Section 1 Behavioral Aspects

**3**

theory

**1. Introduction**

**Chapter 1**

**Abstract**

Disorders

*Ana Carolina Tavares Lopes* 

BDNF Protein and Anxiety

*Tatiana Marins Farias, Rebeca Ataíde Cerqueira,* 

An increase in the prevalence of anxiety disorders (ADs), in individual, social, and economic losses, due to the high prevalence, chronicity, and disability of the individual besides the growth of multiple environmental stressors that are related to lifestyles, has been observed, which are all more harmful to one's health, and associated with genetic inheritances, among other factors. This reality may contribute to the risk of losing neurological functions, for example, cognition and memory, as well as to the development of more severe psychiatric disorders, with high levels of heritability and risk of suicide. Brain-derived neurotrophic factor (BDNF) is one of the most abundant neurotrophins in the human brain. Studies with neurotrophins allowed the introduction of one more hypothesis, called neurotrophic hypothesis, that would explain the physiopathology of mental disorders (MD), where deficits of neuroplasticity would occur and cause atrophy of certain regions of the brain (mainly cortical and the hippocampus), contributing to the development of mental disorders. Knowing the neurobiology of the ADs, as well as its relation to BDNF levels, may contribute to preventive actions regarding the said disorder in the general population. The objective of this chapter is to analyze the relation between levels of BDNF and AD.

**Keywords:** anxiety disorders, BDNF, mental disorders, neurobiology, neurotrophic

Anxiety disorders (ADs) have become a significant public health issue worldwide, with individual, social, and economic losses, due to their high prevalence,

This reality may contribute to the risk of losing neurological functions, for example, cognition and memory, as well as to the development of more severe psychiatric disorders, with high levels of heritability and risk of suicide.

Anxious disorders like panic disorder (PD) with or without agoraphobia, generalized anxiety disorder (GAD), social anxiety disorder (SAD), specific phobias (SPs), and separation anxiety disorder are the most prevalent mental disorders (MD) and are associated with immense healthcare costs and a high burden of disease [1].

The word anxiety is derived from Latin *anxietatis* (desire, worry); *anxi* (contract, narrow); *anxietas* (narrowing); and *anxia* (craving, vulgar Latin) and is considered

chronic condition, and the individual's disability [1].

*Danton Ferraz Sousa, João Vitor Costa Freire,* 

*and Silvia Fernanda Lima De Moura Cal*

#### **Chapter 1**

## BDNF Protein and Anxiety Disorders

*Tatiana Marins Farias, Rebeca Ataíde Cerqueira, Danton Ferraz Sousa, João Vitor Costa Freire, Ana Carolina Tavares Lopes and Silvia Fernanda Lima De Moura Cal*

#### **Abstract**

An increase in the prevalence of anxiety disorders (ADs), in individual, social, and economic losses, due to the high prevalence, chronicity, and disability of the individual besides the growth of multiple environmental stressors that are related to lifestyles, has been observed, which are all more harmful to one's health, and associated with genetic inheritances, among other factors. This reality may contribute to the risk of losing neurological functions, for example, cognition and memory, as well as to the development of more severe psychiatric disorders, with high levels of heritability and risk of suicide. Brain-derived neurotrophic factor (BDNF) is one of the most abundant neurotrophins in the human brain. Studies with neurotrophins allowed the introduction of one more hypothesis, called neurotrophic hypothesis, that would explain the physiopathology of mental disorders (MD), where deficits of neuroplasticity would occur and cause atrophy of certain regions of the brain (mainly cortical and the hippocampus), contributing to the development of mental disorders. Knowing the neurobiology of the ADs, as well as its relation to BDNF levels, may contribute to preventive actions regarding the said disorder in the general population. The objective of this chapter is to analyze the relation between levels of BDNF and AD.

**Keywords:** anxiety disorders, BDNF, mental disorders, neurobiology, neurotrophic theory

#### **1. Introduction**

Anxiety disorders (ADs) have become a significant public health issue worldwide, with individual, social, and economic losses, due to their high prevalence, chronic condition, and the individual's disability [1].

This reality may contribute to the risk of losing neurological functions, for example, cognition and memory, as well as to the development of more severe psychiatric disorders, with high levels of heritability and risk of suicide.

Anxious disorders like panic disorder (PD) with or without agoraphobia, generalized anxiety disorder (GAD), social anxiety disorder (SAD), specific phobias (SPs), and separation anxiety disorder are the most prevalent mental disorders (MD) and are associated with immense healthcare costs and a high burden of disease [1].

The word anxiety is derived from Latin *anxietatis* (desire, worry); *anxi* (contract, narrow); *anxietas* (narrowing); and *anxia* (craving, vulgar Latin) and is considered

a physiological manifestation when facing some type of danger (real or imaginary), with adaptability in forming responses to threatening stimuli, in order to foment the individual's safety and survival, leading to an unpleasant somatic and psychological experience [2].

When the severity, frequency, and persistence of the anxious symptoms become inconsistent with the presented circumstances, and the anxious reaction causes the behavior to be dysfunctional, then these are characterized as the anxiety disorders, which present high levels of morbidity, with a possible increase in mortality [1], since 6.1% of suicide cases are associated with AD [3].

Mental disorders were only recognized as a serious public health problem in 1996, in a study conducted by researchers from Harvard University and the World Health Organization (WHO), when out of the 10 main causes of disability worldwide, 5 were associated with mental disorders [4]. In the metropolitan region of São Paulo, 29.6% of individuals presented mental disorders with anxiety disorders being the most common, affecting 19.9% of the population, occurring twice as much in females [5]. Among the types of anxiety disorders, it is estimated that up to 5% of the population suffers from generalized anxiety disorder [1].

Generalized anxiety disorder, a type of AD, has high rates of comorbidity and stands out from mood disorders and other types of anxiety disorders. A recent study indicates that in 67% of the cases, GAD precedes (or is concomitant) depressive disorders (unipolar), 17% have bipolar disorder, and only 16% have no lifetime mood disorder and can be considered a risk factor. Furthermore, it is also associated with renal and cardiovascular diseases, rendering a more reserved prognosis in either situation [5, 6].

According to Bandelow and Michaelis, 33.7% of the world population suffers from anxiety disorders; however, it is difficult to find reliable evidence to demonstrate the evolution of this prevalence. Because the patients with anxiety disorders are mostly treated as outpatients, they probably receive less attention from clinical psychiatrists [1].

Epidemiological data from the National Comorbidity Survey suggest that 67% of the individual with GAD have depressive disorder (unipolar), 17% have bipolar disorder, and only 16% have no lifetime mood disorder [6].

ADs are highly comorbid with other mental problems like additive psychiatric disorders, leading to disability and impairment in quality of life [6].

Brain-derived neurotrophic factor (BDNF) is one of the most abundant neurotrophins in the human brain. Studies with neurotrophins allowed the introduction of one more hypothesis, called neurotrophic hypothesis, that would explain the physiopathology of mental disorders, where deficits of neuroplasticity would occur and cause atrophy of certain regions of the brain (mainly cortical and the hippocampus), contributing to the development of mental disorders [7]. Knowing the neurobiology of the AD, as well as its relation to BDNF levels, may contribute to preventative actions regarding the said disorder in the general population. The objective of this chapter is to analyze the relation between levels of BDNF and AD.

#### **2. Methods**

The two main types of review articles are commonly found in the scientific literature: systematic and narrative review of the literature. These two types of review articles have distinct characteristics and goals. The review of narrative or traditional literature, when compared to systematic review, presents a more open theme. This makes part of a specific and well-defined problem difficult and does not require a strict protocol for its preparation. The search for sources is not predetermined and

**5**

**5. Etiology**

*BDNF Protein and Anxiety Disorders*

**3. Clinical picture**

**4. Classification**

*DOI: http://dx.doi.org/10.5772/intechopen.92341*

and the learning process may be quite intense.

memory, and impairing the capability of association.

(6) specific phobias, and (7) selective mutism [10].

specific and is generally less comprehensive. Studies on BDNF protein and anxiety

For the individual, anxiety is a form of protection, a defense mechanism, with

Anxiety tends to produce confusion and perspective distortions, not only in terms of time and space but also of people and the significance of events. These distortions may cause interference in learning, lowering concentration, reducing

Pathological anxiety constitutes an inadequate response to a certain stimulus, as a result of its greater intensity and duration. Pathological anxiety paralyzes the individual, not allowing him/her to be prepared and to face threatening situations, differentiating itself from normal anxiety by the assessment of the intensity from the patient, his/her family, as well as from the physician [1]. The state of anxiety, its traits, and the ADs are differentiated by the degree of impairment and the duration of the anxiety symptoms on the individual. The state of anxiety is normally defined as a measure of acute or intermediate level of anxiety. Now, the anxiety trait is considered a tendency of the individual to produce an anxious response to environmental events. And, lastly, the anxiety disorders are the most severe, due to the excessive worry and fear and the greater duration and complexity of the anxious

symptoms, which are dysfunctional and accompanied by impairment [8].

There are two types of international classification for anxiety disorders. According to the International Classification of Diseases, 10th edition, and more utilized in clinical psychiatry, there are seven main anxiety disorders: specific phobias, social phobia, panic disorder, generalized anxiety, obsessive-compulsive disorder, reaction to severe stress, and mixed anxiety-depressive disorder [9].

On the other hand, with the main goal of research purposes, the *Diagnostic and Statistical Manual of Mental Disorders, 5th edition* (DSM-V), classifies the most important ADs as (1) generalized anxiety disorder, (2) panic disorder, (3) agoraphobia, (4) separation anxiety disorder, (5) social anxiety disorder or social phobia,

Biologically, the etiology of anxiety, with complex neurobiological mechanisms,

according to the literature in neuroscience [2] seems to be related to the noradrenergic, GABAergic, and serotoninergic systems and the frontal lobe and limbic

an important role in the preservation of life, with symptoms that are somatic (breathing discomfort, tachycardia and precordial chest pain, excessive perspiration, increased peristalsis, epigastric pain, nausea, pallor or skin redness and flushing, paresthesia, chills, muscular changes, headache, dizziness, dry mouth, inability to remain seated or immobile for very long, etc.) and psychic (feeling of internal unrest, insomnia, feeling of oppression and discomfort, exaggerated worry, insecurity, irritability, undefined uneasiness, difficulty concentrating, depersonalization and derealization, among others). The effects of anxiety on thought, perception,

disorders are the focus of this narrative review of the literature [8].

specific and is generally less comprehensive. Studies on BDNF protein and anxiety disorders are the focus of this narrative review of the literature [8].

#### **3. Clinical picture**

*Neurological and Mental Disorders*

since 6.1% of suicide cases are associated with AD [3].

the population suffers from generalized anxiety disorder [1].

disorder, and only 16% have no lifetime mood disorder [6].

disorders, leading to disability and impairment in quality of life [6].

experience [2].

either situation [5, 6].

psychiatrists [1].

a physiological manifestation when facing some type of danger (real or imaginary), with adaptability in forming responses to threatening stimuli, in order to foment the individual's safety and survival, leading to an unpleasant somatic and psychological

When the severity, frequency, and persistence of the anxious symptoms become inconsistent with the presented circumstances, and the anxious reaction causes the behavior to be dysfunctional, then these are characterized as the anxiety disorders, which present high levels of morbidity, with a possible increase in mortality [1],

Mental disorders were only recognized as a serious public health problem in 1996, in a study conducted by researchers from Harvard University and the World Health Organization (WHO), when out of the 10 main causes of disability worldwide, 5 were associated with mental disorders [4]. In the metropolitan region of São Paulo, 29.6% of individuals presented mental disorders with anxiety disorders being the most common, affecting 19.9% of the population, occurring twice as much in females [5]. Among the types of anxiety disorders, it is estimated that up to 5% of

Generalized anxiety disorder, a type of AD, has high rates of comorbidity and stands out from mood disorders and other types of anxiety disorders. A recent study indicates that in 67% of the cases, GAD precedes (or is concomitant) depressive disorders (unipolar), 17% have bipolar disorder, and only 16% have no lifetime mood disorder and can be considered a risk factor. Furthermore, it is also associated with renal and cardiovascular diseases, rendering a more reserved prognosis in

According to Bandelow and Michaelis, 33.7% of the world population suffers from anxiety disorders; however, it is difficult to find reliable evidence to demonstrate the evolution of this prevalence. Because the patients with anxiety disorders are mostly treated as outpatients, they probably receive less attention from clinical

Epidemiological data from the National Comorbidity Survey suggest that 67% of the individual with GAD have depressive disorder (unipolar), 17% have bipolar

ADs are highly comorbid with other mental problems like additive psychiatric

Brain-derived neurotrophic factor (BDNF) is one of the most abundant neurotrophins in the human brain. Studies with neurotrophins allowed the introduction of one more hypothesis, called neurotrophic hypothesis, that would explain the physiopathology of mental disorders, where deficits of neuroplasticity would occur and cause atrophy of certain regions of the brain (mainly cortical and the hippocampus), contributing to the development of mental disorders [7]. Knowing the neurobiology of the AD, as well as its relation to BDNF levels, may contribute to preventative actions regarding the said disorder in the general population. The objective of this chapter is to analyze the relation between levels of BDNF and AD.

The two main types of review articles are commonly found in the scientific literature: systematic and narrative review of the literature. These two types of review articles have distinct characteristics and goals. The review of narrative or traditional literature, when compared to systematic review, presents a more open theme. This makes part of a specific and well-defined problem difficult and does not require a strict protocol for its preparation. The search for sources is not predetermined and

**4**

**2. Methods**

For the individual, anxiety is a form of protection, a defense mechanism, with an important role in the preservation of life, with symptoms that are somatic (breathing discomfort, tachycardia and precordial chest pain, excessive perspiration, increased peristalsis, epigastric pain, nausea, pallor or skin redness and flushing, paresthesia, chills, muscular changes, headache, dizziness, dry mouth, inability to remain seated or immobile for very long, etc.) and psychic (feeling of internal unrest, insomnia, feeling of oppression and discomfort, exaggerated worry, insecurity, irritability, undefined uneasiness, difficulty concentrating, depersonalization and derealization, among others). The effects of anxiety on thought, perception, and the learning process may be quite intense.

Anxiety tends to produce confusion and perspective distortions, not only in terms of time and space but also of people and the significance of events. These distortions may cause interference in learning, lowering concentration, reducing memory, and impairing the capability of association.

Pathological anxiety constitutes an inadequate response to a certain stimulus, as a result of its greater intensity and duration. Pathological anxiety paralyzes the individual, not allowing him/her to be prepared and to face threatening situations, differentiating itself from normal anxiety by the assessment of the intensity from the patient, his/her family, as well as from the physician [1]. The state of anxiety, its traits, and the ADs are differentiated by the degree of impairment and the duration of the anxiety symptoms on the individual. The state of anxiety is normally defined as a measure of acute or intermediate level of anxiety. Now, the anxiety trait is considered a tendency of the individual to produce an anxious response to environmental events. And, lastly, the anxiety disorders are the most severe, due to the excessive worry and fear and the greater duration and complexity of the anxious symptoms, which are dysfunctional and accompanied by impairment [8].

#### **4. Classification**

There are two types of international classification for anxiety disorders. According to the International Classification of Diseases, 10th edition, and more utilized in clinical psychiatry, there are seven main anxiety disorders: specific phobias, social phobia, panic disorder, generalized anxiety, obsessive-compulsive disorder, reaction to severe stress, and mixed anxiety-depressive disorder [9].

On the other hand, with the main goal of research purposes, the *Diagnostic and Statistical Manual of Mental Disorders, 5th edition* (DSM-V), classifies the most important ADs as (1) generalized anxiety disorder, (2) panic disorder, (3) agoraphobia, (4) separation anxiety disorder, (5) social anxiety disorder or social phobia, (6) specific phobias, and (7) selective mutism [10].

#### **5. Etiology**

Biologically, the etiology of anxiety, with complex neurobiological mechanisms, according to the literature in neuroscience [2] seems to be related to the noradrenergic, GABAergic, and serotoninergic systems and the frontal lobe and limbic

#### *Neurological and Mental Disorders*

systems. The anxious patients tend to have increased sympathetic tone, causing delays in adapting to changes in the autonomic nervous system [1].

However, studies with neurotrophins gave rise to one more hypothesis that would explain the physiopathology of mental disorders in general, called the neurotrophic hypothesis, where deficits in the neuroplasticity would occur as well as cause atrophy of certain brain regions, mainly the cortex and hippocampus [7]. Nevertheless, there are gaps in the literature on whether the ADs take this explanation into consideration.

Increased activity in emotion-processing brain regions in patients who have an anxiety disorder could result from decreased inhibitory signaling by g-aminobutyric-acid (GABA) or increased excitatory neurotransmission by glutamate [11].

The connection between the sympathetic nervous system and the psyche is best seen in anxiety and especially in social phobia. The hippocampus may predominantly control the avoidance components of phobic anxiety by the serotonergic system, with other regions, such as the dorsomedial hypothalamus, controlling the escape components with the cholinergic system. Furthermore, the autonomic dysfunction and the overactivity of the sympathetic nervous system appear to induce many of the symptoms of anxiety, such as sweating, trembling, and heart racing [12].

There is increasing evidence that development and maturation of neuronal connectivity are critical components in the pathophysiology of essentially all neuropsychiatric disorders. As neurotrophins have been implicated in brain development and in particular in the plasticity and maturation of neuronal circuits, it is understandable that neurotrophins have been popular candidate genes for psychiatric diseases [13]. However, there are gaps in the literature on whether anxiety disorders include this explanation.

#### **6. Genetic predisposition and precursor factors**

More well-defined classifications tend to standardize the studies on ADs, contributing toward the biological evidence associated with these disorders, as well as making the "phenotypic complexity" a challenge to genetic psychiatry [14].

Upon including twins and their biological families, a meta-analysis indicated a heritability between 30 and 40% for anxiety disorders [15]. Now, a longitudinal study estimated a heritability ranging from 72 to 89%. The results of this study also showed a "developmental dynamic" pattern, for, over time, there is a mitigation of the genetic influence as a risk factor for anxious and depressive symptoms [16], leading one to ponder over the influence of protective factors in the prognosis of ADs.

#### **7. Environmental factors**

Individuals with AD present attentional bias to the threatening stimulus, which increases the vulnerability to stress, considering these "complex disorders," due to being influenced by multiple factors that flee from what are called "deterministic effects" of the genes, therefore making them liable to modulation by interference [2].

According to an experimental study with laboratory animals, stress by social subjugation is able to foster hyperalgesia with a decrease in the BDNF levels; this condition is more evident in "susceptible" subjects rather than in "resilient" ones [17], reinforcing the complex multifactorial theory that the neurobiological response to stress is not only genetic but also environmental.

**7**

other factors [22].

highest-level recommendation [23].

*BDNF Protein and Anxiety Disorders*

and behavior therapies [19, 20].

frequency and intensity of panic attacks [21].

as substance P and cholecystokinin [21].

**8. Pharmacologic and non-pharmacologic treatments**

its methylation [19].

constant [18].

*DOI: http://dx.doi.org/10.5772/intechopen.92341*

BDNF exons decrease markedly after high corticosterone levels. BDNF levels are controlled by epigenetic mechanisms with extinction assisted by partial NMDA receptor agonists (e.g., D-cycloserine) and histone deacetylase inhibitors [18]. Environmental factors, via epigenetic factors, control the alterations of BDNF gene expression, especially when young. Harmful environmental influences while growing can cause a decrease in BDNF expression in adulthood, in addition to the serotonin transporter and FKBP5, leading to problems in patient response to drug

Problems during youth lead to DNA methylation of BDNF promoter IV and a decrease in prefrontal cortex total BDNF mRNA [21]. However, after exercise and a healthy environment, total BDNF mRNA in the hippocampus increases due to increases in histone acetylation at promoter IV or decreases in

In response to fear conditioning, the levels of BDNF exon mRNAs change markedly. As an example, after fear conditioning using light shock, exon I and III mRNA levels increase markedly, different from the exons II and IV which remain

Several psychological factors have been associated with increased risk for anxiety disorders. Among the most intensively researched has been the concept of anxiety sensitivity (AS). AS has been defined as the individual response to physiological alterations associated with anxiety and fear. Patients with anxiety disorders have exaggerated psychological reactions that are reflective of misinterpretation of bodily cues such that the patient misperceives these sensations inappropriately as being harmful and dangerous, leading in a circular fashion to increased anxiety and fear. AS is associated with a selective cognitive bias toward threat. AS predicts the

The above section identifies several possible mediators of the psychobiological response to extreme stress and how each may contribute, alone or through functional interactions, to resilience or vulnerability to anxiety disorders. One prediction is that individuals in the highest quartile for measures of HPA axis, CRH, LC-NE, and estrogen activity and the lowest quartile for DHEA, NPY, galanin, testosterone, and 5-HT1A receptor and benzodiazepine receptor function will have an increased risk for anxiety disorders. Other mediators that can be included for the characterization of the vulnerable or resilient profile are glutamate and neurotrophic factors, such as brain-derived neurotrophic factor, and neuropeptides, such

Patients should receive "psychoeducation" about their diagnosis, the possible etiology, and the mechanisms of action of the available treatment approaches. The treatment plan should include psychotherapy, pharmacotherapy, and other interventions, which should be chosen after careful consideration of individual factors, e.g., the patient's preference, the patient's history with previous treatment attempts, illness severity, comorbidities such as personality disorders, suicidality, local availability of treatment methods, wait time for psychotherapy appointments, costs, and

For all types of anxiety disorder, cognitive-behavioral therapy is the type of psychotherapy for which there is the strongest evidence and which receives the

Cognitive-behavioral therapy has been found to have a moderately strong beneficial effect against all types of anxiety disorder compared to a placebo drug

#### *BDNF Protein and Anxiety Disorders DOI: http://dx.doi.org/10.5772/intechopen.92341*

*Neurological and Mental Disorders*

tion into consideration.

racing [12].

this explanation.

sis of ADs.

**7. Environmental factors**

**6. Genetic predisposition and precursor factors**

response to stress is not only genetic but also environmental.

systems. The anxious patients tend to have increased sympathetic tone, causing

However, studies with neurotrophins gave rise to one more hypothesis that would explain the physiopathology of mental disorders in general, called the neurotrophic hypothesis, where deficits in the neuroplasticity would occur as well as cause atrophy of certain brain regions, mainly the cortex and hippocampus [7]. Nevertheless, there are gaps in the literature on whether the ADs take this explana-

Increased activity in emotion-processing brain regions in patients who have an anxiety disorder could result from decreased inhibitory signaling by g-aminobutyric-acid (GABA) or increased excitatory neurotransmission by glutamate [11]. The connection between the sympathetic nervous system and the psyche is best seen in anxiety and especially in social phobia. The hippocampus may predominantly control the avoidance components of phobic anxiety by the serotonergic system, with other regions, such as the dorsomedial hypothalamus, controlling the escape components with the cholinergic system. Furthermore, the autonomic dysfunction and the overactivity of the sympathetic nervous system appear to induce many of the symptoms of anxiety, such as sweating, trembling, and heart

There is increasing evidence that development and maturation of neuronal connectivity are critical components in the pathophysiology of essentially all neuropsychiatric disorders. As neurotrophins have been implicated in brain development and in particular in the plasticity and maturation of neuronal circuits, it is understandable that neurotrophins have been popular candidate genes for psychiatric diseases [13]. However, there are gaps in the literature on whether anxiety disorders include

More well-defined classifications tend to standardize the studies on ADs, contributing toward the biological evidence associated with these disorders, as well as making the "phenotypic complexity" a challenge to genetic psychiatry [14]. Upon including twins and their biological families, a meta-analysis indicated a heritability between 30 and 40% for anxiety disorders [15]. Now, a longitudinal study estimated a heritability ranging from 72 to 89%. The results of this study also showed a "developmental dynamic" pattern, for, over time, there is a mitigation of the genetic influence as a risk factor for anxious and depressive symptoms [16], leading one to ponder over the influence of protective factors in the progno-

Individuals with AD present attentional bias to the threatening stimulus, which increases the vulnerability to stress, considering these "complex disorders," due to being influenced by multiple factors that flee from what are called "deterministic effects" of the genes, therefore making them liable to modulation by interference [2]. According to an experimental study with laboratory animals, stress by social subjugation is able to foster hyperalgesia with a decrease in the BDNF levels; this condition is more evident in "susceptible" subjects rather than in "resilient" ones [17], reinforcing the complex multifactorial theory that the neurobiological

delays in adapting to changes in the autonomic nervous system [1].

**6**

BDNF exons decrease markedly after high corticosterone levels. BDNF levels are controlled by epigenetic mechanisms with extinction assisted by partial NMDA receptor agonists (e.g., D-cycloserine) and histone deacetylase inhibitors [18].

Environmental factors, via epigenetic factors, control the alterations of BDNF gene expression, especially when young. Harmful environmental influences while growing can cause a decrease in BDNF expression in adulthood, in addition to the serotonin transporter and FKBP5, leading to problems in patient response to drug and behavior therapies [19, 20].

Problems during youth lead to DNA methylation of BDNF promoter IV and a decrease in prefrontal cortex total BDNF mRNA [21]. However, after exercise and a healthy environment, total BDNF mRNA in the hippocampus increases due to increases in histone acetylation at promoter IV or decreases in its methylation [19].

In response to fear conditioning, the levels of BDNF exon mRNAs change markedly. As an example, after fear conditioning using light shock, exon I and III mRNA levels increase markedly, different from the exons II and IV which remain constant [18].

Several psychological factors have been associated with increased risk for anxiety disorders. Among the most intensively researched has been the concept of anxiety sensitivity (AS). AS has been defined as the individual response to physiological alterations associated with anxiety and fear. Patients with anxiety disorders have exaggerated psychological reactions that are reflective of misinterpretation of bodily cues such that the patient misperceives these sensations inappropriately as being harmful and dangerous, leading in a circular fashion to increased anxiety and fear. AS is associated with a selective cognitive bias toward threat. AS predicts the frequency and intensity of panic attacks [21].

The above section identifies several possible mediators of the psychobiological response to extreme stress and how each may contribute, alone or through functional interactions, to resilience or vulnerability to anxiety disorders. One prediction is that individuals in the highest quartile for measures of HPA axis, CRH, LC-NE, and estrogen activity and the lowest quartile for DHEA, NPY, galanin, testosterone, and 5-HT1A receptor and benzodiazepine receptor function will have an increased risk for anxiety disorders. Other mediators that can be included for the characterization of the vulnerable or resilient profile are glutamate and neurotrophic factors, such as brain-derived neurotrophic factor, and neuropeptides, such as substance P and cholecystokinin [21].

#### **8. Pharmacologic and non-pharmacologic treatments**

Patients should receive "psychoeducation" about their diagnosis, the possible etiology, and the mechanisms of action of the available treatment approaches. The treatment plan should include psychotherapy, pharmacotherapy, and other interventions, which should be chosen after careful consideration of individual factors, e.g., the patient's preference, the patient's history with previous treatment attempts, illness severity, comorbidities such as personality disorders, suicidality, local availability of treatment methods, wait time for psychotherapy appointments, costs, and other factors [22].

For all types of anxiety disorder, cognitive-behavioral therapy is the type of psychotherapy for which there is the strongest evidence and which receives the highest-level recommendation [23].

Cognitive-behavioral therapy has been found to have a moderately strong beneficial effect against all types of anxiety disorder compared to a placebo drug (Cohen's d = 0.57); the same is true of pharmacotherapy (e.g., sertraline, d = 0.54; venlafaxine, d = 0.50) [24, 25].

It is important to highlight that no articles were found that evaluated the effectiveness of Jungian and integrative psychotherapy.

Pharmacological treatments for anxiety disorders have become more tolerable, available, and numerous over the past half century. At the same time, research has yielded a vastly improved understanding of the neurobiological and physiological mechanisms involved in chronic anxiety and stress responses, suggesting new approaches to the treatment of anxiety disorders [26].

Numerous neurotransmitters play a role in normal states and in pathological anxiety states. Each of these systems is a potential target for pharmacological intervention, but relatively few classes of medications are used in clinical practice for the treatment of anxiety [27].

Due to their positive benefit/risk balance, selective serotonin reuptake inhibitors (SSRIs) and selective serotonin norepinephrine reuptake inhibitors (SNRIs) are recommended as first-line drugs. Patients should be informed that the onset of the anxiolytic effect of these antidepressants has a latency of 2–4 weeks (in some cases up to 6 weeks) [22].

We should continue to test alternative therapies for treating and preventing anxiety disorders and to help patients whose anxiety is resistant to conventional treatments; also, we need to consider the patient's feelings about mental illness and address their responses early in treatment. All of these measures will enhance the care of patients with anxiety [27].

#### **9. Brain-derived neurotrophic factor**

BDNF is one of the most abundant neurotrophins in the human brain, identified in 1982 by Yves Barde and Hans [17]. It is found in two distinct forms, pro-BDNF and the mature BDNF, which have antagonistic functions. The pro-BDNF is the precursor protein that is synthesized and undergoes cleavage to produce its mature form, BDNF, presenting greater physiological activity in the central nervous system [28, 29].

The pro-BDNF has high affinity to the p75 neurotrophin receptor, triggering pro-apoptotic effects and anti-plasticity [17]. On the other hand, the main receptor where the binding of the mature BDNF occurs is the tropomyosin-related kinase receptor type B (TrkB), distributed in the cortex, hippocampus, multiple bridged nuclei, and the spinal cord. When activated, this receptor causes a series of intracellular cascades that are responsible for growth, survival, and neural differentiation [15, 18].

Studies on neurotrophins allowed the release of one more hypothesis that would explain the physiopathology of mental disorders, called neurotrophic hypothesis, where deficits of neuroplasticity would occur and cause atrophy of certain regions of the brain (mainly cortical and the hippocampus), contributing to the development of mental disorders [7].

The main origin of these alterations is a decrease in the BDNF expression, caused by stress [19]. However, the association between the BDNF serum levels and mental disorders has yet to be completely clarified. There is evidence that the BDNF serum levels are reduced in patients with mental disorders, regardless of the diagnosis [7].

A meta-analysis that studied the peripheral values of BDNF in different mental disorders with the hypothesis of proving its nonspecificity obtained results pointing

**9**

*BDNF Protein and Anxiety Disorders*

the HPA axis [31].

memory [32].

studies [7].

to stress, and a decrease in anxiety.

changes resulting from physical exercise [24].

effects resulting from stressful situations [24].

illness prevention [24].

*DOI: http://dx.doi.org/10.5772/intechopen.92341*

comparing groups of patients with healthy controls [30].

to a valid reduction of BDNF levels in acute cases as well as in other periods of treatment (i.e., with symptom remission and in the presence of residual symptoms), in

of glucocorticoid (GC) hormone levels due to the activation of the HPA axis, neuroplastic changes occur, as well as a decrease in the BDNF hippocampal levels. Thus, a persistence and intensity of stressors may produce hippocampal dysfunction, causing a decline in the inhibitory control that the hippocampus exerts over

It is known that in a severe and prolonged state of stress, with sustained increase

The BDNF has become an important tool in understanding cognitive deficits, especially those related to memory loss. One of the reasons to use this neurotrophin in these studies is its participation not only in processes of differentiation, neuronal survival, and synaptic plasticity but also in processes involving learning and

The BDNF also enables the strengthening of connections between neurons (synapsis), mainly in the hippocampus, cortex, and basal forebrain—important

The BDNF may cause neurogenesis mainly in the hippocampal region of adult brains. At the same time, in patients who suffer from psychiatric illnesses, a smaller hippocampus has been identified, associated with a decrease in BDNF plasma levels, than healthy individuals. Clarifying the exact mechanism of the action of

BDNF crosses the blood-brain barrier, possibly through its dosage in peripheral blood, whose serum levels correlate with the levels in the central nervous system [7]. However, this has not become a clinical reality, despite the biological plausibility, due to great heterogeneity between the studies, which presented low power of detection of differences and biases of publication, and influence of confounding variables (physical exercise, smoking, body mass index, laboratory techniques that lack standardization, kits that do not distinguish between pro-BDNF and mature BDNF). The high number of variations limits comparisons between the

The regular practice of physical activity has been shown to be a prophylactic and therapeutic intervention for several dysfunctions, such as stress, by way of the increase in adaptive responses of the HPA axis, improvement of adaptive response

It is believed that identifying variations of the epigenetic pattern of DNA and of the gene expression of rats exposed to stress, as well as rat practitioners and nonpractitioners of physical activity, may reveal additional data that could be extrapolated to the human population, regarding the importance of physical activity in

The interest in knowing the molecular aspects of the effect of physical activity and/or exercise is evident; however, little is known yet regarding the epigenetic

Thus, several studies have been conducted to clarify the connection between the regular practice of physical exercise and the increased concentration of BDNF, making it necessary to shed light on the role of this gene in suppressing the harmful

regions for learning, maintaining memory, and higher thinking.

BDNF will permit a better understanding of the cognitive deficits.

**10. Changes in BDNF levels in psychiatric illnesses**

#### *BDNF Protein and Anxiety Disorders DOI: http://dx.doi.org/10.5772/intechopen.92341*

*Neurological and Mental Disorders*

venlafaxine, d = 0.50) [24, 25].

for the treatment of anxiety [27].

care of patients with anxiety [27].

**9. Brain-derived neurotrophic factor**

up to 6 weeks) [22].

ferentiation [15, 18].

diagnosis [7].

ment of mental disorders [7].

tiveness of Jungian and integrative psychotherapy.

approaches to the treatment of anxiety disorders [26].

