Autism Spectrum Disorder PDF

14 Autism Spectrum Disorder Deborah Fein and Eva Troyb Definition Autism spectrum disorder (ASD) is a spectrum of autism phenotypes characterized by deficits in communication and socialization, as well as by the presence of restricted and repetitive behaviors (RRBs). In the fourth edition o...

14 Autism Spectrum Disorder Deborah Fein and Eva Troyb Definition Autism spectrum disorder (ASD) is a spectrum of autism phenotypes characterized by deficits in communication and socialization, as well as by the presence of restricted and repetitive behaviors (RRBs). In the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM- IV), the autism spectrum included autistic disorder (AD); pervasive developmental disorder, not otherwise specified (PDD-NOS); Asperger’s disorder; childhood disintegrative disorder; and Rett’s disorder. However, in DSM-5, the disorders have been collapsed into a single diagnostic category of “autism spectrum disorder.” This was done because the American Psychiatric Committee responsible for the DSM-5 revision concluded that while ASD vs. non-ASD is a reliable distinction, distinctions among the subtypes are not. Deficits in Communication and Socialization A diagnosis of ASD requires that individuals present with a persistent deficit in social communication and social interaction across multiple contexts, defined as all of the following in DSM-5 (Table 14.1): Impaired social-emotional reciprocity, ranging, for example, from abnormal social approach and failure of normal back-and-forth conversation; to reduced sharing of interests, emotions, or affect; to failure to initiate or respond to social interaction. Deficits in nonverbal communicative behaviors used for social interaction, ranging, for example, from poorly integrated verbal and nonverbal communication; to abnormalities in eye contact and body language or deficits in understanding and use of gestures; to a total lack of facial expressions and nonverbal communication. Deficits in developing, maintaining, and understanding relationships, ranging, for example, from difficulties adjusting behavior to suit various social contexts; to difficulties in sharing imaginative play or in making friends; to absence of interest in peers. Presence of Restricted and Repetitive Behaviors (RRBs) and Interests A core feature of ASDs is restricted and repetitive patterns of behaviors or interests, defined as at least two of the following in DSM-5: Stereotyped or repetitive motor movements, use of objects, or speech Insistence on sameness, inflexible adherence to routines, or ritualized patterns of verbal or nonverbal behavior Highly restricted, fixated interests that are abnormal in intensity or focus Hyper- or hypo-reactivity to sensory input or unusual interest in sensory aspects of the environment In addition, DSM-5 provides a severity dimension, along which symptoms should be rated, from Level 1 (requiring support) to Level 2 (requiring substantial support) to Level 3 (requiring very substantial support). Language disorder and intellectual disability (ID) are separately coded as ancillary features. Table 14.1 Diagnostic and Statistical Manual of Mental Disorders (DSM-5) Diagnostic Criteria Impairment in social communication and Impaired social-emotional social interaction (all three must be present) reciprocity Impaired nonverbal communication Failure to develop or maintain appropriate peer relationships Restricted, repetitive patterns of behavior Repetitive behaviors or and interest (at least two must be present) speech Insistence on sameness Unusual preoccupations or interests Sensory interests NOTE: The DSM-5 requires both social/communicative impairments and RRBs. In the DSM-5, children with social communication deficits but no or only one repetitive behavior or interest may qualify for a diagnosis of Social (Pragmatic) Communication Disorder, which is a subcategory of Communication Disorder. The practical and research consequences of this change in diagnosis remain to be seen. Asperger’s Disorder Note: Asperger’s disorder is no longer a separate diagnosis in DSM-5 but is discussed here for historical background. Many individuals and families still identify as having Asperger’s disorder. Asperger’s disorder was defined in DSM-IV by the presence of impaired social ability and RRBs in the absence of a language delay or significant impairment in adaptive functioning. Children and adolescents with Asperger’s disorder were said to be interested in interacting with others, but these interactions were thought to be often odd or awkward. Controversy remains regarding the distinction between autistic disorder and Asperger’s, including whether differences exist in genetic risk factors, family history, pathophysiology, treatment, and outcome of these conditions. Rett’s Disorder Note: Rett’s disorder is no longer a separate diagnosis in DSM-5 but is discussed here for historical background. Rett’s disorder is a rare (affects 1 in 10,000–15,000) genetic disorder that occurs primarily in females. It is associated with the MeCP2 gene and is characterized by early typical development until the age of 6 to 18 months, followed