Clinical Manifestations

The core features of autistic disorder (AD) include impairments in 3 symptom domains: social interaction; communication; and developmentally appropriate behavior, interests, or activities (Table 28-2). Stereotypical body movements, a marked need for sameness, and a very narrow range of interests are also common.

Aberrant development of social skills and impaired ability to engage in reciprocal social interactions are hallmark symptoms of AD. Early social skill deficits can include abnormal eye contact, failure to orient to name, failure to use gestures to point or show, lack of interactive play, failure to smile, lack of sharing, and lack of interest in other children. Some children with AD make no eye contact and seem totally aloof, whereas others show intermittent engagement with their environment and can make inconsistent eye contact, smile, or hug. Most children have some impairment in joint attention, which is the ability to use eye contact and pointing for the purposes of sharing experiences with others. These children show deficits in empathy for what another person might be feeling. They also demonstrate deficits in understanding what another person might be thinking, a lack of a theory of mind.

Children with AD vary in their verbal abilities. They can range from being nonverbal to having some speech (e.g., capable of imitating songs, rhymes, or television commercials). Speech might have an odd prosody or intonation and may be characterized by echolalia (imitative repetition of words), pronoun reversal, nonsense rhyming, and other idiosyncratic language forms. Early abnormal language concerns include absent babbling or gestures by 12 mo, absent single words by 16 mo, absent 2-word purposeful phrases by 24 mo, and any loss of language or social skills at any time.

Play skills in AD are typically aberrant, characterized by little symbolic play, ritualistic rigidity, and preoccupation with parts of objects. The child with AD is often withdrawn and spends hours in solitary play, often with restrictive or repetitive interests and behaviors. Ritualistic behavior prevails, reflecting the child’s need to maintain a consistent, predictable environment. Tantrum-like rages can accompany disruptions of routine.

Intellectual functioning can vary from mental retardation to superior intellectual functioning in select areas (splinter skills, savant behavior). Some children show typical development in certain skills and can even show areas of strength in specific areas, such as puzzles, art, or music.

Visual scanning of hand and finger movements, mouthing of objects, and rubbing of surfaces can indicate a heightened awareness of and sensitivity to some stimuli, whereas diminished responses to pain and lack of startle responses to sudden loud noises reflect lowered sensitivity to other stimuli.

Diagnosis

AD is diagnosed by the clinical examination. The gold standard diagnostic tools are the Autism Diagnostic Interview—Revised (ADI-R) and the Autism Diagnostic Observation Schedule (ADOS), which require referral to a trained professional for administration.

Neuropsychologic and achievement assessment should include intelligence testing to establish overall cognitive function and eligibility for services. Intelligence, as measured by conventional psychologic testing, falls in the functionally retarded range in 30-60% of children with AD. Deficits in language and socialization often make it difficult to obtain an accurate estimate of a child’s intellectual potential. Some children with AD perform adequately in nonverbal tests, and those with developed speech can show adequate intellectual capacity. Separate estimates of verbal and nonverbal (performance) intelligence quotient (IQ) should be obtained. A measure of adaptive functioning such as the Vineland Adaptive Behavior Scales is essential to establish priorities for treatment planning.

Critical elements of the evaluation should include a detailed developmental history with a review of communicative and motor milestones, a medical history including discussion of possible seizures, sensory deficits such as hearing or visual impairment, or other medical conditions associated with AD including fragile-X, Prader-Willi, Smith-Lemli-Opitz, Rett’s, and Angelman’s syndromes, fetal alcohol syndrome, tuberous sclerosis, neurofibromatosis, congenital rubella, or untreated phenylketonuria. The family history should be reviewed for the presence of other developmental disorders. A review of current and past psychotropic medications should include a review of medication dosages and behavioral response, along with adverse effects. The impact of other medications on behavioral status should also be reviewed.

The medical and genetic evaluation of children with PDD must consider a broad range of disorders (Table 28-3). Approximately 20% of children with AD have macrocephaly, but enlarged head size might not be apparent until after the 2nd yr of life. In the absence of dysmorphic features or focal neurologic signs, additional neuroimaging for investigation of macrocephaly is not usually indicated. Multidisciplinary assessment of AD is optimal in facilitating early diagnosis, treatment, and coordinated multiagency collaboration. Evaluations from various other professionals, including a developmental pediatrician or pediatric neurologist, medical geneticist, child and adolescent psychiatrist, speech-language pathologist, occupational or physical therapist, or medical social worker may be indicated.

Differential Diagnosis

The differential diagnosis includes consideration of the various PDD, mental retardation not associated with PDD (Chapter 33), specific developmental disorders (e.g., of language), early onset psychosis (e.g., schizophrenia), selective mutism, social anxiety (Chapter 23), obsessive-compulsive disorder, stereotypic movement disorder, inhibited-type reactive attachment disorder, and rarely, childhood-onset dementia.

