29]. On the other hand, studies have shown that psychiatric disorders are a frequent finding in patients suffering trauma [30–32]. Nevertheless, the connection between mental disorders and specific injury patterns has not been adequately described. Furthermore, the elucidation of patterns of injury incurred after accidental falls and after intentional suicide jumps, might be of help to forensic pathologists while investigating the circumstances of a death after a fall

From January 1990 to October 2012, 64 patients (15 males and 49 females) were studied as a result of falls from height. Fall from height ≥ 3 m is classified as high energy trauma in accordance to ATLS guidelines [33]. The mean patient age was 34 years (range 16–65 years). These 64 cases comprised our series and, for comparison, were divided into those without mental disorders (n = 32, group I) and those with mental disorders (n = 32, group II). Group II cases were further stratified

The principles of Advanced Trauma Life Support were followed in the management of all patients. Basic laboratory screening included haemoglobin level, prothrombin time, type and crossmatch and arterial blood gas analysis. Data collected included age, gender, associated trauma, injury severity score (ISS), Glasgow Coma

trauma, with a characteristic distribution of damage (multiple lesions in a variety of body areas) [1, 12, 13]. The most common form of trauma are fractures, followed by other areas, such as the head, the thorax, the abdomen as well as the retroperitoneum, being injured by varied degrees [14]. The quantity and the quality of traumatic load absorbed depend on factors like the height from which the fall occurred, the part of the patient's body that had the first impact, the surface where the impact occurred and the victim's age, taking into account the associated comorbidity, and reduced physiologic reserve that advanced age implies [15–17]. Anticipation and prediction of the exact areas being injured are not possible, because of the multitude of factors involved, and the exact unpre-

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from height.

**2. Materials and methods**

according to their psychiatric diagnosis.

The mean height of fall was 5.4 m (range, 3–25 m). The patients were separated in two groups: group I, without mental disorders (n = 32), and group II, with mental disorders (n = 32). The demographic data, including age, gender, height of fall, ISS, GCS, initial shock (SBP <90 mm Hg), hospital stay (days), ICU stay (days) and deaths are summarized in **Table 1**. The mean hospital stay was 29 days (range 19–45) and the mean ICU stay was 9 (range, 5–13) (**Table 1**).

Concerning their background psychiatric disorder in group II, the diagnosis was schizophrenia in 32 patients, depression in 12, drugs or alcohol abuse in 3, personality disorder in one, manic depression in one, another psychiatric condition in one and 14 cases without a specific diagnosis (generally marital or work related).


**Table 1.**

*Comparisons of demographic data of patients with suicide attempts from height.*

#### **4. Socioeconomic factors**

Patients due to suicide attempts from height comprised of 15 males and 49 females with a mean of age 35 years (range: 18–65 years). Of those, 16 were single, 14 were married and 2 were divorced. Thirty-three patients were employed, 6 were housewives, 7 were unemployed, 3 were students/pupils and 15 had various occupations. As far as religion was concerned, 48 were Christian Orthodox, one Roman Catholic, one Jewish, one Muslim and 13 of other religions.

Regarding their family status: 20 had children, 6 had only their parents, 3 had only their spouse, 2 had a step family, 2 had parents who were divorced, 6 had parents and/or siblings, one had both parents and children and 24 had no family at all.

#### **5. Mechanism of fall, severity of injuries and associated lesions**

The falls had occurred from a roof or balcony in 39 cases, from a window in 12, from a bridge in 7 and inside the house in 6. The mean injury severity score (ISS) was 20 (range 12–58) for all victims of fall. Sixteen patients arrived at the emergency department in shock. The most common body region having sustained severe trauma were the fractured extremities and/or spine, followed by the chest, the head and the abdomen for both groups (**Table 2**).

Head injuries were revealed by CT scan in 16 patients. The mean GCS was 9 (range 6–13) for both groups. The most common intracranial injury was brain contusion and subarachnoid haemorrhage, followed by subdural hematoma and epidural hematoma. The incidence of subarachnoid haemorrhage in the suicide group was significantly higher than in the accidental group.

Associated abdominal injuries were present in 4 patients. The most common injury was liver laceration, followed by kidney and spleen laceration. One died with an operative finding of a large central retroperitoneal haematoma due to a vena cava rupture. In the remaining 3 patients, ultrasonography showed minimal intraperitoneal blood and these patients were not operated on. Thoracic injuries were present in 32 patients. The most common of these were rib fractures—26 cases. Twelve of these patients had a haemopneumothorax and 6 had a sternum fracture. Conservative treatment with assisted ventilation was necessary in these cases (**Table 3**).

Upper extremity fractures were found in 37 patients, while pelvic and lower extremity fractures were found in 198 cases. Spinal fractures were noted in 32 patients. As far as the level of injury was concerned, in 16 cases, it was in the lumbar level, in 9 cases in the cervical, in 5 cases in thoracic and in 2 cases the sacral vertebrae were concerned. Regarding the neurologic deficit, in 23 cases, the injury was incomplete (14 with ASIA C and 9 with ASIA D), and in 9 cases, it was complete (4 with ASIA A and 5 with ASIA B). Further details with our data of 32 patients with spinal cord injury as a result of deliberate self-harm have been published previously [34]. It seems that the neurological complications of spinal injuries were correlated with the increase of the height from which the fall occurred.

Patients with psychiatric disorders were more frequently shocked on arrival at the emergency department than those in the accidental group, the most common reason for death being head injury. Fatalities were more common when patients fell from greater heights (over 4 m), or when their head hit a hard surface, such as concrete.


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hospital stay.

**Table 3.**

*Suicide Attempts from Height and Injury Patterns: An Analysis of 64 Cases*

Skull 16 (25%) Shoulder 4 (6.2%) Scapula 6 (9.3%) Sternum 6 (9.3%) Ribs 26 (40.6%) Humerus 8 (12.5%) Elbow joint 8 (12.5%) Distal radius 7 (10.9%) Hand 4 (6.2%) **Spinal fractures** 32 (50%) **Pelvis** 27 (42.1%)

Acetabulum 9 (14%) Femoral neck 38 (59.3%) Femur 18 (28.1%) Knee joint 17 (26.5%) Tibia 19 (29.6%) Ankle joint 36 (56.2%) Calcaneum 34 (53.1%)

*The distribution of fractures in percentage across body region for the two groups of patients.*

**Patients**

The final causes of inpatients' death were: head injury in 8 cases, multiple organ failure in 3 cases, pneumonia in one case and cardiac complications in another one. The majority of patients who died of organ failure had sustained significant head injury. In one case, death occurred after a second suicide attempt 2 years later.

Each patient underwent a psychiatric evaluation by a consulting psychiatrist as soon as his condition and cooperation permitted. The assessment comprised of an interview. Regarding the type of treatment for the spinal fracture—dislocations, instrumentation devices included titanium rods, transpedicular screws, sacral bars and bone grafting in all patients. No new suicide attempt was recorded during the

All patients were discharged from hospital approximately 6–8 weeks after the operation with a custom-made thermoplastic thoracolumbar or lumbosacral orthosis for another 8 weeks and instructions for physical therapy and rehabilitation programs. The mean follow-up was 6 years (12 months to 10 years range). At follow-up, 27 patients were available for evaluation due to the death of 5 patients, 1–3 years post initial injury, because of suicide in one case (patient 7 of group II) and medical complications in 4 cases [renal failure in 3 cases (patients 8, 14 and 30 in group II) and pneumonia in one (patient 21)]. In the remaining patients, new

*DOI: http://dx.doi.org/10.5772/intechopen.89477*

**Skull, thorax and upper extremities**

**Lower extremities**

**6. Medical management—outcome**

#### **Table 2.**

*Location where the fall occurred and associated injuries.*


#### **Table 3.**

*Neurological and Mental Disorders*

and the abdomen for both groups (**Table 2**).

group was significantly higher than in the accidental group.

with the increase of the height from which the fall occurred.

**Fall from Patients** Roof/balcony 39 Window 12 Bridge 7 Inside the house 6

Abdominal trauma 4 Thoracic trauma 32 Head injuries 16 Extremity fractures 199 Spinal fractures 32

**5. Mechanism of fall, severity of injuries and associated lesions**

The falls had occurred from a roof or balcony in 39 cases, from a window in 12, from a bridge in 7 and inside the house in 6. The mean injury severity score (ISS) was 20 (range 12–58) for all victims of fall. Sixteen patients arrived at the emergency department in shock. The most common body region having sustained severe trauma were the fractured extremities and/or spine, followed by the chest, the head

Head injuries were revealed by CT scan in 16 patients. The mean GCS was 9 (range 6–13) for both groups. The most common intracranial injury was brain contusion and subarachnoid haemorrhage, followed by subdural hematoma and epidural hematoma. The incidence of subarachnoid haemorrhage in the suicide

Associated abdominal injuries were present in 4 patients. The most common injury was liver laceration, followed by kidney and spleen laceration. One died with an operative finding of a large central retroperitoneal haematoma due to a vena cava rupture. In the remaining 3 patients, ultrasonography showed minimal intraperitoneal blood and these patients were not operated on. Thoracic injuries were present in 32 patients. The most common of these were rib fractures—26 cases. Twelve of these patients had a haemopneumothorax and 6 had a sternum fracture. Conservative treatment with assisted ventilation was necessary in these cases (**Table 3**).

Upper extremity fractures were found in 37 patients, while pelvic and lower extremity fractures were found in 198 cases. Spinal fractures were noted in 32 patients. As far as the level of injury was concerned, in 16 cases, it was in the lumbar level, in 9 cases in the cervical, in 5 cases in thoracic and in 2 cases the sacral vertebrae were concerned. Regarding the neurologic deficit, in 23 cases, the injury was incomplete (14 with ASIA C and 9 with ASIA D), and in 9 cases, it was complete (4 with ASIA A and 5 with ASIA B). Further details with our data of 32 patients with spinal cord injury as a result of deliberate self-harm have been published previously [34]. It seems that the neurological complications of spinal injuries were correlated

Patients with psychiatric disorders were more frequently shocked on arrival at the emergency department than those in the accidental group, the most common reason for death being head injury. Fatalities were more common when patients fell from greater heights (over 4 m), or when their head hit a hard surface, such as

**106**

**Table 2.**

concrete.

**Associated injuries**

*Location where the fall occurred and associated injuries.*

*The distribution of fractures in percentage across body region for the two groups of patients.*

The final causes of inpatients' death were: head injury in 8 cases, multiple organ failure in 3 cases, pneumonia in one case and cardiac complications in another one. The majority of patients who died of organ failure had sustained significant head injury. In one case, death occurred after a second suicide attempt 2 years later.

#### **6. Medical management—outcome**

Each patient underwent a psychiatric evaluation by a consulting psychiatrist as soon as his condition and cooperation permitted. The assessment comprised of an interview. Regarding the type of treatment for the spinal fracture—dislocations, instrumentation devices included titanium rods, transpedicular screws, sacral bars and bone grafting in all patients. No new suicide attempt was recorded during the hospital stay.

All patients were discharged from hospital approximately 6–8 weeks after the operation with a custom-made thermoplastic thoracolumbar or lumbosacral orthosis for another 8 weeks and instructions for physical therapy and rehabilitation programs. The mean follow-up was 6 years (12 months to 10 years range). At follow-up, 27 patients were available for evaluation due to the death of 5 patients, 1–3 years post initial injury, because of suicide in one case (patient 7 of group II) and medical complications in 4 cases [renal failure in 3 cases (patients 8, 14 and 30 in group II) and pneumonia in one (patient 21)]. In the remaining patients, new unsuccessful attempts were recorded in 2 cases (7%) due to psychiatric disorders, 1–3 years after the first attempt (patients 10 and 24). All survivors received psychiatric follow-up. The overall mortality was significantly higher in those patients who fell from more than 10 m.

#### **7. Discussion**

Suicides and suicide attempts constitute a major concern for public health services, with implications for both families and society [35]. Trauma incurred due to falls from height poses a great burden on health services due to its severity. This is particularly important if we take into account the fact that this is a largely preventable mechanism of injury. Prior knowledge of the possible traumatic patterns incurred after a fall from height can prove helpful in the initial evaluation of this group of patients. From an epidemiologic point of view, trauma due to falls may occur across all age groups, but it is the two extremes, the very young and elderly, which are particularly susceptible to it [36].

In this study, we have considered two groups of patients. Group I represented patients with no mental disorders and group II with mental disorders. It is quite difficult to identify someone who is prone to committing suicide. In addition, the observed number of suicides and suicide attempts being committed at a younger age (i.e. adolescence) has been a cause of concern worldwide and particularly in Europe [37]. The male-female ratio of suicide attempts varies across age groups. Thus, in the younger age group (15–24 years old), it is 1:1.9; and in the middle age group (45–54 years old) it is 1:1.7. This ratio further decreases for those older than 55 years to 1:1.4 [38]. In this study, the male-female ratio was 1:3. The female sex was associated with an increased likelihood of death due to a higher amount of energy involved in their attempted fall.

According to other studies [39, 40], young males tend to repeat suicide attempts more frequently than females and the methods used by them lead to an increased mortality. A suicide attempt in the past is a red flag for a possible attempt in the future; so, there is a strong correlation between suicide attempts and deaths from suicide both regionally and nationally, and particularly in young males [41]. Also, there is a strong correlation between repeated attempts and completed suicide, especially in the group of males who have used a violent method [42, 43].

The study by Dickson et al. had the aim of establishing a correlation between mortality and various factors, such as the patients' injury severity score (ISS), the height from which the fall took place, the patient's intention and the body regions that were injured. In addition, the height of the fall strongly correlated with the patient's ISS and was an important predictor of mortality [44]. Head and/or chest injuries, if due to a fall from height, were strongly associated with an increased incidence of death. According to the authors, this mechanism of injury should be a triage priority when tasking ambulances. In addition, the best way of treating these injuries is their prevention. No other significant predictors of mortality were found in this study.

In the case series by Kent and Pearce, 282 suicide attempts were studied, 13 of which were completed. Of those, 8 happened at home, all patients were older than 49 years; and in 7 out of 8 deaths, ladders were implicated [45]. The retrospective study by Petratos et al. analysed in detail the musculoskeletal traumatic pattern resulting from falls from height, and focused particularly on the correlation between specific fracture patterns and the height from which the fall happened, as well as on the causation of the fall (suicide attempt vs. accident). According to their findings, with an increase in the height from which the fall occurred, the frequency

**109**

particular.

direct impact injuries [49].

*Suicide Attempts from Height and Injury Patterns: An Analysis of 64 Cases*

of limb, thoracic and pelvic fractures also increased. Such a correlation was not evident for head injuries. Nevertheless, the anatomical regions having sustained fractures (including the cranium) varied in accordance with the height of the fall. Thus, we can infer a mechanism of injury that is varying proportionately to the height of the fall. There was no significant difference between the patients who attempted suicide and those who fell by accident as far as the number of fractures incurred or the regions having been injured were concerned. Nevertheless, with regard to our results that have been published previously, patients who attempted suicide had a significantly greater number of bilateral lower limb fractures than their accidental fall counterpart. In addition, logistic regression analysis shows a significant correlation between the cause of the fall and the presence of lower limb fractures. According to the authors, further research is necessary in order to establish a correlation between incurred traumatic pattern, the height of the fall and the

Choi et al. in his recent study attempted to differentiate the characteristics of traumatic pattern between intentional and non-intentional falls [47]. In addition, he attempted to determine prognostic factors for suicide attempt-related injury and promote adequate measures for the prevention and management of such injuries. In this study, 8992 patients with an accidental fall (non-intentional group) and 144 patients who committed a suicide attempt (intentional group) were included. Falls from a height greater than 4 metres were more frequently encountered in the intentional group. Death prior to patient's arrival in the accident and emergency department occurred in 54.9% of the cases of suicide attempt. Patients within the intentional group, having sustained increased traumatic load, had fallen from higher, were older and were more likely to be of lower educational level (highschool graduates, instead of college). Due to the fact that injuries sustained after an intentional fall were more likely to have a reserved outcome, the authors highlighted

the importance of prevention. Such measures include telephone support and counselling lines, the installation of signs advising against suicide in high risk areas for an intentional fall, such as bridges, along with suggestions for governmentcoordinated programs aiming for the education of the public and the improvement of social conditions generally and the support of the community and family in

The reasons behind a suicide attempt are multifactorial, hard to quantify and unique in every case. Nevertheless, the study of multiple suicide attempts puts into evidence some risk factors that would lead to such a decision. These are common across all age groups and include: the presence of mental illness, either currently or in the past, a history of alcohol or drug dependence, as well as the presence of depression [10]. Epidemiologically, one out of five persons who have attempted suicide will try once more within a year, and 10% of them will succeed in the end. Drug ingestion is the most common mechanism for a suicide attempt. Violent mechanisms such as hanging, falls from height and use of weapons are not common [48]. The persons who have attempted suicide by falling from height usually become polytrauma patients. The types of injuries incurred are two: deceleration injuries due to inertial phenomena, usually at viscera with vascular pedicles, and

The severity of fractures incurred will depend on factors like the area over which the impact is applied [50]. The smaller the area of spread of the impact, the greater the local load. Therefore, patients landing on their legs tend to suffer more severe injuries than those who have landed on their flanks, or prone, or supine [51]. Patients due to accidental falls mostly suffered spinal fractures and upper extremities fractures in an attempt to protect themselves. Patients due to suicidal high falls attempts suffered mostly of lower limb fractures, pelvis, spinal fractures

*DOI: http://dx.doi.org/10.5772/intechopen.89477*

patient's intention [46].

#### *Suicide Attempts from Height and Injury Patterns: An Analysis of 64 Cases DOI: http://dx.doi.org/10.5772/intechopen.89477*

*Neurological and Mental Disorders*

fell from more than 10 m.

which are particularly susceptible to it [36].

involved in their attempted fall.

**7. Discussion**

unsuccessful attempts were recorded in 2 cases (7%) due to psychiatric disorders, 1–3 years after the first attempt (patients 10 and 24). All survivors received psychiatric follow-up. The overall mortality was significantly higher in those patients who

Suicides and suicide attempts constitute a major concern for public health services, with implications for both families and society [35]. Trauma incurred due to falls from height poses a great burden on health services due to its severity. This is particularly important if we take into account the fact that this is a largely preventable mechanism of injury. Prior knowledge of the possible traumatic patterns incurred after a fall from height can prove helpful in the initial evaluation of this group of patients. From an epidemiologic point of view, trauma due to falls may occur across all age groups, but it is the two extremes, the very young and elderly,

In this study, we have considered two groups of patients. Group I represented patients with no mental disorders and group II with mental disorders. It is quite difficult to identify someone who is prone to committing suicide. In addition, the observed number of suicides and suicide attempts being committed at a younger age (i.e. adolescence) has been a cause of concern worldwide and particularly in Europe [37]. The male-female ratio of suicide attempts varies across age groups. Thus, in the younger age group (15–24 years old), it is 1:1.9; and in the middle age group (45–54 years old) it is 1:1.7. This ratio further decreases for those older than 55 years to 1:1.4 [38]. In this study, the male-female ratio was 1:3. The female sex was associated with an increased likelihood of death due to a higher amount of energy

According to other studies [39, 40], young males tend to repeat suicide attempts more frequently than females and the methods used by them lead to an increased mortality. A suicide attempt in the past is a red flag for a possible attempt in the future; so, there is a strong correlation between suicide attempts and deaths from suicide both regionally and nationally, and particularly in young males [41]. Also, there is a strong correlation between repeated attempts and completed suicide, especially in the group of males who have used a violent method [42, 43].

The study by Dickson et al. had the aim of establishing a correlation between mortality and various factors, such as the patients' injury severity score (ISS), the height from which the fall took place, the patient's intention and the body regions that were injured. In addition, the height of the fall strongly correlated with the patient's ISS and was an important predictor of mortality [44]. Head and/or chest injuries, if due to a fall from height, were strongly associated with an increased incidence of death. According to the authors, this mechanism of injury should be a triage priority when tasking ambulances. In addition, the best way of treating these injuries is their prevention. No other significant predictors of mortality were found

In the case series by Kent and Pearce, 282 suicide attempts were studied, 13 of which were completed. Of those, 8 happened at home, all patients were older than 49 years; and in 7 out of 8 deaths, ladders were implicated [45]. The retrospective study by Petratos et al. analysed in detail the musculoskeletal traumatic pattern resulting from falls from height, and focused particularly on the correlation between specific fracture patterns and the height from which the fall happened, as well as on the causation of the fall (suicide attempt vs. accident). According to their findings, with an increase in the height from which the fall occurred, the frequency

**108**

in this study.

of limb, thoracic and pelvic fractures also increased. Such a correlation was not evident for head injuries. Nevertheless, the anatomical regions having sustained fractures (including the cranium) varied in accordance with the height of the fall. Thus, we can infer a mechanism of injury that is varying proportionately to the height of the fall. There was no significant difference between the patients who attempted suicide and those who fell by accident as far as the number of fractures incurred or the regions having been injured were concerned. Nevertheless, with regard to our results that have been published previously, patients who attempted suicide had a significantly greater number of bilateral lower limb fractures than their accidental fall counterpart. In addition, logistic regression analysis shows a significant correlation between the cause of the fall and the presence of lower limb fractures. According to the authors, further research is necessary in order to establish a correlation between incurred traumatic pattern, the height of the fall and the patient's intention [46].

Choi et al. in his recent study attempted to differentiate the characteristics of traumatic pattern between intentional and non-intentional falls [47]. In addition, he attempted to determine prognostic factors for suicide attempt-related injury and promote adequate measures for the prevention and management of such injuries. In this study, 8992 patients with an accidental fall (non-intentional group) and 144 patients who committed a suicide attempt (intentional group) were included. Falls from a height greater than 4 metres were more frequently encountered in the intentional group. Death prior to patient's arrival in the accident and emergency department occurred in 54.9% of the cases of suicide attempt. Patients within the intentional group, having sustained increased traumatic load, had fallen from higher, were older and were more likely to be of lower educational level (highschool graduates, instead of college). Due to the fact that injuries sustained after an intentional fall were more likely to have a reserved outcome, the authors highlighted the importance of prevention. Such measures include telephone support and counselling lines, the installation of signs advising against suicide in high risk areas for an intentional fall, such as bridges, along with suggestions for governmentcoordinated programs aiming for the education of the public and the improvement of social conditions generally and the support of the community and family in particular.

The reasons behind a suicide attempt are multifactorial, hard to quantify and unique in every case. Nevertheless, the study of multiple suicide attempts puts into evidence some risk factors that would lead to such a decision. These are common across all age groups and include: the presence of mental illness, either currently or in the past, a history of alcohol or drug dependence, as well as the presence of depression [10]. Epidemiologically, one out of five persons who have attempted suicide will try once more within a year, and 10% of them will succeed in the end. Drug ingestion is the most common mechanism for a suicide attempt. Violent mechanisms such as hanging, falls from height and use of weapons are not common [48]. The persons who have attempted suicide by falling from height usually become polytrauma patients. The types of injuries incurred are two: deceleration injuries due to inertial phenomena, usually at viscera with vascular pedicles, and direct impact injuries [49].

The severity of fractures incurred will depend on factors like the area over which the impact is applied [50]. The smaller the area of spread of the impact, the greater the local load. Therefore, patients landing on their legs tend to suffer more severe injuries than those who have landed on their flanks, or prone, or supine [51]. Patients due to accidental falls mostly suffered spinal fractures and upper extremities fractures in an attempt to protect themselves. Patients due to suicidal high falls attempts suffered mostly of lower limb fractures, pelvis, spinal fractures and head injuries. Distal radius and hand was the most common affected region in upper extremities in patients with non-intentional falls, in an attempt to protect mainly the head and grab something stable to prevent further fall. In patients with intentional falls, kinetic energy is absorbed mainly by the lower limbs, pelvis, spine and head, leading to characteristic fracture patterns [52]. The most common cause for death is head injury [51, 53, 54] and this is accordance to our results. Turk and Tsokos reviewed 68 medicolegal autopsy cases (22 females, 46 males, age range 13–89 years) of fatal falls from height from 1997 to 2001 [55]. The cause of instant death was head trauma in 24 (35%), internal blood loss in 9 (13%) and polytrauma in 30 (44%) cases. Other causes of death, when the individuals survived the trauma for a longer period, included septic multiple organ dysfunction syndrome and pulmonary embolism. In general, suicides were from greater heights than accidents (mean height 22.7 m for suicides and 10.8 m for accidents, respectively). Strikingly, severe head injuries predominantly occurred in falls from heights below 10 m (84%) and above 25 m (90%). Head trauma was the cause of death in 11 of the 19 cases that were from 9 m or less (58%). Of all cases, 51 (75%) died within a few minutes. A survival time of several hours up to 1 day was observed in 8 cases. Nine patients survived for several days (up to 16 days). Five of them fell from heights below 10 m. Patients with intentional fall from height have a higher early mortality than patients due to accidental fall from height [56].

The easiest way to underline the suspicion that the mode is suicide is if a suicide note is found at the jumping site; this is, however, closer to being the exception than the rule. Analysing the distance of the body from the site of descent may sometimes also help us determine the manner of death. The distance of the body from the site of descent includes the falling height and the horizontal distance. The falling height in suicide was statistically higher than that in accident [57, 58]. For similar heights, Wischhusen et al. have demonstrated that in passive falls, the horizontal distance is usually farther than jumps [59]. From a mechanical point of view, during a fall from height, potential (dynamic) energy is converted into kinetic and this leads to fractures upon impact. Another important factor of the severity of injuries is the height of fall, as the kinetic energy is increasing due to acceleration during the fall and is maximum at the time of impact [60]. In suicide falls, kinetic energy is absorbed mainly by the lower limbs, pelvis and spine, leading to characteristic fracture patterns. In accidental falls, patients most probably extend their arms and flex their hips, which lead to a damping effect that protects the spine [61]. Hence, the most important determinant of survival after a free fall is the position of the body at the time of impact [49]. There were only 3 patients (cases 1, 22 and 31) in group II who have sustained solely upper extremity fractures. The most common body position at the time of impact is with the patient standing and landing with the lower extremities first. This usually leads to calcaneal or pilon fractures, as well as thoracolumbar fractures. If the impact takes place with the patient seated, then higher thoracic or cervical injuries are more likely to happen, which are associated with a higher rate of mortality. Finally, an unpredictable fracture pattern takes place when the victim suffers multiple secondary impacts, in various postures, after bouncing from the primary impact. The amount of injury incurred will depend on the rate of dissipation and absorption of energy, through the patient's body.

According to the paper by Teh et al., there is a difference to the traumatic pattern incurred by jumpers compared to fallers [13]. Namely, the jumpers tend to impact their dominant lower limb first, as well as sustaining right sided thoracic injuries in the process. We did not confirm the above-mentioned findings in our study. The severity of spinal cord injuries was more important in the suicide than the accidental group [52]. This was in accordance with studies performed in the past, which also showed the early neurologic involvement in such cases. As far as prognosis of

**111**

to this population.

for this group of patients.

*Suicide Attempts from Height and Injury Patterns: An Analysis of 64 Cases*

patients are in accordance with current knowledge [63].

in patients with a spinal fracture, but without cord injury.

these patients, 4 were successful in subsequent suicide attempts [28].

dependence and abuse, personality disorder and schizophrenia.

spinal cord injury is concerned, complete injuries will be unaltered both in level and extent in a year's time. On the other hand, incomplete injuries may show signs of improvement for a period of 2 years after the impact [62]. Our results regarding prognosis for ambulation in ASIA A patients and for functionality in ASIA C

Anderson et al. performed a retrospective study, regarding the rehabilitation outcome of patients with spinal cord injury, as a result of deliberate self-harm (DSH) [29]. According to them, spinal fractures in the DSH group were mainly the result of falls from height. Underlying causes were revealed, such as psychiatric disorders and substance abuse, necessitating formal psychiatric review. There was no difference in short-term rehabilitation results between the DSH and accidental spinal cord injury group. In addition, DSH seemed to impact the length of stay only

According to the literature, there are three studies on the subject of acute spinal cord injury following a suicide attempt that stand apart. The first is by Stanford et al. In his paper, 56 cases were followed over a period of 30 years (1970–2000). Fifty five cases were due to a fall from height and one open injury, through the use of a gun. Follow-up of 8 years on average was available for 47 cases (84%). The vertebral levels most frequently injured were C5 and L1. About 23 patients suffered from a complete spinal cord injury and 32 had a severe traumatic load (ISS > 15). The psychiatric background of these patients included personality disorder in 27, schizophrenia in 16, depression in 14 and substance abuse/dependence in 20. Of

The following two studies on this subject are from the UK [26] and Denmark [27]. Both of those are observational and retrospective, with a long follow-up. According to the latter, there is an increasing incidence of suicide attempts and associated spinal cord injury from 1965 to 1987. Approximately one third of the patients who attempted suicide suffered from schizophrenia. According to other papers [64, 65], schizophrenia is strongly correlated with falls from height (from bridges in particular). There were 7 patients in our study who have sustained a fall from a bridge. Damage control surgery principles are followed initially for the treatment of life-threatening injuries and for both limb and spinal trauma [66]. The primary goals of fracture fixation are timely mobilization and safe transfer to psychiatric services. Conservative treatment measures are not usually recommended

Our findings are in accordance with relevant bibliography [67, 68], regarding the psychiatric background of patients who attempt suicide by falling from height. The spectrum of conditions encountered encompasses bipolar disorder, substance

From an epidemiological point of view, schizophrenia is encountered in 5–10% of cases of suicide attempt. These patients may have well planned their suicide or even suffered from an active self-harm ideation. From the above-mentioned, we gather that management of these patients from a trauma point of view must take into consideration their psychiatric needs. The latter may cause significant disturbance in the delivery of medical care [69]. Most of the patients in this study had a positive response following adequate psychiatric intervention. Hence, we gather that prevention and early identification of persons at risk for a suicide attempt with the use of appropriate screening tools by health care professionals are invaluable. Education of medical and nursing staff regarding the demands and particularities of care of this population, suffering from both spinal cord injury and psychiatric disorders, cannot be overemphasized. Regular follow-up with multidisciplinary team input and future research are necessary for the provision of high-quality care

*DOI: http://dx.doi.org/10.5772/intechopen.89477*

#### *Suicide Attempts from Height and Injury Patterns: An Analysis of 64 Cases DOI: http://dx.doi.org/10.5772/intechopen.89477*

*Neurological and Mental Disorders*

than patients due to accidental fall from height [56].

tion and absorption of energy, through the patient's body.

and head injuries. Distal radius and hand was the most common affected region in upper extremities in patients with non-intentional falls, in an attempt to protect mainly the head and grab something stable to prevent further fall. In patients with intentional falls, kinetic energy is absorbed mainly by the lower limbs, pelvis, spine and head, leading to characteristic fracture patterns [52]. The most common cause for death is head injury [51, 53, 54] and this is accordance to our results. Turk and Tsokos reviewed 68 medicolegal autopsy cases (22 females, 46 males, age range 13–89 years) of fatal falls from height from 1997 to 2001 [55]. The cause of instant death was head trauma in 24 (35%), internal blood loss in 9 (13%) and polytrauma in 30 (44%) cases. Other causes of death, when the individuals survived the trauma for a longer period, included septic multiple organ dysfunction syndrome and pulmonary embolism. In general, suicides were from greater heights than accidents (mean height 22.7 m for suicides and 10.8 m for accidents, respectively). Strikingly, severe head injuries predominantly occurred in falls from heights below 10 m (84%) and above 25 m (90%). Head trauma was the cause of death in 11 of the 19 cases that were from 9 m or less (58%). Of all cases, 51 (75%) died within a few minutes. A survival time of several hours up to 1 day was observed in 8 cases. Nine patients survived for several days (up to 16 days). Five of them fell from heights below 10 m. Patients with intentional fall from height have a higher early mortality

The easiest way to underline the suspicion that the mode is suicide is if a suicide note is found at the jumping site; this is, however, closer to being the exception than the rule. Analysing the distance of the body from the site of descent may sometimes also help us determine the manner of death. The distance of the body from the site of descent includes the falling height and the horizontal distance. The falling height in suicide was statistically higher than that in accident [57, 58]. For similar heights, Wischhusen et al. have demonstrated that in passive falls, the horizontal distance is usually farther than jumps [59]. From a mechanical point of view, during a fall from height, potential (dynamic) energy is converted into kinetic and this leads to fractures upon impact. Another important factor of the severity of injuries is the height of fall, as the kinetic energy is increasing due to acceleration during the fall and is maximum at the time of impact [60]. In suicide falls, kinetic energy is absorbed mainly by the lower limbs, pelvis and spine, leading to characteristic fracture patterns. In accidental falls, patients most probably extend their arms and flex their hips, which lead to a damping effect that protects the spine [61]. Hence, the most important determinant of survival after a free fall is the position of the body at the time of impact [49]. There were only 3 patients (cases 1, 22 and 31) in group II who have sustained solely upper extremity fractures. The most common body position at the time of impact is with the patient standing and landing with the lower extremities first. This usually leads to calcaneal or pilon fractures, as well as thoracolumbar fractures. If the impact takes place with the patient seated, then higher thoracic or cervical injuries are more likely to happen, which are associated with a higher rate of mortality. Finally, an unpredictable fracture pattern takes place when the victim suffers multiple secondary impacts, in various postures, after bouncing from the primary impact. The amount of injury incurred will depend on the rate of dissipa-

According to the paper by Teh et al., there is a difference to the traumatic pattern incurred by jumpers compared to fallers [13]. Namely, the jumpers tend to impact their dominant lower limb first, as well as sustaining right sided thoracic injuries in the process. We did not confirm the above-mentioned findings in our study. The severity of spinal cord injuries was more important in the suicide than the accidental group [52]. This was in accordance with studies performed in the past, which also showed the early neurologic involvement in such cases. As far as prognosis of

**110**

spinal cord injury is concerned, complete injuries will be unaltered both in level and extent in a year's time. On the other hand, incomplete injuries may show signs of improvement for a period of 2 years after the impact [62]. Our results regarding prognosis for ambulation in ASIA A patients and for functionality in ASIA C patients are in accordance with current knowledge [63].

