Austistic disorder

Fred R. Volkmar, M.D., and Ami Klin, Ph.D.

DEFINITION

The pervasive developmental disorders are early-onset conditions characterized by delay and deviance in the development of social, communicative, and other skills. The individual lacks interest in the social environment, but unusual behavioral responses to the inanimate environment are typical, including various motor mannerisms (stereotypies), resistance to change, and idiosyncratic interests and preoccupations. In the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) this category includes autistic disorder, Rett's disorder, childhood disintegrative disorder, Asperger's disorder, and pervasive developmental disorder not otherwise specified.

AUTISTIC DISORDER

Definition

Autistic disorder, also known as childhood autism, infantile autism, or early infantile autism, is by far the best known of the pervasive developmental disorders. In this condition there is marked and sustained impairment in social interaction, deviance in communication, and restricted or stereotyped patterns of behavior and interest. Abnormalities in functioning in each of these areas must be present by age 3 years. Approximately 70 percent of individuals with autistic disorder function at the mentally retarded level, and mental retardation is the most common comorbid diagnosis.

History

Comparative Nosology

Table 38-1. ICD-10 Diagnostic Criteria for Pervasive Developmental Disorders

Childhood autism

(1) receptive or expressive language as used in social communication;

(a) failure adequately to use eye-to-eye gaze, facial expression, body posture, and gesture to regulate social interaction;

A. Abnormal or impaired development is evident before the age of 3 years in at least one of the following areas:

(2) the development of selective social attachments or of reciprocal social interaction;

(3) functional or symbolic play.

B. A total of at least six symptoms from (1), (2), and (3) must be present, with at least two from (1) and at least one from each of (2) and (3):

(1) Qualitative abnormalities in reciprocal social interaction are manifest in at least two of the following areas:

(b) failure to develop (in a manner appropriate to mental age, and despite ample opportunities) peer relationships that involve a mutual sharing of interests, activities, and emotions;

(c) lack of socioemotional reciprocity as shown by an impaired or deviant response to other people's emotions; or lack of modulation of behavior according to social context; or a weak integration of social, emotional, and communicative behaviors;

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

(2) Qualitative abnormalities in communication are manifest in at least one of the following areas:

(a) a delay in, or total lack of, development of spoken language that is not accompanied by an attempt to compensate through the use of gesture or mime as an alternative mode of communication (often preceded by a lack of communicative babbling);

(b) relative failure to initiate or sustain conversational interchange (at whatever level of language skills is present), in which there is reciprocal responsiveness to the communications of the other person;

(c) stereotyped and repetitive use of language or idiosyncratic use of words or phrases;

(d) lack of varied spontaneous make-believe or (when young) social imitative play.

(3) Restricted, repetitive, and stereotyped patterns of behavior, interests, and activities are manifest in at least one of the following areas:

(a) an encompassing preoccupation with one or more stereotyped and restricted patterns of interest that are abnormal in content or focus; or one or more interests that are abnormal in their intensity and circumscribed nature though not in their content or focus;

(b) apparently compulsive adherence to specific, nonfunctional routines or rituals;

(c) stereotyped and repetitive motor mannerisms that involve either hand or finger flapping or twisting, or complex whole body movements;

(d) preoccupations with part-objects or nonfunctional elements of play materials (such as their odor, the feel of their surface, or the noise or vibration that they generate).

C. The clinical picture is not attributable to the other varieties of

.

Table 38-2. DSM-IV Field Trial Group Characteristics by Clinical Diagnosis

Table 38-3. Results of

DSM-IV Field Trial:

Sensitivity/Specificity

for DSM-III, DSM-III-R,

and ICD-10

Epidemiology

Table 38-4.

Representative

Epidemiological

Studies of Autism

disorders which fit the general description for pervasive developmental disorders but in which contradictory findings or a lack of adequate information mean that the criteria for any of the other pervasive developmental disorders codes cannot be met.

Reprinted with permission from World Health Organization: The ICD-10 Classification of Mental and Behavioural Disorders: Diagnostic Criteria for Research. © World Health Organization, Geneva, 1993.

Clinically Autistic Other PDDs Non-PDD

(N 454) (N 240) (N 283)

Sex ratio (M:F) 4.49:1 3.71:1 2.29:1

% Mute 54% 35% 33%

X Age (SD) 8.99 (7.18) 9.68 (6.57) 9.72 (8.26)

X I.Q. (SD) 58.1 (25.6) 77.2 (29.6) 66.9 (23.4)

PPD, pervasive developmental disorder. Data from Volkmar FR, Klin A, Siegel B, et al: Field trial for autistic disorder in DSM-IV. Am J Psychiatry 151:1361, 1994.

