**3. The domains of alcohol-related neurodevelopmental disorder**

Although nearly every type of Axis I and II disorder in both DSM IV –TR and ICD 10 Classi‐ fications, as well as most disorders from the 0-3 coding manual can be expressed by individuals with effects of prenatal alcohol exposure, there have been efforts to better characterize the common clinical features associated with ARND. While neurodevelopmental deficits may exist in a range of severity, all cases of individuals with FAS have some degree of ARND. The following neurodevelopmental domains have been found to be disrupted in clinical psychi‐ atric cases of both FAS and ARND (Figure 1). As indicated in the diagram, prenatal alcohol exposure can lead to mood dysregulation and autonomic arousal, cognitive and executive dysfunctions, language and social skills deficits, and multi-sensory functional and perceptual deficits. Some individuals can have one or more domains of impairment, as indicated by the overlapping areas in the Venn diagram. (Rich et al 2009, Solomon et al 2009, Rich & O'Malley 2012)

or arousal state appropriately in response to sometimes minor challenges i.e. failure of examination, break up from boyfriend. This can lead to emotional incontinence with uncon‐

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461

These developmental psychiatric disorders presenting from infancy reflect the impact of prenatal alcohol on the developing neurotransmitter system. This teratogenic effect on the serotonin, GABA ergic Glutaminergic and other neurotransmitter systems can lead to anxiety disorders, mood disorders (such as depression), aggression, and possibly later substance abuse. As infants and toddlers, they are often temperamentally difficult to settle and do not seem to enjoy/bond with their parents, birth, foster or adoptive These infants may have pervasive sleep problems (with disruptions in the sleep/wake cycle, initial insomnia and decreased non REM sleep).As well they can display a whole range of regulatory problems in

As young children, the sensory integration issues involving sensitivity to sounds, environ‐ mental noise, lights, fans, easily irritated by voices, loud music, smells, tastes, even touch

This is commonly a clinical arena in which so called 'autistic 'features are noticed. In other words, the young child with ARND may either seek out tactile stimulation (touch and/or movement) or may, alternatively, be sensitive to touch and/or easily over-aroused by vigorous

Generally, transition periods are a challenge, not unlike autistic children. These children require intensive one-on-one adult attention being unable to self-soothe easily, and having difficulty in free /creative play. However, self regulation techniques can be taught and guide

Brain structural, neurophysiological or neurotransmitter abnormalities belie the cognitive deficits in ARND. These include: working memory deficits, difficulty with executive func‐ tioning (organization, concentration, auditory processing, processing speed, problem solving, attention and impulse control.); deficits in IQ compared with their biological parents; mathe‐ matics disorders, reading disorders (e.g., dyslexia), spelling issues, and other learning disabilities with or without mental retardation due to a hypoaroused, misconnected, or disconnected prefrontal cortex, individuals with ARND may have a variety of deficits in cognitive areas,. A variety of developmental disabilities (speech/language issues, visual integration, gross and/or fine motor skills deficits (i.e., poor handwriting), spasticity, hyper‐

Disruptions in cognitive functioning often lead to a failure to understand consequences, poor judgment, and limited insight into the origins or the impact of one's behaviors. This subse‐ quently leads to significant and debilitating deficits in basic day to day functional abilities. The child with ARND therefore, rather than thinking through actions, acts impulsively often in a naïve/ primitive manner (as though driven by basic instinct rather than measured intellect).

play therapy has a role in integration of the child's exploration of self expression.

trollable crying or laughing, or maybe intermittent unpredictable explosive episodes.

hyper or hyposensivity to auditory, visual,, olfactory, gustatory or tactile stimuli.

continue, and are often misunderstood as deliberate defiance.

**3.1. Cognitive and executive dysfunction**

proprioceptive stimuli (e.g., movement on swings, roller coasters, etc.).

flexibility, etc.) can also be seen in many individuals with ARND.

