Chapter 34. Autism and the Pervasive Developmental Disorders

Autism and the related pervasive developmental disorders are disorders of early onset in which abnormalities in the development of social interaction and communication are associated with problems in behavior and unusual sensitivity to the inanimate environment. Autism is the best known of these conditions. DSM-IV-TR criteria for it are listed in Table 34–1. In autism a marked and sustained impairment in social interaction is associated with delayed and deviant communication and restricted, stereotyped patterns of interest and behavior. The condition was first described by Leo Kanner in 1943. Kanner emphasized two key features: autism (social disinterest) and restricted interests and trouble with change. His report underscored the importance of the lack of social interest for other aspects of development and social factors are consistently identified as central to the diagnosis of the condition. In the first decades after its description, autism was often incorrectly assumed to be a form of schizophrenia. Only in 1980 was it officially recognized as a diagnostic category (Volkmar & Klin, 2005).

DSM-IV-TR Criteria for Autistic Disorder

1. A total of at least six items from (1), (2), and (3), with at least two from (1), and one each from (2) and (3):

   1. Qualitative impairment in social interaction, as manifested by at least two of the following:

      1. Marked impairment in the use of multiple nonverbal behaviors such as eye-to-eye gaze, facial expression, body postures, and gestures to regulate social interaction

      2. Failure to develop peer relationships appropriate to developmental level

      4. A lack of spontaneous seeking to share enjoyment, interests, or achievements with other people (e.g., by a lack of showing, bringing, or pointing out objects of interest to other people)

      6. Lack of social or emotional reciprocity

   2. Qualitative impairments in communication as manifested by at least one of the following:

      1. Delay in, or total lack of, the development of spoken language (not accompanied by an attempt to compensate through alternative modes of communication, such as gestures or mime)

      2. In individuals with adequate speech, marked impairment in the ability to initiate or sustain a conversation with others

      4. Stereotyped and repetitive use of language or idiosyncratic language

      6. Lack of varied spontaneous make-believe play or social imitative play appropriate to developmental level

   3. Restricted repetitive and stereotyped patterns of behavior, interests, and activities, as manifested by at least one of the following:

      1. Encompassing preoccupation with one or more stereotyped and restricted patterns of interest that are abnormal either in intensity or focus

      2. Apparently compulsive adherence to specific, nonfunctional routines or rituals

      4. Stereotyped and repetitive motor mannerisms (e.g., hand or finger flapping or twisting, or complex whole body movements)

      6. Persistent preoccupation with parts of objects

2. Delays or abnormal functioning in at least one of the following areas, with onset prior to age 3: (1) social interaction, (2) language as used in social communication, or (3) symbolic or imaginative play

3. Not better accounted for by Rhett disorder or childhood disintegrative disorder

(Reprinted, with permission, from Diagnostic and Statistical Manual of Mental Disorders, 4th edn. Text Revision. Copyright 2000 American Psychiatric Association.)

The term “pervasive developmental disorder (PDD)” was coined in 1980 as the overarching term for a class of disorders to which autism was then assigned. The term is essentially synonymous with “autism spectrum disorders.” The current diagnostic system includes other conditions within this class including Asperger syndrome (social disability but with good verbal skills), childhood disintegrative disorder (a rare condition in which a condition like autism develops after a period of normal development), Rett disorder (a neurodegenerative disorder with a strong genetic basis), and pervasive developmental disorder not otherwise specified (PDD-NOS). The latter is, somewhat paradoxically, the least well defined of the PDDs and least frequent studied, yet the most common type. The clinical features of the PDDs are summarized in Table 34–1.

Epidemiology

The first studies of epidemiology reported a prevalence rate of 4.5 per 10,000. Subsequent studies have tended to report higher rates, on balance around 9 children per 10,000. Although there has been much interest in higher rates in recent years, that is, whether the frequency of autism is increasing, several factors make it difficult to interpret the nature of the apparent increase. For example, diagnostic criteria have changed and current approaches were designed to work well in children over the range of cognitive ability levels. Secondly, rates reported vary depending on other factors, (e.g., sample size, with highest rates in reported in the smallest samples). There is also more general awareness of the condition. Given the importance of labels for service delivery (particularly in the United States), diagnostic substitution (e.g., assignment to PDD rather than mental retardation) can be problematic particularly for studies based on reports from schools and service providers.