by significant deterioration of motor and social skills. Rett’s disorder is marked by a loss of purposeful hand movements, which are replaced by repetitive hand mannerisms, the most common of which is described as “hand-wringing” or “hand-washing.” The disorder is also accompanied by progressive cerebral atrophy. After a period of regression, there is usually a plateau lasting months to years, followed by slow growth of skills. Outcome for these children is generally poor, with nonambulatory status and severe cognitive deficits expected. Neuropathology Autism is a neurodevelopmental syndrome highly determined by genetics that affects complex brain functions. Investigations into the neuroanatomy of autism implicate numerous structures and systems throughout the brain. The pathological effects are varied and have an unclear anatomical basis. There is no single region of abnormality that is consistent across individuals with autism, and brain structure and function often present in different ways across individuals and throughout development. Neuroanatomical investigations are complicated by the heterogeneity of clinical presentation, high rates of psychological and medical comorbidity, and early-life onset and presentation in a still developing brain. Current theories posit that dysfunction originates on both a biological level (e.g., genes, proteins, molecules) and across the hierarchy of levels of integration (e.g., subcellular assemblies to cells, tissues, brain regions, neural systems, and large brain units). It is thought that feedback from the environment shapes the phenotypic expression of autism’s core symptomatology. High concordance rates in monozygotic twins and low concordance rates in dizygotic twins suggest that ASDs are complex genetic disorders with multiple loci contributing to a global phenotype. Despite heterogeneity, a number of anatomical findings have been demonstrated consistently across studies. The most replicated biological finding is that brain size (i.e., weight, volume, and/or head circumference) is often larger than average in younger subjects. This shows a distinctive developmental course: brain size is normal or slightly small at birth, followed by a growth spurt between six and 24 months that results in larger than average brains, followed by a slowed growth that returns the brain size to average by later childhood. The corpus callosum is typically undersized and not enlarged proportionally to overall enlargement of the brain. There is involvement in the cerebellum, limbic system, basal ganglia, thalamus, and white matter, although this involvement varies markedly across age group and studies. Perfusion within the brain is lower, although the distribution of this perfusion has varied in measures across studies. Metabolic and diffusion tensor imaging measures suggest a reduction in fiber integrity and the density of metabolites, and recent studies suggest that some of these differences can be detected as young as 6 months of age. Research into the neurochemical basis of autism has demonstrated that monoamines may have an influence on systems that are commonly impaired in autism including mood, arousal, and attention. Hyperserotonemia (an increase in the serotonin levels in blood platelets) in blood was the earliest biological finding in autism and is generally replicated. The glutamate and gamma aminobutyric acid (GABA) systems show decreased activation and abnormalities in receptors across individuals with ASDs. In the last several years, researchers have focused on connections among brain networks as likely to be fruitful. For example, although not confirmed across multiple studies, some findings have suggested overconnected close brain areas and underconnected long-distance areas. Others have suggested atypical connections among the default mode network, social cognition network, and reward network. Some research centers are attempting to follow the growth of connections from the first year of life, for children likely to be at risk for autism (e.g., baby siblings of affected children, premature infants). A growing body of empirical evidence supports a number of neuropsychological theories of ASDs, none of which is mutually exclusive. Individuals with ASDs are thought to have impairment of the higher level cognitive skills that underlie goal-oriented behavior in executive functioning, contributing to multiple aspects of executive functions, especially impairments in working memory, inhibition, flexibility, and self- monitoring. Individuals with autism are thought to have “weak central coherence,” which contributes to difficulties in the integration of information from the environment into a meaningful whole. In particular, these individuals process featural and local elements of stimuli at the expense of global meaning. They have strengths in understanding and acquiring rote skills rather than those that require abstract thinking, inferences, or complex problem solving. Social motivation theories suggest that individuals with ASDs have a decreased level of motivation to orient to social stimuli, which derails emergence of normal developmental pathways