**Figure 1.** Mood dysregulation and/or Autonomic Arousal:

It is slowly being recognized that the autonomic or involuntary (parasympathetic and sympathetic) nervous system is affected by prenatal alcohol exposure, Animal research indicated this many years ago but human studies are beginning to unravel its effect from the infancy, early child hood and through to adolescence. Regulatory Disorders are prime clinical examples of this effect of prenatal alcohol exposure. The classic dichotomy in temperament is seen in the predisposition for a hyporesponsive infant or child, shy, inhibited, cautious and, anxious or hyperreponsive, a dis-inhibited, impulsive, intense infant or child. the effect of alcohol on the CNS produces a highly mood dysregulated child, having random or easily provoked episodes of frustration, irritability, aggression, and anger. Infants and toddlers with FASD can present with Regulatory Disorder Type I, II, or III (DC Zero to Three, 2005). The type of mood dysregulation may be related to "brain irritability" as epileptiform activity and spike and wave forms can be seen in sleep deprived or 24-hour EEGs for some individuals. This phenomenon is akin to a faulty thermostat which instead of controlling temperature controls emotional and arousal regulation. Thus the patient is unable to adjust their emotional or arousal state appropriately in response to sometimes minor challenges i.e. failure of examination, break up from boyfriend. This can lead to emotional incontinence with uncon‐ trollable crying or laughing, or maybe intermittent unpredictable explosive episodes.

These developmental psychiatric disorders presenting from infancy reflect the impact of prenatal alcohol on the developing neurotransmitter system. This teratogenic effect on the serotonin, GABA ergic Glutaminergic and other neurotransmitter systems can lead to anxiety disorders, mood disorders (such as depression), aggression, and possibly later substance abuse. As infants and toddlers, they are often temperamentally difficult to settle and do not seem to enjoy/bond with their parents, birth, foster or adoptive These infants may have pervasive sleep problems (with disruptions in the sleep/wake cycle, initial insomnia and decreased non REM sleep).As well they can display a whole range of regulatory problems in hyper or hyposensivity to auditory, visual,, olfactory, gustatory or tactile stimuli.

As young children, the sensory integration issues involving sensitivity to sounds, environ‐ mental noise, lights, fans, easily irritated by voices, loud music, smells, tastes, even touch continue, and are often misunderstood as deliberate defiance.

This is commonly a clinical arena in which so called 'autistic 'features are noticed. In other words, the young child with ARND may either seek out tactile stimulation (touch and/or movement) or may, alternatively, be sensitive to touch and/or easily over-aroused by vigorous proprioceptive stimuli (e.g., movement on swings, roller coasters, etc.).

Generally, transition periods are a challenge, not unlike autistic children. These children require intensive one-on-one adult attention being unable to self-soothe easily, and having difficulty in free /creative play. However, self regulation techniques can be taught and guide play therapy has a role in integration of the child's exploration of self expression.

#### **3.1. Cognitive and executive dysfunction**

exist in a range of severity, all cases of individuals with FAS have some degree of ARND. The following neurodevelopmental domains have been found to be disrupted in clinical psychi‐ atric cases of both FAS and ARND (Figure 1). As indicated in the diagram, prenatal alcohol exposure can lead to mood dysregulation and autonomic arousal, cognitive and executive dysfunctions, language and social skills deficits, and multi-sensory functional and perceptual deficits. Some individuals can have one or more domains of impairment, as indicated by the overlapping areas in the Venn diagram. (Rich et al 2009, Solomon et al 2009, Rich & O'Malley

It is slowly being recognized that the autonomic or involuntary (parasympathetic and sympathetic) nervous system is affected by prenatal alcohol exposure, Animal research indicated this many years ago but human studies are beginning to unravel its effect from the infancy, early child hood and through to adolescence. Regulatory Disorders are prime clinical examples of this effect of prenatal alcohol exposure. The classic dichotomy in temperament is seen in the predisposition for a hyporesponsive infant or child, shy, inhibited, cautious and, anxious or hyperreponsive, a dis-inhibited, impulsive, intense infant or child. the effect of alcohol on the CNS produces a highly mood dysregulated child, having random or easily provoked episodes of frustration, irritability, aggression, and anger. Infants and toddlers with FASD can present with Regulatory Disorder Type I, II, or III (DC Zero to Three, 2005). The type of mood dysregulation may be related to "brain irritability" as epileptiform activity and spike and wave forms can be seen in sleep deprived or 24-hour EEGs for some individuals. This phenomenon is akin to a faulty thermostat which instead of controlling temperature controls emotional and arousal regulation. Thus the patient is unable to adjust their emotional

