Pervasive Developmental Disorder 

Updated: Oct 19, 2018
Author: Sufen Chiu, MD, PhD; Chief Editor: Caroly Pataki, MD 

Overview

Practice Essentials

Historically, pervasive developmental disorder (PDD) described a group of several disparate disorders unified under the main principle of delayed language development and deficits in social interaction. As molecular genetics and cognitive neuroscience developed, furthering the understanding of these disorders, new criteria now grouped them under autism spectrum disorder (ASD), emphasizing deficits in social interaction. This group of disorders will be referred to as ASD throughout the article.

In an effort to increase diagnostic sensitivity and specificity for disorders on the autism spectrum, various revisions to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria were made in 2013. These revisions have generated new diagnostic criteria for ASD in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5).[1, 2]  Specifiers are used to designate conditions associated with known medical or genetic conditions. Conditions with social communication deficits without clear social interaction issues are now grouped under communication disorders.

The new criteria have raised concerns that a redefinition of the diagnosis of autism may exclude some children and render them ineligible for services. In a study from New York, the new DSM-5 criteria for ASD were found to identify 91% of children previously diagnosed with pervasive developmental disorder (PDD) on the basis of DSM-IV criteria. Many of the remaining 9% would probably have the diagnosis reinstated on the basis of clinician input.[3, 4]  Even when the researchers examined different PDD subgroups, they found that the new criteria had a high sensitivity for identifying girls with ASD, as well as those in the high-functioning range of cognitive ability and those with a nonverbal IQ of 70 or less. Previous DSM-IV criteria often overidentified children with intellectual disability (IQ of 70 or less) and missed girls or those who were high functioning.

Several additional retrospective studies assessed the impact of DSM-5 changes on diagnostic rates and reported considerably lower sensitivities. These studies demonstrated regional variation in application of  DSM-IV criteria. With the improved specificity of DSM-5 criteria, including the introduction of the new diagnosis "social (pragmatic) communication disorder," more consistent prevalence rates of communication disorders, distinct from ASDs, were determined. Further molecular genetic and cognitive neuroscience research will likely continue to shape the ASD criteria over time.

Background

Under DSM-IV, pervasive developmental disorder included four separate disorders: autistic disorder, Asperger’s disorder, childhood disintegrative dsorder, and Rett syndrome in addition to the catch-all diagnosis of pervasive developmental disorder not otherwise specified (PDD-NOS). Molecular genetic research indentified a single defect as the basis of Rett's disorder, which then clarified that not all individuals with Rett syndrome have social deficits. The new diagnostic category of autism spectrum disorders (ASD) in DSM-5 sought to improve specificty of diagnosis by clarifying that ASD is not a degenerative disorder, thereby eliminating childhood disintegrative disorder. Most individuals diagnosed with a pervasive developmental disorder (PDD) from DSM-IV should still meet the criteria for ASD in DSM-5 or another, more accurate DSM-5 diagnosis.[2]

ASD in its most severe presentation may describe a preschool-aged child who presents with no expressive language, seeks comfort from parents in atypical ways, engages in repetitive hand flapping, and makes no eye contact. In the mildest presentation, the disorder may include a child aged 9 years with poor peer interactions, normal verbal abilities, and mild nonverbal disabilities. The mild nonverbal disabilities make it difficult for the child to follow subtle social cues and affective signals that most children easily interpret as anxiety, anger, or sadness. The child's preoccupation with a restricted interest and attention to detail often tries the patience of peers with similar interests who are developing normally. (See History, Etiology.)

Symptoms of PDD or ASD that may begin during the first year of life include lack of joint attention. A normally developing 1-year-old infant would make eye contact with a parent, point at an object for the parent to see, and smile responsively if the parent identifies the object. A child at risk for PDD or ASD often lacks these behaviors. While some toddlers may be identified through pediatric screening using instruments such as the M-CHAT,[5]  many children may escape clinical attention until adolescence. Adolescents with normal development begin to use abstract thinking, realize that people have differing opinions, and learn to accept them. Adolescents with PDD or ASD often present with rigid thinking, are unable to accept other's opinions, and explode behaviorally when they cannot convince others to adhere only to their opinion.