of social and communication skills. Social cognitive theories focus on impairments in the capacity to represent and reason about the thoughts, intentions, beliefs, desires, feelings, memories, and knowledge of others (poor “theory of mind”). In addition, individuals with poor theory of mind may fail to understand that the points of view or knowledge of others may differ from their own. They will, therefore, be able to predict specific concrete actions of others from their experience but will not be able to modify these predictions based on the others’ nonverbal communication cues or the social context. Risk Factors The heritability of autism, based on twin studies, is high. It is currently thought that genetic polymorphisms acting together, influenced by environmental contributions, are related to a complex etiology. There is some convergence of risk gene research on genes controlling synaptic functioning. Research currently suggests that heredity and early fetal development may play a causal role in autism, possibly in interaction with environmental risk factors. Other factors that may confer some risk for autism are being a younger sibling of an affected child, prematurity, advanced paternal age, and obstetric complications. Epidemiology Estimates of prevalence depend on the methods used and have generally increased over the last 30 years. Estimates across different countries and different ascertainment methods range from one in 38, to one in 200. Using 2014 data, the CDC reported an overall prevalence of one in 68, with prevalence in boys of one in 42 and in girls of one in 189. There is ongoing debate about the reality of the apparent increase in prevalence. One study in England that cast some doubt on the increase found similar prevalence across the adult lifespan, rather than increased prevalence in younger adults. Fombonne (2009) concludes: “There is evidence that the broadening of the concept, the expansion of diagnostic criteria, the development of services, and improved awareness of the condition have played a major role in explaining this increase, although it cannot be ruled out that other factors might have also contributed to that trend.” ASDs occur more commonly in males than females, with the most commonly accepted gender ratio of 4:1 male to female. The sex ratio appears to vary based on IQ, with females with ASDs tending to have lower verbal and nonverbal IQs. The male-to-female ratio approaches 2:1 in those with ASD and moderate to severe ID. Current evidence and research suggests that, on the whole, individuals with ASDs have reduced life expectancy. Elevated death rates have been linked to several specific causes, including seizures and accidents such as suffocation and drowning. Excess mortality is more significantly increased among individuals with ASDs with severe ID. Comorbidity Autism spectrum disorder is commonly comorbid with a number of psychological and emotional conditions. These comorbid conditions include: ID (comorbidity estimates vary from 40–70%), anxiety disorders (22–84% of cases, with high rates of specific phobia), depression (4–58%), tic disorders (6%), and seizure disorders (11–39%). Seizure disorders are more common in cases with comorbid ID. As many as 55% of individuals with ASD also commonly demonstrate symptoms of ADHD. The relationship between ASD and ADHD is still unclear and under active investigation. Some findings indicate that children with both diagnoses have more severe social impairments than children with ASD alone, that children with ASD plus ADHD combined subtype are more likely to have more deficits in social and adaptive functioning than children with ASD plus ADHD-inattentive subtype, and that ASD and ADHD may share genetic vulnerability. Determinants of Severity A diagnostic evaluation, involving both direct behavioral observation and parent interview, is helpful in determining the severity of an autism spectrum disorder. If the child is in an early intervention or school program, teacher informants can also be very helpful. The Autism Diagnostic Interview-Revised (ADI-R) is a parent interview that gathers information about early development and core deficits involved in ASDs. The ADI-R is useful in evaluating repetitive behaviors, stereotyped interests, and rigid preferences that may not be directly observable during an evaluation. It is more valid for children over the age of 2. The Autism Diagnostic Observation Schedule (ADOS) and ADOS-2 and ADOS-Toddler are interactive tools that involve direct observation of a behavioral sample through a series of reciprocal play and social routines. The ADOS allows a clinician to directly observe the presence and severity of ASD symptomatology, and there are different modules for children with different levels of language. The Modified Checklist for Autism in Toddlers (M- CHAT) and M-CHAT-Revised are autism-specific screening tools that identify children at elevated risk for autism. The American Academy of Pediatrics advises broad developmental screening at multiple ages, and autism specific screening at 18 and 24 months. The Childhood Autism Rating Scale (CARS) is a behavior rating