(Cohen's d = 0.57); the same is true of pharmacotherapy (e.g., sertraline, d = 0.54;

It is important to highlight that no articles were found that evaluated the effec-

Pharmacological treatments for anxiety disorders have become more tolerable, available, and numerous over the past half century. At the same time, research has yielded a vastly improved understanding of the neurobiological and physiological mechanisms involved in chronic anxiety and stress responses, suggesting new

Numerous neurotransmitters play a role in normal states and in pathological anxiety states. Each of these systems is a potential target for pharmacological intervention, but relatively few classes of medications are used in clinical practice

(SSRIs) and selective serotonin norepinephrine reuptake inhibitors (SNRIs) are recommended as first-line drugs. Patients should be informed that the onset of the anxiolytic effect of these antidepressants has a latency of 2–4 weeks (in some cases

We should continue to test alternative therapies for treating and preventing anxiety disorders and to help patients whose anxiety is resistant to conventional treatments; also, we need to consider the patient's feelings about mental illness and address their responses early in treatment. All of these measures will enhance the

BDNF is one of the most abundant neurotrophins in the human brain, identified in 1982 by Yves Barde and Hans [17]. It is found in two distinct forms, pro-BDNF and the mature BDNF, which have antagonistic functions. The pro-BDNF is the precursor protein that is synthesized and undergoes cleavage to produce its mature form, BDNF,

Studies on neurotrophins allowed the release of one more hypothesis that would explain the physiopathology of mental disorders, called neurotrophic hypothesis, where deficits of neuroplasticity would occur and cause atrophy of certain regions of the brain (mainly cortical and the hippocampus), contributing to the develop-

The main origin of these alterations is a decrease in the BDNF expression, caused by stress [19]. However, the association between the BDNF serum levels and mental disorders has yet to be completely clarified. There is evidence that the BDNF serum levels are reduced in patients with mental disorders, regardless of the

A meta-analysis that studied the peripheral values of BDNF in different mental disorders with the hypothesis of proving its nonspecificity obtained results pointing

presenting greater physiological activity in the central nervous system [28, 29]. The pro-BDNF has high affinity to the p75 neurotrophin receptor, triggering pro-apoptotic effects and anti-plasticity [17]. On the other hand, the main receptor where the binding of the mature BDNF occurs is the tropomyosin-related kinase receptor type B (TrkB), distributed in the cortex, hippocampus, multiple bridged nuclei, and the spinal cord. When activated, this receptor causes a series of intracellular cascades that are responsible for growth, survival, and neural dif-

Due to their positive benefit/risk balance, selective serotonin reuptake inhibitors

**8**

to a valid reduction of BDNF levels in acute cases as well as in other periods of treatment (i.e., with symptom remission and in the presence of residual symptoms), in comparing groups of patients with healthy controls [30].

It is known that in a severe and prolonged state of stress, with sustained increase of glucocorticoid (GC) hormone levels due to the activation of the HPA axis, neuroplastic changes occur, as well as a decrease in the BDNF hippocampal levels. Thus, a persistence and intensity of stressors may produce hippocampal dysfunction, causing a decline in the inhibitory control that the hippocampus exerts over the HPA axis [31].

The BDNF has become an important tool in understanding cognitive deficits, especially those related to memory loss. One of the reasons to use this neurotrophin in these studies is its participation not only in processes of differentiation, neuronal survival, and synaptic plasticity but also in processes involving learning and memory [32].

The BDNF also enables the strengthening of connections between neurons (synapsis), mainly in the hippocampus, cortex, and basal forebrain—important regions for learning, maintaining memory, and higher thinking.

#### **10. Changes in BDNF levels in psychiatric illnesses**

The BDNF may cause neurogenesis mainly in the hippocampal region of adult brains. At the same time, in patients who suffer from psychiatric illnesses, a smaller hippocampus has been identified, associated with a decrease in BDNF plasma levels, than healthy individuals. Clarifying the exact mechanism of the action of BDNF will permit a better understanding of the cognitive deficits.

BDNF crosses the blood-brain barrier, possibly through its dosage in peripheral blood, whose serum levels correlate with the levels in the central nervous system [7]. However, this has not become a clinical reality, despite the biological plausibility, due to great heterogeneity between the studies, which presented low power of detection of differences and biases of publication, and influence of confounding variables (physical exercise, smoking, body mass index, laboratory techniques that lack standardization, kits that do not distinguish between pro-BDNF and mature BDNF). The high number of variations limits comparisons between the studies [7].

The regular practice of physical activity has been shown to be a prophylactic and therapeutic intervention for several dysfunctions, such as stress, by way of the increase in adaptive responses of the HPA axis, improvement of adaptive response to stress, and a decrease in anxiety.

It is believed that identifying variations of the epigenetic pattern of DNA and of the gene expression of rats exposed to stress, as well as rat practitioners and nonpractitioners of physical activity, may reveal additional data that could be extrapolated to the human population, regarding the importance of physical activity in illness prevention [24].

The interest in knowing the molecular aspects of the effect of physical activity and/or exercise is evident; however, little is known yet regarding the epigenetic changes resulting from physical exercise [24].

Thus, several studies have been conducted to clarify the connection between the regular practice of physical exercise and the increased concentration of BDNF, making it necessary to shed light on the role of this gene in suppressing the harmful effects resulting from stressful situations [24].

#### **11. Conclusion**

There is evidence that it is important to study aspects in common of the neurobiology of anxiety disorders, and its relation to the BNDF protein, to obtain preventive measures in mental health.

Recent clinical trials, in animals and humans, increasingly seek an association between different spectra of mental disorders and BDNF levels and their subforms, in different collection sites, leading to the question of the possibility of using it as a biomarker of susceptibility to anxious disorders. The early titration and serialization of BDNF and subforms in families with a high probability of ED heritability are shown as a future perspective for primary and integrated actions in mental health, with modulation of gene expression, using the "dynamic developmental" pattern for a reduction of future medication for susceptible individuals, as well as the possibility of discovering acute illnesses early, with a positive change in the history of the disease and a reduction in social economic losses. From this perspective, we highlight the importance of further studies on the neurobiology of anxiety disorders, on BDNF protein and its physiology, and the association between both for preventive measures in mental health.

### **Author details**

Tatiana Marins Farias1,2,3, Rebeca Ataíde Cerqueira1 , Danton Ferraz Sousa1 , João Vitor Costa Freire1 , Ana Carolina Tavares Lopes1 and Silvia Fernanda Lima De Moura Cal1 \*

1 UNIME - Metropolitan Union for the Development of Education and Culture, Brazil

2 Federal University of Bahia (UFBa), Brazil

3 Federal Government Economy Ministry, Brazil

\*Address all correspondence to: silviacal@uol.com.br

© 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.

**11**

nrd3366

*BDNF Protein and Anxiety Disorders*

[1] Bandelow B, Michaelis S.

nih.gov/pubmed/26487813

**References**

*DOI: http://dx.doi.org/10.5772/intechopen.92341*

Epidemiology of anxiety disorders in the 21st century. Dialogues in Clinical Neuroscience. 2015;**17**(3):327-335. Available from: http://www.ncbi.nlm.

php?script=sci\_arttext&pid=S0100-

[9] Publication AP. Diagnostic and Statistical Manual of Mental Disorders. DSM-5 [Internet]. Washington DC: American Psychiatric Publication; 2013. Available from: https://books.google. com.br/books?hl=pt-BR&lr=&id=-Jiv BAAAQBAJ&oi=fnd&pg=PT18&dq =diagnostic+and+statistical+mental+ disorders&ots=ceSN16OHyc&sig=V BVXcQ2KuBON36zYhC84Nflx\_-o#v- =onepage&q=diagnostic and statistical

69912007000600012&lng=

mental disorders&f=false

2013;**32**(3):549-575

[10] Martin E, Ressler K, Binder E, Nemeroff C. The neurobiology of anxiety disorders: Brain imaging, genetics, and

Psychoneuroendocrinology. The Psychiatric Clinics of North America.

[11] Pohjavaara P, Telaranta T,

[12] Castrén E. Neurotrophins and psychiatric disorders. Handb Exp Pharmacol [Internet]. 2014;**220**: 461-479. Available from: http://www. ncbi.nlm.nih.gov/pubmed/24668483

[13] Kupfer DJ. Anxiety and DSM-5. Dialogues in Clinical Neuroscience.

[14] Hettema JM, Neale MC, Kendler KS. A review and meta-analysis of the genetic epidemiology of anxiety disorders. Am J Psychiatry [Internet]. 2001;**158**(10):1568-1578. Available from: http://www.ncbi.nlm.nih.gov/

2015;**17**(3):245-246

pubmed/11578982

Väisänen E. The role of the sympathetic nervous system in anxiety: Is it possible to relieve anxiety with endoscopic sympathetic block? Nordic Journal of Psychiatry. 2003;**57**(1):55-60. Available from: https://www.tandfonline.com/ doi/abs/10.1080/08039480310000266

pt&tlng=pt

[2] Crocq M-A. A history of anxiety: From Hippocrates to DSM. Dialogues in Clinical Neuroscience. 2015;**17**(3):319- 325. Available from: http://www.ncbi. nlm.nih.gov/pubmed/26487812

[3] Bertolote JM, Fleischmann A. Suicide and psychiatric diagnosis: A worldwide

[4] Lopez AD, Murray CC. The global burden of disease, 1990-2020. Nature Medicine. 1998;**4**(11):1241-1243. Available from: http://www.ncbi.nlm.

[5] Andrade LH, Wang YP, Andreoni S, Silveira CM, Alexandrino-Silva C, Siu ER, et al. Mental disorders in megacities: Findings from the São Paulo megacity mental health survey, Brazil.

[6] Simon NM. Generalized anxiety disorder and psychiatric comorbidities such as depression, bipolar disorder, and substance abuse. The Journal of Clinical Psychiatry. 2009;**70**(Suppl 2):10-14

[7] Nagahara AH, Tuszynski MH. Potential therapeutic uses of BDNF in neurological and psychiatric disorders. Nat Rev Drug Discov [Internet]. 2011;**10**(3):209-219. Available from: https://www.nature.com/articles/

[8] Cordeiro AOG. Revisão sistemática: uma revisão narrativa. Rev do Colégio Bras Cir. 2007;**6**(34):428-431. Available from: http://www.scielo.br/scielo.

perspective. World Psychiatry. 2002;**1**(3):181-185. Available from: http://www.ncbi.nlm.nih.gov/

pubmed/16946849

nih.gov/pubmed/9809543

PLoS One. 2012;**7**(2):1-11

*BDNF Protein and Anxiety Disorders DOI: http://dx.doi.org/10.5772/intechopen.92341*

#### **References**

*Neurological and Mental Disorders*

tive measures in mental health.

measures in mental health.

**11. Conclusion**

**10**

**Author details**

Brazil

João Vitor Costa Freire1

Silvia Fernanda Lima De Moura Cal1

2 Federal University of Bahia (UFBa), Brazil

provided the original work is properly cited.

3 Federal Government Economy Ministry, Brazil

\*Address all correspondence to: silviacal@uol.com.br

Tatiana Marins Farias1,2,3, Rebeca Ataíde Cerqueira1

, Ana Carolina Tavares Lopes1

1 UNIME - Metropolitan Union for the Development of Education and Culture,

© 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,

There is evidence that it is important to study aspects in common of the neurobiology of anxiety disorders, and its relation to the BNDF protein, to obtain preven-

Recent clinical trials, in animals and humans, increasingly seek an association between different spectra of mental disorders and BDNF levels and their subforms, in different collection sites, leading to the question of the possibility of using it as a biomarker of susceptibility to anxious disorders. The early titration and serialization of BDNF and subforms in families with a high probability of ED heritability are shown as a future perspective for primary and integrated actions in mental health, with modulation of gene expression, using the "dynamic developmental" pattern for a reduction of future medication for susceptible individuals, as well as the possibility of discovering acute illnesses early, with a positive change in the history of the disease and a reduction in social economic losses. From this perspective, we highlight the importance of further studies on the neurobiology of anxiety disorders, on BDNF protein and its physiology, and the association between both for preventive

\*

, Danton Ferraz Sousa1

and

,

[1] Bandelow B, Michaelis S. Epidemiology of anxiety disorders in the 21st century. Dialogues in Clinical Neuroscience. 2015;**17**(3):327-335. Available from: http://www.ncbi.nlm. nih.gov/pubmed/26487813

[2] Crocq M-A. A history of anxiety: From Hippocrates to DSM. Dialogues in Clinical Neuroscience. 2015;**17**(3):319- 325. Available from: http://www.ncbi. nlm.nih.gov/pubmed/26487812

[3] Bertolote JM, Fleischmann A. Suicide and psychiatric diagnosis: A worldwide perspective. World Psychiatry. 2002;**1**(3):181-185. Available from: http://www.ncbi.nlm.nih.gov/ pubmed/16946849

[4] Lopez AD, Murray CC. The global burden of disease, 1990-2020. Nature Medicine. 1998;**4**(11):1241-1243. Available from: http://www.ncbi.nlm. nih.gov/pubmed/9809543

[5] Andrade LH, Wang YP, Andreoni S, Silveira CM, Alexandrino-Silva C, Siu ER, et al. Mental disorders in megacities: Findings from the São Paulo megacity mental health survey, Brazil. PLoS One. 2012;**7**(2):1-11

[6] Simon NM. Generalized anxiety disorder and psychiatric comorbidities such as depression, bipolar disorder, and substance abuse. The Journal of Clinical Psychiatry. 2009;**70**(Suppl 2):10-14

[7] Nagahara AH, Tuszynski MH. Potential therapeutic uses of BDNF in neurological and psychiatric disorders. Nat Rev Drug Discov [Internet]. 2011;**10**(3):209-219. Available from: https://www.nature.com/articles/ nrd3366

[8] Cordeiro AOG. Revisão sistemática: uma revisão narrativa. Rev do Colégio Bras Cir. 2007;**6**(34):428-431. Available from: http://www.scielo.br/scielo.

php?script=sci\_arttext&pid=S0100- 69912007000600012&lng= pt&tlng=pt

[9] Publication AP. Diagnostic and Statistical Manual of Mental Disorders. DSM-5 [Internet]. Washington DC: American Psychiatric Publication; 2013. Available from: https://books.google. com.br/books?hl=pt-BR&lr=&id=-Jiv BAAAQBAJ&oi=fnd&pg=PT18&dq =diagnostic+and+statistical+mental+ disorders&ots=ceSN16OHyc&sig=V BVXcQ2KuBON36zYhC84Nflx\_-o#v- =onepage&q=diagnostic and statistical mental disorders&f=false

[10] Martin E, Ressler K, Binder E, Nemeroff C. The neurobiology of anxiety disorders: Brain imaging, genetics, and Psychoneuroendocrinology. The Psychiatric Clinics of North America. 2013;**32**(3):549-575

[11] Pohjavaara P, Telaranta T, Väisänen E. The role of the sympathetic nervous system in anxiety: Is it possible to relieve anxiety with endoscopic sympathetic block? Nordic Journal of Psychiatry. 2003;**57**(1):55-60. Available from: https://www.tandfonline.com/ doi/abs/10.1080/08039480310000266

[12] Castrén E. Neurotrophins and psychiatric disorders. Handb Exp Pharmacol [Internet]. 2014;**220**: 461-479. Available from: http://www. ncbi.nlm.nih.gov/pubmed/24668483

[13] Kupfer DJ. Anxiety and DSM-5. Dialogues in Clinical Neuroscience. 2015;**17**(3):245-246

[14] Hettema JM, Neale MC, Kendler KS. A review and meta-analysis of the genetic epidemiology of anxiety disorders. Am J Psychiatry [Internet]. 2001;**158**(10):1568-1578. Available from: http://www.ncbi.nlm.nih.gov/ pubmed/11578982

[15] Kendler KS, Gardner CO, Lichtenstein P. A developmental twin study of symptoms of anxiety and depression: Evidence for genetic innovation and attenuation. Psychological Medicine. 2008;**38**(11):1567-1575. Available from: https://www.cambridge. org/core/product/identifier/ S003329170800384X/type/ journal\_article

[16] Lu B, Pang PT, Woo NH. The yin and yang of neurotrophin action. Nature Reviews. Neuroscience. 2005;**6**(8):603- 614. Available from: http://www.ncbi. nlm.nih.gov/pubmed/16062169

[17] Farach FJ, Pruitt LD, Jun JJ, Jerud AB, Zoellner LA, Roy-Byrne PP. Pharmacological treatment of anxiety disorders: Current treatments and future directions. Journal of Anxiety Disorders. 2012;**26**(8):833-843. Available from: http://www.ncbi.nlm. nih.gov/pubmed/23023162

[18] Boulle F, van den Hove DLA, Jakob SB, Rutten BP, Hamon M, van Os J, et al. Epigenetic regulation of the BDNF gene: Implications for psychiatric disorders. Molecular Psychiatry. 2012;**17**(6):584-596. Available from: http://www.ncbi.nlm.nih.gov/ pubmed/21894152

[19] van Winkel R, van Nierop M, Myin-Germeys I, van Os J. Childhood trauma as a cause of psychosis: Linking genes, psychology, and biology. Canadian Journal of Psychiatry. 2013;**58**(1):44-51. Available from: http://journals.sagepub.com/ doi/10.1177/070674371305800109

[20] Bennett M, Lagopoulos J. Stress, Trauma and Synaptic Plasticity [Internet]. Cham: Springer International Publishing; 2018. Available from: https://link.springer. com/book/10.1007/978-3-319-91116-8

[21] Charney DS. The psychobiology of resilience and vulnerability to anxiety

disorders: Implications for prevention and treatment. Dialogues in Clinical Neuroscience. 2003;**5**(3):207-221. Available from: http://www.ncbi.nlm. nih.gov/pubmed/22034473

[22] Bandelow B, Michaelis S, Wedekind D. Treatment of anxiety disorders. Dialogues in Clinical Neuroscience. 2017;**19**(2):93-107. Available from: http://www.ncbi.nlm. nih.gov/pubmed/28867934

[23] Ströhle A, Gensichen J, Domschke K. The diagnosis and treatment of anxiety disorders. Deutsches Ärzteblatt International. 2018;**155**(37):611-620. Available from: http://www.ncbi.nlm.nih.gov/ pubmed/30282583

[24] Bandelow B, Reitt M, Röver C, Michaelis S, Görlich Y, Wedekind D. Efficacy of treatments for anxiety disorders. International Clinical Psychopharmacology. 2015;**30**(4):183-192. Available from: http://content.wkhealth.com/linkback/ openurl?sid=WKPTLP:landingpage &an=00004850-201507000-00002

[25] Bystritsky A, Khalsa SS, Cameron ME, Schiffman J. Current diagnosis and treatment of anxiety disorders. PT. 2013;**38**(1):30-57. Available from: http://www.ncbi.nlm. nih.gov/pubmed/23599668

[26] Teche SP, Nuernberg GL, Sordi AO, De Souza LH, Remy L, Ceresér KMM, et al. Measurement methods of bdnf levels in major depression: A qualitative systematic review of clinical trials. The Psychiatric Quarterly. 2013;**84**(4):485-497

[27] Farooqui T, Farooqui AA, editors. Diet and Exercise in Cognitive Function and Neurological Diseases. John Wiley & Sons, Inc: Hoboken, NJ; 2015. Available from: https:// onlinelibrary.wiley.com/doi/ book/10.1002/9781118840634

**13**

*BDNF Protein and Anxiety Disorders*

Molendijk ML, Gonzalez-

2015;**20**(9):1108-1119

[29] Nooshinfar E, Akbarzadeh-Baghban A, Meisami E. Effects of increasing durations of immobilization stress on plasma corticosterone level, learning and memory and hippocampal

BDNF gene expression in rats.

nih.gov/pubmed/19412541

factors. BMB Rep [Internet].

nih.gov/pubmed/21081796

pubmed/19470236

Neuroscience Letters. 2011;**500**(1):63- 66. Available from: http://www.ncbi. nlm.nih.gov/pubmed/21683767

[30] Li G, Peskind ER, Millard SP, Chi P, Sokal I, Yu C-E, et al. Cerebrospinal fluid concentration of brain-derived neurotrophic factor and cognitive function in non-demented subjects. PLOS One [Internet]. 2009;**4**(5):e5424. Available from: http://www.ncbi.nlm.

[31] Lee E, Son H. Adult hippocampal neurogenesis and related neurotrophic

2009;**42**(5):239-244. Available from: http://www.ncbi.nlm.nih.gov/

[32] Zoladz JA, Pilc A. The effect of physical activity on the brain derived neurotrophic factor: From animal to human studies. Journal of Physiology and Pharmacology. 2010;**61**(5):533-541. Available from: http://www.ncbi.nlm.

*DOI: http://dx.doi.org/10.5772/intechopen.92341*

[28] Fernandes BS, Steiner J, Berk M,

Pinto A, Turck CW, et al. Peripheral brain-derived neurotrophic factor in schizophrenia and the role of antipsychotics: Meta-analysis and implications. Molecular Psychiatry.

*BDNF Protein and Anxiety Disorders DOI: http://dx.doi.org/10.5772/intechopen.92341*

*Neurological and Mental Disorders*

[15] Kendler KS, Gardner CO, Lichtenstein P. A developmental twin study of symptoms of anxiety and depression: Evidence for genetic innovation and

journal\_article

attenuation. Psychological Medicine. 2008;**38**(11):1567-1575. Available from: https://www.cambridge. org/core/product/identifier/ S003329170800384X/type/

disorders: Implications for prevention and treatment. Dialogues in Clinical Neuroscience. 2003;**5**(3):207-221. Available from: http://www.ncbi.nlm.

nih.gov/pubmed/22034473

nih.gov/pubmed/28867934

[23] Ströhle A, Gensichen J, Domschke K. The diagnosis and treatment of anxiety disorders. Deutsches Ärzteblatt International. 2018;**155**(37):611-620. Available from: http://www.ncbi.nlm.nih.gov/

pubmed/30282583

[24] Bandelow B, Reitt M, Röver C, Michaelis S, Görlich Y, Wedekind D. Efficacy of treatments for anxiety disorders. International Clinical Psychopharmacology. 2015;**30**(4):183-192. Available from: http://content.wkhealth.com/linkback/ openurl?sid=WKPTLP:landingpage &an=00004850-201507000-00002

[25] Bystritsky A, Khalsa SS, Cameron ME, Schiffman J. Current diagnosis and treatment of anxiety disorders. PT. 2013;**38**(1):30-57. Available from: http://www.ncbi.nlm.

nih.gov/pubmed/23599668

2013;**84**(4):485-497

[26] Teche SP, Nuernberg GL, Sordi AO, De Souza LH, Remy L, Ceresér KMM, et al. Measurement methods of bdnf levels in major depression: A qualitative systematic review of clinical trials. The Psychiatric Quarterly.

[27] Farooqui T, Farooqui AA, editors. Diet and Exercise in Cognitive Function and Neurological Diseases. John Wiley & Sons, Inc: Hoboken, NJ; 2015. Available from: https:// onlinelibrary.wiley.com/doi/ book/10.1002/9781118840634

[22] Bandelow B, Michaelis S, Wedekind D. Treatment of anxiety disorders. Dialogues in Clinical Neuroscience. 2017;**19**(2):93-107. Available from: http://www.ncbi.nlm.

[16] Lu B, Pang PT, Woo NH. The yin and yang of neurotrophin action. Nature Reviews. Neuroscience. 2005;**6**(8):603- 614. Available from: http://www.ncbi. nlm.nih.gov/pubmed/16062169

[17] Farach FJ, Pruitt LD, Jun JJ, Jerud AB, Zoellner LA, Roy-

nih.gov/pubmed/23023162

[18] Boulle F, van den Hove DLA, Jakob SB, Rutten BP, Hamon M, van Os J, et al. Epigenetic regulation of the BDNF gene: Implications for psychiatric

disorders. Molecular Psychiatry. 2012;**17**(6):584-596. Available from: http://www.ncbi.nlm.nih.gov/

[19] van Winkel R, van Nierop M, Myin-Germeys I, van Os J. Childhood trauma as a cause of psychosis: Linking

genes, psychology, and biology. Canadian Journal of Psychiatry. 2013;**58**(1):44-51. Available from: http://journals.sagepub.com/ doi/10.1177/070674371305800109

[20] Bennett M, Lagopoulos J. Stress, Trauma and Synaptic Plasticity [Internet]. Cham: Springer International Publishing; 2018. Available from: https://link.springer. com/book/10.1007/978-3-319-91116-8

[21] Charney DS. The psychobiology of resilience and vulnerability to anxiety

pubmed/21894152

Byrne PP. Pharmacological treatment of anxiety disorders: Current treatments and future directions. Journal of Anxiety Disorders. 2012;**26**(8):833-843. Available from: http://www.ncbi.nlm.

**12**

[28] Fernandes BS, Steiner J, Berk M, Molendijk ML, Gonzalez-Pinto A, Turck CW, et al. Peripheral brain-derived neurotrophic factor in schizophrenia and the role of antipsychotics: Meta-analysis and implications. Molecular Psychiatry. 2015;**20**(9):1108-1119

[29] Nooshinfar E, Akbarzadeh-Baghban A, Meisami E. Effects of increasing durations of immobilization stress on plasma corticosterone level, learning and memory and hippocampal BDNF gene expression in rats. Neuroscience Letters. 2011;**500**(1):63- 66. Available from: http://www.ncbi. nlm.nih.gov/pubmed/21683767

[30] Li G, Peskind ER, Millard SP, Chi P, Sokal I, Yu C-E, et al. Cerebrospinal fluid concentration of brain-derived neurotrophic factor and cognitive function in non-demented subjects. PLOS One [Internet]. 2009;**4**(5):e5424. Available from: http://www.ncbi.nlm. nih.gov/pubmed/19412541

[31] Lee E, Son H. Adult hippocampal neurogenesis and related neurotrophic factors. BMB Rep [Internet]. 2009;**42**(5):239-244. Available from: http://www.ncbi.nlm.nih.gov/ pubmed/19470236

[32] Zoladz JA, Pilc A. The effect of physical activity on the brain derived neurotrophic factor: From animal to human studies. Journal of Physiology and Pharmacology. 2010;**61**(5):533-541. Available from: http://www.ncbi.nlm. nih.gov/pubmed/21081796

**15**

skills as well [3].

**Chapter 2**

**Abstract**

therapy

**1. Introduction**

extraversion, and effortful control [2].

Personality Disorders in

Therapeutic Approaches

*Hojka Gregoric Kumperscak*

Adolescents and Different

A personality disorder can be diagnosed at any age if the diagnostic criteria are met, which means also in adolescence. Diagnosing personality disorders is important since only with clear diagnosis specialized treatment can be applied. Several specialized (psycho)therapies have been developed for treating adolescent personality disorder with evidence-based efficiency, especially in borderline personality disorder—adolescent identity treatment (AIT), mentalization-based therapy (MBT), and dialectical behavior therapy (DBT). All are evidence-based therapies. Pharmacotherapy is not the therapy of choice and only a few studies have clearly demonstrated its efficiency; however, it is still largely utilized in clinical practice.

**Keywords:** personality disorders, adolescent, borderline personality disorder, adolescent identity treatment, mentalization-based therapy, dialectical behavior

Each person has a set of personality traits that are unique and make up one's personality. *Personality* can be defined as recognizable and permanent characteristics and attitudes that are reflected in thinking, feeling, and behaving (impulse control, the way of establishing and managing interpersonal relationships) [1]. Personality develops and evolves since childhood and shapes throughout life. *Temperament* is a biologically determined trait manifested from birth [2]. Rothbart et al. introduced three factors of temperament for the early and middle childhood that, later on in the development, shape personality dimensions, such as negative affectivity,

Temperamental characteristics show high stability and are developmentally associated with personality traits during adulthood including extraversion or high energetic level, agreeableness, conscientiousness, neuroticism (emotional stability), and openness [2]. An important personality trait is *character*, which mainly refers to the substantive aspects of experiencing and related behavior. At the heart of the psychological understanding of character are traits that are important in terms of the individual's will, morality, and ethical and value orientation [3]. Naturally, our achievements in solving mental and life's problems depend on our abilities. The great scope of competence can be combined with various talents and the scope of

#### **Chapter 2**

## Personality Disorders in Adolescents and Different Therapeutic Approaches

*Hojka Gregoric Kumperscak*

#### **Abstract**

A personality disorder can be diagnosed at any age if the diagnostic criteria are met, which means also in adolescence. Diagnosing personality disorders is important since only with clear diagnosis specialized treatment can be applied. Several specialized (psycho)therapies have been developed for treating adolescent personality disorder with evidence-based efficiency, especially in borderline personality disorder—adolescent identity treatment (AIT), mentalization-based therapy (MBT), and dialectical behavior therapy (DBT). All are evidence-based therapies. Pharmacotherapy is not the therapy of choice and only a few studies have clearly demonstrated its efficiency; however, it is still largely utilized in clinical practice.

**Keywords:** personality disorders, adolescent, borderline personality disorder, adolescent identity treatment, mentalization-based therapy, dialectical behavior therapy

#### **1. Introduction**

Each person has a set of personality traits that are unique and make up one's personality. *Personality* can be defined as recognizable and permanent characteristics and attitudes that are reflected in thinking, feeling, and behaving (impulse control, the way of establishing and managing interpersonal relationships) [1]. Personality develops and evolves since childhood and shapes throughout life. *Temperament* is a biologically determined trait manifested from birth [2]. Rothbart et al. introduced three factors of temperament for the early and middle childhood that, later on in the development, shape personality dimensions, such as negative affectivity, extraversion, and effortful control [2].

Temperamental characteristics show high stability and are developmentally associated with personality traits during adulthood including extraversion or high energetic level, agreeableness, conscientiousness, neuroticism (emotional stability), and openness [2]. An important personality trait is *character*, which mainly refers to the substantive aspects of experiencing and related behavior. At the heart of the psychological understanding of character are traits that are important in terms of the individual's will, morality, and ethical and value orientation [3]. Naturally, our achievements in solving mental and life's problems depend on our abilities. The great scope of competence can be combined with various talents and the scope of skills as well [3].

Personality disorder (PD) is defined as an enduring pattern of inner experience and behavior that deviates markedly from the expectations of the individual's culture, is pervasive and inflexible, and leads to distress or impairment [4]. People with PD have disrupted behavior, cognition, and emotions when in contact with other people and society, while the individuals and the people around them suffer [1]. The ICD-10 classifies the following PD: paranoid, schizoid, dissocial, emotionally unstable (impulsive and borderline type), histrionic, anankastic, anxious (avoidant), dependent, and other (e.g., narcissistic) [5]. The DSM-5 divides PD into three clusters. Cluster A personality disorders are characterized by unusual and odd-eccentric behavior and introverted individuals including paranoid, schizoid, and schizotypal PD. Cluster B personality disorders are associated with dramatic, emotional, and erratic behavior: antisocial, borderline, histrionic, and narcissistic PD. Cluster C includes avoidant, dependent, and obsessive-compulsive PD associated with anxious and fearful disorders. The division into three groups is useful for educational and research purposes; however, it also has its limitations. Clinically, there is a lot of overlapping between various PDs. The frequency of individual PD varies from study to study, and even greater differences are present when looking at the frequency of individual PD in a given population. Borderline PD is present in 0.9–3% of the general adolescent population, in 11% of outpatient adolescents, and 49% of admitted adolescents [4].

People diagnosed with PD from one group may also meet the diagnostic criteria of PD from the other, which occurs in about 9% [4]. Individuals from group C and A most commonly have an associated PD (6.0 and 5.7%, respectively), while this occurs only in 1.5% of individuals in the group B [4]. Due to PD overlapping and for other reasons as well, the PD criteria in ICD-11, which will come into effect in January 2022, have been modified [6]. ICD-11 follows a dimensional understanding of PD and largely abandons the categorical view. The new division of PD follows the psychodynamic tradition, the scientific model of the core PD characteristics, and thus provides guidance for clinical treatment [7]. It provides an assessment of the severity of the disorder, and enables to diagnose three levels of PD and code subthreshold personality difficulty. ICD-11 specifies five domain qualifiers of personality, which include negative affectivity, detachment, dissociality, disinhibition, and anankastia. In addition to these five markers, a borderline pattern qualifier can also be specified. The latter may be applied if at least five out of nine borderline PD criteria according to DSM-5 are present. An example of a diagnosis of borderline PD following the new features in ICD-11 is for example a moderate PD with borderline pattern, negative affectivity, disinhibition, and dissociality [7].

#### **2. Borderline personality disorder**

Borderline PD is one of the most common PDs and these individuals are also more likely to seek medical help and suffer from significantly more associated mental disorders (depression, anxiety disorders, psychoactive substances abuse, and hyperkinetic disorder) compared to the general population [8]. Vulnerability for borderline PD can be clearly recognized during the development period. The concept of borderline personality has evolved throughout history. Morel and Kraepelin used this term to describe the states between neurotic and psychotic conditions primarily based on phenomenological clinical descriptions and by ignoring the developmental and dynamic aspects of pathology [9].

Kernberg linked the classical psychoanalysis, the object relations theories, the psychology of self (immature integrative self-functions) with the psychobiological and neurobiological theories, and defined the concept of borderline personality

**17**

*Personality Disorders in Adolescents and Different Therapeutic Approaches*

1.Frantic efforts to avoid real or imagined abandonment

8.Displays of inappropriate anger (verbal/physical fights)

3.Identity disturbance, seen in an unstable self-image or sense of self

6.Affective instability (episodic dysphoria, irritability, anxiety: lasting a few

9.Micropsychotic episodes, transient stress-related paranoid ideation/

In addition, these patterns are enduring, inflexible, and clinically relevant to diminish social, educational, or professional functioning. The onset of this pattern is traced back at least to adolescence or early adulthood and it is not a manifestation of another mental disorder and is not due to the consumption of psychoactive

Quite a few features of borderline PD (impulsivity, emotional instability, dysfunctional interpersonal relationships, impaired self-image, and identity diffusion) may also—to some extent—be characteristics of adolescent period. In order to diagnose a borderline PD in an individual during adolescence, the features must have been present for at least 1 year and cause severe dysfunction [4]. If the adolescent reacts highly destructive, has transient psychotic reactions and behavioral problems, uses psychoactive substances, has emotional disorders associated with the loss of a relationship with the important other or negative emotions, one can

In the clinical picture of borderline PD in adolescents, one often sees anger towards parents, depression without any existential despair, tension, loss of empathy, impulsive behavior, and brief psychotic episodes including a paranoid thoughts

It is a legitimate question whether to diagnose or not to diagnose PD before the age of 18. That is during adolescence – the time of major developmental changes, when the personality is not yet fully formed. However, relevant classifications and guidelines, based on a number of studies, allow us to diagnose a PD before 18 years

disorder as a pathological personality organization that is intermediate between psychotic disorders and neuroses—symptomatically, structurally, and geneticallydynamically [10, 11]. This concept was further enhanced by the Linehan's biosocial

According to DSM-5, at least five of the following nine criteria must be present

*DOI: http://dx.doi.org/10.5772/intechopen.93110*

to code borderline personality disorder [4].