Epidemiology

The incidence of AD has increased steadily over the past 15 yr. There is evidence that the increase in the number of children identified with AD is likely related to changes in the definition of and diagnostic criteria for AD, as well as improvements in the recognition of AD at younger ages. Current estimates of the prevalence rate of all PDD (63.7/10,000) are approximately 1 in 150-160. Disorder-specific prevalence rate estimates includes AD (20.6/10,000), Asperger’s disorder (6/10,000), PDD-NOS (37.1/10,000), Rett’s disorder (0.5-1/10,000 females), and childhood disintegrative disorder (2/100,000). The male : female ratios are estimated to be 4 : 1 for AD and 5 : 1 for Asperger’s disorder.

Pathology

Retrospective analysis of head circumference, in conjunction with MRI studies, has shown differences in the brain structure of children with AD. The head circumference in AD is normal or slightly smaller than normal at birth until 2 mo of age. Afterward children with AD show an abnormally rapid increase in head circumference from 6-14 mo of age, increased brain volume in 2-4 yr olds, increased volume of the cerebellum, cerebrum, and amygdala, and marked abnormal growth in the frontal, temporal, cerebellar, and limbic regions of the brain. Early, accelerated brain growth during the 1st several years of life is followed by abnormally slow or arrested growth, resulting in areas of underdeveloped and abnormal circuitry in parts of the brain. Areas of the brain responsible for higher-order cognitive, language, emotional, and social functions are most affected.

Etiology

The basis for AD is diverse and complex. Multiple genetic regions (chromosomes 16p11.2, 15q24, 11p12-p13) and gene variants (copy number variation, deletions, microdeletions, duplications, inversions, translocations) potentially contribute to abnormal neuronal and axonal growth, synapse formation, and myelination via gene-gene and gene-environment interactions over the course of prenatal and postnatal development. Inheritance patterns of AD demonstrate a 60% concordance rate for monozygotic twins and no concordance in dizygotic twins. A 4 : 1 male : female AD prevalence ratio suggests a sex-linked mechanism in a significant number of cases. An emerging etiologic hypothesis of AD describes spontaneous paternal or maternal genetic mutations that delete or inactivate areas of the genome affecting early brain development.

In utero toxic insults are also thought to carry the potential to produce disruptions in CNS development that can manifest as mental retardation and autistic symptoms. There is no scientifically substantiated association between the administration of the measles-mumps-rubella vaccine and the development of AD. As yet undiscovered environmental factors cannot be ruled out. There may be genetic associations between AD and premature birth as well as childhood-onset schizophrenia, suggesting possible common core neurobiologic processes for subsets of these two heterogeneous clinical groups.

Early Identification

Early identification and intervention of PDD are associated with better outcomes. Several instruments have been developed for screening of PDD in primary care settings including the Checklist for Autism in Toddlers (CHAT), the Modified Checklist for Autism in Toddlers (M-CHAT), and the Pervasive Developmental Disorders Screening Test (PDDST) (Chapter 18) (Fig. 28-1). Failures to meet age-expected language or social milestones are important early red flags for PDD and should prompt an immediate evaluation. Early signs include unusual use of language or loss of language skills, nonfunctional rituals, inability to adapt to new settings, lack of imitation, and absence of imaginary play. Deviations in social and emotional development (such as decreased eye contact, failure to orient to name, and lack of joint attention) can often be detected by 1 yr of age. The absence of expected social, communication, and play behavior often precedes the emergence of odd or stereotypical behaviors or the unusual language usage that is seen in AD in the later years.

Figure 28-1 Surveillance and screening algorithm: autism spectrum disorders (ASDs).

(From Plauche Johnson C, Myers SM, Council on Children with Disabilities: Identification and evaluation of children with autism spectrum disorders, Pediatrics 120:1183–1215, 2007.)

Treatment

The primary goals of treatment are to maximize the child’s ultimate functional independence and quality of life by minimizing the core features of the disorder, facilitating development and learning, promoting socialization, reducing maladaptive behaviors, and educating and supporting families. Educational interventions, including behavioral and habilitative (speech, occupational, and physical) therapies, are the cornerstones of treatment for the PDDs. These interventions address communication, social skills, daily-living skills, play and leisure skills, academic achievement, and maladaptive behaviors.

