1. health and fitness
2. disease
3. autism and pdd

Treatment in Psychiatry
Treatment in Psychiatry begins with a hypothetical case illustrating a problem in current clinical practice. The authors
review current data on prevalence, diagnosis, pathophysiology, and treatment. The article concludes with the authors'
treatment recommendations for cases like the one presented.
Asperger’s Syndrome: Diagnosis and Treatment
Karen Toth, Ph.D.
Bryan H. King, M.D.
“Marc” is a 15-year-old male who presents with his parents for evaluation because of significant symptoms of anxiety
and depressed mood. Marc responds verbally when greeted in the waiting room
but avoids eye contact. He has an aboveaverage IQ, with significantly higher verbal than nonverbal abilities. Academic
difficulties in elementary school led to a
diagnosis at age 8 of nonverbal learning
disability. Marc continues to struggle academically and is falling further and further behind in school. He has strong interests in the Titanic and baseball that
involve recitation of facts, dates, and
numbers. He will talk at length on these
topics, often using language that is more
formal than expected for his age, but he
is unable to sustain conversations on
other topics. Although Marc prefers to interact with adults, he does describe himself as having friends; later his parents reveal that he does not interact with peers
outside of school, and when asked, Marc
is unable to describe what it means to be
a friend. Marc’s parents are very concerned about the widening gap between
Marc’s social development and that of his
peers. Marc’s history includes perinatal
problems, and his family history includes
autism spectrum disorder.
Asperger’s syndrome (AS) is considered to be a variant of
autism rather than a distinct disorder, similar if not equivalent to high-functioning autism. The condition was first
recognized and labeled “autistic psychopathy” by Asperger in 1944 (1). Asperger’s most famous cases were patients described as having above-average intellectual and
language abilities, with significant disturbances in social
and affective communication. However, Asperger also described cases of patients with low intellectual and lan-
guage abilities, similar to those Kanner (2) described as
autistic in 1943. The similarities Asperger noted among
these individuals with widely varying intellectual and language abilities presaged the current notion of a “spectrum” of autistic disorders (3). Asperger’s contribution to
the field went beyond merely identifying and describing
this condition; he was concerned that affected children
would be misunderstood and maltreated, so he sought to
increase awareness of autism. He also advocated an approach to education that involved individualized attention, an emphasis on strengths rather than weaknesses,
and engagement in learning by tapping into the child’s
special interests. These approaches continue to be used
today in the education of children with AS.
Diagnosis
Although Asperger first described cases in 1944, the
term “Asperger’s syndrome” as a diagnostic label did not
come into use until several decades later when Wing (4)
argued that autism included not only children who were
aloof but also those who were socially active but odd in
their behavior. Wing proposed a spectrum of disorders
with varying degrees of severity in each of the three symptom domains that together comprise the diagnostic criteria for autism, namely, impairment in social interaction,
impairment in communication, and restricted, repetitive,
and stereotyped patterns of interests and behaviors. At
about the same time that AS became a widely used descriptive label, the term “high-functioning autism” was
also being used to refer to children with autism who were
relatively more able, in either verbal or nonverbal intelligence (5). Clinically, these two labels are sometimes used
interchangeably, often describing children with autism
who are atypical in their presentation and who frequently
initiate social interactions (albeit lacking in reciprocity) as
opposed to those who are more avoidant or aloof.
DSM-IV-TR provides criteria for a differential diagnosis of
AS based on intact cognitive ability (absence of mental retardation or intellectual disability), no delays in early language
milestones (i.e., use of single words by age 2 and phrases by
age 3; see Table 1). However, this does not imply that language acquisition in AS is normal; for example, there may be
deficits in pragmatic (i.e., social use of) language or use of
overly formal or repetitive language. Hence, this distinction
remains problematic. Results of research that has attempted
to support a distinction between AS and high-functioning
autism have thus far been mixed. The following section presents a brief review of this research (see also reference 6).
This article is featured in this month’s AJP Audio.
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Asperger’s Syndrome vs. High-Functioning
Autism
are defined on the basis of severity of impairment, so studies that appear to confirm differences relating to severity
of impairment are to be expected. More systematic studies
of both quantitative and qualitative aspects of functioning
are needed.
Over the past two decades, a growing body of research
has attempted to address the diagnostic and phenotypic
ambiguity between AS and high-functioning autism.
