AUTISM AND ATTENTION DEFICIT/HYPERACTIVITY DISORDER

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CHAPTER 10 AUTISM AND ATTENTION DEFICIT/HYPERACTIVITY DISORDER

Autism and attention deficit hyperactivity disorder (ADHD) are the two main classes of neurodevelopmental disorders that begin in early childhood. The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR)1 specifies that the diagnosis of ADHD cannot be made if the symptoms occur in a child with autism. However, symptoms of attention deficit and hyperactivity are common problems in children with autism, which points toward some neuropathophysiological characteristics shared between these two groups of neurodevelopmental disorders. Autism is a generic term referring to a group of related conditions defined in the DSM-IV-TR1 and the International Classification of Diseases, Tenth Revision (ICD-10),2 as pervasive developmental disorders. The term autistic spectrum disorders is frequently used but lacks any international agreement regarding its definition.3 The term is sometimes used to refer to a group of related conditions similar to pervasive developmental disorders. It is also used to describe the range of intellectual abilities, from severe disability to normal ability, found in children with autism. The concept of a spectrum has also been applied to describe developmental changes, such as improvement in language ability, which might occur over time in an individual with autism. In this chapter, autism refers to the pervasive developmental disorders, which share the core features of severe and pervasive impairment in social and communication skills, together with the presence of restricted and repetitive patterns of behavior and interests. The onset of these disorders occurs within the first 3 years of life, but the clinical picture may change with development. In DSM-IV-TR1 the pervasive developmental disorders comprise the categories of Autistic Disorder, Asperger Disorder, Rett’s Disorder, Childhood Disintegrative Disorder, and Pervasive Developmental Disorder–Not Otherwise Specified (PDD-NOS). Autism was first described by Leo Kanner in 1943 for a group of 11 children who had the distinctive core features of social, language, and communication disturbance and an obsessive desire for sameness.4 In the following year, Hans Asperger described a group of 16 children and adolescents who had deficits in communication and social skills together with obsessional interest, intolerance of change, and motor clumsiness.5 Unlike the children described by Kanner, these young people were of normal intellectual ability and did not have any delay or abnormality in their language development. This has become the differentiating feature of Asperger’s disorder from autistic disorder. This review focuses on the assessment, pathophysiologic aspects, and treatment of the two main pervasive developmental disorders, autistic disorder and Asperger’s disorder.

The problem of excessive hyperactive, inattentive, and impulsive behavior in children has been described in the medical literature from the 19th century.6 Current theories regarding the etiology of developmentally excessive inattentiveness and hyperactivity encompass an interaction of genetic predisposition, central nervous system dysfunction resulting from prenatal and early postnatal traumatic or toxic events, and environmental and social influences. The concept of minimal brain damage with associated soft neurological signs led to theories of dysfunction of the thalamus and prefrontal circuits to account for the hyperactivity and inattention, respectively. Current interest is focused on deficiencies of executive function and inhibition of attention resulting from such dysfunction, particularly affecting the right prefrontal cortex and associated basal ganglia structures.7 These primary deficits affect the development of working memory, emotional regulation, motivation, and the development of language and morality.7 Historically, the approach to the diagnosis of ADHD has differed between North America and Europe. Clinicians in Europe have sought for evidence of neurological dysfunction and pervasive symptoms of inattention and hyperactivity in all contexts. Clinicians in North America have taken a more qualitative approach to diagnosis, acknowledging that symptoms may vary in different settings and subdividing the diagnosis into the number of symptoms in each of the dimensions of inattention or hyperactivity/impulsiveness. Thus, a child may receive a diagnosis of ADHD predominantly hyperactive type or predominantly inattentive type. There has been an attempt to bring the diagnostic criteria for ADHD in the DSM-IV-TR into line with the criteria for hyperkinetic disorder in the ICD-10.2 Although the criteria used in both classification systems are now virtually identical, there are still differences regarding the number of criteria required and the pervasiveness of symptoms. As a consequence, application of ICD-10 criteria is more restrictive and conservative, which has implications for studies of epidemiology and etiology. The discovery in 1937 of the therapeutic effect of dextroamphetamine on concentration and hyperactivity in children with disruptive behavior has also influenced approaches to diagnosis and the interest taken by society in these behavioral problems.8

Regardless of an element of social determinism inherent in the diagnosis of ADHD, there is no doubt that young people with pervasive difficulties with attention, impulsiveness, and motor hyperactivity are at great risk of suffering educational, social, emotional, and behavioral problems during childhood and subsequent mental health, relationship, occupational, forensic, and substance abuse problems in adult life. This chapter focuses on advances in the understanding of the neuropathophysiology and treatment of ADHD.