Anderson et al. performed a retrospective study, regarding the rehabilitation outcome of patients with spinal cord injury, as a result of deliberate self-harm (DSH) [29]. According to them, spinal fractures in the DSH group were mainly the result of falls from height. Underlying causes were revealed, such as psychiatric disorders and substance abuse, necessitating formal psychiatric review. There was no difference in short-term rehabilitation results between the DSH and accidental spinal cord injury group. In addition, DSH seemed to impact the length of stay only in patients with a spinal fracture, but without cord injury.

According to the literature, there are three studies on the subject of acute spinal cord injury following a suicide attempt that stand apart. The first is by Stanford et al. In his paper, 56 cases were followed over a period of 30 years (1970–2000). Fifty five cases were due to a fall from height and one open injury, through the use of a gun. Follow-up of 8 years on average was available for 47 cases (84%). The vertebral levels most frequently injured were C5 and L1. About 23 patients suffered from a complete spinal cord injury and 32 had a severe traumatic load (ISS > 15). The psychiatric background of these patients included personality disorder in 27, schizophrenia in 16, depression in 14 and substance abuse/dependence in 20. Of these patients, 4 were successful in subsequent suicide attempts [28].

The following two studies on this subject are from the UK [26] and Denmark [27]. Both of those are observational and retrospective, with a long follow-up. According to the latter, there is an increasing incidence of suicide attempts and associated spinal cord injury from 1965 to 1987. Approximately one third of the patients who attempted suicide suffered from schizophrenia. According to other papers [64, 65], schizophrenia is strongly correlated with falls from height (from bridges in particular). There were 7 patients in our study who have sustained a fall from a bridge. Damage control surgery principles are followed initially for the treatment of life-threatening injuries and for both limb and spinal trauma [66]. The primary goals of fracture fixation are timely mobilization and safe transfer to psychiatric services. Conservative treatment measures are not usually recommended for this group of patients.

Our findings are in accordance with relevant bibliography [67, 68], regarding the psychiatric background of patients who attempt suicide by falling from height. The spectrum of conditions encountered encompasses bipolar disorder, substance dependence and abuse, personality disorder and schizophrenia.

From an epidemiological point of view, schizophrenia is encountered in 5–10% of cases of suicide attempt. These patients may have well planned their suicide or even suffered from an active self-harm ideation. From the above-mentioned, we gather that management of these patients from a trauma point of view must take into consideration their psychiatric needs. The latter may cause significant disturbance in the delivery of medical care [69]. Most of the patients in this study had a positive response following adequate psychiatric intervention. Hence, we gather that prevention and early identification of persons at risk for a suicide attempt with the use of appropriate screening tools by health care professionals are invaluable.

Education of medical and nursing staff regarding the demands and particularities of care of this population, suffering from both spinal cord injury and psychiatric disorders, cannot be overemphasized. Regular follow-up with multidisciplinary team input and future research are necessary for the provision of high-quality care to this population.

### **8. Conclusions**

According to the literature, it has been difficult to obtain comparable international data on suicide attempts, owing to disparities in definitions, survey designs and study methods, because the combination of free falls and mental disorders produces a unique group of patients. It has been our experience that psychiatric conditions, and especially the suicidal risk, should be evaluated and treated as early as possible during the orthopaedic or surgical hospitalization. Management requires both psychopharmacological therapy and psychotherapy. It has to be directed towards the achievement of symptomatic relief and, if possible, towards the remission of the primary psychiatric disorder.

The management of these patients in the orthopaedic or surgical ward is difficult, because of restlessness, non-cooperation of the patient and the problem of staff inexperienced in handling the psychiatric patient. When prolonged orthopaedic and rehabilitation management are necessary, it is suggested that the patient be transferred to a psychiatric hospital while continuing the necessary orthopaedic treatment. The outcome data provide critical information concerning those individuals who have attempted suicide and suggests future methods for the identification of suicidal factors.

#### **Conflicts of interest**

The authors declare that they have no conflicts of interest.

## **Author details**

Stamatios A. Papadakis1 \*, Dimitrios Pallis1 , Spyridon Galanakos1 , Konstantinos Kateros2 , Grigorios Leon3 , George Machairas1 and George Sapkas4

1 Department of Orthopaedics, KAT General Hospital of Attica, Athens, Greece

2 Department of Orthopaedics, "G. Gennimatas" General Hospital, Athens, Greece


\*Address all correspondence to: snapmd@gmail.com

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

**113**

*Suicide Attempts from Height and Injury Patterns: An Analysis of 64 Cases*

factors for suicide in blacks and whites: An analysis of data from the 1993 National mortality followback survey. The American Journal of Psychiatry.

[11] Scalea T, Goldstein A, Phillips T, et al. An analysis of 161 falls from a height: The "jumper syndrome". The Journal of Trauma. 1986;**26**(8):706-712

[12] Velmahos GC, Demetriades D, Theodorou D, Cornwell EE,

Belzberg H, Asensio J, et al. Patterns of injury in victims of urban freefalls. World Journal of Surgery.

Reznek R, Chan O. Jumpers and fallers: A comparison of the distribution of skeletal injury. Clinical Radiology.

[13] Teh J, Firth M, Sharma A,

[14] Fang JF, Shih LY, Lin BC, Hsu YP. Pelvic fractures due to falls from a height in people with mental disorders. Injury. 2008;**39**:881-888

[15] Agalar F, Cakmakci M, Sayek I. Factors effecting mortality in urban vertical free falls: Evaluation of 180 cases. International Surgery.

[16] Demetriades D, Murray J, Brown C, et al. High-level falls: Type and severity of injuries and survival outcome

according to age. The Journal of Trauma.

[17] Bertocci GE, Pierce MC, Deemer E, et al. Influence of fall height and impact

surface on biomechanics of feetfirst free falls in children. Injury.

[18] Adamec J, Jelen K, Kubovy P, Lopot F, Schuller E. Forensic biomechanical analysis of falls from height using numerical human body

2004;**161**:452-458

1997;**21**:816-821

2003;**58**:482-486

1999;**84**:271-274

2005;**58**:342-345

2004;**35**:417-424

*DOI: http://dx.doi.org/10.5772/intechopen.89477*

Imperative. Geneva, Switzerland: World

[2] Εurostat. Causes of deaths statistics. Retrieved from: http://ec.europa.eu/ eurostat/statisticsexplained/index. php/Causes\_of\_death\_statistics [Last

[1] World Health Organization Preventing Suicide: A Global

Health Organization; 2014

**References**

accessed: 27 October 2016]

[3] Kentikelenis A, Karanikolos M, Reeves A, McKee M, Stuckler D. Greece's

health crisis: From austerity to denialism. Lancet. 2014;**383**:748-753

[4] Economou M, Madianos M, Peppou LE, Theleritis C, Patelakis A, Stefanis C. Suicidal ideation and reported suicide attempts in Greece during the economic crisis. World

Psychiatry. 2013;**12**:53-59

[6] Isbister ES, Roberts JA.

Autokabalesis: A study of intentional vertical deceleration injuries. Injury.

[7] Lewis WS, Lee AB, Grantham SA. "Jumpers syndrome": The trauma of high free fall as seen at Harlem hospital. The Journal of Trauma.

[8] Mathis RD, Levine SH, Phifer S. An analysis of accidental free falls from a height: The "spring break" syndrome. The Journal of Trauma.

[9] Steedman DJ. Severity of free-fall injury. Injury. 1989;**20**:259-261

Meldrum S, Conner KR, Conwell Y. Risk

[10] Castle K, Duberstein PR,

2013;**24**:170-174

1992;**23**:119-122

1965;**5**(6):812-818

1993;**34**(1):123-126

[5] Kontaxakis V, Papaslanis T, Havaki-Kontaxaki B, Tsouvelas G, Giotakos O, Papadimitriou G. Suicide in Greece: 2001-2011. Psychiatriki.

*Suicide Attempts from Height and Injury Patterns: An Analysis of 64 Cases DOI: http://dx.doi.org/10.5772/intechopen.89477*

#### **References**

*Neurological and Mental Disorders*

sion of the primary psychiatric disorder.

**8. Conclusions**

**112**

**Author details**

Stamatios A. Papadakis1

**Conflicts of interest**

Konstantinos Kateros2

\*, Dimitrios Pallis1

The authors declare that they have no conflicts of interest.

4 Department of Orthopaedics, Metropolitan Hospital, Athens, Greece

1 Department of Orthopaedics, KAT General Hospital of Attica, Athens, Greece

2 Department of Orthopaedics, "G. Gennimatas" General Hospital, Athens, Greece

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

According to the literature, it has been difficult to obtain comparable international data on suicide attempts, owing to disparities in definitions, survey designs and study methods, because the combination of free falls and mental disorders produces a unique group of patients. It has been our experience that psychiatric conditions, and especially the suicidal risk, should be evaluated and treated as early as possible during the orthopaedic or surgical hospitalization. Management requires both psychopharmacological therapy and psychotherapy. It has to be directed towards the achievement of symptomatic relief and, if possible, towards the remis-

The management of these patients in the orthopaedic or surgical ward is difficult,

because of restlessness, non-cooperation of the patient and the problem of staff inexperienced in handling the psychiatric patient. When prolonged orthopaedic and rehabilitation management are necessary, it is suggested that the patient be transferred to a psychiatric hospital while continuing the necessary orthopaedic treatment. The outcome data provide critical information concerning those individuals who have attempted suicide and suggests future methods for the identification of suicidal factors.

, Grigorios Leon3

3 Private Forensic Pathology Practice, Athens, Greece

\*Address all correspondence to: snapmd@gmail.com

provided the original work is properly cited.

, Spyridon Galanakos1

, George Machairas1

,

and George Sapkas4

[1] World Health Organization Preventing Suicide: A Global Imperative. Geneva, Switzerland: World Health Organization; 2014

[2] Εurostat. Causes of deaths statistics. Retrieved from: http://ec.europa.eu/ eurostat/statisticsexplained/index. php/Causes\_of\_death\_statistics [Last accessed: 27 October 2016]

[3] Kentikelenis A, Karanikolos M, Reeves A, McKee M, Stuckler D. Greece's health crisis: From austerity to denialism. Lancet. 2014;**383**:748-753

[4] Economou M, Madianos M, Peppou LE, Theleritis C, Patelakis A, Stefanis C. Suicidal ideation and reported suicide attempts in Greece during the economic crisis. World Psychiatry. 2013;**12**:53-59

[5] Kontaxakis V, Papaslanis T, Havaki-Kontaxaki B, Tsouvelas G, Giotakos O, Papadimitriou G. Suicide in Greece: 2001-2011. Psychiatriki. 2013;**24**:170-174

[6] Isbister ES, Roberts JA. Autokabalesis: A study of intentional vertical deceleration injuries. Injury. 1992;**23**:119-122

[7] Lewis WS, Lee AB, Grantham SA. "Jumpers syndrome": The trauma of high free fall as seen at Harlem hospital. The Journal of Trauma. 1965;**5**(6):812-818

[8] Mathis RD, Levine SH, Phifer S. An analysis of accidental free falls from a height: The "spring break" syndrome. The Journal of Trauma. 1993;**34**(1):123-126

[9] Steedman DJ. Severity of free-fall injury. Injury. 1989;**20**:259-261

[10] Castle K, Duberstein PR, Meldrum S, Conner KR, Conwell Y. Risk factors for suicide in blacks and whites: An analysis of data from the 1993 National mortality followback survey. The American Journal of Psychiatry. 2004;**161**:452-458

[11] Scalea T, Goldstein A, Phillips T, et al. An analysis of 161 falls from a height: The "jumper syndrome". The Journal of Trauma. 1986;**26**(8):706-712

[12] Velmahos GC, Demetriades D, Theodorou D, Cornwell EE, Belzberg H, Asensio J, et al. Patterns of injury in victims of urban freefalls. World Journal of Surgery. 1997;**21**:816-821

[13] Teh J, Firth M, Sharma A, Reznek R, Chan O. Jumpers and fallers: A comparison of the distribution of skeletal injury. Clinical Radiology. 2003;**58**:482-486

[14] Fang JF, Shih LY, Lin BC, Hsu YP. Pelvic fractures due to falls from a height in people with mental disorders. Injury. 2008;**39**:881-888

[15] Agalar F, Cakmakci M, Sayek I. Factors effecting mortality in urban vertical free falls: Evaluation of 180 cases. International Surgery. 1999;**84**:271-274

[16] Demetriades D, Murray J, Brown C, et al. High-level falls: Type and severity of injuries and survival outcome according to age. The Journal of Trauma. 2005;**58**:342-345

[17] Bertocci GE, Pierce MC, Deemer E, et al. Influence of fall height and impact surface on biomechanics of feetfirst free falls in children. Injury. 2004;**35**:417-424

[18] Adamec J, Jelen K, Kubovy P, Lopot F, Schuller E. Forensic biomechanical analysis of falls from height using numerical human body models. Journal of Forensic Sciences. 2010;**55**(6):1615-1623

[19] Guyomarc'h P, Campagna-Vaillancourt M, Chaltchi A, Sauvageau A. Skull fracture with brain expulsion in a one-level jumpingfall. Journal of Forensic Sciences. 2009;**54**(6):1463-1465

[20] Fracasso T, Schmidt S, Schmeling A. Commentary on: Kremer C, Racette S, Dionne CA, Sauvageau A. Discrimination of falls and blows in blunt head trauma: Systematic study of the hat brim rule in relation to skull fractures. Journal of Forensic Sciences. May 2008;**53**(3): 716-719. Journal of Forensic Sciences. 2011;**56**(6):1662. Author reply 1663

[21] Hong J, Lee WK, Park H. Change in causes of injury-related deaths in South Korea, 1996-2006. Journal of Epidemiology. 2011;**21**:500-506

[22] Im JS, Choi SH, Hong D, Seo HJ, Park S, Hong JP. Proximal risk factors and suicide methods among suicide completers from national suicide mortality data 2004-2006 in Korea. Comprehensive Psychiatry. 2011;**52**:231-237

[23] Lee CA, Choi SC, Jung KY, et al. Characteristics of patients who visit the emergency department with selfinflicted injury. Journal of Korean Medical Science. 2012;**27**:307-312

[24] Rockett IR, Regier MD, Kapusta ND, et al. Leading causes of unintentional and intentional injury mortality: United States, 2000-2009. American Journal of Public Health. 2012;**102**:e84-e92

[25] Richter D, Hahn MP, Ostermann PA, Ekkernkamp A, Muhr G. Vertical deceleration injuries: A comparative study of the injury patterns of 101 patients after accidental and intentional high falls. Injury. 1996;**27**:655-659

[26] Kennedy P, Rogers B, Speer S, Frankel H. Spinal cord injuries and attempted suicide: A retrospective review. Spinal Cord. 1999;**37**(12):847-852

[27] Biering-Sorensen F, Pederson W, Giortz Muller P. Spinal cord injury due to suicide attempts. Paraplegia. 1992;**30**(2):139-144

[28] Stanford RE, Soden R, Bartrop R, Mikk M, Taylor TKF. Spinal cord and related injuries after attempted suicide: Psychiatric diagnosis and longterm follow-up. Spinal Cord. 2007;**45**(6):437-443

[29] Anderson J, Allan DB. Vertebral fracture secondary to suicide attempt: Demographics and patient outcome in a Scottish spinal rehabilitation unit. The Journal of Spinal Cord Medicine. 2011;**34**(4):380-387

[30] Zatzick DF, Kang SM, Kim SY, et al. Patients with recognized psychiatric disorders in trauma surgery: Incidence, inpatient length of stay, and cost. The Journal of Trauma. 2000;**49**:487-495

[31] Demetriades D, Gkiokas G, Velmahos GC, et al. Alcohol and illicit drugs in traumatic deaths: Prevalence and association with type and severity of injuries. Journal of the American College of Surgeons. 2004;**199**:687-692

[32] Schecter WP, Klassen C, O'Connor P, et al. The unmet challenge of the trauma system. Archives of Surgery. 2005;**140**:902-904

[33] The ATLS Subcommittee and the International ATLS Working Group AC of SC on T. Advanced trauma life support (ATLS®): The ninth edition. Journal of Trauma and Acute Care Surgery. 2013;**74**:1363-1366

[34] Papadakis SA, Galanakos S, Apostolaki A, Kateros K, Antoniadou O, et al. Spinal cord injuries following

**115**

*Suicide Attempts from Height and Injury Patterns: An Analysis of 64 Cases*

[43] Hawton K, Fagg J, Platt S, Hawkins M. Factors associated with suicide after parasuicide in young people. British Journal of Psychiatry.

[44] Dickinson A, Roberts M, Kumar A, Weaver A, Lockey DJ. Falls from height:

[46] Petaros A, Slaus M, Coklo M, Sosa I, Cengija M, Bosnar A. Retrospective analysis of free-fall fractures with regard to height and cause of fall. Forensic Science International.

[47] Choi JH, Kim SH, Kim SP, Jung KY, Ryu JY, Choi SC, et al. Characteristics of intentional fall injuries in the ED. The American Journal of Emergency Medicine. 2014;**32**(6):529-534

[49] Maull KI, Whitley RE, Cardea JA. Vertical deceleration injuries. Surgery,

[50] Snyder RG. Human tolerance to extreme impacts in free-fall. Aeroscace

[51] Layton TR, Villella R, Kelly EG. High free fall with survival. The Journal of

[52] Pallis D, Georgiou DF, Abadiotaki M, Galanakos S, Sapkas G, Macheras G, et al.

Injury and mortality. Journal of the Royal Army Medical Corps.

[45] Kent A, Pearce A. Review of morbidity and mortality associated with falls from heights among patients presenting to a major trauma Centre. Emergency Medicine Australasia.

1993;**306**:1641-1644

2012;**158**(2):123-127

2006;**18**(1):23-30

2013;**226**(1-3):290-295

[48] Crandall M, Luchette F, Esposito TJ, West M, Shapiro M, Bulger E. Attempted suicide and the elderly trauma patient: Risk factors and outcomes. The Journal of Trauma.

2007;**62**(4):1021-1027

Gynecology & Obstetrics. 1981;**153**(2):233-236

Medicine. 1963;**34**:695-709

Trauma. 1981;**21**(11):983-985

*DOI: http://dx.doi.org/10.5772/intechopen.89477*

suicide attempts. Topics in paraplegia. ed. Yannis Dionysiotis, IntechOpen. 2nd

Association. International Standards for Neurological Classification of Spinal Cord Injury, Revised 2002. Chicago: American Spinal Injury

[36] Lambert DA, Sattin RW. Deaths from falls, 1978-1984. MMWR. CDC

Hjelmeland H, et al. Repetition of attempted suicide among teenagers in Europe: Frequency, timing and risk factors. European Child & Adolescent

July 2014. pp. 53-70. Chapter 3

[35] American Spinal Injury

Association; 2002

1988;**37**(1):21-26

Surveillance Summaries.

[37] Hultιn A, Jiang G-X, Wasserman D, Hawton K,

Psychiatry. 2001;**10**:161-169

[38] Petronis KR, Samuels JF, Moscicki EK, Anthony JC. An

risk factors for suicide attempts. Social Psqchiatry and Psychiatric Epidemiology. 1990;**25**:193-199

[39] Beautrais AL. Serious suicide

1996;**153**:1009-1014

[40] Li G, Ling J, Di Scala C.

Prevention. 1997;**3**:115-119

[41] Hawton K, Arensman E,

Health. 1998;**52**:191-194

[42] Granboulan V, Rabain D,

Characteristics and outcomes of self inflicted paediatric injuries: The role of method of suicide attempt. Injury

Wasserman D, et al. Relation between attempted suicide and suicide rates among young people in Europe. Journal of Epidemiology and Community

Basquin M. The outcome of adolescent suicide attempts. Acta Psychiatrica Scandinavica. 1995;**91**:265-270

epidemiologic investigation of potential

attempts in young people: A case control study. American Journal of Psychiatry.

*Suicide Attempts from Height and Injury Patterns: An Analysis of 64 Cases DOI: http://dx.doi.org/10.5772/intechopen.89477*

suicide attempts. Topics in paraplegia. ed. Yannis Dionysiotis, IntechOpen. 2nd July 2014. pp. 53-70. Chapter 3

*Neurological and Mental Disorders*

[19] Guyomarc'h P, Campagna-Vaillancourt M, Chaltchi A,

2010;**55**(6):1615-1623

2009;**54**(6):1463-1465

[20] Fracasso T, Schmidt S, Schmeling A. Commentary on: Kremer C, Racette S, Dionne CA, Sauvageau A. Discrimination of falls and blows in blunt head trauma: Systematic study of the hat brim rule in relation to skull fractures. Journal of Forensic Sciences. May 2008;**53**(3): 716-719. Journal of Forensic Sciences. 2011;**56**(6):1662. Author reply 1663

models. Journal of Forensic Sciences.

[26] Kennedy P, Rogers B, Speer S, Frankel H. Spinal cord injuries and attempted suicide: A retrospective review. Spinal Cord.

[27] Biering-Sorensen F, Pederson W, Giortz Muller P. Spinal cord injury due to suicide attempts. Paraplegia.

[28] Stanford RE, Soden R, Bartrop R, Mikk M, Taylor TKF. Spinal cord and related injuries after attempted suicide:

[29] Anderson J, Allan DB. Vertebral fracture secondary to suicide attempt: Demographics and patient outcome in a Scottish spinal rehabilitation unit. The Journal of Spinal Cord Medicine.

[30] Zatzick DF, Kang SM, Kim SY, et al. Patients with recognized psychiatric disorders in trauma surgery: Incidence, inpatient length of stay, and cost. The Journal of Trauma. 2000;**49**:487-495

[31] Demetriades D, Gkiokas G, Velmahos GC, et al. Alcohol and illicit drugs in traumatic deaths: Prevalence and association with type and severity of injuries. Journal of the American College of Surgeons. 2004;**199**:687-692

[32] Schecter WP, Klassen C,

O'Connor P, et al. The unmet challenge of the trauma system. Archives of Surgery. 2005;**140**:902-904

[33] The ATLS Subcommittee and the International ATLS Working Group AC of SC on T. Advanced trauma life support (ATLS®): The ninth edition. Journal of Trauma and Acute Care Surgery. 2013;**74**:1363-1366

[34] Papadakis SA, Galanakos S,

Apostolaki A, Kateros K, Antoniadou O, et al. Spinal cord injuries following

Psychiatric diagnosis and longterm follow-up. Spinal Cord.

1999;**37**(12):847-852

1992;**30**(2):139-144

2007;**45**(6):437-443

2011;**34**(4):380-387

Sauvageau A. Skull fracture with brain expulsion in a one-level jumpingfall. Journal of Forensic Sciences.

[21] Hong J, Lee WK, Park H. Change in causes of injury-related deaths in South Korea, 1996-2006. Journal of Epidemiology. 2011;**21**:500-506

[22] Im JS, Choi SH, Hong D, Seo HJ, Park S, Hong JP. Proximal risk factors and suicide methods among suicide completers from national suicide mortality data 2004-2006 in Korea. Comprehensive Psychiatry.

[23] Lee CA, Choi SC, Jung KY, et al. Characteristics of patients who visit the emergency department with selfinflicted injury. Journal of Korean Medical Science. 2012;**27**:307-312

Kapusta ND, et al. Leading causes of unintentional and intentional injury mortality: United States, 2000-2009. American Journal of Public Health.

[25] Richter D, Hahn MP, Ostermann PA, Ekkernkamp A, Muhr G. Vertical deceleration injuries: A comparative study of the injury patterns of 101 patients after accidental and intentional high falls. Injury. 1996;**27**:655-659

[24] Rockett IR, Regier MD,

2012;**102**:e84-e92

2011;**52**:231-237

**114**

[35] American Spinal Injury Association. International Standards for Neurological Classification of Spinal Cord Injury, Revised 2002. Chicago: American Spinal Injury Association; 2002

[36] Lambert DA, Sattin RW. Deaths from falls, 1978-1984. MMWR. CDC Surveillance Summaries. 1988;**37**(1):21-26

[37] Hultιn A, Jiang G-X, Wasserman D, Hawton K, Hjelmeland H, et al. Repetition of attempted suicide among teenagers in Europe: Frequency, timing and risk factors. European Child & Adolescent Psychiatry. 2001;**10**:161-169

[38] Petronis KR, Samuels JF, Moscicki EK, Anthony JC. An epidemiologic investigation of potential risk factors for suicide attempts. Social Psqchiatry and Psychiatric Epidemiology. 1990;**25**:193-199

[39] Beautrais AL. Serious suicide attempts in young people: A case control study. American Journal of Psychiatry. 1996;**153**:1009-1014

[40] Li G, Ling J, Di Scala C. Characteristics and outcomes of self inflicted paediatric injuries: The role of method of suicide attempt. Injury Prevention. 1997;**3**:115-119

[41] Hawton K, Arensman E, Wasserman D, et al. Relation between attempted suicide and suicide rates among young people in Europe. Journal of Epidemiology and Community Health. 1998;**52**:191-194

[42] Granboulan V, Rabain D, Basquin M. The outcome of adolescent suicide attempts. Acta Psychiatrica Scandinavica. 1995;**91**:265-270

[43] Hawton K, Fagg J, Platt S, Hawkins M. Factors associated with suicide after parasuicide in young people. British Journal of Psychiatry. 1993;**306**:1641-1644

[44] Dickinson A, Roberts M, Kumar A, Weaver A, Lockey DJ. Falls from height: Injury and mortality. Journal of the Royal Army Medical Corps. 2012;**158**(2):123-127

[45] Kent A, Pearce A. Review of morbidity and mortality associated with falls from heights among patients presenting to a major trauma Centre. Emergency Medicine Australasia. 2006;**18**(1):23-30

[46] Petaros A, Slaus M, Coklo M, Sosa I, Cengija M, Bosnar A. Retrospective analysis of free-fall fractures with regard to height and cause of fall. Forensic Science International. 2013;**226**(1-3):290-295

[47] Choi JH, Kim SH, Kim SP, Jung KY, Ryu JY, Choi SC, et al. Characteristics of intentional fall injuries in the ED. The American Journal of Emergency Medicine. 2014;**32**(6):529-534

[48] Crandall M, Luchette F, Esposito TJ, West M, Shapiro M, Bulger E. Attempted suicide and the elderly trauma patient: Risk factors and outcomes. The Journal of Trauma. 2007;**62**(4):1021-1027

[49] Maull KI, Whitley RE, Cardea JA. Vertical deceleration injuries. Surgery, Gynecology & Obstetrics. 1981;**153**(2):233-236

[50] Snyder RG. Human tolerance to extreme impacts in free-fall. Aeroscace Medicine. 1963;**34**:695-709

[51] Layton TR, Villella R, Kelly EG. High free fall with survival. The Journal of Trauma. 1981;**21**(11):983-985

[52] Pallis D, Georgiou DF, Abadiotaki M, Galanakos S, Sapkas G, Macheras G, et al.

Comparison of traumatic pattern between accidental falls from height and suicide attempts. In: Presented orally at 20th Congress Efort. Lisbon; 2019

[53] Turgut K, Sarihan ME, Colak C, Güven T, Gür A, Gürbüz S. Falls from height: A retrospective analysis. World Journal of Emergency Medicine. 2018;**9**(1):46-50

[54] Kohli A, Banerjee KK. Pattern of injuries in fatal falls from buildings. Medicine, Science, and the Law. 2006;**46**(4):335-341

[55] Turk EE, Tsokos M. Pathologic features of fatal falls from height. The American Journal of Forensic Medicine and Pathology. 2004;**25**:194-199

[56] Kiran Kumar KV, Srivastava AK. Pattern of injuries in fall from height. Journal of Indian Academy of Forensic Medicine. 2013;**35**(1):47-50

[57] Goren S, Subasi M, Tyrasci Y, Gurkan F. Fatal falls from heights in and around Diyarbakir, Turkey. Forensic Science International. 2003;**137**:37-40

[58] Mao SW, Liu XJ, Su CP, Zhang M, Mu ZQ, et al. Analysis of 574 cases of high-fall death. Fa Yi Xue Za Zhi. 2009;**25**:276-278

[59] Wischhusen F, Patra S, Braumann M, Turk EE, Puschel K. Analysis of jumping/falling distance from a height. Forensic Science International. 2006;**156**:150-153

[60] Piazzalunga D, Rubertà F, Fugazzola P, Allievi N, Ceresoli M, Magnone S, et al. Suicidal fall from heights trauma: Difficult management and poor results. European Journal of Trauma and Emergency Surgery. 2019

[61] Cifu D, Wehman P, Mckinley W. Determining impairment following spinal cord injury. In: Rondinelli R, Katz R, editors. Disability evaluation. Physical Medicine and Rehabilitation Clinics of North America. 2001;**12**(3):603-612

**Chapter 8**

**Abstract**

depressive disorder

**1. Introduction**

**117**

tion and acquisition of emotion information.