2012)

**Figure 1.** Mood dysregulation and/or Autonomic Arousal:

460 Recent Advances in Autism Spectrum Disorders - Volume I

Brain structural, neurophysiological or neurotransmitter abnormalities belie the cognitive deficits in ARND. These include: working memory deficits, difficulty with executive func‐ tioning (organization, concentration, auditory processing, processing speed, problem solving, attention and impulse control.); deficits in IQ compared with their biological parents; mathe‐ matics disorders, reading disorders (e.g., dyslexia), spelling issues, and other learning disabilities with or without mental retardation due to a hypoaroused, misconnected, or disconnected prefrontal cortex, individuals with ARND may have a variety of deficits in cognitive areas,. A variety of developmental disabilities (speech/language issues, visual integration, gross and/or fine motor skills deficits (i.e., poor handwriting), spasticity, hyper‐ flexibility, etc.) can also be seen in many individuals with ARND.

Disruptions in cognitive functioning often lead to a failure to understand consequences, poor judgment, and limited insight into the origins or the impact of one's behaviors. This subse‐ quently leads to significant and debilitating deficits in basic day to day functional abilities. The child with ARND therefore, rather than thinking through actions, acts impulsively often in a naïve/ primitive manner (as though driven by basic instinct rather than measured intellect).

Self care is another area of concern. able to care for oneself (e.g., hygiene, meal preparation, scheduling appointments), manage a household (take on responsibilities for chores, balance a checkbook, etc.) and perform other activities of daily living may be limited depending on the extent of a person's ARND.

insulting /silly or negative). These behavior problems range from silly or irritating socially inappropriate behaviors to overtly aggressive and sometimes risky behaviors. Severe social functioning problems may result in lack of long term friendships, being labeled by peers as "weird" or "odd," and/or appearing withdrawn, socially-isolated, and avoidant. At times, ARND may lead to socially indiscriminate behaviors (i.e., individuals engaging in early or

Clinical Implications of a Link between Fetal Alcohol Spectrum Disorders (FASD) and Autism or Asperger's…

http://dx.doi.org/10.5772/54924

463

The clinical understanding of the effect of pseudo word decoding and alexithymia in man‐ agement and understanding is critical to the psychiatrist, psychologist and educator. These children and adolescents can be seen in an 'autistic ' or 'defiant' light but have specific decoding

Case Examples: Two female adolescents with ARND were diagnosed with Autism and Atypical Autism respectively after fulfilling the ADOS criteria. However both had clear documented history of prenatal alcohol exposure. One normal I.Q. I4 year old girl with Atypical Autism had a clinical presentation of ASD and ADD and deteriorated with psychos‐ timulant medication which markedly increased her perseveration. She responded to low dose liquid fluoxetine, and as her attention problems, especially visual, ameliorated, so her 'autistic' features deceased. The other girl 15 years old, with moderate intellectual functioning, had very debilitating social anxiety triggered by oversensitivity to facial cues. She eventually settled for a while with a GABA ergic agent.( Lyrica, pregabulin), but now needs a specialized therapeutic community placement. She had a history of many unexplained physical problems which were

Sensory integration issues, including hypo or hypersensitivities to noise, touch, proprioceptive stimuli, smells, tastes, and light may all be seen in children prenatally exposed to alcohol. This may lead to infants and toddlers seeming to be easily agitated, over-stimulated, and overaroused. Adolescents and adults may cope by avoiding or over-reacting in situations or environments which provoke their sensitivities. Adolescents or adults who misread or misunderstand social cues may result in paranoid behaviors, such as over-reactions to the tone

Prenatal alcohol exposure can have very disabling outcomes for alcohol-exposed children and their families due to the interaction between psychosocial risk factors (Mukarjee et al, 2006), cognitive deficits, and neuropsychiatric sequelae ( O'Malley 2011b). In addition to a higher prevalence of chronic exposure to domestic violence, neglect, child abuse, adjudicated youth

The sensory functional and perceptual deficits are commonly' hidden' and included in a generic autistic diagnosis frame. However they are fundamental to understanding the acquired brain damage caused by alcohol, which pervades brain structures, neurotransmitters

Case example: A 21 year old previously adopted male Caucasian patient presented with a long history of autism and psychotic features. He had been hospitalized a number of times and had

have higher rates of psychiatric illness, learning disabilities, and academic failure.

and electrophysiology (Hagerman 1999, O'Malley 2008, O'Malley & Mukarjee 2010).

promiscuous sexual activity, gang membership, and peer pressure).

struggles which effect their receptive).