Demographic, Gender, Cultural, and Ethnic Issues

In Kanner's first paper, many parents of autistic children were remarkably successful, leading to the impression of an association between social class and autism. However, subsequent studies have failed to reveal such an association. It appears that Kanner's initial sample reflected referral bias. Ethnic and cultural issues have been little studied in autism. While current diagnostic criteria appear to work well, there may be major differences in treatment. Gender differences have been consistently reported in autism, boys being 3–4 more times more likely than girls to have autism. However, this disparity is more marked at the upper end of the IQ distribution and, conversely, the ratio is less among children with more severe cognitive disability. This might either reflect a lower threshold for brain dysfunction in males or the fact that factor(s) causing autism in females must be more severe (Fombonne, 2005).

Etiology

In the first decades after autism was identified, there was much speculation that experiential factors might be involved in autism. However, as time went on, evidence (e.g., high rates of seizure disorder, persistence of primitive reflexes, “soft” neurological signs) suggested brain involvement. When the confusion between autism and schizophrenia was clarified, the focus began to shift toward brain and genetic mechanisms.

Genetics

The initial impression that there was no role for genetic factors in autism was discarded when the first twin samples were collected. Twin studies have revealed high levels of concordance for monozygotic twins compared to same-sex fraternal twins (although even in the latter the rate of autism was significantly increased over the population rate). Family studies reveal prevalence rates of between 2% and 10% in siblings. Even when siblings do not have autism, they have an increased risk for language, learning, and social development problems. There are higher rates of mood and anxiety problems in family members. Although specific modes of inheritance are not yet well established, it is clear that autism is a strongly genetic disorder. Efforts are now underway to identify potential genetic mechanisms. Of the multiple genes involved, at least some of these are likely to be identified in the next few years (Rutter, 2005).

Neurobiology

As noted, high rates of seizure disorder in autism suggest brain involvement. Although autism has been reported in association with many other conditions, these reports are based on case association rather than controlled studies with careful methodology. So, for example, what appeared to be a strong association of autism with congenital rubella became much less clear as, over time, the “autistic features” of such children markedly diminish. The strongest associations of autism with medical conditions are with two strongly genetic disorders: Fragile X syndrome and tuberous sclerosis (Minshew et al., 2005).

As the importance of genetic factors became apparent there has been less attention to studies of obstetrical risk, but some recent work has appeared. It is possible that a predisposition to autism interacts with perinatal factors in the pathogenesis of the condition. Although there has been much interest in the role of environmental factors in autism, supporting data are limited at present.

Different brain systems have been studied. Given the diversity of symptoms and clinical features it seems likely that multiple neural systems are involved. On the other hand it is clear that not all systems are involved, and sometimes autism is seen in children with good cognitive ability. Abnormalities in the limbic system, temporal and frontal lobes have been suggested. Postmortem studies have revealed abnormalities in the cortex (e.g., in the microarchitecture and cortical “minicolumns,” and in neuronal packing and size). A recent finding has been the report of overall brain size increase in children with autism. It remains unclear whether the increase is generalized or local. There is much speculation that brain connectivity is adversely affected.

The possible role of immunological factors in autism has been hypothesized, for example, that maternal antibodies are directed against the fetus during the pregnancy. A recent paper reports abnormalities in the placentas of children with autism.

There has been much controversy about the role of environmental factors in autism, particularly the MMR vaccine. Persistent measles infection in combination with gastrointestinal vulnerability or the effect of thimerasol (a mercury containing compound) have been hypothesized, but larger, controlled studies have not provided consistent support. A small set of children with autism clearly do have significant developmental regression, but this may be both coincident with and unrelated to immunization. The study of “regressive” autism remains an important topic.