2.Unstable and intense relationships

model [12].

4.Impulsivity

5.Suicidal behavior

hours to days)

substances [4].

7.Chronic feelings of emptiness

dissociative symptoms

suspect a borderline PD [13].

and depersonalization without thought disorder [14].

**3. Personality disorders during adolescence**

#### *Personality Disorders in Adolescents and Different Therapeutic Approaches DOI: http://dx.doi.org/10.5772/intechopen.93110*

disorder as a pathological personality organization that is intermediate between psychotic disorders and neuroses—symptomatically, structurally, and geneticallydynamically [10, 11]. This concept was further enhanced by the Linehan's biosocial model [12].

According to DSM-5, at least five of the following nine criteria must be present to code borderline personality disorder [4].


*Neurological and Mental Disorders*

49% of admitted adolescents [4].

Personality disorder (PD) is defined as an enduring pattern of inner experience and behavior that deviates markedly from the expectations of the individual's culture, is pervasive and inflexible, and leads to distress or impairment [4]. People with PD have disrupted behavior, cognition, and emotions when in contact with other people and society, while the individuals and the people around them suffer [1]. The ICD-10 classifies the following PD: paranoid, schizoid, dissocial, emotionally unstable (impulsive and borderline type), histrionic, anankastic, anxious (avoidant), dependent, and other (e.g., narcissistic) [5]. The DSM-5 divides PD into three clusters. Cluster A personality disorders are characterized by unusual and odd-eccentric behavior and introverted individuals including paranoid, schizoid, and schizotypal PD. Cluster B personality disorders are associated with dramatic, emotional, and erratic behavior: antisocial, borderline, histrionic, and narcissistic PD. Cluster C includes avoidant, dependent, and obsessive-compulsive PD associated with anxious and fearful disorders. The division into three groups is useful for educational and research purposes; however, it also has its limitations. Clinically, there is a lot of overlapping between various PDs. The frequency of individual PD varies from study to study, and even greater differences are present when looking at the frequency of individual PD in a given population. Borderline PD is present in 0.9–3% of the general adolescent population, in 11% of outpatient adolescents, and

People diagnosed with PD from one group may also meet the diagnostic criteria of PD from the other, which occurs in about 9% [4]. Individuals from group C and A most commonly have an associated PD (6.0 and 5.7%, respectively), while this occurs only in 1.5% of individuals in the group B [4]. Due to PD overlapping and for other reasons as well, the PD criteria in ICD-11, which will come into effect in January 2022, have been modified [6]. ICD-11 follows a dimensional understanding of PD and largely abandons the categorical view. The new division of PD follows the psychodynamic tradition, the scientific model of the core PD characteristics, and thus provides guidance for clinical treatment [7]. It provides an assessment of the severity of the disorder, and enables to diagnose three levels of PD and code subthreshold personality difficulty. ICD-11 specifies five domain qualifiers of personality, which include negative affectivity, detachment, dissociality, disinhibition, and anankastia. In addition to these five markers, a borderline pattern qualifier can also be specified. The latter may be applied if at least five out of nine borderline PD criteria according to DSM-5 are present. An example of a diagnosis of borderline PD following the new features in ICD-11 is for example a moderate PD with borderline

pattern, negative affectivity, disinhibition, and dissociality [7].

the developmental and dynamic aspects of pathology [9].

Borderline PD is one of the most common PDs and these individuals are also more likely to seek medical help and suffer from significantly more associated mental disorders (depression, anxiety disorders, psychoactive substances abuse, and hyperkinetic disorder) compared to the general population [8]. Vulnerability for borderline PD can be clearly recognized during the development period. The concept of borderline personality has evolved throughout history. Morel and Kraepelin used this term to describe the states between neurotic and psychotic conditions primarily based on phenomenological clinical descriptions and by ignoring

Kernberg linked the classical psychoanalysis, the object relations theories, the psychology of self (immature integrative self-functions) with the psychobiological and neurobiological theories, and defined the concept of borderline personality

**2. Borderline personality disorder**

**16**


In addition, these patterns are enduring, inflexible, and clinically relevant to diminish social, educational, or professional functioning. The onset of this pattern is traced back at least to adolescence or early adulthood and it is not a manifestation of another mental disorder and is not due to the consumption of psychoactive substances [4].

Quite a few features of borderline PD (impulsivity, emotional instability, dysfunctional interpersonal relationships, impaired self-image, and identity diffusion) may also—to some extent—be characteristics of adolescent period. In order to diagnose a borderline PD in an individual during adolescence, the features must have been present for at least 1 year and cause severe dysfunction [4]. If the adolescent reacts highly destructive, has transient psychotic reactions and behavioral problems, uses psychoactive substances, has emotional disorders associated with the loss of a relationship with the important other or negative emotions, one can suspect a borderline PD [13].

In the clinical picture of borderline PD in adolescents, one often sees anger towards parents, depression without any existential despair, tension, loss of empathy, impulsive behavior, and brief psychotic episodes including a paranoid thoughts and depersonalization without thought disorder [14].

#### **3. Personality disorders during adolescence**

It is a legitimate question whether to diagnose or not to diagnose PD before the age of 18. That is during adolescence – the time of major developmental changes, when the personality is not yet fully formed. However, relevant classifications and guidelines, based on a number of studies, allow us to diagnose a PD before 18 years of age. According to ICD-10, a PD can be diagnosed regardless the age of person if the diagnostic criteria are met; however, this is exceptionally rare before the age 16 or 17 years [5]. This is even more clearly defined in ICD-11, where the diagnosis of PD is made whenever the diagnostic criteria are met [6].

The DSM-5 allows for a diagnosis of PD in children and adolescents, when personality traits are particularly maladapted, permanent, and not related to a specific developmental period, mental disorder, or cultural background with the exception of antisocial PD, which cannot be diagnosed before the age of 18. For a diagnosis to be made, the characteristics of PD should have been present persistently for at least 1 year [4]. One should keep in mind that the characteristics of PD identified in childhood will change and that some types of PD will become less obvious or even disappear in later developmental periods (borderline, antisocial PD). The NICE recommendations do not define a chronological age at which a PD can be diagnosed. Instead, they focus on the individual level of developmental maturity and an understandable therapeutic plan to be provided to the person diagnosed with PD [15]. However, PD should not be diagnosed in individuals under the age of 13 and is not applicable until an individual finishes puberty. Because PDs have long been considered as therapy resistant, this diagnosis is misused even today as an excuse to refuse a patient. When diagnosing a person with PD, especially if it is an adolescent, an appropriate treatment must be provided along with the diagnosis. Prevention, early detection, and timely treatment are essential [15].

#### **4. Personality disorders treatment in a development period**

The purpose of diagnosing PD is to provide the adolescent with the appropriate treatment. It is the adolescent period that has a corrective potential and by introducing a therapy in time, we can significantly influence the course of PD. Adolescents with PD should be treated by a team of highly qualified professionals with a clearly structured intervention model and therapeutic plan [8, 13, 15]. Primarily, the patient must be provided with continuity and consistency. Adolescents with PD, especially borderline patients, have a tendency to form intense relationships; therefore, it is necessary to set clear time and space framework for treatments with different therapists. It is essential to organize treatments adequately—not too much and too little. Team members often have different views on the adolescent's problems and symptoms, which often lead to conflicts within the team; therefore, supervision is necessary. Often, many services (social services, school, general physician, previous therapist) are involved in the treatment; therefore, roles and tasks need to be clearly identified and coordinated. One of the main treatment goals of all team members is to support the adolescent in his separation and individualization and to actively involve him in the decision-making process. Many adolescents with borderline PD have experienced traumatic events; however, trauma processing is often not the primary intervention. Primarily, it is necessary to reduce suicidality and increase emotional stability [15, 16].

There are many different psychotherapeutic approaches to treat PD. Mentalization-based therapy (MBT), dialectical-behavioral therapy (DBT), and adolescent identity treatment (AIT) are among the most common. It is not so important which specific psychotherapeutic approach is used in the therapy but that certain changes outside the therapeutic relationship are triggered [13, 16]. According to Lambert, these changes are to be accountable for 40% of success in psychotherapy [17]. It is important to include the rest of the family in the therapy, to generate changes in the school, and that all significant others receive appropriate psychoeducation. Psychotherapeutic factors such as therapeutic posture, curiosity,

**19**

*Personality Disorders in Adolescents and Different Therapeutic Approaches*

will be explained in more detail than the last two therapies below.

optimism, consistency, empathy, and warmth contribute 30% to the success of a therapy. The adolescent's expectations of how successful the therapy will be contributing a further 15%. In addition, 15% is contributed by the specific psycho-

To achieve an optimal therapeutic process, regardless of the type of therapy, the therapist needs to be open, accepting, and optimistic and maintain a positive mental representation of the adolescent as well as curiosity and interest in getting to know the adolescent as a holistic personality, not only in the context of his or her disorder [16]. Since AIT is a younger and not so known therapy as MBT and DBT, it

Adolescent identity treatment (AIT) is an integrative therapeutic approach based on the principles of Paulina Kernberg, which includes modified elements of transference- focused psychotherapy, psychoeducation, behavior-oriented home plans, therapeutic contract, and intensive family work with adolescents and parents (adapted from [16]). Identity diffusion and interpersonal misfunctioning are regarded as the core of the borderline PD in adolescents and, as such, forming a base for the essential principles of AIT. The AIT focuses on identity stabilizing and integration of the concepts of the self and significant others, which gradually affects interpersonal relationships and leads to resolving interpersonal conflicts. The AIT applies verbal and nonverbal communication as well as countertransference. The basic principle of the AIT is to work on the dominant affect. The therapist focuses on the dominant affect the adolescent is affected by—here and now. Clarification,

confrontation, and interpretation are applied as therapeutic techniques.

in borderline patients. Examples of clarification:

• Please, could you explain that to me in detail?

• I did not understand…

thought about it?

• Did I get this right? You said…

• What did you mean by saying…?

and understand what the patient is saying. The adolescent's subjective feelings and perceptions are explored in detail until the therapist is able to understand exactly what the patient has in mind. Clarification is the therapist's invitation to the adolescent to explain information that is vague, not clear, confusing, chaotic, and contradictory. It allows the adolescent to fully access the internalized, unconscious meaning of his/her actions and encourages self-reflection. This method is of essential importance for borderline PD, as identity diffusion is strongly pronounced

• Is it because you do not have words to describe it, or because you have not

*Confrontation* is not a common therapeutic technique, especially not at the beginning of a therapy, as adolescents may feel attacked when it is used too soon. Confrontation is supposed to be an invitation to the adolescent to look at the inconsistencies and contradictions and to bring to attention information (verbal or nonverbal) he or she is not aware of or regards as completely normal. It is important

*Clarification* is the most common AIT therapeutic technique. It is used to explore

*DOI: http://dx.doi.org/10.5772/intechopen.93110*

**5. Adolescent identity treatment**

therapeutic techniques [17].

*Personality Disorders in Adolescents and Different Therapeutic Approaches DOI: http://dx.doi.org/10.5772/intechopen.93110*

optimism, consistency, empathy, and warmth contribute 30% to the success of a therapy. The adolescent's expectations of how successful the therapy will be contributing a further 15%. In addition, 15% is contributed by the specific psychotherapeutic techniques [17].

To achieve an optimal therapeutic process, regardless of the type of therapy, the therapist needs to be open, accepting, and optimistic and maintain a positive mental representation of the adolescent as well as curiosity and interest in getting to know the adolescent as a holistic personality, not only in the context of his or her disorder [16]. Since AIT is a younger and not so known therapy as MBT and DBT, it will be explained in more detail than the last two therapies below.

#### **5. Adolescent identity treatment**

*Neurological and Mental Disorders*

of age. According to ICD-10, a PD can be diagnosed regardless the age of person if the diagnostic criteria are met; however, this is exceptionally rare before the age 16 or 17 years [5]. This is even more clearly defined in ICD-11, where the diagnosis of

The DSM-5 allows for a diagnosis of PD in children and adolescents, when personality traits are particularly maladapted, permanent, and not related to a specific developmental period, mental disorder, or cultural background with the exception of antisocial PD, which cannot be diagnosed before the age of 18. For a diagnosis to be made, the characteristics of PD should have been present persistently for at least 1 year [4]. One should keep in mind that the characteristics of PD identified in childhood will change and that some types of PD will become less obvious or even disappear in later developmental periods (borderline, antisocial PD). The NICE recommendations do not define a chronological age at which a PD can be diagnosed.

Instead, they focus on the individual level of developmental maturity and an understandable therapeutic plan to be provided to the person diagnosed with PD [15]. However, PD should not be diagnosed in individuals under the age of 13 and is not applicable until an individual finishes puberty. Because PDs have long been considered as therapy resistant, this diagnosis is misused even today as an excuse to refuse a patient. When diagnosing a person with PD, especially if it is an adolescent, an appropriate treatment must be provided along with the diagnosis. Prevention,

PD is made whenever the diagnostic criteria are met [6].

early detection, and timely treatment are essential [15].

and increase emotional stability [15, 16].

**4. Personality disorders treatment in a development period**

There are many different psychotherapeutic approaches to treat

PD. Mentalization-based therapy (MBT), dialectical-behavioral therapy (DBT), and adolescent identity treatment (AIT) are among the most common. It is not so important which specific psychotherapeutic approach is used in the therapy but that certain changes outside the therapeutic relationship are triggered [13, 16]. According to Lambert, these changes are to be accountable for 40% of success in psychotherapy [17]. It is important to include the rest of the family in the therapy, to generate changes in the school, and that all significant others receive appropriate psychoeducation. Psychotherapeutic factors such as therapeutic posture, curiosity,

The purpose of diagnosing PD is to provide the adolescent with the appropriate treatment. It is the adolescent period that has a corrective potential and by introducing a therapy in time, we can significantly influence the course of PD. Adolescents with PD should be treated by a team of highly qualified professionals with a clearly structured intervention model and therapeutic plan [8, 13, 15]. Primarily, the patient must be provided with continuity and consistency. Adolescents with PD, especially borderline patients, have a tendency to form intense relationships; therefore, it is necessary to set clear time and space framework for treatments with different therapists. It is essential to organize treatments adequately—not too much and too little. Team members often have different views on the adolescent's problems and symptoms, which often lead to conflicts within the team; therefore, supervision is necessary. Often, many services (social services, school, general physician, previous therapist) are involved in the treatment; therefore, roles and tasks need to be clearly identified and coordinated. One of the main treatment goals of all team members is to support the adolescent in his separation and individualization and to actively involve him in the decision-making process. Many adolescents with borderline PD have experienced traumatic events; however, trauma processing is often not the primary intervention. Primarily, it is necessary to reduce suicidality

**18**

Adolescent identity treatment (AIT) is an integrative therapeutic approach based on the principles of Paulina Kernberg, which includes modified elements of transference- focused psychotherapy, psychoeducation, behavior-oriented home plans, therapeutic contract, and intensive family work with adolescents and parents (adapted from [16]). Identity diffusion and interpersonal misfunctioning are regarded as the core of the borderline PD in adolescents and, as such, forming a base for the essential principles of AIT. The AIT focuses on identity stabilizing and integration of the concepts of the self and significant others, which gradually affects interpersonal relationships and leads to resolving interpersonal conflicts. The AIT applies verbal and nonverbal communication as well as countertransference. The basic principle of the AIT is to work on the dominant affect. The therapist focuses on the dominant affect the adolescent is affected by—here and now. Clarification, confrontation, and interpretation are applied as therapeutic techniques.

*Clarification* is the most common AIT therapeutic technique. It is used to explore and understand what the patient is saying. The adolescent's subjective feelings and perceptions are explored in detail until the therapist is able to understand exactly what the patient has in mind. Clarification is the therapist's invitation to the adolescent to explain information that is vague, not clear, confusing, chaotic, and contradictory. It allows the adolescent to fully access the internalized, unconscious meaning of his/her actions and encourages self-reflection. This method is of essential importance for borderline PD, as identity diffusion is strongly pronounced in borderline patients. Examples of clarification:


*Confrontation* is not a common therapeutic technique, especially not at the beginning of a therapy, as adolescents may feel attacked when it is used too soon. Confrontation is supposed to be an invitation to the adolescent to look at the inconsistencies and contradictions and to bring to attention information (verbal or nonverbal) he or she is not aware of or regards as completely normal. It is important to use it as an encouragement to talk about auto- and hetero-aggressive thoughts and behaviors that interfere with therapy. Examples of confrontation are:


*Interpretation* helps the adolescent to self-reflect and explain the meaning of his/ her thoughts and actions. The interpretation does not reflect the therapist's point of view, who knows everything, but as a hypothesis offered to the adolescents for their consideration. It is applied when clarification and confrontation have not had the desired effect and when the therapist thinks it is unrealistic to expect the adolescent will reach a certain insight on his or her own. Interpretation must follow the emotions (anger, hatred, anxiety, envy). Examples of interpretation are:


Regardless of the psychotherapeutic approach, sincerity, empathy, and warmth are the key characteristics of a therapist. AIT, however, added playful flexibility to the list, with the therapist explaining his/her thoughts, offering possible explanations as a hypothesis (interpretation) and adjusting to the adolescent. The therapist maintains a sound and meaningful stance, knows right from wrong, and maintains his or her position. Optimism is a necessary condition for the therapist to develop an idea of the adolescent as a healthy and stable person, including therapist's attitude that the adolescent is able to cooperate in sessions and that he or she can develop. The therapist maintains hope for change during therapy stagnation and when the risk of discontinuation of therapy occurs. The absolute presence of the therapist is crucial for the therapy. It can be manifested as curiosity and a genuine interest in the adolescent's experiences. The therapist is absolutely present when his or her nonverbal/body language and tone of speech reflect the adolescent's experience of the here and now. The therapist is a role model. For an adolescent, therapist may be the first person to ever really take a truly interest in him or her. By doing so, the therapist engages the adolescent to be curious, motivated, and interested in himself/herself.

Body language is an important factor in AIT. Therapists must be fully aware of their tone, facial expressions, thinking, and interest, paying attention to the adolescent in the treatment, and how all of this is being acknowledged by the adolescent. Nonverbal information is vital in therapy with PD adolescents, who are overly sensitive to possible rejection, split, and are not able to recognize contradictions in verbal and nonverbal communication or are prone to misjudging it. It does matter how the therapist dresses and whether he/she has a piercing or a tattoo. The latter, in particular, can be an important message of how a therapist treats his/her body or allows for various manipulations.

**21**

*Personality Disorders in Adolescents and Different Therapeutic Approaches*

Intensive parental involvement in therapy is especially important in adolescents with PD and is therefore a crucial element of AIT. Working with parents can only be successful if there is no attribution of blame to the parents for the development of PD in their adolescent. If the parents are viewed as the "bad guys," then the therapist may cause the adolescent to see him/her as a "better parent" and a "savior," which brings many risks to the therapy. At the beginning of therapy, even very competent and functional parents can appear to be "pathological" due to psychological

It is important that the parents are not viewed as bad and invalidating by the therapist. If parents are not included in the therapy, the power of family dynamics and interactions significantly shaping the adolescent is being underestimated. It is essential to educate parents on the adolescent's heightened sensitivity to emotional stressors, such as criticism, rejection, and separation, and how stressors can be avoided or reduced. Parents need an explanation that the therapy will not change the adolescent's temperament; however, it will help him to control it more easily.

Therefore, *a contract with the parents* is delineated as well, which covers all issues

A home plan involves clearly agreed responsibilities of both the adolescent and parents. This includes clear measures for self-injurious behavior such as addressing the wound without any additional comments, threats, rewards, or conversation; the adolescent will discuss this with his/her therapist at the next regular session. If the wounds are deep, the adolescent should be taken to see a surgeon. Behaviors that violate the home plan resulting in the revocation of privileges are agreed upon and set out in the contract, including a reward system for behavior if the adolescent

Mentalization-based therapy is a psychosocial therapy to treat borderline PD (adapted from [18]). It derives from psychoanalysis, attachment theory, and developmental psychopathology and is based on mentalization. It was first intended for the treatment of adults with borderline PD, later on a version for adolescents (MBT-A) was developed. Mentalization is the ability to understand our own mental states and the mental states of other people and represents the capacity that makes us human. We mentalize when we are aware of the mental states of others and ourselves. MBT is based on the assumption that instability in mentalization is a

described above. The goal of the contract is to optimize the family's potential in therapy and to record the expectations and limitations of therapy. Possible factors that could lead to discontinuation of therapy are also included in the contract. The contract contains previously agreed and expected changes in the family (and not just in the adolescent) and clear rules regarding suicidal and self-harming behavior. At the beginning of therapy, a *treatment contract with the adolescent* is drawn up with the adolescent and therapist responsibilities. The adolescent undertakes to attend therapy regularly, that is, 25 weekly sessions, to arrive "clean" and not to use any psychoactive substances before therapy, to talk about important issues (e.g., self-harming) at the very beginning of each therapy and not at the end of therapy. The contract also includes the duties of the therapist and exceptions to confidentiality (such as severe abuse of psychoactive substances, suicide, pregnancy), support for the patient not to discontinue therapy (external superego; e.g., the therapist calls the adolescent 2 hours prior to the therapy and reminds him or her of the appointment), and clear rules of a therapist conduct in case of suicidal and/or self-harming

*DOI: http://dx.doi.org/10.5772/intechopen.93110*

burden when living with an adolescent with PD.

Their job is to encourage the adolescent to go to therapy.

behavior (to call parents, hospitalization).

sticks to the home plan.

**6. Mentalization-based therapy**

#### *Personality Disorders in Adolescents and Different Therapeutic Approaches DOI: http://dx.doi.org/10.5772/intechopen.93110*

*Neurological and Mental Disorders*

Can you explain this?

wounds on your arm.

to use it as an encouragement to talk about auto- and hetero-aggressive thoughts and behaviors that interfere with therapy. Examples of confrontation are:

• You are telling me about a rather excruciating pain, but you are laughing at the same time. This does not fit. Do you have any idea what could this mean?

• You are saying that you are fine, but I see fresh cuts. How do these things fit?

• You are telling me you are not disappointed, yet you are struggling with tears.

*Interpretation* helps the adolescent to self-reflect and explain the meaning of his/ her thoughts and actions. The interpretation does not reflect the therapist's point of view, who knows everything, but as a hypothesis offered to the adolescents for their consideration. It is applied when clarification and confrontation have not had the desired effect and when the therapist thinks it is unrealistic to expect the adolescent will reach a certain insight on his or her own. Interpretation must follow the emo-

• On the one hand, you are telling me that you are fine, but I see many fresh

• Could it be that all these contradictory images are within you and that you do not know exactly whether you are feeling well or maybe you are still sad?

Regardless of the psychotherapeutic approach, sincerity, empathy, and warmth are the key characteristics of a therapist. AIT, however, added playful flexibility to the list, with the therapist explaining his/her thoughts, offering possible explanations as a hypothesis (interpretation) and adjusting to the adolescent. The therapist maintains a sound and meaningful stance, knows right from wrong, and maintains his or her position. Optimism is a necessary condition for the therapist to develop an idea of the adolescent as a healthy and stable person, including therapist's attitude that the adolescent is able to cooperate in sessions and that he or she can develop. The therapist maintains hope for change during therapy stagnation and when the risk of discontinuation of therapy occurs. The absolute presence of the therapist is crucial for the therapy. It can be manifested as curiosity and a genuine interest in the adolescent's experiences. The therapist is absolutely present when his or her nonverbal/body language and tone of speech reflect the adolescent's experience of the here and now. The therapist is a role model. For an adolescent, therapist may be the first person to ever really take a truly interest in him or her. By doing so, the therapist engages the adolescent to be curious, motivated, and interested in himself/herself. Body language is an important factor in AIT. Therapists must be fully aware of their tone, facial expressions, thinking, and interest, paying attention to the adolescent in the treatment, and how all of this is being acknowledged by the adolescent. Nonverbal information is vital in therapy with PD adolescents, who are overly sensitive to possible rejection, split, and are not able to recognize contradictions in verbal and nonverbal communication or are prone to misjudging it. It does matter how the therapist dresses and whether he/she has a piercing or a tattoo. The latter, in particular, can be an important message of how a therapist treats his/her body or

tions (anger, hatred, anxiety, envy). Examples of interpretation are:

• Then you tell me that no one would be sad if you killed yourself.

• This is how I see it, but correct me, if I am wrong.

**20**

allows for various manipulations.

Intensive parental involvement in therapy is especially important in adolescents with PD and is therefore a crucial element of AIT. Working with parents can only be successful if there is no attribution of blame to the parents for the development of PD in their adolescent. If the parents are viewed as the "bad guys," then the therapist may cause the adolescent to see him/her as a "better parent" and a "savior," which brings many risks to the therapy. At the beginning of therapy, even very competent and functional parents can appear to be "pathological" due to psychological burden when living with an adolescent with PD.

It is important that the parents are not viewed as bad and invalidating by the therapist. If parents are not included in the therapy, the power of family dynamics and interactions significantly shaping the adolescent is being underestimated. It is essential to educate parents on the adolescent's heightened sensitivity to emotional stressors, such as criticism, rejection, and separation, and how stressors can be avoided or reduced. Parents need an explanation that the therapy will not change the adolescent's temperament; however, it will help him to control it more easily. Their job is to encourage the adolescent to go to therapy.

Therefore, *a contract with the parents* is delineated as well, which covers all issues described above. The goal of the contract is to optimize the family's potential in therapy and to record the expectations and limitations of therapy. Possible factors that could lead to discontinuation of therapy are also included in the contract. The contract contains previously agreed and expected changes in the family (and not just in the adolescent) and clear rules regarding suicidal and self-harming behavior.

At the beginning of therapy, a *treatment contract with the adolescent* is drawn up with the adolescent and therapist responsibilities. The adolescent undertakes to attend therapy regularly, that is, 25 weekly sessions, to arrive "clean" and not to use any psychoactive substances before therapy, to talk about important issues (e.g., self-harming) at the very beginning of each therapy and not at the end of therapy. The contract also includes the duties of the therapist and exceptions to confidentiality (such as severe abuse of psychoactive substances, suicide, pregnancy), support for the patient not to discontinue therapy (external superego; e.g., the therapist calls the adolescent 2 hours prior to the therapy and reminds him or her of the appointment), and clear rules of a therapist conduct in case of suicidal and/or self-harming behavior (to call parents, hospitalization).

A home plan involves clearly agreed responsibilities of both the adolescent and parents. This includes clear measures for self-injurious behavior such as addressing the wound without any additional comments, threats, rewards, or conversation; the adolescent will discuss this with his/her therapist at the next regular session. If the wounds are deep, the adolescent should be taken to see a surgeon. Behaviors that violate the home plan resulting in the revocation of privileges are agreed upon and set out in the contract, including a reward system for behavior if the adolescent sticks to the home plan.

#### **6. Mentalization-based therapy**

Mentalization-based therapy is a psychosocial therapy to treat borderline PD (adapted from [18]). It derives from psychoanalysis, attachment theory, and developmental psychopathology and is based on mentalization. It was first intended for the treatment of adults with borderline PD, later on a version for adolescents (MBT-A) was developed. Mentalization is the ability to understand our own mental states and the mental states of other people and represents the capacity that makes us human. We mentalize when we are aware of the mental states of others and ourselves. MBT is based on the assumption that instability in mentalization is a

key problem of borderline PD. Similar to AIT, the therapist takes the position of a curious listener, who does not know what is going on and therefore encourages the adolescent to explain. The therapist observes the capacity for attachment and mentalization and applies various interventions to improve or at least maintain the adolescent's capacity to mentalize.

#### **7. Dialectical behavioral therapy**

Dialectical behavioral therapy was developed by the psychologist Marsha M. Linehan and colleagues in the late 1980s to treat borderline PD [19]. Later on, Rathus and Miller developed a version of DBT for adolescents (DBT-A) [20].

The DBT is based on cognitive-behavioral therapy, dialectical philosophy, and on the findings of M. Linehan that people with borderline PD are prone to more intense and dramatic responses when facing specific emotional situations (e.g., romantic, friendly, and family relationships) compared to people without PD. People with borderline PD have quick and strong emotional reactions in the situations described above, remain emotionally aroused, and require more time to calm down than people without borderline PD [19]. As a result, DBT does not focus on the core unconscious conflict, such as in MBT. Instead, it focuses on how to change problematic responses with a range of different behavioral strategies [21].

DBT-A is a 16-week treatment that includes individual adolescent therapy once a week, family therapy as required, and a skills training group for families of adolescents with borderline PD [22]. It is aimed at reducing life-threatening and undesirable behaviors in therapy and behaviors that impair the quality of life. It empowers the adolescents to regulate their emotions, to appropriately deal with interpersonal relationships and cope with stress, and encourages mindfulness [20].

#### **8. Pharmacotherapy**

The 2001 American Psychiatric Association recommendations [23], the 2009 NICE guidelines [15], which were reaffirmed in 2018 [24], and the Australian NHMRC guidelines for the treatment of borderline PD [25] do not recommend the use of pharmacotherapy as the first-line therapy. The World Federation of Societies of Biological Psychiatry recommendations mentions several studies reporting the efficacy of serotonin reuptake inhibitors (SSRIs), such as fluoxetine and fluvoxamine and second-generation antipsychotics in the treatment of PD [26].

The 2019 Timaus et al. study confirms clinical observations that most patients with PD are also treated pharmacotherapeutically [27]. Polypharmacy is high, which can also be attributed to the great comorbidity of PD with at least one additional mental disorder. For the most part, tricyclics, first-generation antipsychotics, and mood stabilizers are being omitted in the pharmacotherapy of PD. The mood stabilizer lamotrigine did not prove to be successful in the treatment of PD in a 2018 study [28]. The use of the atypical antipsychotic quetiapine and the opioid antagonist naltrexone has been increasing [27]. However, more studies are required to support the justification for using these medicines.

#### **9. Conclusions**

Prevention and early detection of PD are essential in order to prevent long-lasting effect of PD on adolescent's overall functioning and interpersonal relationships.

**23**

**Author details**

Slovenia

Hojka Gregoric Kumperscak1,2

provided the original work is properly cited.

1 Child and Adolescent Psychiatry Unit, University Medical Centre, Maribor,

© 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,

2 Faculty of Medicine, University of Maribor, Maribor, Slovenia

\*Address all correspondence to: hojka.gregoric@guest.arnes.si

*Personality Disorders in Adolescents and Different Therapeutic Approaches*

When diagnosing a PD in adolescence, we are obliged to provide an appropriate and a PD specialized treatment (AIT, DBT-A, MBT-A). By introducing a therapy in time and by a licensed therapist PD treatment is very effective especially in the adolescent

This work was part of a Slovenian Research Agency project J4-9434.

*DOI: http://dx.doi.org/10.5772/intechopen.93110*

period which has a strong corrective potential.

**Acknowledgements**

#### *Personality Disorders in Adolescents and Different Therapeutic Approaches DOI: http://dx.doi.org/10.5772/intechopen.93110*

When diagnosing a PD in adolescence, we are obliged to provide an appropriate and a PD specialized treatment (AIT, DBT-A, MBT-A). By introducing a therapy in time and by a licensed therapist PD treatment is very effective especially in the adolescent period which has a strong corrective potential.

## **Acknowledgements**

*Neurological and Mental Disorders*

adolescent's capacity to mentalize.

**7. Dialectical behavioral therapy**

with a range of different behavioral strategies [21].

to support the justification for using these medicines.

**8. Pharmacotherapy**

key problem of borderline PD. Similar to AIT, the therapist takes the position of a curious listener, who does not know what is going on and therefore encourages the adolescent to explain. The therapist observes the capacity for attachment and mentalization and applies various interventions to improve or at least maintain the

Dialectical behavioral therapy was developed by the psychologist Marsha M. Linehan and colleagues in the late 1980s to treat borderline PD [19]. Later on, Rathus and Miller developed a version of DBT for adolescents (DBT-A) [20].

The DBT is based on cognitive-behavioral therapy, dialectical philosophy, and on the findings of M. Linehan that people with borderline PD are prone to more intense and dramatic responses when facing specific emotional situations (e.g., romantic, friendly, and family relationships) compared to people without PD. People with borderline PD have quick and strong emotional reactions in the situations described above, remain emotionally aroused, and require more time to calm down than people without borderline PD [19]. As a result, DBT does not focus on the core unconscious conflict, such as in MBT. Instead, it focuses on how to change problematic responses

DBT-A is a 16-week treatment that includes individual adolescent therapy once a week, family therapy as required, and a skills training group for families of adolescents with borderline PD [22]. It is aimed at reducing life-threatening and undesirable behaviors in therapy and behaviors that impair the quality of life. It empowers the adolescents to regulate their emotions, to appropriately deal with interpersonal

The 2001 American Psychiatric Association recommendations [23], the 2009 NICE guidelines [15], which were reaffirmed in 2018 [24], and the Australian NHMRC guidelines for the treatment of borderline PD [25] do not recommend the use of pharmacotherapy as the first-line therapy. The World Federation of Societies of Biological Psychiatry recommendations mentions several studies reporting the efficacy of serotonin reuptake inhibitors (SSRIs), such as fluoxetine and fluvoxamine and second-generation antipsychotics in the treatment of PD [26].

The 2019 Timaus et al. study confirms clinical observations that most patients with PD are also treated pharmacotherapeutically [27]. Polypharmacy is high, which can also be attributed to the great comorbidity of PD with at least one additional mental disorder. For the most part, tricyclics, first-generation antipsychotics, and mood stabilizers are being omitted in the pharmacotherapy of PD. The mood stabilizer lamotrigine did not prove to be successful in the treatment of PD in a 2018 study [28]. The use of the atypical antipsychotic quetiapine and the opioid antagonist naltrexone has been increasing [27]. However, more studies are required

Prevention and early detection of PD are essential in order to prevent long-lasting

effect of PD on adolescent's overall functioning and interpersonal relationships.

relationships and cope with stress, and encourages mindfulness [20].