*and Zhengzhi Feng*

Advances in Emotion Recognition:

Emotion recognition enables real-time analysis, tagging, and inference of cognitive affective states from human facial expression, speech and tone, body posture and physiological signal, as well as social text on social network platform. Recognition of emotion pattern based on explicit and implicit features extracted through wearable and other devices could be decoded through computational modeling. Meanwhile, emotion recognition and computation are critical to detection and diagnosis of potential patients of mood disorder. The chapter aims to summarize the main findings in the area of affective recognition and its applications in major depressive disorder (MDD), which have made rapid progress in the last decade.

**Keywords:** emotion recognition, computational modeling, machine learning,

Making computers capable of emotional computing was first proposed by Minsky (one of the founders of artificial intelligence) of the MIT. In his book *The Society of Mind* he proposed that "The question is not whether intelligent machines can have any emotions, but whether machines can be intelligent without emotions" [1]. Picard [2] proposed the concept of affective computing (AC) in 1995. Her monograph "Affective Computing" published in 1997 defined affective computing as "calculation related to, derived from or capable of emotions." She divided the research content of affective computing into nine aspects: mechanism of emotion, acquisition of emotion information, recognition of emotion pattern, modeling and understanding of emotion, synthesis and expression of emotion, application of emotion computing, interface of emotion computer, transmission and communication of emotion, and wearable computer. Among these aspects, the practical research of emotion recognition is largely based on theories of mechanism of emo-

The mechanism of emotion is based on phenomenal and mechanistic views of emotion. The phenomenal views typical involved two approaches: discrete and dimensional views of emotion. The former proposed that emotion can be labeled as a limited set of basic emotions which could be combined into complex emotions. This method is problematic because the labels for emotions may be too restrictive to reflect complex emotions. Additionally, these labels may be culture dependent which could not reflect common substrates of different affective labels.

Link to Depressive Disorder

*Xiaotong Cheng, Xiaoxia Wang,Tante Ouyang*

[62] Kirshblum S, O'Connor K. Levels of spinal cord injury and predictors for neurologic recovery. Physical Medicine and Rehabilitation Clinics of North America. 2000;**11**(1):1-27. Edited by Hammond M. Topics in spinal cord injury medicine

[63] Whiteneck G, Tate D, Charlifue S. Predicting community reintegration after spinal cord injury from demographic and injury characteristics. Archives of Physical Medicine and Rehabilitation. 1999;**80**(11):1485-1491

[64] Abel SM, Ramsey S. Patterns of skeletal trauma in suicidal bridge jumpers: A retrospective study from the southeastern United States. Forensic Science International. 2013;**231**(1-3): 399.e1-399.e5

[65] Cetin G, Günay Y, Fincanci SK, Ozdemir Kolusayin R. Suicides by jumping from Bosphorus bridge in Istanbul. Forensic Science International. 2001;**116**(2-3):157-162

[66] Burri C, Kreuzer U, Limmer J. Principles and practice of fracture treatment in the multiply injured patient. Injury. 1982;**14**(1):44-50

[67] Sims A, O'Brien K. Autokabalesis: An account of mentally ill people who jump from buildings. Medicine, Science, and the Law. 1979 Jul;**19**(3):195-198

[68] Prasad A, Lloyd GG. Attempted suicide by jumping. Acta Psychiatrica Scandinavica. 1983;**68**(5):394-396

[69] Katz K, Gonen N, Goldberg I, Mizrahit J, et al. Injuries in attempted suicide by jumping from a height. Injury. 1988;**19**:371-374

#### **Chapter 8**

*Neurological and Mental Disorders*

Comparison of traumatic pattern between accidental falls from height and suicide attempts. In: Presented orally at 20th Congress Efort. Lisbon; 2019

Physical Medicine and Rehabilitation

[62] Kirshblum S, O'Connor K. Levels of spinal cord injury and predictors for neurologic recovery. Physical Medicine and Rehabilitation Clinics of North America. 2000;**11**(1):1-27. Edited by Hammond M. Topics in spinal cord

[63] Whiteneck G, Tate D, Charlifue S. Predicting community reintegration

demographic and injury characteristics. Archives of Physical Medicine and Rehabilitation. 1999;**80**(11):1485-1491

[64] Abel SM, Ramsey S. Patterns of skeletal trauma in suicidal bridge jumpers: A retrospective study from the southeastern United States. Forensic Science International. 2013;**231**(1-3):

[65] Cetin G, Günay Y, Fincanci SK, Ozdemir Kolusayin R. Suicides by jumping from Bosphorus bridge in Istanbul. Forensic Science International.

[66] Burri C, Kreuzer U, Limmer J. Principles and practice of fracture treatment in the multiply injured patient. Injury. 1982;**14**(1):44-50

[67] Sims A, O'Brien K. Autokabalesis: An account of mentally ill people who jump from buildings. Medicine, Science, and the Law. 1979 Jul;**19**(3):195-198

[68] Prasad A, Lloyd GG. Attempted suicide by jumping. Acta Psychiatrica Scandinavica. 1983;**68**(5):394-396

[69] Katz K, Gonen N, Goldberg I, Mizrahit J, et al. Injuries in attempted suicide by jumping from a height.

Injury. 1988;**19**:371-374

after spinal cord injury from

Clinics of North America. 2001;**12**(3):603-612

injury medicine

399.e1-399.e5

2001;**116**(2-3):157-162

[53] Turgut K, Sarihan ME, Colak C, Güven T, Gür A, Gürbüz S. Falls from height: A retrospective analysis. World Journal of Emergency Medicine.

[54] Kohli A, Banerjee KK. Pattern of injuries in fatal falls from buildings. Medicine, Science, and the Law.

[55] Turk EE, Tsokos M. Pathologic features of fatal falls from height. The American Journal of Forensic Medicine

and Pathology. 2004;**25**:194-199

Medicine. 2013;**35**(1):47-50

2009;**25**:276-278

[59] Wischhusen F, Patra S,

Braumann M, Turk EE, Puschel K. Analysis of jumping/falling distance from a height. Forensic Science International. 2006;**156**:150-153

[60] Piazzalunga D, Rubertà F, Fugazzola P, Allievi N, Ceresoli M, Magnone S, et al. Suicidal fall from heights trauma: Difficult management and poor results. European Journal of Trauma and Emergency Surgery. 2019

[61] Cifu D, Wehman P, Mckinley W. Determining impairment following spinal cord injury. In: Rondinelli R, Katz R, editors. Disability evaluation.

[56] Kiran Kumar KV, Srivastava AK. Pattern of injuries in fall from height. Journal of Indian Academy of Forensic

[57] Goren S, Subasi M, Tyrasci Y, Gurkan F. Fatal falls from heights in and around Diyarbakir, Turkey. Forensic Science International. 2003;**137**:37-40

[58] Mao SW, Liu XJ, Su CP, Zhang M, Mu ZQ, et al. Analysis of 574 cases of high-fall death. Fa Yi Xue Za Zhi.

2018;**9**(1):46-50

2006;**46**(4):335-341

**116**

## Advances in Emotion Recognition: Link to Depressive Disorder

*Xiaotong Cheng, Xiaoxia Wang,Tante Ouyang and Zhengzhi Feng*

#### **Abstract**

Emotion recognition enables real-time analysis, tagging, and inference of cognitive affective states from human facial expression, speech and tone, body posture and physiological signal, as well as social text on social network platform. Recognition of emotion pattern based on explicit and implicit features extracted through wearable and other devices could be decoded through computational modeling. Meanwhile, emotion recognition and computation are critical to detection and diagnosis of potential patients of mood disorder. The chapter aims to summarize the main findings in the area of affective recognition and its applications in major depressive disorder (MDD), which have made rapid progress in the last decade.

**Keywords:** emotion recognition, computational modeling, machine learning, depressive disorder

#### **1. Introduction**

Making computers capable of emotional computing was first proposed by Minsky (one of the founders of artificial intelligence) of the MIT. In his book *The Society of Mind* he proposed that "The question is not whether intelligent machines can have any emotions, but whether machines can be intelligent without emotions" [1]. Picard [2] proposed the concept of affective computing (AC) in 1995. Her monograph "Affective Computing" published in 1997 defined affective computing as "calculation related to, derived from or capable of emotions." She divided the research content of affective computing into nine aspects: mechanism of emotion, acquisition of emotion information, recognition of emotion pattern, modeling and understanding of emotion, synthesis and expression of emotion, application of emotion computing, interface of emotion computer, transmission and communication of emotion, and wearable computer. Among these aspects, the practical research of emotion recognition is largely based on theories of mechanism of emotion and acquisition of emotion information.

The mechanism of emotion is based on phenomenal and mechanistic views of emotion. The phenomenal views typical involved two approaches: discrete and dimensional views of emotion. The former proposed that emotion can be labeled as a limited set of basic emotions which could be combined into complex emotions. This method is problematic because the labels for emotions may be too restrictive to reflect complex emotions. Additionally, these labels may be culture dependent which could not reflect common substrates of different affective labels.

The latter proposed that emotions can be distributed in a multidimensional space which continuously evolves. Two common dimensions are valence (pleasantness) and arousal (activation level). The emotion recognition algorithms using emotion representation based on emotional labels are intuitive which are ambiguous for computer processing. Additionally, recognition of emotion pattern involves the classification of emotional data according to a large group of labels. For these reasons, researchers developed a number of dimensional model of emotions, such as Russell's circumplex model, Whissell's evaluation-activation space model, and Plutchik's wheel of emotions [3].

emotion recognition, and posture recognition (see Sections 2.1–2.3); (2) physiological pattern, which means objective emotional index after measuring PNS and CNS physiological signals (see Section 2.5); and (3) psychological measures and multimodal emotion signals, such as textual information and multimodal emotion infor-

Faces may be one of the most important methods for visual communication of emotion. Though started from the 1970s, facial expression recognition is the most studied field in natural emotions machine recognition, especially in the USA and Japan, wherein studies on facial expression recognition have grown to be a hotspot of AI emotion recognition. In 1971, American psychologists Ekman and Friesen categorized facial expression into six types: anger, disgust, happiness, fear, surprise, and sadness. They also established the Facial Action Coding System (FACS) in 1978 [7], which is the earliest research of facial expression recognition. Facial expressions were deemed as observable indicators of internal emotional states, which make

Currently, the most-used facial expression databases included Ekman's FACS and its updated version, automated facial image analysis (AFIA) developed by Carnegie Mellon University, Japanese female expression database JAFFE and its expansion set in Japan ATR Media Information Science Laboratory, Cohn-Kanade expression database, CK+ expression database, and Rafd facial expression database established by CMU Robotics Research Institute, USA. Common facial expression picture libraries in China include the USTC-NVIE image library [8], the CFAPS facial emotion stimulating materials [9], and the Chinese facial expression intensity

The facial expression recognition included the following steps: (1) facial image acquisition, (2) image preprocessing, (3) feature extraction, and (4) emotion clas-

Apart from Ekman's discrete emotion model, facial expression recognition was also conducted under the other emotional models (such as dimensional model). Ballano et al. proposed a method for continuous facial affect recognition from videos based on evaluation-activation 2D model proposed by Whissell [11].

Facial images are obtained from images and videos, including static expressions

Face detection and positioning, face adjustment, editing, scale normalization, histogram equalization, dimming, light compensation, homomorphic filtering,

(a) Static image. Gabor wavelet transformation, local binary patterns (LBP), scaleinvariant feature transformation (SIFT), discrete cosine transformation (DCT),

(b) Dynamic image. Optical flow method, difference image method, feature point

Canonical correlation analysis, sparse representation classification, expert rule-

tracking, model-based method, elastic graph matching.

*An expert rule-based method classifies the emotion according to a set of "if-then" statements based on expert*

mation (see Sections 2.3 and 2.6).

*Advances in Emotion Recognition: Link to Depressive Disorder*

*DOI: http://dx.doi.org/10.5772/intechopen.92019*

**2.1 Facial expression recognition**

emotion differentiation possible.

grading picture library [10].

**Processes Sub-processes and related work**

based method<sup>a</sup>

*experience or sampling with rule acquisition algorithm.*

*Facial expression recognition process.*

and dynamic expressions

graying, Gaussian smoothing

regional covariance matrix.

sification (**Table 1**).

Facial image acquisition

Image preprocessing

Feature extraction

Emotion classification

*a*

**119**

**Table 1.**

According to the mechanistic views of emotion, emotion pattern recognition not only relies on semantic labels but also physiological signals which originate in the peripheral nervous system (PNS) and central nervous system (CNS) dynamics [3]. (1) *The PNS emotion patterns*. The PNS included the autonomic and the somatic nervous systems (ANS and SNS). According to Schachter and Singer's peripheral theories of emotion (or cognition-arousal theory), people assess their emotional state by physiological arousal. Emotion states are inherent in these physiological dynamics and feasibly recognized by using PNS physiological data, according to the work from the lab led by Picard. Ekman and colleges provided the first evidence of PNS differences (including hand temperature, heart rate, skin conductance, and forearm tension) among four negative emotions [4]. However, their algorithms are based on intentionally expressed emotion and are user dependent, which may restrict generalization to other users [5]. (2) *The CNS emotion patterns*. The large majority of computational models of emotion stem from appraisal theory of emotion, which emphasized the CNS process of emotion. Frijda criticized the arousal theory of emotion and proposed that awareness of autonomic responding is not prerequisite for emotional experience or behavior. The differentiation of the emotions is explained as the result of the sequential appraisal for affective stimulus. Scherer suggests that there may be as many emotions as there are different appraisal outcomes. Thus there exists the minimal set of appraisal criteria necessary to the differentiation of primary emotional states. However, it should be noted that physiological changes is not only determined by appraisal meaning but also by factors outside of the appraisal or emotion realm. Therefore, there is not adequate evidence for consistent and specific PNS response during emotional episodes [6].

Practically, the acquisition of emotional information is required for emotion recognition. Emotional information characteristics included a variety of physiological or behavioral reactions concurrent with emotional state changes, including internal and external emotional features. (1) *Internal emotional information*. It refers to physiological reactions that cannot be detected from the outside of human body, such as the electrical or mechanical/chemical output of human brain activity (EEG), heart muscle activity(ECG, heart rate, pulse), skeletal muscle activity (EMG), breathing activity (respiration), and blood vessel activity (blood pressure, hemangiectasis). (2) *External emotional information*. It refers to the reactions that can be directly observed from the appearance, such as facial expression, speech, and posture. The extraction of common features for highly individualized emotion information constitutes the fundamental basis of emotion recognition. A great amount of features could be extracted from internal and external emotional signals, by calculating their mean, standard deviation, transformation, wave band power and peak detection, and others.

#### **2. Methods for emotion recognition**

The main methods for emotion recognition involve the following emotion indexes: (1) emotional behavior, namely, facial expression recognition, speech emotion recognition, and posture recognition (see Sections 2.1–2.3); (2) physiological pattern, which means objective emotional index after measuring PNS and CNS physiological signals (see Section 2.5); and (3) psychological measures and multimodal emotion signals, such as textual information and multimodal emotion information (see Sections 2.3 and 2.6).

#### **2.1 Facial expression recognition**

The latter proposed that emotions can be distributed in a multidimensional space which continuously evolves. Two common dimensions are valence (pleasantness) and arousal (activation level). The emotion recognition algorithms using emotion representation based on emotional labels are intuitive which are ambiguous for computer processing. Additionally, recognition of emotion pattern involves the classification of emotional data according to a large group of labels. For these reasons, researchers developed a number of dimensional model of emotions, such as Russell's circumplex model, Whissell's evaluation-activation space model, and

According to the mechanistic views of emotion, emotion pattern recognition not only relies on semantic labels but also physiological signals which originate in the peripheral nervous system (PNS) and central nervous system (CNS) dynamics [3]. (1) *The PNS emotion patterns*. The PNS included the autonomic and the somatic nervous systems (ANS and SNS). According to Schachter and Singer's peripheral theories of emotion (or cognition-arousal theory), people assess their emotional state by physiological arousal. Emotion states are inherent in these physiological dynamics and feasibly recognized by using PNS physiological data, according to the work from the lab led by Picard. Ekman and colleges provided the first evidence of PNS differences (including hand temperature, heart rate, skin conductance, and forearm tension) among four negative emotions [4]. However, their algorithms are based on intentionally expressed emotion and are user dependent, which may restrict generalization to other users [5]. (2) *The CNS emotion patterns*. The large majority of computational models of emotion stem from appraisal theory of emotion, which emphasized the CNS process of emotion. Frijda criticized the arousal theory of emotion and proposed that awareness of autonomic responding is not prerequisite for emotional experience or behavior. The differentiation of the emotions is explained as the result of the sequential appraisal for affective stimulus. Scherer suggests that there may be as many emotions as there are different appraisal outcomes. Thus there exists the minimal set of appraisal criteria necessary to the differentiation of primary emotional states. However, it should be noted that physiological changes is not only determined by appraisal meaning but also by factors outside of the appraisal or emotion realm. Therefore, there is not adequate evidence

for consistent and specific PNS response during emotional episodes [6].

**2. Methods for emotion recognition**

**118**

Practically, the acquisition of emotional information is required for emotion recognition. Emotional information characteristics included a variety of physiological or behavioral reactions concurrent with emotional state changes, including internal and external emotional features. (1) *Internal emotional information*. It refers to physiological reactions that cannot be detected from the outside of human body, such as the electrical or mechanical/chemical output of human brain activity (EEG), heart muscle activity(ECG, heart rate, pulse), skeletal muscle activity (EMG), breathing activity (respiration), and blood vessel activity (blood pressure, hemangiectasis). (2) *External emotional information*. It refers to the reactions that can be directly observed from the appearance, such as facial expression, speech, and posture. The extraction of common features for highly individualized emotion information constitutes the fundamental basis of emotion recognition. A great amount of features could be extracted from internal and external emotional signals, by calculating their mean, standard deviation, transformation, wave band power and peak detection, and others.

The main methods for emotion recognition involve the following emotion indexes: (1) emotional behavior, namely, facial expression recognition, speech

Plutchik's wheel of emotions [3].

*Neurological and Mental Disorders*

Faces may be one of the most important methods for visual communication of emotion. Though started from the 1970s, facial expression recognition is the most studied field in natural emotions machine recognition, especially in the USA and Japan, wherein studies on facial expression recognition have grown to be a hotspot of AI emotion recognition. In 1971, American psychologists Ekman and Friesen categorized facial expression into six types: anger, disgust, happiness, fear, surprise, and sadness. They also established the Facial Action Coding System (FACS) in 1978 [7], which is the earliest research of facial expression recognition. Facial expressions were deemed as observable indicators of internal emotional states, which make emotion differentiation possible.

Currently, the most-used facial expression databases included Ekman's FACS and its updated version, automated facial image analysis (AFIA) developed by Carnegie Mellon University, Japanese female expression database JAFFE and its expansion set in Japan ATR Media Information Science Laboratory, Cohn-Kanade expression database, CK+ expression database, and Rafd facial expression database established by CMU Robotics Research Institute, USA. Common facial expression picture libraries in China include the USTC-NVIE image library [8], the CFAPS facial emotion stimulating materials [9], and the Chinese facial expression intensity grading picture library [10].

The facial expression recognition included the following steps: (1) facial image acquisition, (2) image preprocessing, (3) feature extraction, and (4) emotion classification (**Table 1**).

Apart from Ekman's discrete emotion model, facial expression recognition was also conducted under the other emotional models (such as dimensional model). Ballano et al. proposed a method for continuous facial affect recognition from videos based on evaluation-activation 2D model proposed by Whissell [11].


*a An expert rule-based method classifies the emotion according to a set of "if-then" statements based on expert experience or sampling with rule acquisition algorithm.*

#### **Table 1.**

*Facial expression recognition process.*

The evaluation dimension defines the valence of emotion, while the activation dimension defines the action tendencies (e.g., active versus passive) under the emotional state. Their model extended the emotion information to continuous emotional trajectory.

recognition. Zhang et al. [21] use a multilayer deep belief network (DBN) to automatically extract the emotional features in speech signals, piece together consecutive multi-frame speeches to form an abstract high-dimensional feature, use features trained by the deep belief network as the input end of the extreme learning machine (ELM) classifier, and ultimately establish a speech emotion recognition system. Zhu et al. [22] propose a track-based space-time spectral signature speech emotion recognition method and obtain relatively accurate results. Liu and Qin [23] study the application of speech emotion recognition in manned space flight, establish a stress emotion corpus, and build speech emotion recognition model and software through feature extraction and Gaussian mixture model (GMM) to verify

The emotional speech features extracted in the abovementioned study are mostly targeted at personalized speech emotion recognition, while the feature extraction for non-personalized speech emotion recognition is still a challenge. Recent efforts have been made toward development of large corpus [24]. The current speech emotion recognition study is limited by lack of unified, public and standard mandarin emotion corpus, as well as an authoritative and unified standard for building emotion corpus. Many researches are conducted based on self-recorded databases which vary in terms of age, gender, number of participants, text information, and the scale of the final corpus, making it difficult to compare between different research results. Furthermore, most of the studies are conducted based on discrete emotions, taking into consideration limited emotional dimension corpus.

Posture refers to the expressional actions of other parts of human body than face. It can coordinate or supplement speech content and effectively convey emotional information. Postures can be divided into body expression and gestures. Body expression is one of the ways to express emotions. People would have different postures under different emotional state, such as belly laugh when happy, arched shoulders when scared, and being fidgeted when nervous. Postures such as raising hands and akimbo can express individual emotions. People may have different postures at different emotional state and level, hence it is possible to analyze and predict emotional state by observing different expressions and intensity of the expression. Researchers have pointed out at early times that posture and movements can only reflect intensity of emotion, but not the essence and type of the emotions. Later, some put forward that posture is conducive to the expression of emotional intensity although it cannot reflect accurately emotional state. Some scholars have studied the ability of subjects to understand six basic postures, the subjects were expressionless throughout the test, and the result showed that posture

can be used to identify certain emotional state, such as sorrow and fear.

Generally, there are two posture recognition methods: (1) recognizing affective content of daily behavior through analysis and (2) using the temporal and spatial characteristics of gestures (such as the rhythm, amplitude, and strength of the motion) to analyze the affective content. For example, Castellano et al. [25] proposed a method for recognizing emotions based on human motion indicators (such as amplitude, velocity, and mobility) and establishing emotional models with image sequences and motion test indicators; Bernhardt and Robinson [26] used segmentation techniques to quantify high-dimensional motion into a set of simple motion data, extract motion features, and pair them with corresponding emotions; Liu et al. [27] classified the body movement and combined motion and velocity parameters for weighting function calculation to identify the emotion expressed by certain movement. Shao and Wang [28] extracted two 3D texture features by processing

the accuracy of speech emotion recognition.

*Advances in Emotion Recognition: Link to Depressive Disorder*

*DOI: http://dx.doi.org/10.5772/intechopen.92019*

**2.3 Posture emotion recognition**

**121**

Micro-expressions are quick, unconscious, and spontaneous facial movements that occur when people experience strong emotions. The duration of microexpression is about 1/25 to 1/2 s. The fleeting micro-expression has small movement and does not appear in the upper face and the lower face at the same time, so it is quite difficult to observe and recognize correctly. Therefore, the collection and selection of micro-expression data sets are very important. Micro-expression recognition requires (1) the image acquisition and preprocessing of face image, (2) the detection of micro-expressions from the face and the extraction of its features, and (3) classifying and recognizing the categories of the micro-emoticon. Different research teams have developed different automatic micro-expression recognition systems and established databases.

Polikovsky et al. [12] explored the 3D gradient histogram method for feature extraction of facial micro-expressions in video sequences based on the Polikovsky expression library. They proposed a new approach to capture micro-expression using 200fps high-speed camera. Shreve et al. [13] established the USF-HD database and applied the optical flow method for automatic micro-expression recognition research. They developed a method of automatically spotting continuously changing facial expressions in long videos. The University of Oulu in Finland developed the spontaneous micro-expression corpus (SMIC) and SMIC2. Yan et al. [14] improved the micro-expression elicitation paradigm and developed the Chinese micro-expression database CASME. Later on they further expanded the sample number, improved the frame rate and image quality of CASME, and created CASMEII. They differentiated full suppression of facial movements from selfperceived suppression of facial movements. The micro-expressions were elicited in a well-controlled laboratory context and had high temporal resolution (200 frames/s). The best performance is 63.41% for 5-class classification.

#### **2.2 Speech emotion recognition**

As the easiest, most basic, and direct way of information communication, speech contains rich emotional information. Speech could not only convey semantic information but also reveal speaker's emotional state, for instance, a person may have a voice with high volume, heavy tones, and accelerated speed when getting angry, but sullen intonation and slow speed when feeling sad. Therefore, in order to make the computer understand people's emotions better and interact more naturally with people, it is necessary to study speech emotions. Speech emotion recognition is widely applied in man-machine interaction, such as automatic customer service system, which can transfer emotional users to manual service [15]; it monitors the driver's emotional fluctuations based upon his speech speed and volume to remind him of staying calm, thus preventing him from a car accident [16]; it helps the disabled to speak [17]; and it detects emotional state of patients with mental disorders based upon context analysis [18].

Most of the studies use prosodic features as characteristic parameters of speech emotion recognition. For example, Gharavian et al. [19] extracted parameters such as fundamental frequency, resonance peak, and Mel coefficient and then analyzed the correlation among them. The obtained 25-dimensional vectors were classified by FAMNN classification algorithm to gain a more credible emotion recognition result. Devi et al. [20] summarized speech signal preprocessing techniques, common short-term energy, MFCC features, and their applications in speech emotion

#### *Advances in Emotion Recognition: Link to Depressive Disorder DOI: http://dx.doi.org/10.5772/intechopen.92019*

The evaluation dimension defines the valence of emotion, while the activation dimension defines the action tendencies (e.g., active versus passive) under the emotional state. Their model extended the emotion information to continuous

that occur when people experience strong emotions. The duration of micro-

Micro-expressions are quick, unconscious, and spontaneous facial movements

expression is about 1/25 to 1/2 s. The fleeting micro-expression has small movement and does not appear in the upper face and the lower face at the same time, so it is quite difficult to observe and recognize correctly. Therefore, the collection and selection of micro-expression data sets are very important. Micro-expression recognition requires (1) the image acquisition and preprocessing of face image, (2) the detection of micro-expressions from the face and the extraction of its features, and (3) classifying and recognizing the categories of the micro-emoticon. Different research teams have developed different automatic micro-expression recognition

Polikovsky et al. [12] explored the 3D gradient histogram method for feature extraction of facial micro-expressions in video sequences based on the Polikovsky expression library. They proposed a new approach to capture micro-expression using 200fps high-speed camera. Shreve et al. [13] established the USF-HD database and applied the optical flow method for automatic micro-expression recognition research. They developed a method of automatically spotting continuously changing facial expressions in long videos. The University of Oulu in Finland developed the spontaneous micro-expression corpus (SMIC) and SMIC2. Yan et al. [14] improved the micro-expression elicitation paradigm and developed the Chinese micro-expression database CASME. Later on they further expanded the sample number, improved the frame rate and image quality of CASME, and created CASMEII. They differentiated full suppression of facial movements from selfperceived suppression of facial movements. The micro-expressions were elicited in

a well-controlled laboratory context and had high temporal resolution (200 frames/s). The best performance is 63.41% for 5-class classification.

As the easiest, most basic, and direct way of information communication, speech contains rich emotional information. Speech could not only convey semantic information but also reveal speaker's emotional state, for instance, a person may have a voice with high volume, heavy tones, and accelerated speed when getting angry, but sullen intonation and slow speed when feeling sad. Therefore, in order to make the computer understand people's emotions better and interact more naturally with people, it is necessary to study speech emotions. Speech emotion recognition is widely applied in man-machine interaction, such as automatic customer service system, which can transfer emotional users to manual service [15]; it monitors the driver's emotional fluctuations based upon his speech speed and volume to remind him of staying calm, thus preventing him from a car accident [16]; it helps the disabled to speak [17]; and it detects emotional state of patients with mental disor-

Most of the studies use prosodic features as characteristic parameters of speech emotion recognition. For example, Gharavian et al. [19] extracted parameters such as fundamental frequency, resonance peak, and Mel coefficient and then analyzed the correlation among them. The obtained 25-dimensional vectors were classified by FAMNN classification algorithm to gain a more credible emotion recognition result. Devi et al. [20] summarized speech signal preprocessing techniques, common short-term energy, MFCC features, and their applications in speech emotion

emotional trajectory.

*Neurological and Mental Disorders*

systems and established databases.

**2.2 Speech emotion recognition**

ders based upon context analysis [18].

**120**

recognition. Zhang et al. [21] use a multilayer deep belief network (DBN) to automatically extract the emotional features in speech signals, piece together consecutive multi-frame speeches to form an abstract high-dimensional feature, use features trained by the deep belief network as the input end of the extreme learning machine (ELM) classifier, and ultimately establish a speech emotion recognition system. Zhu et al. [22] propose a track-based space-time spectral signature speech emotion recognition method and obtain relatively accurate results. Liu and Qin [23] study the application of speech emotion recognition in manned space flight, establish a stress emotion corpus, and build speech emotion recognition model and software through feature extraction and Gaussian mixture model (GMM) to verify the accuracy of speech emotion recognition.

The emotional speech features extracted in the abovementioned study are mostly targeted at personalized speech emotion recognition, while the feature extraction for non-personalized speech emotion recognition is still a challenge. Recent efforts have been made toward development of large corpus [24]. The current speech emotion recognition study is limited by lack of unified, public and standard mandarin emotion corpus, as well as an authoritative and unified standard for building emotion corpus. Many researches are conducted based on self-recorded databases which vary in terms of age, gender, number of participants, text information, and the scale of the final corpus, making it difficult to compare between different research results. Furthermore, most of the studies are conducted based on discrete emotions, taking into consideration limited emotional dimension corpus.

#### **2.3 Posture emotion recognition**

Posture refers to the expressional actions of other parts of human body than face. It can coordinate or supplement speech content and effectively convey emotional information. Postures can be divided into body expression and gestures. Body expression is one of the ways to express emotions. People would have different postures under different emotional state, such as belly laugh when happy, arched shoulders when scared, and being fidgeted when nervous. Postures such as raising hands and akimbo can express individual emotions. People may have different postures at different emotional state and level, hence it is possible to analyze and predict emotional state by observing different expressions and intensity of the expression. Researchers have pointed out at early times that posture and movements can only reflect intensity of emotion, but not the essence and type of the emotions. Later, some put forward that posture is conducive to the expression of emotional intensity although it cannot reflect accurately emotional state. Some scholars have studied the ability of subjects to understand six basic postures, the subjects were expressionless throughout the test, and the result showed that posture can be used to identify certain emotional state, such as sorrow and fear.

