Disorders usually first diagnosed in
infancy, childhood, or adolescence.
Asperger’s Disorder--

Mental Asperger syndrome (also Asperger's syndrome, Asperger's disorder, Asperger's, or AS) is one of several
autism spectrum disorders (ASD) that are characterized by difficulties in social communication and interaction, and
in intense but narrow interests[1]. Asperger's have normal or even superior intelligence[2] and, unlike autistics, have
no significant delay in language development[3] . Although not mentioned in standard diagnostic criteria, odd
speech, language peculiarities and abnormal clumsiness are frequently reported features of AS.[4][5]

Asperger syndrome was named in honor of Hans Asperger who, in 1944, described children in his practice who
appeared to have normal intelligence but lacked nonverbal communication skills, failed to demonstrate empathy with
their peers, and were physically clumsy. AS was introduced to the English-speaking world in 1981 when British
doctor Lorna Wing published a series of case studies[1]. In 1994, AS was recognized in the Diagnostic and
Statistical Manual of Mental Disorders (DSM-IV) as Asperger's Disorder. Questions about many aspects of AS
remain: the diagnostic validity of Asperger syndrome is disputed, there is lingering doubt about the distinction
between AS and high-functioning autism (HFA)[6], and the prevalence of AS is unclear. Further, experienced
clinicians use characteristics beyond the diagnostic criteria to diagnose AS and to distinguish between AS and HFA.

There is no single treatment for AS, and there is little evidence that any particular intervention is effective.
Researchers and people with AS have contributed to a shift in attitudes, away from the notion that AS is a deviation
from the norm that must be treated or cured, and towards the view that AS is a difference rather than a disability.
Intervention is aimed at ameliorating symptoms and improving function. The mainstay of treatment is behavioral
therapy, focusing on specific deficits to address poor communication skills, obsessive or repetitive routines, and
clumsiness.

Most individuals with AS can learn to cope with their differences, but may continue to need moral support and
encouragement to maintain an independent life.[1] The deficits associated with AS may be debilitating, but many
individuals are able to excel, especially in areas that are less dependent on social interaction, including
mathematics, music, and computer sciences.[2]. The exact cause of AS is unknown, although research supports the
likelihood of a genetic contribution, and advanced brain imaging techniques have identified structural and functional
differences in specific regions of the brain.

Classification

Asperger syndrome is one of the pervasive developmental- (PDD) or autism spectrum disorders (ASD), which are
characterized by widespread abnormalities of social interaction and communication, restricted interests and
repetitive behavior.[7] Of the other four autism spectrum disorders, autism is most similar to AS in signs and likely
causes; Rett syndrome and childhood disintegrative disorder share several signs with autism, but may have
unrelated causes; and pervasive developmental disorder not otherwise specified (PDD-NOS) is diagnosed when the
criteria are not met for a more specific disorder.[8] Unlike autism, AS has no substantial delay in language or
cognitive development under the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) and World Health
Organization ICD-10 diagnostic criteria.[9]

The extent of the overlap between AS and high-functioning autism (HFA—autism unaccompanied by mental
retardation) is unclear;[10] there is significant debate over the difference between AS and HFA and whether they
are distinct and separate disorders.[11][12] Some clinicians deny that AS is differentiated from other autistic
spectrum disorders and indicate that a "DSM-IV diagnosis of Asperger's disorder is unlikely or impossible".[13]
Instead they refer to Asperger's as HFA, or treat the diagnoses interchangeably, arguing that language delay is a
difference in degree and not kind.[2][13] While HFA has no standardized definition, and AS has several distinct
definitions,[14][15] diagnosticians and other clinicians often distinguish the two according to speech development.
[16][17][18] However, objective tests have yet to demonstrate the validity of this position,[11][16][17] and at least
one diagnostic guide takes the position that delayed speech may be a sign of AS.[19]

The diagnoses of AS or HFA are sometimes used interchangeably; the same child can receive different diagnoses
depending on the screening tool the doctor uses.[1] Some researchers argue that there should be no boundary
between high-functioning autism and AS, and that the fact that some people do not start to produce speech until a
later age is no reason to divide the two groups, since they are identical in the way they need to be treated.[20] In
some countries, diagnoses may be influenced by non-technical issues, such as availability of government benefits
for one condition but not the other; clinicians may diagnose autism rather than the more correct Asperger's if that
helps a child receive classroom support, government funding or services covered by insurance.[21]

Canadian researcher Peter Szatmari writes that the current classification of the pervasive developmental disorders
is "deeply unsatisfying to many parents, front-line clinicians, and academic researchers", and may not reflect the
true nature of the conditions; he writes that the DSM-IV and ICD-10 focus on the idea that discrete biological entities
exist within PDD, which "leads to a preoccupation with searching for cross-sectional differences between PDD
subtypes, a strategy which has not been very useful in classification or in clinical practice".[22]