**22**

**9. Conclusions**

This work was part of a Slovenian Research Agency project J4-9434.

## **Author details**

Hojka Gregoric Kumperscak1,2

1 Child and Adolescent Psychiatry Unit, University Medical Centre, Maribor, Slovenia

2 Faculty of Medicine, University of Maribor, Maribor, Slovenia

\*Address all correspondence to: hojka.gregoric@guest.arnes.si

© 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.

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[26] Herpertz SC, Zanarini M,

Schulz CS, Siever L, Lieb K, Möller HJ. WFSBP task force on personality disorders; world Federation of Societies of biological psychiatry (WFSBP). WFSBP guidelines for biological treatment of personality disorders. The World Journal of Biological Psychiatry.

[27] Timäus C, Meiser M, Bandelow B, et al. Pharmacotherapy of borderline personality disorder: What has changed over two decades? A retrospective evaluation of clinical practice. BMC Psychiatry. 2019;**19**:393. DOI: 10.1186/

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*DOI: http://dx.doi.org/10.5772/intechopen.93110*

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[19] Linehan MM, Armstrong HE, Suarez A, Allmon D, Heard HL. Cognitive-behavioral treatment of chronically parasuicidal borderline patients. Archives of General Psychiatry.

[20] Rathus JH, Miller AL. Dialectical behavior therapy adapted for suicidal adolescents. Suicide & Life-Threatening

Behavior. 2002;**32**:146-157. DOI: 10.1521/suli.32.2.146.24399

[21] Swenson CR, Choi-Kain LW. Mentalization and dialectical

behavior therapy. American Journal of Psychotherapy. 2015;**69**(2):199-217

[22] Fleischhaker C, Böhme R, Sixt B, Brück C, Schneider C, Schulz E. Dialectical behavioral therapy for adolescents (DBT-A): A clinical trial for patients with suicidal and self-injurious behavior and borderline symptoms with a one-year follow-up. Child and Adolescent Psychiatry and Mental

[23] American Psychiatric Association. Practice guideline for the treatment of patients with borderline personality disorder. The American Journal of

1992. pp. 94-129

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Health. 2011;**5**(1):3

Psychiatry. 2001;**158**:1-52

[24] National institute for health and care excellence. Surveillance of personality disorders (NICE

2018. Available from: https:// www.nice.org.uk/guidance/cg78/ resources/2018-surveillance-of personality-disorders-nice-guidelinescg77-and-cg78-pdf-6358811143669

[Accessed: 08 March 2020]

guidelines CG77 and CG78) [Internet].

*Personality Disorders in Adolescents and Different Therapeutic Approaches DOI: http://dx.doi.org/10.5772/intechopen.93110*

Integration. New York: Basic Books; 1992. pp. 94-129

[18] Fonagy P, Gergeley G, Jurist E, Target M, editors. Affect Regulation, Mentalization, and the Development of the Self. New York: Other Press; 2002

[19] Linehan MM, Armstrong HE, Suarez A, Allmon D, Heard HL. Cognitive-behavioral treatment of chronically parasuicidal borderline patients. Archives of General Psychiatry. 1991;**48**:1060-1064

[20] Rathus JH, Miller AL. Dialectical behavior therapy adapted for suicidal adolescents. Suicide & Life-Threatening Behavior. 2002;**32**:146-157. DOI: 10.1521/suli.32.2.146.24399

[21] Swenson CR, Choi-Kain LW. Mentalization and dialectical behavior therapy. American Journal of Psychotherapy. 2015;**69**(2):199-217

[22] Fleischhaker C, Böhme R, Sixt B, Brück C, Schneider C, Schulz E. Dialectical behavioral therapy for adolescents (DBT-A): A clinical trial for patients with suicidal and self-injurious behavior and borderline symptoms with a one-year follow-up. Child and Adolescent Psychiatry and Mental Health. 2011;**5**(1):3

[23] American Psychiatric Association. Practice guideline for the treatment of patients with borderline personality disorder. The American Journal of Psychiatry. 2001;**158**:1-52

[24] National institute for health and care excellence. Surveillance of personality disorders (NICE guidelines CG77 and CG78) [Internet]. 2018. Available from: https:// www.nice.org.uk/guidance/cg78/ resources/2018-surveillance-of personality-disorders-nice-guidelinescg77-and-cg78-pdf-6358811143669 [Accessed: 08 March 2020]

[25] National Health and Medical Research Council. Clinical practice guideline for the management of borderline personality disorder – Appendix H [Internet]. 2012. Available from: https://www.nhmrc.gov.au/ sites/default/files/documents/reports/ clinical%20guidelines/mh25c-bpdappendix-h.pdf [Accessed: 08 March 2020]

[26] Herpertz SC, Zanarini M, Schulz CS, Siever L, Lieb K, Möller HJ. WFSBP task force on personality disorders; world Federation of Societies of biological psychiatry (WFSBP). WFSBP guidelines for biological treatment of personality disorders. The World Journal of Biological Psychiatry. 2007;**8**:212-244

[27] Timäus C, Meiser M, Bandelow B, et al. Pharmacotherapy of borderline personality disorder: What has changed over two decades? A retrospective evaluation of clinical practice. BMC Psychiatry. 2019;**19**:393. DOI: 10.1186/ s12888-019-2377-z

[28] Crawford MJ, Sanatinia R, Barrett B, Cunningham G, Dale O, Ganguli P, et al. The clinical effectiveness and cost-effectiveness of Lamotrigine in borderline personality disorder: A randomized placebocontrolled trial. The American Journal of Psychiatry. 2018;**175**(8):756-764

**24**

*Neurological and Mental Disorders*

[1] Pregelj P, Kores-Plesnicar B, Tomori M, Zalar B, Ziherl S, editors. Psychiatry. Ljubljana: Psihiatricna

[3] Musek J, editor. Personality, Values and Psychological Well-Being. Ljubljana: University of Ljubljana,

[5] World health organization.

[6] World health organization.

[7] Bach B, First MB. Application of the ICD-11 classification of

s12888-018-1908-3

personality disorders. BMC Psychiatry. 2018;**18**(351):1-14. DOI: 10.1186/

[8] Friedel RO. Borderline personality disorder demystified [Internet]. 2018. Available from: http://www. bpddemystified.com/overview/ [Accessed: 08 March 2020]

International classification of diseases for mortality and morbidity statistics (11th Revision) [Internet]. 2018. Available from: https://icd.who.int/ browse11/l-m/en [Accessed: 08 March

Classification of mental and behavioural disorders (ICD-10) [Internet]. 1993. Available from: https://www.who.int/ classifications/icd/en/GRNBOOK. pdf?ua=1 [Accessed: 08 March 2020]

[4] American psychiatric association. Diagnostic and Statistical Manual of Mental Disorders 5 (DSM – 5) [Internet]. 2013. Available from: https:// www.psychiatry.org/psychiatrists/ practice/dsm [Accessed: 08 March

Philosophic Faculty; 2015

[2] Rothbart M, Ahadi SA, Hershley KL, Fisher P. Investigations of temperament at three to seven years: The children's behaviour questionnaire. Child Development. 2001;**72**:1394-1408

[9] Steinert T, Schmidt-Michel PO. Borderlinestorungen und schizophrenie.

Der Nervenarzt. 1995;**66**:858-863

[10] Volkan VD, Ast G, editors. Eine Borderline-therapie. Gottingen: Vandenbboeck & Ruprecht; 1996

[11] Caran N. Borderline Case. Naučna

[12] Linehan MM, Tutek DA, Heard HL, Armstrong HE. Interpersonal outcome of cognitive behavioral treatment for chronically suicidal borderline patients. The American Journal of Psychiatry.

knjiga: Beograd; 1983

1994;**151**:1771-1776

1982;**32**(1):9-27

[13] Nagy Zunter AM, Stamos V,

[14] Bennett Roth E. Six types of borderline and narcissistic patients: An initial typology. International Journal of Group Psychotherapy.

[15] National collaborating centre for mental health, British psychological society. Borderline personality disorder: treatment and management. National clinical practice guidelines Number 78 [Internet]. 2009. Available from: https://www.nice.org.uk/guidance/cg78/ evidence/bpd-full-guideline-242147197

[Accessed: 08 March 2020]

[16] Foelsch PA, Schlüter-Müller S, Odom AE, Arena HT, Borzutzky HA, Schmeck K, editors. Adolescent

New York, Dordrecht, London:

[17] Lambert MJ. Psychotherapy outcome research: Implications for integrative and eclectic therapists. In: Norcross JC, Goldfried MR, editors. Handbook of Psychotherapy

Springer; 2014

Identity Treatment. Cham, Heidelberg,

Jogan H, editors. Borderline Personality Disorder. Pozeg: Tiskarna Grafis; 1999

klinika; 2013

**References**

2020]

2020]

**27**

**Chapter 3**

**Abstract**

Neurofeedback Training on

*Valeska Kouzak Campos da Paz and Carlos Tomaz*

Cognitive Reserve

SMR protocol, prefrontal cortex

**1. Introduction**

memory [2].

Aging: Prospects on Maintaining

Neurofeedback is a neuromodulation technique based on a brain-computer interface. An individual receives feedback from a computer about their brain activity and is conditioned to improve performance according to a training target. Therefore, it may be used to help individuals who suffer from cognitive decline, which is predicted to occur during aging. Cognitive decline affects working memory, which involves the medial temporal lobe—an important area for temporarily storing information—and recruits the prefrontal cortex, an area associated with higher cognitive functions, such as executive function. Since memory and executive function are fundamental components for every healthy and independent human life, cognitive decline fundamentally impairs a person's well-being. As such, since the aging population has been increasing at higher rates, methods to enhance their cognitive performance have become increasingly important. These methods may be used to increase brain reserve and help the elderly maintain a socially active life. The purpose of this chapter is to add neurofeedback to the box of promising tools that

maintain cognitive reserve and as such promote a healthy and active life.

**Keywords:** neurofeedback, memory storage, executive function, brain reserve,

Across a life span, changes in cognition are expected to occur as individuals grow older. Most of the changes experienced in aging are related to a decline in fluid intelligence, defined as the capacity to solve problems and articulate ideas, to navigate new situations, and to acquire knowledge. On the other hand, crystallized intelligence, defined as acquired general knowledge (e.g., vocabulary and procedures), is preserved for longer periods [1]. Moreover, during aging, other neuropsychological abilities are known to decline, such as attention, working memory, and episodic

Some faculties related to crystalized intelligence might increase over time, such as general knowledge and wisdom [2]. And this amount of additional information, when integrated to crystalized intelligence, can become an advantage. On the other hand, the attentional and working memory decline, related to fluid intelligence,

Image studies have shown atrophy in white matter and gray matter, synaptic degeneration, blood flow reduction, and neurochemical alterations [3].

makes it more challenging to solve problems and articulate ideas.

#### **Chapter 3**

## Neurofeedback Training on Aging: Prospects on Maintaining Cognitive Reserve

*Valeska Kouzak Campos da Paz and Carlos Tomaz*

#### **Abstract**

Neurofeedback is a neuromodulation technique based on a brain-computer interface. An individual receives feedback from a computer about their brain activity and is conditioned to improve performance according to a training target. Therefore, it may be used to help individuals who suffer from cognitive decline, which is predicted to occur during aging. Cognitive decline affects working memory, which involves the medial temporal lobe—an important area for temporarily storing information—and recruits the prefrontal cortex, an area associated with higher cognitive functions, such as executive function. Since memory and executive function are fundamental components for every healthy and independent human life, cognitive decline fundamentally impairs a person's well-being. As such, since the aging population has been increasing at higher rates, methods to enhance their cognitive performance have become increasingly important. These methods may be used to increase brain reserve and help the elderly maintain a socially active life. The purpose of this chapter is to add neurofeedback to the box of promising tools that maintain cognitive reserve and as such promote a healthy and active life.

**Keywords:** neurofeedback, memory storage, executive function, brain reserve, SMR protocol, prefrontal cortex

#### **1. Introduction**

Across a life span, changes in cognition are expected to occur as individuals grow older. Most of the changes experienced in aging are related to a decline in fluid intelligence, defined as the capacity to solve problems and articulate ideas, to navigate new situations, and to acquire knowledge. On the other hand, crystallized intelligence, defined as acquired general knowledge (e.g., vocabulary and procedures), is preserved for longer periods [1]. Moreover, during aging, other neuropsychological abilities are known to decline, such as attention, working memory, and episodic memory [2].

Some faculties related to crystalized intelligence might increase over time, such as general knowledge and wisdom [2]. And this amount of additional information, when integrated to crystalized intelligence, can become an advantage. On the other hand, the attentional and working memory decline, related to fluid intelligence, makes it more challenging to solve problems and articulate ideas.

Image studies have shown atrophy in white matter and gray matter, synaptic degeneration, blood flow reduction, and neurochemical alterations [3]. Those changes are more prominent at the prefrontal cortex; however, older adults that maintain their performance on pair with young adults tend to increase activation in order to keep performance, and this increased activation creates more hemispheric asymmetry in elderly than in youth. Consequently, Cabeza et al. [3] proposed a model called hemispheric asymmetry reduction in older adults (HAROLD), in which an older adult tends to compensate the neuropsychological decline with higher activation at the frontal cortex.

Cognitive training with the intent of increasing abilities and enriching neural networks has been a tendency since the 1960s, when the first behavior protocols sought to train memory using strategies of "chunking" (grouping information bits to be stored as single concepts) and using metacognitive strategies for dealing with complex information. Those strategies to enhance memory capacity were based in conscious and external mechanisms [4].

In the late 1980s, Baltes et al. [1] have demonstrated that older adults may benefit from cognitive training by creating reserve and increasing their performance in cognitive tasks. Afterward, many studies and protocols have been developed to provide cognitive training for the aging population. Some of them are related to strategy making, where the individual has to identify a difficulty level and naturally self-adjust. Reasoning, problem-solving, and goal management also have been used to enhance cognition. Multimodal approaches have also been tried, in which an unrelated task is trained in order to provide skill transfer (e.g., video games or cardiovascular exercise). Lastly, there is the process training, which includes a set of cognitive tasks to be trained heavily and specifically [5].

Recent technological developments have supported new forms of training, nowadays using tools such as computer games to enhance cognitive capacity [6]. Therefore, cognitive training has increasingly become a potential tool to aid healthy individuals with cognitive aging and patients with cognitive decline.

Training working memory—a component of the executive function—is one of the tendencies to enhance cognition and enrich neural networks [7], especially to form cognitive and neuronal reserve in aging people. Most of working memory training is based on computer game protocols, such as Cogmed [4], that might transfer the skill learned to other tasks [5, 8, 9].

Therefore, generally, executive function is trained by two interventional models: behavioral and neuroscientific. The behavioral model focuses on one's acquired ability and trains executive function using computational tasks, with diverse protocols; the neuroscientific model by neuromodulation uses neurofeedback training or neuronal direct stimulation—direct current or magnetic current [10].

Transcranial direct current stimulation (TDCS) is a form of noninvasive neuromodulation based on a small current applied by two electrodes positioned in the scalp in order to create neuronal membrane excitability and enhance neuronal firing. Transcranial magnetic stimulation (TMS) is also noninvasive neuromodulation but instead based on a magnetic field applied to the scalp focused at target areas to create a neuronal action potential to induce firing. Both models provide neuroplasticity at the area applied and, consequently, benefit cognition [10].

#### **2. Working memory model**

Working memory is a neuropsychological function that allow us to deal with daily information, such as keeping in mind a telephone number while dialing, organizing the mental operations to accomplish a task in hands, or listening and remembering a sequence of facts in a story in order to understand it.

**29**

**Figure 1.**

*Working memory model developed by Baddeley and Hitch [12].*

*Neurofeedback Training on Aging: Prospects on Maintaining Cognitive Reserve*

humans, require a complex cognitive model and several brain areas.

four components, one attentional and three mnemonic (**Figure 1**).

Working memory can be described as a multimodal system, and Baddeley [11] defines it as a system of temporary storage under attentional control, encompassing our ability for complex thought and comprising diverse neuropsychological constructs. The abilities which working memory allows, although natural to most

For about 50 years, working memory has been studied to define its main proper-

ties. The model adopted in this chapter is based on a construct of Baddeley and Hitch [12], in which working memory orchestrates information received through

According to the Baddeley and Hitch model [12], the first component of the working memory is the central executive: an attentional control system that is connected to other three storage systems—the phonological loop, visuospatial sketchpad, and the episodic buffer. The episodic buffer component was included posteriorly [13] and all the components work interconnectedly. Further, each

Briefly stating, the phonological loop is able to temporarily keep linguistic expression (e.g., verbal and emotional) and acoustic information, and the visuospatial sketchpad works similarly to the phonological loop, but only for visual and spatial information. Then, the episodic buffer acts as a mechanism that connects perceptual information from the two subsystems to long-term memory, integrating information into a limited number of episodes [11, 15]. Besides that, the phonological loop and the visuospatial sketchpad are considered two slave subsystems of the central executive, a system that accesses long-term memory information by atten-

The central executive is responsible to keep information in mind while complet-

ing a task. Its proposed mechanism is based in frontal lobe patient studies that provided evidence from the connection between the supervisory attentional system (SAS), developed by Norman and Shallice [11], and the central executive [16]. Therefore, according to Baddeley [11], there are four candidates to compound the executive processes: the ability to focus attention, divide attention, change attention, and secure the connection between working memory and long-term memory. The episodic buffer, completing this model of working memory, is responsible for temporary storage of perceptual information from both the phonological loop and visuospatial sketchpad, combining the information to form long-term memory

*DOI: http://dx.doi.org/10.5772/intechopen.90847*

system is limited in capacity [14].

tional control [14, 15].

#### *Neurofeedback Training on Aging: Prospects on Maintaining Cognitive Reserve DOI: http://dx.doi.org/10.5772/intechopen.90847*

Working memory can be described as a multimodal system, and Baddeley [11] defines it as a system of temporary storage under attentional control, encompassing our ability for complex thought and comprising diverse neuropsychological constructs. The abilities which working memory allows, although natural to most humans, require a complex cognitive model and several brain areas.

For about 50 years, working memory has been studied to define its main properties. The model adopted in this chapter is based on a construct of Baddeley and Hitch [12], in which working memory orchestrates information received through four components, one attentional and three mnemonic (**Figure 1**).

According to the Baddeley and Hitch model [12], the first component of the working memory is the central executive: an attentional control system that is connected to other three storage systems—the phonological loop, visuospatial sketchpad, and the episodic buffer. The episodic buffer component was included posteriorly [13] and all the components work interconnectedly. Further, each system is limited in capacity [14].

Briefly stating, the phonological loop is able to temporarily keep linguistic expression (e.g., verbal and emotional) and acoustic information, and the visuospatial sketchpad works similarly to the phonological loop, but only for visual and spatial information. Then, the episodic buffer acts as a mechanism that connects perceptual information from the two subsystems to long-term memory, integrating information into a limited number of episodes [11, 15]. Besides that, the phonological loop and the visuospatial sketchpad are considered two slave subsystems of the central executive, a system that accesses long-term memory information by attentional control [14, 15].

The central executive is responsible to keep information in mind while completing a task. Its proposed mechanism is based in frontal lobe patient studies that provided evidence from the connection between the supervisory attentional system (SAS), developed by Norman and Shallice [11], and the central executive [16]. Therefore, according to Baddeley [11], there are four candidates to compound the executive processes: the ability to focus attention, divide attention, change attention, and secure the connection between working memory and long-term memory.

The episodic buffer, completing this model of working memory, is responsible for temporary storage of perceptual information from both the phonological loop and visuospatial sketchpad, combining the information to form long-term memory

**Figure 1.** *Working memory model developed by Baddeley and Hitch [12].*

*Neurological and Mental Disorders*

decline with higher activation at the frontal cortex.

cognitive tasks to be trained heavily and specifically [5].

transfer the skill learned to other tasks [5, 8, 9].

**2. Working memory model**

individuals with cognitive aging and patients with cognitive decline.

neuronal direct stimulation—direct current or magnetic current [10].

ticity at the area applied and, consequently, benefit cognition [10].

remembering a sequence of facts in a story in order to understand it.

conscious and external mechanisms [4].

Those changes are more prominent at the prefrontal cortex; however, older adults that maintain their performance on pair with young adults tend to increase activation in order to keep performance, and this increased activation creates more hemispheric asymmetry in elderly than in youth. Consequently, Cabeza et al. [3] proposed a model called hemispheric asymmetry reduction in older adults (HAROLD), in which an older adult tends to compensate the neuropsychological

Cognitive training with the intent of increasing abilities and enriching neural networks has been a tendency since the 1960s, when the first behavior protocols sought to train memory using strategies of "chunking" (grouping information bits to be stored as single concepts) and using metacognitive strategies for dealing with complex information. Those strategies to enhance memory capacity were based in

In the late 1980s, Baltes et al. [1] have demonstrated that older adults may benefit from cognitive training by creating reserve and increasing their performance in cognitive tasks. Afterward, many studies and protocols have been developed to provide cognitive training for the aging population. Some of them are related to strategy making, where the individual has to identify a difficulty level and naturally self-adjust. Reasoning, problem-solving, and goal management also have been used to enhance cognition. Multimodal approaches have also been tried, in which an unrelated task is trained in order to provide skill transfer (e.g., video games or cardiovascular exercise). Lastly, there is the process training, which includes a set of

Recent technological developments have supported new forms of training, nowadays using tools such as computer games to enhance cognitive capacity [6]. Therefore, cognitive training has increasingly become a potential tool to aid healthy

Training working memory—a component of the executive function—is one of the tendencies to enhance cognition and enrich neural networks [7], especially to form cognitive and neuronal reserve in aging people. Most of working memory training is based on computer game protocols, such as Cogmed [4], that might

Therefore, generally, executive function is trained by two interventional models:

behavioral and neuroscientific. The behavioral model focuses on one's acquired ability and trains executive function using computational tasks, with diverse protocols; the neuroscientific model by neuromodulation uses neurofeedback training or

Transcranial direct current stimulation (TDCS) is a form of noninvasive neuromodulation based on a small current applied by two electrodes positioned in the scalp in order to create neuronal membrane excitability and enhance neuronal firing. Transcranial magnetic stimulation (TMS) is also noninvasive neuromodulation but instead based on a magnetic field applied to the scalp focused at target areas to create a neuronal action potential to induce firing. Both models provide neuroplas-

Working memory is a neuropsychological function that allow us to deal with daily information, such as keeping in mind a telephone number while dialing, organizing the mental operations to accomplish a task in hands, or listening and

**28**

content [13]. In conclusion, the function of working memory is to manipulate the information for a limited period of time, and it may increase or decrease in its capacity according to demand and practice [17].

#### **3. Executive function**

The executive function consists of multiple top-down neuropsychological functions that enable us to deal with problem-solving in a non-automatic way. It may involve activities demanding attention, such as when writing and remembering a map on way to school [18], as well as activities demanding planning, controlling, and monitoring [19], such as keeping a diet prescription, physical training, or working long hours. All these abilities, also natural to most humans, again require a complex cognitive model that involves inhibition (including self-control), working memory, and flexibility.

Therefore, executive function has three neuropsychological functions associated with it. Firstly, there is inhibitory control, which is the ability to control internal and external stimulus that interfere with thought process while executing an activity that demands attention, filtering out the concurrent stimulus. Inhibition gives rise to what is commonly called self-control, an ability to prevent habits and instinctive behavior to dominate over careful planning [20]. Secondly, there is mental flexibility, which is the capability to alter between stimuli and adjust during the execution of a task in order to complete it [21]. Thirdly, there is a working memory, which has been described in the previous topic.

#### **4. Neurofeedback**

Neurofeedback (NF) is a neuromodulation by operant conditioning of brain activity, where physiological signal is acquired by electroencephalogram (EEG), functional magnetic resonance (fMRI), or functional near-infrared spectroscopy (fNIRS), and a computational interface provides a feedback (visual or/and sound) to self-regulation [22].

The neurofeedback works dynamically in the cortex. For instance, when electrical activity is used as parameter, subjects can enhance a brain wave frequency in a region while reducing another brainwave frequency in another region. The Lacroix [23] cognitive model provides a broader view of NF training, as he proposes that a change in a subject's perception of his physiological self-regulation provides a cognitive integration from the conditioned behavior. Consequently, neurofeedback involves a cognitive component associated with a conditioned behavior.

Additionally, the neuronal mechanisms of neurofeedback training are based in the neuromodulation model: the feedback provides a persistent functional brain reorganization and generates neuroplasticity, as pointed out by cortical changes after training in evidence-based studies, while those changes are ruled by a Hebbian learning process [22].

Electroencephalogram is the most common tool for neurofeedback, in which physiological information is collected and fed back to the same individual to induce self-regulation. EEG captures electrocortical activity and decomposes it into brainwaves. Generally it has four components: electrodes, an amplifier, a converter, and software. The electrodes often collect the electrocortical activity from layers III and V at pyramidal cells that occur close to the scalp.

**31**

*Neurofeedback Training on Aging: Prospects on Maintaining Cognitive Reserve*

difference forms a bidimensional (amplitude and frequency) topographic

representation of the cortical activity that will be mathematically calculated by the Fourier transformation. Therefore, the Fourier transform makes a decomposition of sinusoidal signals from the cortical depolarization, forming the following frequency band waves: delta, 1–4 Hz; theta, 4–8 Hz; alpha, 8–13 Hz; beta, 13–30 Hz; and

When applying EEG to neurofeedback, the electrodes are placed according to the international system 10–20, where 10–20 means 10 or 20% distance between electrodes. The placement areas are classified by the distance measured from the middle point between nasion and inion at sagittal direction and right and left temporomandibular disc measurement at coronal direction, placing the vertex at location Cz. From the vertex, a measurement of 10% for the total sagittal and total coronal mark and 20% for the subsequent regions is placed, or in other words, if the distance between nasion and inion is 32 cm, then the vertex is 16 cm, and 10% of each sagittal mark is 3.2 cm. The classification follows the cortical regions F (frontal), C (central), P (parietal), and O (occipital), odds to left hemisphere and evens

The voltage received by cortical electrodes is very low, around a thousand times

lower than cardiac electrical impulse and hundred times lower than muscular activity. Despite capturing a low amplitude, there are further challenges in capturing brain wave signals: electrical information from brain waves must be excluded from many layers of interference, such as the skin, scalp, pia mater, and fluid, beyond external noises and electrical current from electrical apparatus. Therefore, an amplifier and filter must be used to improve the signal [26]. The filters act by reducing noise, leaving mostly the biopotential desired to be converted; the amplifier amplifies the signal to a range of 100–100,000 times the information from electrodes [25]. The converter then changes the analogical signal from the amplifier to digital form. In this process, the analogical signal is decoded as repeated samples over fixed intervals, forming a sampling rate and transforms the signal into a digital information, where the converted resolution has lower amplitude [26]. Lastly, the software presents the digital signal to the experimenter that will be now able to analyze it. There is a general association between frequency band and cortical activity: higher cortical activity provides higher frequency band waves and is usually involved in higher brain activity. Symmetrically, lower cortical frequency bands are generally associated with lower brain activity. Hence, delta brain waves are associated with sleep, theta and alpha band waves are associated with working memory, attention and creativity, beta and gamma band waves are associated with intense thoughts and stimulus integration [27]. Those associations are based in several evidence-based studies, including the creation of EEG by Berger [28] that firstly divided brain activity into two brain wave frequencies, alpha and beta, and favored the understanding of mental states and electrophysiology, promoting the

Another form to capture brain signal and provide neurofeedback is from functional magnetic resonance image (fMRI) that will offer data of cortical activity from hemodynamic signals—blood-oxygen-level-dependent (BOLD)—in which the magnetic resonance captures changes in blood flow during brain activity. In other words, when there is a neuronal activation, creating a metabolic demand, oxygen venous blood increases to regulate the de-oxygenated arterial blood. This increase of oxy-deoxyhemoglobin also increases the resonance signal around the activated nervous tissue, forming the image. This technique has high spatial resolution but low time resolution, as to capture an image it is necessary to wait for a metabolic process, which may take minutes. Therefore, the protocols used in fMRI

*DOI: http://dx.doi.org/10.5772/intechopen.90847*

gamma, 30–60 Hz.

to right hemisphere [25].

development of the neurofeedback technique.

neurofeedback must contemplate this temporal delay [29].

The brain activity is characterized by the postsynaptic potential difference of billions of neurons and captures data closest to the scalp [24]. The potential

#### *Neurofeedback Training on Aging: Prospects on Maintaining Cognitive Reserve DOI: http://dx.doi.org/10.5772/intechopen.90847*

difference forms a bidimensional (amplitude and frequency) topographic representation of the cortical activity that will be mathematically calculated by the Fourier transformation. Therefore, the Fourier transform makes a decomposition of sinusoidal signals from the cortical depolarization, forming the following frequency band waves: delta, 1–4 Hz; theta, 4–8 Hz; alpha, 8–13 Hz; beta, 13–30 Hz; and gamma, 30–60 Hz.

When applying EEG to neurofeedback, the electrodes are placed according to the international system 10–20, where 10–20 means 10 or 20% distance between electrodes. The placement areas are classified by the distance measured from the middle point between nasion and inion at sagittal direction and right and left temporomandibular disc measurement at coronal direction, placing the vertex at location Cz. From the vertex, a measurement of 10% for the total sagittal and total coronal mark and 20% for the subsequent regions is placed, or in other words, if the distance between nasion and inion is 32 cm, then the vertex is 16 cm, and 10% of each sagittal mark is 3.2 cm. The classification follows the cortical regions F (frontal), C (central), P (parietal), and O (occipital), odds to left hemisphere and evens to right hemisphere [25].

The voltage received by cortical electrodes is very low, around a thousand times lower than cardiac electrical impulse and hundred times lower than muscular activity. Despite capturing a low amplitude, there are further challenges in capturing brain wave signals: electrical information from brain waves must be excluded from many layers of interference, such as the skin, scalp, pia mater, and fluid, beyond external noises and electrical current from electrical apparatus. Therefore, an amplifier and filter must be used to improve the signal [26]. The filters act by reducing noise, leaving mostly the biopotential desired to be converted; the amplifier amplifies the signal to a range of 100–100,000 times the information from electrodes [25]. The converter then changes the analogical signal from the amplifier to digital form. In this process, the analogical signal is decoded as repeated samples over fixed intervals, forming a sampling rate and transforms the signal into a digital information, where the converted resolution has lower amplitude [26]. Lastly, the software presents the digital signal to the experimenter that will be now able to analyze it.

There is a general association between frequency band and cortical activity: higher cortical activity provides higher frequency band waves and is usually involved in higher brain activity. Symmetrically, lower cortical frequency bands are generally associated with lower brain activity. Hence, delta brain waves are associated with sleep, theta and alpha band waves are associated with working memory, attention and creativity, beta and gamma band waves are associated with intense thoughts and stimulus integration [27]. Those associations are based in several evidence-based studies, including the creation of EEG by Berger [28] that firstly divided brain activity into two brain wave frequencies, alpha and beta, and favored the understanding of mental states and electrophysiology, promoting the development of the neurofeedback technique.

Another form to capture brain signal and provide neurofeedback is from functional magnetic resonance image (fMRI) that will offer data of cortical activity from hemodynamic signals—blood-oxygen-level-dependent (BOLD)—in which the magnetic resonance captures changes in blood flow during brain activity. In other words, when there is a neuronal activation, creating a metabolic demand, oxygen venous blood increases to regulate the de-oxygenated arterial blood. This increase of oxy-deoxyhemoglobin also increases the resonance signal around the activated nervous tissue, forming the image. This technique has high spatial resolution but low time resolution, as to capture an image it is necessary to wait for a metabolic process, which may take minutes. Therefore, the protocols used in fMRI neurofeedback must contemplate this temporal delay [29].

*Neurological and Mental Disorders*

**3. Executive function**

memory, and flexibility.

**4. Neurofeedback**

to self-regulation [22].

learning process [22].

capacity according to demand and practice [17].

which has been described in the previous topic.

content [13]. In conclusion, the function of working memory is to manipulate the information for a limited period of time, and it may increase or decrease in its

The executive function consists of multiple top-down neuropsychological functions that enable us to deal with problem-solving in a non-automatic way. It may involve activities demanding attention, such as when writing and remembering a map on way to school [18], as well as activities demanding planning, controlling, and monitoring [19], such as keeping a diet prescription, physical training, or working long hours. All these abilities, also natural to most humans, again require a complex cognitive model that involves inhibition (including self-control), working

Therefore, executive function has three neuropsychological functions associated with it. Firstly, there is inhibitory control, which is the ability to control internal and external stimulus that interfere with thought process while executing an activity that demands attention, filtering out the concurrent stimulus. Inhibition gives rise to what is commonly called self-control, an ability to prevent habits and instinctive behavior to dominate over careful planning [20]. Secondly, there is mental flexibility, which is the capability to alter between stimuli and adjust during the execution of a task in order to complete it [21]. Thirdly, there is a working memory,

Neurofeedback (NF) is a neuromodulation by operant conditioning of brain activity, where physiological signal is acquired by electroencephalogram (EEG), functional magnetic resonance (fMRI), or functional near-infrared spectroscopy (fNIRS), and a computational interface provides a feedback (visual or/and sound)

The neurofeedback works dynamically in the cortex. For instance, when electrical activity is used as parameter, subjects can enhance a brain wave frequency in a region while reducing another brainwave frequency in another region. The Lacroix [23] cognitive model provides a broader view of NF training, as he proposes that a change in a subject's perception of his physiological self-regulation provides a cognitive integration from the conditioned behavior. Consequently, neurofeedback

Additionally, the neuronal mechanisms of neurofeedback training are based in the neuromodulation model: the feedback provides a persistent functional brain reorganization and generates neuroplasticity, as pointed out by cortical changes after training in evidence-based studies, while those changes are ruled by a Hebbian

Electroencephalogram is the most common tool for neurofeedback, in which physiological information is collected and fed back to the same individual to induce self-regulation. EEG captures electrocortical activity and decomposes it into brainwaves. Generally it has four components: electrodes, an amplifier, a converter, and software. The electrodes often collect the electrocortical activity from layers III

The brain activity is characterized by the postsynaptic potential difference of billions of neurons and captures data closest to the scalp [24]. The potential

involves a cognitive component associated with a conditioned behavior.

and V at pyramidal cells that occur close to the scalp.