Genetic and cognitive neuroscience research is starting to provide a framework for understanding the biology of social interactions. Identification of social deficits is now possible even before one year of age. Early identification and treatment leads to better outcomes. For these reasons, mandated insurance coverage of  treatment for autism spectrum disorder is now available in California. Delayed treatment leads to greater impairment and utilization of future resources.

Go to Autism, Asperger Syndrome, and PET Scanning in Autism Spectrum Disorders for additional information on these topics.

Associated morbidities

Identified organic disorders that occur with PDD/ASD include epilepsy (the most common medical condition associated), cerebral palsy, fragile X syndrome, fragile X premutation involvement, tuberous sclerosis, phenylketonuria, neurofibromatosis, Down syndrome, and congenital rubella. Roughly 30% of patients with PDD/ASD present with a known medical disorder.[6] Seizures are the most frequent comorbidity. Deletions or duplications (eg, 15q duplication) are the most common genetic abnormality associated with PDD/ASD.[7] (See Etiology.)

ASD is commonly comorbid with intellectual disability. Fragile X syndrome is the most common genetic cause of intellectual disability. Therefore, autistic disorder should be common in those with fragile X syndrome. Several studies have demonstrated an excess of autistic symptom clusters and clinical findings, such as larger head circumference, in individuals with fragile X syndrome greater than would be expected among persons with intellectual disability without a genetic etiology.[8] These features are absent in cases of fragile X syndrome without autism. Therefore, a subtype of fragile X syndrome may be an ASD behavioral phenotype. As evidence mounts that ASDs have biological origins, these genetic syndromes may be used as models to develop new treatment strategies for them. (See Etiology.)

Symptoms of obsessive-compulsive disorder (OCD) and attention deficit hyperactivity disorder (ADHD) are often present in patients with ASD. Some clinicians label the OCD and ADHD symptoms separately, whereas others include them as part of the presentation of ASD. Regardless of the approach, the symptoms of OCD and ADHD may be disabling and require treatment with standard approaches that include, but are not limited to, medications and behavioral therapy.

Aggression is a symptom not specific to any particular psychiatric disorder but may be particularly troubling in ASD because the children cannot always communicate the cause of their distress. The etiologies are broad and include constipation, anxiety, depression, anxiety, psychosis, or adjustment disorder. Treatment requires clarification of etiology to help select medications and other appropriate therapies.[9, 10]

A study using subjects recruited from the Autism Speaks Autism Treatment Network consortium identified depression in 7% of individuals with ASD based on parent report. Age, IQ, history of seizures, and gastric complications increase the likelihood of depression.[11] Therefore, the prevalence of depression is likely to be higher because many children with ASD are unable to provide the subjective self-report that is traditionally needed for the identification and diagnosis of depression.

The evaluation of anxiety disorders in ASD is problematic as well given that symptoms often require subjective self-report. Evidence-based guidelines have been developed by a multidisciplinary work group of clinicians and researchers through the Autism Speaks Autism Treatment Network.[12] These assessments take extended time and sensitivity. For example, an assessment of the child's ability to understand and express emotion would first involve questions like, "Do you know what worried means?" Modified cognitive-behavioral therapy (CBT) has been shown to be beneficial for children with ASD in preliminary studies.

Sleep problems are extremely common in ASD. A study using the Children's Sleep Habits Questionnaire identified 715 of children with clinically significant sleep problems.[13] The number of children meeting criteria for a sleep disorder was 30%. Medications prescribed to 46% of 4- to 10-year-olds with a sleep disorder diagnosis.

Sensory integrations disorder is not found in the DSM-IV, DSM-5 or the International Statistical Classification of Diseases and Related Health Problems, 10th revision (ICD-10) but best captures the behavioral problems that result when individuals with ASD become disruptive when bothered by loud noises, tags on clothing, or textures of food. They may also be disruptive while trying to seek alternative methods of self-soothing, such as swinging, wrapping themselves in heavy blankets, or eating nonnutritive items. Identification of these sensory needs or deficits is integral to the behavioral management of individuals with ASD. Emerging controlled studies support the efficacy of these interventions in improving behavior in ASD.

