James Mcpartland, PhD

This activity offers CE credits for:
1. Physicians (CME)
2. Other

The focus of this article is on diagnostic and treatment considerations in autism spectrum disorder (ASD).

At the end of this CE activity, participants should be able to:

• Determine best assessment practices for ASD during the developmental stages of early childhood, middle childhood, adolescence, and adulthood

• Identify the differential diagnoses for each developmental stage

• Decide which interventions are best suited for each particular patient

This continuing medical education activity is intended for psychiatrists, psychologists, primary care physicians, physician assistants, nurse practitioners, and other health care professionals who seek to improve their care for patients with mental health disorders.

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Rather than having separate diagnostic categories as in the previous DSM, DSM-5 conceptualizes autism spectrum disorder (ASD) as a broader diagnosis. The traditional triad of impairments-social interaction, communicative behavior, and repetitive and restricted behaviors (RRBs)-was collapsed into 2 domains. While the RRB domain remains separate and largely intact, with the addition of atypical sensory responses, the social and communication domains are merged.

Diagnostic specifiers have also been added in DSM-5. The first is for known etiological factors (eg, medical or genetic conditions). The second is a severity specifier that describes the degree to which an individual’s level of functioning is affected and the level of support he or she requires. This specifier is applied separately for the social interaction/communication and RRB domains. The third and fourth specifiers indicate whether intellectual and language impairments are present. These specifiers address the vast range of cognitive and language functioning among individuals with ASD. The last specifier marks whether catatonia is present.

DSM-5 criteria for ASD require the presence of symptoms during early development, although a caveat is provided that problems may at times not manifest until social demands exceed limited capacities, which allows later diagnoses to be made. Criteria also include a clause that prequalifies individuals with a DSM-IV diagnosis for a maintained DSM-5 diagnosis. Previously a diagnosis of ADHD could not be made along with ASD; this exclusionary criterion is no longer present, which allows for better capture of comorbid conditions.

A comprehensive assessment for ASD includes direct evaluation of the child and collection of collateral information from parents and other caregivers. This includes information about the child’s birth and his or her functioning at home, at school, and in the community as well as a family history and developmental, medical, and intervention history. Psychological testing should be conducted to assess the child’s developmental/cognitive and adaptive (ie, “real world”) functioning to provide a baseline for understanding the child’s learning capacity and current abilities. Other tests, such as evaluations of academic achievement, motor abilities, neuropsychological functioning, and psychological well-being, may be administered to rule out alternative or comorbid diagnoses (eg, learning, attention, or mood problems) and to inform educational and intervention planning. A speech-language pathologist and/or an occupational or physical therapist may conduct additional assessments. Hearing, vision, and/or genetic testing may be required for specific concerns or to rule out alternative explanations for presenting problems.

Multiple screening and diagnostic tools are available for evaluating children and adults for ASD. The Autism Diagnostic Observation Schedule (ADOS), now in its second edition, is a semi-structured, clinician-administered, play- and conversation-based instrument that is widely considered to be the gold standard.

 While the ADOS is the most psychometrically robust assessment tool available, it also requires extensive training and demonstration of reliability to be used with fidelity. The Autism Diagnostic Interview-Revised (ADI-R) is a structured clinical interview.

It has good reliability; however, because of its length, it is used infrequently in clinical practice.

New tools are being developed to assist with expedient ASD-specific history taking and assessment in psychiatric practices. In the interim, a brief clinical interview with direct inquiry about current and historical presentations of DSM-5 symptom domains can often suffice.

Because of enormous heterogeneity in the clinical presentation of ASD, the diagnosis is almost always made by an expert with specific training and experience. In many cases, consultation among psychologists, psychiatrists, developmental pediatricians, speech-language pathologists, and educators is critical to tease apart the most likely diagnostic explanation for a child’s presenting problems.