Se Sp PPV NPV TPV K

DSM-III (current/residual IA) .82 .80 .78 .84 .81 .62

DSM-III (current IA) .71 .88 .84 .80 .80 .60

DSM-III-R .86 .73 .73 .86 .79 .58

DSM-IV/ICD-10 .79 .87 .87 .83 .85 .70

Se, sensitivity; Sp, specificity; PPV, positive predictive validity; TPV, total predictive validity; K, agreement with clinician's diagnosis of autism. Data from Volkmar FR, Klin A, Siegel B et al: Field Trial for Autistic Disorder in DSM-IV. Am J Psychiatry 151:1361, 1994.

Sex Ratio Studies based on both clinical and epidemiological samples have suggested a higher incidence of autistic disorder in boys than in girls, with reported ratios averaging about 3.5 or 4.0 to 1

Social Class Although a few early studies supported Kanner's impression of an association between autism and upper socioeconomic status, epidemiological studies by L. Wing, Eric Schopler, and others have failed to reveal such association. In addition to the bias for more-educated and successful parents to seek referral, families from disadvantaged backgrounds still seem to be underrepresented in clinically referred samples. Outreach initiatives are needed to give children from all socioeconomic backgrounds equal access to diagnostic and intervention services.

Etiology

Neurochemistry Beginning in 1961 a number of studies have reported that approximately one third of children with autistic disorder have increased peripheral concentrations of the neurotransmitter serotonin. Despite much research the significance of this finding remains unclear since it is not specific to autism and the relation of peripheral concentrations to central concentrations of serotonin is unclear.

Other work has focused on other neurotransmitters, such as dopamine. Hyperdopaminergic functioning of the brain might explain the overactivity and stereotyped movements seen in autism. Administration of stimulants that

Size of Criteria Prevalence

Target Used Rate (per

Study, Year Country Population Based On 10,000)

Lotter, 1966 U.K. 78,000 Kanner, 1943 4.5

Wing et al., 1976 U.K. 25,000 Kanner, 1943 4.8

Hoshino et al., 1982 Japan 609,848 Kanner, 1943 2.3

Gillberg et al., 1984 Sweden 128.600 DSM-III, 1980 4.0

Burd et al., 1987 U.S. 180,986 DSM-III, 1980 3.2

Bryson et al., 1988 Canada 20,800 DSM-III-R, 1987 10.1

Cialdella and Mamelle, 1989 France 135,180 DSM-III, 1980 4.5

Sugiyama and Abe, 1989 Japan 12,263 DSM-III, 1980 13.0

Gillberg et al., 1991 Sweden 78,106 DSM-III-R, 1987 9.5

Fombonne et al., 1997 France 325,347 ICD-10, 1992 5.3

increase dopamine concentration typically worsens behavioral functioning in autistic disorder. Studies of dopamine metabolites and catecholamine metabolites in cerebrospinal fluid (CSF) have yielded inconsistent results; however, agents that block dopamine receptors are effective in reducing the stereotyped and hyperactive behaviors of many autistic children.

The endogenous opioids were investigated given the possibility that these compounds, enkephalins and endorphins, might lead to social withdrawal and unusual sensitivities to the environment. This was the rationale for using opioid antagonists such as naltrexone (ReVia) to treat children with autistic disorder. Although these agents may have a modest effect on the high levels of activity and agitation, overall results have been disappointing.

Immune Theories Some work has suggested a possible role of immunological factors in autistic disorder. There has been a suggestion that maternal antibodies directed against the fetus may be produced in utero. There also have been reports of autism associated with viral infections.

Table 38-5. Diagnostic Criteria for Autistic Disorder

A. A total of six (or more) 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:

(a) 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

(b) failure to develop peer relationships appropriate to developmental level

(c) 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)

(d) lack of social or emotional reciprocity

(2) qualitative impairments in communication as manifested by at least one of the following:

(a) 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 gesture or mime)

(b) in individuals with adequate speech, marked impairment in the ability to initiate or sustain a conversation with others

(c) stereotyped and repetitive use of language or idiosyncratic language

(d) 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:

(a) encompassing preoccupation with one or more stereotyped and restricted patterns of interest that is abnormal either in intensity or focus

(b) apparently inflexible adherence to specific, nonfunctional routines or rituals

(c) stereotyped and repetitive motor mannerisms (e.g., hand or finger flapping or twisting, or complex whole-body movements)

(d) persistent preoccupation with parts of objects

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

C. The disturbance is not better accounted for by Rett's disorder or childhood disintegrative disorder.

FIGURE 38–1 Age of recognition of autism in a series of 174 consecutive cases. (Reprinted with permission from Lewis M, Volkmar F: Clinical Aspects of Child Development, ed 4. Williams & Wilkins, Baltimore, 1996.