Characteristics

AS is characterized in the DSM-IV by impairments in social interaction and restricted interests and behaviors. [23]
Intense preoccupation with a narrow subject, one-sided verbosity, restricted prosody and intonation, and motor
clumsiness are typical of the condition, but are not required for a DSM-IV diagnosis;[6] these features are included
in other diagnostic schemes (see Diagnosis). Experienced clinicians use characteristics beyond the diagnostic
criteria to distinguish between AS and HFA.[6]

Although individuals with AS "have considerable verbal ability, they fail to utilize language appropriately in social
interactions" (UCLA's Kasari and Rotheram-Fuller).[11] "These are kids who talk before they walk," according to
Fred Volkmar, the director of the Yale Child Study Center. "Words are their lifeline, and from a research perspective
that's a critical observation that captures the difference from autism."[24] The DSM-IV does not specify language
delays, but clinicians acknowledge abnormalities in speech and communication. Klin has written that "significant
abnormalities of speech are not typical of individuals with AS", but "aspects of these individuals' communication
patterns" are of clinical interest.[6]

With respect to the restricted interests of those with AS, "one of the most striking features of individuals with AS is
their passionate pursuit of specific areas of interest" (McPartland and Klin of the Yale Child Study Center).[5]

Describing the social interaction of individuals with AS, Harvard Medical School's Baskin, Sperber and Price have
written that "the lack of empathy demonstrated by AS patients is possibly the most dysfunctional aspect of the
syndrome".[4]

Christopher Gillberg writes "Children with autism spectrum disorders, notably those with Asperger syndrome, have
long been reported to suffer from the kind of motor clumsiness currently subsumed under the DCD [Developmental
Coordination Disorder] label."[25]

Social interaction

Individuals with Asperger syndrome experience difficulties in the basic elements of social interaction, which may be
manifested in their impaired use of nonverbal behaviors such as eye contact, facial expressions,[26] and bodily
postures and gestures; a failure to develop friendships or enjoy spontaneous interests or achievements with others;
or deficient social or emotional reciprocity.[23] People with AS have a lower capacity for empathy,[5] which was
confirmed in a controlled study comparing AS and HFA individuals[27] and has significant negative implications to
people with AS.[28]

Within the family, children with AS may or may not bond or show affection, while outside the family, they may make
inappropriate attempts to socialize, leading to peer rejection.[2] Dating and marriage present additional difficulties;
men with AS may want to marry without an understanding of courtship.[2] The concrete nature of emotional
attachment for people with AS (for example, attachment to objects rather than people) may seem curious or be a
cause of concern to others,[29] although the opposite may occur: a person with AS may be unusually affectionate to
significant others and not perceive or misinterpret signals from a partner.[30]

People with AS may find themselves socially isolated, although unlike those with autism, they are not usually
withdrawn around others; they approach others, even if awkwardly, for example by engaging in a one-sided, long-
winded speech about an unusual topic while being insensitive to or unaware of the other person’s feelings or
reactions, such as signs of boredom or wanting to leave.[6] This failure to interpret the context of, or react
appropriately to social interaction may appear as disregard for other people's feelings, and may come across as
highly insensitive. However, the cognitive ability of people with AS sometimes permits them to articulate social norms
in a laboratory context,[5] where they may be able to describe social conventions and show a theoretical
understanding of other people’s emotions, but have difficulty acting on this knowledge in real-life situations[6] and
fluid social interactions.[5] People with AS may analyze and distill their observation of social interaction into rigid
behavioral guidelines, yet apply these rules in ways that are awkward—such as forced eye contact—resulting in a
demeanor that appears rigid or socially naïve.[5]

Repetitive behaviors and restricted interests

People with AS display restricted repetitive and stereotyped patterns of behavior, interests, and activities that can
include interests that are abnormal in intensity or focus, inflexible adherence to routines or rituals, stereotyped and
repetitive motor mannerisms, or a preoccupation with parts of objects.[23]

Individuals with AS may amass volumes of detailed information on unusual topics of special interest[6][5]. While
many children have developmentally appropriate interests in topics such as dinosaurs or trains, a child with AS may
also be interested in transistors, subway tokens, deep fat fryers, or members of congress. These interests may have
an exclusive, obsessive quality and an absence of genuine understanding of broader phenomena related to the
topic.[6][5] For example, "a child might be interested in memorizing the model numbers of antique cameras without
any interest in photography".[5] Asperger described good memory for trivial facts (occasionally even eidetic
memory) in some of his patients;[31] [32] but, despite occasional appearances to the contrary,[33] this may involve
more rote memorization than real understanding.[31]