Challenges and differential diagnoses in early childhood

The most reliable early markers for ASD are failure to respond to one’s name; lack of social smiling and shared attention; delays in babbling and lack of words by 16 to 18 months or phrases by 24 months; and failure to use gestures such as pointing, showing, or reaching. Any loss of language or social skills is cause for concern.

The most common reason a toddler is referred for an ASD evaluation is a delay in spoken language. 

 provides a list of questions that need to be answered when considering a diagnosis of ASD in early childhood. There are several competing reasons for which children can present with language delays. As a result, in young children, assessment for ASD is best done by a team of professionals, including a psychologist with extensive knowledge of early childhood, a speech-language pathologist, and often an occupational or physical therapist or pediatrician who can rule out other causes of delay. For children who have ASD or who show early signs of ASD, early detection and consequent intervention are key predictors of positive outcome.

Challenges and differential diagnosis in middle childhood

As social, behavioral, and academic demands increase in elementary school, a second wave of children is referred for ASD evaluation. Many children present for diagnostic evaluation who had previously received various, less comprehensive diagnoses (eg, speech delay, ADHD, sensory integration disorder). A primary consideration is whether the social deficit is primary (ie, likely to be due to ASD) or secondary to other challenges.

Primary ASD features in middle childhood often relate to difficulty engaging in age-appropriate peer relationships, collaborative and imaginative play, back-and-forth conversation on a flexible range of topics, and age-appropriate interests. Whereas repetitive motor mannerisms (eg, toe walking, hand flapping) are common in typically developing younger children, when these behaviors persist into later years, they are increasingly indicative of ASD.

Differential diagnostic concerns also involve other disorders with overlapping symptoms. For example, children with ADHD and oppositional defiant disorder can have difficulties maintaining friendships because of impulsivity and acting out behaviors. Children with anxiety can have difficulty approaching and engaging peers or show difficulty with transitions and change in routine. Rigid and repetitive behaviors can characterize children with OCD, and some tics can be mistaken as stereotyped motor mannerisms.

Children with continued language delays or communication disorders can also be suspected of having ASD, as can children with global developmental delays or intellectual disability. Differential diagnosis in middle childhood often requires a more comprehensive psychological and/or neuropsychological evaluation to appropriately assess for ASD and rule out other possible explanations for social deficits.

Challenges and differential diagnosis in adolescents and adults

For adolescents and adults who present for a first-time evaluation for ASD, it is important to determine whether social withdrawal and difficulties with peer interactions are truly due to a long-standing ASD or to more recent-onset mood or anxiety disorder. Schizophrenia and other psychotic disorders should also be considered. Clinicians must evaluate whether social and other skills have plateaued versus declined more precipitously. In addition, a developmental and family history is needed with particular attention to symptoms of ASD that best differentiate autism from other psychiatric disorders.

Among patients with ASD, comorbid anxiety and depression commonly emerge in adolescence and may require an additional diagnosis to inform targeted treatment. Self-report of anxiety and depression symptoms can be difficult to elicit in individuals with ASD (eg, due to weaknesses in introspection or to expressive language vulnerabilities); thus, increased reliance on caregiver and teacher reports and on behavioral manifestations is necessary.

With increasing attention paid to ASD, a growing number of adults are presenting to clinics to find out whether they might have ASD that had not been identified previously. Differentials prominent in adolescence continue to be important to consider in adulthood. When adults present because of work-related difficulties, consideration of undetected learning disabilities can be worthwhile. First-time diagnosis in adulthood is often complicated by the fact that a good developmental history is difficult to obtain, often requiring clinicians to rely on assessment of current presentation alone.

Treatment should follow from and be based on a thorough assessment. In addition to characterizing ASD symptomatology, to best inform treatment, an initial assessment should provide information about comorbidities, cognition, academic performance, social behavior, communication skills, and independent living skills. There is no single treatment appropriate for every individual with ASD, and it remains difficult to predict which patients will benefit most from treatment and in which ability domains. The best course of action is to account for age, symptoms, and functioning level when planning treatment.