Milestone regression

Regression, or the loss of developmental milestones, was once a controversial finding in autistic disorder. Today, differing degrees of regression are recognized as part of the developmental presentation of ASD.[14]  However, major losses of multiple developmental milestones suggest Rett syndrome or other genetic or metabolic disorders. Certain mitochondrial disorders occur only in the brain and therefore may present without any motor or peripheral deficits. Landau-Kleffner syndrome (LKS) is an epileptic disorder that typically has a fluctuating course. In LKS, regression in language development occurs repeatedly due to seizure activity. Childhood disintegrative disorder is no longer in the DSM-5 because of the difficulty in clarifying diagnostic criteria. Many cases diagnosed in the past were likely due to genetic causes that now are readily diagnosed with improvements in technology.

Also see Acquired Epileptic Aphasia.

Etiology

Researchers continue to identify multiple etiologies for the underlying pathophysiology of pervasive developmental disorder (PDD/ASD). Different levels of dysfunction in CNS systems are most likely involved. For example, at the molecular level, the type of serotonin-transporter gene promoter may modulate the severity of ASD or increase the risk for its development.[15] Data from a blood genomic study have suggested that the immune system plays a role.[16] At the neuroanatomic level, preliminary brain imaging studies have shown differences that may manifest clinically as a larger head size.[17]  Environmental factors such as paternal age may also contribute to development of ASD, although mercury exposure and vaccinations have mostly been dismissed.

Changes in culture may explain some of the increased rates of ASD. A study correlated increased time spent indoors with increased rates of ASD and suggested that this was caused by increased television viewing.[18] Television may reinforce repetitive behaviors in vulnerable children who, in a different era, would not have spent so much time with computer games and television programming. Screen time may also take away from opportunities for interpersonal interactions and social skill development.

Children with ASD may have other specific cognitive deficits, including central auditory processing problems, which imply distorted pathways between hearing and cortical processing. They may also have specific cognitive strengths. In isolated cases, these special cognitive talents lead to these individuals being labeled savants.

Some of these deficits and strengths may manifest as sensory integration issues. For example, children with ASD may have hyperacoustic hearing, predisposing them to act erratically around loud noises. The hyperacoustic hearing may enable some children with ASD to be gifted musicians.[19] Temple Grandin, a distinguished author and professor with Asperger disorder, writes about her need for increased tactile stimulation, which helped her develop a more humane way to move cattle.[20]

Children with fragile X syndrome have many of these cognitive deficits. The genetic and molecular basis of fragile X syndrome has been described in detail, supporting the premise that deficits in the protein encoded by the fragile X syndrome gene result in glutamate disturbance and abnormal neuronal axonal development.[21] The protein FMRP, encoded by the fragile X syndrome gene, may interact with other neurotransmitters or processes to cause autistic symptoms in fragile X syndrome more often than in other genetic syndromes or nonsyndromic intellectual disability.

Since the identification of the genetic abnormality in Rett syndrome, milder cases of Rett syndrome with smaller deletions have been identified.[22] Individuals with milder cases of Rett syndrome have better intellectual ability and more classic symptoms of ASD. The genetic defect in Rett syndrome results in alterations in the power center equivalents of brain cells, also known as mitochondria.[23]

Epidemiology

Incidence in the United States

A survey of existing literature by Fombonne in 2003 indicated that the rate for all forms of pervasive developmental disorder (PDD/ASD) was 30-60 cases per 10,000 population, while the rate for Asperger disorder was 2.5 cases for 10,000 population and the rate for childhood disintegrative disorder was 0.2 case per 10,000 population. Fombonne attributed an increase in prevalences over time to changes in case definitions and to improved awareness.[24]

An epidemiologic survey confirmed the prevalence of ASD to be 1 in 150 children.[25]  The increase in reported cases of ASD probably results from an increased identification of cases that do not meet specific criteria for autistic disorder or Asperger disorder but are diagnosed as PDD not otherwise specified (PDD-NOS) under DSM-IV. The DSM-5 reports the prevalence as 1%.[2]

The Centers for Disease Control and Prevention reported the prevalence of ASD to be one in 59 children aged 8 years from 11 sites of the Autism and Developmental Disabilities Monitoring (ADDM) Network. Only 86% of the children met both DSM-IV-TR and DSM-5 criteria. They also reported that the prevalence varied among racial/ethnic groups and communities. The main limitation of this study is that the sites were not selected to represent the United States as a whole.[26]

International incidence

No evidence suggests that the international prevalence of ASD differs from the prevalence in the United States. However, the literature indicates that these disorders are identified at a later age in specific regions of the United States than in other countries.[27]

Race predilection

Race has not been implicated as a risk factor for ASD.