**30**

The neurofeedback by fMRI is called real-time functional magnetic resonance image (rt-fMRI) and has the advantage of providing training in deeper and specific regions of the brain. Further, although it is a new technique, its results have been significant [30].

Functional near-infrared spectroscopy is similar to magnetic resonance, since the brain activity captured is from BOLD signals. Therefore, the hemodynamic changes are registered by an infrared proximal light spectrum. However, this spectrum only captures activity from layers closer to the scalp [31]. The neurofeedback training by fNIRS is as recent as the rt-fMRI, but it has the advantage of being more accessible, as it involves simpler equipment and less medical environment [32].

#### **5. The EEG neurofeedback**

#### **5.1 A brief history of neurofeedback**

The first studies that evaluated the association between operant conditioning and cortical changes were conducted by Sterman et al. [32], where he incidentally observed that cats trained to increase their activation in 12–15 Hz at Rolandic cortex were resistant to a convulsion-inducing chemical—hydrazine. Afterward, he conducted this experiment in humans to check if the neurofeedback would be able to inhibit not controlled seizures. This frequency band (12–15 Hz) observed centrally, at the sensorimotor region, became known as the sensorimotor rhythm (SMR).

Another study also related to cortical operant conditioning by neurofeedback is a study conducted by Hardt and Kamiya [33]. The study observed that meditators have higher alpha wave patterns associated with a calm and tranquil state of mind. The study found that increasing alpha wave patterns could successfully reduce symptoms of anxiety.

Afterward, Lubar and Lubar [34] tested the effects of increasing SMR in children with attention deficit hyperactivity disorder with comorbid hyperkinesia and demonstrated that neurofeedback can reduce motor movements and increase attention.

From the mentioned studies, diverse protocols have been developed and applied in order to diminish symptoms of psychiatric disorders, improve cognitive performance, and manage stress. Therefore, neurofeedback has been used since its creation in the 1960s to improve conditions such as convulsion, ADHD, anxiety, depression, and addiction [35–38]. These protocols which have been extensively studied mainly train the central regions of the cortex to change SMR (12–15 Hz) [37].

The SMR occurs precisely over the primary motor cortex. This was observed when cats were operantly conditioned by having the animal press a bar as it waits for a reward. By measuring cortical activity, they found that, when cats increased awareness and reduced movement, this was associated with the activation of 12–15 Hz over primary motor cortex [31].

In humans, the SMR follows the same pattern [39], that is, when there is increased activity (12–15 Hz) over the sensorimotor cortex, there is a suppression of movement and an increased attention.

The mechanism of SMR neurofeedback is through the inhibition of thalamiccortical circuits, which reduces interference of somatosensorial information [40]. Inhibition caused by the increase of SMR rhythm provides a higher integration of information processing over the cortex, by reducing interference of motor activity on cognitive performance [41].

**33**

activity throughout the task [57].

*Neurofeedback Training on Aging: Prospects on Maintaining Cognitive Reserve*

Cognitive training by neurofeedback has been applied over the last 15 years in healthy subjects. Successful protocols have been established with young populations [42–45]. However, there are fewer studies conducted with elderly popula-

Angelakis et al. [46] conducted a study with 30 sessions in 6 health elderly subjects in order to test alpha neurofeedback at occipital region measuring their cognitive ability before and after the training. As a result, despite the fact that the training was conducted at the occipital region, changes in alpha production were observed frontally. Moreover, the alpha pick experimental group had an increase at processing speed and executive function, while the increased alpha amplitude is correlated with increase at verbal, visual, and working memory but decreased

Becerra et al. [47] conducted a study for theta suppression at the cortical region that presented a higher-level amplitude at baseline quantitative EEG with 56 health elderly subjects which were evaluated cognitively before and after training. The results have shown that theta suppression promoted changes at absolute power of alpha and, in cognitive terms, there was a significant change at verbal comprehen-

LeComte and Juhel [48] trained four sessions to increase theta centrally (C3- C4) in order to improve memory in healthy elderly. The training happened with 30 subjects evaluated before and after training using the Signoret memory battery [53]. The results have not indicated any memory changes between tested groups. However, it highlighted how important might be the number of neurofeedback sessions to provide cortical changes. Gruzelier [45] has demonstrated it is necessary

Wang and Hsieh [49] conducted a study comparing how neurofeedback might improve attention and working memory in healthy elderly and young subjects. It had 32 subjects randomically assigned to increase theta activity at frontal vertex (Fz) since studies have shown that that working memory tasks require theta activity in this area [54, 55]. Elderly and young subjects showed improvement in attention and working memory even at rest. This study highlighted the question of whether cognitive enhancement performance protocols developed to young people might be

sion, verbal IQ at WAIS-III [51], and working memory at Neuropsi [52].

applied to elderly as well, although the cortical differences with aging.

A study conducted by Belham et al. [56] suggested that a higher activation in theta centrally in adults and elderly is related to attentional processes as well as cortical integration during mnemonic processes. They also suggested that the mechanism behind brain wave intensity differences observed in elderly in comparison to young people is related to the Compensation-Related Utilization of Neural Circuits Hypothesis (CRUNCH). According to CRUNCH, the elderly brain will recruit higher cognitive resources according to task demand and will have a higher intensity neuronal activity at the beginning and middle of the task, as a way to compensate for the decrease in processing speed and for atrophy. Consequently, elderly will reach the performance ceiling faster, while a young will increase brain

Another study, conducted by Reis et al. [50], tested the neurofeedback using a short but intensive protocol to increase alpha and theta at several regions (Fp1, Fp2, Fz, and Pz) comparing subjects while they trained their cognitive abilities in working memory tasks. All elderly subjects were tested and retested in order to check for improvement. The results demonstrated that the neurofeedback group increased their working memory significantly, while the group of cognitive training

to have at least 10 sessions to produce an effective training.

plus neurofeedback had only shown a tendency to improve.

*DOI: http://dx.doi.org/10.5772/intechopen.90847*

processing speed and executive function.

tions [7, 46–50].

**5.2 Neurofeedback training in the cognitive aging**

#### **5.2 Neurofeedback training in the cognitive aging**

*Neurological and Mental Disorders*

significant [30].

environment [32].

symptoms of anxiety.

attention.

(12–15 Hz) [37].

12–15 Hz over primary motor cortex [31].

movement and an increased attention.

on cognitive performance [41].

**5. The EEG neurofeedback**

**5.1 A brief history of neurofeedback**

The neurofeedback by fMRI is called real-time functional magnetic resonance image (rt-fMRI) and has the advantage of providing training in deeper and specific regions of the brain. Further, although it is a new technique, its results have been

Functional near-infrared spectroscopy is similar to magnetic resonance, since the brain activity captured is from BOLD signals. Therefore, the hemodynamic changes are registered by an infrared proximal light spectrum. However, this spectrum only captures activity from layers closer to the scalp [31]. The neurofeedback training by fNIRS is as recent as the rt-fMRI, but it has the advantage of being more accessible, as it involves simpler equipment and less medical

The first studies that evaluated the association between operant conditioning and cortical changes were conducted by Sterman et al. [32], where he incidentally observed that cats trained to increase their activation in 12–15 Hz at Rolandic cortex were resistant to a convulsion-inducing chemical—hydrazine. Afterward, he conducted this experiment in humans to check if the neurofeedback would be able to inhibit not controlled seizures. This frequency band (12–15 Hz) observed centrally, at the sensorimotor region, became known as the sensorimotor rhythm (SMR). Another study also related to cortical operant conditioning by neurofeedback is a study conducted by Hardt and Kamiya [33]. The study observed that meditators have higher alpha wave patterns associated with a calm and tranquil state of mind. The study found that increasing alpha wave patterns could successfully reduce

Afterward, Lubar and Lubar [34] tested the effects of increasing SMR in children with attention deficit hyperactivity disorder with comorbid hyperkinesia and demonstrated that neurofeedback can reduce motor movements and increase

From the mentioned studies, diverse protocols have been developed and applied in order to diminish symptoms of psychiatric disorders, improve cognitive performance, and manage stress. Therefore, neurofeedback has been used since its creation in the 1960s to improve conditions such as convulsion, ADHD, anxiety, depression, and addiction [35–38]. These protocols which have been extensively studied mainly train the central regions of the cortex to change SMR

The SMR occurs precisely over the primary motor cortex. This was observed when cats were operantly conditioned by having the animal press a bar as it waits for a reward. By measuring cortical activity, they found that, when cats increased awareness and reduced movement, this was associated with the activation of

In humans, the SMR follows the same pattern [39], that is, when there is increased activity (12–15 Hz) over the sensorimotor cortex, there is a suppression of

The mechanism of SMR neurofeedback is through the inhibition of thalamiccortical circuits, which reduces interference of somatosensorial information [40]. Inhibition caused by the increase of SMR rhythm provides a higher integration of information processing over the cortex, by reducing interference of motor activity

**32**

Cognitive training by neurofeedback has been applied over the last 15 years in healthy subjects. Successful protocols have been established with young populations [42–45]. However, there are fewer studies conducted with elderly populations [7, 46–50].

Angelakis et al. [46] conducted a study with 30 sessions in 6 health elderly subjects in order to test alpha neurofeedback at occipital region measuring their cognitive ability before and after the training. As a result, despite the fact that the training was conducted at the occipital region, changes in alpha production were observed frontally. Moreover, the alpha pick experimental group had an increase at processing speed and executive function, while the increased alpha amplitude is correlated with increase at verbal, visual, and working memory but decreased processing speed and executive function.

Becerra et al. [47] conducted a study for theta suppression at the cortical region that presented a higher-level amplitude at baseline quantitative EEG with 56 health elderly subjects which were evaluated cognitively before and after training. The results have shown that theta suppression promoted changes at absolute power of alpha and, in cognitive terms, there was a significant change at verbal comprehension, verbal IQ at WAIS-III [51], and working memory at Neuropsi [52].

LeComte and Juhel [48] trained four sessions to increase theta centrally (C3- C4) in order to improve memory in healthy elderly. The training happened with 30 subjects evaluated before and after training using the Signoret memory battery [53]. The results have not indicated any memory changes between tested groups. However, it highlighted how important might be the number of neurofeedback sessions to provide cortical changes. Gruzelier [45] has demonstrated it is necessary to have at least 10 sessions to produce an effective training.

Wang and Hsieh [49] conducted a study comparing how neurofeedback might improve attention and working memory in healthy elderly and young subjects. It had 32 subjects randomically assigned to increase theta activity at frontal vertex (Fz) since studies have shown that that working memory tasks require theta activity in this area [54, 55]. Elderly and young subjects showed improvement in attention and working memory even at rest. This study highlighted the question of whether cognitive enhancement performance protocols developed to young people might be applied to elderly as well, although the cortical differences with aging.

A study conducted by Belham et al. [56] suggested that a higher activation in theta centrally in adults and elderly is related to attentional processes as well as cortical integration during mnemonic processes. They also suggested that the mechanism behind brain wave intensity differences observed in elderly in comparison to young people is related to the Compensation-Related Utilization of Neural Circuits Hypothesis (CRUNCH). According to CRUNCH, the elderly brain will recruit higher cognitive resources according to task demand and will have a higher intensity neuronal activity at the beginning and middle of the task, as a way to compensate for the decrease in processing speed and for atrophy. Consequently, elderly will reach the performance ceiling faster, while a young will increase brain activity throughout the task [57].

Another study, conducted by Reis et al. [50], tested the neurofeedback using a short but intensive protocol to increase alpha and theta at several regions (Fp1, Fp2, Fz, and Pz) comparing subjects while they trained their cognitive abilities in working memory tasks. All elderly subjects were tested and retested in order to check for improvement. The results demonstrated that the neurofeedback group increased their working memory significantly, while the group of cognitive training plus neurofeedback had only shown a tendency to improve.

#### *Neurological and Mental Disorders*

The neurofeedback group was also able to increase theta and alpha frontally (Fz), while neurofeedback with cognitive training presented only a tendency to increase alpha and theta frontally. An interesting result about neurofeedback observed by Reis et al. [50] was that the placebo group was also able to increase their alpha rhythm, as alpha is predominantly involved at attentional tasks, and when a simulation of neurofeedback was presented, the cortical activity was recruited even in a placebo situation. Therefore, the study has demonstrated that neurofeedback was able to change alpha and theta rhythm, consequently improving the performance in working memory task.

#### **6. Neurofeedback training to improve working memory**

We conducted a study with 17 healthy elderly subjects in order to increase SMR activity centrally (Cz) in 10 sessions to improve working memory performance, based on the assumption that attentional control is required at the central executive to keep the information continuously accessible [58]. The study conducted was an experimental-placebo randomized study. Quantitative EEG was collected during a working memory task called delayed matching-to-sample (DMTS) task before and after training to check for the cortical changes observed [7].

The DMTS task is a type of match-to-sample task, a pictorial working memory task which subjects are presented with a visual stimulus they are required to remember. It consists of two phases: the first phase presents the subject with an image for 500 ms, and then the image disappears for an interval of 15,000 ms. Then, in the second phase, two images are presented for 2000 ms, one being the same image as in the first phase and another being randomly chosen from a database. The objective is to click using a computer mouse on the picture that was initially presented at the first phase. An auditory feedback is provided (pinched sound to correct answers and bass sound to incorrect or not answered).

The neurofeedback protocol was developed by the authors, where the subjects sit comfortably in front of a computer screen and three cortical electrodes were installed, one at Cz and two other at ears lobes, one for reference and another for grounding. Two other electrophysiological electrodes were installed, one for heart rate frequency and another for breath frequency, both being only for measurement and not analyzed or used as feedback. The objective of the training was to increase SMR in 10% higher of each baseline measurement. The training took 3 min and was divided in three intervals, whereas in every interval it was collected a baseline frequency for 1 min. In other words, the training protocol consisted of 1-min baseline and 3 min of neurofeedback distributed in three blocks.

The equipment used for the neurofeedback training was ProComp Infiniti from Thought Technology, Canada. The amplifier pattern of the ProComp sampled the raw EEG at 256 Hz and converted A/D for live feedback. The software applied an infinite impulse response (IIR) filter to the recorded signal to extract frequency domain information. Spectral amplitude estimates were calculated for the active site (Cz) on raw 1-s EEG segments. A band-pass filter was used to extract the reward EEG frequency band for SMR (12–15 Hz) for feedback.

The EEG equipment used to measure brain wave activity while subject were performing DMTS task was Neuron-spectrum from NeuroSoft, Russia, with a 19 channels WaveGuard Connect cap, ANT Neuro, Deutschland, in a monopolar montage, decoded by Neuron-Spectrum software, NeuroSoft, that capture cortical activity of regions according to the 10/20 system. It was applied a rejection rate of 120 dB established by the program, sample rate of 2000 Hz, higher band filter pass of 0.5 Hz, lower band filter pass of 35 Hz and notch of 60 Hz.

**35**

**Figure 2.**

*Neurofeedback Training on Aging: Prospects on Maintaining Cognitive Reserve*

might be responsible for the change in the performance.

The experimental group did ten sessions of SMR neurofeedback twice a week for 5 weeks. The placebo group did one session and then replayed their first session for the other nine sessions, twice a week for 5 weeks. The control group did the DMTS task firstly, waited 5 weeks, and did another DMTS task, without any contact to

The results have demonstrated an improvement in working memory performance at the neurofeedback group comparing to placebo group and control. That is, subjects from the experimental group presented a higher number of correct response in the DMTS after neurofeedback training, demonstrating that neurofeedback facilitates attentional process that is critical for a good performance in working

Besides that, a comparison between groups at the pre-training phase has demonstrated that they were not different in performance as a sample (p > 0.05 ANOVA). Therefore, there was no performance difference between group compositions that could justify the observed changes. Consequently, the neurofeedback training

Moreover, the ANOVA between groups after training have demonstrated no difference between experimental group and placebo, although there are differences between experimental and control groups (p < 0.05) as well as placebo and control groups (p < 0.05) (**Figure 2**). However, the placebo group presented some improvement at their performance on DMTS after training, suggesting that the training procedure, even when without contingency, is capable of facilitating effects over attentional processes that reflect on working

Therefore, merely being at the office, having the electrodes put on and playing a neurofeedback session that does not give real feedback can exert and facilitate cognitive processes. And although the placebo group also did demonstrate an improvement in performance, it was not statistically significant as in the

Thereby, it can be stated that from the principles of operant conditioning, the reward must be contingent to achieve conditioning; however the incontigency

*ANOVA delayed matching-to-sample mean of correct response between groups after neurofeedback training in* 

*p < 0.05.*

*all groups: NF, experimental group; SNF, placebo group; and NNF, control group. \**

of reward can also influence in the results [59], since somehow there is a feedback acting over the subject action. Moreover, it can be observed that none of the participants noticed the placebo condition. That is, even though the training was a repetition of their first session and there is no real feedback, the contingencial expectation over the results interferes in the self-regulation of those

*DOI: http://dx.doi.org/10.5772/intechopen.90847*

neurofeedback.

memory tasks.

memory performance [50].

neurofeedback group.

subjects [60].

#### *Neurofeedback Training on Aging: Prospects on Maintaining Cognitive Reserve DOI: http://dx.doi.org/10.5772/intechopen.90847*

The experimental group did ten sessions of SMR neurofeedback twice a week for 5 weeks. The placebo group did one session and then replayed their first session for the other nine sessions, twice a week for 5 weeks. The control group did the DMTS task firstly, waited 5 weeks, and did another DMTS task, without any contact to neurofeedback.

The results have demonstrated an improvement in working memory performance at the neurofeedback group comparing to placebo group and control. That is, subjects from the experimental group presented a higher number of correct response in the DMTS after neurofeedback training, demonstrating that neurofeedback facilitates attentional process that is critical for a good performance in working memory tasks.

Besides that, a comparison between groups at the pre-training phase has demonstrated that they were not different in performance as a sample (p > 0.05 ANOVA). Therefore, there was no performance difference between group compositions that could justify the observed changes. Consequently, the neurofeedback training might be responsible for the change in the performance.

Moreover, the ANOVA between groups after training have demonstrated no difference between experimental group and placebo, although there are differences between experimental and control groups (p < 0.05) as well as placebo and control groups (p < 0.05) (**Figure 2**). However, the placebo group presented some improvement at their performance on DMTS after training, suggesting that the training procedure, even when without contingency, is capable of facilitating effects over attentional processes that reflect on working memory performance [50].

Therefore, merely being at the office, having the electrodes put on and playing a neurofeedback session that does not give real feedback can exert and facilitate cognitive processes. And although the placebo group also did demonstrate an improvement in performance, it was not statistically significant as in the neurofeedback group.

Thereby, it can be stated that from the principles of operant conditioning, the reward must be contingent to achieve conditioning; however the incontigency of reward can also influence in the results [59], since somehow there is a feedback acting over the subject action. Moreover, it can be observed that none of the participants noticed the placebo condition. That is, even though the training was a repetition of their first session and there is no real feedback, the contingencial expectation over the results interferes in the self-regulation of those subjects [60].

#### **Figure 2.**

*ANOVA delayed matching-to-sample mean of correct response between groups after neurofeedback training in all groups: NF, experimental group; SNF, placebo group; and NNF, control group. \* p < 0.05.*

*Neurological and Mental Disorders*

the performance in working memory task.

**6. Neurofeedback training to improve working memory**

after training to check for the cortical changes observed [7].

and 3 min of neurofeedback distributed in three blocks.

EEG frequency band for SMR (12–15 Hz) for feedback.

of 0.5 Hz, lower band filter pass of 35 Hz and notch of 60 Hz.

The neurofeedback group was also able to increase theta and alpha frontally (Fz), while neurofeedback with cognitive training presented only a tendency to increase alpha and theta frontally. An interesting result about neurofeedback observed by Reis et al. [50] was that the placebo group was also able to increase their alpha rhythm, as alpha is predominantly involved at attentional tasks, and when a simulation of neurofeedback was presented, the cortical activity was recruited even in a placebo situation. Therefore, the study has demonstrated that neurofeedback was able to change alpha and theta rhythm, consequently improving

We conducted a study with 17 healthy elderly subjects in order to increase SMR activity centrally (Cz) in 10 sessions to improve working memory performance, based on the assumption that attentional control is required at the central executive to keep the information continuously accessible [58]. The study conducted was an experimental-placebo randomized study. Quantitative EEG was collected during a working memory task called delayed matching-to-sample (DMTS) task before and

The DMTS task is a type of match-to-sample task, a pictorial working memory

The neurofeedback protocol was developed by the authors, where the subjects sit comfortably in front of a computer screen and three cortical electrodes were installed, one at Cz and two other at ears lobes, one for reference and another for grounding. Two other electrophysiological electrodes were installed, one for heart rate frequency and another for breath frequency, both being only for measurement and not analyzed or used as feedback. The objective of the training was to increase SMR in 10% higher of each baseline measurement. The training took 3 min and was divided in three intervals, whereas in every interval it was collected a baseline frequency for 1 min. In other words, the training protocol consisted of 1-min baseline

The equipment used for the neurofeedback training was ProComp Infiniti from Thought Technology, Canada. The amplifier pattern of the ProComp sampled the raw EEG at 256 Hz and converted A/D for live feedback. The software applied an infinite impulse response (IIR) filter to the recorded signal to extract frequency domain information. Spectral amplitude estimates were calculated for the active site (Cz) on raw 1-s EEG segments. A band-pass filter was used to extract the reward

The EEG equipment used to measure brain wave activity while subject were performing DMTS task was Neuron-spectrum from NeuroSoft, Russia, with a 19 channels WaveGuard Connect cap, ANT Neuro, Deutschland, in a monopolar montage, decoded by Neuron-Spectrum software, NeuroSoft, that capture cortical activity of regions according to the 10/20 system. It was applied a rejection rate of 120 dB established by the program, sample rate of 2000 Hz, higher band filter pass

task which subjects are presented with a visual stimulus they are required to remember. It consists of two phases: the first phase presents the subject with an image for 500 ms, and then the image disappears for an interval of 15,000 ms. Then, in the second phase, two images are presented for 2000 ms, one being the same image as in the first phase and another being randomly chosen from a database. The objective is to click using a computer mouse on the picture that was initially presented at the first phase. An auditory feedback is provided (pinched

sound to correct answers and bass sound to incorrect or not answered).

**34**

#### **Figure 3.**

*Mean of the correct responses pre- and post-training at delayed matching-to-sample between condition and groups. NF, experimental group; SNF, placebo group; and NNF, control group. \* p < 0.05.*

Hence, if the participant believed the training to be true and received the impression of feedback, even not-contingency over their action, it might be able to modify its self-regulation and consequently obtain an improvement of performance.

Thus, the improvement of working memory does not occur only by the effective training but also by placebo, demonstrating that the exposition to the technique is sufficient to induce a positive changes in cognitive abilities, while the lack of stimulation demonstrate to be deleterious to the participant, as the control group does not present any changes between the conditions (**Figure 3**).

As stated before, the working memory model is multicomponent and involves more than one cortical area: mainly regions of medial temporal lobe and dorsolateral prefrontal cortex. The activation of EEG is superficial, unable to capture neural activity from deeper areas such as hippocampus and inferior parietal cortex. However, in the study, it was possible to observe a higher activation at the pretraining DMTS task from recruited areas associate to working memory task, frontal and central, mainly in alpha and theta frequency band.

It can be also highlighted that at the pre-training condition, all frequency bands had an increased intensity in almost every region measured and, on the other hand, at the post-training there were changes at position with less intensity of some frequency bands. In theta, all cortexes were activated during a DMTS task, but at the post-training, less regions were activated during a DMTS task, with significant difference at the frontal, temporal, central, and occipital areas (**Figure 4**).

For beta band, at the pre-training and post-training, all regions measured presented significant differences, predominantly at the right hemisphere.

It was also possible to observe statistically significant differences at the interaction between the placebo and control groups in gamma activation, at pre- and posttraining condition. The activations in both conditions and for all subjects reinforce the role of gamma activity to provide integration at connectivity during working memory tasks [61].

In relation to activation between pre- and post-training, the results of the study have indicated that participants of experimental groups have less activation in all frequency bands at the post-training DMTS task than the placebo group. However, the performance at task increased. Therefore, it can be inferred that the

**37**

**Figure 4.**

*Neurofeedback Training on Aging: Prospects on Maintaining Cognitive Reserve*

neurofeedback training resulted in a less-generalized cortical activation, which is

*ANOVA between condition (pre- and post-training) and interaction of theta (4–8 Hz), alpha (8–13 Hz), beta (13–30 Hz), and gamma (30–60 Hz) frequency band (columns). The first role is placebo (SNF) to left and experimental (NF) to right, at pre-training and post-training; second role is placebo (SNF) to left and control (NNF) to right, at pre-training and post-training; and third role is experimental (NF) to left and control* 

In aging populations, cognitive and behavioral changes are evident by neurobiological changes that occur due to volumetric changes in brain structure, and lower efficiency is observed at information processing, including a diminish in speed, working memory, inhibition, and long-term memory [62]. And in compensation for their inefficiency, the elderly increase the intensity of activation during complex

Therefore, brain wave changes observed at placebo group as higher activation during DMTS task before and post-training neurofeedback might have occurred to keep performance, which is in line with the CRUNCH hypothesis, previously stated, in which elderly will overcome their difficulty with an increment of brain activity [57]. On the other hand, in the neurofeedback group, the activation was less statistically different from pre- to post-training at DMTS task, but their working memory performance increased. Therefore, the neuromodulation of neurofeedback relies on persistent human functional reorganization and neuroplasticity that is observed in pre- and post-test EEG comparison [63–65]. These changes are based on the

Hence, the neuroplasticity observed at the neurofeedback group is in accordance

• First, when a task involves a learning characteristic based on repetition, it is

• On the other hand, if the learning process of a training is based on metacogni-

associated with less activation and more specificity of the area.

tive strategies, there is a higher activation of several cortical areas.

related to a better performance at the working memory task.

*(NNF) to right, at pre-training and post-training. The red dots are p < 0.05.*

task performance, as observed at the placebo group.

combination of Hebbian and homeostatic plasticity [22].

to the interactive model [66] that is based in two principles:

*DOI: http://dx.doi.org/10.5772/intechopen.90847*

#### *Neurofeedback Training on Aging: Prospects on Maintaining Cognitive Reserve DOI: http://dx.doi.org/10.5772/intechopen.90847*

#### **Figure 4.**

*Neurological and Mental Disorders*

performance.

**Figure 3.**

areas (**Figure 4**).

memory tasks [61].

Hence, if the participant believed the training to be true and received the impression of feedback, even not-contingency over their action, it might be able to modify its self-regulation and consequently obtain an improvement of

*Mean of the correct responses pre- and post-training at delayed matching-to-sample between condition and* 

*p < 0.05.*

present any changes between the conditions (**Figure 3**).

*groups. NF, experimental group; SNF, placebo group; and NNF, control group. \**

and central, mainly in alpha and theta frequency band.

Thus, the improvement of working memory does not occur only by the effective training but also by placebo, demonstrating that the exposition to the technique is sufficient to induce a positive changes in cognitive abilities, while the lack of stimulation demonstrate to be deleterious to the participant, as the control group does not

As stated before, the working memory model is multicomponent and involves more than one cortical area: mainly regions of medial temporal lobe and dorsolateral prefrontal cortex. The activation of EEG is superficial, unable to capture neural activity from deeper areas such as hippocampus and inferior parietal cortex. However, in the study, it was possible to observe a higher activation at the pretraining DMTS task from recruited areas associate to working memory task, frontal

It can be also highlighted that at the pre-training condition, all frequency bands had an increased intensity in almost every region measured and, on the other hand, at the post-training there were changes at position with less intensity of some frequency bands. In theta, all cortexes were activated during a DMTS task, but at the post-training, less regions were activated during a DMTS task, with significant difference at the frontal, temporal, central, and occipital

For beta band, at the pre-training and post-training, all regions measured presented significant differences, predominantly at the right hemisphere.

In relation to activation between pre- and post-training, the results of the study have indicated that participants of experimental groups have less activation in all frequency bands at the post-training DMTS task than the placebo group. However, the performance at task increased. Therefore, it can be inferred that the

It was also possible to observe statistically significant differences at the interaction between the placebo and control groups in gamma activation, at pre- and posttraining condition. The activations in both conditions and for all subjects reinforce the role of gamma activity to provide integration at connectivity during working

**36**

*ANOVA between condition (pre- and post-training) and interaction of theta (4–8 Hz), alpha (8–13 Hz), beta (13–30 Hz), and gamma (30–60 Hz) frequency band (columns). The first role is placebo (SNF) to left and experimental (NF) to right, at pre-training and post-training; second role is placebo (SNF) to left and control (NNF) to right, at pre-training and post-training; and third role is experimental (NF) to left and control (NNF) to right, at pre-training and post-training. The red dots are p < 0.05.*

neurofeedback training resulted in a less-generalized cortical activation, which is related to a better performance at the working memory task.

In aging populations, cognitive and behavioral changes are evident by neurobiological changes that occur due to volumetric changes in brain structure, and lower efficiency is observed at information processing, including a diminish in speed, working memory, inhibition, and long-term memory [62]. And in compensation for their inefficiency, the elderly increase the intensity of activation during complex task performance, as observed at the placebo group.

Therefore, brain wave changes observed at placebo group as higher activation during DMTS task before and post-training neurofeedback might have occurred to keep performance, which is in line with the CRUNCH hypothesis, previously stated, in which elderly will overcome their difficulty with an increment of brain activity [57]. On the other hand, in the neurofeedback group, the activation was less statistically different from pre- to post-training at DMTS task, but their working memory performance increased. Therefore, the neuromodulation of neurofeedback relies on persistent human functional reorganization and neuroplasticity that is observed in pre- and post-test EEG comparison [63–65]. These changes are based on the combination of Hebbian and homeostatic plasticity [22].

Hence, the neuroplasticity observed at the neurofeedback group is in accordance to the interactive model [66] that is based in two principles:


Consequently, as the neurofeedback was related to the increase of SMR repeatedly, it was a repeated training, and a reduction of activation was observed and an increase of efficiency.

Afterward, the neurofeedback training even at placebo condition was able to change cortical activity. However, the changes on the experimental group were more precise and specific.

## **7. Conclusion**

The studies mentioned above have demonstrated that the training protocols with elderly involve diverse proposals and sometimes may have inconsistent results. However, despite the diversity of protocols, the studies have demonstrated positive neurophysiological and cognitive effects related to working memory and attention. Therefore, these results suggest that neurofeedback might be an important tool to increase cognitive reserve at aging.

To conclude, since


Techniques and tools that favor the formation of cognitive reserve have become of fundamental importance to society, once the increase in life expectancy leads to a longer period in this later stage of life.

### **Acknowledgements**

We thank Dr. Ana Garcia for assistance in analysis of the data and Psy. Aloysio Campos da Paz Neto for the protocol design and the Laboratory of Neuroscience and Behavior at the University of Brasília, Brazil.

**39**

**Author details**

1 UnB, Brasília, Brazil

Valeska Kouzak Campos da Paz1

2 UniCeuma, São Luís, Brazil

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

provided the original work is properly cited.

\* and Carlos Tomaz2

© 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,

*Neurofeedback Training on Aging: Prospects on Maintaining Cognitive Reserve*

*DOI: http://dx.doi.org/10.5772/intechopen.90847*

### **Conflicts of interest**

The authors declare no conflict of interest.

*Neurofeedback Training on Aging: Prospects on Maintaining Cognitive Reserve DOI: http://dx.doi.org/10.5772/intechopen.90847*

### **Author details**

*Neurological and Mental Disorders*

increase of efficiency.

**7. Conclusion**

more precise and specific.

increase cognitive reserve at aging.

longer period in this later stage of life.

and Behavior at the University of Brasília, Brazil.

The authors declare no conflict of interest.

To conclude, since

**Acknowledgements**

**Conflicts of interest**

Consequently, as the neurofeedback was related to the increase of SMR repeatedly, it was a repeated training, and a reduction of activation was observed and an

Afterward, the neurofeedback training even at placebo condition was able to change cortical activity. However, the changes on the experimental group were

The studies mentioned above have demonstrated that the training protocols with elderly involve diverse proposals and sometimes may have inconsistent results. However, despite the diversity of protocols, the studies have demonstrated positive neurophysiological and cognitive effects related to working memory and attention. Therefore, these results suggest that neurofeedback might be an important tool to

1.Neurofeedback is an accessible technique for neuromodulation by EEG that

2.Aging individuals experience decline in their neuropsychological abilities.

Techniques and tools that favor the formation of cognitive reserve have become of fundamental importance to society, once the increase in life expectancy leads to a

We thank Dr. Ana Garcia for assistance in analysis of the data and Psy. Aloysio Campos da Paz Neto for the protocol design and the Laboratory of Neuroscience

provides operant conditioning and cognitive self-perception.

**38**

Valeska Kouzak Campos da Paz1 \* and Carlos Tomaz2

1 UnB, Brasília, Brazil

2 UniCeuma, São Luís, Brazil

\*Address all correspondence to: valeskakcp@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.

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[24] Teplan M. Fundamentals of EEG measurement. Measurement Science Review. 2002;**2**:1-11

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[56] Belham FS, Satler C, Garcia A, Tomaz C, Gasbarri A, Rego A, et al. Aged-related differences in cortical activity during visuo-spatial working memory task with facial stimuli. PLoS

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[58] Vogel EK, Woodman GF, Luck SJ. The time course of consolidation in visual working memory. Journal of Experimental Psychology. Human Perception and Performance.