EPIDEMIOLOGY

Autism

There is evidence that the prevalence of autism is increasing. More than 23 prevalence studies of autism have been reported in the literature from 1966 to 1997. In most studies before 1990, investigators reported prevalence rates of 4 to 5 per 10,000. In more recent studies in which rigorous diagnostic criteria and standardized diagnostic assessment were used, investigators have found rates of approximately 10 to 12 per 10,000.9 Since the mid-1990s in a number of countries, specialist children’s services have reported an increasing demand for services for children with autism. For example, in Iceland, the prevalence of autism and the demand for services are reported to have doubled.10 Reviews indicate that the apparent increase in prevalence is probably a result of differences in ascertainment and diagnosis and an increasing awareness of autism by the general public.9 At least 14 different approaches to diagnosis have been used in prevalence studies. For example, when DSM-IV-TR or ICD-10 diagnostic criteria are used, the prevalence of autism is two to three times higher than that found with the application of the earlier criteria of Kanner.9 The inclusion of subcategory diagnoses of pervasive developmental disorders such as PDD-NOS or atypical autism leads to further increases of prevalence to approximately 27 to 30 per 10,000.9 In several longitudinal studies, researchers using equivalent methods of diagnosis over time, but with relatively small sample sizes, have not found significant changes in prevalence rates in subsequent birth cohorts.9,11

There is no evidence that prevalence varies between countries or racial groups, and social class and level of parental education are not associated with autism.9 Autistic disorder is more common in boys than in girls (ratio, 4:1), and the gender distribution is even more marked for Asperger’s disorder (ratio, 10:1 to 13:1). This gender distribution might point to the possibility of an X-linked element to the disorder, but research has failed to confirm this explanation.

Attention Deficit/Hyperactivity Disorder

Estimates of the prevalence of ADHD vary widely according to the diagnostic criteria, measures used, ascertainment methods, and demographics of the population. For example, in a populationwide study in the United States in which parent- and self-report screening questionnaires were used, a prevalence of ADHD of up to 20% was identified.12 Population rates of 1% to 2% are found if prevalence is based on the application of the restrictive ICD-10 criteria2 without the presence of comorbid conditions.13 Prevalence rates of 5% to 10% are found in studies in which the more inclusive DSM-IV-TR criteria, which allow some variability of symptoms and the presence of comorbidity, are used.14

Studies with DSM-IV-TR criteria reveal that the combined inattentive-hyperactive subtype of ADHD is the most common manifestation. For example, a clinic study demonstrated that 60% of young people with a diagnosis of ADHD had the combined subtype, 30% had the inattentive subtype, and 10% had the hyperactive-impulsive subtype.15 Note that the subtypes are designated on the basis of symptom predominance; meeting criteria for one subtype, such as inattentive subtype, does not preclude the presence of some symptoms from another subtype, such as hyperactive symptoms. Community studies reveal that the childhood prevalence of ADHD is approximately three times higher in boys than in girls but is more likely to decrease over time in male patients while remaining stable into adulthood in female patients.16

Symptoms usually reduce with maturation, but at least 30% of children with ADHD continue to suffer from the disorder in adulthood.17 Because of differences in diagnostic criteria and methods of ascertainment, the prevalence of ADHD in adults varies between 0.3% and 5%.17 Approximately a third of these adults are likely to suffer from a comorbid affective disorder as well, and the majority have associated social, marital, employment, and legal problems.18

CLINICAL FEATURES

Autism

Autism manifests with delays and abnormalities in the development of language and social skills, and the presence of rigid, repetitive, stereotyped play and behavior, often in association with intellectual disability and a variety of neurological conditions such as epilepsy. Therefore, the assessment and diagnosis is multifaceted, involving medical, cognitive, language, developmental, and mental state assessments.19 A reliable diagnosis can be made in patients aged 2 years and older. In view of the value of early intervention, early diagnosis is important and can be facilitated with the use of screening tools completed by parents (e.g., the Developmental Behavior Checklist),20 and clinician-completed checklists (e.g., the Checklist for Autism in Toddlers).21 Diagnosis is enhanced by the use of a structured, reliable, and valid parental interview and child observation schedule,22 such as the Autism Diagnostic Interview/Revised23 and the Autism Diagnostic Observation Schedule.24