The passionate pursuit of special interests is usually apparent by the time children with AS enter grade school
(typically age 5 or 6 in the US). This may be at the expense of their developing typical peer relationships or pursuing
other activities.[2][5] The topic of interest may change over time, but often dominates social relationships,
contributing to the social difficulties accompanying AS.[6][5] The entire family may become immersed in the narrow
topic of interest.[6] Because topics such as dinosaurs and fictional characters often capture the interest of children,
this symptom may go unrecognized, and may not be apparent until the interests become more unusual and focused
over time.[6]

Special interests may dominate the social interaction of a child with AS and the monologues characteristic of their
preoccupations may alienate other children. They are "notoriously oblivious" to the effect their conversation is
having on the listener, and their excessive enthusiasm to share the interest with others causes them to engage in a
socially awkward manner that has been called "active but odd".[5] Childhood desires for social companionship can
be numbed through a history of failed social encounters.[5]

Stereotyped and repetitive motor mannerisms may involve hand movements such as flapping or twisting, or complex
whole-body movements;[23] people with AS may display compulsive finger, hand, arm or leg movements,[34]
including tics and stims.[35][36] Stereotypies are typically repeated in longer bursts and look more voluntary or
ritualistic than tics, which are usually faster, less rhythmical and more often asymmetrical than stereotypies.
Although there is overlap, experienced clinicians rarely have difficulty distinguishing tics from stereotypies.[37]

Speech and language

Although language skills are not mentioned in the DSM-IV or ICD-10 diagnostic criteria, there is evidence that while
children with AS acquire language on time, their use of language may be atypical;[5] "speech and language
peculiarities" and "odd speech" are included in other diagnostic schemes.[23][19] Individuals with AS may
demonstrate abnormal speech and language, including pedantic speech; oddities in pitch, intonation, prosody, and
rhythm; literal interpretations and miscomprehension of nuance; a lack of sensitivity or an inability to use language
in social contexts (for example, interrupting others or inserting irrelevant commentary and inappropriate personal
remarks); unusually formal or idiosyncratic speech; verbosity, speech reflecting the idiosyncratic interests of the
speaker or the use of metaphors meaningful only to the individual; selective mutism; and auditory discrimination
issues, particularly when multiple people are speaking simultaneously.[2]

According to Klin, at least three aspects of these individuals' communication patterns are of clinical interest: poor
prosody, tangential and circumstantial speech, and marked verbosity.[6] Although inflection and intonation may be
less rigid or monotonic than in autism, people with AS often have a limited range of intonation; speech may be overly
fast, jerky or loud. Speech may convey a sense of incoherence; although some of these cases may be symptomatic
of a thought disorder, there is often a conversational style that includes monologues about topics of little or no
interest the listener, a failure to provide context or background for comments, and a failure to suppress internal
thoughts. Individuals with AS may talk incessantly about a favorite topic, and may fail to monitor whether the listener
is interested or engaged in the conversation. The conclusion or point of long-winded monologues may never be
made, and attempts by the listener to elaborate on the content or logic of the exchange, or to shift the focus to
related topics, are often unsuccessful.[6]

Children with AS may have an unusually sophisticated vocabulary at a young age (and have been colloquially
referred to as "little professors") but have difficulty understanding metaphorical language and tend to use language
literally.[5][38] Autism researcher Tony Attwood gives the example of a girl with AS who answered the telephone and
was asked, "Is Paul there?" Although Paul was in the house, he was not in the room with her, so she said "no" and
hung up. The caller had to call back and explain that he meant for her to find Paul and have him pick up the
telephone.[39] Individuals with AS appear to have particular weaknesses in several areas of nonliteral language,
including humor, irony and teasing.[11] A study analyzing adolescents’ responses to cartoons found that individuals
with AS and HFA had difficulty comprehending humor.[40] Another study of young adults with AS found they
understood ironic jokes less readily than typical controls and were poor at using social context to interpret
conversational meaning;[41] people with AS usually understand the cognitive basis of humor, but may lack
understanding of the intent of humor—to "share enjoyment with others".[11]

Other

Problems with motor skills are not part of the DSM-IV diagnostic criteria, but Asperger’s initial accounts[5] and other
diagnostic schemes[19] include descriptions of motor clumsiness. Children with AS may be delayed in acquiring
motor skills that require motor dexterity, such as bicycle riding or opening a jar, and may appear awkward or
"uncomfortable in their own skin". They may be poorly coordinated, or have an odd or bouncy gait or posture, poor
handwriting, or problems with visual–motor integration, visual–perceptual skills, and conceptual learning,[6][5] while
having "relative strengths in auditory and verbal skills and rote learning".[6] Research also shows problems with
proprioception and "deficits on measures of apraxia, balance tandem gait, and finger–thumb apposition".[42] There
is no evidence that these motor skills problems differentiate AS from other high-functioning ASDs.[5]