Signs & Symptoms

Autism is characterized by a wide range of symptoms—over both age and developmental level. Less able children have significant behavioral problems and are typically mute whereas more able children are verbal and may have unusual special interests. Difficulties with social interaction are the major commonality running through this range. As first noted by Kanner, social skills are a source of major difference and impairment from early in life. Early social deficits take the form of lack of interest in joint attention, abnormalities in eye contact, and defective imitation. Social skills often do improve, but they remain a source of disability even for the most able individuals. Delays in language development are frequent concerns. When language develops it is associated with echolalia, pronoun reversal, and abnormal prosody and pragmatics. Many fail to develop symbolic–imaginative play.

In contrast to his relative lack of interest in the social environment, the nonsocial (inanimate) environment may seem highly relevant to the child with autism. Difficulties with change in routine, repetitive behavior, and unusual attachments may be observed (e.g., the child may be fascinated with spinning objects).

Autism is a disorder of early onset. Increasingly, there has been a focus early diagnosis, and autism is now often diagnosed in the first year of life. Occasionally children develop normally or near normally for a time before losing skills and developing a typical autistic profile.

Other problems are not essential diagnostic features, but are typically seen. These include problems with hyper- or hyposensitivity, problems with sleeping and eating, and difficulties with mood regulation. Self-injurious behavior is sometimes encountered.

Psychological Tests

Kanner's early impression of normal intellectual potential proved incorrect. It became apparent that, while children with autism often have strengths in nonverbal tasks (e.g., puzzles), they are markedly deficient in verbal cognitive abilities. Most autistic children function, overall, in the mentally retarded range, but scattered subtest scores are common. It appears that overall cognitive abilities improve with early detection and intervention. In autism areas of weakness typically include verbal concept formation, abstract thinking, and social reasoning. A different profile may be observed in individuals with Asperger disorder where verbal abilities are relatively intact.

Islets of special ability (“savant skills”) are sometimes observed. Highly developed skills in special areas such as drawing, musical performance, or calendar calculation are much greater than would be expected given overall IQ. Special ability is also reflected in the relatively frequent phenomenon of hyperlexia, a precocious interest in letters and numbers (Hermelin, 2001).

Laboratory Findings

At this point no specific biological markers have been identified. High peripheral levels of serotonin, a central neurotransmitter, have been reported in groups of children with autism since the 1960s. The significance of this finding is unclear. Research findings on other neurotransmitter systems, such as dopaminergic, is of interest. EEG abnormalities may be seen in autism but are not diagnostic. EEG abnormalities and epilepsy are more likely in cognitive impaired autistic children. Approximately 20–25% of children with strictly diagnosed autism develop seizures; these are of diverse types. There are two peaks of seizure onset: early childhood and adolescence. Studies of evoked potentials have shown abnormalities on social tasks.

Neuroimaging

MRI studies have focused both on structure and function. For example studies of the amygdala and hippocampus have not found differences in volume but fMRI studies have shown hypoactivity of the amygdala in tasks involving social and affective judgments. Probably the best replicated finding from fMRI has been the hypoactivation, relative to normal controls, of the fusiform gyrus during face perception tasks. This observation is consistent with an extensive literature on performance deficits in face processing tasks and facial expression recognition in autism, and provides an important key to understanding the core social deficits in autism. Other research has focused on the regions of the prefrontal cortex presumed to be involved in social cognitive tasks (Schultz et al., 2000). These difficulties may, in part, account for some aspects of the social difficulty in autism (see Figure 34–1).

Although the outcome of autism is improving, autism is a life long disability. As many as 20% or more of autistic individuals now becoming adults may be able to function with independence and self-sufficiency. Gains can be made by individuals of all ages and levels of functioning. Positive prognostic signs for autism include some communicative speech by the age of 5 or 6 years and average nonverbal cognitive skills. As adolescents, a few individuals make gains while others lose ground. As noted previously, epilepsy sometimes has its onset in adolescence. More able individuals (e.g., those with Asperger disorder) generally have the best outcome in terms of marriage and personal self-sufficiency (Howlin, 2005).