scale that helps to identify children with an ASD and differentiate them from developmentally disabled children who do not have an ASD. The clinician rates a child on 15 items that are each representative of a characteristic, ability, or behavior common to children with autism and/or developmental disability more generally. Scores for each item are assigned based on severity and indicate how noticeably the child’s behavior deviates from the behavior expected of a typically developing child of the same developmental level. The severity of an ASD is noted by elevated scores in each core domain for all of these measures; higher scores indicate more severe impairment in social and communicative abilities and elevated amounts and intensity of repetitive behaviors and stereotyped interests. Severity of cognitive delay and language delay are other very important measures of severity of impairment. Presentation, Disease Course, and Outcome Clear stages of progression of ASD are only evident in Rett’s disorder. The behavioral presentation of the remaining phenotypes of ASD varies considerably across individuals, as well as across development.  First Year of Life Autism spectrum disorder can be reliably diagnosed as early as 18–24 months; however, some signs of ASD may be evident in children as young as 6 months of age. Between 6 and 12 months of age, children who later receive an ASD diagnosis may exhibit the following behaviors: Delayed vocal sound production Decreased frequency of simple babbling Reduced frequency of pointing or failure of pointing to develop Atypical eye contact or gaze avoidance Lack of social smiling Failure to respond to name Emotional flatness Atypical disengagement of visual attention Diminished interest in social interaction and adult language Unusual and repetitive hand and finger mannerisms Several biologic markers for ASD may also be present during this period and may include accelerated head growth, macrocephaly, and enlarged brain volume (including cerebral white and gray matter). Recent studies suggest that hyper-growth of the cortical surface can be seen in the second half of the first year. Second Year of Life During the second year of life (12–24 months), symptoms described above become more evident. Additional symptoms that are generally noted during the second year include: Delayed speech: Delayed comprehension of phrases Limited use of complex babble, single words, and phrases Unusual prosody Delayed and immediate echolalia Limited use of nonverbal communication: Reduced frequency of pointing and use of other gestures Limited range of facial expressions Facial expressions less commonly directed at others  Less integration of gaze with vocalization Lack of interest in peers Limited imitation of others Low rates of joint attention (pointing, showing, following gaze and point) Restricted range of functional and imaginative play Greater frequency and duration of repetitive hand and finger mannerisms and preoccupation with parts of objects Regressive Onset Between 20% and 47% of children with ASDs appear to exhibit few symptoms of ASDs until they experience a marked loss of language and/or socialization skills around the age of 15–24 months of age. Whether any developmental abnormalities are present before the onset of the regression remains unclear. Some longitudinal studies do suggest subtle delays or abnormalities before the frank regression, and some suggest a plateau rather than regression in some children. The relationship between vaccines and regressive onset of ASDs has received much attention in the media; however, a causal relationship is not empirically supported in multiple high-quality studies. Third, Fourth, and Fifth Years Symptoms of ASDs during the third, fourth, and fifth years of life appear similar. In many, communicative ability improves with time. Often, as it improves, language begins to contain other abnormalities, including echolalia, unusual prosody, and limited ability to engage in reciprocal conversation. Nonverbal communication continues to be impaired and includes limited use of gesture and joint attention, unusual eye contact, and limited range and use of facial expression. Functional and imaginative play continues to be restricted in range and/or frequency. The frequency of restricted interests and repetitive behaviors often increases during this period. In children with phrase speech and full sentences, they tend to repeat immediately what they have heard or repeat favorite phrases; conversation is one-sided rather than reciprocal. Middle Childhood With time and intervention, children may gain daily living skills during middle childhood and become more capable of acquiescing to the demands of their environments. Some children with  ASDs become more aware of societal rules and more interested in fulfilling the wishes of others, resulting in a decrease of public displays of repetitive behaviors. However, abnormalities in verbal and nonverbal communication and socialization skills generally remain. However, there is strong evidence that a small minority (perhaps 5– 20%) of individuals with ASD can lose symptoms of autism and function