Pathology and Laboratory Examination

Electroencephalography A variety of electroencephalographic (EEG) abnormalities may be seen in autistic disorder, including diffuse and focal spikes, paroxysmal spike and wave patterns, multifocal spike activity, and a mixed discharge. The prevalance of EEG abnormalities in autistic disorder (in the absence of a clinical seizure disorder) ranges from 10 to 83 percent and depends on the number of recordings and the nature of the sample obtained. The prevelance of abnormal EEGs is significantly higher in individuals with mental retardation and autistic disorder. The high prevalance of EEG abnormalities and seizure disorders in autism were among the first compelling pieces of evidence supporting a biological basis for the condition.

Evoked Potential Recording Both early and more-recent studies of auditory brainstem evoked potentials in autistic disorder indicate that if children with underlying neurological conditions are excluded and age and gender are controlled, no evidence exists for abnormalities in the auditory brainstem pathways. However, abnormalities of cognitive potentials, particularly the auditory P300 (which represents the brain's processing of sensory stimuli) have been demonstrated in autistic disorder. This presumably reflects abnormalities in higher auditory processing and neural pathways.

Oculomotor and Postural Physiology Studies that focus on oculomotor and postural physiology of motor pathways have found bilaterally symmetric abnormalities in functions that depend on neocortical circuitry, with subtle or no abnormalities in parameters that depend on widely distributed pathways between posterior fossa and cortex and intact oculovestibular reflexes and posterior fossa circuitry.

Neuroimaging Studies

Computed Tomography Although some CT studies have shown enlargement of the lateral and third ventricles in approximately 15 to 45 percent of autistic individuals, several subsequent studies failed to corroborate this finding. Additionally, with the exception of the ventricular finding, the CT scans of subjects participating in these studies were otherwise normal, and since ventricular size was unrelated to all clinical indices examined in these studies, the implications of ventricular enlargement for the pathophysiology of autism are unknown.

Magnetic Resonance Imaging Two MRI studies of total brain area and volume found increased total brain volume above the lower boundary of the brainstem, reflecting increased tissue volume and lateral ventricular volume.

A follow-up study reported that the enlargement of the cerebral hemisphere was regional, involving occipital, parietal, and temporal regions but not the frontal lobe. A series of MRI studies focusing on the cerebellar vermis revealed decrease in the midsagittal area of vermal lobules VI and VII, but these findings have not been independently replicated in studies controlling for age and I.Q. A small number of MRI studies of the brainstem revealed a reduction in area, although most studies found no differences from controls; similarly, volumetric studies of hippocampus revealed no abnormalities. While an early MRI study of corpus callosum found no abnormalities in the midsagittal area, a recent study reported decreases in the middle and posterior regions when measurements were adjusted for total brain volume. The latter study involved the same subjects in whom increased volumes of the parietal, temporal, and occipital lobes but not the frontal lobes were found. The dissociation between the sizes of the cerebral cortex and corpus callosum was interpreted as evidence of abnormal development of neural connectivity between the hemispheres.

Neuropathological Studies

Autopsy studies of a small number of autistic individuals have failed to reveal gross brain abnormalities. However, microscopic analysis has revealed reduced neuronal size and increased cell packing density in the hippocampus, amygdala, mammillary body, anterior cingulate cortex, and septum. These areas are known to be related to each other by interconnecting circuits making up a major portion of the limbic system of the brain. There is evidence of decreased numbers of Purkinje's cells and granule cells in the neocerebellar cortex.

Table 38-6. Differential Diagnostic Features of Autism and Nonautistic Pervasive

Developmental Disorders

Scroll right to see more columns.

John was the second of two children born to middle-class parents after normal pregnancy, labor, and delivery. As an infant, John appeared undemanding and relatively placid; motor development proceeded appropriately, but language development was delayed. Although his parents indicated that they were first concerned about his development when he was 18 months of age and still not speaking, in retrospect they noted that in comparison to their previous child, he had seemed relatively uninterested in social interaction and the social games of infancy. Stranger anxiety had never really developed, and John did not exhibit differential attachment behaviors toward his parents. Their pediatrician initially reassured John's parents that he was a "late talker," but they continued to be concerned. Although John seemed to respond to some unusual sounds, the pediatrician

Childhood Pervasive

Autistic Asperger's Rett's Disintegrative Developmental

Feature Disorder Disorder Disorder Disorder Disorder NOS

Age at recognition 0–36 Usually 36 5–30 24 Variable (months)

Sex ratio MF MF F MF MF

Loss of skills Variable Usually not Marked Marked Usually not

Social skills Very poor Poor Varies with Very poor Variable age

Communication skills Usually poor Fair Very poor Very poor Fair to good

Circumscribed interests Variable Marked (facts) NA NA Variable (mechanical)