Sex predilection

Sex bias for ASD is significant. ASD may be 5 times more common in boys than in girls. Asperger syndrome as defined in the DSM-IV may be 10 times more common in boys than in girls.

Only Rett syndrome affects more girls than boys; in fact, Rett syndrome is rarely diagnosed in boys. However, new molecular testing for Rett syndrome indicates that the incidence of the condition is greater in boys than previously reported.

Age predilection

Previously, autistic disorder carried an onset criterion; evidence of the disorder must be present by age 3 years. DSM-5 allows for a wider range of age onset, specifying only that symptoms begin in the early developmental period. Symptoms may have onset later if more subtle or may be masked in adults who developed compensatory behaviors. Regression in domains other than social communication after age 2 years usually warrants further evaluation for Rett syndrome and other genetic disorders. 

As noted earlier, ASDs are diagnosed relatively late in United States compared with other countries.[27] Within the United States, geographical differences in age of diagnosis present a significant public health challenge as evidence mounts to support early diagnosis and intervention.

Patient Education

Many parents of children with ASD need legal guidance to help them understand their legal rights to benefits and services available from public schools and from the medical system. Educational advocates are often necessary. Alternative treatments may drain the financial resources of families and potentially cause harm to the child.[28]

One study showed that parents with private insurance have a much higher financial burden for medical care than those with combined public (Medicaid) and private insurance.[29] Parents should be informed that they may qualify for Medicaid through the Family Opportunity Act of 2005, eligibility rules that exclude parental income. Interestingly, parents preferred Medicaid alone to combined coverage even though they had the greatest financial burden. Having combined insurance may lead to more difficulties in navigating health care systems.

For patient education information, see the Brain and Nervous System Center, as well as Autism and Asperger Syndrome.

Pathophysiology

A unified pathophysiology understanding of autism spectrum disorders will include a complex model of genetic, molecular, and system changes. For example, genes like SHANK, which are postsynaptic scaffolding proteins, alter synapse formation and maintence.[30] Scaffolding proteins interact with cell adhesion molecules (CAMs). Mouse models with altered CAM functioning have social deficits. These molecular changes then lead to altered inhibitory GABAergic synaptic transmission in the somatosensory cortex. Downstream effects on excitatory transmission and long-term potentiation may result. The mTor Pathway is important in growth regulation and protein synthesis, which affects neuronal plasticity. Changes in these systems ultimately result in neuroanatomical and cognitive deficits found in ASD. Environmental influences from toxins to learning will modulate and ultimately determine the severity of the symptoms associated with ASD.

Prognosis

Absence of intellectual disability and languague disability are the best prognostic factors for pervasive developmental disorders (PDD/ASD).[2] Functional language by age 5 is associated with better outcomes. In contrast, epilepsy associated with intellectual disability predicts poorer outcomes. Adaptive skills are usually below expected for intellectual ability which then impacts education and independence as adults. 

 

Presentation

History

When eliciting history from the parents, reviewing pregnancy, peripartum, and infancy behaviors can yield clues to the genetic etiology of pervasive developmental disorder (PDD/ASD) behaviors or inform the decision whether to perform brain imaging. Many parents of children later diagnosed with autism can recall that, as an infant, their child had poor eye contact and was unlike older siblings in interpersonal interactions. Studies using the 1-year birthday party as a developmental milestone show that these children lack interest in the party, do not engage with adults, and/or show inappropriate interest in the gifts or activities.

A significant history of neglect or failure to thrive requires consideration of reactive attachment disorder, which is an important differential diagnosis of ASD. If the child has a clinically significant history of physical or emotional deprivation, a diagnosis of ASD should be deferred until the child has had an opportunity to recover in an enriched environment.

A common misconception is that children with a ASD do not show attachment to parent figures. In fact, many children with ASD have an emotional attachment to parental figures, but the attachment may manifest mostly as separation anxiety or as a seeking of comfort in odd ways. Children whose first language is not English may pose additional challenges in differentiating ASD from selective mutism and language disorders.

A thorough medical review is important, because none of the ASDs have a medical cure. Treatable conditions may cause symptoms of ASD, or they may worsen behaviors associated with these disorders.