Model early childhood educational programs for children with PDD can be categorized as behavior analytic, developmental, or structured teaching on the basis of the underlying theoretical orientation. Although programs differ in relative emphasis, they share many common goals, including beginning intervention as early as possible; providing intensive intervention (at least 25 hr/wk, 12 mo/yr) in systematically planned educational activities; providing a low student-to-teacher ratio; including parent training; promoting opportunities for interaction with typically developing peers incorporating a high degree of structure through elements such as a predictable routine, visual activity schedules, and clear physical boundaries; implementing strategies to apply learned skills to new environments and situations; and using curricula that address functional spontaneous communication, social skills, functional adaptive skills, reduction of maladaptive behaviors, cognitive skills, and traditional academic skills. Some well-regarded programs that address at least some of these skills include Applied Behavioral Analysis (ABA), Discrete Trial Training (DTT), and Treatment and Education of Autistic and related Communication-handicapped Children (TEACCH). Most educational programs available to young children with PDDs are based in communities in the context of an Individualized Education Program (Chapter 15), and offer an eclectic treatment approach, which may be less effective than standardized protocols.

Parent training and family involvement includes educating parents about PDDs, providing access to needed ongoing supports and services, training and involving them as co-therapists, assisting them in advocating for their child’s needs, and providing emotional support.

Older children and adolescents with relatively higher intelligence, but with poor social skills and psychiatric symptoms, can benefit from more-intensive behavioral or cognitive-behavioral therapy (CBT) and/or supportive psychotherapy. The focus on achieving social communication competence, emotional and behavioral regulation, and functional adaptive skills necessary for independence continues. Every adolescent should be provided with a school-based individualized transition plan, where the focus may shift from academic to vocational services and from remediating deficits to fostering abilities. A vocational assessment can be helpful in this regard.

Pharmacotherapy can increase the ability of persons with AD to benefit from educational and other interventions and to remain in less-restrictive environments (Table 28-4). Common targets for pharmacological intervention include associated comorbid conditions and problematic behaviors such as aggression, self-injurious behavior, hyperactivity, inattention, anxiety, mood lability, irritability, compulsive-like behaviors, stereotypic behaviors, and sleep disturbances. After treatable medical causes and modifiable environmental factors have been ruled out, a trial of medication may be considered if the behavioral symptoms cause significant impairment in functioning. Prescribing is best approached with consultation from a practitioner with background and training in developmental disabilities.

Table 28-4 SELECTED POTENTIAL MEDICATION OPTIONS FOR COMMON TARGET SYMPTOMS OR COEXISTING DIAGNOSIS IN CHILDREN WITH AUTISM SPECTRUM DISORDERS

Epidemiology

The average age of onset of schizophrenia is 18 yr in men and 25 yr in women. The prevalence of childhood-onset schizophrenia is 1/10,000; prevalence of adult schizophrenia is 1/100. Men tend to be affected twice as often as women, with males affected approximately 5 yr earlier than females. Less than 20% of patients with schizophrenia diagnosed before age 12 yr were younger than 10 yr, and boys were predominant in most studies. More than half of patients with onset before age 18 yr have moderate to severe impairment in adulthood.

Etiology

Schizophrenia is a disorder of brain development, with susceptibility genes acting in conjunction with developmental and environmental factors to effect brain pathophysiologic processes long before the overt manifestation of clinical symptoms. Although schizophrenia has a significant genetic component, with heritability of about 80%, the genetics are complex and the interpretation of genetic data has proved difficult. Lifetime risk of developing this disorder is 5-20 times higher in first-degree biological relatives of affected persons when compared to the general population. Twin and family studies have revealed increased familial aggregation for childhood-onset schizophrenia and a higher concordance in earlier age of onset in monozygotic compared to dizygotic twins with schizophrenia.

Velocardiofacial syndrome (VCFS or diGeorge Syndrome; Chapter 119) is associated with psychosis in childhood and in adult life. The deletion on chromosome 22q11.2 found in VCFS is 80 times more common in adults with schizophrenia and 240 times more common in childhood-onset schizophrenia. Childhood-onset schizophrenia is preceded by and comorbid with PDD in 30-50% of cases.

Neurotransmitter systems, particularly CNS dopamine circuits, are hypothesized to have a key role in the pathophysiology of schizophrenia. The dopamine hypothesis is derived in part from the identification of D₂ receptor blockade as the mechanism for the action of antipsychotic medications. Increased lateral ventricular volume, decreased gray matter volume, increased basal ganglia volume, and abnormal hemispheric asymmetries are noted in childhood-onset schizophrenia.

Treatment

Children with schizophrenia and their families require an array of mental health services to address their psychologic, social, educational, and cultural needs. Given the insidious onset and chronic course of the disorder, the patient must be followed longitudinally, with periodic reassessment to hone diagnostic accuracy and tailor services to meet the patient’s and family’s needs. Integrated psychopharmacologic, psychotherapeutic, psychoeducational, and case-management services are often necessary. Psychoeducation about the illness with an assessment of the potential role of stigma in treatment participation is critical for improving adherence with treatment recommendations. Assessing a child’s strengths and vulnerabilities as well as available environmental resources is critical in devising an effective treatment plan. School and community liaison work to develop and maintain a day-to-day schedule for the patient is important. Specialized educational programs should be considered within the school system. Effective and collaborative communication among the family, the primary care clinician, a child psychiatrist, and other mental health providers increases the potential for the patient’s optimal functioning.