Some authors believe that the neuropsychological and beEpidemiology and Pathophysiology
havioral profiles of AS and high-functioning autism differ
Current estimates indicate that AS occurs at a rate of
(e.g., reference 7), while others have argued that there is
about
2.5/10,000, as compared to 60/10,000 for all autism
little empirical evidence for a distinction between these
spectrum
disorders (that is, autistic disorder, pervasive detwo disorders (e.g., references 8, 9). Ozonoff and colvelopmental disorder not otherwise specified, and AS).
leagues (10) conducted a comprehensive study that examThese rates represent an upward trend over time, due at
ined differences based on external criteria (cognitive/
least in part to changes in case definition and improved
intellectual profiles, executive funcawareness (13). The rates for AS have
tion, language, current symptoms,
not been well established because of the
early history, and course of illness) as
paucity of research with carefully diag“A
primary
focus
of
most
opposed to criteria involving the defsamples. Likewise, relatively few
inition of the two syndromes. They
intervention programs nosed
studies
of genetic and environmental
found few group differences in current symptom presentation and cog- for individuals with AS is factors in the pathophysiology of AS
have involved large and well-characternitive function but many differences
on enhancing social
ized samples. One such study examined
in early history. Individuals with AS
competence.”
in detail the family, prenatal, and perinoutperformed those with high-funcatal histories of 100 male children with
tioning autism on the comprehenAS who were followed into late adolession subtest of the WISC-III and in
cent
and
early
adulthood
(14). Results indicated a paternal
expressive language ability, but there were no differences
family
history
of
autism
spectrum
disorder in about 50% of
on measures of executive function (flexibility and planthe sample, and pre- and perinatal risk factors in about
ning). Individuals with AS also had better imaginative and
25% of cases. Pre- and perinatal factors included prenatal
creative abilities and more circumscribed interests,
exposure to alcohol, severe postnatal asphyxia, neonatal
whereas those with high-functioning autism showed a
seizures, and prematurity.
greater insistence on sameness. Early history variables
Even fewer studies have examined risk factors by diagwere best able to differentiate the two disorders. Comnostic
subgroup. One such study examined obstetric risk
pared with children with AS, those with high-functioning
factors
and found fewer pregnancy and labor complicaautism were more impaired in early language developtions
in
patients with AS than in those with autism, pervament and behavior over the preschool period, had more
sive developmental disorder not otherwise specified, and
severe lifetime symptoms, and had a greater need for specomparison subjects; those with AS were more likely to
cialized education services. Ozonoff et al. concluded that
have a forceps or vacuum delivery than those with autism,
AS and high-functioning autism appear to be on the same
but they did not differ from comparison subjects on a
spectrum but differ primarily in severity of developmental
number of other pre- and perinatal variables (15).
course. However, in terms of prognosis, the preschool-age
Most studies of pre- and perinatal risk factors conclude
differences they identified had largely disappeared by adthat
these factors do not operate independently in autism
olescence, indicating that the prognosis for individuals
but
may
be related to extant fetal abnormalities or to
with high-functioning autism may be better than previous
genetic or environmental factors. This has led many restudies have reported.
searchers to speculate whether children with similar
A more recent study (11) examined the core symptom
genetic
risk factors vary in phenotypic expression (i.e.,
domain of social interaction and used the Wing and Gould
symptom
severity) due to exposure to different levels of en(12) classification system (aloof, passive, and active but
vironmental
risk. Regarding genetic factors, a genome-wide
odd) to evaluate potential differences in quality of social
scan
for
susceptibility
loci was performed on a sample of ininteraction between individuals with AS and those with
dividuals
with
AS,
identifying
two loci (on chromosomes 1
autism. Results showed that individuals with AS tended to
and
3)
that
have
similarly
been
implicated in the genetics of
be active but odd in presentation as compared with the
autistic disorder (16). Studies such as these support the premore aloof and passive profile of those with autism, supvailing view that AS is not a separate disorder from autism
porting the view that these two groups may differ both in
but a variant on the milder end of the spectrum (5).
symptom severity (i.e., quantitatively) and in the quality of
their social impairment.