Family history of similar Sometimes Frequent Not usually No Unknown problems

Seizure disorder Common Uncommon Frequent Common Uncommon

Head growth decelerates No No Yes No No

I.Q. range Severe MR Mild MR to Severe MR Severe MR Severe MR to normal normal to normal

Outcome Poor to fair Fair to good Very poor Very poor Fair to good

Adapted with permission from Volkmar FR, Cohen D: Nonautistic pervasive developmental disorders. In Psychiatry, R Michaels, editor. Lippincott-Raven, Philadelphia, 1998.

obtained a hearing test when John was 24 months old. His hearing appeared adequate for development of speech, and John was referred for developmental evaluation. At 24 months, motor skills were age appropriate, and John exhibited some nonverbal problem-solving skills close to age level. His language and social development, however, were severely delayed, and he was noted to be resistant to changes in routine and unusually sensitive to aspects of the inanimate environment. His play skills were quite limited, and he used play materials in unusual and idiosyncratic ways. His older sister had a history of some learning difficulties, but the family history was otherwise negative. A comprehensive medical evaluation revealed no EEG and CT abnormalities; results of genetic screening and chromosome analysis were normal as well. John was enrolled in a special education program, where he gradually began to speak. His speech was characterized by echolalia, extreme literalness, a monotonic voice quality, and pronoun reversal. He rarely used language in interaction and remained quite isolated. By school age, John had developed some evidence of differential attachments to family members; he also had developed a number of self-stimulatory behaviors and engaged in occasional periods of head banging. Extreme sensitivity to change continued. Intelligence testing revealed marked scatter, with a full-scale I.Q. in the moderately retarded range. As an adolescent, John's behavioral functioning deteriorated, and he developed a seizure disorder. Now an adult, he lives in a group home and attends a sheltered workshop. He has a rather passive interactional style but exhibits occasional outbursts of aggression and self-abuse. (Reprinted with permission from Volkmar F: Autism and the pervasive developmental disorders. In Child and Adolescent Psychiatry: A Comprehensive Approach, ed 2, M Lewis, editor. Williams & Wilkins Baltimore, 1996.

Treatment

The goals of treatment for children with autistic disorder are to reduce disruptive behaviors and to promote learning, particularly language acquisition and communication and self-help skills. These goals are best achieved after a comprehensive assessment has determined a profile of strengths and needs and a highly structured and individualized intervention program is put in place that addresses the child's weaknesses and maximizes the child's assets. This program should usually take place in a special education setting and should be carried out by professionals experienced in working with children with autistic disorder. A recent review of several treatment studies highlighted the importance of intensive, early intervention to individual

outcome. Treatment goals should be updated regularly, because different issues should be prioritized as a function of the child's rate and profile of progress and age (e.g., vocational training and independent living skills should be aggressively promoted in adolescence). Additionally, psychopharmacological treatments may be beneficial when specific symptoms are not amenable to other treatment modalities.

Educational Approaches Children with autistic disorder require intensive, highly structured special education, starting as early as the child can tolerate a school routine. Given the challenges involved in teaching autistic disorder children, usually a classroom setting with a low student to teacher ratio is essential. For the more impaired children, a typical hierarchy of priorities should include the ability (1) to tolerate individual adult guidance in performing tasks, (2) to follow a daily routine consistently, (3) to develop communication intent and communication means, and (4) to move from associative to conceptual learning. Learning should take place in an environment that minimizes such distractions as nearby windows or richly decorated walls; the more-challenged children may require individual work stations and forceful adult intrusion. Highly predictable, consistent routines are necessary to promote the child's own internal sense of order, scheduling, and organization of experiences and thus more-systematic learning. Children with autistic disorder often learn skills in a highly circumscribed fashion, exhibiting a capacity only in a very concrete and specific setting. Therefore, one must ensure that the child both begins to use the skill spontaneously (e.g., uses new words for requesting in an unpromoted fashion) and generalizes from the setting in which the skill was acquired to a different setting (e.g., uses the new words at home and in other settings where they would be appropriate). An improved ability to predict impending activities and to express one's wishes and protest usually help reduce frustration and associated disruptive behaviors.

Speech and language therapy focuses on the use of words for meaningful communication. Children with autistic disorder may acquire a considerable vocabulary that is dissociated from the act of communication. Therefore, language acquisition should go hand in hand with promotion of the child's intent to communicate with others. For this purpose, vocabulary expansion should focus on words that are relevant to the child's attempt to negotiate the demands of everyday life. Children who do not vocalize should be engaged in programs that use alternative forms of communication, including signs, communication boards, or other forms of augmentative communication. The use of nonvocal forms of communication should not preclude the simultaneous use of words by children whose vocalizations are just emerging and for whom vocal communication is a realistic goal. For older or higher-functioning children, the educational program should focus intensively on social and communication skills training. Positive actions in frequently troublesome situations may have to be rehearsed and scripted; concrete

social and communication skills—eye gaze, voice modulation, gestural communication, posture, proximity, greeting behaviors, rules of conversation, and social expectations—may have to taught in a very explicit fashion. Social and communication skills therapy may have to alternate between small group instruction (where appropriate behaviors can be practiced and supportive feedback can be gained) and naturalistic settings (where the newly acquired skill can be practiced or where additional target problematic behaviors can be identified for practice in the small setting). Successful techniques include modeling of behaviors by an instructor, self-observation, role-playing, and the use of individualized social stories.