Across all age ranges, interventions must intensively address the individual’s most pressing needs. At the same time, progress should be monitored so that interventions can be started, adjusted, or discontinued in a way that is developmentally sensitive, supports the patient, and allows for emerging independence.

Early, intensive, individualized behavioral intervention is highly recommended for toddlers and young children with ASD. Traditional guidelines recommended 25 or more hours per week of direct intervention between a child and a trained clinician

; newer models increasingly utilize parents in the role of interventionist to maximize the number of engaged, face-to-face hours a child receives.

Applied Behavior Analysis (ABA), derived from early studies done at UCLA by Ivar Lovaas, has been shown to be effective.

More recently, ABA approaches have evolved to include increasingly developmentally based and naturalistic models (

 Although more randomized clinical trials are needed-including direct comparisons between active interventions-given the benefits of early intensive interventions for young children with ASD, the ABA approach remains a best-practice recommendation.

As children age, a variety of behavioral, therapeutic, academic, and often psychopharmacological interventions may be necessary. Most children will need a combination of supports, which may change across development and settings. Many children will require speech and language therapy to help them develop basic expressive and receptive language. Some will need intensive speech and behavioral interventions that target the development of alternative communication systems (eg, sign language, picture exchange) when language does not emerge. Even among children with ASD and higher cognitive and language skills, speech and language therapy is often recommended to hone pragmatic skills. Supplemental use of visual communication strategies (eg, picture schedules) is often helpful in conjunction with verbal communication interventions and supports.

Teaching and rehearsing social rules and scripts-first in therapeutic settings and then in more naturalistic settings-are effective for many children. Several manualized social skills programs, such as the Program for Education and Enrichment of Relational Skills (PEERS),10 have been developed to structure social skills interventions.

Behavioral interventions for children with ASD-both clinician- and parent-mediated-help build skills for the classroom, increase on-task behavior, ease difficulties with transitions and changes in routine, build social and communication skills, improve executive functioning, and decrease challenging behaviors.

 Functional behavioral analyses can be helpful for identifying behavioral treatment goals and appropriate ways to address them across settings. Overall, intervention plans are best designed when they use strengths (eg, cognitive skills) to compensate for weaknesses, while simultaneously employing additional external supports to facilitate learning and socialization.

For adolescents and adults, support is usually necessary for transitioning from school to community and vocational settings. Many families require assistance to connect with disability services and to consider housing and support options, such as group home settings. Mental health clinicians can be helpful in supporting discussions of long-term planning, legal guardianship, and reasonable expectations for an individual’s work and day-to-day living plans.

For cognitively able individuals, college is often possible, but social and academic support is frequently required to help with navigating the challenges of a more self-directed academic program and dorm life.

 An increasing number of universities now offer ASD-specific programs. However, these can be costly, and there is little indication of their effectiveness. For many families, it may be necessary to select a college and work with administrators to develop a custom plan to support the student in the college transition.

Persons with ASD often have significant difficulty with obtaining and maintaining employment because of their social vulnerabilities. Psychotherapy and job coaching may be necessary to build interview, interpersonal, and on-the-job vocational skills and to identify employment settings where an individual can be most successful.

Finally, many individuals with ASD desire romantic relationships, and issues of sex and sexuality are common. Guiding exploration and navigation of sexuality and relationship issues can be an important role for mental health clinicians.

There are no medications that effectively target the core social symptoms of ASD. However, many individuals with ASD benefit from drug treatment to address a subset of their presenting symptoms or associated psychiatric problems. Risperidone and aripiprazole are atypical antipsychotics that have demonstrated efficacy and are FDA approved for reducing irritability, challenging behaviors, and repetitive behaviors in children with ASD.

 There is, however, strong evidence for adverse effects, such as weight gain, sedation, and extrapyramidal effects.