Any history of deficiencies in the following areas is an indication for an evaluation for PDD:

  • Language development

  • Social interaction

  • Sensory integration

Language development

Delay suggests autism or PDD not otherwise specified.

Regression is consistent with Rett disorder or childhood disintegrative disorder but may also be an important subtype of autistic disorder.[31]

Normal language development is a diagnostic feature of Asperger disorder. Problems with the pragmatics of language become more apparent with age.

Poor social interaction

Features include the following:

  • Social isolation

  • Poor eye contact

  • Attachment to unusual objects

  • Overdeveloped, circumscribed interests in odd or specific topics

  • Inability to engage in imaginative play

Sensory integration difficulties

Features include the following:

  • Oral aversion to certain textures or colors

  • Olfactory aversion

  • Tactile aversion to certain fabrics (eg, tags on clothing, position of socks)

  • Auditory aversion to loud noises or types of music

Stereotyped behaviors/Restrictive Interests

Stereotyped behaviors are also an indication for an evaluation for ASD. Such behaviors include hand flapping and self-injurious behavior (eg, head banging). Children with stereotyped behavior may have difficulty making a transition between activities. In older children or adults, narrow interests which cause conflict in social interactions also warrant evaluation for ASD. High functioning individuals may present as experts in obscure topics.

Screening in the pediatric visit

The social communication questionnaire (SCQ) is a short parent report of current and past behavior. It has been validated to be consistent with the Autism Diagnostic Observation Schedule (ADOS) and has excellent sensitivity and specificity for ASDs.[32] The form is filled out by parents of children who are aged 4 years or older and have a mental age of 2 years. It is short enough to be completed in the waiting room.

The Developmental and Behavioral Pediatrics subgroup of the American Academy of Pediatrics recommends using the Modified Checklist for Autism in Toddlers (M-CHAT) form[5] to screen for symptoms in children aged 16-30 months. The checklist has been translated into Chinese[33] and many other languages, with differing degrees of validation in progress.

Physical Examination

Physical examination findings in children with pervasive developmental disorder (PDD/ASD) are usually normal, but the evaluation should be thorough in order to identify genetic or metabolic disorders.

The most important exception is Rett disorder; almost all patients who present with this disorder have the characteristic findings of hand-wringing, hyperventilation, or both. Unlike children with autism, who tend to have larger head circumference (>90%), children with Rett disorder have smaller head circumference (< 10%). Children with fragile X syndrome have a larger head circumference, while children with both fragile X syndrome and autistic disorder have even larger mean head circumference as a group.[8]

Children with ASD often have constipation, diarrhea, or reflux that they may lack the verbal ability to report. Untreated conditions present as disruptive behavior. A physical examination may be the only method to identify these issues. Food allergies may be the etiology of these gastrointestinal issues. Physical findings of eczema, wheezing, and poor weight gain should heighten the suspicion for food allergies.[34]

Complications

Early identification and treatment leads to better prognosis and outcomes. As discussed earlier, in the United States, age of identification varies from state to state. Resources for treatment are also geographically dependent. Non-verbal children have difficulty reporting symptoms and signs of acute illness and should warrant a careful physical exam for changes in behavior.

 

DDx

Diagnostic Considerations

Psychosis is often the most difficult symptom to elicit and diagnose appropriately in children with pervasive developmental disorder (PDD/ASD). Not long ago, children with ASD were often identified as having childhood-onset schizophrenia. The DSM establishes criteria that clearly distinguish ASD from childhood-onset schizophrenia. The DSM recognizes that children with ASD may develop psychotic disorders if they present with clear evidence of auditory, visual, tactile, and/or olfactory hallucinations. Nevertheless, determining whether a child has ASD or psychosis may be difficult during the initial clinical evaluation. For example, individuals with intellectual disability may present with cognitive disorganization; they may link irrelevant thoughts together or have beliefs in magical beings, even as adults. These findings are considered normal in a person with intellectual disability.

Conditions to consider in the differential diagnosis of pervasive developmental disorder, along with those in the next section, include the following:

  • Reactive attachment disorder

  • Landau-Kleffner syndrome

  • Schizotypal personality disorder

  • Intellectual Disability (Mental retardation)

  • Selective Mutism

Differential Diagnoses

 

Workup

Approach Considerations

Fragile X DNA testing should be the first test ordered.