Behavior Therapy Behavior therapy, which is based on learning theory principles, uses behavior modification technique to establish desired behaviors and eliminate problem behaviors. Most educational programs for children with austistic disorder use behavioral management technique, although they vary in how integrated these procedures are in the comprehensive educational program. Behavior therapy is particularly useful in managing disruptive behaviors, which range from difficulties in attention and compliance to tantruming and self-injurious behaviors. After a functional analysis of the target behavior is performed and patterns of reinforcement are identified, techniques such as shaping, prompting, and extinction are used to promote the desired alternative behavior, which is then reinforced by increasingly mature rewards. Behavior therapy is also used to facilitate learning, including the promotion of early cognitive skills such as categorization and elicitation of vocalization and speech. Given the autistic child's tendency to learn things in isolation, skills learned through behavior interventions must be relevant to the child's adaptation and must be increasingly used spontaneously and in different settings. Thus, an appropriate behavioral curriculum should place special emphasis on generalization and self-initiated skills. Although most agree that children with autistic disorder profit from behavior therapy, it is still unclear whether some claims of extraordinarily good outcome for autistic children receiving intensive behavior treatment are justified. One must also ensure that higher-level forms of teaching are not more appropriate to a given child (e.g., a more intellectually able child) before most of the educational resources are focused on behavior therapy.

Psychotherapy With the shift from a psychogenic to a biological understanding of autistic disorder, it became clear that psychodynamic psychotherapy and unstructured play therapies in general were not appropriate for the treatment of young children. Individual psychotherapy may be appropriate for higher-functioning individuals who may present with anxiety and depressive symptoms as they grow older and become more aware of their differences and difficulties relating to others. In these instances, psychotherapy should focus on rather explicit problem-solving skills

rather than being insight oriented, with the goal of promoting better adjustment and self-satisfaction.

Psychopharmacology No pharmacological agent has proved curative, but certain medications may be of benefit for specific symptoms such as self-injury, aggression, stereotyped movements, and overactivity. Because autistic individuals are often enrolled in educational and behavioral programs, it may be possible to have staff participate, for example, by collecting behavioral data that can be used to monitor the effectiveness of the drug. As with all medications the potential benefits and adverse effects should be considered; for example, the major tranquilizers carry a potential for oversedation, which can be mistaken for a positive therapeutic response. Prior to beginning drug treatment, baseline laboratory studies (tests of liver and renal function, electrocardiogram [ECG], urinalysis, blood count, weight, blood pressure) should be conducted. An examination for abnormal movements is usually performed (typically with the Abnormal Involuntary Movements Scales [AIMS]).

ANTIPSYCHOTICS The dopamine receptor antagonists are the most extensively studied agents in autistic disorder. At relatively low dosages they may decrease stereotyped behaviors and agitation and may help the individual profit from remedial programming. Some data suggest that the combination of these agents with behavior therapy is more effective than either treatment alone. Adverse effects may limit the usefulness of these agents (e.g., sedation, withdrawal, and tardive dyskinesia). The higher-potency neuroleptics have often been used because of their lower likelihood of sedation, although these agents do carry increased risk for dystonias. Recent interest has centered on the serotonin–dopamine antagonists, which appear to offer considerable potential promise.

SELECTIVE SEROTONIN REUPTAKE INHIBITORS Several reports suggested the potential usefulness of the selective serotonin reuptake inhibitors (SSRIs) in autistic disorder and related conditions with the observation of higher peripheral serotonin concentrations in autistic persons. In several controlled studies these medications have proved superior to placebo in treating such symptoms as repetitive behaviors, impulsive aggression, or both. There is a suggestion that seizure disorders may be exacerbated in some cases.

CLONIDINE The use of clonidine (Catapres) was suggested because of the apparently high levels of arousal in autistic disorder. This agent, an 2-adrenergic receptor agonist, reduced noradrenergic activity. It may exert a modest effect on activity levels, but sedation and hypotension can be serious adverse effects.

NALTREXONE Interest in the endogenous opioid system was spurred by early studies that reported high endogenous opioid concentrations. The

opioid receptor antagonist naltrexone has been evaluated in several studies. The major effect of this agent appears to be a mild decrease in activity levels. Neither increased social engagement nor facilitation of learning has been observed.