Generally, there are two posture recognition methods: (1) recognizing affective content of daily behavior through analysis and (2) using the temporal and spatial characteristics of gestures (such as the rhythm, amplitude, and strength of the motion) to analyze the affective content. For example, Castellano et al. [25] proposed a method for recognizing emotions based on human motion indicators (such as amplitude, velocity, and mobility) and establishing emotional models with image sequences and motion test indicators; Bernhardt and Robinson [26] used segmentation techniques to quantify high-dimensional motion into a set of simple motion data, extract motion features, and pair them with corresponding emotions; Liu et al. [27] classified the body movement and combined motion and velocity parameters for weighting function calculation to identify the emotion expressed by certain movement. Shao and Wang [28] extracted two 3D texture features by processing

the image sequences of body movement and used this as a basis for emotion classification. The recognition rate can reach 77.0% in experiment which tests seven common natural emotions in the FABO database.

supervised learning for the classification and prediction of emotional polarity in microblogs, and the accuracy of the experimental analysis reached 79.9%. Huang et al. [31] proposed a multifeature fusion-based microblog theme and emotion mining model TMMMF and verified its validity; Zhang et al. [32] proposed a joint model of microblog emotion recognition and emotion incentive extraction based on neural network. The experiment shows that the F value of the model in the emotion incentive extraction task is 82.70% and the F value in the emotion recognition task

William James [33] proposed that emotions derive from peripheral physiological responses. Kreibig [34] examined the patterns of autonomic nervous system activity under different emotions, showing the specificities in different physiological responses. For example, fear would cause accelerated heart rate and respiratory rhythm and strengthened galvanic skin response. The theory confirms the role of autonomous physiological activities in emotional expression but ignores the role of the brain center in emotions. In 1929, Cannon questioned James's theory and came up with the Cannon-Bard theory (also known as the thalamus theory) with Bard. According to this theory, emotions and their corresponding physiological changes occur simultaneously, both of which are controlled by the thalamus, and the central brain determines the nature of emotions, which affirms the central nervous system's role in regulating and controlling emotions. In conclusion, the occurrence of emotions is accompanied by certain degree of physiological activation of the central and peripheral nervous system. This provides a theoretical basis for studying emotion

Early studies mainly focused on the PNS physiological signals such as skin temperature, blood pressure, electrocardiogram, electromyography, respiratory action, galvanic skin response, and blood volume fluctuation for emotion recognition. Picard et al. [35] collected four physiological signals of galvanic skin response, blood volume fluctuation, electromyographic signal, and respiratory action under different emotional states and reached 81% in terms of recognition accuracy for eight emotions. Kim and Andre [36] developed a short-term monitoring emotion recognition system based on physiological signals of multiple users. They used support vector machine (SVM) to classify and identify four emotions including sadness, depression, surprise, and anger, achieving a classification rate at 95%. Yan et al. [37] collected a variety of physiological signals through multipurpose polygraph MP150: used Fisher, k-NN, and other intelligent algorithms for feature extraction and analysis; and identified six basic emotional states with recognition rate being at 60–90%. Li et al. [38] proposed emotion recognition based on recursive quantitative analysis of physiological signals. They extracted 10 sets of

nonlinear features from the recursive graphs of skin conductance signals, myoelectric signals, and respiratory signals and achieved higher emotion recognition rate. Jin et al. [39] used the updated LSTSVM for emotion recognition based on the physiological signals of electroencephalography, skin conductance, myoelectricity,

In recent years, with the development of neurophysiology and the rise of brain imaging technology, CNS brain signals have attracted the attention of researchers and been used in emotion recognition because of their high temporal resolution and strong functional specificity. In the early stage of the study, the most common measurement index was electroencephalogram (EEG). Some scholars pointed out that the frontal brain asymmetry is closely related to emotional valence. Studies have shown that high-frequency parts of EEG can reflect people's emotional and

and respiration and obtained higher recognition accuracy.

is 74.74%.

**123**

**2.5 Physiological model recognition**

*Advances in Emotion Recognition: Link to Depressive Disorder*

*DOI: http://dx.doi.org/10.5772/intechopen.92019*

recognition in different physiological patterns.

The posture recognition process mainly includes four steps: motion data acquisition, preprocessing, motion feature extraction, and emotion classification. *Firstly*, motion data collection. Generally, there are two types of motion data collection methods: (1) contact type which is a wearable device embedded with various sensors, such as electronic gloves and data shoe covers, and (2) noncontact type, which generally obtains image information through the camera. The contact recognition technology has high equipment cost, uncomfortable user experience, and goes against the objective of natural man–machine interaction. *Secondly*, data preprocessing. This generally includes human body detection, image denoising, image segmentation, image binarization processing, time window, filtering processing, and others. Among them, human body detection mainly includes basic image segmentation, background difference method, interframe difference method, optical flow method, and energy minimization method. *Thirdly*, motion feature extraction. Generally speaking, motion features can be divided into four categories: (1) static features which include size, color, outline, shape, and depth; (2) dynamic features which include speed, optical flow, direction, and trajectory; (3) spatiotemporal features which include spatiotemporal context, spatiotemporal shape, and spatiotemporal interest points; and (4) descriptive features which include scenes, attributes, objects, and poses. There are three types of most-used methods for motion feature extraction, namely, time domain analysis, frequency domain analysis, and time-frequency domain analysis. *Fourthly*, emotional classification. Other classifiers than the commonly used ones are dynamic time warping, dynamic programming, potential Dirichlet distribution, probabilistic latent semantic analysis, context-free grammar, finite state machines, conditional random fields, and others.

#### **2.4 Textual emotion recognition**

Emotions are not exactly linguistic constructs. However the most convenient to emotion is through language. With the advent of social media, social media platforms are becoming a rich source of multimodal affective information, including text, videos, images, and audios. One of them is textual analysis. Affect recognition from text analysis is often used for a public opinion mining. The process of text recognition contains four steps: material collection, text preprocessing, feature extraction, and emotion classification. (1) The first step is material collection. Web crawlers are commonly used to collect materials from blogs, e-commerce sites, and news sites. (2) The second step is text preprocessing, which includes word segmentation, part-of-speech tagging, tag filtering, affix trimming, simplification and replacement, and so on. (3) The third step is feature extraction. Main text features involve words, phrases, n-gram, concepts, and others. Words containing general features can be automatically extracted, while others need to be identified by human efforts before creating emotional glossary. Other methods used are frequent pattern mining techniques and associated rule mining techniques. (4) The fourth step is emotion classification. In addition to some commonly used classifiers, it also includes central vector classification, maximum entropy, emotion-based words labeling, and word frequency-weighted statistics.

Domestic researches on text recognition mainly center around emotion recognition of social platforms such as microblog. For example, Hao et al. [29] proposed a microblog emotion recognition method based on wording features of microblogs and verified its validity. Hao et al. [30] proposed a classification method based on

supervised learning for the classification and prediction of emotional polarity in microblogs, and the accuracy of the experimental analysis reached 79.9%. Huang et al. [31] proposed a multifeature fusion-based microblog theme and emotion mining model TMMMF and verified its validity; Zhang et al. [32] proposed a joint model of microblog emotion recognition and emotion incentive extraction based on neural network. The experiment shows that the F value of the model in the emotion incentive extraction task is 82.70% and the F value in the emotion recognition task is 74.74%.

#### **2.5 Physiological model recognition**

the image sequences of body movement and used this as a basis for emotion classification. The recognition rate can reach 77.0% in experiment which tests seven

The posture recognition process mainly includes four steps: motion data acquisition, preprocessing, motion feature extraction, and emotion classification. *Firstly*, motion data collection. Generally, there are two types of motion data collection methods: (1) contact type which is a wearable device embedded with various sensors, such as electronic gloves and data shoe covers, and (2) noncontact type, which generally obtains image information through the camera. The contact recognition technology has high equipment cost, uncomfortable user experience, and goes against the objective of natural man–machine interaction. *Secondly*, data preprocessing. This generally includes human body detection, image denoising, image segmentation, image binarization processing, time window, filtering

processing, and others. Among them, human body detection mainly includes basic image segmentation, background difference method, interframe difference method, optical flow method, and energy minimization method. *Thirdly*, motion feature extraction. Generally speaking, motion features can be divided into four categories: (1) static features which include size, color, outline, shape, and depth; (2) dynamic features which include speed, optical flow, direction, and trajectory; (3) spatiotemporal features which include spatiotemporal context, spatiotemporal shape, and spatiotemporal interest points; and (4) descriptive features which include scenes, attributes, objects, and poses. There are three types of most-used methods for motion feature extraction, namely, time domain analysis, frequency domain analysis, and time-frequency domain analysis. *Fourthly*, emotional classification. Other classifiers than the commonly used ones are dynamic time warping, dynamic programming, potential Dirichlet distribution, probabilistic latent semantic analysis, context-free grammar, finite state machines, conditional random fields,

Emotions are not exactly linguistic constructs. However the most convenient to emotion is through language. With the advent of social media, social media platforms are becoming a rich source of multimodal affective information, including text, videos, images, and audios. One of them is textual analysis. Affect recognition from text analysis is often used for a public opinion mining. The process of text recognition contains four steps: material collection, text preprocessing, feature extraction, and emotion classification. (1) The first step is material collection. Web crawlers are commonly used to collect materials from blogs, e-commerce sites, and news sites. (2) The second step is text preprocessing, which includes word segmentation, part-of-speech tagging, tag filtering, affix trimming, simplification and replacement, and so on. (3) The third step is feature extraction. Main text features involve words, phrases, n-gram, concepts, and others. Words containing general features can be automatically extracted, while others need to be identified by human efforts before creating emotional glossary. Other methods used are frequent pattern mining techniques and associated rule mining techniques. (4) The fourth step is emotion classification. In addition to some commonly used classifiers, it also includes central vector classification, maximum entropy, emotion-based words

Domestic researches on text recognition mainly center around emotion recognition of social platforms such as microblog. For example, Hao et al. [29] proposed a microblog emotion recognition method based on wording features of microblogs and verified its validity. Hao et al. [30] proposed a classification method based on

common natural emotions in the FABO database.

*Neurological and Mental Disorders*

and others.

**122**

**2.4 Textual emotion recognition**

labeling, and word frequency-weighted statistics.

William James [33] proposed that emotions derive from peripheral physiological responses. Kreibig [34] examined the patterns of autonomic nervous system activity under different emotions, showing the specificities in different physiological responses. For example, fear would cause accelerated heart rate and respiratory rhythm and strengthened galvanic skin response. The theory confirms the role of autonomous physiological activities in emotional expression but ignores the role of the brain center in emotions. In 1929, Cannon questioned James's theory and came up with the Cannon-Bard theory (also known as the thalamus theory) with Bard. According to this theory, emotions and their corresponding physiological changes occur simultaneously, both of which are controlled by the thalamus, and the central brain determines the nature of emotions, which affirms the central nervous system's role in regulating and controlling emotions. In conclusion, the occurrence of emotions is accompanied by certain degree of physiological activation of the central and peripheral nervous system. This provides a theoretical basis for studying emotion recognition in different physiological patterns.

Early studies mainly focused on the PNS physiological signals such as skin temperature, blood pressure, electrocardiogram, electromyography, respiratory action, galvanic skin response, and blood volume fluctuation for emotion recognition. Picard et al. [35] collected four physiological signals of galvanic skin response, blood volume fluctuation, electromyographic signal, and respiratory action under different emotional states and reached 81% in terms of recognition accuracy for eight emotions. Kim and Andre [36] developed a short-term monitoring emotion recognition system based on physiological signals of multiple users. They used support vector machine (SVM) to classify and identify four emotions including sadness, depression, surprise, and anger, achieving a classification rate at 95%. Yan et al. [37] collected a variety of physiological signals through multipurpose polygraph MP150: used Fisher, k-NN, and other intelligent algorithms for feature extraction and analysis; and identified six basic emotional states with recognition rate being at 60–90%. Li et al. [38] proposed emotion recognition based on recursive quantitative analysis of physiological signals. They extracted 10 sets of nonlinear features from the recursive graphs of skin conductance signals, myoelectric signals, and respiratory signals and achieved higher emotion recognition rate. Jin et al. [39] used the updated LSTSVM for emotion recognition based on the physiological signals of electroencephalography, skin conductance, myoelectricity, and respiration and obtained higher recognition accuracy.

In recent years, with the development of neurophysiology and the rise of brain imaging technology, CNS brain signals have attracted the attention of researchers and been used in emotion recognition because of their high temporal resolution and strong functional specificity. In the early stage of the study, the most common measurement index was electroencephalogram (EEG). Some scholars pointed out that the frontal brain asymmetry is closely related to emotional valence. Studies have shown that high-frequency parts of EEG can reflect people's emotional and

cognitive states and the γ and β bands can better tell the change of emotional state than the low-frequency band [40]. Jie et al. [41] realized the recognition of high and low arousal and high and low pleasure through nonlinear feature sample entropy. Duan et al. [42] used differential entropy in machine classification learning for emotion recognition, and the classification accuracy rate was up to 84.22%. It is shown that as a nonlinear EEG feature, differential entropy shows higher classification efficiency. Later, some scholars combined spontaneous physiological signals with EEG and used comprehensive information to improve the recognition rate [43, 44].

c. **Time-frequency feature**. The time-frequency feature extraction considers joint distribution information in terms of time domain and frequency domain. This method describes the changing relationship between signal frequencies and time and contains more comprehensive contents. Commonly used analysis methods are wavelet transform, short-time Fourier transform, Hilbert-Huang transform, and others. Wavelet transform has multiresolution, adjustable sliding time window, has good resolution in both time domain and frequency domain, and has become an effective tool for analyzing nonstationary signals, such as EEG, ECG, EMG, and other signals underlying emotion

d. **Nonlinear feature**. EEG signals are created in complex limbic system with noticeable nonlinearity and chaos characteristic, so the extraction of EEG features is more complex and diverse than other physiological signals. In recent years, the analysis of nonlinear features such as entropy, correlation dimension, and fractal dimension has gradually increased in the study of emotional EEG recognition. Konstantinidis et al. [48] calculated the correlation dimension of emotional EEG for online recognition research; Liu et al. [49] extracted the nonlinear features such as the fractal dimension of EEG to obtain the ideal

Most recent researches have focused on multimodal emotion recognition using visual and aural information. Human expression of emotion is mostly multimodal, including visual, audio, and textual modalities for effective communication [3]. Furthermore, physiological signals can reveal emotional state objectively, even if the subject conceals his/her expression of emotion due to complex reasons. Hence emotion recognition integrating multiple modalities has gained increasing attention, and research hotspot has shifted from single modality to multimodal emotion recognition in practical applications. D'Mello and Kory [50] used statistical methods to compare the accuracy of single modality and multimodal on different databases. Multimodal expression recognition was superior to single modality performance in the experiments. The McGurk [51] phenomenon reveals that in the process of brain perception, different senses are automatically combined unconsciously to process the information, and any lack or inaccuracy of sensory information will lead to deviations in the brain's understanding of external information. Therefore, multimodal feature fusion recognition technology has become a research hotspot in the

The widely used multimodal emotion databases are HUMAINE database [52], the Belfast database [53], the large-scale audiovisual database SEMAINE [54], the IEMOCAP emotional database [55], the audiovisual database eNTERFACE [56], the Acted Facial Expression in the Wild database (AFEW) [57] composed of audio and video clips from English movies and TV programs, and the Chinese multimodal

Multichannel information fusion levels can be divided into three categories: data layer, feature layer, and decision layer: (1) Data layer fusion refers to the fusion of collected raw data and then extracting feature vector from the fused data, finally classifying the emotion; (2) feature layer fusion refers to conducting preprocessing and feature extraction of the collected data of each channel first, then obtaining the

recognition effect and built an online application.

processes.

*Advances in Emotion Recognition: Link to Depressive Disorder*

*DOI: http://dx.doi.org/10.5772/intechopen.92019*

**2.6 Multimodal emotion recognition**

past few years.

**125**

emotional data set CHEAVD [58].

However, the EEG acquisition process is relatively complicated and often has the interference with external noise and electromyography. The cerebral blood oxygen parameter measurement method based on functional near-infrared spectroscopy (NIRS) is gaining greater popularity in emotion recognition because of its high portability, insensitivity to noise and motion, and high possibility for long-term continuous measurement. Tai and Chau [45] extracted the time domain features of prefrontal signals during affective states to identify positive and negative emotions elicited by emotional pictures. The recognition rate of 13 subjects was within the range of 75.0–96.67%.

The most critical steps in emotion recognition based on physiological signals are signal preprocessing, feature extraction and optimization, and classification identification.

	- a. **Time domain**. Time domain feature extraction is found first and relatively simple. It obtains information in amplitude, mean value, standard deviation, partiality, and kurtosis by analyzing the time domain waveform of signal. In this processing, less information is lost. Common time domain analysis methods include zero-crossing analysis, histogram analysis, analysis of variance, correlation analysis, peak detection, waveform parameter analysis, and waveform recognition. Emotion recognition studies using cerebral blood oxygen parameters more often involve time domain feature analysis and extraction.
	- b. **Frequency domain**. Frequency domain feature extraction is based on power spectrum analysis and widely used in analysis of ECG, respiration, EEG, and other signals, such as power spectrum ratio, power spectrum energy, and sub-band power spectral density in different frequency bands.

cognitive states and the γ and β bands can better tell the change of emotional state than the low-frequency band [40]. Jie et al. [41] realized the recognition of high and low arousal and high and low pleasure through nonlinear feature sample entropy. Duan et al. [42] used differential entropy in machine classification learning for emotion recognition, and the classification accuracy rate was up to 84.22%. It is shown that as a nonlinear EEG feature, differential entropy shows higher classification efficiency. Later, some scholars combined spontaneous physiological signals with EEG and used comprehensive information to improve the

However, the EEG acquisition process is relatively complicated and often has the interference with external noise and electromyography. The cerebral blood oxygen parameter measurement method based on functional near-infrared spectroscopy (NIRS) is gaining greater popularity in emotion recognition because of its high portability, insensitivity to noise and motion, and high possibility for long-term continuous measurement. Tai and Chau [45] extracted the time domain features of prefrontal signals during affective states to identify positive and negative emotions elicited by emotional pictures. The recognition rate of 13 subjects was within the

The most critical steps in emotion recognition based on physiological signals are signal preprocessing, feature extraction and optimization, and classification

1.**Emotion signal preprocessing**. This step mainly retains valid data segments during emotion induction process at its highest level and then removes noise and artifacts from the signal. The artifact removal methods mainly include filtering, normalization, independent component analysis, and so on. (a) Filters with different frequency band parameters, such as adaptive filters and Butterworth filters, are commonly used for denoising physiological signals, such as smoothing filtering of the galvanic skin to remove high-frequency glitch. (b) Normalization could reduce the adverse effects of baseline individual differences on emotion recognition [46]. (c) Independent component analysis or principal component analysis may remove electro-

2.**Feature extraction**. There are four main types of features: time domain,

a. **Time domain**. Time domain feature extraction is found first and relatively simple. It obtains information in amplitude, mean value, standard deviation, partiality, and kurtosis by analyzing the time domain waveform of signal. In this processing, less information is lost.

Common time domain analysis methods include zero-crossing

peak detection, waveform parameter analysis, and waveform

analysis, histogram analysis, analysis of variance, correlation analysis,

recognition. Emotion recognition studies using cerebral blood oxygen parameters more often involve time domain feature analysis and

b. **Frequency domain**. Frequency domain feature extraction is based on power spectrum analysis and widely used in analysis of ECG,

respiration, EEG, and other signals, such as power spectrum ratio, power spectrum energy, and sub-band power spectral density in different

frequency domain, time-frequency, and nonlinear features.

recognition rate [43, 44].

*Neurological and Mental Disorders*

range of 75.0–96.67%.

oculogram and artifacts [47].

extraction.

frequency bands.

**124**

identification.


#### **2.6 Multimodal emotion recognition**

Most recent researches have focused on multimodal emotion recognition using visual and aural information. Human expression of emotion is mostly multimodal, including visual, audio, and textual modalities for effective communication [3]. Furthermore, physiological signals can reveal emotional state objectively, even if the subject conceals his/her expression of emotion due to complex reasons. Hence emotion recognition integrating multiple modalities has gained increasing attention, and research hotspot has shifted from single modality to multimodal emotion recognition in practical applications. D'Mello and Kory [50] used statistical methods to compare the accuracy of single modality and multimodal on different databases. Multimodal expression recognition was superior to single modality performance in the experiments. The McGurk [51] phenomenon reveals that in the process of brain perception, different senses are automatically combined unconsciously to process the information, and any lack or inaccuracy of sensory information will lead to deviations in the brain's understanding of external information. Therefore, multimodal feature fusion recognition technology has become a research hotspot in the past few years.

The widely used multimodal emotion databases are HUMAINE database [52], the Belfast database [53], the large-scale audiovisual database SEMAINE [54], the IEMOCAP emotional database [55], the audiovisual database eNTERFACE [56], the Acted Facial Expression in the Wild database (AFEW) [57] composed of audio and video clips from English movies and TV programs, and the Chinese multimodal emotional data set CHEAVD [58].

Multichannel information fusion levels can be divided into three categories: data layer, feature layer, and decision layer: (1) Data layer fusion refers to the fusion of collected raw data and then extracting feature vector from the fused data, finally classifying the emotion; (2) feature layer fusion refers to conducting preprocessing and feature extraction of the collected data of each channel first, then obtaining the feature vector by fusing extracted emotion features, and then finally classifying the emotion; and (3) decision layer fusion refers to making separate emotion classification decision for collected data of each channel and then fusing the single modality recognition result to obtain the final classification result. The commonly used information fusion methods are D-S evidence theory, artificial neural network, fuzzy set theory, Bayesian inference, cluster analysis, expert system method, and others.

diagnostic categories (e.g., MDD), with the potential for alternative diagnostic

Ample evidence showed that specific brain regions including the PFC, amygdala, anterior cingulate, and insula play a major role in the neuropathological basis of affective disorders. Recent meta-analyses found evidence which is against the locationist account of emotion and suggested that brain regions corresponding to basic psychological operations are involved in emotion processing across emotional categories and are not specifically localized to discrete brain networks [67]. With its advantages in superior soft tissue contrast, high spatial resolution, and noninvasive detection, magnetic resonance imaging (MRI) has become a promising tool for detection of neurological alterations in

Using an experimental therapeutics approach coupled with machine learning, Liu et al. investigated the effect of a pharmacological challenge aiming to enhance dopaminergic signaling on whole-brain's response to reward-related stimuli in MDD. Artificial intelligence technology combined with MRI technology was used to find the objective biological markers of depression. The brain regions with diagnostic value included anterior cuneate lobe, cingulate gyrus, inferior marginal angular gyrus, insular, thalamus, and hippocampus. The brain regions with preventive value included the precuneus, postcentral gyrus, dorsolateral prefrontal lobe, orbitofrontal lobe, and middle temporal gyrus. The brain regions with predictive therapeutic response included the precuneus, cingulate gyrus, inferior marginal angular gyrus, middle frontal gyrus, middle occipital gyrus, inferior occipital gyrus,

Studies have shown that machine learning and deep learning techniques have been widely used in the diagnosis, prevention, and treatment of depression and other neuropsychiatric diseases in recent years. Abnormal brain regions may be used as predictors of diagnostic and therapeutic responses. Research hotspot mainly focused on cortical areas rather than the midbrain limbic system or dopamine system. Collectively, the literature review suggested that the cingulate gyrus and precuneus may be the most important candidate brain regions among the objective biological markers of depression. Due to complex pathophysiological changes and etiological heterogeneity of depression, combining imaging biomarkers with other indicators (e.g., biochemical, genetic) is necessary to achieve more objective

With the growing amount of emotional information from social media, including text, photos, and videos, emotion recognition through multimodal information using machine learning technique is becoming a trend. Absolutist thinking represents a form of cognitive distortion typical of anxiety and depression. Al-Mosaiwi and Johnstone conducted a text analysis of 63 Internet forums (over 6400 members) using the Linguistic Inquiry and Word Count software to examine absolutist thinking. The results suggested that absolutist words, rather than negative emotion words, tracked the severity of affective disorder forums. They found elevated levels of absolutist words in depression recovery forums. This suggests that absolutist thinking may be a vulnerability factor for relapse of affective disorder [70].

The project of Proactive Suicide Prevention Online (PSPO) identified suicideprone individuals to provide further crisis management. A microblog group was

assessment of course and prognosis of depression [69].

**3.2 Textual emotion recognition**

**127**

processes [66].

**3.1 Physiological emotion recognition**

*DOI: http://dx.doi.org/10.5772/intechopen.92019*

*Advances in Emotion Recognition: Link to Depressive Disorder*

mental disorders such as depression.

and lingual gyrus [68].

Current studies on postures mainly concentrate on bimodal emotion recognition of facial expressions and postures. Castellano et al. [25] conducted a comparative study of the processing of body language and facial expression and found that body language and facial expression have similar visual processing mechanisms. The two are highly similar in terms of event-related potential (ERP) components, psychological functions, and influencing factors and are partially overlapping or adjacent to each other in potential neural bases. Gunes and Piccardi [59, 60] conducted longterm research on bimodal emotion recognition of facial expressions and postures and established the Bi-modal Face and Body Gesture Database for Automatic Analysis of Human Nonverbal Affective Behavior (FABO). Yan et al. [61] studied videobased bimodal emotion recognition of facial expression and postures and proposed an emotion recognition method based on bilateral sparse partial least squares which has low computational complexity but low recognition rate. In order to tell human emotions through video data, Wang and Shao [62] extracted emotional features of facial expression and body movements from the FABO database, used a fusion algorithm based on canonical correlation analysis (CCA) to fuse two features, and then used nearest neighbor classifier and support vector machine for emotion recognition. After using updated sparsity preserving CCA (SPCCA), they combined emotion features of facial expressions and body movements, achieving an emotion recognition rate at 90.48%. Wang et al. [63] focused on the problem of high computational complexity in video emotion recognition and proposed a bimodal emotion recognition method based on temporal-spatial local binary pattern moment (TSLBPM) which has been proven effective. Jiang et al. [64] proposed a spatiotemporal local ternary orientational pattern (SLTOP) feature description method and cloud-weighted decision fusion classification method for bimodal emotion recognition of facial expressions and postures in video sequences, achieving better recognition result than other classification recognition methods in the comparative experiments.

#### **3. Application of emotion recognition in depressive disorder**

Depressive disorder is characteristic of negative mood and anhedonia, which are two core symptoms for diagnosis of the disease. Traditionally, the clinical diagnosis for depression requires the clinicians to assess the severity of depressive symptoms according to verbal statements of patients as well as nonverbal indicators such as voices (pitch, speaking speed, and volumes) and facial expressions. Additionally, structured questionnaires (such as Beck Depression Inventory, Hamilton Depression Rating Scale) have been developed and validated in clinical populations to assess the severity of depressive symptoms. However, the physiological biomarkers of depression are still unclear. Since the 1950s the consensus has emerged that psychiatric diagnoses could be defined according to relevant biological characteristics. However, the empirical diagnostic categories such as depressive disorder failed to be reified and objectified by valid biological measures [65]. The Research Domain Criteria (RDoC) initiative attempted to link physiologic mechanisms (esp. circuit level) to dimensional constructs (e.g., positive/negative valence) rather than

diagnostic categories (e.g., MDD), with the potential for alternative diagnostic processes [66].

#### **3.1 Physiological emotion recognition**

feature vector by fusing extracted emotion features, and then finally classifying the emotion; and (3) decision layer fusion refers to making separate emotion classification decision for collected data of each channel and then fusing the single modality recognition result to obtain the final classification result. The commonly used information fusion methods are D-S evidence theory, artificial neural network, fuzzy set theory, Bayesian inference, cluster analysis, expert system

Current studies on postures mainly concentrate on bimodal emotion recognition of facial expressions and postures. Castellano et al. [25] conducted a comparative study of the processing of body language and facial expression and found that body language and facial expression have similar visual processing mechanisms. The two are highly similar in terms of event-related potential (ERP) components, psychological functions, and influencing factors and are partially overlapping or adjacent to each other in potential neural bases. Gunes and Piccardi [59, 60] conducted longterm research on bimodal emotion recognition of facial expressions and postures and established the Bi-modal Face and Body Gesture Database for Automatic Analysis of Human Nonverbal Affective Behavior (FABO). Yan et al. [61] studied videobased bimodal emotion recognition of facial expression and postures and proposed an emotion recognition method based on bilateral sparse partial least squares which has low computational complexity but low recognition rate. In order to tell human emotions through video data, Wang and Shao [62] extracted emotional features of facial expression and body movements from the FABO database, used a fusion algorithm based on canonical correlation analysis (CCA) to fuse two features, and then used nearest neighbor classifier and support vector machine for emotion recognition. After using updated sparsity preserving CCA (SPCCA), they combined emotion features of facial expressions and body movements, achieving an emotion recognition rate at 90.48%. Wang et al. [63] focused on the problem of high computational complexity in video emotion recognition and proposed a bimodal emotion recognition method based on temporal-spatial local binary pattern moment (TSLBPM) which has been proven effective. Jiang et al. [64] proposed a spatiotemporal local ternary orientational pattern (SLTOP) feature description method and cloud-weighted decision fusion classification method for bimodal emotion recognition of facial expressions and postures in video sequences, achieving better recognition result than other classification recognition methods in the comparative

**3. Application of emotion recognition in depressive disorder**

Depressive disorder is characteristic of negative mood and anhedonia, which are two core symptoms for diagnosis of the disease. Traditionally, the clinical diagnosis for depression requires the clinicians to assess the severity of depressive symptoms according to verbal statements of patients as well as nonverbal indicators such as voices (pitch, speaking speed, and volumes) and facial expressions. Additionally, structured questionnaires (such as Beck Depression Inventory, Hamilton Depression Rating Scale) have been developed and validated in clinical populations to assess the severity of depressive symptoms. However, the physiological biomarkers of depression are still unclear. Since the 1950s the consensus has emerged that psychiatric diagnoses could be defined according to relevant biological characteristics. However, the empirical diagnostic categories such as depressive disorder failed to be reified and objectified by valid biological measures [65]. The Research Domain Criteria (RDoC) initiative attempted to link physiologic mechanisms (esp. circuit level) to dimensional constructs (e.g., positive/negative valence) rather than

method, and others.

*Neurological and Mental Disorders*

experiments.

**126**

Ample evidence showed that specific brain regions including the PFC, amygdala, anterior cingulate, and insula play a major role in the neuropathological basis of affective disorders. Recent meta-analyses found evidence which is against the locationist account of emotion and suggested that brain regions corresponding to basic psychological operations are involved in emotion processing across emotional categories and are not specifically localized to discrete brain networks [67]. With its advantages in superior soft tissue contrast, high spatial resolution, and noninvasive detection, magnetic resonance imaging (MRI) has become a promising tool for detection of neurological alterations in mental disorders such as depression.

Using an experimental therapeutics approach coupled with machine learning, Liu et al. investigated the effect of a pharmacological challenge aiming to enhance dopaminergic signaling on whole-brain's response to reward-related stimuli in MDD. Artificial intelligence technology combined with MRI technology was used to find the objective biological markers of depression. The brain regions with diagnostic value included anterior cuneate lobe, cingulate gyrus, inferior marginal angular gyrus, insular, thalamus, and hippocampus. The brain regions with preventive value included the precuneus, postcentral gyrus, dorsolateral prefrontal lobe, orbitofrontal lobe, and middle temporal gyrus. The brain regions with predictive therapeutic response included the precuneus, cingulate gyrus, inferior marginal angular gyrus, middle frontal gyrus, middle occipital gyrus, inferior occipital gyrus, and lingual gyrus [68].