Evidence-Based Assessment
There continues to be much debate regarding the overIn spite of the continuing debate regarding diagnostic
lap and differentiation of these two disorders. It is fueled
issues, an evidence-based, best-practice assessment apin part by a tautological dilemma wherein the disorders
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TABLE 1. DSM-IV-TR Criteria for Autistic Disorder and Asperger’s Disorder
Domain of Functioning and Symptom Checklist
Social interaction
Criteria for Autistic
Disorder
2 or more
symptoms
Marked impairment in the use of multiple nonverbal
behaviors such as eye-to-eye gaze, facial expression, body
postures, and gestures to regulate social interaction
Failure to develop peer relationships appropriate to
developmental level
A lack of spontaneous seeking to share enjoyment, interests,
or achievements with other people (e.g., by a lack of
showing, bringing, or pointing out objects of interest)
Lack of social or emotional reciprocity
Communication
1 or more
symptoms
Criteria for Asperger’s Disorder
2 or more symptoms
No clinically significant delay in cognitive or adaptive
abilities; early language milestones met on time
(single words by age 2, phrases by age 3); other
communication impairments may be present
Delay in, or total lack of, the development of spoken
language (not accompanied by an attempt to compensate
through alternative modes of communication such as
gesture or mime)
In individuals with adequate speech, marked impairment in
the ability to initiate or sustain a conversation with others
Stereotyped and repetitive use of language or idiosyncratic
language
Lack of varied, spontaneous make-believe play or social
imitative play appropriate to developmental level
Restricted, repetitive, stereotyped interests and behaviors
Encompassing preoccupation with one or more stereotyped
and restricted patterns of interest that is abnormal either
in intensity or focus
Apparently inflexible adherence to specific, nonfunctional
routines or rituals
Stereotyped and repetitive motor mannerisms (e.g., hand or
finger flapping or twisting, or complex whole-body
movements)
Persistent preoccupation with parts of objects
proach for autism spectrum disorders, including AS, includes a core diagnostic assessment as well as additional
assessment for treatment planning, as described below.
The instruments mentioned here are tools only and
should not be used, in and of themselves, to make a diagnosis (17).
Core Diagnostic Assessment
A comprehensive assessment for AS should include, at
minimum, a detailed developmental history and review of
social, communication, and behavioral development.
Most centers use a tool such as the Autism Diagnostic Interview—Revised (18, 19) for this purpose. Direct observation of the patient, using the Autism Diagnostic Observation Schedule (20, 21), is also essential to gather the kind of
information (i.e., observations of social behavior) necessary for a diagnosis. The Autism Diagnostic Observation
Schedule is a semistructured interview that requires established reliability and therefore is often conducted by
practitioners specifically trained in autism spectrum disorders. Diagnostic tools specific to AS have been developed, but in general they have not been standardized with
participants with confirmed diagnoses of AS, and psychometric properties have not been well studied. These include the Autism Spectrum Screening Questionnaire (22),
the Gilliam Asperger Disorder Scale (23), the Asperger Syn-
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1 or more
symptoms
1 or more symptoms
drome Diagnostic Scale (24), and the Adult Asperger Assessment (25).
Additional Assessment for Treatment Planning
A comprehensive evaluation should also include
screening for medical and psychiatric issues, including
seizures, sleep difficulties, significant sensory issues disrupting daily function, anxiety and depression, and other
psychiatric and behavioral issues. In addition, a review of
school records and previous testing and interventions, as
well as consultation with the child’s teachers for their observations, particularly of peer interactions, is important
to inform diagnosis and treatment planning. Assessment
of intellectual, language, adaptive, and neuropsychological functioning may be conducted to further inform educational planning and treatment. Finally, an occupational
therapy evaluation, with assessment of strategies to mitigate sensory issues, may be warranted, along with assessment of the family system (e.g., stress, depression, access
to community resources), to improve outcomes for children with AS (26).