If the history or physical findings suggest additional concerns, consider the following:

  • High-resolution cytogenic studies with fluorescence in situ hybridization (FISH) testing for Prader-Willi, Angelman, and Williams syndromes

  • Creatine phosphokinase measurement - To rule out muscular dystrophy

  • Determination of lead level - To rule out lead poisoning

  • Urine organic acid test

  • Plasma amino acid test

  • Lactate and/or pyruvate test - To rule out mitochondrial disorders

  • Serum ammonia test - To rule out urea cycle defects

  • Test for very long fatty acids - To rule out peroxisomal disorders

  • Test of thyroid-stimulating hormone - To rule out hypothyroidism

  • Gene sequencing for MECP2 (Rett's Syndrome)

  • Polymerase Chain Reaction (PCR) for Fragile X syndrome

Hearing testing

A hearing test should be administered.[35] A hearing test should be performed by a pediatric audiologist and should be repeated even if the test results were normal at birth. Testing of children usually requires the presence of 2 pediatric audiologists.

DNA Testing and High-Resolution Cytogenetic Studies with FISH

Fragile-site mental retardation 1 gene (FMR1) deoxyribonucleic acid (DNA) testing for Fragile X syndrome and premutation involvement as indicated.[21]  

Genetic testing should be considered, even if no obvious dysmorphic features are found in the physical examination. Many individuals with Fragile X syndrome appear physically normal (see the image below).

Young child with fragile X syndrome who does not h Young child with fragile X syndrome who does not have obvious dysmorphic features. Courtesy of Randi J Hagerman, MD, FAAP.

Gene Sequencing for MECP2 (Rett's Syndrome)

High-resolution cytogenetic studies with FISH are used to test for 15q duplication, which has been found in 3%–5% of individuals with autism.[7]

Comparative Genomic Hybridization

Comparative genomic hybridization (CGH) is now often recommended to identify a greater number of subtle cytogenetic abnormalities in pervasive developmental disorder (PDD). Up to 20% of individuals with a ASD may have these slight abnormalities.[6]

 

Imaging Studies

Brain magnetic resonance imaging (MRI), but not head computed tomography (CT) scanning, may be helpful in the clinical assessment of global developmental delay, as the Practice Committee of the Child Neurology Society outlined in 2003.[36, 37]

Functional MRI, magnetic resonance spectroscopy (MRS), positron emission-tomography (PET) scanning, and single photon CT (SPECT) scanning remain research tools. MRS is growing in promise as a tool in screening for conditions such as a deficiency in the creatine transporter gene.[38]

Also see PET Scanning in Autism Spectrum Disorders.

Electroencephalography

Results are abnormal in 25% of children with ASD.

Results are abnormal in all children with Rett syndrome.

Results can be diagnostic for children with Landau-Kleffner syndrome (LKS), because seizure activity in the brain speech centers often causes this rare disorder.

Psychological and Neuropsychological Testing

In older children, testing may help distinguish atypical ASD or pervasive developmental disorder (PDD) not otherwise specified from a mood disorder, early presentation of schizophrenia, or schizotypal personality disorder.[39]

Testing may reveal verbal and nonverbal learning disabilities.

 

Treatment

Approach Considerations

Thorough medical evaluation is warranted before psychiatric hospitalization is considered.

Inpatient care is warranted to manage acute medical issues or for a workup of subclinical medical disorders.

Patients often present with medical problems that manifest as changes in behavior.

Psychiatric hospitalization is indicated whenever the safety of the patient cannot be maintained.

Go to Autism and Asperger Syndrome for complete information on these topics.

Applied behavioral analysis

Applied behavioral analysis (ABA) is considered the best evidence-based treatment for ASD. ABA focuses on reinforcement and extinction of behaviors. Skills are taught using discrete trial training or pivotal response training. Problematic behaviors are addressed through functional communication training (FCT). Functional analysis (FA) identifies factors that maintain the challenging behaviors.

Widespread implementation of FA and FCT via in-home therapy is limited by cost and geographic availability. A preliminary telehealth study demonstrated the feasiblity of providing these services with >90% reduction of problematic behavior at reduced cost compared to in-home therapy.[40]

Consultations

Consult a child psychiatrist and/or a developmental/behavioral pediatrician to evaluate and treat comorbid diagnoses such as depression, ADHD, or OCD and to lead a multidisciplinary team for case management, which may include family psychoeducational therapy, psychopharmacologic treatment, speech therapy, occupational therapy, physical therapy, and behavioral therapy.