Studies have shown that machine learning and deep learning techniques have been widely used in the diagnosis, prevention, and treatment of depression and other neuropsychiatric diseases in recent years. Abnormal brain regions may be used as predictors of diagnostic and therapeutic responses. Research hotspot mainly focused on cortical areas rather than the midbrain limbic system or dopamine system. Collectively, the literature review suggested that the cingulate gyrus and precuneus may be the most important candidate brain regions among the objective biological markers of depression. Due to complex pathophysiological changes and etiological heterogeneity of depression, combining imaging biomarkers with other indicators (e.g., biochemical, genetic) is necessary to achieve more objective assessment of course and prognosis of depression [69].

#### **3.2 Textual emotion recognition**

With the growing amount of emotional information from social media, including text, photos, and videos, emotion recognition through multimodal information using machine learning technique is becoming a trend. Absolutist thinking represents a form of cognitive distortion typical of anxiety and depression. Al-Mosaiwi and Johnstone conducted a text analysis of 63 Internet forums (over 6400 members) using the Linguistic Inquiry and Word Count software to examine absolutist thinking. The results suggested that absolutist words, rather than negative emotion words, tracked the severity of affective disorder forums. They found elevated levels of absolutist words in depression recovery forums. This suggests that absolutist thinking may be a vulnerability factor for relapse of affective disorder [70].

The project of Proactive Suicide Prevention Online (PSPO) identified suicideprone individuals to provide further crisis management. A microblog group was

#### *Neurological and Mental Disorders*

identified as a high-risk population, who commented around a Sina microblogger who committed suicide. They were assessed for suicidal thought and behavior. The frequency of death-oriented words significantly decreased after the intervention, while the frequency of future-oriented words significantly increased. This model may help people with suicidal thoughts and behaviors but with a low motivation to seek help [71].

They found that four voice features (PC1, PC6, PC17, PC24, P < 0.05, corrected) made significant contribution to depression and that the contribution effect of the voice features alone reached 35.65%. These results demonstrate that voice features have great potential in applications such as clinical diagnosis and prediction.

Facial, video, and textual information are the most available affective information in clinical context. Therefore, recent studies explored multimodal emotion recognition methods to improve the accuracies and specificities when the multimodal emotion information was input as predictors. Haque et al. present a machine learning method for measuring the severity of depressive symptoms. Their multimodal method uses 3D facial expressions and spoken language, commonly available from modern cell phones. It demonstrates an average error of 3.67 points (15.3% relative) on the clinically validated Patient Health Questionnaire (PHQ) scale. For detecting major depressive disorder, their model demonstrates 83.3% sensitivity and 82.6% specificity [79]. Yang et al. proposed new text and video features and hybridizes deep and shallow models for depression estimation and classification from audio, video, and text descriptors. They demonstrated that the proposed hybrid framework effectively improves the accuracies of both depression estimation and depression classification [80]. SimSensei Kiosk was a virtual human interviewer which aims to automatically assess the verbal and nonverbal behaviors indicative of depression, anxiety, or post-traumatic stress disorder (PSTD). A multimodal real-time sensing system was used to simultaneously capture different modalities (e.g., smile intensity, 3D head position and orientation, intensity or lack of facial expressions like anger, disgust, and joy) to model the relation between

This chapter summarized the recognition of human affect based on internal and external signals of emotion, which has gained intensive attention in research fields such as artificial intelligence, psychology, cognitive neuroscience, and physiology. The reviewed empirical researches rarely deal with "social emotions" such as guilt, shame, and embarrassment. Instead of the more traditional cognitive and biological perspectives of emotion, the sociological perspective focused on functions of emotions to control social interactions and sustain the social order. Future studies need

to deal with its extension to social emotions and the relevant theoretical

research is needed about the way they relate to human affect.

Emotion recognition is based on discrete and dimensional views of emotion, with underlying CNS and PNS dynamics. Single modal as well as multimodal emotion recognition rely on facial, speech, posture, physiological, and textual emotional information, which could function separately or concurrently. Integrating multimodal emotion information for emotion recognition remains challenging, and much

Furthermore, the application of emotion recognition in depressive disorder may pave an avenue for more precise diagnosis of the syndrome and prediction of its disease course. Identifying specific physiological substrates of depressive disorder, combined with emotion classification technique such as machine learning, may help identify the dimensional constructs of RDoC, which are implicit in the clinical

**3.4 Multimodal emotion recognition**

*DOI: http://dx.doi.org/10.5772/intechopen.92019*

*Advances in Emotion Recognition: Link to Depressive Disorder*

mental states and human behavior [81].

phenomena of depressive disorder.

**4. Conclusions**

foundations.

**129**

The modeling of textual and visual features from Instagram photos successfully identified individuals diagnosed with depression. The results showed that depressed people are more likely to upload photos that are bluer, grayer, and darker. The human rating of photo attributes (happiness, sadness, interestingness, and likability) is a weak predictor of depression [72]. These findings suggest new avenues for early screening and detection of mental illness.

#### **3.3 Facial expression and speech recognition**

The physiological approaches using specific sensors for emotion signals have the advantage of being more precise, but are generally more costly and need more effort in clinical context. Facial and speech information is more applicable in these natural environments. Chronic stress, anxiety, and depressive states are three intertwined processes which constitute the vicious circle in common affective disorders such as depression. Chronic stress may induce autonomic responses concurrent with anxiety states, and anxiety may lead to depressive states when stress continues and coping strategies are ineffective. Gavrilescu and Vizireanu for the first time proposed a neural network-based architecture for predicting levels of stress, anxiety, and depression based on FACS in a nonintrusive and real-time manner. Their method allows the experts to monitor the three emotional states in real time. Additionally, 93% accuracy was achieved discriminating between healthy individuals and those with major depressive disorder (MDD) or post-traumatic stress disorder (PTSD) [73]. This method is an attractive alternative to traditional self-report measurements based on questionnaires.

A new approach to predict the depressive symptoms with Beck Depression Inventory II (BDI-II) scores from video data is proposed based on the deep convolutional neutral networks (DCNN). The proposed framework is designed to capture both the facial appearance and dynamics in the video data by integrating two deep networks into one. The method could predict with over 80% accuracy depressive behavior, achieving a comparable performance to most methods combing video and audio data [74]. Thus their method provided a more efficient and convenient way of prediction than multimodal methods.

Harati et al. used several metrics of variability to extract unsupervised features from video recordings of patients before and after deep brain stimulation (DBS) treatment for major depressive disorder (MDD). Their goal was to quantify the treatment effects on emotion indicated with facial expression. Their preliminary results indicate that unsupervised features learned from these video recordings using dynamic latent variable model (DLVM) based on multiscale entropy (MSE) of pixel intensities can distinguish different phases of depression and recovery [75]. Therefore, their methods may provide more precise markers of treatment response.

As a relatively objective and easily available variable, speech has potential value in the diagnosis of depression. The acoustic analysis of patients with mental illness showed that there is greater than moderate correlation between speech-related variables and symptom indicators [76, 77]. Pan et al. build a speech-based depression recognition model with logical regression (LR) classification methods. The results show that the speech recognition accuracy reached 82.9% [78].

They found that four voice features (PC1, PC6, PC17, PC24, P < 0.05, corrected) made significant contribution to depression and that the contribution effect of the voice features alone reached 35.65%. These results demonstrate that voice features have great potential in applications such as clinical diagnosis and prediction.

#### **3.4 Multimodal emotion recognition**

identified as a high-risk population, who commented around a Sina microblogger who committed suicide. They were assessed for suicidal thought and behavior. The frequency of death-oriented words significantly decreased after the intervention, while the frequency of future-oriented words significantly increased. This model may help people with suicidal thoughts and behaviors but with a low motivation to

The modeling of textual and visual features from Instagram photos successfully identified individuals diagnosed with depression. The results showed that depressed people are more likely to upload photos that are bluer, grayer, and darker. The human rating of photo attributes (happiness, sadness, interestingness, and likability) is a weak predictor of depression [72]. These findings suggest new

The physiological approaches using specific sensors for emotion signals have the

advantage of being more precise, but are generally more costly and need more effort in clinical context. Facial and speech information is more applicable in these natural environments. Chronic stress, anxiety, and depressive states are three intertwined processes which constitute the vicious circle in common affective disorders such as depression. Chronic stress may induce autonomic responses concurrent with anxiety states, and anxiety may lead to depressive states when stress continues and coping strategies are ineffective. Gavrilescu and Vizireanu for the first time proposed a neural network-based architecture for predicting levels of stress, anxiety, and depression based on FACS in a nonintrusive and real-time manner. Their method allows the experts to monitor the three emotional states in real time. Additionally, 93% accuracy was achieved discriminating between healthy individuals and those with major depressive disorder (MDD) or post-traumatic stress disorder (PTSD) [73]. This method is an attractive alternative to traditional

A new approach to predict the depressive symptoms with Beck Depression Inventory II (BDI-II) scores from video data is proposed based on the deep convolutional neutral networks (DCNN). The proposed framework is designed to capture both the facial appearance and dynamics in the video data by integrating two deep networks into one. The method could predict with over 80% accuracy depressive behavior, achieving a comparable performance to most methods combing video and audio data [74]. Thus their method provided a more efficient and

Harati et al. used several metrics of variability to extract unsupervised features from video recordings of patients before and after deep brain stimulation (DBS) treatment for major depressive disorder (MDD). Their goal was to quantify the treatment effects on emotion indicated with facial expression. Their preliminary results indicate that unsupervised features learned from these video recordings using dynamic latent variable model (DLVM) based on multiscale entropy (MSE) of pixel intensities can distinguish different phases of depression and recovery [75]. Therefore, their methods may provide more precise markers of treatment

As a relatively objective and easily available variable, speech has potential value in the diagnosis of depression. The acoustic analysis of patients with mental illness showed that there is greater than moderate correlation between speech-related variables and symptom indicators [76, 77]. Pan et al. build a speech-based depression recognition model with logical regression (LR) classification methods. The results show that the speech recognition accuracy reached 82.9% [78].

avenues for early screening and detection of mental illness.

**3.3 Facial expression and speech recognition**

self-report measurements based on questionnaires.

convenient way of prediction than multimodal methods.

seek help [71].

*Neurological and Mental Disorders*

response.

**128**

Facial, video, and textual information are the most available affective information in clinical context. Therefore, recent studies explored multimodal emotion recognition methods to improve the accuracies and specificities when the multimodal emotion information was input as predictors. Haque et al. present a machine learning method for measuring the severity of depressive symptoms. Their multimodal method uses 3D facial expressions and spoken language, commonly available from modern cell phones. It demonstrates an average error of 3.67 points (15.3% relative) on the clinically validated Patient Health Questionnaire (PHQ) scale. For detecting major depressive disorder, their model demonstrates 83.3% sensitivity and 82.6% specificity [79]. Yang et al. proposed new text and video features and hybridizes deep and shallow models for depression estimation and classification from audio, video, and text descriptors. They demonstrated that the proposed hybrid framework effectively improves the accuracies of both depression estimation and depression classification [80]. SimSensei Kiosk was a virtual human interviewer which aims to automatically assess the verbal and nonverbal behaviors indicative of depression, anxiety, or post-traumatic stress disorder (PSTD). A multimodal real-time sensing system was used to simultaneously capture different modalities (e.g., smile intensity, 3D head position and orientation, intensity or lack of facial expressions like anger, disgust, and joy) to model the relation between mental states and human behavior [81].

#### **4. Conclusions**

This chapter summarized the recognition of human affect based on internal and external signals of emotion, which has gained intensive attention in research fields such as artificial intelligence, psychology, cognitive neuroscience, and physiology. The reviewed empirical researches rarely deal with "social emotions" such as guilt, shame, and embarrassment. Instead of the more traditional cognitive and biological perspectives of emotion, the sociological perspective focused on functions of emotions to control social interactions and sustain the social order. Future studies need to deal with its extension to social emotions and the relevant theoretical foundations.

Emotion recognition is based on discrete and dimensional views of emotion, with underlying CNS and PNS dynamics. Single modal as well as multimodal emotion recognition rely on facial, speech, posture, physiological, and textual emotional information, which could function separately or concurrently. Integrating multimodal emotion information for emotion recognition remains challenging, and much research is needed about the way they relate to human affect.

Furthermore, the application of emotion recognition in depressive disorder may pave an avenue for more precise diagnosis of the syndrome and prediction of its disease course. Identifying specific physiological substrates of depressive disorder, combined with emotion classification technique such as machine learning, may help identify the dimensional constructs of RDoC, which are implicit in the clinical phenomena of depressive disorder.

*Neurological and Mental Disorders*

#### **Conflict of interest**

The authors declare no conflict of interest.

**References**

2017.02.003

Press; 1978

2011.01.011

**131**

1985

[1] Minsky M. The Society of Mind. New York, NY: Simon & Schuster Imprint;

*DOI: http://dx.doi.org/10.5772/intechopen.92019*

*Advances in Emotion Recognition: Link to Depressive Disorder*

[10] Liu J et al. Establishment of the Chinese facial emotion images database with intensity classification. Chinese Journal of Mental Health. 2019;**33**:

[11] Ballano S, Hupont I, Cerezo E, Baldassarri S. Recognizing Emotions from Video in a Continuous 2D Space. Berlin, Heidelberg: Springer Berlin Heidelberg; 2011. pp. 600-603

[12] Polikovsky S, Kameda Y, Ohta Y. Facial micro-expressions recognition using high speed camera and 3Dgradient descriptor. In: Proceedings of the 3rd International Conference on Crime Detection and Prevention; 3 December 2009; London. London, UK: IEEE; 2009. pp. 1-6. DOI: 10.1049/

120-125. DOI: 10.3969/j. issn.1000-6729.2019.02.009

ic.2009.0244

[13] Shreve M, Godavarthy S, Manohar V, Goldgof D, Sarkar S. Towards macro- and micro-expression spotting in video using strain patterns. In: Proceedings of the IEEE Workshop on Applications of Computer Vision; 2009/12; 7-8 December 2009; Snowbird, UT. Snowbird, UT: IEEE; 2009. pp. 1-6

[14] Yan W-J, Li X, Wang S-J, Zhao G, Liu Y-J, Chen Y-H, et al. CASME II: An

[15] Lee CM, Narayanan SS. Toward detecting emotions in spoken dialogs. IEEE Transactions on Speech and Audio Processing. 2005;**13**:293-303. DOI:

[16] Schuller B, Rigoll G, Lang M. Speech emotion recognition combining acoustic features and linguistic information in a hybrid support vector machine-belief network architecture. In: Proceedings of the 2004 IEEE International Conference

improved spontaneous microexpression database and the baseline evaluation. PLoS One. 2014;**9**:e86041. DOI: 10.1371/journal.pone.0086041

10.1109/tsa.2004.838534

[2] Picard RW. Affective Computing. Cambridge, MA: The MIT Press; 1997

[3] Poria S, Cambria E, Bajpai R, Hussain A. A review of affective computing: From unimodal analysis to multimodal fusion. Information Fusion. 2017;**37**:98-125. DOI: 10.1016/j.inffus.

[4] Ekman P, Levenson RW,

Friesen WV. Autonomic nervous system activity distinguishes among emotions. Science. 1983;**221**(4616):1208-1210. DOI: 10.1126/science.6612338

[5] Singh D. Human emotion recognition system. International Journal of Image, Graphics and Signal Processing. 2012; **4**(8):50-56. DOI: 10.5815/ijigsp.2012.08.07

[6] Quigley KS, Barrett LF. Is there consistency and specificity of autonomic changes during emotional episodes? Guidance from the conceptual act theory and psychophysiology. Biological

Psychology. 2014;**98**:82-94. DOI: 10.1016/j.biopsycho.2013.12.013

[7] Ekman P, Friesen WV. Facial Action Coding System: A Technique for the Measurement of Facial Movement. Palo Alto, CA: Consulting Psychologists

[8] Yang C, Li H. Validity study on facereader's images recognition from Chinese facial expression database. Ergonomics. 2015;**21**:38-41. DOI: 10.13837/j.issn.1006-8309.2015.01.0008

[9] Gong X et al. Revision of the Chinese facial affective picture system. Chinese Journal of Mental Health. 2011;**250**: 40-46. DOI: 10.3969/j.issn.1000-6729.

#### **Author details**

Xiaotong Cheng1†, Xiaoxia Wang<sup>2</sup> \*†, Tante Ouyang1 and Zhengzhi Feng<sup>1</sup>

1 College of Psychology, Army Medical University, Chongqing, China

2 Department of Basic Psychology, College of Psychology, Army Medical University, Chongqing, China

\*Address all correspondence to: lemonowang@gmail.com

†Cheng and Wang contributed equally to this article and should be considered co-first authors.

© 2020 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

### **References**

**Conflict of interest**

*Neurological and Mental Disorders*

**Author details**

co-first authors.

**130**

Xiaotong Cheng1†, Xiaoxia Wang<sup>2</sup>

University, Chongqing, China

provided the original work is properly cited.

1 College of Psychology, Army Medical University, Chongqing, China

\*Address all correspondence to: lemonowang@gmail.com

2 Department of Basic Psychology, College of Psychology, Army Medical

†Cheng and Wang contributed equally to this article and should be considered

© 2020 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

\*†, Tante Ouyang1 and Zhengzhi Feng<sup>1</sup>

The authors declare no conflict of interest.

[1] Minsky M. The Society of Mind. New York, NY: Simon & Schuster Imprint; 1985

[2] Picard RW. Affective Computing. Cambridge, MA: The MIT Press; 1997

[3] Poria S, Cambria E, Bajpai R, Hussain A. A review of affective computing: From unimodal analysis to multimodal fusion. Information Fusion. 2017;**37**:98-125. DOI: 10.1016/j.inffus. 2017.02.003

[4] Ekman P, Levenson RW, Friesen WV. Autonomic nervous system activity distinguishes among emotions. Science. 1983;**221**(4616):1208-1210. DOI: 10.1126/science.6612338

[5] Singh D. Human emotion recognition system. International Journal of Image, Graphics and Signal Processing. 2012; **4**(8):50-56. DOI: 10.5815/ijigsp.2012.08.07

[6] Quigley KS, Barrett LF. Is there consistency and specificity of autonomic changes during emotional episodes? Guidance from the conceptual act theory and psychophysiology. Biological Psychology. 2014;**98**:82-94. DOI: 10.1016/j.biopsycho.2013.12.013

[7] Ekman P, Friesen WV. Facial Action Coding System: A Technique for the Measurement of Facial Movement. Palo Alto, CA: Consulting Psychologists Press; 1978

[8] Yang C, Li H. Validity study on facereader's images recognition from Chinese facial expression database. Ergonomics. 2015;**21**:38-41. DOI: 10.13837/j.issn.1006-8309.2015.01.0008

[9] Gong X et al. Revision of the Chinese facial affective picture system. Chinese Journal of Mental Health. 2011;**250**: 40-46. DOI: 10.3969/j.issn.1000-6729. 2011.01.011

[10] Liu J et al. Establishment of the Chinese facial emotion images database with intensity classification. Chinese Journal of Mental Health. 2019;**33**: 120-125. DOI: 10.3969/j. issn.1000-6729.2019.02.009

[11] Ballano S, Hupont I, Cerezo E, Baldassarri S. Recognizing Emotions from Video in a Continuous 2D Space. Berlin, Heidelberg: Springer Berlin Heidelberg; 2011. pp. 600-603

[12] Polikovsky S, Kameda Y, Ohta Y. Facial micro-expressions recognition using high speed camera and 3Dgradient descriptor. In: Proceedings of the 3rd International Conference on Crime Detection and Prevention; 3 December 2009; London. London, UK: IEEE; 2009. pp. 1-6. DOI: 10.1049/ ic.2009.0244

[13] Shreve M, Godavarthy S, Manohar V, Goldgof D, Sarkar S. Towards macro- and micro-expression spotting in video using strain patterns. In: Proceedings of the IEEE Workshop on Applications of Computer Vision; 2009/12; 7-8 December 2009; Snowbird, UT. Snowbird, UT: IEEE; 2009. pp. 1-6

[14] Yan W-J, Li X, Wang S-J, Zhao G, Liu Y-J, Chen Y-H, et al. CASME II: An improved spontaneous microexpression database and the baseline evaluation. PLoS One. 2014;**9**:e86041. DOI: 10.1371/journal.pone.0086041

[15] Lee CM, Narayanan SS. Toward detecting emotions in spoken dialogs. IEEE Transactions on Speech and Audio Processing. 2005;**13**:293-303. DOI: 10.1109/tsa.2004.838534

[16] Schuller B, Rigoll G, Lang M. Speech emotion recognition combining acoustic features and linguistic information in a hybrid support vector machine-belief network architecture. In: Proceedings of the 2004 IEEE International Conference on Acoustics, Speech, and Signal Processing; 17-21 May 2004; Montreal. Montreal, Quebec: IEEE; 2004. pp. I-577

[17] Ververidis D, Kotropoulos C. Emotional speech recognition: Resources, features, and methods. Speech Communication. 2006;**48**: 1162-1181. DOI: 10.1016/j. specom.2006.04.003

[18] Rickheit G, Strohner H. Handbook of Communication Competence. Germany: Mouton de Gruyter; 2008

[19] Gharavian D, Sheikhan M, Nazerieh A, Garoucy S. Speech emotion recognition using FCBF feature selection method and GA-optimized fuzzy ARTMAP neural network. Neural Computing and Applications. 2012;**21**: 2115-2126. DOI: 10.1007/s00521-011- 0643-1

[20] Devi JS, Yarramalle S, Prasad NS. Speaker emotion recognition based on speech features and classification techniques. International Journal of Image, Graphics and Signal Processing. 2014;**6**:61-77. DOI: 10.5815/ijigsp.2014. 07.08

[21] Zhang L et al. Speech emotion recognition based on deep belief network. Journal of Taiyuan University of Technology. 2019;**50**:101-107. DOI: 10.16355/j.cnki.isn1007-9432tyut.2019. 01.016

[22] Zhu Y, Bodong S, Lichen Z. Temporal and spatial spectral feature speech emotion recognition algorithm based on trajectory. Computer System Application. 2019;**28**:146-151. DOI: 10.15888/j.cnki.csa.006794

[23] Liu Y, Qin H. The application of speech emotion recognition technology in the field of manned space. In: People's Forum Academic Frontiers. 2018. pp. 69-73. DOI: 10.16619/j.cnki. rmltxsqy.2018.17.008

[24] Tao J, Tan T. Affective Computing: A Review. Berlin, Heidelberg: Springer Berlin Heidelberg; 2005

**38**:2464-2468+2476. DOI: 10.11772/j.

*DOI: http://dx.doi.org/10.5772/intechopen.92019*

*Advances in Emotion Recognition: Link to Depressive Disorder*

recognition with manifold regularized

extreme learning machine. In: Proceedings of the 2014 36th Annual International Conference of the IEEE Engineering in Medicine and Biology Society; 26-30 August 2014; Chicago. Chicago, IL: IEEE; 2014. pp. 974-977

[41] Jie X, Cao R, Li L. Emotion recognition based on the sample entropy of EEG. Bio-Medical Materials and Engineering. 2014;**24**:1185-1192.

[42] Duan R-N, Zhu J-Y, Lu B-L. Differential entropy feature for EEGbased emotion classification. In: Proceedings of the 2013 6th

International IEEE/EMBS Conference on Neural Engineering (NER);

November 2013; San Diego. San Diego,

[43] Soleymani M, Lichtenauer J, Pun T, Pantic M. A multimodal database for affect recognition and implicit tagging.

[44] Koelstra S, Muhl C, Soleymani M, Jong-Seok L, Yazdani A, Ebrahimi T, et al. Deap: A database for emotion analysis using physiological signals. IEEE Transactions on Affective Computing. 2012;**3**:18-31. DOI:

DOI: 10.3233/bme-130919

CA: IEEE; 2013. pp. 81-84

10.1109/t-affc.2011.25

10.1109/t-affc.2011.15

6-39

ijhcs.2006.11.011

[45] Tai K, Chau T. Single-trial classification of NIRS signals during emotional induction tasks: Towards a corporeal machine interface. Journal of NeuroEngineering and Rehabilitation. 2009;**6**:1-14. DOI: 10.1186/1743-0003-

[46] Mandryk RL, Atkins MS. A fuzzy physiological approach for continuously modeling emotion during interaction with play technologies. International Journal of Human-Computer Studies. 2007;**65**:329-347. DOI: 10.1016/j.

IEEE Transactions on Affective Computing. 2012;**3**:42-55. DOI:

[33] James W. The physical basis of emotion. Psychological Review. 1994; **101**(2): 205-210. DOI: 10.1037/0033-

[34] Kreibig SD. Autonomic nervous system activity in emotion: A review. Biological Psychology. 2010;**84**: 394-421. DOI: 10.1016/j. biopsycho.2010.03.010

[35] Picard RW, Vyzas E, Healey J. Toward machine emotional intelligence: Analysis of affective physiological state. IEEE Transactions on Pattern Analysis and Machine Intelligence. 2001;**23**: 1175-1191. DOI: 10.1109/34.954607

[36] Kim J, Andre E. Emotion recognition based on physiological changes in music listening. IEEE Transactions on Pattern Analysis and Machine Intelligence. 2008;**30**:

2067-2083. DOI: 10.1109/tpami.2008.26

algorithm design with improved OWA in affective regulation system based on human-computer interaction. Journal of Information and Computational Science. 2013;**10**: 4477-4486. DOI: 10.12733/jics20102223

[38] Li C-L, Ye N, Huang H-P, Wang R-

Technology and Development. 2018;**28**:

physiological signal emotion recognition

Application of Electronic Technology. 2018;**44**:112-116. DOI: 10.16157/j.

[40] Yong P, Jia-Yi Z, Wei-Long Z, Bao-

C. Physiological signal emotion recognition based on recursive quantitative analysis. Computer

[39] Jin C, Chen G. Multi-modal

based on optimized LSTSVM.

Liang L. EEG-based emotion

issn.0258-7998.171839

94-98. +102

**133**

[37] Yan F, Liu GY, Lai XW. The research on material selection

issn.1001-9081.2018020481

295X.101.2.205

[25] Castellano G, Villalba SD, Camurri A. Recognising human emotions from body movement and gesture dynamics. In: Paiva ACR, Prada R, Picard RW, editors. Affective Computing and Intelligent Interaction. ACII 2007. Lecture Notes in Computer Science. Berlin, Heidelberg: Springer; 2007. pp. 71-82

[26] Bernhardt D, Robinson P. Detecting Emotions from Everyday Body Movements [EB/OL]. 2007. Available from: https://www.cl.cam.ac.uk/

[27] Liu Y, Liu D, Han Z. Research on emotion extraction method based on motion recognition. Computer Engineering. 2015;**41**:300-305

[28] Shao J, Wang W. Emotion recognition based on three-dimensional texture features of body movement sequences. Journal of Computer Applications. 2018;**35**:3497-3499. DOI: 10.3969 /j.issn.1001-3695.2018.11.071

[29] Hao Y et al. Method of microblog emotion recognition based on word fusion features. Computer Science. 2018;**45**:105-109. DOI: 10.11896/j. issn.1002-137X.2018.11A.018

[30] Hao M et al. Emotion classification and prediction algorithm based on Chinese microblog. Computer Application. 2018;**38**:89-96

[31] Huang F-L et al. Weibo themed emotion mining based on multi-feature fusion. Chinese Journal of Computers. 2017;**40**:872-888. DOI: 10.11897/SP. J.1016.2017.00872

[32] Zhang C, Qian T, Ji D. A joint model of microblogging emotion recognition and incentive extraction based on neural network. Computer Application. 2018;

*Advances in Emotion Recognition: Link to Depressive Disorder DOI: http://dx.doi.org/10.5772/intechopen.92019*

**38**:2464-2468+2476. DOI: 10.11772/j. issn.1001-9081.2018020481

on Acoustics, Speech, and Signal Processing; 17-21 May 2004; Montreal. Montreal, Quebec: IEEE; 2004. pp. I-577

*Neurological and Mental Disorders*

[24] Tao J, Tan T. Affective Computing: A Review. Berlin, Heidelberg: Springer

[26] Bernhardt D, Robinson P. Detecting

[27] Liu Y, Liu D, Han Z. Research on emotion extraction method based on motion recognition. Computer Engineering. 2015;**41**:300-305

recognition based on three-dimensional texture features of body movement sequences. Journal of Computer Applications. 2018;**35**:3497-3499. DOI: 10.3969 /j.issn.1001-3695.2018.11.071

[29] Hao Y et al. Method of microblog emotion recognition based on word fusion features. Computer Science. 2018;**45**:105-109. DOI: 10.11896/j. issn.1002-137X.2018.11A.018

[30] Hao M et al. Emotion classification and prediction algorithm based on Chinese microblog. Computer Application. 2018;**38**:89-96

[31] Huang F-L et al. Weibo themed emotion mining based on multi-feature fusion. Chinese Journal of Computers. 2017;**40**:872-888. DOI: 10.11897/SP.

[32] Zhang C, Qian T, Ji D. A joint model of microblogging emotion recognition and incentive extraction based on neural network. Computer Application. 2018;

J.1016.2017.00872

Emotions from Everyday Body Movements [EB/OL]. 2007. Available from: https://www.cl.cam.ac.uk/

[28] Shao J, Wang W. Emotion

Berlin Heidelberg; 2005

2007. pp. 71-82

[25] Castellano G, Villalba SD, Camurri A. Recognising human emotions from body movement and gesture dynamics. In: Paiva ACR, Prada R, Picard RW, editors. Affective Computing and Intelligent Interaction. ACII 2007. Lecture Notes in Computer Science. Berlin, Heidelberg: Springer;

[17] Ververidis D, Kotropoulos C. Emotional speech recognition: Resources, features, and methods. Speech Communication. 2006;**48**:

[18] Rickheit G, Strohner H. Handbook of Communication Competence. Germany: Mouton de Gruyter; 2008

Nazerieh A, Garoucy S. Speech emotion

[20] Devi JS, Yarramalle S, Prasad NS. Speaker emotion recognition based on speech features and classification techniques. International Journal of Image, Graphics and Signal Processing. 2014;**6**:61-77. DOI: 10.5815/ijigsp.2014.

[21] Zhang L et al. Speech emotion recognition based on deep belief network. Journal of Taiyuan University of Technology. 2019;**50**:101-107. DOI: 10.16355/j.cnki.isn1007-9432tyut.2019.

[22] Zhu Y, Bodong S, Lichen Z. Temporal and spatial spectral feature speech emotion recognition algorithm based on trajectory. Computer System Application. 2019;**28**:146-151. DOI:

10.15888/j.cnki.csa.006794

rmltxsqy.2018.17.008

**132**

[23] Liu Y, Qin H. The application of speech emotion recognition technology in the field of manned space. In: People's Forum Academic Frontiers. 2018. pp. 69-73. DOI: 10.16619/j.cnki.