within the normal limits of social relationships; most of these individuals got intensive early intervention. Adolescence Symptoms during this period may be particularly challenging to treat. As many as 11–39% of individuals with ASDs experience seizures that most commonly begin in infancy or adolescence; seizures are often associated with significant intellectual impairment. Some adolescents with ASDs may also present with behavioral difficulties including resistance to change, self-injurious behaviors, compulsive behaviors, tantrums, and aggressive behaviors, which can be severe. In addition, daily living skills often continue to be impaired in adolescence. However, increased communicative and social skills may allow adolescents with ASDs to become more interested in participating in therapeutic interventions to help alleviate difficult behaviors and other remaining deficits. Aggression and irritability often worsen with the beginning of puberty and abate somewhat toward the end of adolescence, but some adolescents remain aggressive and irritable. Adulthood Little is known about ASD symptomatology during adulthood. Recent reports indicate that 50% of adults have poor outcomes (i.e., require high level of residential assistance, have few friends, and have supported or no employment). Although most adults with ASDs continue to require support from others, many are employed for at least several hours each week. Rett’s Disorder Rett’s disorder is associated with the X-linked gene MECP2; it typically progresses through four stages:  First Stage Marked by head growth deceleration, reduced interest in play, atypical hand mannerisms, deterioration in communicative abilities, and unusual eye contact. This often follows a period of 6 to 18 months of apparently normal development. Second Stage Marked by the presence of classic symptoms of autism, frequent and unusual motor stereotypies, loss of cognitive and language skills, and deteriorating motor abilities. Third Stage Symptoms of ASD typically diminish, and cognitive gains are made. However, motor skills continue to decline, and seizure onset is common. Daily living skills are poor, impacted by intellectual impairment and motor disability. Fourth Stage Motor abilities continue to deteriorate during the fourth stage of RD, and the majority of children with RD become wheelchair dependent during this time. Rule-Outs Numerous medical conditions present with similar symptomatology as in ASD including, but not limited to, Landau-Kleffner syndrome, fragile X syndrome, Heller’s syndrome, and Klinefelter’s syndrome. Appropriate medical and genetic tests can help identify the presence of these disorders, in addition to the autism phenotype. ASD is a behavioral syndrome, and often occurs in association with more established medical, especially genetic and metabolic, disorders. Expectations for Neuropsychological Assessment Results  Intelligence/Achievement Individuals with ASDs exhibit cognitive profiles with a high degree of variability between domains and subtests. There is no standard profile of intelligence for an individual with an ASD. As noted above, 40–70% of cases score within the ID range (IQ < 70). Individuals with ASD tend to demonstrate most difficulty on tasks that require language, abstract reasoning, flexible thinking, inferential reasoning, and sequencing. Strongest performance is often seen on tasks that require visuospatial processing, rote memory skills, and attention to detail. Many studies show that individuals with ASD overall tend to score higher on measures of nonverbal as compared to verbal reasoning, with significant variability observed among subtests. However, this pattern has not been consistently found among high- functioning individuals with ASD. As such, IQ should not inform diagnostic definitions. Attention/Concentration As noted above, many individuals with ASD exhibit attentional deficits, but significant variability has been reported across different forms of attention. Individuals with ASD appear to have particular difficulty disengaging and shifting attention. In contrast, sustained attention is relatively spared, especially with materials of interest to them. Individuals with ASDs may also have heightened attention to personally salient stimuli. Processing Speed Processing speed is likely to be impaired if measured with a verbally loaded task. In spatial, nonverbal tasks, processing speed may be unimpaired. When processing speed is unimpaired on testing, it is still often found to be slowed in natural settings where distractions place burdens on attention. Language There are many components to language, each of which may be differentially affected across individuals with ASDs. Often, children with ASD exhibit language delays as toddlers and preschoolers. Many of these children begin speaking with time and appropriate intervention; however, approximately 20–30% remain nonverbal. Verbal individuals with ASDs generally show relative strengths in phonology and articulation, basic grammar, and single- word receptive and expressive vocabulary. Grammar is important to assess because a subgroup of children may have grammatical