[59] Strehl U. What learning theories can teach us in designing neurofeedback

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treatments. Frontiers in Human Neuroscience. 2014;**8**(894):1-8

brain oscillations and EEG

1998;**244**(2):73-76

One. 2013;**8**(9):1-8

2008;**17**(3):177-182

2006;**32**(6):1436-1451

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*Neurofeedback Training on Aging: Prospects on Maintaining Cognitive Reserve DOI: http://dx.doi.org/10.5772/intechopen.90847*

Paulo, Brasil: Editora Casa do Psicólogo; 2004

*Neurological and Mental Disorders*

Regulation. 1996;**21**:3-33

1998;**23**(4):243-263

self-regulation. Biofeedback and Self-

http://research.gold.ac.uk/500/1/

connectivity and psychological

[44] Gruzelier J. A theory of alpha/theta neurofeedback, creative performance enhancement, long distance functional

integration. Research Report - Cognitive

[45] Gruzelier J. EEG-neurofeedback for optimising performance. I: A review of cognitive and affective outcome in healthy participants. Neuroscience and Biobehavioral Reviews. 2013;**44**:124-141

[46] Angelakis E, Stathopoulou S, Frymiare JL, Green DL, Lubar J, Kounios J. EEG neurofeedback: A brief overview and an example of peak alpha frequency training for cognitive enhancement in the elderly. The Clinical Neuropsychologist. 2007;**21**:110-129

[47] Becerra J, Fernández T, Roca-Stappung M, Díaz-Comas L, Galán L, Bosch J, et al. Neurofeedback in healthy elderly human subjects with electroencephalographic risk for cognitive disorder. Journal of Alzheimer's Disease. 2012;**28**:357-367. DOI: 10.3233/JAD-2011-111055

[48] Lecomte G, Juhel J. The effects of neurofeedback training on memory performance in elderly subjects. Psychology. 2011;**2**:846-852. DOI:

[49] Wang JR, Hsieh S. Neurofeedback training improves working memory and attention performance. Clinical Neurophysiology. 2013;**124**(12):1-15

[50] Reis J, Portugal AM, Fernandes L, Afonso N, Pereira M, Sousa N, et al. An alpha and theta intensive and short neurofeedback protocol for healthy aging working memory training. Frontiers in Aging Neuroscience. 2016;**8**:1-11

[51] Wechsler D. Escala de Inteligência

Wechsler para adultos -III. São

10.4236/psych.2011.28129

PSY\_Gruzelier\_2006a.pdf

process. 2008;**10**:101-109

Neurofeedback combine with training in metacognitive strategies: Effectiveness

[37] Monastra VJ et al. Electroencephalographic biofeedback in the treatment of attention deficit/hyperactivity disorder. Applied Psychophysiology and

[38] Hammond D. Neurofeedback training for anxiety and depression. Journal of Adult Development. 2005;**12**:131-137

[39] Sterman MB. Basic concepts and clinical findings in the treatment of seizures disorders with EEG operant conditioning. Clinical

Electroencephalography. 2000;**31**:45-55

neurofeedback training study. Clinical Neurophysiology. 2015;**126**(1):82-95

[40] Kober SE, Witte M, Stangl M, Valjamae A, Neuper C, Wood G. Shutting

down sensorimotor interference unblocks the networks for stimuling processing: An SMR

[41] Egner T, Gruzelier J. EEG biofeedback of low beta band components: Frequency specific effects on variables of attention and event- related brain potentials. Clinical Neurophysiology. 2004;**115**:131-139

[42] Vernon D, Egner T, Cooper N, Compton T, Neilands C, Sheri A, et al.

[43] Gruzelier J, Egner T, Vernon D.

Validating the Efficacy of Neurofeedback for Optimizing Performance. 2006. Available from:

The effects of training distinct neurofeedback protocols aspects of cognitive performance. International Journal of Psychophysiology. 2003;**47**:

Biofeedback. 2005;**30**(2):95-114

[36] Thompson M, Thompson L.

in student with ADD. Applied Psychophysiology and Biofeedback.

**42**

77-88

[52] Ostrosky-Solis F, Gómez-Perez ME, Matute E, Rosseli M, Ardila A, Pineda D. NEUROPSI Atención y memoria 6 a 85 anos. Manual, instructivo e pontuaciones totales. Cidade do México, México: American Book Store; 2003

[53] Signoret JL. B.E.C. 96: Evaluation des troubles de mémoire et des dêsordres cognitifs associés. Paris, França; 1996

[54] Klimesch W. Memory processes, brain oscillations and EEG synchronization. International Journal of Psychophysiology. 1996;**24**:61-100

[55] Klimesch W, Doppelmayr M, Russengger H, Pachinger T, Schwaiger J. Induced alpha band power changes in human EEG and attention. Neuroscience Letters. 1998;**244**(2):73-76

[56] Belham FS, Satler C, Garcia A, Tomaz C, Gasbarri A, Rego A, et al. Aged-related differences in cortical activity during visuo-spatial working memory task with facial stimuli. PLoS One. 2013;**8**(9):1-8

[57] Reuter-Lorenz PA, Cappell KA. Neurocognitive aging and the compensation hypothesis. Current Directions in Psychological Science. 2008;**17**(3):177-182

[58] Vogel EK, Woodman GF, Luck SJ. The time course of consolidation in visual working memory. Journal of Experimental Psychology. Human Perception and Performance. 2006;**32**(6):1436-1451

[59] Strehl U. What learning theories can teach us in designing neurofeedback treatments. Frontiers in Human Neuroscience. 2014;**8**(894):1-8

[60] Witte M, Kober SE, Nimaus M, Christa N, Wood G. Control beliefs

can predict the ability to up-regulate sensorimotor rhythm in neurofeedback training. Frontiers in Human Neuroscience. 2013;**07**:1-8

[61] Constantinidis C, Klingberg T. The neuroscience of working memory capacity and training. Nature Reviews. 2016;**17**(7):438-449. DOI: 10.1038/ nrn.2016.43

[62] Park DC, Reuter-Lorenz P. The adaptive brain: Aging and neurocognitive scaffolding. Annual Review of Psychology. 2009;**60**:173-196

[63] Chein JM, Schneider W. Neuroimaging studies of practicerelated change: fMRI and meta-analytic evidence of a domain-general control network for learning. Cognitive Brain Research. 2005;**25**:607-623. DOI: 10.1016/j.cogbrainres.2005.08.013

[64] Ghaziri J, Tucholka A, Larue V, Blanchette-Sylvestre M, Reyburn G, Gilbert G, et al. Neurofeedback training induces changes in white and gray matter. Clinical EEG and Neuroscience. 2013;**44**:265-272. DOI: 10.1177/1550059413476031

[65] Scholz J, Klein MC, Behrens TEJ, Johansen-Berg H. Training induces changes in white matter architecture. Nature Neuroscience. 2012;**12**:1370- 1371. DOI: 10.1038/nn.2412

[66] Belleville S, Mellah S, de Boysson C, Demonet JF, Bier B. The pattern and loci of training-induced brain changes in healthy older adults are predicted by the nature of the intervention. PLoS One. 2014;**9**:e102710. DOI: 10.1371/journal. pone.0102710

**45**

**Chapter 4**

**Abstract**

Feeding and Eating Disorders

Eating disorders, which are well known as a substantial mental health problem in society, have been reclassified as feeding and eating disorders in DSM-5 and also in the 11th revision of ICD. The new classification includes binge eating disorder and avoidant-restrictive food intake disorder (ARFID), in addition to anorexia and bulimia nervosa. They are considered serious disorders, with high morbidity and mortality risks, that affect the young community in particular. Current research shows increases in all genders and age groups. Various genetic and biologic factors, an insecure personality type, impulsive traits, dysfunctional emotion regulation, and society's ideal of slimness have been found to play a role in the development of these disorders. A dual approach with focus on the symptom and the underlying problems is needed for all types of eating disorders throughout the psychotherapeutic interventions. Assessing comorbid psychiatric and medical symptoms is extremely important. Further research and new directions of treatment are needed

**Keywords:** eating disorders, anorexia nervosa, bulimia nervosa, binge eating

Eating disorders, which are well known as a substantial mental health problem in society, can come across all ages, but anorexia nervosa and avoidant-restrictive food intake are more common in childhood and adolescents, while bulimia nervosa and binge eating disorder are less prevalent in pediatric patients, but also with

Recently, a systematic review analyzed the lifetime prevalence of eating disorders and found for anorexia nervosa a prevalence of 1.4% for women and 0.2% for men. Bulimia nervosa had higher prevalence scores 1.9% for women and 0.6% for men. Binge eating disorder had the highest prevalence percentage with 2.8% in women and 1% in men. The prevalence for avoidant-restrictive food intake disorder was investigated and was found to be 0.3% [2, 3]. All these results must be cautiously taken into consideration because the real community incidence of eating and feeding disorders is unknown. Other studies found an increasing number of cases diagnosed with bulimia nervosa or binge eating disorder [4, 5]. In the young women's population, anorexia nervosa seems to be the most predominant form of feeding and eating disorders, while binge eating disorder is more common

*Bianca Suciu and Cătălina-Angela Crișan*

with regard to the expanded classifications.

significant functional impairment [1].

disorder, treatment

**1. Introduction**

**2. Epidemiology**

## **Chapter 4** Feeding and Eating Disorders

*Bianca Suciu and Cătălina-Angela Crișan*

### **Abstract**

Eating disorders, which are well known as a substantial mental health problem in society, have been reclassified as feeding and eating disorders in DSM-5 and also in the 11th revision of ICD. The new classification includes binge eating disorder and avoidant-restrictive food intake disorder (ARFID), in addition to anorexia and bulimia nervosa. They are considered serious disorders, with high morbidity and mortality risks, that affect the young community in particular. Current research shows increases in all genders and age groups. Various genetic and biologic factors, an insecure personality type, impulsive traits, dysfunctional emotion regulation, and society's ideal of slimness have been found to play a role in the development of these disorders. A dual approach with focus on the symptom and the underlying problems is needed for all types of eating disorders throughout the psychotherapeutic interventions. Assessing comorbid psychiatric and medical symptoms is extremely important. Further research and new directions of treatment are needed with regard to the expanded classifications.

**Keywords:** eating disorders, anorexia nervosa, bulimia nervosa, binge eating disorder, treatment

### **1. Introduction**

Eating disorders, which are well known as a substantial mental health problem in society, can come across all ages, but anorexia nervosa and avoidant-restrictive food intake are more common in childhood and adolescents, while bulimia nervosa and binge eating disorder are less prevalent in pediatric patients, but also with significant functional impairment [1].

### **2. Epidemiology**

Recently, a systematic review analyzed the lifetime prevalence of eating disorders and found for anorexia nervosa a prevalence of 1.4% for women and 0.2% for men. Bulimia nervosa had higher prevalence scores 1.9% for women and 0.6% for men. Binge eating disorder had the highest prevalence percentage with 2.8% in women and 1% in men. The prevalence for avoidant-restrictive food intake disorder was investigated and was found to be 0.3% [2, 3]. All these results must be cautiously taken into consideration because the real community incidence of eating and feeding disorders is unknown. Other studies found an increasing number of cases diagnosed with bulimia nervosa or binge eating disorder [4, 5]. In the young women's population, anorexia nervosa seems to be the most predominant form of feeding and eating disorders, while binge eating disorder is more common

in men [6]. Overall, studies show a higher prevalence of eating disorders among females and the young population [7].

#### **3. Causes**

Genetic predisposition is associated with the diagnosis of anorexia nervosa. Studies demonstrated that it is also a vulnerability inherited for anxiety and obsessiveness, by examining the family members of patients suffering from eating disorders and identifying anxiety disorders, obsessive compulsive disorder and autistic spectrum disorders diagnosed in the family members. The families with eating disorders have higher levels of academic achievement, traits of perfectionism and sensitivity, being above the average [8]. On the other hand, some studies explained the onset of anorexic episodes in the context of nonspecific triggers such as puberty, changes of schools or home, exams, conflicts with friends, family members, being bullied and bereavement. The anorexic behavior becomes a mechanism that manifest's in discomfort situations rather than confronting them [9]. A report showed that bulimia and binge eating disorders are being influenced by environmental factors, but theses play also a part in the onset and evolution of anorexia nervosa. In the same study it was mentioned that 17–18 years old was the peak age onset for bulimia and binge eating disorders [10].

#### **4. Symptoms**

Typical symptoms describing patients with anorexia nervosa are an obsessive fear of gaining weight, body dysmorphia, voluntary and deliberate purging and over exercising. Purging is a voluntary action, characterized by putting the fingers down the throat to induce vomiting. Because of this repeated action on the knuckles of the right hand appear calluses, known as Russell sign, caused by the repeated pressure from the teeth during purging. In time purging becomes a reflex and patients can vomit without effort, quickly, within seconds. Due to the gastric acidity after vomiting, teeth may become denuded of enamel and the parotid gland becomes enlarged. As a consequence of many hours of physical exercise joint problems can be precipitated and, on the long term, osteoporosis can develop caused by malnutrition and endocrine abnormalities [11, 12].

Specific behaviors usually used by patients in order to lose more weight are represented by avoidance of calorie intake such as a restrictive diet, consuming vegan food, hiding or disposing the food that is served by offering to pets or friends, chewing gum or smoking just to feel the mouth full with something, trying to mimic the feel of fullness by drinking water or diet drinks, always calculating the amount of calories intake by reading all food labels or avoiding medication that can lead to weight gain. Another way to maintain or reduce weight is to overcome the calorie intake by inducing vomiting, using laxatives in excessive doses, exposing the body to cold just for burning more calories, doing exhausting physical exercises, administering pain killers to release pain in order to be able to over exercise, using and buying substances for losing weight. Also, compulsive behaviors of rechecking ones weight, examining oneself in mirrors for hours, seeking to feel their bones through skin, comparing their body to magazines or online pictures can be present [13].

To define compulsive exercises we must assume any form of physical activity that cannot be stopped or cut down even in the presence of detrimental effects on health status [14, 15]. For persons who associate excessive physical exercises,

**47**

*Feeding and Eating Disorders*

admissions [22, 23].

CT scanning or barium passage [25].

between the interval of 20–25 kg/m2

young old patients [26].

**5. Examination**

*DOI: http://dx.doi.org/10.5772/intechopen.92218*

this behavior usually started for healthy issues, prior to the presence of eating symptoms, and patients describe themselves as having greater levels of physical activity than their friends during childhood, or even being athletes during that period [16, 17]. For normal subjects, usually these activities come unplanned and are done in a spontaneous manner, with joy in participating, but for patients with eating disorders activities become carefully planned and self-conscious. A possible explanation of this behavior comes from ancient times, as an evolutionary adaptation; despite weight loss individuals are able to search food in wider areas [18]. Also, a strong emotional involvement is attached to physical activities [19, 20], and it is considered to be the last symptom that resolves [21]. Examples of such exercises are: swimming, running, cycling, all of this done in privet and solitude; go up and down the stairs more than it is required for a task, getting of public transport for walking long distances, standing on feet for longer than it is required or pacing all the time. Studies connect the over activity that is still present after discharge with a more chronic evolution, earlier relapse rates and longer periods of time spent in hospital

Gastrointestinal functional symptoms can also associate in the course evolution of an eating disorder. Patients with anorexia nervosa reported postprandial fullness, abdominal distension and unspecific abdominal pain. On the other hand, for bulimia nervosa more frequent were reported bloating, flatulence and constipation as gastrointestinal functional symptoms [24]. If these symptoms are severe enough and require more investigations, for patients that are malnourished, invasive investigations of the gut such as colonoscopy or upper gastrointestinal endoscopy, could lead to important risks. Patients diagnosed with anorexia nervosa have the gut much thinner than well-nourished patients, and so the risk of tear or perforation is much higher, therefore, less invasive investigation are considered to be safer, such as

Osteopenia represents a consequence of bone loss after a long period of low weight and sex steroid suppression. This effect may become irreversible in patients with severe anorexia nervosa, and implies a high risk for bone fracture even in

One of the most important phases in physical examination consists in determining the body mass index, which expresses weight in kilograms reported to height in squared meters (height is greater early in the morning). It is a simple formula to measure the nutritional risk but always needs to be interpreted in the clinical context. Sometimes based on this measurement, the case management plan can be influenced in determining which patient needs the most to be admitted and which can be treated in the community [27]. A so-called normal BMI is considered

quence of inappropriate restriction of food intake, this has to be taken into consideration. Measuring the physical resilience of the patient with a simple screening test can be done by telling the patient to sit up, squat and stand, or by using handgrip for measuring strength [28]. Another important step is measuring pulse, blood pressure, and ECG for investigating the risk of prolonged QTc interval (over 450 ms) that can indicate electrolyte disturbances (hypokalemia, hypomagnesaemia, and hypocalcemia), heart disease (myocardial ischemia and cardiomyopathies), and improper use of drugs such as antipsychotics, antidepressants, antihistamines, antibiotics, and antiarrhythmics. Commonly anorexic patients present cardiovascular instability as bradycardia, showing a pulse under 50 bpm, or resting tachycardia

, but if this parameter keeps falling as a conse-

#### *Feeding and Eating Disorders DOI: http://dx.doi.org/10.5772/intechopen.92218*

*Neurological and Mental Disorders*

**3. Causes**

**4. Symptoms**

females and the young population [7].

bulimia and binge eating disorders [10].

and endocrine abnormalities [11, 12].

in men [6]. Overall, studies show a higher prevalence of eating disorders among

Genetic predisposition is associated with the diagnosis of anorexia nervosa. Studies demonstrated that it is also a vulnerability inherited for anxiety and obsessiveness, by examining the family members of patients suffering from eating disorders and identifying anxiety disorders, obsessive compulsive disorder and autistic spectrum disorders diagnosed in the family members. The families with eating disorders have higher levels of academic achievement, traits of perfectionism and sensitivity, being above the average [8]. On the other hand, some studies explained the onset of anorexic episodes in the context of nonspecific triggers such as puberty, changes of schools or home, exams, conflicts with friends, family members, being bullied and bereavement. The anorexic behavior becomes a mechanism that manifest's in discomfort situations rather than confronting them [9]. A report showed that bulimia and binge eating disorders are being influenced by environmental factors, but theses play also a part in the onset and evolution of anorexia nervosa. In the same study it was mentioned that 17–18 years old was the peak age onset for

Typical symptoms describing patients with anorexia nervosa are an obsessive fear of gaining weight, body dysmorphia, voluntary and deliberate purging and over exercising. Purging is a voluntary action, characterized by putting the fingers down the throat to induce vomiting. Because of this repeated action on the knuckles of the right hand appear calluses, known as Russell sign, caused by the repeated pressure from the teeth during purging. In time purging becomes a reflex and patients can vomit without effort, quickly, within seconds. Due to the gastric acidity after vomiting, teeth may become denuded of enamel and the parotid gland becomes enlarged. As a consequence of many hours of physical exercise joint problems can be precipitated and, on the long term, osteoporosis can develop caused by malnutrition

Specific behaviors usually used by patients in order to lose more weight are represented by avoidance of calorie intake such as a restrictive diet, consuming vegan food, hiding or disposing the food that is served by offering to pets or friends, chewing gum or smoking just to feel the mouth full with something, trying to mimic the feel of fullness by drinking water or diet drinks, always calculating the amount of calories intake by reading all food labels or avoiding medication that can lead to weight gain. Another way to maintain or reduce weight is to overcome the calorie intake by inducing vomiting, using laxatives in excessive doses, exposing the body to cold just for burning more calories, doing exhausting physical exercises, administering pain killers to release pain in order to be able to over exercise, using and buying substances for losing weight. Also, compulsive behaviors of rechecking ones weight, examining oneself in mirrors for hours, seeking to feel their bones through skin, comparing their body to magazines or online pictures can

To define compulsive exercises we must assume any form of physical activity that cannot be stopped or cut down even in the presence of detrimental effects on health status [14, 15]. For persons who associate excessive physical exercises,

**46**

be present [13].

this behavior usually started for healthy issues, prior to the presence of eating symptoms, and patients describe themselves as having greater levels of physical activity than their friends during childhood, or even being athletes during that period [16, 17]. For normal subjects, usually these activities come unplanned and are done in a spontaneous manner, with joy in participating, but for patients with eating disorders activities become carefully planned and self-conscious. A possible explanation of this behavior comes from ancient times, as an evolutionary adaptation; despite weight loss individuals are able to search food in wider areas [18]. Also, a strong emotional involvement is attached to physical activities [19, 20], and it is considered to be the last symptom that resolves [21]. Examples of such exercises are: swimming, running, cycling, all of this done in privet and solitude; go up and down the stairs more than it is required for a task, getting of public transport for walking long distances, standing on feet for longer than it is required or pacing all the time. Studies connect the over activity that is still present after discharge with a more chronic evolution, earlier relapse rates and longer periods of time spent in hospital admissions [22, 23].

Gastrointestinal functional symptoms can also associate in the course evolution of an eating disorder. Patients with anorexia nervosa reported postprandial fullness, abdominal distension and unspecific abdominal pain. On the other hand, for bulimia nervosa more frequent were reported bloating, flatulence and constipation as gastrointestinal functional symptoms [24]. If these symptoms are severe enough and require more investigations, for patients that are malnourished, invasive investigations of the gut such as colonoscopy or upper gastrointestinal endoscopy, could lead to important risks. Patients diagnosed with anorexia nervosa have the gut much thinner than well-nourished patients, and so the risk of tear or perforation is much higher, therefore, less invasive investigation are considered to be safer, such as CT scanning or barium passage [25].

Osteopenia represents a consequence of bone loss after a long period of low weight and sex steroid suppression. This effect may become irreversible in patients with severe anorexia nervosa, and implies a high risk for bone fracture even in young old patients [26].

#### **5. Examination**

One of the most important phases in physical examination consists in determining the body mass index, which expresses weight in kilograms reported to height in squared meters (height is greater early in the morning). It is a simple formula to measure the nutritional risk but always needs to be interpreted in the clinical context. Sometimes based on this measurement, the case management plan can be influenced in determining which patient needs the most to be admitted and which can be treated in the community [27]. A so-called normal BMI is considered between the interval of 20–25 kg/m2 , but if this parameter keeps falling as a consequence of inappropriate restriction of food intake, this has to be taken into consideration. Measuring the physical resilience of the patient with a simple screening test can be done by telling the patient to sit up, squat and stand, or by using handgrip for measuring strength [28]. Another important step is measuring pulse, blood pressure, and ECG for investigating the risk of prolonged QTc interval (over 450 ms) that can indicate electrolyte disturbances (hypokalemia, hypomagnesaemia, and hypocalcemia), heart disease (myocardial ischemia and cardiomyopathies), and improper use of drugs such as antipsychotics, antidepressants, antihistamines, antibiotics, and antiarrhythmics. Commonly anorexic patients present cardiovascular instability as bradycardia, showing a pulse under 50 bpm, or resting tachycardia

with a pulse over 100 bpm suggesting infection or dehydration [29]. Also, basic screening is necessary. A full blood cell count has to be done, biochemical assays such as transaminase to evaluate liver function, creatinine and urea for determining renal function. Electrolytes abnormalities are common and need to be measured to exclude hyponatremia after an excessive water intake, hypokalemia in the context of excessive purging, or hypocalcaemia, hypomagnesaemia that can indicate the improper use of laxatives. Thyroid function should be checked together with plasma ferritin, folate, and B12 vitamin [30].

Body temperature frequently drops under 36°C in anorexic patients, who voluntary induce hypothermia in order to start shivering, consume energy and lose some more weight. Fever in a patient with low BMI is always significant and can indicate infection, with negative consequences because even minor episodes of sepsis can have a fatal outcome. Other signs present could be pale conjunctives, dry tongue and teguments, muscular weakness, peripheral edema in the context of low-level albumin, hand calluses after self-induced vomiting. It is not uncommon that patients present constipation, as a paradox effect of withdrawing the laxatives that were used for long periods of time in very high doses [31].

#### **6. Making a diagnosis of eating disorder**

The ICD-11 restructured the chapter of feeding and eating disorders guided by the principles of more clinical utility and relevance around the world, after 25 years of research and evidence based knowledge. The disorders included in this chapter are not better explained by other health problems, developmentally conditions or cultural context. Moreover, two previous distinct conditions were united in one single block named feeding and eating disorders that combines abnormal eating patterns associated with fear of gaining weight, body image and feeding behaviors that imply limited food intake, eating non-edible substances, or voluntary regurgitation of foods that have been eaten. We could say that this grouping decision enhances the clinical importance of feeding problems during infancy and childhood [32].

The ICD-11 guidelines for Pica have not been changed in a substantial way from the previous version of ICD. Pica is still characterized by a frequent and regular ingestion of non-nutritive substances, like different objects or materials, to a persistent and severe degree that requires special clinical attention, in a subject capable to distinguish between substances that can and cannot be eaten. This type of behavior has severe risks on the health and functioning system of an individual [31, 32].

For the rumination and regurgitation disorder the ICD-11 guidelines are almost the same as in the ICD-10. The main symptoms of the disorder need to be frequent as several times per week and present over a sustained period of at least several weeks. Characteristic symptoms that appear in an individual that reached the age of 2 are represented by regurgitation of food that was previous swallowed or the food that was brought up in the mouth could be re-chewed, re-swallowed or spat out [33].

A new ICD-11 diagnosis is avoidant-restrictive food intake disorder, characterized by a very low and insufficient amount or variety of food in order to supply an adequate level of energy or demands. This course of restriction causes weight loss and nutritional deficiencies but without a preoccupation of body weight and shape [33].

For Anorexia nervosa, the major features of the disorder remained unchanged in the ICD-11, such as a low body weight for an individual's height, age and developmental phase without a better explanation of another condition. The low weight

**49**

*Feeding and Eating Disorders*

18.5 and 14.0 kg/m2

*DOI: http://dx.doi.org/10.5772/intechopen.92218*

is defined by a body mass index under 18.5 km/m<sup>2</sup>

weight and requires a BMI below 14.0 kg/m<sup>2</sup>

the regular compensatory behaviors [35].

rather the quantity ingested [36].

in children or adolescents, but these should be used as general aspects of reference permitting in some circumstance to diagnose anorexia nervosa at higher levels of weight. A detailed specification was added to anorexia as a severity qualifier indicating that the level of underweight status can influence the prognosis by other health complications determining a high mortality risk or a poorer outcome. This classification consists in significantly low body weight; defined as a BMI between

percentile in children. The next severity step is named as dangerously low body

loss weight so that anorexia nervosa diagnosis can be confirmed [32–34].

Bulimia nervosa in the ICD-11 remains characterized by binge eating episodes and compensatory behaviors to prevent weight gain but, different from anorexia nervosa, the patient is not underweight even if they are preoccupied by body shape image. A change in the frequency of the binge eating episodes was made by reducing them to once a week or more over a period of at least 1 month. Also, the time criteria have been shortened admitting the importance of receiving clinical care without any further delay. In parallel, for DSM-5 the time criteria include a period of at least 3 months. A binge eating episode represents a distinct period when an individual has no control over the eating or the amount of food intake. The common type of bulimia is the one without purging but with severe fasting or physical exercises and can be difficult to differentiate from binge eating disorder based solely on

A new diagnosis was added to ICD-11, named binge eating disorder, separated by the other eating disorders as a disturbance characterized by recurrent binge eating episodes accompanied by negative emotions and severe distress, without compensatory behaviors to prevent weight gain. This category was previously described in the Appendix of DSM-IV and now forms a new diagnosis in the DSM-5. To assume a correct diagnosis according to DSM-5, 3 out of 5 additional features have to be present, like: eating faster than normal; eating even if the patient does not feel hungry; eating until he feels uncomfortably full; the food intake is done in solitude; and negative emotions such as guilt, disgust or depression can follow the overeating. An important aspect is that ICD-11 guidelines do not require for the binge eating episodes an objective evaluation of the amount of food eaten but suggests the importance of the subjective experience of losing control over eating

While both bulimia nervosa and binge eating disorder associate marked distress

in the ICD-11 criteria, the DSM-5 requires marked distress just for binge eating disorder and not in the case of bulimia nervosa. A possible explanation for these differences between the two diagnostic categories would be the presence of the weight-compensatory behaviors that we can assume to reflect severe distress. In ICD-11 disturbances in body shape are required for anorexia and bulimia nervosa;

percentile. Another important aspect in the ICD-11 is the qualifier anorexia nervosa in recovery with normal body weight, providing a solution for those patients that have regained weight but still need special attention and care. Despite the DSM-5 classifications, ICD-11 emphasizes the behavior patterns (restricting pattern and binge-purge pattern) that are weight related and used by patients in order to lose more weight. In both classification systems, physical symptoms such as amenorrhea, osteopenia are frequent consequences of food restriction, they still occur but they are no longer considered as one of the main criteria for diagnosis. Also, the ICD-11 and DSM-5 do not include as mandatory the presence of a reported fear about gaining weight, considering this symptom as a more culturally based belief. On the other hand, there is a need of modified normal behavior in order to prevent

for adult subjects and between the fifth percentile and the 0.3

or less than the fifth percentile

for adults and for children less than 0.3

#### *Feeding and Eating Disorders DOI: http://dx.doi.org/10.5772/intechopen.92218*

*Neurological and Mental Disorders*

plasma ferritin, folate, and B12 vitamin [30].

**6. Making a diagnosis of eating disorder**

with a pulse over 100 bpm suggesting infection or dehydration [29]. Also, basic screening is necessary. A full blood cell count has to be done, biochemical assays such as transaminase to evaluate liver function, creatinine and urea for determining renal function. Electrolytes abnormalities are common and need to be measured to exclude hyponatremia after an excessive water intake, hypokalemia in the context of excessive purging, or hypocalcaemia, hypomagnesaemia that can indicate the improper use of laxatives. Thyroid function should be checked together with

Body temperature frequently drops under 36°C in anorexic patients, who voluntary induce hypothermia in order to start shivering, consume energy and lose some more weight. Fever in a patient with low BMI is always significant and can indicate infection, with negative consequences because even minor episodes of sepsis can have a fatal outcome. Other signs present could be pale conjunctives, dry tongue and teguments, muscular weakness, peripheral edema in the context of low-level albumin, hand calluses after self-induced vomiting. It is not uncommon that patients present constipation, as a paradox effect of withdrawing the laxatives

The ICD-11 restructured the chapter of feeding and eating disorders guided by the principles of more clinical utility and relevance around the world, after 25 years of research and evidence based knowledge. The disorders included in this chapter are not better explained by other health problems, developmentally conditions or cultural context. Moreover, two previous distinct conditions were united in one single block named feeding and eating disorders that combines abnormal eating patterns associated with fear of gaining weight, body image and feeding behaviors that imply limited food intake, eating non-edible substances, or voluntary regurgitation of foods that have been eaten. We could say that this grouping decision enhances the clinical importance of feeding problems during infancy and

The ICD-11 guidelines for Pica have not been changed in a substantial way from the previous version of ICD. Pica is still characterized by a frequent and regular ingestion of non-nutritive substances, like different objects or materials, to a persistent and severe degree that requires special clinical attention, in a subject capable to distinguish between substances that can and cannot be eaten. This type of behavior has severe risks on the health and functioning system of an individual [31, 32]. For the rumination and regurgitation disorder the ICD-11 guidelines are almost the same as in the ICD-10. The main symptoms of the disorder need to be frequent as several times per week and present over a sustained period of at least several weeks. Characteristic symptoms that appear in an individual that reached the age of 2 are represented by regurgitation of food that was previous swallowed or the food that was brought up in the mouth could be re-chewed, re-swallowed or

A new ICD-11 diagnosis is avoidant-restrictive food intake disorder, characterized by a very low and insufficient amount or variety of food in order to supply an adequate level of energy or demands. This course of restriction causes weight loss and nutritional deficiencies but without a preoccupation of body weight and

For Anorexia nervosa, the major features of the disorder remained unchanged in the ICD-11, such as a low body weight for an individual's height, age and developmental phase without a better explanation of another condition. The low weight

that were used for long periods of time in very high doses [31].

**48**

childhood [32].

spat out [33].

shape [33].

is defined by a body mass index under 18.5 km/m<sup>2</sup> or less than the fifth percentile in children or adolescents, but these should be used as general aspects of reference permitting in some circumstance to diagnose anorexia nervosa at higher levels of weight. A detailed specification was added to anorexia as a severity qualifier indicating that the level of underweight status can influence the prognosis by other health complications determining a high mortality risk or a poorer outcome. This classification consists in significantly low body weight; defined as a BMI between 18.5 and 14.0 kg/m2 for adult subjects and between the fifth percentile and the 0.3 percentile in children. The next severity step is named as dangerously low body weight and requires a BMI below 14.0 kg/m<sup>2</sup> for adults and for children less than 0.3 percentile. Another important aspect in the ICD-11 is the qualifier anorexia nervosa in recovery with normal body weight, providing a solution for those patients that have regained weight but still need special attention and care. Despite the DSM-5 classifications, ICD-11 emphasizes the behavior patterns (restricting pattern and binge-purge pattern) that are weight related and used by patients in order to lose more weight. In both classification systems, physical symptoms such as amenorrhea, osteopenia are frequent consequences of food restriction, they still occur but they are no longer considered as one of the main criteria for diagnosis. Also, the ICD-11 and DSM-5 do not include as mandatory the presence of a reported fear about gaining weight, considering this symptom as a more culturally based belief. On the other hand, there is a need of modified normal behavior in order to prevent loss weight so that anorexia nervosa diagnosis can be confirmed [32–34].

Bulimia nervosa in the ICD-11 remains characterized by binge eating episodes and compensatory behaviors to prevent weight gain but, different from anorexia nervosa, the patient is not underweight even if they are preoccupied by body shape image. A change in the frequency of the binge eating episodes was made by reducing them to once a week or more over a period of at least 1 month. Also, the time criteria have been shortened admitting the importance of receiving clinical care without any further delay. In parallel, for DSM-5 the time criteria include a period of at least 3 months. A binge eating episode represents a distinct period when an individual has no control over the eating or the amount of food intake. The common type of bulimia is the one without purging but with severe fasting or physical exercises and can be difficult to differentiate from binge eating disorder based solely on the regular compensatory behaviors [35].