Comorbid Psychiatric Disorders
The most common comorbid diagnosis in individuals
with AS and high-functioning autism is depression, occurAm J Psychiatry 165:8, August 2008
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ring in as many as 41% of patients (27). Other psychiatric
disorders or symptoms that have been reported include
anxiety (8%), bipolar disorder (9%), schizophrenia (9%),
attempted suicide (7%), hallucinations (6%), mania (5%),
psychotic disorder not otherwise specified (3%), schizoid
personality disorder (3%), and obsessive-compulsive disorder (OCD) (1%). To compare these rates to those in children with autism, in a recent study of 109 children with
autism (28), the most prevalent diagnoses were specific
phobia (44%), OCD (37%), attention deficit hyperactivity
disorder (ADHD) (31%), and depression (10%). The relatively high rate of ADHD in Leyfer and colleagues’ sample
(28) is of interest in light of the fact that the current DSM
specifically excludes comorbidity with autism. Whether
such a trumping rule is appropriate is the subject of current debate. Care must be taken when diagnosing certain
other disorders, such as schizophrenia and psychosis, because the intense preoccupations and interests seen in individuals with AS can resemble delusions and disorders of
thinking (29). In these cases, a detailed history must be obtained to determine the presence of such idiosyncratic interests prior to the onset of a presumed psychosis. It could
also be argued that personality traits, for example schizoid
or obsessive-compulsive, are much more common than
currently reported in individuals with high-functioning
autism or AS and that the differential diagnosis in this domain is potentially very complicated.
Treatment
The average age at diagnosis of AS is about 11 years,
compared with 5.5 years for autism (30). This is problematic, as prognosis is related not only to cognitive and language abilities but also to the provision of early, appropriate, structured education programs (31) and interventions
aimed at improving social competence (32, 33). A limited
number of studies have examined the efficacy of treatment approaches specific to AS or high-functioning autism. No single methodology or intervention strategy has
been identified as the most effective or shown to be successful for all participants, nor is there a single comprehensive treatment program for individuals with these disorders. Common approaches to treatment include adultdirected behavioral programs, such as those using principles of applied behavior analysis, naturalistic child-centered approaches, or a combination approach drawing on
behavioral, developmental, and social-pragmatic principles (34). The National Research Council and the Committee on Educational Interventions for Children With Autism
have identified critical variables for treatment planning,
including prioritizing goals based on core challenges in
social communication, establishing proactive approaches
to problem behaviors, individualizing modes of instruction, implementing supports across contexts, planning for
transitions, addressing psychiatric comorbidity, and providing family support and education (35).
Am J Psychiatry 165:8, August 2008
Interventions to Improve Social Competence
A primary focus of most intervention programs for individuals with AS is on enhancing social competence; here
we describe both general and newer, targeted approaches.
Social skills are typically taught using a variety of methods and in different settings, such as friendship groups at
school, classroom activities, privately taught social skills
group therapy programs, buddy or mentoring programs,
and through individual and dyadic (i.e., pairing the child
with AS with a peer) therapy. Methods or strategies for
teaching social skills include direct instruction, role playing, modeling, social stories, in vivo practice with peers,
and constructive feedback. The social stories technique
refers to stories that can be written and illustrated to fit
any scenario, with the goal of providing information on
what people in a given situation are doing, thinking, and
feeling. Social stories indicate the sequence of events,
identify significant social cues and their meaning, and
script for the child what he or she should do or say. Social
stories are especially helpful in new situations, which often cause anxiety because they are unknown and unpredictable, but they are useful in any situation to enhance
the child’s understanding of what is likely to occur and to
explain what is expected of the child. The perspective of all
participants in a given social story is carefully delineated,
as theory of mind skills (i.e., the ability to take another’s
point of view) are often impaired in people with AS and
must be directly taught (36).
Other general techniques for teaching social skills include first breaking skills down into smaller subskills and
then teaching each skill through modeling and role plays.
For example, conversation skills can be broken down into
a number of subskills, such as greeting others, initiating
topics, staying on topic, maintaining reciprocity, using
nonverbal communication (eye contact, facial expressions, gestures) appropriately, checking in to see if the listener is still interested, and appropriately ending conversations (i.e., saying goodbye). Higher-level skills can
include accepting suggestions, handling criticism, resolving conflicts, and showing empathy. Understanding the
child’s cognitive profile is essential in tailoring a social
skills program to an individual child’s needs and strengths.
For example, verbal strategies should be utilized with children with better-developed verbal abilities, while visual
strategies (e.g., social stories) should be emphasized with
children with higher visual problem-solving skills.