1162-1181. DOI: 10.1016/j. specom.2006.04.003

[19] Gharavian D, Sheikhan M,

recognition using FCBF feature selection method and GA-optimized fuzzy ARTMAP neural network. Neural Computing and Applications. 2012;**21**: 2115-2126. DOI: 10.1007/s00521-011-

0643-1

07.08

01.016

[33] James W. The physical basis of emotion. Psychological Review. 1994; **101**(2): 205-210. DOI: 10.1037/0033- 295X.101.2.205

[34] Kreibig SD. Autonomic nervous system activity in emotion: A review. Biological Psychology. 2010;**84**: 394-421. DOI: 10.1016/j. biopsycho.2010.03.010

[35] Picard RW, Vyzas E, Healey J. Toward machine emotional intelligence: Analysis of affective physiological state. IEEE Transactions on Pattern Analysis and Machine Intelligence. 2001;**23**: 1175-1191. DOI: 10.1109/34.954607

[36] Kim J, Andre E. Emotion recognition based on physiological changes in music listening. IEEE Transactions on Pattern Analysis and Machine Intelligence. 2008;**30**: 2067-2083. DOI: 10.1109/tpami.2008.26

[37] Yan F, Liu GY, Lai XW. The research on material selection algorithm design with improved OWA in affective regulation system based on human-computer interaction. Journal of Information and Computational Science. 2013;**10**: 4477-4486. DOI: 10.12733/jics20102223

[38] Li C-L, Ye N, Huang H-P, Wang R-C. Physiological signal emotion recognition based on recursive quantitative analysis. Computer Technology and Development. 2018;**28**: 94-98. +102

[39] Jin C, Chen G. Multi-modal physiological signal emotion recognition based on optimized LSTSVM. Application of Electronic Technology. 2018;**44**:112-116. DOI: 10.16157/j. issn.0258-7998.171839

[40] Yong P, Jia-Yi Z, Wei-Long Z, Bao-Liang L. EEG-based emotion

recognition with manifold regularized extreme learning machine. In: Proceedings of the 2014 36th Annual International Conference of the IEEE Engineering in Medicine and Biology Society; 26-30 August 2014; Chicago. Chicago, IL: IEEE; 2014. pp. 974-977

[41] Jie X, Cao R, Li L. Emotion recognition based on the sample entropy of EEG. Bio-Medical Materials and Engineering. 2014;**24**:1185-1192. DOI: 10.3233/bme-130919

[42] Duan R-N, Zhu J-Y, Lu B-L. Differential entropy feature for EEGbased emotion classification. In: Proceedings of the 2013 6th International IEEE/EMBS Conference on Neural Engineering (NER); November 2013; San Diego. San Diego, CA: IEEE; 2013. pp. 81-84

[43] Soleymani M, Lichtenauer J, Pun T, Pantic M. A multimodal database for affect recognition and implicit tagging. IEEE Transactions on Affective Computing. 2012;**3**:42-55. DOI: 10.1109/t-affc.2011.25

[44] Koelstra S, Muhl C, Soleymani M, Jong-Seok L, Yazdani A, Ebrahimi T, et al. Deap: A database for emotion analysis using physiological signals. IEEE Transactions on Affective Computing. 2012;**3**:18-31. DOI: 10.1109/t-affc.2011.15

[45] Tai K, Chau T. Single-trial classification of NIRS signals during emotional induction tasks: Towards a corporeal machine interface. Journal of NeuroEngineering and Rehabilitation. 2009;**6**:1-14. DOI: 10.1186/1743-0003- 6-39

[46] Mandryk RL, Atkins MS. A fuzzy physiological approach for continuously modeling emotion during interaction with play technologies. International Journal of Human-Computer Studies. 2007;**65**:329-347. DOI: 10.1016/j. ijhcs.2006.11.011

[47] Zhang D, Wan B, Ming D. Research progress on emotion recognition based on physiological signals. Journal of Biomedical Engineering. 2015;**32**: 229-234

[48] Konstantinidis EI, Frantzidis CA, Pappas C, Bamidis PD. Real time emotion aware applications: A case study employing emotion evocative pictures and neuro-physiological sensing enhanced by graphic processor units. Computer Methods and Programs in Biomedicine. 2012;**107**:16-27. DOI: 10.1016/j.cmpb.2012.03.008

[49] Liu Y, Sourina O, Nguyen MK. Realtime EEG-based emotion recognition and its applications. Transactions on Computational Science XII. 2011;**6670**: 256-277. DOI: 10.1007/978-3-642-22336- 5\_13

[50] D'Mello SK, Kory J. A review and meta-analysis of multimodal affect detection systems. ACM Computing Surveys. 2015;**47**:1-36. DOI: 10.1145/ 2682899

[51] McGurk H, Macdonald J. Hearing lips and seeing voices. Nature. 1976;**264**: 746-748. DOI: 10.1038/264746a0

[52] Douglas-Cowie E, Cowie R, Sneddon I, Cox C, Lowry O, McRorie M, et al. The HUMAINE data-base: Addressing the collection and annotation of naturalistic and induced emotional data. In: Proceedings of the 2nd International Conference on Affective Computing and Intelligent Interaction. Berlin: Springer Berlin Heidelberg; 2007. pp. 488-500

[53] Douglas-Cowie E, Cowie R, Campbell N. A new emotion database: Considerations, sources and scope. In: Proceedings of the ISCA Workshop on Speech and Emotion; April 2003. Belfast: Textflow; 2000. pp. 39-44

[54] McKeown G, Valstar M, Cowie R, Pantic M, Schroder M. The SEMAINE database: Annotated multimodal records of emotionally colored conversations between a person and a limited agent. IEEE Transactions on Affective Computing. 2012;**3**:5-17. DOI: 10.1109/taffc.2011.20

Network and Computer Applications. 2007;**30**:1334-1345. DOI: 10.1016/j.

*DOI: http://dx.doi.org/10.5772/intechopen.92019*

*Advances in Emotion Recognition: Link to Depressive Disorder*

learning identifies large-scale reward-

Neuroimaging. 2020;**5**(2):163-172. DOI:

[69] Sun YT, Chen T, He D, Dong Z, Cheng B, Wang S, et al. Research progress of biological markers for depression based on psychoradiology and artificial intelligence. Progress in Biochemistry and Biophysics. 2019;**46**:

[70] Al-Mosaiwi M, Johnstone T. In an absolute state: Elevated use of absolutist words is a marker specific to anxiety, depression, and suicidal ideation. Clinical Psychological Science. 2019;**7**: 636-637. DOI: 10.1177/216770261

[71] Liu X, Liu X, Sun J, Yu NX, Sun B, Li Q, et al. Proactive suicide prevention online (PSPO): Machine identification and crisis management for Chinese social media users with suicidal thoughts and behaviors. Journal of Medical Internet Research. 2019;**21**:

[72] Reece AG, Danforth CM. Instagram photos reveal predictive markers of depression. EPJ Data Science. 2017;**6**:15. DOI: 10.1140/epjds/s13688-017-0118-4

e11705. DOI: 10.2196/11705

[73] Gavrilescu M, Vizireanu N. Predicting depression, anxiety, and stress levels from videos using the facial action coding system. Sensors (Basel). 2019;**19**(17). DOI: 10.3390/s19173693

[74] Zhu Y, Shang Y, Shao Z, Guo G. Automated depression diagnosis based on deep networks to encode facial appearance and dynamics. IEEE Transactions on Affective Computing. 2018;**9**(4):578-584. DOI: 10.1109/

[75] Harati S, Crowell A, Mayberg H, Kong J, Nemati S. Discriminating

TAFFC.2017.2650899

related activity modulated by dopaminergic enhancement in major depression. Biological Psychiatry: Cognitive Neuroscience and

10.1016/j.bpsc.2019.10.002

879-899

9843297

[61] Yan J, Zheng W, Xin M, Qiu W. Bimodal emotion recognition based on body gesture and facial expression. Journal of Image and Graphics. 2013;**18**:

[62] Wang W, Shao J. Emotion recognition combining facial expressions and body movement characteristics. Television Technology. 2018;**42**:73-76.+83. DOI: 10.16280/j.

[63] Wang X, Hou D, Hu M, Ren F. Bimodal emotion recognition of composite spatiotemporal features. Journal of Image and Graphics. 2017;**22**: 39-48. DOI: 10.11834/jig.20170105

[64] Jiang M et al. Bimodal emotion recognition of expressions and postures in video sequences. Progress in Laser and Optoelectronics. 2018;**55**:167-174.

[65] Yee CM, Javitt DC, Miller GA. Replacing DSM categorical analyses with dimensional analyses in psychiatry research: The research domain criteria initiative. JAMA Psychiatry. 2015:

[66] Kraemer HC. Research domain criteria (RDoC) and the DSM-two methodological approaches to mental health diagnosis. JAMA Psychiatry. 2015:1163-1164. DOI: 10.1001/ jamapsychiatry.2015.2134

[67] Lindquist KA, Wager TD, Kober H, Bliss-Moreau E, Barrett LF. The brain basis of emotion: A meta-analytic review. The Behavioral and Brain Sciences. 2012;**35**(3):121-143. DOI: 10.1017/S0140525X11000446

[68] Liu Y, Admon R, Belleau EL, Kaiser RH, Clegg R, Beltzer M, et al. Machine

**135**

DOI: 10.3788/LOP55.071004

1159-1160. DOI: 10.1001/ jamapsychiatry.2015.1900

jnca.2006.09.007

videoe.2018.01:014

1101-1106

[55] Busso C, Bulut M, Lee C-C, Kazemzadeh A, Mower E, Kim S, et al. IEMOCAP: Interactive emotional dyadic motion capture database. Language Resources and Evaluation. 2008;**42**: 335-359. DOI: 10.1007/s10579-008- 9076-6

[56] Martin O, Kotsia I, Macq B, Pitas I. The eNTERFACE 05 audio-visual emotion database. In: Proceedings of the 22nd International Conference on Data Engineering Workshops (ICDEW'06); 3-7 April 2006; Atlanta. Atlanta, GA, USA: IEEE; 2006. p. 8

[57] Dhall A, Goecke R, Joshi J, Hoey J, EmotiW GT. Video and group-level emotion recognition challenges. In: Proceedings of the 18th ACM International Conference on Multimodal Interaction—ICMI 2016. ACM Press; 2016. pp. 427-432

[58] Li Y, Tao J, Schuller B, Shan S, Jiang D, MEC JJ. The multimodal emotion recognition challenge of CCPR 2016. In: Tan T, Li X, Chen X, Zhou J, Yang J, Cheng H, editors. Pattern Recognition. CCPR 2016. Communications in Computer and Information Science. Vol. 2016. Singapore: Springer; 2016. pp. 667-678

[59] Gunes H, Piccardi M. A bimodal face and body gesture database for automatic analysis of human nonverbal affective behavior. In: Proceedings of the 18th International Conference on Pattern Recognition (ICPR'06); 20-24 August 2006. Hong Kong: IEEE; 2006. pp. 1148-1153

[60] Gunes H, Piccardi M. Bi-modal emotion recognition from expressive face and body gestures. Journal of

*Advances in Emotion Recognition: Link to Depressive Disorder DOI: http://dx.doi.org/10.5772/intechopen.92019*

Network and Computer Applications. 2007;**30**:1334-1345. DOI: 10.1016/j. jnca.2006.09.007

[47] Zhang D, Wan B, Ming D. Research progress on emotion recognition based on physiological signals. Journal of Biomedical Engineering. 2015;**32**:

*Neurological and Mental Disorders*

database: Annotated multimodal records of emotionally colored conversations between a person and a limited agent. IEEE Transactions on Affective

Computing. 2012;**3**:5-17. DOI: 10.1109/t-

[56] Martin O, Kotsia I, Macq B, Pitas I. The eNTERFACE 05 audio-visual emotion database. In: Proceedings of the 22nd International Conference on Data Engineering Workshops (ICDEW'06); 3-7 April 2006; Atlanta. Atlanta, GA,

[57] Dhall A, Goecke R, Joshi J, Hoey J, EmotiW GT. Video and group-level emotion recognition challenges. In: Proceedings of the 18th ACM

International Conference on Multimodal Interaction—ICMI 2016. ACM Press;

[58] Li Y, Tao J, Schuller B, Shan S, Jiang D, MEC JJ. The multimodal emotion recognition challenge of CCPR 2016. In: Tan T, Li X, Chen X, Zhou J, Yang J, Cheng H, editors. Pattern

Communications in Computer and Information Science. Vol. 2016. Singapore: Springer; 2016. pp. 667-678

[59] Gunes H, Piccardi M. A bimodal face and body gesture database for automatic analysis of human nonverbal affective behavior. In: Proceedings of the 18th International Conference on Pattern Recognition (ICPR'06); 20-24 August 2006. Hong Kong: IEEE; 2006.

[60] Gunes H, Piccardi M. Bi-modal emotion recognition from expressive face and body gestures. Journal of

Recognition. CCPR 2016.

pp. 1148-1153

USA: IEEE; 2006. p. 8

2016. pp. 427-432

[55] Busso C, Bulut M, Lee C-C, Kazemzadeh A, Mower E, Kim S, et al. IEMOCAP: Interactive emotional dyadic motion capture database. Language Resources and Evaluation. 2008;**42**: 335-359. DOI: 10.1007/s10579-008-

affc.2011.20

9076-6

[48] Konstantinidis EI, Frantzidis CA, Pappas C, Bamidis PD. Real time emotion aware applications: A case study employing emotion evocative pictures and neuro-physiological sensing enhanced by graphic processor units. Computer Methods and Programs in Biomedicine. 2012;**107**:16-27. DOI:

[49] Liu Y, Sourina O, Nguyen MK. Realtime EEG-based emotion recognition and its applications. Transactions on Computational Science XII. 2011;**6670**: 256-277. DOI: 10.1007/978-3-642-22336-

[50] D'Mello SK, Kory J. A review and meta-analysis of multimodal affect detection systems. ACM Computing Surveys. 2015;**47**:1-36. DOI: 10.1145/

[51] McGurk H, Macdonald J. Hearing lips and seeing voices. Nature. 1976;**264**: 746-748. DOI: 10.1038/264746a0

Sneddon I, Cox C, Lowry O, McRorie M,

annotation of naturalistic and induced emotional data. In: Proceedings of the 2nd International Conference on Affective Computing and Intelligent Interaction. Berlin: Springer Berlin Heidelberg; 2007. pp. 488-500

[52] Douglas-Cowie E, Cowie R,

et al. The HUMAINE data-base: Addressing the collection and

[53] Douglas-Cowie E, Cowie R, Campbell N. A new emotion database: Considerations, sources and scope. In: Proceedings of the ISCA Workshop on Speech and Emotion; April 2003. Belfast: Textflow; 2000. pp. 39-44

[54] McKeown G, Valstar M, Cowie R, Pantic M, Schroder M. The SEMAINE

10.1016/j.cmpb.2012.03.008

229-234

5\_13

2682899

**134**

[61] Yan J, Zheng W, Xin M, Qiu W. Bimodal emotion recognition based on body gesture and facial expression. Journal of Image and Graphics. 2013;**18**: 1101-1106

[62] Wang W, Shao J. Emotion recognition combining facial expressions and body movement characteristics. Television Technology. 2018;**42**:73-76.+83. DOI: 10.16280/j. videoe.2018.01:014

[63] Wang X, Hou D, Hu M, Ren F. Bimodal emotion recognition of composite spatiotemporal features. Journal of Image and Graphics. 2017;**22**: 39-48. DOI: 10.11834/jig.20170105

[64] Jiang M et al. Bimodal emotion recognition of expressions and postures in video sequences. Progress in Laser and Optoelectronics. 2018;**55**:167-174. DOI: 10.3788/LOP55.071004

[65] Yee CM, Javitt DC, Miller GA. Replacing DSM categorical analyses with dimensional analyses in psychiatry research: The research domain criteria initiative. JAMA Psychiatry. 2015: 1159-1160. DOI: 10.1001/ jamapsychiatry.2015.1900

[66] Kraemer HC. Research domain criteria (RDoC) and the DSM-two methodological approaches to mental health diagnosis. JAMA Psychiatry. 2015:1163-1164. DOI: 10.1001/ jamapsychiatry.2015.2134

[67] Lindquist KA, Wager TD, Kober H, Bliss-Moreau E, Barrett LF. The brain basis of emotion: A meta-analytic review. The Behavioral and Brain Sciences. 2012;**35**(3):121-143. DOI: 10.1017/S0140525X11000446

[68] Liu Y, Admon R, Belleau EL, Kaiser RH, Clegg R, Beltzer M, et al. Machine

learning identifies large-scale rewardrelated activity modulated by dopaminergic enhancement in major depression. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging. 2020;**5**(2):163-172. DOI: 10.1016/j.bpsc.2019.10.002

[69] Sun YT, Chen T, He D, Dong Z, Cheng B, Wang S, et al. Research progress of biological markers for depression based on psychoradiology and artificial intelligence. Progress in Biochemistry and Biophysics. 2019;**46**: 879-899

[70] Al-Mosaiwi M, Johnstone T. In an absolute state: Elevated use of absolutist words is a marker specific to anxiety, depression, and suicidal ideation. Clinical Psychological Science. 2019;**7**: 636-637. DOI: 10.1177/216770261 9843297

[71] Liu X, Liu X, Sun J, Yu NX, Sun B, Li Q, et al. Proactive suicide prevention online (PSPO): Machine identification and crisis management for Chinese social media users with suicidal thoughts and behaviors. Journal of Medical Internet Research. 2019;**21**: e11705. DOI: 10.2196/11705

[72] Reece AG, Danforth CM. Instagram photos reveal predictive markers of depression. EPJ Data Science. 2017;**6**:15. DOI: 10.1140/epjds/s13688-017-0118-4

[73] Gavrilescu M, Vizireanu N. Predicting depression, anxiety, and stress levels from videos using the facial action coding system. Sensors (Basel). 2019;**19**(17). DOI: 10.3390/s19173693

[74] Zhu Y, Shang Y, Shao Z, Guo G. Automated depression diagnosis based on deep networks to encode facial appearance and dynamics. IEEE Transactions on Affective Computing. 2018;**9**(4):578-584. DOI: 10.1109/ TAFFC.2017.2650899

[75] Harati S, Crowell A, Mayberg H, Kong J, Nemati S. Discriminating

clinical phases of recovery from major depressive disorder using the dynamics of facial expression. In: 38th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC); January 01, 2016; United States: IEEE. 2016

[76] Cohen AS, Najolia GM, Kim Y, Dinzeo TJ. On the boundaries of blunt affect/alogia across severe mental illness: Implications for research domain criteria. Schizophrenia Research. 2012; **140**(1–3):41-45. DOI: 10.1016/j. schres.2012.07.001

[77] Covington MA, Lunden SLA, Cristofaro SL, Wan CR, Bailey CT, Broussard B, et al. Phonetic measures of reduced tongue movement correlate with negative symptom severity in hospitalized patients with first-episode schizophrenia-spectrum disorders. Schizophrenia Research. 2012;**142**(1): 93-95. DOI: 10.1016/j.schres.2012. 10.005

[78] Pan W, Flint J, Shenhav L, Liu T, Liu M, Hu B, et al. Re-examining the robustness of voice features in predicting depression: Compared with baseline of confounders. PLoS One. 2019;**14**:e0218172. DOI: 10.1371/journal. pone.0218172

[79] Haque A, Guo M, Miner AS, Fei-Fei L. Measuring depression symptom severity from spoken language and 3D facial expressions. Sound. 2018;**2**:1-7

[80] Yang L, Jiang D, Sahli H. Integrating deep and shallow models for multimodal depression analysis—Hybrid architectures. IEEE Transactions on Affective Computing. 2018;**1**:1-16. DOI: 10.1109/TAFFC.2018.2870398

[81] David DeVault RAGB, Georgila K, Gratch J, Hartholt A, Lhommet M, Lucas G, et al. SimSensei kiosk: A virtual human interviewer for healthcare decision support. In: Proceedings of the 13th International Conference on Autonomous Agents and Multiagent Systems (AAMAS 2014). 2014

**137**

**Chapter 9**

**Abstract**

psychoeducation

**1. Introduction**

Reimagining Attachment

for People with Borderline

*Dominik Havsteen-Franklin, Maria Patsou,* 

*Greta Somaini and Jorge Camarena Altamirano*

Personality Disorder

Traumas: Perspectives on Using

Image-Making in Psychoeducation

Integrating arts-based practice within psychological interventions has been widely used to increase accessibility and cultural sensitivity and to enable emotional communication and expression. However, using arts within psychoeducation for people with a diagnosis of borderline personality disorder (BPD) where attachment trauma has led to interpersonal difficulties has been less well-documented. This chapter intends to illustrate the experience of patients and facilitators in a mentalization-based psychoeducational programme being delivered in adult mental health services. We will look at the relevance of how images are used to embody relational struggles and how they are used to work through themes of anticipated attachment trauma. We then describe narratives of a 12-week arts-based psychoeducational programme from both the patient and professional perspectives. We conclude that arts-based mentalization focused psychoeducation is a valuable resource for preparing patients with a diagnosis of BPD for further treatment where attachment injury is central to the presenting issues.

**Keywords:** attachment trauma, borderline personality disorder, art psychotherapy,

Integrating arts-based practice within psychological interventions has been widely used to increase accessibility and cultural sensitivity and to enable emotional communication and expression. However, using arts within psychoeducation for people with a diagnosis of borderline personality disorder where traumatic events have led to interpersonal difficulties has been less well-documented. This chapter intends to illustrate the experience of patients and facilitators engaging in a mentalization-based psychoeducational programme being delivered in adult mental health services. We will look at the relevance of how images are used to embody relational struggles and how they are used to work through themes of anticipated interpersonal trauma. We then describe narratives of a 12-week arts-based psychoeducational programme from both the patient and professional perspectives.

### **Chapter 9**

clinical phases of recovery from major depressive disorder using the dynamics of facial expression. In: 38th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC); January 01, 2016;

*Neurological and Mental Disorders*

United States: IEEE. 2016

schres.2012.07.001

10.005

pone.0218172

**136**

[76] Cohen AS, Najolia GM, Kim Y, Dinzeo TJ. On the boundaries of blunt affect/alogia across severe mental illness: Implications for research domain criteria. Schizophrenia Research. 2012; **140**(1–3):41-45. DOI: 10.1016/j.

[77] Covington MA, Lunden SLA, Cristofaro SL, Wan CR, Bailey CT, Broussard B, et al. Phonetic measures of reduced tongue movement correlate with negative symptom severity in hospitalized patients with first-episode schizophrenia-spectrum disorders. Schizophrenia Research. 2012;**142**(1): 93-95. DOI: 10.1016/j.schres.2012.

[78] Pan W, Flint J, Shenhav L, Liu T, Liu M, Hu B, et al. Re-examining the robustness of voice features in

predicting depression: Compared with baseline of confounders. PLoS One. 2019;**14**:e0218172. DOI: 10.1371/journal.

[79] Haque A, Guo M, Miner AS, Fei-Fei L. Measuring depression symptom severity from spoken language and 3D facial expressions. Sound. 2018;**2**:1-7

[80] Yang L, Jiang D, Sahli H. Integrating deep and shallow models for multimodal depression analysis—Hybrid architectures. IEEE Transactions on Affective Computing. 2018;**1**:1-16. DOI:

[81] David DeVault RAGB, Georgila K, Gratch J, Hartholt A, Lhommet M, Lucas G, et al. SimSensei kiosk: A virtual human interviewer for healthcare decision support. In: Proceedings of the 13th International Conference on Autonomous Agents and Multiagent Systems (AAMAS 2014). 2014

10.1109/TAFFC.2018.2870398

## Reimagining Attachment Traumas: Perspectives on Using Image-Making in Psychoeducation for People with Borderline Personality Disorder

*Dominik Havsteen-Franklin, Maria Patsou, Greta Somaini and Jorge Camarena Altamirano*

### **Abstract**

Integrating arts-based practice within psychological interventions has been widely used to increase accessibility and cultural sensitivity and to enable emotional communication and expression. However, using arts within psychoeducation for people with a diagnosis of borderline personality disorder (BPD) where attachment trauma has led to interpersonal difficulties has been less well-documented. This chapter intends to illustrate the experience of patients and facilitators in a mentalization-based psychoeducational programme being delivered in adult mental health services. We will look at the relevance of how images are used to embody relational struggles and how they are used to work through themes of anticipated attachment trauma. We then describe narratives of a 12-week arts-based psychoeducational programme from both the patient and professional perspectives. We conclude that arts-based mentalization focused psychoeducation is a valuable resource for preparing patients with a diagnosis of BPD for further treatment where attachment injury is central to the presenting issues.

**Keywords:** attachment trauma, borderline personality disorder, art psychotherapy, psychoeducation

#### **1. Introduction**

Integrating arts-based practice within psychological interventions has been widely used to increase accessibility and cultural sensitivity and to enable emotional communication and expression. However, using arts within psychoeducation for people with a diagnosis of borderline personality disorder where traumatic events have led to interpersonal difficulties has been less well-documented. This chapter intends to illustrate the experience of patients and facilitators engaging in a mentalization-based psychoeducational programme being delivered in adult mental health services. We will look at the relevance of how images are used to embody relational struggles and how they are used to work through themes of anticipated interpersonal trauma. We then describe narratives of a 12-week arts-based psychoeducational programme from both the patient and professional perspectives.

We present an overview of the rationale of introducing arts-based psychoeducation into a mental health programme for people with a diagnosis of borderline personality disorder (BPD) followed by a description of the structure and a brief vignette of the programme. Finally, we will explore patient perceptions of the programme. All patients are anonymised and have given consent for this material to be published, including any images produced during the sessions. The authors are experienced clinician-researchers and have substantial experience of working within mental health services and related contexts.

#### **1.1 Background**

We now know that understanding the relationship between attachment, trauma and affect regulation is central to treating patients with a diagnosis of BPD. Evidence suggests that symptoms of BPD have a multifactorial psychobiological aetiology and include attachment trauma reactions to a range of harmful events, including childhood physical and sexual abuse [1–5], early neglect [6, 7] and invalidation [8]. Attachment traumas in this context refer to an intergenerational disorganised condition of relationship that results in disassociation, high affect arousal 'stemming from fright without solution' [9]. In conditions of affect dysregulation due to experiencing attachment traumas, it is hard for the person to make sense of causal factors, including traumatic events and triggers that may produce reactive high arousal states. Stawarczyk et al. [10] proposed that thought suppression is a key survival mechanism developed to mitigate the effects of predictive processing, particularly in relation to interpersonal events. Given the propensity to evade direct linking between affect arousal and events preceding the arousal, acting out emotional experience within an interpersonal context where attachment traumas are perceived to occur is a core part of the work in the restoration of a capacity to mentalize. Here we are referring to mentalizing as having the capacity to imagine intentional states of mind that influence behaviours, for example, desires, beliefs, feelings and thoughts. This is highly relevant to working with patients with a diagnosis of BPD where there is marked reduction in mentalizing [11] due to high affect arousal [12] and attachment trauma triggers within interpersonal contexts [13]. A mentalization-based verbal group model has been developed with this theoretical premise in mind [14]. Mentalizing begins in early infancy through the mirroring actions of parental care that offers a capacity to sensitise to emotional experiences and develop symbolic representations of self-and other as well as narrativisation and restoration of affective homeostasis [12]. The actions of mentalizing another, that is the attuned awareness of internal states influencing behaviours, enable a secure attachment [15]. Where unsuccessful parental mentalizing happens, for example, misattunements, insensitivity, neglect or abuse, the psychobiological vulnerability of the infant is likewise managed with non-mentalizing behaviours. As the pre-requisite for secure attachment is a capacity to mentalize this can cause transgenerational patterns of insecure attachment and attachment traumas, potentially advancing to conditions of severe avoidance of abandonment, identity disturbance, impulsivity and self-harm. These are symptomatic of severe conditions of non- mentalizing and together are considered to be primary symptoms of borderline personality disorder [16]. Most treatments for borderline personality disorder focus on the restoration of mentalizing and enabling a second-order representational system to become established [11, 17, 18]. Second to this, the development of 'positive thinking' to replace anticipated catastrophe is also considered to be helpful, particularly for impulsive behaviours [19]. Most treatments are medium to long-term and psychoeducation, as a brief intervention is still in the early stages of development for this clinical group. Given that mentalizing involves imagining mental states and developing representations of self and others, the use of

**139**

*Reimagining Attachment Traumas: Perspectives on Using Image-Making in Psychoeducation…*

image-making as a reflexive tool is proposed as being a helpful addition to the models of BPD treatment. That said, in order to mobilise the process, framing the problem, understanding the aetiology and reflecting on relational patterns of behaviour are a fundamental first step towards engaging with treatment. Whilst the authors are not intending to describe the effectiveness of the process of using art in psychoeducation for this population, the development of a trauma focused model or the long term benefits, the authors are intending to understand what happens when art is used as a focal point within a psychoeducation programme and how it effects people's experiences, self-understanding and the participant's preparedness for psychological treatment. Psychoeducation is widely used in mental health contexts to help patients to understand living with a diagnosis of borderline BPD [20, 21], how and when presenting issues arise and to consider attachment trauma in the context of interpersonal relationships [22], identity and affect arousal [21]. Further to this, psychoeducation has been used to help impulsivity and suicidality often occurring in relation to attachment traumas [23]. In psychoeducation, participants usually engage between one and 2 hours on a weekly basis for 6–20 weeks. There is some evidence to suggest psychoeducation improves relationships, reducing attachment traumas [22] however the evidence of its effectiveness is limited to feasibility and pilot studies [20–24]. However, the true extent of the use of psychoeducation is not accounted for given that psychoeducation is often part of a psychotherapeutic intervention for borderline personality disorder [25]. Within the context of art psychotherapy this was also clear in a survey conducted by the British Association of Art Therapists [26]; it was evident that 50% of the art therapists that responded used psychoeducation as either a stand-alone intervention or as being integrated within their treatment. Springham and Whittaker [26] reflect on the survey outcomes and conclude that psychoeducation could be a 'crucial unique feature of the practice of art therapy with BPD'. This is also clear in the emerging literature in this field where art psychotherapy methods of practice within a psychoeducational framework are often used alongside conventional methods of treatment [27–31]. For example, Sweig [30] uses a model of arts in psychoeducation and 'the role of art therapy in clarifying issues and mobilizing creative energies in service of personal growth.' Likewise Thorne [32] has published a specific model of using art within a psychoeducational framework for patients diagnosed with BPD similar to the one that we employed, that offers a structured and theme-based approach to engaging in understanding and reflecting upon self- and other-experience. Thorne [23] asserts that the image-making process adds to a psychoeducation model for BPD through enabling emotions and experiences to be more richly expressed and contained. The theoretical assumption guiding the evaluation was that the use of arts in psychoeducation encourages the patient to view the perceived attachment trauma trigger from a 'distance'. An intolerable, affectively charged trauma can be made more tolerable through seeing it as a human pattern of relating that all people may experience, and hence offering some normalisation according to human functioning [33, 34]. The nature of requesting the participant to see their experience through the lens of human patterns of relating and attachment trauma reactions helps the patient to consider potential aetiological factors. This requires the patient to relate to the subject but also to see the problem as an observer of themselves [35]. Psychoeducation uses a teaching-based model that encourages distance from the trauma and desensitisation to the predicated interpersonal response. We hypothesised that in the proposed model of psychoeducation there is a core mechanism that increases the capacity to reflect on the expected attachment trauma. The second key feature of taking a more distanced view of the attachment trauma, relates to the generalisability of the presenting difficulty. Arts psychotherapies engage the person in thinking about what they are expressing, how it is expressed and how the expression

*DOI: http://dx.doi.org/10.5772/intechopen.93406*

#### *Reimagining Attachment Traumas: Perspectives on Using Image-Making in Psychoeducation… DOI: http://dx.doi.org/10.5772/intechopen.93406*

image-making as a reflexive tool is proposed as being a helpful addition to the models of BPD treatment. That said, in order to mobilise the process, framing the problem, understanding the aetiology and reflecting on relational patterns of behaviour are a fundamental first step towards engaging with treatment. Whilst the authors are not intending to describe the effectiveness of the process of using art in psychoeducation for this population, the development of a trauma focused model or the long term benefits, the authors are intending to understand what happens when art is used as a focal point within a psychoeducation programme and how it effects people's experiences, self-understanding and the participant's preparedness for psychological treatment.