All other medications are used off-label for ASD, although several are FDA approved for children with other conditions. Stimulants can be effective for children with ASD and comorbid ADHD or attention problems. One randomized controlled study showed improvement in hyperactivity among children with ASD.

 SSRIs are often used to address comorbid mood and anxiety symptoms. Studies have examined whether they are also effective in reducing ASD-specific repetitive behaviors, but support for their effectiveness in this capacity is insufficient.

Newer drugs are in development. The GABA agonist arbaclofen targets challenging behavioral and social withdrawal,

 and intranasal oxytocin targets social communication deficits.

However, while several potential pharmacological agents have shown promise in pre-clinical animal models, clinical trials have demonstrated more tempered results. More research remains to determine both the efficacy and the safety of these drugs. Overall, it is important to consider whether particular medications are helpful in alleviating symptoms and to remain vigilant to avoid polypharmacy, while chasing elusive symptoms whose biological origin and responsiveness to medication are not yet understood.

There is an enormous range of complementary and alternative medicine (CAM) approaches for ASD. Many families use one or more CAM approaches in an attempt to treat core or comorbid symptoms (eg, sleep or gastrointestinal problems, hyperactivity) or to address adverse effects of conventional treatments. CAMs include dietary supplements (eg, vitamins, amino acids, probiotics); alternative interventions (eg, acupuncture, equine therapy, auditory integration training); and biologically based approaches (eg, antibiotics, antifungal medications, digestive enzymes, chelation, hyperbaric oxygen chambers). Gluten- and/or casein-free diets, secretin, and melatonin are also common CAM strategies.

Empirical support for most CAM interventions is limited. Nevertheless, many families are eager to pursue CAM, in part because of anecdotal support for these approaches and in part out of an understandable desire to pursue all options when symptoms persist despite conventional treatment. Many families, however, obtain their information about CAM approaches from other families, the Internet, or non-medical professionals.

Thus, it is critical that mental health professionals inquire about and maintain an ongoing dialogue with families about their use of CAM and provide information about evidence-based adverse effects.

As a general heuristic, the principle of “do no harm” applies to CAM as in all other aspects of medicine. If (1) the child is not being harmed physically or mentally and (2) the resource burden CAM interventions place on the family is not detracting from other, evidence-based interventions, then clinicians can support families in trying various treatments. Maintaining a dialogue about what treatments are being pursued and ensuring decisions are made in consultation with a physician are of utmost importance.

Precise ASD diagnosis and routinely effective treatment are hampered by the heterogeneity captured under the ASD umbrella and by the as-yet poorly understood etiology of associated deficits. By now, it is widely accepted that ASD is not one disorder, but rather a group of “autisms” that share similar clinical phenotypes but result from diverse genetic and developmental pathways.

A promising avenue for characterizing heterogeneity of ASD has grown from the National Institute of Mental Health Research Domain Criteria (RDoC) initiative.

 Under the RDoC framework, DSM categories are eschewed in favor of cross-cutting, dimensional features that can map biological processes and neurological pathways transdiagnostically. Symptom clusters are conceptualized individually in a manner that allows researchers and clinicians to better understand their respective biological origins and affected brain-based processes, which in turn may lead to more informed and targeted treatment.

At present, the RDoC frame is primarily used in research. However, it may lead to development of more precise subtyping, diagnostic approaches, and treatment strategies that are more congruent with biology and can be more flexibly adapted to heterogeneity in clinical presentation.

Another important avenue within ASD research involves identification of biomarkers as predictors and indicators of treatment response and outcome.

 Researchers and clinicians currently rely primarily on subjective clinician- and parent-report measures to choose treatments and measure outcomes. However, a recently launched project, the Autism Biomarkers Consortium for Clinical Trials (

), aims to develop objective biomarkers to evaluate the effectiveness of ASD interventions for social and communicative function.

Identification of useful biomarkers and targeted outcome measures has the potential to improve ASD treatment on many fronts-leading to more targeted treatment selection, efficient and sensitive measurement of treatment response, and efficient evaluation of novel behavioral and pharmacological interventions. These goals have significant public health benefits and can stand to improve ASD best-practice approaches in the future.