Targeted Intervention Strategies
In recent years, a number of intervention studies have
focused on teaching discrete aspects of social competence, such as joint attention, emotion recognition, and
theory of mind abilities. In general, these studies have indicated positive results, but they have been limited by
small sample sizes (many are best characterized as pilot
studies) and lack of long-term follow-up. Nevertheless,
they point to the utility of focused and individualized
treatment strategies to augment more broad-based educational and social skills interventions for children with
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autism and AS. In a training study of theory of mind and
executive function, Fisher and Happé (37) found that in a
relatively short period (i.e., 5–10 days of training), children
with autism spectrum disorders could improve their performance on theory of mind tasks but not on executive
function tasks. In a study that examined the use of assistive technology to teach emotion recognition to students
with AS, LaCava and colleagues (38) found improved performance not only on basic and complex emotions that
were directly taught via a computer software program but
also on complex voice emotion recognition for emotions
not specifically included in the training software. Finally,
Turner-Brown and colleagues (39) demonstrated the utility of a group-based cognitive behavioral intervention to
teach theory of mind and other social communication
skills to adults with high-functioning autism.
In sum, a comprehensive treatment plan for a child or
adolescent with AS should capitalize on strengths, target
specific areas of impairment (social, academic, adaptive)
as well as comorbid medical or psychiatric disorders, and
be implemented across settings to ensure success and
generalization of skills. Additionally, there is emerging
evidence to support the use of interventions targeting
discrete aspects of social functioning to augment more
broad-based intervention approaches.
Summary and Recommendations
AS, although first identified in 1944, is a relatively new
diagnostic label referring to a set of behavioral characteristics shared by children with autism. Children and adults
with AS typically have higher intellectual and linguistic
abilities than those with autism but are quite impaired in
their social communication skills. Individuals with AS are
also at higher risk for certain psychiatric and medical disorders, such as depression, anxiety, and seizures. Diagnosing AS can be tricky, as the diagnostic criteria are not
clearly differentiated from those defining autistic disorder.
The prevailing view in the literature is that AS is not a distinct disorder but a milder variant of autism. Whether or
not this is so, children with AS are typically diagnosed at
much older ages than those with autism, and thus appropriate and targeted interventions are often not initiated at
early ages, when they may have the greatest impact. Nevertheless, a number of strategies, including those promoting social competence, are widely used with children with
AS and have been shown to have a positive impact on outcomes. Pharmacotherapy for associated conditions in AS
has not been systematically studied and is currently informed by research in the general population.
After careful review of developmental
history, school records, and past medical
records as well as time spent directly observing and interacting with Marc, he was
diagnosed as having Asperger’s syn-
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drome, anxiety disorder not otherwise
specified, and depression not otherwise
specified. Marc’s anxiety was determined
to be related to both school and social interactions. His depression, which did not
meet full criteria, was based on a history
of social failure and rejection and his report of lessened interest in and activities
related to his areas of intense focus (e.g.,
he reported that baseball was less enjoyable). Recommended interventions included working with an autism specialist,
privately or through the school district,
who could advocate for Marc and his parents to ensure that he received additional specialized education services and
accommodations to address his academic difficulties. For Marc’s anxiety and
depression, treatment with a selective serotonin reuptake inhibitor as well as individual psychotherapy was recommended. Since individuals with AS, even
those who are highly verbal, tend to respond best to behavioral strategies, a
concrete, skills-based approach to psychotherapy was recommended rather
than a primarily cognitive approach. Targeted social skills interventions to promote prosocial skills and expand Marc’s
peer group were recommended for implementation once his anxiety and depression improved. Finally, a recommendation for private speech and language
therapy to address pragmatic deficits as
well as social skills deficits was made.
Marc’s parents were directed to state and
local resources and support groups. The
diagnosis was discussed with Marc directly, and he was given a list of excellent
web sites that provide both information
and community for adolescents and
adults with AS.
Received Feb. 21, 2008; revision received April 26, 2008; accepted
April 28, 2008 (doi: 10.1176/appi.ajp.2008.08020272). From the Children’s Hospital and Regional Medical Center; and the Department of
Psychiatry and Behavioral Sciences, University of Washington, Seattle. Address correspondence and reprint requests to Dr. King, Director of Child and Adolescent Psychiatry, Children’s Hospital and Regional Medical Center, 4800 Sand Point Way, N.E., Seattle, WA 98105;
[email protected] (e-mail).
Dr. Toth receives support from NIH. Dr. King has received research
funding from Autism Speaks and NIH and has served as a consultant
for Biomarin and Neuropharm and as an unpaid consultant for Seaside Therapeutics and Nastech.
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