Psychoeducation is widely used in mental health contexts to help patients to understand living with a diagnosis of borderline BPD [20, 21], how and when presenting issues arise and to consider attachment trauma in the context of interpersonal relationships [22], identity and affect arousal [21]. Further to this, psychoeducation has been used to help impulsivity and suicidality often occurring in relation to attachment traumas [23]. In psychoeducation, participants usually engage between one and 2 hours on a weekly basis for 6–20 weeks. There is some evidence to suggest psychoeducation improves relationships, reducing attachment traumas [22] however the evidence of its effectiveness is limited to feasibility and pilot studies [20–24]. However, the true extent of the use of psychoeducation is not accounted for given that psychoeducation is often part of a psychotherapeutic intervention for borderline personality disorder [25]. Within the context of art psychotherapy this was also clear in a survey conducted by the British Association of Art Therapists [26]; it was evident that 50% of the art therapists that responded used psychoeducation as either a stand-alone intervention or as being integrated within their treatment. Springham and Whittaker [26] reflect on the survey outcomes and conclude that psychoeducation could be a 'crucial unique feature of the practice of art therapy with BPD'. This is also clear in the emerging literature in this field where art psychotherapy methods of practice within a psychoeducational framework are often used alongside conventional methods of treatment [27–31]. For example, Sweig [30] uses a model of arts in psychoeducation and 'the role of art therapy in clarifying issues and mobilizing creative energies in service of personal growth.' Likewise Thorne [32] has published a specific model of using art within a psychoeducational framework for patients diagnosed with BPD similar to the one that we employed, that offers a structured and theme-based approach to engaging in understanding and reflecting upon self- and other-experience. Thorne [23] asserts that the image-making process adds to a psychoeducation model for BPD through enabling emotions and experiences to be more richly expressed and contained.

The theoretical assumption guiding the evaluation was that the use of arts in psychoeducation encourages the patient to view the perceived attachment trauma trigger from a 'distance'. An intolerable, affectively charged trauma can be made more tolerable through seeing it as a human pattern of relating that all people may experience, and hence offering some normalisation according to human functioning [33, 34]. The nature of requesting the participant to see their experience through the lens of human patterns of relating and attachment trauma reactions helps the patient to consider potential aetiological factors. This requires the patient to relate to the subject but also to see the problem as an observer of themselves [35]. Psychoeducation uses a teaching-based model that encourages distance from the trauma and desensitisation to the predicated interpersonal response. We hypothesised that in the proposed model of psychoeducation there is a core mechanism that increases the capacity to reflect on the expected attachment trauma. The second key feature of taking a more distanced view of the attachment trauma, relates to the generalisability of the presenting difficulty. Arts psychotherapies engage the person in thinking about what they are expressing, how it is expressed and how the expression

*Neurological and Mental Disorders*

**1.1 Background**

within mental health services and related contexts.

We present an overview of the rationale of introducing arts-based psychoeducation into a mental health programme for people with a diagnosis of borderline personality disorder (BPD) followed by a description of the structure and a brief vignette of the programme. Finally, we will explore patient perceptions of the programme. All patients are anonymised and have given consent for this material to be published, including any images produced during the sessions. The authors are experienced clinician-researchers and have substantial experience of working

We now know that understanding the relationship between attachment, trauma and affect regulation is central to treating patients with a diagnosis of BPD. Evidence suggests that symptoms of BPD have a multifactorial psychobiological aetiology and include attachment trauma reactions to a range of harmful events, including childhood physical and sexual abuse [1–5], early neglect [6, 7] and invalidation [8]. Attachment traumas in this context refer to an intergenerational disorganised condition of relationship that results in disassociation, high affect arousal 'stemming from fright without solution' [9]. In conditions of affect dysregulation due to experiencing attachment traumas, it is hard for the person to make sense of causal factors, including traumatic events and triggers that may produce reactive high arousal states. Stawarczyk et al. [10] proposed that thought suppression is a key survival mechanism developed to mitigate the effects of predictive processing, particularly in relation to interpersonal events. Given the propensity to evade direct linking between affect arousal and events preceding the arousal, acting out emotional experience within an interpersonal context where attachment traumas are perceived to occur is a core part of the work in the restoration of a capacity to mentalize. Here we are referring to mentalizing as having the capacity to imagine intentional states of mind that influence behaviours, for example, desires, beliefs, feelings and thoughts. This is highly relevant to working with patients with a diagnosis of BPD where there is marked reduction in mentalizing [11] due to high affect arousal [12] and attachment trauma triggers within interpersonal contexts [13]. A mentalization-based verbal group model has been developed with this theoretical premise in mind [14]. Mentalizing begins in early infancy through the mirroring actions of parental care that offers a capacity to sensitise to emotional experiences and develop symbolic representations of self-and other as well as narrativisation and restoration of affective homeostasis [12]. The actions of mentalizing another, that is the attuned awareness of internal states influencing behaviours, enable a secure attachment [15]. Where unsuccessful parental mentalizing happens, for example, misattunements, insensitivity, neglect or abuse, the psychobiological vulnerability of the infant is likewise managed with non-mentalizing behaviours. As the pre-requisite for secure attachment is a capacity to mentalize this can cause transgenerational patterns of insecure attachment and attachment traumas, potentially advancing to conditions of severe avoidance of abandonment, identity disturbance, impulsivity and self-harm. These are symptomatic of severe conditions of non- mentalizing and together are considered to be primary symptoms of borderline personality disorder [16]. Most treatments for borderline personality disorder focus on the restoration of mentalizing and enabling a second-order representational system to become established [11, 17, 18]. Second to this, the development of 'positive thinking' to replace anticipated catastrophe is also considered to be helpful, particularly for impulsive behaviours [19]. Most treatments are medium to long-term and psychoeducation, as a brief intervention is still in the early stages of development for this clinical group. Given that mentalizing involves imagining mental states and developing representations of self and others, the use of

**138**

might be received. We propose that introducing arts to a psychoeducation model supports the process of imaginative reflexivity in psychoeducation as a method that enhances the person's capacity to regulate affect and improve relating to the other [36–39]. These features of developing imaginative flexibility are also described as a core mechanism in the capacity to mentalize attachment traumas [34] and therefore we deemed this as a helpful addition to the verbal methods of intervention.

Mentalization-based art psychotherapy is becoming an established method of treatment due to the accessibility, cultural sensitivity and scope for emotional communication and reflection [40, 41]. Mentalization based treatment draws on relational theory from attachment theory [42] and restoring mentalizing in the context of attachment trauma as a key part of the work [43]. The concept of mentalization also has its roots in early dynamic theory and cognitive science [44] and refers to a person's capacity to reflect on self and others' intentional states of mind [45].

#### **2. Arts-based psychoeducation within a mentalization based programme in psychiatry**

#### **2.1 Overview of the psychoeducation programme**

Arts-based mentalization focused psychoeducation is a 12-week programme developed within a secondary care mental health context as both a standalone intervention and as a preparation for an 18-month arts-based mentalization treatment programme. Patients were offered up to four sessions to assess for presenting issues relating to attachment trauma such as self-harm, identity disturbance and affect dysregulation as well as the patient's motivation for receiving therapy. To understand other stressors, a holistic view to the person's life including family, finance, social factors and a risk assessment were assessed in relation to their potential treatment and was shared with patients as an assessment formulation report co-written with the patient. The facilitators regularly reviewed the formulation with the members throughout the programme. Following this process, the facilitators offered a place on the arts-based psychoeducation programme. The sessions included arts and ran for 1 hour and 30 minutes over 12 weeks. The themes for each week were modelled on the programme designed by Karterud and Bateman [46] that described preparatory sessions for mentalization-based treatment (MBT) [47]:

Week 1: Mentalization and mentalizing stance Week 2: What does it mean to have problems with mentalizing? Week 3: Why do we have emotions and what are the core emotions? Week 4: How do we register and regulate emotions? Week 5: The significance of attachment relationships Week 6: Attachment and mentalization Week 7: What is borderline personality disorder? Week 8: Mentalization-based arts therapies - Part 1 Week 9: Mentalization-based arts therapies - Part 2 Week 10: Anxiety, attachment and mentalizing Week 11: Depression, attachment and mentalizing Week 12: Summary and conclusion, feedback

The facilitators informed participants that the focus of the group would be on how we see ourselves and the way we relate to others and how these perceptions link to early attachment patterns and traumas to those attachments. Group rules,

**141**

*Reimagining Attachment Traumas: Perspectives on Using Image-Making in Psychoeducation…*

boundaries, confidentiality, respect for others and punctuality were discussed and agreed. Using alcohol, drugs and violence was prohibited in addition to contact between the members of the group, outside of the group. The format of the group included attendance and a refresher of the previous session, presentation and development of the theme of the current session and discussion, image making, feedback

Each session had the purpose of clarifying the concept of mentalization and the point where it can fail, particularly in relation to anticipating attachment traumas and regulating the associated intense affect. The intention of the group was to work with recent attachment traumas, which group members had identified as being emotionally difficult. At the end of the psychoeducation group, there was a collab-

The arts were introduced by the fourth author of this chapter and a co-facilitator

(both art psychotherapists) to be used in an improvised and explorative way. Materials such as chalks, pens and paints were available to help the patient explore their experience of being in the group in relation to the weekly themes. The narrative uses pseudonyms for the patient names. All members of the group had a primary diagnosis of BPD which had been confirmed through the assessment process. George was a 61 year old, white British man, Henry was a 65 year old white

The artworks were treated as an important part of their personal and group experience and were kept until the end of the 12th session. Over the weeks, the patients' engagement with the arts appeared to develop in emotional complexity, competency and confidence which was reflected in the way they used the arts media. With the presence of anticipated attachment traumas, the arts were also offered as a way of regulating feelings through making doodles or experimental marks when it felt too difficult to reflect on or explore themes. As sessions passed an increasing engagement with the arts was encouraged and there was clear intent to produce figurative drawings with a narrative that related to attachment trauma and

orative decision made whether further treatment was required.

British man, and Dalmar was a 27 year old British Somalian lady.

how mentalizing could be restored in relation to the themes discussed.

A way of developing initial cohesion in the group was clear in Week 3, in response to the theme of 'Why do we have emotions and what are the core emotions?', George described how his image making on the first week was driven by the curiosity of using the pencil colours that were available, as it gave him an opportunity to 'get a feel for being in a group'. In Week 3, his initial anxieties were reformulated to form rhythmically drawn patterns in distinct shades on the right top corner of the paper (**Figure 1**). The early stage of the work in the group and how the forms co-existed became a strong motif for his experience, where the spaces between people, the nuances of emotions and feelings remained compact and connected in a controlled space. We felt that the patient was using the arts materials to regulate his emotional response to feeling cornered, hemmed into a group where he was uncertain about how people could interact and function without disagreement and the resulting personal trauma and potential disassociation. His marks represented a tapestry like presence where form and colour could coexist in a similar way as his

Similarly, in the same session, Dalmar described her artwork (**Figure 2**) she said that her relationships were like these stone structures that had 'collapsed', 'heavy and helpless', 'immovable' and 'stuck'. These terms are typical of the disorganised attachment state where there is no solution or relational flexibility and ultimately there is a

**2.2 Psychoeducation, group work and the clinical process: the art** 

*DOI: http://dx.doi.org/10.5772/intechopen.93406*

and preparation for the next session.

**psychotherapists' perspective**

emergent feelings in the group's context.

#### *Reimagining Attachment Traumas: Perspectives on Using Image-Making in Psychoeducation… DOI: http://dx.doi.org/10.5772/intechopen.93406*

boundaries, confidentiality, respect for others and punctuality were discussed and agreed. Using alcohol, drugs and violence was prohibited in addition to contact between the members of the group, outside of the group. The format of the group included attendance and a refresher of the previous session, presentation and development of the theme of the current session and discussion, image making, feedback and preparation for the next session.

Each session had the purpose of clarifying the concept of mentalization and the point where it can fail, particularly in relation to anticipating attachment traumas and regulating the associated intense affect. The intention of the group was to work with recent attachment traumas, which group members had identified as being emotionally difficult. At the end of the psychoeducation group, there was a collaborative decision made whether further treatment was required.

#### **2.2 Psychoeducation, group work and the clinical process: the art psychotherapists' perspective**

The arts were introduced by the fourth author of this chapter and a co-facilitator (both art psychotherapists) to be used in an improvised and explorative way. Materials such as chalks, pens and paints were available to help the patient explore their experience of being in the group in relation to the weekly themes. The narrative uses pseudonyms for the patient names. All members of the group had a primary diagnosis of BPD which had been confirmed through the assessment process. George was a 61 year old, white British man, Henry was a 65 year old white British man, and Dalmar was a 27 year old British Somalian lady.

The artworks were treated as an important part of their personal and group experience and were kept until the end of the 12th session. Over the weeks, the patients' engagement with the arts appeared to develop in emotional complexity, competency and confidence which was reflected in the way they used the arts media. With the presence of anticipated attachment traumas, the arts were also offered as a way of regulating feelings through making doodles or experimental marks when it felt too difficult to reflect on or explore themes. As sessions passed an increasing engagement with the arts was encouraged and there was clear intent to produce figurative drawings with a narrative that related to attachment trauma and how mentalizing could be restored in relation to the themes discussed.

A way of developing initial cohesion in the group was clear in Week 3, in response to the theme of 'Why do we have emotions and what are the core emotions?', George described how his image making on the first week was driven by the curiosity of using the pencil colours that were available, as it gave him an opportunity to 'get a feel for being in a group'. In Week 3, his initial anxieties were reformulated to form rhythmically drawn patterns in distinct shades on the right top corner of the paper (**Figure 1**). The early stage of the work in the group and how the forms co-existed became a strong motif for his experience, where the spaces between people, the nuances of emotions and feelings remained compact and connected in a controlled space. We felt that the patient was using the arts materials to regulate his emotional response to feeling cornered, hemmed into a group where he was uncertain about how people could interact and function without disagreement and the resulting personal trauma and potential disassociation. His marks represented a tapestry like presence where form and colour could coexist in a similar way as his emergent feelings in the group's context.

Similarly, in the same session, Dalmar described her artwork (**Figure 2**) she said that her relationships were like these stone structures that had 'collapsed', 'heavy and helpless', 'immovable' and 'stuck'. These terms are typical of the disorganised attachment state where there is no solution or relational flexibility and ultimately there is a

*Neurological and Mental Disorders*

**programme in psychiatry**

treatment (MBT) [47]:

**2.1 Overview of the psychoeducation programme**

Week 1: Mentalization and mentalizing stance

Week 6: Attachment and mentalization

Week 4: How do we register and regulate emotions? Week 5: The significance of attachment relationships

Week 7: What is borderline personality disorder? Week 8: Mentalization-based arts therapies - Part 1 Week 9: Mentalization-based arts therapies - Part 2 Week 10: Anxiety, attachment and mentalizing Week 11: Depression, attachment and mentalizing Week 12: Summary and conclusion, feedback

Week 2: What does it mean to have problems with mentalizing? Week 3: Why do we have emotions and what are the core emotions?

The facilitators informed participants that the focus of the group would be on how we see ourselves and the way we relate to others and how these perceptions link to early attachment patterns and traumas to those attachments. Group rules,

might be received. We propose that introducing arts to a psychoeducation model supports the process of imaginative reflexivity in psychoeducation as a method that enhances the person's capacity to regulate affect and improve relating to the other [36–39]. These features of developing imaginative flexibility are also described as a core mechanism in the capacity to mentalize attachment traumas [34] and therefore

Mentalization-based art psychotherapy is becoming an established method of treatment due to the accessibility, cultural sensitivity and scope for emotional communication and reflection [40, 41]. Mentalization based treatment draws on relational theory from attachment theory [42] and restoring mentalizing in the context of attachment trauma as a key part of the work [43]. The concept of mentalization also has its roots in early dynamic theory and cognitive science [44] and refers to a person's capacity to reflect on self and others' intentional states of mind [45].

Arts-based mentalization focused psychoeducation is a 12-week programme developed within a secondary care mental health context as both a standalone intervention and as a preparation for an 18-month arts-based mentalization treatment programme. Patients were offered up to four sessions to assess for presenting issues relating to attachment trauma such as self-harm, identity disturbance and affect dysregulation as well as the patient's motivation for receiving therapy. To understand other stressors, a holistic view to the person's life including family, finance, social factors and a risk assessment were assessed in relation to their potential treatment and was shared with patients as an assessment formulation report co-written with the patient. The facilitators regularly reviewed the formulation with the members throughout the programme. Following this process, the facilitators offered a place on the arts-based psychoeducation programme. The sessions included arts and ran for 1 hour and 30 minutes over 12 weeks. The themes for each week were modelled on the programme designed by Karterud and Bateman [46] that described preparatory sessions for mentalization-based

we deemed this as a helpful addition to the verbal methods of intervention.

**2. Arts-based psychoeducation within a mentalization based** 

**140**

**Figure 1.** *'Myself in the group'.*

**Figure 2.** *'Relationships as collapsing stones'.*

sense of unresponsive or misattuned neglect. These early images showed a capacity to use image making as a tool for embodying complex emotional narratives that anticipated attachment traumas in ways that could be communicated within a group context.

**143**

**Figure 3.** *'Loss of control'.*

*Reimagining Attachment Traumas: Perspectives on Using Image-Making in Psychoeducation…*

By Week 3 some group members mentioned how the use of the arts seemed to enable a capacity to be more aware and talk about their mental and emotional processes within an interpersonal context. In **Figures 1** and **2**, the artwork allowed the opportunity to expressively articulate thoughts and emotions that had remained unspoken. In Week 4, 'How do we register and regulate emotions?' One group member (Henry) described his image as the traffic light in the middle of his drawing (**Figure 3**). He used the image to help the group reflect on his anxieties of being out of control, again in a disorganised state where he felt helpless and unwanted. He described the predominant affect as fear, represented by the sunset as a loss of light and something blinding. He described his wish to be like the lamp on the left of the page which he commented on as having a more 'pleasant and balanced quality'. Again, key themes about the rupture to attachments as losing the sun and associated

high 'fight or flight' arousal of feeling afraid were at the core of the work.

Using themes to structure sessions helped to enable experiences to be shared. For example, another group member (George) (**Figure 4**) described being 'like the hectic river which was crossing and dividing the urban and green space'. In these early sessions, we focused the content on identifying emotional states and understanding how interpersonal contexts stimulate attachment anxieties about anticipated attachment traumas. In **Figure 4**, George described the urban environment as populated with fragile homes with empty windows, and a mass of green fluidity is sharply divided by an insertion of blue. The powerful disruption also described an intense experience of disconnection that he felt was difficult to bridge due to the uncertainties contained in the green grass of the hill and the disappearing, empty-looking town again drawing on the felt experience of the unavailable

The cause of these intolerable conditions of loss of control and disorganised attachment was shared in the group. Dalmar stated that if her family understood her, they would not behave the way they do. Firmly stating, 'It's them that's the

*DOI: http://dx.doi.org/10.5772/intechopen.93406*

and unresponsive others.

problem.' (**Figure 5**).

#### *Reimagining Attachment Traumas: Perspectives on Using Image-Making in Psychoeducation… DOI: http://dx.doi.org/10.5772/intechopen.93406*

By Week 3 some group members mentioned how the use of the arts seemed to enable a capacity to be more aware and talk about their mental and emotional processes within an interpersonal context. In **Figures 1** and **2**, the artwork allowed the opportunity to expressively articulate thoughts and emotions that had remained unspoken. In Week 4, 'How do we register and regulate emotions?' One group member (Henry) described his image as the traffic light in the middle of his drawing (**Figure 3**). He used the image to help the group reflect on his anxieties of being out of control, again in a disorganised state where he felt helpless and unwanted. He described the predominant affect as fear, represented by the sunset as a loss of light and something blinding. He described his wish to be like the lamp on the left of the page which he commented on as having a more 'pleasant and balanced quality'. Again, key themes about the rupture to attachments as losing the sun and associated high 'fight or flight' arousal of feeling afraid were at the core of the work.

Using themes to structure sessions helped to enable experiences to be shared. For example, another group member (George) (**Figure 4**) described being 'like the hectic river which was crossing and dividing the urban and green space'. In these early sessions, we focused the content on identifying emotional states and understanding how interpersonal contexts stimulate attachment anxieties about anticipated attachment traumas. In **Figure 4**, George described the urban environment as populated with fragile homes with empty windows, and a mass of green fluidity is sharply divided by an insertion of blue. The powerful disruption also described an intense experience of disconnection that he felt was difficult to bridge due to the uncertainties contained in the green grass of the hill and the disappearing, empty-looking town again drawing on the felt experience of the unavailable and unresponsive others.

The cause of these intolerable conditions of loss of control and disorganised attachment was shared in the group. Dalmar stated that if her family understood her, they would not behave the way they do. Firmly stating, 'It's them that's the problem.' (**Figure 5**).

**Figure 3.** *'Loss of control'.*

*Neurological and Mental Disorders*

**142**

**Figure 2.**

*'Relationships as collapsing stones'.*

**Figure 1.**

*'Myself in the group'.*

sense of unresponsive or misattuned neglect. These early images showed a capacity to use image making as a tool for embodying complex emotional narratives that anticipated attachment traumas in ways that could be communicated within a group context.

**Figure 4.** *'I live in the space In-between'.*

**Figure 5.** *'It's them that's the problem'.*

The same member, later in the work during the session titled, 'Anxiety Attachment and Mentalizing', responded by describing how she manages those states of helplessness and abandonment rather than describing what causes them. She managed painful feelings by harming herself or attempting to overdose on her medication, depicting a blue and white pill in a smudged, surrounded by

**145**

personal stories.

**Figure 6.**

**perspective**

*Reimagining Attachment Traumas: Perspectives on Using Image-Making in Psychoeducation…*

fingerprint smudges (**Figure 6**). The theme resonated with the group experience. Several people in the group said that this was the first time that they felt that they were being heard. The sense of having a shared experience within the group session contributed positively to the sense of being held in mind by another and developing

a capacity to mentalize the other in the context of anticipated social rupture. By the end of the 12 weeks, participants were asked to conclude the sessions through sharing thoughts about how they engaged with the use of the arts as a medium to foster reflective thinking about thoughts, emotions, beliefs, and their

**2.3 Experiences of image-making, affect and relationships: the patient** 

were extracted and are contextualised within the narrative below.

The first sessions appeared to have a heightened sense of vulnerability and members were tentatively engaging. For example, one member (George.) described drawing an image of a baby without a mother in response to the theme of what it means to have problems with secure attachment, describing the image as having a re-traumatising quality. The image making was originally seen as tentative, bearing no genuine relationship to the psychoeducation, and sometimes felt uncomfortable. Members also expressed cautious engagement through feeling self-conscious and unskilled when using the art media, which they felt expressed a sense of vulnerability and the feeling that using the art media was exposing a sense of vulnerability, feeling like they would fail or not be good

Following the psychoeducation, all members were invited to give feedback about their experience for the purposes of evaluating the group and for the results to be published. Three members came forward and gave consent for their interview to be published (George, Henry and Dalmar). The interviews were conducted by honorary researchers (authors 2 and 3) who were independent from the programme and who were supervised as part of an early career research initiative [48, 49] founded with the NHS by the first author. Each interview lasted about 1 hour and was semistructures. Key extracts that appeared to be prevalent or represent the larger themes

*DOI: http://dx.doi.org/10.5772/intechopen.93406*

*'When I feel abandoned I can only think about dying'.*

*Reimagining Attachment Traumas: Perspectives on Using Image-Making in Psychoeducation… DOI: http://dx.doi.org/10.5772/intechopen.93406*

**Figure 6.** *'When I feel abandoned I can only think about dying'.*

*Neurological and Mental Disorders*

**144**

**Figure 5.**

*'It's them that's the problem'.*

**Figure 4.**

*'I live in the space In-between'.*

The same member, later in the work during the session titled, 'Anxiety Attachment and Mentalizing', responded by describing how she manages those states of helplessness and abandonment rather than describing what causes them. She managed painful feelings by harming herself or attempting to overdose on her medication, depicting a blue and white pill in a smudged, surrounded by

fingerprint smudges (**Figure 6**). The theme resonated with the group experience. Several people in the group said that this was the first time that they felt that they were being heard. The sense of having a shared experience within the group session contributed positively to the sense of being held in mind by another and developing a capacity to mentalize the other in the context of anticipated social rupture.

By the end of the 12 weeks, participants were asked to conclude the sessions through sharing thoughts about how they engaged with the use of the arts as a medium to foster reflective thinking about thoughts, emotions, beliefs, and their personal stories.

#### **2.3 Experiences of image-making, affect and relationships: the patient perspective**

Following the psychoeducation, all members were invited to give feedback about their experience for the purposes of evaluating the group and for the results to be published. Three members came forward and gave consent for their interview to be published (George, Henry and Dalmar). The interviews were conducted by honorary researchers (authors 2 and 3) who were independent from the programme and who were supervised as part of an early career research initiative [48, 49] founded with the NHS by the first author. Each interview lasted about 1 hour and was semistructures. Key extracts that appeared to be prevalent or represent the larger themes were extracted and are contextualised within the narrative below.

The first sessions appeared to have a heightened sense of vulnerability and members were tentatively engaging. For example, one member (George.) described drawing an image of a baby without a mother in response to the theme of what it means to have problems with secure attachment, describing the image as having a re-traumatising quality. The image making was originally seen as tentative, bearing no genuine relationship to the psychoeducation, and sometimes felt uncomfortable. Members also expressed cautious engagement through feeling self-conscious and unskilled when using the art media, which they felt expressed a sense of vulnerability and the feeling that using the art media was exposing a sense of vulnerability, feeling like they would fail or not be good

enough. For example, one member stuttered and looked embarrassed when she was asked about the use of the art materials.

*'I did feel slightly embarrassed, but or not embarrassed, but…conscious and conscious that I couldn't draw really that well in that short time.'*

The unexpected effect of the image was often experienced as both offering helpful insight and emotional disturbance. George described how a sense of profound attachment re-traumatisation was immediately evoked,

*'When [the image], features round something that impacted you like, so bad, so much…When it, when you could see what happened, bulging in front of your eyes… it brought back terrible memories.'*

Henry also expressed an experience of re-traumatisation from being in the presence of others during the group experience whilst attempting to avoid group conflicts. He described an avoidance of unmanageable disorganised attachment arousal in the group that could be provoked by group conflicts to try to keep his stability.

*'It's just that it might have brought up memories that I didn't want to think about… I'm sort of outside the conflicts… … [Relationships] can be rocky, chaotic, so again it's a bit like me, I'm stable now but I feel it's a bit fragile…'*

However, in this early stage, there was a sense that the structure could contain and guide, often helped to reduce anxieties through a sense of being in a group with a direction which felt supportive; being held by the frame of the task. Henry stated,

*'And so to have that...back-up... of other people. Though they, you're not talking... you're, more or less, you know, it's more structured'. Henry said that she had begun to gain a sense of clarity regarding past relationships '[past attachment trauma] is not bothering me so much…cause the only person it's destroying it's me'.*

However, through having a practical task, the sense of accomplishment of improvising was felt to be useful and could express a state of attachment trauma rather than acting out interpersonally. George said that he used the image as a retreat when one he 'could not get a word in'. As the work progressed, members said the image making became more comfortable and automatic, perhaps less pre-meditated, but often members said that the relational tension meant that it was hard to be playful or to improvise. As the work progressed, members began to monitor themselves, restore a capacity to mentalize, using the psychoeducation to make sense of their experience. For example, using images helped Dalmar to reflect on the experience of attachment trauma, exploring what felt like part of an illness and what was felt like a 'normal' response to relationships,

*'….in relation to like my personality disorder erm …there is a lot of up and down and stuff… but it's unhealthy but I was just thinking how a lot of it is just normal…'*

As the group progressed, what seems to accompany the image making and inform the process were several key areas directly related to the aims of the group. Members said that image-making was used to reflect on feeling states relating to attachment traumas that had otherwise been considered as overwhelming and this marked the beginning of feeling more trusting of others.

**147**

*Reimagining Attachment Traumas: Perspectives on Using Image-Making in Psychoeducation…*

*'…yeah, my confidence has come back… I think I can trust them, but it's, I…, I don't* 

Members also described an experience of image-making as a way of processing over-thinking and an opportunity to make sense of the salient teaching points

*'I was just feeling reflective like…erm thinking about myself and thinking about what other people were saying I was just sort of processing it in my head and this is* 

During the latter sessions they described a growing sense of stability and confidence in themselves and their own agency, which enabled a capacity to be more reflective about other people's states of mind. However, this appeared to be less so with the experience of what motivated other people's actions, which often produced feelings of anxiety or distrust. Two of the participants described having a more structured interpersonal experience where they were trying to unravel their problems and consider ways of reflecting on their experience. For example, one participant stated,

*'the psychoeducation group has helped me to step back and think about what is* 

Towards the end, members suggested an experience of hope that was linked with an educational 'structure' that enabled people to be together and learn about how they might experience one another and what might cause a perceived attachment trauma. There was also an experience of being together and appreciating each

other's struggles, in effect beginning to mentalize the others' experience.

*'That other people around you, makes you feel comfortable. Make you feel... they're suffering and all. You know, others are in the same predicament as you are.'* 

The ending marked a hard transition and whilst the psychoeducation was successful in helping members of the group to reflect on their experience and form tentative relationships, there was also a sense that they were left with uncertainties given the brief period of the group. Members described the first steps towards alternative ways of relating, but they seemed to be left with a fragile footing.

*'… well, I'm more positive, I'm more positive in myself. I could lose that stability any* 

This brief narrative echoes some similar anxieties as the therapist's account of the session, and overall, the quality and stories of the members felt like a brief but important encounter that opened up the emotionality and contextual issues in relation to their presenting issues. Following the psychoeducation, most members agreed to continue the work of understanding mentalizing in a non-directive

The arts-based psychoeducation offered a structured experiential approach to understanding attachment traumas and mentalizing relationships. The image

*DOI: http://dx.doi.org/10.5772/intechopen.93406*

*know, I just don't know.'*

*how it came out on paper.'*

provided by the facilitator.

*happening'.*

*(George)*

*moment…'*

**3. Conclusion**

mentalization art psychotherapy group.