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Dr Foss-Feig is Postdoctoral Associate at the Child Study Center of Yale University School of Medicine in New Haven, CT. Dr McPartland is Associate Professor in the Child Study Center and department of psychology at Yale University and Director of the Developmental Disabilities Clinic at the Yale Child Study Center in New Haven, CT.

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Articles

What are the most effective assessment practices for ASD during the developmental stages of early childhood, middle childhood, adolescence, and adulthood? 

Autism Spectrum Disorders and Psychiatry: Update on Diagnostic and Treatment Considerations

Original release date 11/09. Approved for CME credit through November 2010

After reading this article, you will be familiar with:

• How Asperger disorder (AD) differs from other autism spectrum disorders
• Clinical features and assessment of AD
• Pathophysiology associated with AD
• Treatment modalities appropriate for AD



Who will benefit from reading this article?


Psychiatrists, child and adolescent psychiatrists, psychologists, primary care physicians, nurse practitioners, and other health care professionals. To determine whether this article meets the continuing education requirements of your specialty, please contact your state licensing and certification boards.

In 1944, Hans Asperger published a description of 4 boys who had major social problems despite adequate cognitive and verbal skills.

 His original term for the condition was 

Autistischen Psychopathen im Kindesalter,

 usually translated as autistic psychopathy or autistic personality disorder in childhood. His use of the term “autistic” occurred a year after Leo Kanner’s classic description of the syndrome of early infantile autism but, because of the war, Asperger was likely unaware of Kanner’s paper.

Asperger considered the disorder a personality factor rather than a developmental issue. He emphasized the centrality of social deficits in the face of relatively intact intellectual and linguistic abilities along with unusual circumscribed interests, motor difficulties, and a history of similar problems in fathers.

 The condition received scant attention in North America until Lorna Wing’s influential review and case series appeared nearly 40 years later.

In her review, Wing termed the condition “Asperger syndrome,” which shaped the current term “Asperger disorder” (AD). She suggested some modifications to Asperger’s original description, such as the inclusion of females. Contrary to Asperger’s belief that diagnosis would be unlikely until children were of preschool age, Wing observed that some features, such as lack of pleasure in socialization and play, might emerge earlier. Wing suggested that the disorder might best be regarded as a variant of autism.

Once introduced into English-speaking psychiatry, multiple conceptualizations and diagnostic approaches arose. Differences in diagnostic approaches, predominantly small sample sizes, and confusion with other disorders complicate the interpretation of clinical and research reports from this era. As part of the field trial for 

 criteria for pervasive developmental disorders, international clinical reports of persons with AD were used to evaluate potential differences from other pervasive developmental disorders.

 Findings from the field trial suggested that children with a clinical diagnosis of AD:

• Are more likely to exhibit strength in verbal IQ than are those with autism

• Are more likely to show more severe social deficits than those with pervasive developmental disorder-not otherwise specified

• Tend to exhibit circumscribed interests

As a result of the trial, AD was incorporated into both 

 as an official diagnostic category. The diagnostic criteria reflect these observed distinctions. 

. This Table also displays diagnostic criteria for the other autism spectrum disorders (ASDs) to facilitate differential diagnostic comparison. Although the diagnostic criteria for AD in 

 includes detailed accompanying text that is particularly useful for illustrating the differences between AD and other high-functioning (ie, intact cognitive ability) ASDs.

In AD, restricted repetitive and stereotyped interests tend to manifest as the consuming and intrusive pursuit of a particular body of knowledge, also known as a “circumscribed interest,” rather than other behaviors that are more common in autism (atypical motor mannerisms or inappropriate object use). Individuals with AD are also more likely to be socially motivated despite poor social agility (ie “active but odd”) rather than being frankly disinterested in social interactions.