Consult a psychologist and/or an education specialist to assess baseline functions for intellectual capacity and learning disabilities and to design cognitive behavioral strategies for facilitating education and for modifying difficult behaviors. (This area is rapidly growing, with increasing evidence suggesting that specific types of therapy for early intervention can enhance generalization of social skills.)

Additional Patient Management Considerations

Outpatient management requires a multidisciplinary approach.

Comorbid medical problems, including seizures and constipation, are frequent.

Certain behaviors may require medication prescribed by a child and adolescent psychiatrist or behavioral-developmental pediatrician.

A speech pathologist's expertise is essential to develop a communication plan. The use of augmentative and communication devices is essential for the nonverbal child.[41]

A special education professional may be needed to design a specific curriculum for each child with pervasive developmental disorder (PDD).

Occupational and physical therapists may be indicated for motor deficits and sensory processing deficits.

A social worker not only helps find financial, educational, and emotional resources but also provides important psychosocial support for the family.

Psychologists often develop behavioral plans and ongoing therapy to improve social relationships.

 

Medication

Medication Summary

Many types of medications are used to address different behavioral issues and comorbid disorders associated with pervasive developmental disorder (PDD/ASD). For example, the US Food and Drug Administration (FDA) has approved risperidone and aripiprazole for use in children to treat irritability associated with autistic disorder.[42, 43, 44]

Data from several large, randomized, placebo-controlled trials suggested that antipsychotic medications may be helpful, particularly for aggression. In addition, treatment with antipsychotics may improve restricted, repetitive, and stereotyped patterns of behavior and interests. However, no medications substantially change deficits in social interaction and communication.

The use of antipsychotic medications requires careful monitoring of weight, fasting lipid profile, and fasting plasma glucose as recommended by the consensus statement published in Diabetes Care.[45]

Treatment of comorbid conditions such as ADHD and OCD may be indicated, although few research studies support the efficacy of the medications currently approved for use in children who are developing normally. Because FDA guidance is absent, child and adolescent psychiatrists target disruptive behaviors with the class of medications indicated by the symptom clusters.[46]

Innovative treatments currently in the development phase include N-methyl-D-aspartate (NMDA) receptor (a type of glutamate receptor) blockers. A preliminary trial using a similar agent, amantadine, proved promising in a placebo-controlled trial.[47] Inhibition of group 1 metabotropic glutamate receptor is being considered specifically in the use of individuals with Fragile X syndrome, because studies demonstrate that FMRP affects dendrite maturation via this neurotransmitter system.[48]

Herbal and alternative treatments require more research. The most promising is melatonin, the hormone that regulates sleep. A pharmaceutical-grade, melatonin like compound, ramelteon, is available commercially. Children with ASD often have sleep disorder that may be ameliorated with melatonin.[49]  The most commonly prescribed sleep medications are melatonin followed by central alpha agonists.[13]

Other herbal treatments should be carefully weighed like any traditional medication for their risks and benefits. Most importantly, parents should be cautioned that little oversight exists for these compounds and that some have been found to contain unacceptable levels of heavy metals.[50] Intravenous chelation has been identified by the American Academy of Pediatrics as particularly risky without demonstrated benefit, resulting in 1 reported death.[37]

Antipsychotics

Class Summary

Antipsychoticmedications may help with a patient’s aggressive behavior and may improve restricted, repetitive, and stereotyped patterns of behavior and interests.

Risperidone (Risperdal)

Risperidone is an atypical antipsychotic agent. It binds to the dopamine D2-receptor with 20 times lower affinity than for 5-HT2-receptor affinity. It improves negative symptoms of psychoses and reduces the incidence of extrapyramidal adverse effects compared with conventional antipsychotics. Risperidone is indicated for irritability associated with autistic disorder in children and adolescents aged 6-16 years.

Aripiprazole (Abilify)

The mechanism of action of aripiprazole is unknown, but it is hypothesized to work differently from other antipsychotics. Aripiprazole is thought to be a partial dopamine (D2) and serotonin (5-HT1A) agonist and to antagonize serotonin (5-HT2A). Additionally, no QTc interval prolongation has been reported in clinical trials.