*Reimagining Attachment Traumas: Perspectives on Using Image-Making in Psychoeducation… DOI: http://dx.doi.org/10.5772/intechopen.93406*

*'…yeah, my confidence has come back… I think I can trust them, but it's, I…, I don't know, I just don't know.'*

Members also described an experience of image-making as a way of processing over-thinking and an opportunity to make sense of the salient teaching points provided by the facilitator.

*'I was just feeling reflective like…erm thinking about myself and thinking about what other people were saying I was just sort of processing it in my head and this is how it came out on paper.'*

During the latter sessions they described a growing sense of stability and confidence in themselves and their own agency, which enabled a capacity to be more reflective about other people's states of mind. However, this appeared to be less so with the experience of what motivated other people's actions, which often produced feelings of anxiety or distrust. Two of the participants described having a more structured interpersonal experience where they were trying to unravel their problems and consider ways of reflecting on their experience. For example, one participant stated,

#### *'the psychoeducation group has helped me to step back and think about what is happening'.*

Towards the end, members suggested an experience of hope that was linked with an educational 'structure' that enabled people to be together and learn about how they might experience one another and what might cause a perceived attachment trauma. There was also an experience of being together and appreciating each other's struggles, in effect beginning to mentalize the others' experience.

*'That other people around you, makes you feel comfortable. Make you feel... they're suffering and all. You know, others are in the same predicament as you are.' (George)*

The ending marked a hard transition and whilst the psychoeducation was successful in helping members of the group to reflect on their experience and form tentative relationships, there was also a sense that they were left with uncertainties given the brief period of the group. Members described the first steps towards alternative ways of relating, but they seemed to be left with a fragile footing.

*'… well, I'm more positive, I'm more positive in myself. I could lose that stability any moment…'*

This brief narrative echoes some similar anxieties as the therapist's account of the session, and overall, the quality and stories of the members felt like a brief but important encounter that opened up the emotionality and contextual issues in relation to their presenting issues. Following the psychoeducation, most members agreed to continue the work of understanding mentalizing in a non-directive mentalization art psychotherapy group.

#### **3. Conclusion**

The arts-based psychoeducation offered a structured experiential approach to understanding attachment traumas and mentalizing relationships. The image

*Neurological and Mental Disorders*

was asked about the use of the art materials.

*it brought back terrible memories.'*

stability.

enough. For example, one member stuttered and looked embarrassed when she

The unexpected effect of the image was often experienced as both offering helpful insight and emotional disturbance. George described how a sense of profound

*'When [the image], features round something that impacted you like, so bad, so much…When it, when you could see what happened, bulging in front of your eyes…* 

Henry also expressed an experience of re-traumatisation from being in the presence of others during the group experience whilst attempting to avoid group conflicts. He described an avoidance of unmanageable disorganised attachment arousal in the group that could be provoked by group conflicts to try to keep his

*'It's just that it might have brought up memories that I didn't want to think about… I'm sort of outside the conflicts… … [Relationships] can be rocky, chaotic, so again* 

However, in this early stage, there was a sense that the structure could contain and guide, often helped to reduce anxieties through a sense of being in a group with a direction which felt supportive; being held by the frame of the task. Henry stated,

*'And so to have that...back-up... of other people. Though they, you're not talking... you're, more or less, you know, it's more structured'. Henry said that she had begun to gain a sense of clarity regarding past relationships '[past attachment trauma] is* 

However, through having a practical task, the sense of accomplishment of improvising was felt to be useful and could express a state of attachment trauma rather than acting out interpersonally. George said that he used the image as a retreat when one he 'could not get a word in'. As the work progressed, members said the image making became more comfortable and automatic, perhaps less pre-meditated, but often members said that the relational tension meant that it was hard to be playful or to improvise. As the work progressed, members began to monitor themselves, restore a capacity to mentalize, using the psychoeducation to make sense of their experience. For example, using images helped Dalmar to reflect on the experience of attachment trauma, exploring what felt like part of an illness

*'….in relation to like my personality disorder erm …there is a lot of up and down and stuff… but it's unhealthy but I was just thinking how a lot of it is just normal…'*

As the group progressed, what seems to accompany the image making and inform the process were several key areas directly related to the aims of the group. Members said that image-making was used to reflect on feeling states relating to attachment traumas that had otherwise been considered as overwhelming and this

*not bothering me so much…cause the only person it's destroying it's me'.*

and what was felt like a 'normal' response to relationships,

marked the beginning of feeling more trusting of others.

*'I did feel slightly embarrassed, but or not embarrassed, but…conscious and* 

*conscious that I couldn't draw really that well in that short time.'*

attachment re-traumatisation was immediately evoked,

*it's a bit like me, I'm stable now but I feel it's a bit fragile…'*

**146**

#### *Neurological and Mental Disorders*

making seemed to offer powerful access to feelings and experiences that sometimes, and especially at the beginning of the psychoeducation, could be uncomfortable and even 're-traumatising'. The art psychotherapists' perspective of the work provides a comprehensive narrative, highlighting the small but significant positive changes. In the follow-up evaluation we see the patient's autonomy emerging, also describing a tentative grasp of the concepts and emergent alternative forms of relating. We believe that the image-making process facilitated an affective experience of relationships, often revealing vulnerability in safe ways that could be reflected on.

The images offered a powerful account of this process, and particularly the anxieties and uncertainties about developing a secure attachment. The images also revealed anticipated attachment traumas and an invalidating environment, for example in the stuck, rigid invalidating stones; being surrounded by a family that 'should be in therapy'; the constant traffic light 'fight or flight' dance or being stuck in a turbulent place between haunting empty houses and the green grass. Whilst we believe that the use of arts is a valuable tool for communicating, engaging with and reflecting on feeling states; careful, structured and sensitive facilitation is required to maintain safe and effective practice especially where the focus is on how therapists facilitate brief educational work focusing on attachment trauma.

This study revealed that the psychoeducation can expose deep relational vulnerabilities, where the principal focus for members had often been to manage pain in isolation. Perhaps most importantly, the emergent capacity for group members to recover from attachment trauma and to restore mentalizing indicated that there was the conceptual and reflective infrastructure that formed the foundations for further work and would enable members to engage with explorative forms of psychotherapy.

#### **Acknowledgements**

The authors would like to thank the following people for their dedication to the development of the programme as honorary researchers: Charlotte Barker, Kirstin Leyton-Boyce, Dr. Jennifer Townell and the participants for their commitment to the project.

**149**

**Author details**

Dominik Havsteen-Franklin1

and Jorge Camarena Altamirano2

2 CNWL NHS Foundation Trust, London, UK

provided the original work is properly cited.

\*, Maria Patsou2

1 CNWL NHS Foundation Trust, Brunel University, London, UK

\*Address all correspondence to: dominik.havsteen-franklin@nhs.net

© 2020 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

, Greta Somaini2

*Reimagining Attachment Traumas: Perspectives on Using Image-Making in Psychoeducation…*

*DOI: http://dx.doi.org/10.5772/intechopen.93406*

#### **Conflict of interest**

The authors declare no conflict of interest.

*Reimagining Attachment Traumas: Perspectives on Using Image-Making in Psychoeducation… DOI: http://dx.doi.org/10.5772/intechopen.93406*

### **Author details**

*Neurological and Mental Disorders*

psychotherapy.

the project.

**Acknowledgements**

**Conflict of interest**

The authors declare no conflict of interest.

making seemed to offer powerful access to feelings and experiences that sometimes, and especially at the beginning of the psychoeducation, could be uncomfortable and even 're-traumatising'. The art psychotherapists' perspective of the work provides a comprehensive narrative, highlighting the small but significant positive changes. In the follow-up evaluation we see the patient's autonomy emerging, also describing a tentative grasp of the concepts and emergent alternative forms of relating. We believe that the image-making process facilitated an affective experience of relationships, often revealing vulnerability in safe ways that could be reflected on. The images offered a powerful account of this process, and particularly the anxieties and uncertainties about developing a secure attachment. The images also revealed anticipated attachment traumas and an invalidating environment, for example in the stuck, rigid invalidating stones; being surrounded by a family that 'should be in therapy'; the constant traffic light 'fight or flight' dance or being stuck in a turbulent place between haunting empty houses and the green grass. Whilst we believe that the use of arts is a valuable tool for communicating, engaging with and reflecting on feeling states; careful, structured and sensitive facilitation is required to maintain safe and effective practice especially where the focus is on how thera-

pists facilitate brief educational work focusing on attachment trauma.

This study revealed that the psychoeducation can expose deep relational vulnerabilities, where the principal focus for members had often been to manage pain in isolation. Perhaps most importantly, the emergent capacity for group members to recover from attachment trauma and to restore mentalizing indicated that there was the conceptual and reflective infrastructure that formed the foundations for further work and would enable members to engage with explorative forms of

The authors would like to thank the following people for their dedication to the development of the programme as honorary researchers: Charlotte Barker, Kirstin Leyton-Boyce, Dr. Jennifer Townell and the participants for their commitment to

**148**

Dominik Havsteen-Franklin1 \*, Maria Patsou2 , Greta Somaini2 and Jorge Camarena Altamirano2

1 CNWL NHS Foundation Trust, Brunel University, London, UK

2 CNWL NHS Foundation Trust, London, UK

\*Address all correspondence to: dominik.havsteen-franklin@nhs.net

© 2020 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

### **References**

[1] Bailey JM, Shriver A. Does childhood sexual abuse cause borderline personality disorder? Journal of Sex & Marital Therapy. 1999;**25**(1):45-57

[2] Bornovalova MA, Huibregtse BM, Hicks BM, Keyes M, McGue M, Iacono W. Tests of a direct effect of childhood abuse on adult borderline personality disorder traits: A longitudinal discordant twin design. Journal of Abnormal Psychology. 2013;**122**(1):180

[3] Fossati A, Madeddu F, Maffei C. Borderline personality disorder and childhood sexual abuse: A meta-analytic study. Journal of Personality Disorders. 1999;**13**(3):268-280

[4] Howell EF. Back to the "states" victim and abuser states in borderline personality disorder. Psychoanalytic Dialogues. 2002;**12**(6):921-957

[5] Trull TJ. Structural relations between borderline personality disorder features and putative etiological correlates. Journal of Abnormal Psychology. 2001;**110**(3):471-481. DOI: 10.1037/0021-843X.110.3.471

[6] Widom CS, Czaja SJ, Paris J. A prospective investigation of borderline personality disorder in abused and neglected children followed up into adulthood. Journal of Personality Disorders. 2009;**23**(5):433-446

[7] Wildschut M, Swart S, Langeland W, Smit JH, Draijer N. An emotional neglect–personality disorder approach: Quantifying a dimensional transdiagnostic model of traumarelated and personality disorders. Journal of Personality Disorders. 2020;**34**(2):250-261

[8] Rosenthal MZ, Cheavens JS, Lejuez CW, Lynch TR. Thought suppression mediates the relationship between negative affect and borderline personality disorder symptoms. Behaviour Research and Therapy. 2005;**43**(9):1173-1185

[9] Allen JG. Restoring Mentalizing in Attachment Relationships: Treating Trauma with Plain Old Therapy. Washington DC, US & London, UK: American Psychiatric Publishing; 2012

[10] Stawarczyk D, Bezdek MA, Zacks JM. Event representations and predictive processing: The role of the midline default network core. Topics in Cognitive Science; 2019. Wiley Online Library. Available from: https:// onlinelibrary.wiley.com/doi/abs/10.1111/ tops.12450 [Accessed: 07 August 2020]

[11] Bateman A, Fonagy P. Mentalization based treatment for borderline personality disorder. World Psychiatry. 2010;**9**(1):11-15

[12] Fossati A, Feeney J, Maffei C, Borroni S. Thinking about feelings: Affective state mentalization, attachment styles, and borderline personality disorder features among Italian nonclinical adolescents. Psychoanalytic Psychology. 2014;**31**:41-67

[13] Fonagy P, Target M, Gergely G, Allen JG, Bateman AW. The developmental roots of borderline personality disorder in early attachment relationships: A theory and some evidence. Psychoanalytic Inquiry. 2003;**23**(3):412-459

[14] Karterud S. Mentalization-Based Group Therapy (MBT-G): A Theoretical, Clinical, and Research Manual. Oxford: OUP; 2015. Available from: https:// books.google.co.uk/books?hl=en&lr= &id=lUpoCgAAQBAJ&oi=fnd&pg= PP1&dq=karterud+group+MBT&ots= 025IZcQFW5&sig=5B-V\_ Bl0kROHFoN7GrP41nkC42E [Accessed: 02 August 2017]

**151**

*Reimagining Attachment Traumas: Perspectives on Using Image-Making in Psychoeducation…*

psychoeducational groups: From agency and authority to authorship. Bulletin of the Menninger Clinic.

[23] Bergmans Y, Links PS. A description of a psychosocial/psychoeducational intervention for persons with recurrent suicide attempts. Crisis: The Journal of Crisis Intervention and Suicide Prevention. 2002;**23**(4):156

[24] Cavanaugh MM. An Exploration of the Feasibility and Utility of the Dialectical Psychoeducational Workshop (DPEW) as a Preventative Intervention for Males at Potential Risk of Intimate Partner Violence. Pennsylvania, US: University of

[25] Gunderson JG. Handbook of Good Psychiatric Management for Borderline Personality Disorder. Washington DC, US: American Psychiatric Publishing;

[26] Springham N, Whitaker R. How do art therapists structure their approach to borderline personality disorder? The Arts in Psychotherapy. 2015;**43**:31-39

[27] Silverman MJ. The effect of singlesession psychoeducational music therapy on verbalizations and perceptions in psychiatric patients. Journal of Music

[28] Silverman MJ. Psychiatric patients' perception of music therapy and other psychoeducational programming.

Hodermarska M, et al. Healing the Inner City Child: Creative Arts Therapies with At-Risk Youth. London and Philadelphia:

[30] Sweig TL. Women healing women: Time-limited, psychoeducational

Therapy. 2009;**46**(2):105-131

Journal of Music Therapy. 2006;**43**(2):111-122

[29] Summer D, Soble L, Scott-Moncrieff S, Senroy P, Senroy S,

Jessica Kingsley Publishers; 2007

2011;**75**(4):315-343

Pennsylvania; 2007

2014

*DOI: http://dx.doi.org/10.5772/intechopen.93406*

[15] Kelly K, Slade A, Grienenberger JF. Maternal reflective functioning,

communication, and infant attachment: Exploring the link between mental states and observed caregiving behavior in the intergenerational transmission of attachment. Attachment & Human Development. 2005;**7**(3):299-311

[16] Grant BF, Chou SP, Goldstein RB, Huang B, Stinson FS, Saha TD, et al. Prevalence, correlates, disability, and comorbidity of DSM-IV borderline personality disorder: results from the Wave 2 National Epidemiologic Survey on Alcohol and Related Conditions. The Journal of Clinical Psychiatry.

[17] Holmes J. Mentalizing from a psychoanalytic perspective: What's new. In: Handbook of Mentalization-Based

[18] UK NCC for MH. Borderline Personality Disorder: Treatment and Management. British Psychological Society; 2009. Available from: https://www.ncbi.nlm.nih.gov/ pubmed/21796831 [Accessed: 04 July

[19] Swales HLH. Linehan's dialectical behaviour therapy (DBT) for borderline personality disorder: Overview and adaptation. Journal of Mental Health.

[20] Allen JG, Kelly KA, Glodich A. A psychoeducational program for patients with trauma-related disorders. Bulletin of the Menninger Clinic. 1997;**61**(2):222

[21] Banerjee P, Duggan C, Huband N, Watson N. Brief psychoeducation for people with personality disorder: A pilot study. Psychology and Psychotherapy: Theory, Research and Practice.

[22] Groat M, Allen JG. Promoting mentalizing in experiential

Treatment; 2006. pp. 31-49

mother–infant affective

2008;**69**(4):533

2017]

2000;**9**(1):7-23

2006;**79**(3):385-394

*Reimagining Attachment Traumas: Perspectives on Using Image-Making in Psychoeducation… DOI: http://dx.doi.org/10.5772/intechopen.93406*

[15] Kelly K, Slade A, Grienenberger JF. Maternal reflective functioning, mother–infant affective communication, and infant attachment: Exploring the link between mental states and observed caregiving behavior in the intergenerational transmission of attachment. Attachment & Human Development. 2005;**7**(3):299-311

[16] Grant BF, Chou SP, Goldstein RB, Huang B, Stinson FS, Saha TD, et al. Prevalence, correlates, disability, and comorbidity of DSM-IV borderline personality disorder: results from the Wave 2 National Epidemiologic Survey on Alcohol and Related Conditions. The Journal of Clinical Psychiatry. 2008;**69**(4):533

[17] Holmes J. Mentalizing from a psychoanalytic perspective: What's new. In: Handbook of Mentalization-Based Treatment; 2006. pp. 31-49

[18] UK NCC for MH. Borderline Personality Disorder: Treatment and Management. British Psychological Society; 2009. Available from: https://www.ncbi.nlm.nih.gov/ pubmed/21796831 [Accessed: 04 July 2017]

[19] Swales HLH. Linehan's dialectical behaviour therapy (DBT) for borderline personality disorder: Overview and adaptation. Journal of Mental Health. 2000;**9**(1):7-23

[20] Allen JG, Kelly KA, Glodich A. A psychoeducational program for patients with trauma-related disorders. Bulletin of the Menninger Clinic. 1997;**61**(2):222

[21] Banerjee P, Duggan C, Huband N, Watson N. Brief psychoeducation for people with personality disorder: A pilot study. Psychology and Psychotherapy: Theory, Research and Practice. 2006;**79**(3):385-394

[22] Groat M, Allen JG. Promoting mentalizing in experiential

psychoeducational groups: From agency and authority to authorship. Bulletin of the Menninger Clinic. 2011;**75**(4):315-343

[23] Bergmans Y, Links PS. A description of a psychosocial/psychoeducational intervention for persons with recurrent suicide attempts. Crisis: The Journal of Crisis Intervention and Suicide Prevention. 2002;**23**(4):156

[24] Cavanaugh MM. An Exploration of the Feasibility and Utility of the Dialectical Psychoeducational Workshop (DPEW) as a Preventative Intervention for Males at Potential Risk of Intimate Partner Violence. Pennsylvania, US: University of Pennsylvania; 2007

[25] Gunderson JG. Handbook of Good Psychiatric Management for Borderline Personality Disorder. Washington DC, US: American Psychiatric Publishing; 2014

[26] Springham N, Whitaker R. How do art therapists structure their approach to borderline personality disorder? The Arts in Psychotherapy. 2015;**43**:31-39

[27] Silverman MJ. The effect of singlesession psychoeducational music therapy on verbalizations and perceptions in psychiatric patients. Journal of Music Therapy. 2009;**46**(2):105-131

[28] Silverman MJ. Psychiatric patients' perception of music therapy and other psychoeducational programming. Journal of Music Therapy. 2006;**43**(2):111-122

[29] Summer D, Soble L, Scott-Moncrieff S, Senroy P, Senroy S, Hodermarska M, et al. Healing the Inner City Child: Creative Arts Therapies with At-Risk Youth. London and Philadelphia: Jessica Kingsley Publishers; 2007

[30] Sweig TL. Women healing women: Time-limited, psychoeducational

**150**

*Neurological and Mental Disorders*

sexual abuse cause borderline

[1] Bailey JM, Shriver A. Does childhood

between negative affect and borderline personality disorder symptoms. Behaviour Research and Therapy.

[9] Allen JG. Restoring Mentalizing in Attachment Relationships: Treating Trauma with Plain Old Therapy. Washington DC, US & London, UK: American Psychiatric Publishing; 2012

[10] Stawarczyk D, Bezdek MA, Zacks JM. Event representations and predictive processing: The role of the midline default network core. Topics in Cognitive Science; 2019. Wiley Online Library. Available from: https:// onlinelibrary.wiley.com/doi/abs/10.1111/ tops.12450 [Accessed: 07 August 2020]

[11] Bateman A, Fonagy P. Mentalization

personality disorder. World Psychiatry.

based treatment for borderline

[12] Fossati A, Feeney J, Maffei C, Borroni S. Thinking about feelings: Affective state mentalization, attachment

styles, and borderline personality disorder features among Italian

Psychology. 2014;**31**:41-67

Allen JG, Bateman AW. The developmental roots of borderline personality disorder in early attachment relationships: A theory and some evidence. Psychoanalytic Inquiry.

2003;**23**(3):412-459

025IZcQFW5&sig=5B-V\_

02 August 2017]

nonclinical adolescents. Psychoanalytic

[13] Fonagy P, Target M, Gergely G,

[14] Karterud S. Mentalization-Based Group Therapy (MBT-G): A Theoretical, Clinical, and Research Manual. Oxford: OUP; 2015. Available from: https:// books.google.co.uk/books?hl=en&lr= &id=lUpoCgAAQBAJ&oi=fnd&pg= PP1&dq=karterud+group+MBT&ots=

Bl0kROHFoN7GrP41nkC42E [Accessed:

2010;**9**(1):11-15

2005;**43**(9):1173-1185

personality disorder? Journal of Sex & Marital Therapy. 1999;**25**(1):45-57

[2] Bornovalova MA, Huibregtse BM, Hicks BM, Keyes M, McGue M, Iacono W. Tests of a direct effect of childhood abuse on adult borderline personality disorder traits: A

longitudinal discordant twin design. Journal of Abnormal Psychology.

[3] Fossati A, Madeddu F, Maffei C. Borderline personality disorder and childhood sexual abuse: A meta-analytic study. Journal of Personality Disorders.

[4] Howell EF. Back to the "states" victim and abuser states in borderline personality disorder. Psychoanalytic Dialogues. 2002;**12**(6):921-957

[5] Trull TJ. Structural relations

features and putative etiological correlates. Journal of Abnormal Psychology. 2001;**110**(3):471-481. DOI:

[6] Widom CS, Czaja SJ, Paris J. A prospective investigation of borderline personality disorder in abused and neglected children followed up into adulthood. Journal of Personality Disorders. 2009;**23**(5):433-446

[7] Wildschut M, Swart S, Langeland W, Smit JH, Draijer N. An emotional neglect–personality disorder

approach: Quantifying a dimensional transdiagnostic model of traumarelated and personality disorders. Journal of Personality Disorders.

[8] Rosenthal MZ, Cheavens JS, Lejuez CW, Lynch TR. Thought suppression mediates the relationship

2020;**34**(2):250-261

10.1037/0021-843X.110.3.471

between borderline personality disorder

2013;**122**(1):180

**References**

1999;**13**(3):268-280

group therapy for childhood sexual abuse survivors. Art Therapy. 2000;**17**(4):255-264

[31] Weinberg DJ. The potential of rehabilitative computer art therapy for the quadriplegic, cerebral vascular accident and brain trauma patient. Art Therapy. 1985;**2**(2):66-72

[32] Thorne D. Portrait of self and other. In: Hughes R, editor. Time-Limited Art Psychotherapy: Developments in Theory and Practice. London and New York: Routledge; 2016. pp. 92-118

[33] Morton S, Hohman M. "That's the weight of knowing": Practitioner skills and impact when delivering psychoeducational group work for women who have experienced IPV. Social Work with Groups. 2016;**39**(4):277-291

[34] Rivera ET, Fernández IT, Hendricks WA. Psychoeducational and counseling groups with Latinos. In: DeLucia-Waack J, Kalodner C, Riva M, editors. Handbook of Group Counseling and Psychotherapy. Thousand Oaks, CA, US: SAGE Publications; 2004. pp. 213-223

[35] Khalil GE. Understanding the User Experience and Emotional Involvement during eHealth Interventions: A Randomized Controlled Trial of ASPIRE. New York, US: State University of New York at Buffalo; 2015. Available from: https://search.proquest.com/ openview/e9fd0bdd8e4cc5f91bc62c47c6 9c8fd1/1?pq-origsite=gscholar&cbl=187 50&diss=y [Accessed: 07 August 2020]

[36] Collet P. Reflexivity and agency: A study of women's careers in the visual arts as a basis for reflection in art education. Australian Art Education. 1998;**21**(2):20

[37] McCaffrey R, Frock TL, Garguilo H. Understanding chronic pain and the mind-body connection. Holistic Nursing Practice. 2003;**17**(6):281-289

[38] McCaffrey T, Edwards J. Meeting art with art: Arts-based methods enhance researcher reflexivity in research with mental health service users. Journal of Music Therapy. 2015;**52**(4):515-532

[39] Weber S, Mitchell C. Art for accessibility: Art as activism; art for reflexivity; arts informed. 2004;**3**(2):7-19

[40] Havsteen-Franklin D. Mentalization-based art psychotherapy. In: Rubin J, editor. Approaches to Art Therapy Theory and Techniques. New York: Brunner/Mazel; 2016. pp. 144-164

[41] Havsteen-Franklin D. Creative arts therapies. In: Bateman AW, Fonagy P, editors. Handbook of Mentalizing in Mental Health Practice. 2nd ed. Washington, DC, US: American Psychiatric Publishing; 2019. pp. 181-197

[42] Bowlby J. Attachment theory and psychotherapy research. The Journal of Psychotherapy Practice and Research. 2001;**10**(2):133

[43] Allen JG, Fonagy P, Bateman A. The role of mentalizing in treating attachment trauma. In: Vermetten E, Lanius RA, editors. The Hidden Epidemic: The Impact of Early Life Trauma on Health and Disease. New York: Cambridge University Press; 2010. pp. 247-256

[44] Fonagy P, Luyten P, Bateman A, Gergely G, Strathearn L, Target M, et al. Attachment and personality pathology. In: Psychodynamic Psychotherapy for Personality Disorders: A Clinical Handbook. Washington DC and London: American Psychiatric Publishing; 2010. pp. 37-88

[45] Fonagy P. The mentalizationfocused approach to social development. In: Busch FN, editor. Mentalization. New York, US and Hove, UK: The Analytic Press and Taylor & Francis Group; 2006. pp. 3-56

**153**

*Reimagining Attachment Traumas: Perspectives on Using Image-Making in Psychoeducation…*

*DOI: http://dx.doi.org/10.5772/intechopen.93406*

[46] Karterud S, Bateman A. Manual for Mentalization Based Psychoeducational

[47] Bateman A, Fonagy P. Mentalization-

[48] Havsteen-Franklin D, Maratos A, Usiskin M, Heagney M. Examining arts psychotherapies practice elements: Early findings from the Horizons Project. Approaches. 2016;**8**. Available from: http://approaches.gr/havsteenfranklin-a20160324/ [Accessed:

[49] The Horizons Project – Honorary Arts Psychotherapies Clinical Research Posts - CNWL [Internet]. Available from: http://www.cnwl.nhs.uk/healthprofessionals/icapt/the-horizonsproject/ [Accessed: 12 September 2014]

Group Therapy (MBT-I). Oslo: Gyldendal akademisk; 2011

based treatment. Psychoanalytic

Inquiry. 2013;**33**:595-613

04 November 2016]

*Reimagining Attachment Traumas: Perspectives on Using Image-Making in Psychoeducation… DOI: http://dx.doi.org/10.5772/intechopen.93406*

[46] Karterud S, Bateman A. Manual for Mentalization Based Psychoeducational Group Therapy (MBT-I). Oslo: Gyldendal akademisk; 2011

*Neurological and Mental Disorders*

2000;**17**(4):255-264

Therapy. 1985;**2**(2):66-72

Routledge; 2016. pp. 92-118

2016;**39**(4):277-291

[34] Rivera ET, Fernández IT,

Hendricks WA. Psychoeducational and counseling groups with Latinos. In: DeLucia-Waack J, Kalodner C, Riva M, editors. Handbook of Group Counseling and Psychotherapy. Thousand Oaks, CA, US: SAGE Publications; 2004. pp. 213-223

[35] Khalil GE. Understanding the User Experience and Emotional Involvement

ASPIRE. New York, US: State University of New York at Buffalo; 2015. Available from: https://search.proquest.com/ openview/e9fd0bdd8e4cc5f91bc62c47c6 9c8fd1/1?pq-origsite=gscholar&cbl=187 50&diss=y [Accessed: 07 August 2020]

[36] Collet P. Reflexivity and agency: A study of women's careers in the visual arts as a basis for reflection in art education. Australian Art Education.

[37] McCaffrey R, Frock TL, Garguilo H. Understanding chronic pain and the mind-body connection. Holistic Nursing

Practice. 2003;**17**(6):281-289

during eHealth Interventions: A Randomized Controlled Trial of

[33] Morton S, Hohman M. "That's the weight of knowing": Practitioner skills and impact when delivering psychoeducational group work for women who have experienced IPV. Social Work with Groups.

group therapy for childhood sexual abuse survivors. Art Therapy.

[38] McCaffrey T, Edwards J. Meeting art with art: Arts-based methods enhance researcher reflexivity in research with mental health service users. Journal of Music Therapy. 2015;**52**(4):515-532

Mentalization-based art psychotherapy. In: Rubin J, editor. Approaches to Art Therapy Theory and Techniques. New York: Brunner/Mazel; 2016. pp. 144-164

[41] Havsteen-Franklin D. Creative arts therapies. In: Bateman AW, Fonagy P, editors. Handbook of Mentalizing in Mental Health Practice. 2nd ed. Washington, DC, US: American

Psychiatric Publishing; 2019. pp. 181-197

[42] Bowlby J. Attachment theory and psychotherapy research. The Journal of Psychotherapy Practice and Research.

[43] Allen JG, Fonagy P, Bateman A. The role of mentalizing in treating attachment trauma. In: Vermetten E, Lanius RA, editors. The Hidden Epidemic: The Impact of Early Life Trauma on Health and Disease. New York: Cambridge University Press; 2010.

[44] Fonagy P, Luyten P, Bateman A, Gergely G, Strathearn L, Target M, et al. Attachment and personality pathology. In: Psychodynamic Psychotherapy for Personality Disorders: A Clinical Handbook. Washington DC and London: American Psychiatric Publishing; 2010. pp. 37-88

[45] Fonagy P. The mentalization-

Group; 2006. pp. 3-56

focused approach to social development. In: Busch FN, editor. Mentalization. New York, US and Hove, UK: The Analytic Press and Taylor & Francis

[39] Weber S, Mitchell C. Art for accessibility: Art as activism; art for reflexivity; arts informed.

[40] Havsteen-Franklin D.

2004;**3**(2):7-19

2001;**10**(2):133

pp. 247-256

[31] Weinberg DJ. The potential of rehabilitative computer art therapy for the quadriplegic, cerebral vascular accident and brain trauma patient. Art

[32] Thorne D. Portrait of self and other. In: Hughes R, editor. Time-Limited Art Psychotherapy: Developments in Theory and Practice. London and New York:

**152**

1998;**21**(2):20

[47] Bateman A, Fonagy P. Mentalizationbased treatment. Psychoanalytic Inquiry. 2013;**33**:595-613

[48] Havsteen-Franklin D, Maratos A, Usiskin M, Heagney M. Examining arts psychotherapies practice elements: Early findings from the Horizons Project. Approaches. 2016;**8**. Available from: http://approaches.gr/havsteenfranklin-a20160324/ [Accessed: 04 November 2016]

[49] The Horizons Project – Honorary Arts Psychotherapies Clinical Research Posts - CNWL [Internet]. Available from: http://www.cnwl.nhs.uk/healthprofessionals/icapt/the-horizonsproject/ [Accessed: 12 September 2014]

**155**

Section 3

Social Aspects