A new diagnosis was added to ICD-11, named binge eating disorder, separated by the other eating disorders as a disturbance characterized by recurrent binge eating episodes accompanied by negative emotions and severe distress, without compensatory behaviors to prevent weight gain. This category was previously described in the Appendix of DSM-IV and now forms a new diagnosis in the DSM-5. To assume a correct diagnosis according to DSM-5, 3 out of 5 additional features have to be present, like: eating faster than normal; eating even if the patient does not feel hungry; eating until he feels uncomfortably full; the food intake is done in solitude; and negative emotions such as guilt, disgust or depression can follow the overeating. An important aspect is that ICD-11 guidelines do not require for the binge eating episodes an objective evaluation of the amount of food eaten but suggests the importance of the subjective experience of losing control over eating rather the quantity ingested [36].

While both bulimia nervosa and binge eating disorder associate marked distress in the ICD-11 criteria, the DSM-5 requires marked distress just for binge eating disorder and not in the case of bulimia nervosa. A possible explanation for these differences between the two diagnostic categories would be the presence of the weight-compensatory behaviors that we can assume to reflect severe distress. In ICD-11 disturbances in body shape are required for anorexia and bulimia nervosa;

self-body image concerns can be present in the binge eating disorder or avoidantrestrictive food intake disorder but are not necessary criteria. All in all, the new changes have the purpose to broaden the diagnostic process and facilitate clinical practice with the disadvantage of over diagnosing but also with respect to the course of life evolution [37].

If the criteria of behavior frequency are not fulfilled or other symptoms are considered sub-threshold, those eating disorders are classified in the DSM-5 as unspecified feeding and eating disorders, and in the ICD-11 as poorly specified other feeding and eating disorder [34, 37].

#### **7. Differential diagnosis**

Eating disorders must be medically assessed in order to establish if present physical conditions are consequences of the mental illness or different somatic health problems. This strategy allows developing an integrated management plan, because both problems need proper evaluation and treatment and can impact recovery or the quality of life [38].

The most common symptoms in anorexia nervosa are the fear of gaining weight and the excessive preoccupation of being overweight or fat. Despite the fact that they are malnourished, patients try to lose even more weight. In contrast, many gastrointestinal illnesses have as a central symptom the weight loss and in this situation the patient is worried about the loss and tries to regain weight. The main two illnesses with this symptomatology are coeliac disease and inflammatory bowel disease. More family members can be affected by these diseases, but such family predisposition can be present for eating disorders too [39].

On the other hand, functional gastrointestinal disorders cam mimic an eating disorder, but usually they do not associate weight loss and have a long past evolution in the patient's history. Such frequently reported diseases are the irritable bowel syndrome and the non-ulcer dyspepsia, also common in patients with diagnose of eating disorder. Food intolerance and allergies can simultaneously be present in a patient with eating disorders, but in this scenario it is more difficult to precisely discriminate between the two conditions [40]. The loss of appetite is a very common symptom, but nonspecific, in both mental and physical disorders. It can associate with weight lost and needs more investigating. In eating disorders, patients do not lose their appetite, the restriction from food intake has a voluntary component, that is not present in organic disorders, were the loss of appetite is without effort and involuntary. On the other hand, compulsive eating with an increased level of appetite can be present in Prader-Willi syndrome, craniopharyngioma, tumors of the hypothalamus or recovery from acute illnesses. This symptom is characteristic in bulimia nervosa or the binge purge subtype of anorexia [41]. Dysphagia is considered an alarming symptom in old age patients, and needs endoscopy or barium passage, malignancy strictures or achalasia are usually suspected. Other gastrointestinal symptoms that are commonly present include odynophagia, nausea, vomiting, hematemesis or melena, abdominal pain, constipation, diarrhea. Odynophagia described as pain when swallowing can be present in a reflux esophagitis or esophageal candida. Vomiting is a very unspecific symptom usually associated with nausea that can have different causes such as inflammatory bowel disease, side effects of different drugs, a high intracranial pressure, pyloric stenosis, gastro-paresis, but in these circumstances a voluntary control is not present as in eating disorders and it is not hidden [42]. Hematemesis or melena can represent a medical emergency, but frequently represent a consequence of purging and vomiting, with the development of Mallory Weiss tears. For the abdominal pain the doctor should establish

**51**

m2

will lead to death [44].

*Feeding and Eating Disorders*

ulcerative colitis [43].

years or early adulthood [43].

be placed in a chronological order.

**8. Management of eating disorders**

tion phase much easier. Patients with a BMI over 16 kg/m2

*DOI: http://dx.doi.org/10.5772/intechopen.92218*

the level of intensity, quality and localization of the pain in order to differentiate a peptic ulcer, gallstones, pancreatitis or appendicitis. Constipation, diarrhea, and rectal bleeding are symptoms that need to be integrated with other factors and the most important aspect is the change in bowel habit that can imply Crohn's disease or

The age of onset can be a very important clue. Usually, organic conditions, in special malignant illnesses that can manifest with weight loss, become more frequent with old age. If symptoms appear over 50 years, appropriate investigations are required. Moreover, the onset of eating disorders is identified in the teenage

In order to establish a diagnosis of an eating disorder the patient should be physically examined, the mental state evaluation should be done, all of these supported by a detailed medical history, family history and social context. All symptoms must

International guidelines recommend psycho-behavior therapy for all eating disorders, which can be applied in a form of outpatient care, when the treatment is accepted and the patient accepts to cooperate, with major beneficial effects, being more cost-effective, reducing hospitalizations, making patients feel more secure in their own environment, maintaining social contact with friends and family members, being able to perform other pleasant activities and making the rehabilita-

binge purge syndrome are usually treated in outpatient or day care units because the risks are less serious on physical harm and this form of outpatient context has been proved to be highly effective [44]. On the other hand, for more severe forms, when patients' symptoms are not improving with home treatment or the patients' physical status is unstable (weight is rapidly diminishing, the BMI is under 14 kg/

, low pulse, blood pressure, body temperature decreasing or fever being present, difficulty in performing the basic test of physical strength) more restrictive measures must be taken in a partial or day admission, or even a compulsory treatment would be necessary in order for the patient to improve physical and mentally but also, to limit potential harm behavior [45]. Anorexic patients in general do not want to die, but it is needed to understand the psychological drive of an anorexic patient who has an extreme fear of gaining weight, who is unable to rationally see that their physical state has become critical, and if the weight will continue to drop the result

It is highly recommended for these patients to be treated by a multi-disciplinary

team with a minimum of a psychological therapist and a family doctor, but in hospital care additional support is required as a registered dietician, specialist physician, psychiatrist, nurses, physiotherapist, occupational therapist and social worker [46]. Nurses and other medical staff represent a key element in the management treatment approach by limiting mobility, imposing bed rest, monitoring fluid balance and physical symptoms (pulse, blood pressure, temperature), supervising mealtimes (observation for at least 1 h after eating), showers, toilets (patients being alone can consider a perfect opportunity to engage in behaviors such as purging, excessive physical exercises or water loading for a false weight gain). Even with the risk of some saying these rules are unethical; protocols like this can avoid numerous unwanted behaviors done by patients in the purpose of resisting the weight gain and destroying the process of recovery. In the context of bed resting for an easier and closer observation it is important to start prophylaxis for deep vein thrombosis with

, with bulimia nervosa or

#### *Feeding and Eating Disorders DOI: http://dx.doi.org/10.5772/intechopen.92218*

*Neurological and Mental Disorders*

other feeding and eating disorder [34, 37].

of life evolution [37].

**7. Differential diagnosis**

recovery or the quality of life [38].

predisposition can be present for eating disorders too [39].

self-body image concerns can be present in the binge eating disorder or avoidantrestrictive food intake disorder but are not necessary criteria. All in all, the new changes have the purpose to broaden the diagnostic process and facilitate clinical practice with the disadvantage of over diagnosing but also with respect to the course

If the criteria of behavior frequency are not fulfilled or other symptoms are considered sub-threshold, those eating disorders are classified in the DSM-5 as unspecified feeding and eating disorders, and in the ICD-11 as poorly specified

Eating disorders must be medically assessed in order to establish if present physical conditions are consequences of the mental illness or different somatic health problems. This strategy allows developing an integrated management plan, because both problems need proper evaluation and treatment and can impact

The most common symptoms in anorexia nervosa are the fear of gaining weight and the excessive preoccupation of being overweight or fat. Despite the fact that they are malnourished, patients try to lose even more weight. In contrast, many gastrointestinal illnesses have as a central symptom the weight loss and in this situation the patient is worried about the loss and tries to regain weight. The main two illnesses with this symptomatology are coeliac disease and inflammatory bowel disease. More family members can be affected by these diseases, but such family

On the other hand, functional gastrointestinal disorders cam mimic an eating disorder, but usually they do not associate weight loss and have a long past evolution in the patient's history. Such frequently reported diseases are the irritable bowel syndrome and the non-ulcer dyspepsia, also common in patients with diagnose of eating disorder. Food intolerance and allergies can simultaneously be present in a patient with eating disorders, but in this scenario it is more difficult to precisely discriminate between the two conditions [40]. The loss of appetite is a very common symptom, but nonspecific, in both mental and physical disorders. It can associate with weight lost and needs more investigating. In eating disorders, patients do not lose their appetite, the restriction from food intake has a voluntary component, that is not present in organic disorders, were the loss of appetite is without effort and involuntary. On the other hand, compulsive eating with an increased level of appetite can be present in Prader-Willi syndrome, craniopharyngioma, tumors of the hypothalamus or recovery from acute illnesses. This symptom is characteristic in bulimia nervosa or the binge purge subtype of anorexia [41]. Dysphagia is considered an alarming symptom in old age patients, and needs endoscopy or barium passage, malignancy strictures or achalasia are usually suspected. Other gastrointestinal symptoms that are commonly present include odynophagia, nausea, vomiting, hematemesis or melena, abdominal pain, constipation, diarrhea. Odynophagia described as pain when swallowing can be present in a reflux esophagitis or esophageal candida. Vomiting is a very unspecific symptom usually associated with nausea that can have different causes such as inflammatory bowel disease, side effects of different drugs, a high intracranial pressure, pyloric stenosis, gastro-paresis, but in these circumstances a voluntary control is not present as in eating disorders and it is not hidden [42]. Hematemesis or melena can represent a medical emergency, but frequently represent a consequence of purging and vomiting, with the development of Mallory Weiss tears. For the abdominal pain the doctor should establish

**50**

the level of intensity, quality and localization of the pain in order to differentiate a peptic ulcer, gallstones, pancreatitis or appendicitis. Constipation, diarrhea, and rectal bleeding are symptoms that need to be integrated with other factors and the most important aspect is the change in bowel habit that can imply Crohn's disease or ulcerative colitis [43].

The age of onset can be a very important clue. Usually, organic conditions, in special malignant illnesses that can manifest with weight loss, become more frequent with old age. If symptoms appear over 50 years, appropriate investigations are required. Moreover, the onset of eating disorders is identified in the teenage years or early adulthood [43].

In order to establish a diagnosis of an eating disorder the patient should be physically examined, the mental state evaluation should be done, all of these supported by a detailed medical history, family history and social context. All symptoms must be placed in a chronological order.

#### **8. Management of eating disorders**

International guidelines recommend psycho-behavior therapy for all eating disorders, which can be applied in a form of outpatient care, when the treatment is accepted and the patient accepts to cooperate, with major beneficial effects, being more cost-effective, reducing hospitalizations, making patients feel more secure in their own environment, maintaining social contact with friends and family members, being able to perform other pleasant activities and making the rehabilitation phase much easier. Patients with a BMI over 16 kg/m2 , with bulimia nervosa or binge purge syndrome are usually treated in outpatient or day care units because the risks are less serious on physical harm and this form of outpatient context has been proved to be highly effective [44]. On the other hand, for more severe forms, when patients' symptoms are not improving with home treatment or the patients' physical status is unstable (weight is rapidly diminishing, the BMI is under 14 kg/ m2 , low pulse, blood pressure, body temperature decreasing or fever being present, difficulty in performing the basic test of physical strength) more restrictive measures must be taken in a partial or day admission, or even a compulsory treatment would be necessary in order for the patient to improve physical and mentally but also, to limit potential harm behavior [45]. Anorexic patients in general do not want to die, but it is needed to understand the psychological drive of an anorexic patient who has an extreme fear of gaining weight, who is unable to rationally see that their physical state has become critical, and if the weight will continue to drop the result will lead to death [44].

It is highly recommended for these patients to be treated by a multi-disciplinary team with a minimum of a psychological therapist and a family doctor, but in hospital care additional support is required as a registered dietician, specialist physician, psychiatrist, nurses, physiotherapist, occupational therapist and social worker [46]. Nurses and other medical staff represent a key element in the management treatment approach by limiting mobility, imposing bed rest, monitoring fluid balance and physical symptoms (pulse, blood pressure, temperature), supervising mealtimes (observation for at least 1 h after eating), showers, toilets (patients being alone can consider a perfect opportunity to engage in behaviors such as purging, excessive physical exercises or water loading for a false weight gain). Even with the risk of some saying these rules are unethical; protocols like this can avoid numerous unwanted behaviors done by patients in the purpose of resisting the weight gain and destroying the process of recovery. In the context of bed resting for an easier and closer observation it is important to start prophylaxis for deep vein thrombosis with

low molecular weight heparin [47]. Also, clothes need to be checked because they can represent means for falsifying weight or transport regurgitated food. Dieticians are also important for the safe management of patients with eating disorders. They need to be consulted for the risk of re-feeding syndrome, must establish a meal plan for proper nutritional requirements, to include all nutrients, carbohydrates, proteins, fats, vitamins and all kinds of minerals, to use supplements if the case imposes, and monitor weight gaining in a correct pace, and also, on the long term, to provide proper education for a balanced nutrition plan and teach patients how to prepare their meals and eat adequately in social situations [46].

The management of over activity can be treated firstly by providing psychoeducation about the advantages and disadvantages of this behavior and to discourage exercise. Also, relaxation and distractions techniques can be helpful, the use of wheelchairs to reduce the level of energy spent, administer Olanzapine with a good effect on the compulsive behavior, providing a calm and warm environment, with a permanent supervision from medical staff [48].

Treatment goals address numerous aspects such as nutritional, physical, social and mental health comorbidities. Some studies were made on healthy subjects, who voluntarily agreed to be starved, and the effect of this demonstrated that even in normal subjects thought processes were slowed, executive functions were impaired, with decision making disturbances, and personality traits accentuated in a manner that persons were more paranoid, depressed or became psychotic. The majority of these symptoms were reversed by re-feeding treatment in normal individuals and similarities were observed for anorexic patients, who had an improvement in thinking, mood stability and improved the engagement level for psychotherapy [49].

For malnourished patients re-feeding may represent the only solution for surviving. It has to be initiated promptly with benefits on the physical strength, cerebral function. It restores the reduced size of internal organs, heart, gut and their functions, offers a better functioning of the immune system, patients being less susceptible for infections. All of these outcomes appear after a slow process, because the body needs to readapt to the increased availability of calories and nutrients [50]. If the patients have a very low BMI, under 16 kg/m<sup>2</sup> , or had a rapid loss weight within the last 3–6 months of over 15% of the body weight, had little nutritional intake for more than 10 days or have low levels of potassium, phosphate, magnesium prior to the re-feeding, they are at risk of developing a re-feeding syndrome, according to the NICE guidelines [51]. The re-feeding syndrome can be defined as a consequence of trying to re-establish the normal weight of a very malnourished patient. During this phase, the maximal risk is within 72 h and implies potentially fatal shifts in fluids and electrolytes. The characteristic biochemical abnormality is the hypophosphatemia, but hypokalemia and hypomagnesaemia can also occur. NICE recommends starting re-feeding process at 5 kcal/kg/24 h for those with severe anorexia nervosa, through a nasogastric re-feeding tube and progressively increasing the rate of re-feeding to the target calorie intake over the next 4–7 days. Other studies showed that higher initial re-feeding rates can be applied such as 15 or 20 kcal/kg/ 24 h, with or without the association of re-feeding syndrome [52].

In order to avoid this kind of situations the patient has to be admitted in special medical units with experience in re-feeding syndrome, to monitor the blood chemistry twice a day, start with caution and increase quickly if the patient tolerates well. A particular aspect is to start giving thiamine before feeding starts, and to continue with it at least 10 days in order to overcome the development of Wernicke's encephalopathy or Korsakoff syndrome. Hypophosphatemia can have fatal effect through numerous clinical features such as cardiac failure, arrhythmias, seizures, tremor, rhabdomyolysis, and respiratory failure. Hypomagnesaemia can also occur and complicate the feeding treatment by cardiac arrhythmia, hypertension crises,

**53**

*Feeding and Eating Disorders*

cardiomyopathy [53, 54].

oral intake [55].

*DOI: http://dx.doi.org/10.5772/intechopen.92218*

tremor, tetany, confusion, seizures and abdominal pain. Hypokalemia can appear as a consequence of staring to feed the anorexic patient, but more common it is present in patients with binge-purge subtype because of vomiting or induced laxative diarrhea. All of these electrolyte deficiencies must be treated properly to offer a safe outcome. Other complications that can occur during re-feeding are elevated transaminase levels with liver failure, coagulation problems, acute tubular renal necrosis, tubular renal nephritis, cardiac Torsade du Pointes, arrhythmias, prolonged QTc,

If the patients is in a severe state for the re-feeding process doctors have to decide if an enteral tube feeding is required. For this intervention training and experience is need, because the gut wall in malnourished patients is extremely thin and there is the risk of rupture, a lethal complication. Also after passing the tube, the safety position must be checked before it is used. In order to confirm the placement of the tube, gastric fluid can be aspirated, and the level of acidity can be determined, or an X-ray might be required. Gastrostomy tubes are not advisable to use, they need an endoscopic or radiologic approach, with the risk of peritonitis or other infections. Feeding through a tube is just a temporary solution, as part of an integrated plan, and patients need to be responsible and slowly introduce a full

For osteopenia the recommended treatment is weight restoration and a normalization of the endocrine hormones. Also hormones substitution with transdermal estrogen, analogue of parathyroid hormone, bisphosphonates, raloxifene and

Psychotherapy should be the treatment of choice for all eating disorders. The number of sessions required is different in each eating disorder type. In the case of anorexia nervosa no specific psychotherapy has shown clear superiority, but the number of sessions required is the highest, with an average of 40. Adolescents with anorexia nervosa have better outcomes after family therapy. For bulimia nervosa and binge eating disorder psychotherapy should be offered as a first line treatment, especially cognitive behavior therapy, or as an alternative interpersonal psychotherapy, psychodynamic, or family-based therapy in children and adolescent with bulimia nervosa. Usually the number of sessions required is less for bulimia and

Pharmacological therapies with positive results in controlled trials in eating disorders are second generation of antipsychotics and antidepressants. For anorexia nervosa olanzapine had the most beneficial effects, in the case of bulimia nervosa and binge eating disorder Fluoxetine showed a good outcome, with a small effect from Lisdexamfetamine for binge eating disorder and Mirtazapine for avoidant

Eating disorders characterized by low weight associate high morbidity and mortality rates. A follow-up study which monitored hospitalized patients with anorexia nervosa reported an average life expectancy of 39 years. Studies showed that 1/3 of patients suffering from anorexia nervosa tend to have a full recovery, in same percentage patients have just a partial recovery, and approximately 1/3 will have a chronic evolution or die. On a more optimistic point of view, a full recovery has been shown to be possible but with early intervention plan and sustained treatment

In general the prognosis for bulimia nervosa is good with treatment and assistance, but if the patient associate low self-esteem or different forms of personality

denosumab drugs can be prescribed in this case [56].

binge eating disorder, with a medium of 20 weeks [57, 58].

restrictive eating disorder [59, 60].

over a medium of almost 7 to 9 years [61].

**9. Evolution and prognosis**

#### *Feeding and Eating Disorders DOI: http://dx.doi.org/10.5772/intechopen.92218*

*Neurological and Mental Disorders*

low molecular weight heparin [47]. Also, clothes need to be checked because they can represent means for falsifying weight or transport regurgitated food. Dieticians are also important for the safe management of patients with eating disorders. They need to be consulted for the risk of re-feeding syndrome, must establish a meal plan for proper nutritional requirements, to include all nutrients, carbohydrates, proteins, fats, vitamins and all kinds of minerals, to use supplements if the case imposes, and monitor weight gaining in a correct pace, and also, on the long term, to provide proper education for a balanced nutrition plan and teach patients how to

The management of over activity can be treated firstly by providing psychoeducation about the advantages and disadvantages of this behavior and to discourage exercise. Also, relaxation and distractions techniques can be helpful, the use of wheelchairs to reduce the level of energy spent, administer Olanzapine with a good effect on the compulsive behavior, providing a calm and warm environment, with a

Treatment goals address numerous aspects such as nutritional, physical, social and mental health comorbidities. Some studies were made on healthy subjects, who voluntarily agreed to be starved, and the effect of this demonstrated that even in normal subjects thought processes were slowed, executive functions were impaired, with decision making disturbances, and personality traits accentuated in a manner that persons were more paranoid, depressed or became psychotic. The majority of these symptoms were reversed by re-feeding treatment in normal individuals and similarities were observed for anorexic patients, who had an improvement in thinking, mood stability and improved the engagement level for psychotherapy [49].

For malnourished patients re-feeding may represent the only solution for surviving. It has to be initiated promptly with benefits on the physical strength, cerebral function. It restores the reduced size of internal organs, heart, gut and their functions, offers a better functioning of the immune system, patients being less susceptible for infections. All of these outcomes appear after a slow process, because the body needs to readapt to the increased availability of calories and nutrients [50]. If

the last 3–6 months of over 15% of the body weight, had little nutritional intake for more than 10 days or have low levels of potassium, phosphate, magnesium prior to the re-feeding, they are at risk of developing a re-feeding syndrome, according to the NICE guidelines [51]. The re-feeding syndrome can be defined as a consequence of trying to re-establish the normal weight of a very malnourished patient. During this phase, the maximal risk is within 72 h and implies potentially fatal shifts in fluids and electrolytes. The characteristic biochemical abnormality is the hypophosphatemia, but hypokalemia and hypomagnesaemia can also occur. NICE recommends starting re-feeding process at 5 kcal/kg/24 h for those with severe anorexia nervosa, through a nasogastric re-feeding tube and progressively increasing the rate of re-feeding to the target calorie intake over the next 4–7 days. Other studies showed that higher initial re-feeding rates can be applied such as 15 or 20 kcal/kg/

In order to avoid this kind of situations the patient has to be admitted in special medical units with experience in re-feeding syndrome, to monitor the blood chemistry twice a day, start with caution and increase quickly if the patient tolerates well. A particular aspect is to start giving thiamine before feeding starts, and to continue with it at least 10 days in order to overcome the development of Wernicke's encephalopathy or Korsakoff syndrome. Hypophosphatemia can have fatal effect through numerous clinical features such as cardiac failure, arrhythmias, seizures, tremor, rhabdomyolysis, and respiratory failure. Hypomagnesaemia can also occur and complicate the feeding treatment by cardiac arrhythmia, hypertension crises,

24 h, with or without the association of re-feeding syndrome [52].

, or had a rapid loss weight within

prepare their meals and eat adequately in social situations [46].

permanent supervision from medical staff [48].

the patients have a very low BMI, under 16 kg/m<sup>2</sup>

**52**

tremor, tetany, confusion, seizures and abdominal pain. Hypokalemia can appear as a consequence of staring to feed the anorexic patient, but more common it is present in patients with binge-purge subtype because of vomiting or induced laxative diarrhea. All of these electrolyte deficiencies must be treated properly to offer a safe outcome. Other complications that can occur during re-feeding are elevated transaminase levels with liver failure, coagulation problems, acute tubular renal necrosis, tubular renal nephritis, cardiac Torsade du Pointes, arrhythmias, prolonged QTc, cardiomyopathy [53, 54].

If the patients is in a severe state for the re-feeding process doctors have to decide if an enteral tube feeding is required. For this intervention training and experience is need, because the gut wall in malnourished patients is extremely thin and there is the risk of rupture, a lethal complication. Also after passing the tube, the safety position must be checked before it is used. In order to confirm the placement of the tube, gastric fluid can be aspirated, and the level of acidity can be determined, or an X-ray might be required. Gastrostomy tubes are not advisable to use, they need an endoscopic or radiologic approach, with the risk of peritonitis or other infections. Feeding through a tube is just a temporary solution, as part of an integrated plan, and patients need to be responsible and slowly introduce a full oral intake [55].

For osteopenia the recommended treatment is weight restoration and a normalization of the endocrine hormones. Also hormones substitution with transdermal estrogen, analogue of parathyroid hormone, bisphosphonates, raloxifene and denosumab drugs can be prescribed in this case [56].

Psychotherapy should be the treatment of choice for all eating disorders. The number of sessions required is different in each eating disorder type. In the case of anorexia nervosa no specific psychotherapy has shown clear superiority, but the number of sessions required is the highest, with an average of 40. Adolescents with anorexia nervosa have better outcomes after family therapy. For bulimia nervosa and binge eating disorder psychotherapy should be offered as a first line treatment, especially cognitive behavior therapy, or as an alternative interpersonal psychotherapy, psychodynamic, or family-based therapy in children and adolescent with bulimia nervosa. Usually the number of sessions required is less for bulimia and binge eating disorder, with a medium of 20 weeks [57, 58].

Pharmacological therapies with positive results in controlled trials in eating disorders are second generation of antipsychotics and antidepressants. For anorexia nervosa olanzapine had the most beneficial effects, in the case of bulimia nervosa and binge eating disorder Fluoxetine showed a good outcome, with a small effect from Lisdexamfetamine for binge eating disorder and Mirtazapine for avoidant restrictive eating disorder [59, 60].

#### **9. Evolution and prognosis**

Eating disorders characterized by low weight associate high morbidity and mortality rates. A follow-up study which monitored hospitalized patients with anorexia nervosa reported an average life expectancy of 39 years. Studies showed that 1/3 of patients suffering from anorexia nervosa tend to have a full recovery, in same percentage patients have just a partial recovery, and approximately 1/3 will have a chronic evolution or die. On a more optimistic point of view, a full recovery has been shown to be possible but with early intervention plan and sustained treatment over a medium of almost 7 to 9 years [61].

In general the prognosis for bulimia nervosa is good with treatment and assistance, but if the patient associate low self-esteem or different forms of personality disorders these aspects can affect the outcome. Little is known about the prognosis in binge eating disorders or other eating and feeding disorders [62].

For all eating disorders, poor prognostic factors can be considered as: late onset, anxiety in the presence of others when eating, severe weight loss, association of other chronic disorders, difficulties in childhood for social adjustment, being a male, having conflicts with parents or friends, being present binge and purge behaviors, low motivational for change, shame or not having enough money for engaging in psychotherapies sessions, association of concomitant depressed mood and obsessive body imagine preoccupation. Better evolutions have been identified in adolescents than adults, but only in association with family psychotherapy making the majority of these patients partially recovered, with less episodes of relapse. Also, in the young group distribution an onset in adolescents have a much better prognosis than one in early childhood [62].

#### **10. Insight in eating disorders**

There is now a general agreement that insight is not an all-or-none phenomenon, but rather a complex, multidimensional concept in psychiatric disorders. It includes different components, like the ability of a patient to recognize the presence of a mental illness, the capacity to accept that some symptoms are pathological and are determined by a mental disorder, the awareness of illness's consequences and compliance with treatment [63].

Lack of insight has been largely demonstrated in schizophrenia, other psychoses and bipolar disorder [64–67]. DSM-5 included an "insight" specifier in OCD, body dysmorphic and hoarding disorder. Also, different levels of lack of insight, from good to absent, have been found in other psychiatric disorders, like depressive and anxiety disorders, specific and social phobias, Alzheimer disease and other neurocognitive disorders, eating disorders [68–71].

Patients with anorexia nervosa (AN) commonly lack insight, at least in the early stages of illness. This element will determine important difficulties in assessment, lack of compliance or avoidance of treatment, frequent relapses and also may limit the identification of eating disorders. These patients have distorted cognitions about body weight and shape and also, they are ambivalent regarding motivation to recover [72]. On the other hand, patients with bulimia nervosa (BN) have typically a bigger level of motivation to recover.

Until now there is not a disorder-specific scale for the assessment of insight in patients with eating disorders. Many researchers use SAI-ED (the Schedule for the Assessment of Insight for EDs), a short self-report questionnaire, which has only seven items. Even if the SAI-ED has not been fully validated, has a significant level of internal consistency [72].

#### **10.1 Factors associated with insight**

In their study evaluating the clinical insight in 193 patients with anorexia nervosa, Gorwood et al. observed that 88% of patients (171) had a high level of insight (SAI-ED total score > 4) and 12% of patients (22) had a poor insight (SAI-ED < 4).

The authors drew three important conclusions:

1.Insight was not improved in a vast majority of patients, even if they followed 4 months of specialized care and all clinical and cognitive markers improved.

**55**

*Feeding and Eating Disorders*

psychotherapy [72–76].

disorder (BID) [77].

**Conflict of interest**

was minimum BMI.

*DOI: http://dx.doi.org/10.5772/intechopen.92218*

**11. Psychiatric comorbidities in eating disorders**

and personality or conduct disorder [77].

2.In this study, the only factor that has been demonstrated improving insight

Other studies revealed other factors correlated with insight (cognitive functions memory and executive functions), psychiatric and addictive comorbidities, associated personality disorders prescribed psychotropic drugs, social cognitions, use of

Beside comorbid somatic conditions of eating disorders (anemia, arteriosclerosis, hypertension, high cholesterol, high triglycerides, myocardial infarction, lung problems, stomach ulcer, Bowel problems, liver diseases, fibromyalgia, stroke, epilepsy or seizures, cancer, arthritis, osteoporosis, sleep problems), all three EDs (eating disorders) are associated with other psychiatric conditions, especially mood disorders, anxiety disorders, posttraumatic stress disorder, substance use disorder

Regarding mood disorders, most common associated with EDs are major depressive disorder, persistent depression, bipolar I [78]. Affective disorders, substance use disorders and anxiety disorders represent the most common predictive factors for suicide. Researchers have reported also that eating disorders are associated with suicide. The meta-analysis of Smith et al. [78], which included 2611 longitudinal studies, concluded that ED diagnosis is significantly associated with an increased risk for suicide attempt (SA) although the rate of SA varied considerably across studies [78]. In the group of patients with anorexia nervosa (AN), the rate of SA was between 3 and 20% [79]; in bulimia nervosa patients (BN), the rate ranged between 25 and 35% [79]; and in BED patients, the rate was 12.5% [78] and 20.8% when combining all EDs [80]. In the study of Udo et al., which included 36,171 respondents in the Third National Epidemiological Survey on Alcohol and Related Conditions (NESARC-III), the prevalence of suicide attempts was 24.8% for AN, 15.5% for anorexia nervosa-restricted type (AN-R), 44.1% for anorexia nervosa binge/purge type (AN-BP), 31.4% for bulimia nervosa, and 22.9% for binge-eating

Regarding anxiety disorders, most common associated with eating disorders are panic disorder, social anxiety disorder, specific phobias and general anxiety disorder [78]. The association between social anxiety and EDs could be a part of a wider socio-emotional phenotype which it is considered to contribute to the development and maintenance of EDs. SA may be a risk factor for ED, or SA may be secondary to

Abuse of substances is common in EDs, the lifetime prevalence being estimated between 23 and 37% [82]. Tobacco, caffeine and alcohol were the most prevalent SUD in the study of Bahji et al., being followed by cannabis and cocaine [83, 84]. Between axis II DSM diagnoses, most common comorbidities in ED are antisocial, borderline and schizotypal personality disorders and conduct disorders [78].

the ED, as a consequence of ED psychopathology or malnutrition [81].

The authors declare that they have no conflict of interest.

3.Premorbid IQ was highly associated with the level of baseline insight.

*Neurological and Mental Disorders*

prognosis than one in early childhood [62].

**10. Insight in eating disorders**

compliance with treatment [63].

cognitive disorders, eating disorders [68–71].

a bigger level of motivation to recover.

**10.1 Factors associated with insight**

The authors drew three important conclusions:

of internal consistency [72].

disorders these aspects can affect the outcome. Little is known about the prognosis

For all eating disorders, poor prognostic factors can be considered as: late onset, anxiety in the presence of others when eating, severe weight loss, association of other chronic disorders, difficulties in childhood for social adjustment, being a male, having conflicts with parents or friends, being present binge and purge behaviors, low motivational for change, shame or not having enough money for engaging in psychotherapies sessions, association of concomitant depressed mood and obsessive body imagine preoccupation. Better evolutions have been identified in adolescents than adults, but only in association with family psychotherapy making the majority of these patients partially recovered, with less episodes of relapse. Also, in the young group distribution an onset in adolescents have a much better

There is now a general agreement that insight is not an all-or-none phenomenon, but rather a complex, multidimensional concept in psychiatric disorders. It includes different components, like the ability of a patient to recognize the presence of a mental illness, the capacity to accept that some symptoms are pathological and are determined by a mental disorder, the awareness of illness's consequences and

Lack of insight has been largely demonstrated in schizophrenia, other psychoses and bipolar disorder [64–67]. DSM-5 included an "insight" specifier in OCD, body dysmorphic and hoarding disorder. Also, different levels of lack of insight, from good to absent, have been found in other psychiatric disorders, like depressive and anxiety disorders, specific and social phobias, Alzheimer disease and other neuro-

Patients with anorexia nervosa (AN) commonly lack insight, at least in the early stages of illness. This element will determine important difficulties in assessment, lack of compliance or avoidance of treatment, frequent relapses and also may limit the identification of eating disorders. These patients have distorted cognitions about body weight and shape and also, they are ambivalent regarding motivation to recover [72]. On the other hand, patients with bulimia nervosa (BN) have typically

Until now there is not a disorder-specific scale for the assessment of insight in patients with eating disorders. Many researchers use SAI-ED (the Schedule for the Assessment of Insight for EDs), a short self-report questionnaire, which has only seven items. Even if the SAI-ED has not been fully validated, has a significant level

In their study evaluating the clinical insight in 193 patients with anorexia nervosa, Gorwood et al. observed that 88% of patients (171) had a high level of insight (SAI-ED total score > 4) and 12% of patients (22) had a poor insight

1.Insight was not improved in a vast majority of patients, even if they followed 4 months of specialized care and all clinical and cognitive markers improved.

in binge eating disorders or other eating and feeding disorders [62].