First-generation (typical) and second-generation (atypical) antipsychotic medications have been shown to be effective in reducing psychotic symptoms (Chapter 19 and Table 19-5). In general, the atypical medications have become the first line of treatment in this disorder. Although clozapine has been shown to be effective in treating both positive and negative symptoms, its increased risk for agranulocytosis and seizures has limited its use until after multiple trials of other antipsychotic medications have failed.

These medications all have significant side effects including extrapyramidal symptoms (EPS) (e.g., restlessness and dyskinesias), weight gain, metabolic syndrome, hyperprolactinemia, diabetes, hematologic adverse effects (e.g., leukopenia or neutropenia), seizures, hepatotoxicity, neuroleptic malignant syndrome, and cardiovascular effects. For atypical antipsychotics, body mass index, blood pressure, fasting blood glucose, fasting lipid profiles, and abnormal movements should be closely monitored. Significant weight gain occurs early in treatment with these medications. Regular physical activity and nutritional balance should be part of a comprehensive treatment plan. Abnormal movements can be monitored using the AIMS (Abnormal Involuntary Movement Scale). If there is a family or personal history suggesting cardiac disease, electrocardiograms should also be monitored.

Clinical Manifestations

Hallucinations are perceptions (typically auditory, visual, tactile, or olfactory) that occur in the absence of identifiable external stimuli. Hallucinations can be further categorized as nondiagnostic (such as hearing footsteps, knocking, or one’s name) and diagnostic (such as hearing one or more voices saying words other than one’s own name).

In children with nonpsychotic hallucinations, the symptoms of psychosis are absent. Nonpsychotic hallucinations commonly occur in the context of severe traumatic stress, developmental difficulties, social and emotional deprivation, parents whose own psychopathology promotes a breakdown in the child’s sense of reality, cultural beliefs in mysticism, and unresolved mourning. Auditory hallucinations of voices telling the child to do bad things may be more often associated with disruptive behavior disorders than with psychotic diagnoses. Hearing a voice invoking suicide is often associated with depression. Trauma-related auditory hallucinations are commonly associated with post-traumatic stress disorder or a brief psychotic disorder with marked stressors. Thus, the content of the hallucinations may be relevant in understanding the underlying psychopathology and/or developmental issues.

Diagnosis and Differential Diagnosis

The differential diagnosis of hallucinations comprises a broad range of psychiatric disorders, including diagnoses in which hallucinations are not the hallmark feature, but may be viewed as associated symptoms (e.g., post-traumatic stress disorder, nonpsychotic mood disorders, and disruptive behavior disorders); diagnoses that are defined by psychotic features (e.g., brief psychotic disorder, schizophrenia, major depression with psychotic features, bipolar disorder with psychotic features); and at-risk clinical states (poor reality testing). In addition, nonpsychiatric disorders can manifest with hallucinations, including drug intoxications (cannabis, LSD, cocaine, amphetamines, barbiturates), medication side effects (steroids, anticholinergic medications, stimulant medications), and physical illnesses (thyroid, parathyroid, adrenal, and Wilson’s disease; electrolyte imbalance; infections; migraines; seizures; and brain tumors).

Acute phobic hallucinations are benign and common and occur in previously healthy preschool children. The hallucinations are often visual or tactile, last 10-60 min, and occur at any time but most often at night. The child is quite frightened and might complain that bugs or snakes are crawling over him or her and attempt to remove them. The cause is unknown. The differential diagnosis includes drug overdose or poisoning, high fever, encephalitis, and psychosis. The child’s fear is not alleviated by reassurance by the parents or physician, and the child is not amenable to reason. Findings on physical and mental status examinations are otherwise normal. Symptoms can persist for 1-3 days, slowly abating over 1-2 wk. Treatment with benzodiazepines may be beneficial.

Treatment

The evaluation of the underlying condition directs the type of treatment needed. Nonpsychotic hallucinations suggest the need for disorder-specific psychotherapy (e.g., trauma-focused CBT for post-traumatic stress disorder) and perhaps adjunctive medication (e.g., an antidepressant for depression or anxiety, or a brief trial of antipsychotic medication). CBT focused on helping the youth understand the origin of the hallucinations and develop coping strategies for stressful situations also may be helpful for older children and adolescents. Psychotic hallucinations suggest the need for antipsychotic medication.