Autism must be differentiated from other developmental disorders (including related PDDs) and from sensory impairments. A detailed history and mental and physical examination are required. The early onset of problems in social interaction and communication are typical, and unusual behaviors often develop somewhat later (often around age 3 years). In mental retardation without autism, social skills are preserved and commensurate to cognitive level. In specific language disorders, language difficulties are seen in the context of good social skills. Rett disorder and childhood disintegrative disorder have highly distinctive patterns of early onset. In Asperger disorder verbal abilities are relatively preserved. It is more typical for parental concern to arise rather later in early childhood (after age 3 years); the differentiation of high-functioning autism from Asperger disorder can be problematic.

In obtaining historical information, aides to memory, such as baby books and videos, can be useful. A history of normal development followed by regression should prompt careful diagnostic investigation. Similarly, unusual features in the family history, child examination, and so forth may require specific investigation (Volkmar & Klin, 2005).

Educational and Behavioral Interventions

Autism is a disorder of development. At the same time, development affects autism. The goal of treatment is to minimize the disruptive effects of autism on development and maximize normative developmental processes. Goals change with the child's age and level of functioning, but always involve an explicit focus on social, language, and adaptive (self-help) skills. A structured, comprehensive program is needed with input from various professionals. The approaches used vary on several dimensions (e.g., how much they emphasize a child-centered or a developmental approach as contrasted to an adult-centered behavioral approach); however, all approaches share many features (National Research Council, 2001).

The focus of speech and language therapy is to expand the range of the child's communication skills. This should include teaching broader communication skills and beyond more vocabulary. Children who are not yet verbal can be helped by augmentative strategies (e.g., manual signing, picture exchange, and so forth). For more advanced children, the focus is more on social language use. Behavioral interventions are used in educational program. These techniques help with management of disruptive behavior and facilitate learning. Given the tendency of children with autism to learn things in isolation, the generalization of skills is important and is an essential aim.

Psychopharmacological Interventions

Medications do not affect the central social and communicative aspects of autism but may ameliorate the problem behavior that interfere with programming. Neuroleptic medication, particularly the atypical neuroleptics, are effective in decreasing stereotypic behavior and agitation; however, side effects may limit their usefulness. Much interest has centered on the SSRIs (selective serotonin reuptake inhibitors) given their potential for alleviating anxiety and behavioral rigidity. For adolescents with depression, antidepressants can be helpful. Mood stabilizers are sometimes useful (Scahill & Martin, 2005).

Psychotherapeutic Interventions

In the 1950s and 1960s, intervention often involved the psychotherapy of parents and children, with little apparent benefit. The role for dynamic psychotherapy is limited except in the case of more able individuals who can respond to supportive and directive treatment. There is a risk of depression in adolescence, which may respond to a combination of psychotherapy and pharmacology.

Alternative Treatments

Many different treatments have been proposed. Most lack an empirical foundation. A majority of parents engage in such treatments (although they may not always discuss them with physicians). Generally, there are no supportive data other than case report; single cures are not particularly informative. Furthermore the first follow-up studies demonstrated good outcome in a small number of cases without what, today, would be recognized as effective treatment, i.e., some children do well anyway. Furthermore there is a strong placebo (nonspecific treatment) effect. Occasionally alternative treatment is dangerous, either in terms of loss of access to effective programs or because of physical harm (Jacobson et al., 2005).

Seizures are the most common medical complication. The usual risks associated with pharmacological intervention are observed. Given difficulties with judgment and cognition, there is an increased risk for injury and accidental death.

The earliest studies of autism suggested relatively poor prognosis, only a small number of individuals (1–2%) being able to function independently as adults. Recent research reveals major gains with early diagnosis and treatment. Outcome is significantly improved if early intervention is provided. On the other hand, some children make few gains despite appropriate programs. Some children make gains in early childhood, others in adolescence. Despite good intervention, some children do not substantively progress (Howlin, 2005).

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