All children with autism have impaired social interactions, which may change as they develop. Infants with autism do not anticipate social interactions, such as being picked up, or seek physical comfort or parental attention. Preschool children with autism usually avoid eye contact and do not engage in social imitation such as waving goodbye. They are unresponsive to the feelings and emotions of others. They are aloof and unable to engage effectively with other children or understand reciprocal social interactions. As such children grow older, there may be an increased interest in other people, but social skills are often stilted and learned in an inflexible manner, leading the children to appear odd and socially clumsy. Parents usually first seek help because their children have language delay and a lack of nonverbal communication and easily becomes frustrated. About 50% of children with autism fail to develop functional speech and learn only slowly to compensate with gesture. Language development is often abnormal in the remainder, with echolalia, self-directed jargon, and the repetition of irrelevant phrases (for example, from a television show). The correct use of pronouns and the related development of a sense of self and others are delayed. Poor comprehension, problems expressing needs by words and gesture, and difficulty in social understanding are frequently the causes of frustration and disturbed behavior. Children who do develop functional language usually have difficulty in using language socially and in initiating or sustaining a reciprocal conversation. For example, the child may talk at others in a socially inappropriate manner. In contrast to children with autistic disorder, young people with Asperger’s disorder have no delay in the development of normal expressive and receptive language, including the use of communicative phrases by the age of 3 years. However, children with Asperger’s disorder have problems in their social use of language, such as being verbose and preoccupied with a favorite topic. Their speech may appear odd because of the use of an unusual accent or because of the presence of abnormalities in pitch and volume; for example, delivery may be flat and monotonous.

The play, behavior, and daily life of children with autism are usually rigid and repetitive. Younger autistic children may line up toys or objects or may be preoccupied with special objects such as stones, and they become distressed if these activities are interrupted. Their ritualistic play lacks imagination and social imitation. With development, play may become more complex, such as reenacting scenes from a favorite video story, but is usually still repetitive. Older autistic children may develop preoccupations with themes such as train timetables or dinosaurs, and this is the focus of their play, drawing, and conversation. They may have a number of rituals associated with daily life, such as a fixed order for bathing and dressing or an insistence on wearing the same clothes or taking the same route to a familiar place. Change or unexpected events, such as the arrival of a new student in the classroom, can be distressing. There may be a number of perceptual or sensory abnormalities such as hyperacusis or tactile sensitivity, manifesting, for example, as an aversion to having their hair brushed. Some children with autism have a remarkable lack of sensitivity to pain. Children with autism are usually visually attentive; for example, they may study the detail in a picture book or closely observe spinning wheels, the edges of objects, or reflections in water. There are usually some motor mannerisms, such as hand flapping, tiptoe walking, and gait abnormality.

Approximately 80% of children with autism also have intellectual disability, and other emotional and behavioral disturbances are common. Children with autistic disorder who have intellectual abilities within the normal range are referred to as high functioning. The individual cognitive profiles of children with autism usually show a wide scatter of abilities, with deficits in verbal and social comprehension tasks and more ability with visuomotor performance skills. In contrast, children with Asperger’s disorder have overall normal intellectual abilities but usually have relative deficits in visuomotor tasks and motor skills in comparison with their verbal performance.

Children with autism often have a range of disruptive behaviors such as stubbornness, self-injury, and aggression, which place a high burden of care on parents and teachers. These disruptive behaviors are the main cause of failure in school and community activities and lead to more restrictive care. High levels of anxiety are common and prevent these children from learning, coping with change, and participating in family and community activities. The anxiety associated with autism is likely to persist into adult life.25 Children with autism are also likely to suffer from depression, particularly during adolescence. This may manifest as mood disturbance and irritability, sleep and appetite disturbance, and thoughts of suicide, which may be enacted.26 The increased vulnerability to depression during adolescence may be associated with self-awareness of the disability, but pubertal brain development and a family history of depression may also contribute.

At least 13% of children with autism also meet diagnostic criteria for ADHD,27 but the DSM-IV-TR specifically precludes the diagnosis of ADHD “during the course of a Pervasive Developmental Disorder” (p. 93).1 Nevertheless, symptoms of attention deficit and hyperactivity in children with autism impede and disrupt their learning, school adjustment, and family life. These symptoms of ADHD are responsive to educational, behavioral, and pharmacological managements used for children with ADHD, although not always as successfully.26 Children with autism also have an increased risk of suffering tic disorder or Gilles de la Tourette syndrome, with the tics becoming more prevalent during times of stress and anxiety, such as a change in school placement.26 Epilepsy occurs in approximately 20% of young people with autism, emerging most commonly in early childhood or during adolescence. It is seen more frequently in children with more severe levels of intellectual disability.26 Young people with Asperger’s disorder also suffer from a similar range of mental health problems but are even more likely to have higher levels of disruptive and antisocial behavior and to suffer from anxiety and depression.28 They may also have an increased risk of developing psychosis during adolescence or early adult life.