OTHER AGENTS Various other agents have been reported to sometimes be effective in treating at least some of the symptoms of autistic disorder. Such evidence is usually based on single case reports, and controlled studies are often lacking. Lithium (Eskalith) is generally not clearly helpful unless a personal or family history of bipolar disorder exists. Although the available data are limited, in general, psychostimulants appear to exacerbate behavioral difficulties in autistic disorder, probably because of their effect on dopamine. -Adrenergic receptor antagonists (beta-blockers) have been used in several open trials concerned with reducing aggressive, self-injurious, and impulsive behaviors. These agents may decrease arousal levels, and positive responses have been noted, although the potential for serious adverse effects limits their more general use.

Parents are often interested in so-called alternative treatments, including diet and vitamin therapy. Although they are the focus of much interest, substantive data are lacking. Various somatic treatments have not proven clinically useful. In general, unproved treatments should be avoided, particularly if they are pursued at the expense of educational and behavioral interventions that are known to be efficacious. Treatments that pose actual danger to the child are sometimes proposed and clearly should be avoided. Given the relatively poor prognosis associated with autistic disorder, parents are easily attracted to treatments that propose a rapid cure. Parents should be encouraged to pursue treatments with known efficacy.

RETT'S DISORDER

Definition

Rett's disorder is a progressive condition that develops after some months of apparently normal development. Head circumference at birth is normal, and early developmental milestones are unremarkable. Between 5 months and 48 months (usually between 6 months and 1 year), head growth begins to decelerate. Purposeful hand movements are lost, and characteristic midline hand-wringing or hand-washing stereotypies develop. Expressive and receptive language skills become severely impaired and are associated with marked mental retardation. Gait apraxia and truncal apraxia and ataxia develop in the preschool years. A loss of social interactional skills is frequently observed during the preschool years, but social interest often increases later. To date the condition has been convincingly demonstrated only in girls.

Table 38-7. DSM-IV Diagnostic Criteria for Rett's Disorder

Darla was born at term after an uncomplicated pregnancy. An amniocentesis obtained because of maternal age was normal. At birth, Darla was in good condition; weight, height, and head circumference were all near the 50th percentile. Her development during the first months of life was within normal limits. At about 8 months of age, her development seemed to stagnate, and her interest in the environment, including the social environment, waned. Her developmental milestones then became markedly delayed; she was just starting to walk at her second birthday and had no spoken language. Evaluation at that time revealed that head growth had decelerated. Some self-stimulatory behaviors were present. Marked cognitive and communicative delays were noted on formal testing. Darla began to lose purposeful hand movements and developed unusual hand-washing stereotyped behaviors. By age 6, her EEG was abnormal, and purposeful hand movements were markedly impaired. Subsequently, she developed truncal ataxia and breath-holding spells, and motor skills deteriorated further. (Reprinted with permission from Volkmar F: Autism and the pervasive developmental disorders. In Child and Adolescent Psychiatry: A

A. All of the following:

(1) apparently normal prenatal and perinatal development

(2) apparently normal psychomotor development through the first 5 months after birth

(3) normal head circumference at birth

B. Onset of all of the following after the period of normal development:

(1) deceleration of head growth between ages 5 and 48 months

(2) loss of previously acquired purposeful hand skills between ages 5 and 30 months with the subsequent development of stereotyped hand movements (e.g., hand-wringing or hand-washing)

(3) loss of social engagement early in the course (although often social interaction develops later)

(4) appearance of poorly coordinated gait or trunk movements

(5) severely impaired expressive and receptive language development with severe psychomotor retardation

Reprinted with permission from American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, ed 4. © American Psychiatric Association, Washington, DC, 1994.

Comprehensive Approach, ed 2, M Lewis, editor. Williams & Wilkins, Baltimore, 1996.)

Treatment

There is no specific treatment for Rett's disorder. Special education, behavior modification, and physical and respiratory therapies may be useful. No specific pharmacological treatment is available. Given the high rate of seizure disorder, caution is needed in the use of medications that lower the seizure threshold. As with other pervasive developmental disorders, consideration should also be given to support for the parents and siblings of affected individuals.

CHILDHOOD DISINTEGRATIVE DISORDER

Definition

Childhood disintegrative disorder is a rare condition characterized by a marked regression in multiple areas of development after several years of normal development.

Table 38-8. DSM-IV Diagnostic Criteria for Childhood Disintegrative Disorder

Onset is usually between the ages of 3 and 4 years and may be either abrupt or gradual. There may be nonspecific agitation or anxiety prior to developmental deterioration. Figure 38–4 provides a summary of clinical features. The loss of social and communicative skills is (understandably) of great concern to parents. Stereotyped behaviors, problems with transitions and change, and nonspecific overactivity often develop. Deterioration in self-help skills can be striking and is in contrast to autistic disorder, in which such skills are acquired somewhat later than usual but typically are not lost.