AD is commonly detected in children 4 years or older, although the diagnosis often may not be made until the child is 10 or 11. As such, a diagnosis of AD is typically made later than a diagnosis of autism.

 This delay probably reflects the relative subtlety of developmental effects and the absence of language-based red flags rather than a different pattern of onset. Indeed, retrospective reports indicate social and behavioral anomalies as early as 20 months of age.

 Despite efforts to better operationalize the distinction between AD and other ASDs-especially high-functioning autism-the distinction remains controversial.

Significant social disability is the primary feature of AD. This disability extends from basic elements of social behavior-such as eye contact, gesture, and facial expression-to more sophisticated aspects, such as empathy and perspective taking.

The social deficits may be more subtle than in persons with autism; this may reflect intact cognition better enabling individuals with AD to compensate through analysis of social situations and distillation of guiding rules for behavior.

 This analytical, rather than intuitive, approach to social interaction frequently results in a rigid social style or awkward patterns of eye contact and gesture.

Intense areas of preoccupation are a second salient clinical feature. In contrast to typical topical infatuations of childhood, the circumscribed interests in children with AD tend to be obsessive, intrusive, exclusive of other activities, and factually driven-often without comprehension of broader relevant contexts. These often stand out during psychiatric evaluations as intrusive conversation topics foisted on the interviewer.

Despite the absence of diagnostic criteria specifying language impairment, individuals with AD tend to display difficulties with the social use of language. Children with AD may develop a precocious vocabulary and pedantic speech patterns, orating at length on their preferred topics with insufficient regard for the contributions or interest level of a conversational partner. Speech volume may be poorly modulated, with nasal tone, limited prosody, and dysfluent rhythm or pace.

 Individuals with AD generally experience difficulty in using and comprehending figurative language.

 Loose associations may be evident but usually reflect poor perspective of the listener’s need (eg, inadequate expository information, inclusion of extraneous details) rather than disorganized thought processes.

Strong language skills and a concrete cognitive style make individuals with AD receptive to strategies aimed at establishing straightforward rules to guide behavior and memorization of verbal social scripts.

Additional clinical characteristics focus on motor control and learning profile. Clumsiness and motor difficulties were observed in Asperger’s initial report, and unusual gait patterns, odd posture, poor handwriting, problems with visuomotor integration, and difficulties with activities that require motor dexterity have been noted in subsequent accounts.

 Individuals with AD may also display proprioceptive difficulties, such as problems with apraxia, balance, tandem gait, and finger-thumb apposition.

 Some research suggests that individuals with AD possess a distinct neuropsychological profile, featuring deficits in fine and gross motor skills, visuomotor integration, visuospatial perception, nonverbal concept formation, and visual memory with preserved articulation, verbal output, auditory perception, vocabulary, and verbal memory.

 This pattern of stronger verbal abilities relative to performance abilities, with a particular weakness in visuospatial organization and graphomotor skills, resembles, and may overlap with, nonverbal learning disability.

AD is often comorbid with several other psychiatric disorders. The boundaries between symptoms and syndromes can be difficult to determine, and limited data (mainly from case reports and a few large, epidemiologically drawn studies) are available to inform such decisions.

 Depression and anxiety frequently coexist with AD; estimates of comorbidity are as high as 65% and increased rates of anxiety and depression have been reported in family members.

 Anxiety often stems from behavioral rigidity and divergence from predicted or routine events; it may resemble social anxiety. Depressive symptoms often emerge in adolescence secondary to social failings. Hyperactivity and inattention are common among children with AD, which has also been associated with Tourette syndrome, obsessive-compulsive disorder, and psychotic conditions-particularly schizophrenia.

Data on the epidemiology of AD are more limited than those for autism, which reflects the continuing disagreement about best diagnostic approaches and the fact that official recognition of AD is relatively recent. Fombonne

 estimated that prevalence of AD is approximately 2.6 per 10,000, about one-fifth as common as autism. The disorder occurs at a much higher rate in boys than in girls. In Asperger’s original report, all cases were male

; in reanalysis of his subsequent cases, approximately 5% were girls.