Alcohol Related Birth Defects.

**3.3. Multi-sensory functional and perceptual deficits**

of someone's voice or an otherwise harmless look in their direction.

Time, homework and money management difficulties lead to multitudes of practical daily living problems. Children with ARND are seen as willful, lazy and showing clear oppositional defiant features. The level of IQ does not offer a guide to these cognitive issues and often can suggest a greater capability than is possible. Children with ARND not uncommonly present a mixture of autistic features with ADHD and so are doubly challenged. Medication can have a vital role in this group as they are misunderstood as having faulty 'theory of mind' deficits, whereas their distractibility and lack of focus makes them unable to fully participate in social situation.

It is more common sense in the later grades/years in school to guide the student towards a vocational training certificate rather than a diploma/ A level, Leaving Certificate track and to master the basic life skills to be productive, employed in a semi-skilled trade (e.g., construction worker, brick mason, landscape worker, plumber's assistant, etc.). However, for many individuals with a higher degree of functioning and with appropriate academic/examination support it may not be unreasonable to expect completion of secondary/ high school and even the entering of a two or four year college or university programme. This is especially true for FAS or ARND patients with an autistic profile and average or above average intellectual functioning.

On the other hand, more cognitively impaired patients with FAS or ARND may have frequent rudimentary behaviors (skin picking, pica, compulsive self harm or inappropriate/selfstimulating sexual behaviors). These can be a primitive expression of emotional distress, not unlike non verbal autistic children. The central alexithymia, (inability to understand others feelings or have words for one's own feelings) irrespective of IQ level is a fundamental clinical construct in FASD.(Greene et al 1991)

#### **3.2. Language and social skills deficits**

The traditional view of language deficits come from the wealth of studies in expressive/ articulation problems and the more complicated so called 'receptive' language problems where the person has fundamental problems in the processing of language. this latter deficits was described by wernicke as long ago as 1874 in his classic treatise on sensory aphasia. It is in this area that patients withFASD truly show their 'autistic type clinical features. misuse of language integral to social cognition and communication are quite common problems in adolescents or young adults with ARND. It is important to understand that prenatal alcohol-induced organic brain damage underpins the language deficits. At times, these patients are misdiagnosed with Autistic Spectrum Disorder or Asperger's Disorder. The term "social language disorder" better fits this population. This does not preclude the fact that medication may engender a positive effect on language functioning, and specifically social communication. Individuals with ARND suffer from indiscriminate or immature behaviors (e.g., telling inappropriate jokes in the classroom or workplace, blurting out what they think of a person even if it is quite insulting /silly or negative). These behavior problems range from silly or irritating socially inappropriate behaviors to overtly aggressive and sometimes risky behaviors. Severe social functioning problems may result in lack of long term friendships, being labeled by peers as "weird" or "odd," and/or appearing withdrawn, socially-isolated, and avoidant. At times, ARND may lead to socially indiscriminate behaviors (i.e., individuals engaging in early or promiscuous sexual activity, gang membership, and peer pressure).

The clinical understanding of the effect of pseudo word decoding and alexithymia in man‐ agement and understanding is critical to the psychiatrist, psychologist and educator. These children and adolescents can be seen in an 'autistic ' or 'defiant' light but have specific decoding struggles which effect their receptive).