FIGURE 38–4 Clinical features in childhood disintegrative disorder. (Data from Volkmar F, Klin A, Marons W, Cohen DJ: Childhood

A. Apparently normal development for at least the first two years after birth as manifested by the presence of age-appropriate verbal and nonverbal communication, social relationships, play, and adaptive behavior.

B. Clinically significant loss of previously acquired skills (before age 10 years) in at least two of the following areas:

(1) expressive or receptive language

(2) social skills or adaptive behavior

(3) bowel or bladder control

(4) play

(5) motor skills

C. Abnormalities of functioning in at least two of the following areas:

(1) qualitative impairment in social interaction (e.g., impairment in nonverbal behaviors, failure to develop peer relationships, lack of social or emotional reciprocity)

(2) qualitative impairments in communication (e.g., delay or lack of spoken language, inability to initiate or sustain a conversation, stereotyped and repetitive use of language, lack of varied make-believe play)

(3) restricted, repetitive, and stereotyped patterns of behavior, interests, and activities, including motor stereotypes and mannerisms

D. The disturbance is not better accounted for by another specific pervasive developmental disorder or by schizophrenia.

Reprinted with permission from American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, ed 4. © American Psychiatric Association, Washington, DC, 1994.

disintegrative disorder. In Handbook of Autism and Pervasive Developmental Disorders, ed 2, DJ Cohen, FR Volkmar, editors. Wiley, New York, 1997.)

Bob's early history was within normal limits. By age 2, he was speaking in sentences, and his development appeared to be proceeding appropriately. At age 40 months he abruptly exhibited a period of marked behavioral regression shortly after the birth of a sibling. He lost previously acquired skills in communication and was no longer toilet trained. He became uninterested in social interaction, and various unusual self-stimulatory behaviors became evident. Comprehensive medical examination failed to reveal any conditions that might account for this developmental regression. Behaviorally, he exhibited features of autistic disorder. At follow-up at age 12 he spoke only an occasional single word and was severely retarded. (Reprinted with permission from Volkmar F: Autism and the pervasive developmental disorders. In Child and Adolescent Psychiatry: A Comprehensive Approach, ed 2, M Lewis, editor. Baltimore, Williams & Wilkins, 1996.)

Treatment

As with autistic disorder, special education and behavioral treatments are indicated to help encourage reacquisition of skills. No specific pharmacological treatments exist.

ASPERGER'S DISORDER

Definition

Asperger's disorder is characterized by impairments in social interaction and restricted interests and behaviors as seen in autism, but its early developmental course is marked by a lack of any clinically significant delay in spoken or receptive language, cognitive development, self-help skills, or curiosity about the environment. All-absorbing and intense circumscribed interests and motor clumsiness are typical of the condition but are not required for diagnosis.

Table 38-9. DSM-IV Diagnostic Criteria for Asperger's Disorder

Tom was an only child. Birth, medical, and family histories were unremarkable. His motor development was somewhat delayed, but

A. 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

(3) 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)

(4) lack of social or emotional reciprocity

B. 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 is abnormal either in intensity or focus

(2) apparently inflexible adherence to specific, nonfunctional routines or rituals

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

(4) persistent preoccupation with parts of objects

C. The disturbance causes clinically significant impairment in social, occupational, or other important areas of functioning.

D. There is no clinically significant general delay in language (e.g., single words used by age 2 years, communicative phrases used by age 3 years).

E. There is no clinically significant delay in cognitive development or in the development of age-appropriate self-help skills, adaptive behavior (other than in social interaction), and curiosity about the environment in childhood.

F. Criteria are not met for another specific pervasive developmental disorder or schizophrenia.

Reprinted with permission from American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, ed 4. © American Psychiatric Association, Washington, DC, 1994.

communicative milestones were within normal limits. His parents became concerned about him at age 4 when he was enrolled in a nursery school and displayed marked difficulties in peer interaction that were so pronounced that he could not continue in the program. In grade school, he was enrolled in special education classes and was noted to have some learning problems. His greatest difficulties arose in peer interaction; he was viewed as markedly eccentric and had no friends. His preferred activity, watching the weather channel on television, was pursued with great interest and intensity. On examination at age 13, he had markedly circumscribed interests and exhibited pedantic and odd patterns of communication with a monotonic voice quality. Psychological testing revealed an I.Q. within the normal range, with marked scatter evident. Formal communication examination revealed age-appropriate skills in receptive and expressive language but marked impairment in pragmatic language skills. (Reprinted with permission from Volkmar F: Autism and the pervasive developmental disorders. In Child and Adolescent Psychiatry: A Comprehensive Approach, ed 2, M Lewis, editor. Williams & Wilkins, Baltimore, 1996.)