**54**

(SAI-ED < 4).


Other studies revealed other factors correlated with insight (cognitive functions memory and executive functions), psychiatric and addictive comorbidities, associated personality disorders prescribed psychotropic drugs, social cognitions, use of psychotherapy [72–76].

#### **11. Psychiatric comorbidities in eating disorders**

Beside comorbid somatic conditions of eating disorders (anemia, arteriosclerosis, hypertension, high cholesterol, high triglycerides, myocardial infarction, lung problems, stomach ulcer, Bowel problems, liver diseases, fibromyalgia, stroke, epilepsy or seizures, cancer, arthritis, osteoporosis, sleep problems), all three EDs (eating disorders) are associated with other psychiatric conditions, especially mood disorders, anxiety disorders, posttraumatic stress disorder, substance use disorder and personality or conduct disorder [77].

Regarding mood disorders, most common associated with EDs are major depressive disorder, persistent depression, bipolar I [78]. Affective disorders, substance use disorders and anxiety disorders represent the most common predictive factors for suicide. Researchers have reported also that eating disorders are associated with suicide. The meta-analysis of Smith et al. [78], which included 2611 longitudinal studies, concluded that ED diagnosis is significantly associated with an increased risk for suicide attempt (SA) although the rate of SA varied considerably across studies [78]. In the group of patients with anorexia nervosa (AN), the rate of SA was between 3 and 20% [79]; in bulimia nervosa patients (BN), the rate ranged between 25 and 35% [79]; and in BED patients, the rate was 12.5% [78] and 20.8% when combining all EDs [80]. In the study of Udo et al., which included 36,171 respondents in the Third National Epidemiological Survey on Alcohol and Related Conditions (NESARC-III), the prevalence of suicide attempts was 24.8% for AN, 15.5% for anorexia nervosa-restricted type (AN-R), 44.1% for anorexia nervosa binge/purge type (AN-BP), 31.4% for bulimia nervosa, and 22.9% for binge-eating disorder (BID) [77].

Regarding anxiety disorders, most common associated with eating disorders are panic disorder, social anxiety disorder, specific phobias and general anxiety disorder [78]. The association between social anxiety and EDs could be a part of a wider socio-emotional phenotype which it is considered to contribute to the development and maintenance of EDs. SA may be a risk factor for ED, or SA may be secondary to the ED, as a consequence of ED psychopathology or malnutrition [81].

Abuse of substances is common in EDs, the lifetime prevalence being estimated between 23 and 37% [82]. Tobacco, caffeine and alcohol were the most prevalent SUD in the study of Bahji et al., being followed by cannabis and cocaine [83, 84].

Between axis II DSM diagnoses, most common comorbidities in ED are antisocial, borderline and schizotypal personality disorders and conduct disorders [78].

#### **Conflict of interest**

The authors declare that they have no conflict of interest.

*Neurological and Mental Disorders*

### **Author details**

Bianca Suciu\* and Cătălina-Angela Crișan Department of Neuroscience, Discipline of Psychiatry and Pediatric Psychiatry, Iuliu Haţieganu University of Medicine and Pharmacy Cluj-Napoca, Romania

\*Address all correspondence to: biancabobocel@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.

**57**

*Feeding and Eating Disorders*

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*DOI: http://dx.doi.org/10.5772/intechopen.92218*

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[5] Udo T, Grilo CM. Prevalence and correlates of DSM-5–defined eating disorders in a nationally representative

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[7] Mulders-Jones B, Mitchison D, Girosi F, Hay P. Socioeconomic correlates of eating disorder symptoms in an Australian population-based sample.

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*Neurological and Mental Disorders*

**56**

**Author details**

Bianca Suciu\* and Cătălina-Angela Crișan

provided the original work is properly cited.

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

Department of Neuroscience, Discipline of Psychiatry and Pediatric Psychiatry, Iuliu Haţieganu University of Medicine and Pharmacy Cluj-Napoca, Romania

© 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] Hay P. Current approach to eating disorders: A clinical update. Internal Medicine Journal. 2020;**50**(1):24-29

[2] Galmiche M, Déchelotte P, Lambert G, Tavolacci MP. Prevalence of eating disorders over the 2000-2018 period: A systematic literature review. The American Journal of Clinical Nutrition. 2019;**109**:1402-1413

[3] Hudson J, Hiripi E, Pope H, Kessler R. The prevalence and correlates of eating disorders in the National Comorbidity Survey Replication. Biological Psychiatry. 2007;**61**(3):348-358

[4] Hay P, Mitchison D, Lopez Collado AE, González-Chica DA, Stocks N, Touyz S. Burden and health-related quality of life of eating disorders, including avoidant/restrictive food intake disorder (ARFID), in the Australian population. Journal of Eating Disorders. 2017;**5**:21

[5] Udo T, Grilo CM. Prevalence and correlates of DSM-5–defined eating disorders in a nationally representative sample of US adults. Biological Psychiatry. 2018;**84**:345-354

[6] Smink FR, Van Hoeken D, Hoek HW. Epidemiology of eating disorders: Incidence, prevalence and mortality rates. Current Psychiatry Reports. 2012;**14**:406-414

[7] Mulders-Jones B, Mitchison D, Girosi F, Hay P. Socioeconomic correlates of eating disorder symptoms in an Australian population-based sample. PLoS One. 2017;**12**:e0170603

[8] Collier D, Treasure J. The aetiology of eating disorders. The British Journal of Psychiatry. 2004;**185**(5):363-365

[9] Whitney J, Murray J, Gavan K, Todd G, Whitaker W, Treasure J. Experience

of caring for someone with anorexia nervosa: Qualitative study. The British Journal of Psychiatry. 2005;**187**(5):444-449

[10] Stice E, Marti C, Durant S. Risk factors for onset of eating disorders: Evidence of multiple risk pathways from an 8-year prospective study. Behaviour Research and Therapy. 2011;**49**(10):622-627

[11] Arcelus J, Witcomb G, Mitchell A. Prevalence of eating disorders amongst dancers: A systemic review and metaanalysis. European Eating Disorders Review. 2013;**22**(2):92-101

[12] Arcelus J. Mortality rates in patients with anorexia nervosa and other eating disorders. Archives of General Psychiatry. 2011;**68**(7):724

[13] Smith J. The Parent' s Guide to Eating Disorders. Oxford: Lion Hutton; 2011

[14] Davis C, Katzman D, Kaptein S, Kirsh C, Brewer H, Kalmbach K, et al. The prevalence of high-level exercise in the eating disorders: Etiological implications. Comprehensive Psychiatry. 1997;**38**(6):321-326

[15] Beumont P, Arthur B, Russell J, Touyz S. Excessive physical activity in dieting disorder patients: Proposals for a supervised exercise program. The International Journal of Eating Disorders. 1994;**15**(1):21-36

[16] Davis C, Kennedy S, Ravelski E, Dionne M. The role of physical activity in the development and maintenance of eating disorders. Psychological Medicine. 1994;**24**(4):957-967

[17] Touyz SW, Beumont PJV, Hook S. Exercise anorexia: A new dimension in anorexia nervosa. In: Handbook of

Eating Disorders: Part 1. Amsterdam: Elsevier; 1987. pp. 143-157

[18] Epling WF, Pierce WD. Activity Anorexia: Theory, Research and Treatment. Lawarence Erlbaum Associates: Mahwan NJ; 1996

[19] Ackard D, Brehm B, Steffen J. Exercise and eating disorders in collegeaged women: Profiling excessive exercisers. Eating Disorders. 2002;**10**(1):31-47

[20] Steffen J, Brehm B. The dimensions of obligatory exercise. Eating Disorders. 1999;**7**(3):219-226

[21] Kron L, Katz J, Gorzynski G, Weiner H. Hyperactivity in anorexia nervosa: A fundamental clinical feature. Comprehensive Psychiatry. 1978;**19**(5):433-440

[22] Solenberger S. Exercise and eating disorders. Eating Behaviors. 2001;**2**(2):151-168

[23] Strober M, Freeman R, Morrell W. The long-term course of severe anorexia nervosa in adolescents: Survival analysis of recovery, relapse, and outcome predictors over 10-15 years in a prospective study. The International Journal of Eating Disorders. 1997;**22**(4):339-360

[24] Norris M, Harrison M, Isserlin L, Robinson A, Feder S, Sampson M. Gastrointestinal complications associated with anorexia nervosa: A systematic review. The International Journal of Eating Disorders. 2015;**49**(3):216-237

[25] Chami T, Nikoomanesh P, Katz P. An unusual presentation of pill-induced esophagitis. Gastrointestinal Endoscopy. 1995;**42**(3):263-265

[26] Miller K. Medical findings in outpatients with anorexia nervosa. Archives of Internal Medicine. 2005;**165**(5):561

[27] Douglas G, Nicol F, Robertson C. Macleod's Clinical Examination. 13th ed. Edinburgh: Churchill Livingstone Elsevier; 2013

[28] Stratton R, Dixon R, Longmore D, Stroud M, Elia M. Effect of recalled weight and height on malnutrition risk. Clinical Nutrition. 2003;**22**:S9-S10

[29] Sachs K, Harnke B, Mehler P, Krantz M. Cardiovascular complications of anorexia nervosa: A systematic review. The International Journal of Eating Disorders. 2015;**49**(3):238-248

[30] Weed LL. Medical Records that Guide and Teach. The New England Journal of Medicine. 1968;278(11):593- 600. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (5th ed.) (DSM-5). Washington DC: American Psychiatric Association; 2013

[31] World Health Organization. International Statistical Classification of Diseases and Related Health Problems, 11th Revision ICD-11. Geneva: World Health Organization; 2019

[32] International Advisory Group for the Revision of ICD-10 Mental Behavioural Disorders. A conceptual framework for the revision of the ICD-10 classification of mental and behavioural disorders. World Psychiatry. 2011;**10**(2):86-92. DOI: 10.1002/j.2051-5545.2011.tb00022.x

[33] Keeley JW, Reed GM, Roberts MC, Evans SC, Medina-Mora ME, Robles R. Developing a science of clinical utility in diagnostic classification systems: Field study strategies for ICD-11 mental and behavioral disorders. American Psychologist Journal. 2016;**71**(1):3. DOI: 10.1037/a0039972

**59**

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disorders. World Psychiatry. 2015;**14**(1):82-90. DOI: 10.1002/

[36] Attia E, Becker AE, Bryant-Waugh R, Hoek HW, Kreipe RE, Marcus MD. Feeding and eating disorders in DSM-5. The American Journal of Psychiatry. 2013;**170**(11):1237-1239. DOI: 10.1176/

appi.ajp.2013.13030326

[37] Al-Adawi S, Bax B, Bryant-Waugh R, Claudino AM, Hay P, Monteleone P. Revision of ICD status

update on feeding and eating disorders. Advances in Eating Disorders. 2013;**1**(1):10-20. DOI: 10.1080/21662630.2013.742971

10.1542/peds.2011-3663

DOI: 10.1002/erv.2297

[38] Field AE, Sonneville KR, Micali N, Crosby RD, Swanson SA, Laird NM, et al. Prospective association of common eating disorders and adverse outcomes. Pediatrics. 2012;**130**(2):e289-e295. DOI:

[39] Fitzsimmons-Craft EE, Ciao AC, Accurso EC, Pisetsky EM, Peterson CB, Byrne CE. Subjective and objective binge eating in relation to eating disorder symptomatology, depressive symptoms, and self-esteem among treatment-seeking adolescents with bulimia nervosa. European Eating Disorders Review. 2014;**22**(4):230-236.

[40] Watson HJ, Fursland A, Bulik CM, Nathan P. Subjective binge eating with compensatory behaviors: A variant presentation of bulimia nervosa.

wps.20189

*DOI: http://dx.doi.org/10.5772/intechopen.92218*

The International Journal of Eating Disorders. 2013;**46**(2):119-126. DOI:

[41] Salvioli B, Pellicciari A, Iero L, Di Pietro E, Moscano F, Gualandi S, et al. Audit of digestive complaints and psychopathological traits in patients with eating disorders: A prospective study. Digestive and Liver Disease.

[42] Aziz Q, Fass R, Gyawali C, Miwa H, Pandolfino J, Zerbib F. Esophageal disorders. Gastroenterology. 2016;**150**(6):1368-1379

[43] Lacy B, Mearin F, Chang L, Chey W, Lembo A, Simren M, et al. Bowel disorders. Gastroenterology.

2016;**150**(6):1393.e5-1407.e5

[44] Hay P, Chinn D, Forbes D,

[45] National Institute for Health and Care Excellence (NICE). Eating disorders: Recognition and Treatment Full Guideline. 2017. Available from: https://www.nice. org.uk/guidance/ng69/evidence/ full-guideline-pdf-161214767896

[46] Hilbert A, Hoek HW, Schmidt R. Evidence-based clinical guidelines foreating disorders: International comparison. Current Opinion in Psychiatry. 2017;**30**:423-437

[47] Hay PJ, Touyz S, Claudino AM, Lujic S, Smith CA, Madden S. Inpatient

versusoutpatient care, partial hospitalization and waiting list for people with eating disorders. Cochrane Database of Systematic Reviews. 2019:CD010827. DOI: 10.1002/14651858.

CD010827.pub2

Madden S, Newton R, Sugenor L. Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for the treatment of eating disorders. The Australian and New Zealand Journal of Psychiatry. 2014;**48**:977-1008

10.1002/eat.22052

2013;**45**(8):639-644

[34] First MB, Reed GM, Hyman SE, Saxena S. The development of the ICD-11 clinical descriptions and diagnostic guidelines for mental and behavioural

[35] Uher R, Rutter M. Classification of feeding and eating disorders: Review of evidence and proposals for ICD-11. World Psychiatry. 2012;**11**(2):80-92. DOI: 10.1016/j.wpsyc.2012.05.005

#### *Feeding and Eating Disorders DOI: http://dx.doi.org/10.5772/intechopen.92218*

*Neurological and Mental Disorders*

Elsevier; 1987. pp. 143-157

Eating Disorders: Part 1. Amsterdam:

Archives of Internal Medicine.

[27] Douglas G, Nicol F, Robertson C. Macleod's Clinical Examination. 13th ed. Edinburgh: Churchill Livingstone

[28] Stratton R, Dixon R, Longmore D, Stroud M, Elia M. Effect of recalled weight and height on malnutrition risk. Clinical Nutrition. 2003;**22**:S9-S10

[29] Sachs K, Harnke B, Mehler P,

[30] Weed LL. Medical Records that Guide and Teach. The New England Journal of Medicine. 1968;278(11):593- 600. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (5th ed.) (DSM-5). Washington DC: American Psychiatric

[31] World Health Organization.

[32] International Advisory Group for the Revision of ICD-10 Mental Behavioural Disorders. A conceptual framework for the revision of the ICD-10 classification of mental and behavioural disorders. World Psychiatry. 2011;**10**(2):86-92. DOI: 10.1002/j.2051-5545.2011.tb00022.x

[33] Keeley JW, Reed GM, Roberts MC,

Psychologist Journal. 2016;**71**(1):3. DOI:

Evans SC, Medina-Mora ME, Robles R. Developing a science of clinical utility in diagnostic classification systems: Field study strategies for ICD-11 mental and behavioral disorders. American

10.1037/a0039972

Health Organization; 2019

International Statistical Classification of Diseases and Related Health Problems, 11th Revision ICD-11. Geneva: World

Krantz M. Cardiovascular complications of anorexia nervosa: A systematic review. The International Journal of Eating Disorders. 2015;**49**(3):238-248

2005;**165**(5):561

Elsevier; 2013

Association; 2013

[18] Epling WF, Pierce WD. Activity Anorexia: Theory, Research and Treatment. Lawarence Erlbaum Associates: Mahwan NJ; 1996

[19] Ackard D, Brehm B, Steffen J. Exercise and eating disorders in collegeaged women: Profiling excessive exercisers. Eating Disorders.

[20] Steffen J, Brehm B. The dimensions of obligatory exercise. Eating Disorders.

[21] Kron L, Katz J, Gorzynski G, Weiner H. Hyperactivity in anorexia nervosa: A fundamental clinical feature. Comprehensive Psychiatry.

[22] Solenberger S. Exercise and eating disorders. Eating Behaviors.

nervosa in adolescents: Survival analysis of recovery, relapse, and outcome predictors over 10-15 years in a prospective study. The International

Journal of Eating Disorders.

[24] Norris M, Harrison M, Isserlin L, Robinson A, Feder S, Sampson M. Gastrointestinal

1997;**22**(4):339-360

1995;**42**(3):263-265

[23] Strober M, Freeman R, Morrell W. The long-term course of severe anorexia

complications associated with anorexia nervosa: A systematic review. The International Journal of Eating Disorders. 2015;**49**(3):216-237

[25] Chami T, Nikoomanesh P, Katz P. An unusual presentation of pill-induced esophagitis. Gastrointestinal Endoscopy.

[26] Miller K. Medical findings in outpatients with anorexia nervosa.

2002;**10**(1):31-47

1999;**7**(3):219-226

1978;**19**(5):433-440

2001;**2**(2):151-168

**58**

[34] First MB, Reed GM, Hyman SE, Saxena S. The development of the ICD-11 clinical descriptions and diagnostic guidelines for mental and behavioural disorders. World Psychiatry. 2015;**14**(1):82-90. DOI: 10.1002/ wps.20189

[35] Uher R, Rutter M. Classification of feeding and eating disorders: Review of evidence and proposals for ICD-11. World Psychiatry. 2012;**11**(2):80-92. DOI: 10.1016/j.wpsyc.2012.05.005

[36] Attia E, Becker AE, Bryant-Waugh R, Hoek HW, Kreipe RE, Marcus MD. Feeding and eating disorders in DSM-5. The American Journal of Psychiatry. 2013;**170**(11):1237-1239. DOI: 10.1176/ appi.ajp.2013.13030326

[37] Al-Adawi S, Bax B, Bryant-Waugh R, Claudino AM, Hay P, Monteleone P. Revision of ICD status update on feeding and eating disorders. Advances in Eating Disorders. 2013;**1**(1):10-20. DOI: 10.1080/21662630.2013.742971

[38] Field AE, Sonneville KR, Micali N, Crosby RD, Swanson SA, Laird NM, et al. Prospective association of common eating disorders and adverse outcomes. Pediatrics. 2012;**130**(2):e289-e295. DOI: 10.1542/peds.2011-3663

[39] Fitzsimmons-Craft EE, Ciao AC, Accurso EC, Pisetsky EM, Peterson CB, Byrne CE. Subjective and objective binge eating in relation to eating disorder symptomatology, depressive symptoms, and self-esteem among treatment-seeking adolescents with bulimia nervosa. European Eating Disorders Review. 2014;**22**(4):230-236. DOI: 10.1002/erv.2297

[40] Watson HJ, Fursland A, Bulik CM, Nathan P. Subjective binge eating with compensatory behaviors: A variant presentation of bulimia nervosa.

The International Journal of Eating Disorders. 2013;**46**(2):119-126. DOI: 10.1002/eat.22052

[41] Salvioli B, Pellicciari A, Iero L, Di Pietro E, Moscano F, Gualandi S, et al. Audit of digestive complaints and psychopathological traits in patients with eating disorders: A prospective study. Digestive and Liver Disease. 2013;**45**(8):639-644

[42] Aziz Q, Fass R, Gyawali C, Miwa H, Pandolfino J, Zerbib F. Esophageal disorders. Gastroenterology. 2016;**150**(6):1368-1379

[43] Lacy B, Mearin F, Chang L, Chey W, Lembo A, Simren M, et al. Bowel disorders. Gastroenterology. 2016;**150**(6):1393.e5-1407.e5

[44] Hay P, Chinn D, Forbes D, Madden S, Newton R, Sugenor L. Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for the treatment of eating disorders. The Australian and New Zealand Journal of Psychiatry. 2014;**48**:977-1008

[45] National Institute for Health and Care Excellence (NICE). Eating disorders: Recognition and Treatment Full Guideline. 2017. Available from: https://www.nice. org.uk/guidance/ng69/evidence/ full-guideline-pdf-161214767896

[46] Hilbert A, Hoek HW, Schmidt R. Evidence-based clinical guidelines foreating disorders: International comparison. Current Opinion in Psychiatry. 2017;**30**:423-437

[47] Hay PJ, Touyz S, Claudino AM, Lujic S, Smith CA, Madden S. Inpatient versusoutpatient care, partial hospitalization and waiting list for people with eating disorders. Cochrane Database of Systematic Reviews. 2019:CD010827. DOI: 10.1002/14651858. CD010827.pub2

[48] Long C. Assessment and management of eating disordered patients who over-exercise: A fouryear follow-up of six single case studies. Journal of Mental Health. 1995;**4**(3):309-316

[49] Thien V, Thomas A, Markin D, Birmingham C. Pilot study of a graded exercise program for the treatment of anorexia nervosa. The International Journal of Eating Disorders. 2000;**28**(1):101-106

[50] Saudek C, Felig P. The metabolic events of starvation. The American Journal of Medicine. 1976;**60**(1):117-126

[51] Boateng A, Sriram K, Meguid M, Crook M. Refeeding syndrome: Treatment considerations based on collective analysis of literature case reports. Nutrition. 2010;**26**(2):156-167

[52] Keys A. The biology of human starvation. The American Journal of Clinical Nutrition. 1978;**31**(2):197-197

[53] Madden S, Miskovic-Wheatley J, Clarke S, Touyz S, Hay P, Kohn MR. Outcomes of a rapid refeeding protocol in adolescent anorexia nervosa. Journal of Eating Disorders. 2015;**3**:8

[54] Schorr M, Klibanski A. Anorexia nervosa and bone. Current Opinion Endocrine and Metabolic Research. 2018;**3**:74-82

[55] Treasure J, Cardi V, Leppanen J, Turton R. New treatment approaches for severe and enduring eating disorders. Physiology & Behavior. 2015;**152**:456-465

[56] Zipfel S, Giel K, Bulik C, Hay P, Schmidt U. Anorexia nervosa: Aetiology, assessment, and treatment. The Lancet Psychiatry. 2015;**2**(12):1099-1111

[57] Dalle Grave R, Calugi S, Sartirana M, Fairburn CG.

Transdiagnostic cognitive behaviour therapy for adolescents with an eating disorder who are not underweight. Behaviour Ressearch and Therapy. 2015;**73**:79-82

[58] Schmidt U, Startup H, Treasure J. A Cognitive-Interpersonal Therapy Workbook for Treating Anorexia Nervosa: The Maudsley Model. Abingdon, UK: Routledge; 2018

[59] Attia E, Steinglass JE, Walsh BT, Wang Y, Wu P, Schreyer C. Olanzapine versus placebo in adult outpatients with anorexia nervosa: A randomized clinical trial. The American Journal of Psychiatry. 2019;**176**:449-456

[60] Hilbert A, Petroff D, Herpertz S, Pietrowsky R, Tuschen-Caffier B, Vocks S. Meta-analysis of the efficacy of psychological and medical treatments for binge-eating disorder. Journal of Consulting and Clinical Psychology. 2019;**87**:91-105

[61] Eddy KT, Tabri N, Thomas JJ, Murray HB, Keshaviah A, Hastings E. Recovery from anorexia nervosa and bulimia nervosa at 22-year followup. The Journal of Clinical Psychiatry. 2017;**78**:184-189

[62] Vall E, Wade TD. Predictors of treatment outcome in individuals with eating disorders: A systematic review and meta-analysis. The International Journal of Eating Disorders. 2015;**48**:946-971

[63] Marková IS. Insight in Psychiatry. Cambridge University Press; 2005

[64] David AS. Insight and psychosis. The British Journal of Psychiatry. 1990;**156**:798-808

[65] Amador XF, Strauss DH, Yale SA, Gorman JM. Awareness of illness in schizophrenia. Schizophrenia Bulletin. 1991;**17**:113-132

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Quarterly. 1993;**64**:305-318

2015;**37**(3):152-156

*DOI: http://dx.doi.org/10.5772/intechopen.92218*

[74] Nair A, Palmer EC, Aleman A, David AS. Relationship between cognition, clinical and cognitive insight in psychotic disorders: A review and meta-analysis. Schizophrenia Research.

[75] Steinglass JE, Eisen JL, Attia E, Mayer L, Walsh BT. Is anorexia nervosa a delusional disorder? An assessment of eating beliefs in anorexia nervosa. Journal of Psychiatric Practice.

[76] Yen CF, Hsiao RC, Chen CC, Lin HC, Yen CN, Ko CH, et al. The role of insight to alcohol use disorders

[77] Udo T, Grilo CM. Psychiatric and medical correlates of DSM-5 eating disoders in a nationally representative sample of adults in the United States. The International Journal of Eating

[79] Franko DL, Keel PK. Suicidality in eating disorders: Occurrence, correlates, and clinical implications. Clinical Psychology Review. 2006;**26**(6):769-782

[80] Carano A, De Berardis D, Campanella D, Serroni N, Ferri F, Di Lorio G, et al. Alexithymia and suicide ideation in a sample of patients with binge eating disorder. Journal of Psychiatric Practice. 2012;**18**(1):5-11

[81] Ahn J, Lee J, Jung Y. Predictors of suicide attempts in individuals with eating disorders. Suicide and Life-Threatening Behavior.

2018;**49**(3):789-797

in insight to schizophrenia. Comprehensive Psychiatry.

Disorders. 2019;**52**:42-50

2018;**49**(1):221-239

[78] Smith AR, Velkoff EA, Ribeiro JD, Franklin J. Are eating disorders and related symptoms risk factors for suicidal thoughts and behaviors? A meta-analysis. Suicide & Life-Threatening Behavior.

2014;**152**(1):191-200

2007;**13**(2):65-71

2009;**50**(1):58-62

[66] Amador XF, Strauss DH. Poor insight in schizophrenia. Psychiatric

[67] de Assis da Silva R, Mograbi DC, Camelo EVM, Bifano J, Wainstok M, Silveira LAS, et al. Insight in bipolar disorder: A comparison between mania, depression and euthymia using the insight scale for affective disorders. Trends in Psychiatry and Psychotherapy.

[68] Lee MS, Lee HY, Kang SG, Yang J, Ahn H, Rhee M. Variables influencing antidepressant medication adherence for treating outpatients with depressive

[69] Menzies RG, Harris LM, Jones MK. Evidence from three fearful samples for poor insight type specific phobia. Depression and Anxiety. 1998;**8**:29-32

[71] Konstantakopoulos G, Tchanturia K, Surguladze SA, David AS. Insight in eating disoders: Clinical and cognitive correlates. Psychological Medicine.

[72] Gorwood P, Duriez P, Lengvenyte A, Guillaume S. Criquillion, on behalf of the FFAB network. Clinical insight in anorexia nervosa: Associated and predictive factors. Psychiatry Research.

[73] Catapano F, Perris F, Fabrazzo M, Cioffi V, Giacco D, De Santis V, et al. Obssessive-compulsive disorder with poor-insight: a three-year prospective study. Progress in Neuropsychopharmacology and Biological Psychiatry. 2010;**34**(2):323-330

disorders. Journal of Affective Disorders. 2010;**123**:216-221

[70] Vigne P, de Menezes GB, Harrison BJ, Fontenelle LF. A study of poor insight in social anxiety disorders. Psychiatry Reaserch.

2014;**219**:556-561

2011;**41**:1951-1961

2019;**281**:112561

*Feeding and Eating Disorders DOI: http://dx.doi.org/10.5772/intechopen.92218*

[66] Amador XF, Strauss DH. Poor insight in schizophrenia. Psychiatric Quarterly. 1993;**64**:305-318

*Neurological and Mental Disorders*

[48] Long C. Assessment and management of eating disordered patients who over-exercise: A fouryear follow-up of six single case studies. Journal of Mental Health.

Transdiagnostic cognitive behaviour therapy for adolescents with an eating disorder who are not underweight. Behaviour Ressearch and Therapy.

[58] Schmidt U, Startup H, Treasure J. A Cognitive-Interpersonal Therapy Workbook for Treating Anorexia Nervosa: The Maudsley Model. Abingdon, UK: Routledge; 2018

[59] Attia E, Steinglass JE, Walsh BT, Wang Y, Wu P, Schreyer C. Olanzapine versus placebo in adult outpatients with anorexia nervosa: A randomized clinical trial. The American Journal of

[60] Hilbert A, Petroff D, Herpertz S, Pietrowsky R, Tuschen-Caffier B, Vocks S. Meta-analysis of the efficacy of psychological and medical treatments for binge-eating disorder. Journal of Consulting and Clinical Psychology.

[61] Eddy KT, Tabri N, Thomas JJ,

Hastings E. Recovery from anorexia nervosa and bulimia nervosa at 22-year followup. The Journal of Clinical Psychiatry. 2017;**78**:184-189

[62] Vall E, Wade TD. Predictors of treatment outcome in individuals with eating disorders: A systematic review and meta-analysis. The International

[63] Marková IS. Insight in Psychiatry. Cambridge University Press; 2005

[64] David AS. Insight and psychosis. The British Journal of Psychiatry.

[65] Amador XF, Strauss DH, Yale SA, Gorman JM. Awareness of illness in schizophrenia. Schizophrenia Bulletin.

Journal of Eating Disorders.

2015;**48**:946-971

1990;**156**:798-808

1991;**17**:113-132

Murray HB, Keshaviah A,

Psychiatry. 2019;**176**:449-456

2019;**87**:91-105

2015;**73**:79-82

[49] Thien V, Thomas A, Markin D, Birmingham C. Pilot study of a graded exercise program for the treatment of anorexia nervosa. The International

[50] Saudek C, Felig P. The metabolic events of starvation. The American Journal of Medicine. 1976;**60**(1):117-126

[52] Keys A. The biology of human starvation. The American Journal of Clinical Nutrition. 1978;**31**(2):197-197

[53] Madden S, Miskovic-Wheatley J, Clarke S, Touyz S, Hay P, Kohn MR. Outcomes of a rapid refeeding protocol in adolescent anorexia nervosa. Journal

[54] Schorr M, Klibanski A. Anorexia nervosa and bone. Current Opinion Endocrine and Metabolic Research.

[55] Treasure J, Cardi V, Leppanen J, Turton R. New treatment approaches for severe and enduring eating disorders. Physiology & Behavior.

[56] Zipfel S, Giel K, Bulik C, Hay P, Schmidt U. Anorexia nervosa: Aetiology, assessment, and treatment. The Lancet Psychiatry. 2015;**2**(12):1099-1111

[57] Dalle Grave R, Calugi S, Sartirana M, Fairburn CG.

of Eating Disorders. 2015;**3**:8

2018;**3**:74-82

2015;**152**:456-465

Journal of Eating Disorders.

[51] Boateng A, Sriram K, Meguid M, Crook M. Refeeding syndrome: Treatment considerations based on collective analysis of literature case reports. Nutrition.

2010;**26**(2):156-167

1995;**4**(3):309-316

2000;**28**(1):101-106

**60**

[67] de Assis da Silva R, Mograbi DC, Camelo EVM, Bifano J, Wainstok M, Silveira LAS, et al. Insight in bipolar disorder: A comparison between mania, depression and euthymia using the insight scale for affective disorders. Trends in Psychiatry and Psychotherapy. 2015;**37**(3):152-156

[68] Lee MS, Lee HY, Kang SG, Yang J, Ahn H, Rhee M. Variables influencing antidepressant medication adherence for treating outpatients with depressive disorders. Journal of Affective Disorders. 2010;**123**:216-221

[69] Menzies RG, Harris LM, Jones MK. Evidence from three fearful samples for poor insight type specific phobia. Depression and Anxiety. 1998;**8**:29-32

[70] Vigne P, de Menezes GB, Harrison BJ, Fontenelle LF. A study of poor insight in social anxiety disorders. Psychiatry Reaserch. 2014;**219**:556-561

[71] Konstantakopoulos G, Tchanturia K, Surguladze SA, David AS. Insight in eating disoders: Clinical and cognitive correlates. Psychological Medicine. 2011;**41**:1951-1961

[72] Gorwood P, Duriez P, Lengvenyte A, Guillaume S. Criquillion, on behalf of the FFAB network. Clinical insight in anorexia nervosa: Associated and predictive factors. Psychiatry Research. 2019;**281**:112561

[73] Catapano F, Perris F, Fabrazzo M, Cioffi V, Giacco D, De Santis V, et al. Obssessive-compulsive disorder with poor-insight: a three-year prospective study. Progress in Neuropsychopharmacology and Biological Psychiatry. 2010;**34**(2):323-330

[74] Nair A, Palmer EC, Aleman A, David AS. Relationship between cognition, clinical and cognitive insight in psychotic disorders: A review and meta-analysis. Schizophrenia Research. 2014;**152**(1):191-200

[75] Steinglass JE, Eisen JL, Attia E, Mayer L, Walsh BT. Is anorexia nervosa a delusional disorder? An assessment of eating beliefs in anorexia nervosa. Journal of Psychiatric Practice. 2007;**13**(2):65-71

[76] Yen CF, Hsiao RC, Chen CC, Lin HC, Yen CN, Ko CH, et al. The role of insight to alcohol use disorders in insight to schizophrenia. Comprehensive Psychiatry. 2009;**50**(1):58-62

[77] Udo T, Grilo CM. Psychiatric and medical correlates of DSM-5 eating disoders in a nationally representative sample of adults in the United States. The International Journal of Eating Disorders. 2019;**52**:42-50

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[79] Franko DL, Keel PK. Suicidality in eating disorders: Occurrence, correlates, and clinical implications. Clinical Psychology Review. 2006;**26**(6):769-782

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Section 2

Medical Aspects