Case Examples: Two female adolescents with ARND were diagnosed with Autism and Atypical Autism respectively after fulfilling the ADOS criteria. However both had clear documented history of prenatal alcohol exposure. One normal I.Q. I4 year old girl with Atypical Autism had a clinical presentation of ASD and ADD and deteriorated with psychos‐ timulant medication which markedly increased her perseveration. She responded to low dose liquid fluoxetine, and as her attention problems, especially visual, ameliorated, so her 'autistic' features deceased. The other girl 15 years old, with moderate intellectual functioning, had very debilitating social anxiety triggered by oversensitivity to facial cues. She eventually settled for a while with a GABA ergic agent.( Lyrica, pregabulin), but now needs a specialized therapeutic community placement. She had a history of many unexplained physical problems which were Alcohol Related Birth Defects.

#### **3.3. Multi-sensory functional and perceptual deficits**

Self care is another area of concern. able to care for oneself (e.g., hygiene, meal preparation, scheduling appointments), manage a household (take on responsibilities for chores, balance a checkbook, etc.) and perform other activities of daily living may be limited depending on the

Time, homework and money management difficulties lead to multitudes of practical daily living problems. Children with ARND are seen as willful, lazy and showing clear oppositional defiant features. The level of IQ does not offer a guide to these cognitive issues and often can suggest a greater capability than is possible. Children with ARND not uncommonly present a mixture of autistic features with ADHD and so are doubly challenged. Medication can have a vital role in this group as they are misunderstood as having faulty 'theory of mind' deficits, whereas their distractibility and lack of focus makes them unable to fully participate in social

It is more common sense in the later grades/years in school to guide the student towards a vocational training certificate rather than a diploma/ A level, Leaving Certificate track and to master the basic life skills to be productive, employed in a semi-skilled trade (e.g., construction worker, brick mason, landscape worker, plumber's assistant, etc.). However, for many individuals with a higher degree of functioning and with appropriate academic/examination support it may not be unreasonable to expect completion of secondary/ high school and even the entering of a two or four year college or university programme. This is especially true for FAS or ARND patients with an autistic profile and average or above average intellectual

On the other hand, more cognitively impaired patients with FAS or ARND may have frequent rudimentary behaviors (skin picking, pica, compulsive self harm or inappropriate/selfstimulating sexual behaviors). These can be a primitive expression of emotional distress, not unlike non verbal autistic children. The central alexithymia, (inability to understand others feelings or have words for one's own feelings) irrespective of IQ level is a fundamental clinical

The traditional view of language deficits come from the wealth of studies in expressive/ articulation problems and the more complicated so called 'receptive' language problems where the person has fundamental problems in the processing of language. this latter deficits was described by wernicke as long ago as 1874 in his classic treatise on sensory aphasia. It is in this area that patients withFASD truly show their 'autistic type clinical features. misuse of language integral to social cognition and communication are quite common problems in adolescents or young adults with ARND. It is important to understand that prenatal alcohol-induced organic brain damage underpins the language deficits. At times, these patients are misdiagnosed with Autistic Spectrum Disorder or Asperger's Disorder. The term "social language disorder" better fits this population. This does not preclude the fact that medication may engender a positive effect on language functioning, and specifically social communication. Individuals with ARND suffer from indiscriminate or immature behaviors (e.g., telling inappropriate jokes in the classroom or workplace, blurting out what they think of a person even if it is quite

extent of a person's ARND.

462 Recent Advances in Autism Spectrum Disorders - Volume I

situation.

functioning.

construct in FASD.(Greene et al 1991)

**3.2. Language and social skills deficits**

Sensory integration issues, including hypo or hypersensitivities to noise, touch, proprioceptive stimuli, smells, tastes, and light may all be seen in children prenatally exposed to alcohol. This may lead to infants and toddlers seeming to be easily agitated, over-stimulated, and overaroused. Adolescents and adults may cope by avoiding or over-reacting in situations or environments which provoke their sensitivities. Adolescents or adults who misread or misunderstand social cues may result in paranoid behaviors, such as over-reactions to the tone of someone's voice or an otherwise harmless look in their direction.

Prenatal alcohol exposure can have very disabling outcomes for alcohol-exposed children and their families due to the interaction between psychosocial risk factors (Mukarjee et al, 2006), cognitive deficits, and neuropsychiatric sequelae ( O'Malley 2011b). In addition to a higher prevalence of chronic exposure to domestic violence, neglect, child abuse, adjudicated youth have higher rates of psychiatric illness, learning disabilities, and academic failure.