Treatment

As in autistic disorder, treatment of Asperger's disorder is essentially supportive and symptomatic and to a great extent overlaps with the treatment guidelines applicable to individuals with autistic disorder unaccompanied by mental retardation. One initial difficulty encountered by families is proving eligibility for special services. Since these children are often very verbal and many of them do well academically, educational authorities might judge that the deficits—primarily social and communicative—are not within the scope of educational intervention. In fact, these two aspects should be the core of any educational intervention and curriculum for individuals with this condition. Skills, concepts, appropriate procedures, cognitive strategies, and behavioral norms may be more effectively taught in an explicit and rote fashion using a parts-to-whole verbal instruction approach, in which the verbal steps are in the correct sequence for effective behavior. Additional guidelines should be derived from the individual's neuropsychological profile of assets and deficits. Acquisition of self-sufficiency skills in all areas of functioning should be a priority. The tendency of individuals with Asperger's disorder to rely on rigid rules and routines can be used to foster positive habits and enhance the person's quality of life and that of family members. Specific problem-solving strategies (usually following a verbal algorithm) may be taught for handling the requirements of frequently occurring, troublesome situations (e.g., involving novelty, intense social demands, or frustration). Training is usually necessary in recognizing troublesome situations and selecting the best available learned strategy to

use in such situations. Social and communication skills are best taught by a communication specialist with an interest in pragmatics in speech, in the context of both individual and small group therapy. Communication therapy should include appropriate nonverbal behavior (e.g., the use of gaze for social interaction, monitoring and patterning of voice inflection), verbal decoding of nonverbal behaviors of others, social awareness, perspective-taking skills, and correct interpretation of ambiguous communications (e.g., nonliteral language). Often, adults with Asperger's disorder fail to meet entry requirements for jobs in their area of training (e.g., college degree) or fail to maintain a job because of their poor interviewing skills, social disabilities, eccentricities, or anxiety attacks. Thus they must be trained for and placed in jobs for which they are not neuropsychologically impaired and in which they will enjoy some support and shelter. Preferably the job should not involve intensive social demands, time pressure, or the need to improvise quickly or generate solutions to novel situations. The little experience available with self-support groups suggests that individuals with Asperger's disorder enjoy the opportunity to meet others with similar problems and may develop relationships around an activity or subject of shared interest. Special interests may be used to create social opportunities through hobby groups. Supportive psychotherapy as well as pharmacological interventions may be helpful in dealing with feelings of despondency, frustration, and anxiety, although a more direct, problem-solving focus is thought to be more beneficial than an insight-oriented approach.

PERVASIVE DEVELOPMENTAL DISORDER NOT OTHERWISE SPECIFIED

Table 38-10. DSM-IV Diagnostic Criteria for Pervasive Developmental Disorder Not

Otherwise Specified

Leslie was the oldest of two children. She had been a difficult baby who was not easy to console but whose motor and

communicative development

seemed appropriate.

She was socially related and sometimes enjoyed social interaction, but

This category should be used when there is a severe and pervasive impairment in the development of reciprocal social interaction or verbal and nonverbal communication skills, or when stereotyped behavior, interests, and activities are present, but the criteria are not met for a specific pervasive developmental disorder, schizophrenia, schizotypal personality disorder, or avoidant personality disorder. For example, this category includes "atypical autism"—presentations that do not meet the criteria for autistic disorder because of late age at onset, atypical symptomatology, or subthreshold symptomatology, or all of these.

Reprinted with permission from American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, ed 4. © American Psychiatric Association, Washington, DC, 1994.

was easily overstimulated. She exhibited some unusual sensitivities to aspects of the environment and, at times of excitement, exhibited some hand flapping. Her parents sought evaluation when she was 4 years of age because of difficulties in nursery school. Leslie had problems with peer interaction. She was often preoccupied with possible adverse events. At evaluation she displayed both communicative and cognitive functions within the normal range. Although differential social relatedness was present, Leslie had difficulty using her parents as sources of support and comfort. She displayed behavioral rigidity and a tendency to impose routines on social interaction. Leslie was enrolled in a therapeutic nursery school where she made significant gains in social skills. Subsequently, she was placed in a transitional kindergarten and did well academically, although problems in peer interaction and unusual affective responses persisted. As an adolescent, she describes herself as a "loner" who has difficulties with social interaction and tends to enjoy solitary activities. (Reprinted with permission from Volkmar F: Autism and the pervasive developmental disorders. In Child and Adolescent Psychiatry: A Comprehensive Approach, ed 2, M Lewis, editor. Williams & Wilkins, Baltimore, 1996.)