Attention Deficit/Hyperactivity Disorder

The diagnosis of ADHD is based on a clinical judgment that there are sufficient symptoms of inattention and hyperactivity/impulsivity, together with the decision that these symptoms cause significant impairment in daily functioning in at least two settings and are not consistent with the developmental level of the child.1 Therefore, the diagnosis requires a careful and comprehensive history of the child’s development and behavior from the parents and other informants such as the teacher, together with observation of the child during both structured and unstructured activities. A structured cognitive assessment, apart from providing information on specific learning difficulties and related problems such as deficits in short-term auditory memory, also reveals problems with concentration and distractibility—that is, with sustained, directed attention. The use of structured behavior rating scales, such as the Conner’s Parent and Teacher Rating Scales,29 may be useful for screening and as a measure of response to treatment.

Apart from high levels of distractibility and inattention, children with ADHD are disorganized and are usually unable to follow routine or complete tasks.1 They have difficulty monitoring their behavior and therefore often interrupt others, have difficulty following rules, and display inappropriate and impulsive behavior.1 Those who also suffer from hyperactivity are constantly restless and fidgety, have difficulty remaining seated, and behave as if they are driven by a motor. These behaviors are influenced by aspects of the environment, such as the degree of external stimulation and sensory complexity. Therefore, observers may report differences in behavior, depending on the context. For example, a teacher in a busy, noisy classroom setting is more likely to observe inattention than is a teacher’s aide who has the child for individual teaching in a quiet library environment. However, the symptoms and impairments are usually observed, at least to some extent, in all aspects of the child’s daily life.

Young people with ADHD have a range of associated problems. Their primary symptoms often lead to hostile interactions with other children, who may reject them. ADHD is frequently complicated by the presence of other psychopathological conditions: in particular, conduct disorder (25%), oppositional defiant disorder (35%), depression (15%), and anxiety disorder (25%).30 The majority of children with ADHD have various learning difficulties and poor school performance in relation to their intellectual abilities.31 Approximately 25% of individuals with ADHD have intellectual disability, including delayed language development.31

Children with ADHD have difficulty falling asleep and wake early, and their sleep is often unsettled and complicated by breathing and snoring difficulties.32 Adolescents with ADHD are at risk for delinquent behavior and abuse of nicotine, alcohol, and other substances, perhaps as a means of self-medication.33 Young people who are treated with stimulant medication for ADHD are less likely to use substances than are adolescents with ADHD who are not receiving treatment.33 There is also an association between the use of alcohol, tobacco, and other substances during pregnancy and the birth of a child with ADHD, but the mechanisms for these associations are likely to reflect the complex interaction of genes and environment.33

The assessment and diagnosis of ADHD for the first time in adults is difficult.34 Such an adult may not be living in a situation in which others can report on behaviors and symptoms to help the clinician reach a judgment on the severity of symptoms and the degree of disability. The presence of other comorbid psychiatric illnesses complicates the presentation. Adults are not able to reliably remember their childhood; therefore, if possible, a history of the manifestation of the disorder throughout childhood should be obtained from other persons or from school reports.34 Adults with ADHD are usually less disruptive and hyperactive than are children with ADHD, but they usually remain impulsive, disorganized, inattentive, and restless.34

ETIOLOGY AND PATHOPHYSIOLOGY

Autism

Neurocognitive Theories

There are three main cognitive theories of autism: the “theory-of-mind,”35 the “executive dysfunction” theory,36 and the theory of “weak central coherence.”37 Deficiencies in theory-of-mind—that is, the ability to understand that other people have unique perspectives and thoughts that are sometimes contextually independent—are thought to be linked to the social-communicative deficits associated with autism.35 Weak central coherence, a deficit in the ability to integrate details into a coherent global perception, is thought to be linked to the tendency of individuals with autism to be preoccupied with parts of objects and to miss the “bigger picture.”37 Executive functioning refers to the role of the frontostriatal circuits in coordinating cognitive-motor output so that behavior is well timed, planned, adaptable, appropriate, and relevant38 (and see Chapter 7). The repetitive, stereotyped, and restricted behaviors seen in autism are thought to result, in part, from deficient executive functioning.39 Poor performance on tests of executive functioning “… is found more consistently in autism than in any other form of childhood psychopathology” (p. 103).40

It is not clear which, if any, of these cognitive deficits is central to the psychiatric and neurological symptoms that characterize autism.41 Volkmar and colleagues42 argued that the main criticism leveled at theory-of-mind is that it cannot account for the clinical phenomenology of autism, because the social deficits characteristic of autism appear at a point in development before normally developing children demonstrate the acquisition of a theory-of-mind. Furthermore, children with autism and normal intelligence are reported to perform at an age-appropriate level on theory-of-mind tasks,43 although some authors disagree with this conclusion.44,45 Other, more primary deficits reflect problems with “weak central coherence.” Studies suggest that problems in moving attentional focus away from the detail of an object may better account for why individuals with autism appear to get “stuck” on detail and have a poor ability to appreciate the object’s gestalt.46,47

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