The sensory functional and perceptual deficits are commonly' hidden' and included in a generic autistic diagnosis frame. However they are fundamental to understanding the acquired brain damage caused by alcohol, which pervades brain structures, neurotransmitters and electrophysiology (Hagerman 1999, O'Malley 2008, O'Malley & Mukarjee 2010).

Case example: A 21 year old previously adopted male Caucasian patient presented with a long history of autism and psychotic features. He had been hospitalized a number of times and had need restraint because of his reactivity to the environment. He had not responded to high doses of SSRIs (which produced increased suicidality thoughts), and atypical, especially risperidone which made him more affectively unmanageable. When he was assessed in the community his clear history of sensory reactivity to tactile, olfactory, gustatory, visual and auditory stimuli was unraveled as was his history of significant prenatal alcohol exposure. Which had been ignored in previous assessments. A combined multi-modal approach addressing his sensory reactivity combined with low dose buspirione was much more effective and he did not need psychiatric hospitalization. As well he did not present any facial features as adult or as a young child. He had been labeled as having unusual paranoid features but these were really his correct sensitivity to what he perceived as a hostile challenging environment. His adoptive parents recounted many stories of his oversensitivity to noise, light,fabrics food when he was growing op and just saw him as 'over fussy'.

Infants and toddlers with FASD can present with Regulatory Disorder Type I, II, or III (DC Zero to 3, 2005). Autistic behaviors have been noted in both younger children as well as school age children prenatally exposed to alcohol (Streissguth et al, 1996; Streissguth & O'Malley,

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You could build a case that nearly all disorders developing during childhood listed in the DSM IV-TR may be induced by exposure to alcohol in utero. Co-morbidities of FASD include other behavioral, mood, anxiety, and conduct problems. The link between ADHD and FASD is finding more universal acceptance and the link between autism and Aspergers disorder and FASD will not be far behind. (O'Malley 2011a).The lifetime prevalence of mental health or psychiatric disorders in individuals with FASD is as high as 90% (Streissguth et al 1996, HHS, 2000), highlighting the importance of correct diagnosis and clinical management. Accurate, informed diagnosis is critical in psychiatry to avoid over-medication or inappropriate treat‐

The current standard of care or "treatment as usual" for individuals with FASD is inadequate due to lack of diagnostic clarity, lack of accepted psychiatric treatment protocols, and further complicated by the presence of Alcohol Related Birth Defects (ARBD) which are multisystem organ involvement (i.e., seizure disorders; renal, eye, cardiac, g.i. problems and skeletal).

Early accurate diagnosis and intervention may be effective in preventing the development of secondary disabilities (i.e., academic or school failure, conduct disorders and antisocial behaviours leading to legal problems, sexually inappropriate behaviours, lack of steady

The utilization of a neurodevelopmental formulation can guide the development of effective multiisystem and multimodal intervention strategies, including appropriate psychopharma‐

**1.** Thus, shifting diagnostic paradigms in children with prenatal alcohol exposure to the dysmorphic (FAS) and non-dysmorphic (ARND) phenotypic expression of in utero alcohol exposure would allow psychiatrists, pediatricians, and other medical professio‐ nals to have a richer, clearer and more holistic interpretation and understanding of the wide range of neurocognitive, neurobehavioral, and neuropsychiatric disorders affecting

**2.** The social or environmental context includes childhood exposure to domestic or com‐ munity violence, child abuse/neglect, early institutionalization, community violence, and other early life events that may contribute to development of reactive attachment disorder (RAD), post traumatic stress disorder (PTSD), developmental trauma disorder and other

The interaction of the childhood experience on the expressed FASD phenotype cannot be overlooked. Therefore, the neurodevelopmental biological vulnerability profile of FASD during infancy, toddlerhood, childhood, and adolescence predisposes an individual to adverse

the individual rather than simply the degree of facial dysmorphology.

ment, leading to worsening of symptoms and poor outcomes.

**4.2. The utilization of a neurodevelopmental formulation**

2000, Mukarjee et al 2012).

employment and housing).

cologic management (O'Malley 2008).

psychiatric (Axis I and II) co-morbidities.