As with autism, more research is needed on cultural and ethnic factors. Cases have been reported from many different countries, although most are from the developed regions of the world.

Initially considered a consequence of psychosocial phenomena, ASDs are now understood to be brain-based biological disorders, although no clear universal cause has been revealed. Medical conditions, such as aminoaciduria and ligamentous laxity, and perinatal difficulties have been reported to co-occur with AD, but robust correlations have not been documented across studies.

 Increased rates of epilepsy have been observed in persons with AD.

Neurochemical studies of ASDs have produced inconsistent results; the most common finding suggests elevated blood serotonin levels.

The most consistent neuroanatomical findings in ASD reflect rapid brain growth in early childhood. This leads to increased brain volume that normalizes in mid-childhood and results in a relatively small corpus callosum.

 Several studies that have focused specifically on AD have shown associated abnormalities, including left frontal macrogyria and bilateral opercular polymicrogyria, gray tissue anomalies, left temporal lobe damage, left occipital hypoperfusion, and dysmorphology superior to the ascending ramus of the Sylvian fissure proximal to the intersection of the mid frontal gyrus and the precentral sulcus.

 Replication is required to determine whether distinct brain regions are implicated in AD.

Similar brain regions may be involved in ASDs, with quantitative differences in functioning that lead to the observed phenotypic heterogeneity and variation in severity.

 Functional imaging has revealed abnormalities in brain activity associated with social information processing and social cognition as well as problems with functional connectivity among separate brain regions.

 Research has not yet identified the brain regions implicated in AD or in the broader autism spectrum.

Genetic factors have been considered since Asperger’s original account.

 Case series have reported AD, ASD, or autistic-like traits in family members, particularly among fathers. Also, the rate of autistic-like traits in siblings of children with an ASD is considerably higher than that in the general population.

 Some family history studies also indicate associations with other psychiatric disorders, including depression, schizophrenia, and schizoid personality disorders.

Although AD may have stronger heritability than autism, most evidence indicates shared genetic mechanisms common to all ASDs.

 No consistent genetic etiology has been established for AD, and the ASDs probably feature a polygenetic etiology with as-yet-unspecified epigenetic gene-environment interactions.

 Individual studies have reported specific genetic abnormalities, including balanced translocations, and de novo

translocations-chromosomes 1, 5, 11, 13, 14, 15, 17, autosomal fragile site, fragile X syndrome, fragile Y, and 21p+.35,53-57

Diagnostic assessment of AD entails a comprehensive developmental history, including early social development. The individual’s social and communicative characteristics should be assessed by direct observation in multiple contexts; social difficulties are often most pronounced during unstructured periods without clear social expectations or adult-directed interactions. Psychiatric interviewers should observe social behaviors, such as use of eye contact, gesture, and social reciprocity. Social communicative competency can be assessed by making leading conversational bids, asking open-ended questions, and forcing the interviewee to sustain the burden of maintaining the conversation. The interview should elicit details about social relationships, circumscribed interests, self-awareness, and insight into others. Input from teachers and parents about the child’s behavior with peers is also important. The assessment should address obsessions and compulsions, ritualized behaviors, depression and panic attacks, and integrity of thought processes and should include reality testing.

Numerous self-report, parent/teacher report, and direct observation measures have been developed to screen for and diagnose AD.

 To date, these instruments have not been empirically demonstrated to reliably distinguish AD from other high-functioning ASDs.

 Gold standard diagnostic procedures for ASDs include a parent interview; the Autism Diagnostic Interview–Revised; and a semi-structured conversation/play-based interview, the Autism Diagnostic Observation Schedule.

 The last 2 instruments are publicly available but require training to administer and score. Neither instrument offers an algorithm to distinguish AD from other ASDs, although the information they provide is useful in this regard. Differential diagnosis, therefore, relies primarily on clinical judgment.

Because ASDs, including AD, entail impairment across domains of function, it is advisable to refer children with suspected AD for a multidisciplinary assessment by a team with expertise in this area. Such an assessment should entail a developmental and health history, psychological assessment (cognitive ability, psychomotor control, adaptive function), communication assessment (receptive/expressive language, nonverbal communication, nonliteral language, pragmatics, prosody, and content), and a formal diagnostic evaluation using standardized diagnostic assessments. When necessary, consultation regarding behavioral management, motor disabilities, neurological concerns, psychopharmacology, college-readiness, or vocational training may be indicated. The aim of such an assessment is to determine a profile of strengths and weaknesses to inform intervention.

Psychosocial treatment of AD focuses on teaching appropriate social and communication behaviors. The guiding principle is the explicit inculcation of information that is not learned through natural, implicit methods. Treatment guidelines and strategies are akin to those for other ASDs and should take into account the verbal strengths that characterize AD.

 Broadly speaking, recommended interventions use strengths (eg, cognitive or memory skills) to compensate for areas of weakness while establishing environmental supports to facilitate learning and socialization. Intervention programs must be developed according to the individualized needs of each person with AD, based on a nuanced assessment.

 Intervention programs should address basic social and communication skills (with focus on pragmatic communication), adaptive functioning, and academic or vocational skills, while ensuring that learned skills generalize to naturalistic environments.

Strong language skills and a concrete cognitive style make individuals with AD receptive to strategies aimed at establishing straightforward rules to guide behavior and memorization of verbal social scripts. These rules and scripts can be learned and practiced, first in therapeutic settings and then in more naturalistic settings. Social skills groups are a recommended treatment modality for children with AD because they provide a forum for both teaching and applying social lessons.

Challenging behaviors, such as aggression, should be addressed through functional behavior analysis and positive behavior management. For older children and adults with AD, vocational training should teach appropriate etiquette for job interviews and workplace behavior. Assistive technology, such as organizational software and personal data assistants, is often appropriate for supporting organization and work and life management in persons with AD.

The core social vulnerability of AD has not proved responsive to drug treatment. However, associated psychiatric problems are often responsive to pharmacological as well as behavioral and psychotherapeutic interventions. Medications can help with comorbid mood disorders, which are common during adolescence and young adulthood.

 As noted, adolescents and adults with AD are particularly prone to anxiety and depression; as such, SSRIs are frequently prescribed for this group. Children often exhibit attentional problems and sometimes receive a concurrent diagnosis of attention-deficit/hyperactivity disorder. Mental health professionals should be knowledgeable about the potential for comorbidity but must try to avoid the temptation to “chase symptoms” and to employ polypharmacy.

 was optimistic about outcome in the patients he identified, given the presence of similar problems in fathers and his conceptualization of the condition as a personality characteristic rather than a developmental disorder. His view tempered over time, although he maintained that the outcome was more favorable than in persons with autism, probably because at the time autism was conceptualized as primarily associated with intellectual deficiency.

Considering the enduring debate about diagnostic conceptualization, discussion about differences in outcome of AD versus higher-functioning ASDs remains controversial. The limited data suggest that, in contrast to autism, more individuals with AD are self-sufficient and married, but this has not held true in all samples.

 Extrication of symptom severity and adaptive capacity is needed to better understand differences in outcome among persons with ASDs.

In the 65 years that have elapsed since the publication of Asperger’s original manuscript, much progress has been made in understanding the disorder and, more important, in developing methods to detect and treat AD. Despite considerable research, however, psychiatry is yet to elucidate the genetic or brain bases of the disorder and parsimoniously and robustly distinguish AD from similar ASDs. This ongoing topic of debate promises to enter a new chapter with the publication of 

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Hans Asperger considered the disorder a personality factor rather than a developmental issue. How things have changed.

Author | James Mcpartland, PhD

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