Children with AS may be sensitive to sound (hyperacusis), touch, taste, sight, smell, pain, temperature, and the
texture of foods; they may exhibit synesthesia,[2] a neurologically based phenomenon in which the stimulation of
one sensory or cognitive pathway leads to automatic, involuntary experiences in a second sensory or cognitive
pathway. A review of all controlled investigations published since 1960 showed that sensory symptoms were more
frequent in children with autism, but there was little support for hyperarousal or habituation in autism; there was
evidence of hyporesponsiveness to sensory stimuli, although many of these findings have not been replicated.[43]

According to McPartland and Klin (2006), a unique neuropsychological profile has been described for AS and
confirmed in a review of the literature;[44] if verified, it could differentiate between AS and HFA and aid in differential
diagnosis. Relative to HFA, people with AS have deficits in "fine and gross motor skills; visual motor integration;
visual-spatial perception; nonverbal concept formation; and visual memory with preserved articulation, verbal output,
auditory perception, vocabulary, and verbal memory".[45] Verbal abilities are stronger than performance abilities
and indicate weakness in visual–spatial organization and graphomotor skills.[46] Most subjects with AS in another
study had a "neuropsychologic profile consistent with a nonverbal learning disability".[47] The literature review did
not reveal consistent findings of "nonverbal weaknesses or increased spatial or motor problems relative to
individuals with HFA", leading some researchers to argue that increased cognitive ability is evidenced in AS relative
to HFA regardless of differences in verbal and nonverbal ability.[48]

Alexithymia is a personality trait of people who have difficulty recognizing, processing and regulating emotions.[49]
Uta Frith reported that alexithymia overlaps with AS, and that at least half of the Asperger syndrome subjects in a
study obtained scores that indicate severe impairment.[50] Other researchers concur that both conditions are
characterized by core disturbances in speech and language and social relationships[51][52] and the limbic system
and prefrontal cortex may be involved in both.[4][53] Alexithymic traits in AS may be linked to depression or anxiety;
[50] the mediating factors are unknown and it is possible that alexithymia predisposes a person to anxiety.[53]

Diagnosis of Asperger syndrome

Asperger's Disorder is defined in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) by six main
criteria.[23]

The ICD-10 criteria are almost identical to DSM-IV:[54] ICD-10 adds the statement that motor clumsiness is usual
(although not necessarily a diagnostic feature); ICD-10 adds the statement that isolated special skills, often related
to abnormal preoccupations, are common but are not required for diagnosis; and the DSM-IV requirement for
clinically significant impairment in social, occupational, or other important areas of functioning is not included in ICD-
10.[55][4]

The DSM-IV and ICD-10 diagnostic criteria have been criticized for being too broad and inadequate for assessing
adults,[56] overly narrow (particularly in relation to Hans Asperger's original description of individuals with AS),[13]
[54] and vague;[19] results of a large study in 2007 comparing the four sets of criteria point to a "huge need to
reconsider the diagnostic criteria of AS."[55] The study found complete overlap across all sets of diagnostic criteria
in the impairment of social interaction with the exception of four cases not diagnosed by the Szatmari et al. criteria
because of its emphasis on social solitariness. Lack of overlap was strongest in the language delay and odd speech
requirements of the Gillberg and the Szatmari requirements relative to DSM-IV and ICD-10, in the differing
requirements regarding general delays, and in DSM's requirement for impairment.[55]

Signs suggestive of AS are often noted by a general practitioner or pediatrician during a routine developmental
check up. The National Institute of Neurological Disorders and Stroke advise that this be followed up with a
comprehensive team evaluation to either confirm or exclude a diagnosis of AS.[5] Foster and King state that the
determination of whether there is a family history of autism spectrum conditions can be important.[57] Fitzgerald
states that a multidisciplinary team approach can be critical to avoiding misdiagnosis;:[54] an accurate assessment
of the individual's strengths and weaknesses is claimed to be more useful than a diagnostic label.[5] Delayed or
mistaken diagnosis is regarded as a serious problem that can be traumatic for individuals and families; diagnosis
based solely on a neurological, speech and language, or educational attainment may yield only a partial diagnosis.
[54]

It has been found that parents of children with AS can typically trace differences in their children's development to
as early as 30 months of age, although diagnosis is not made on average until the age of 11.[57] By definition,
children with AS develop language and self-help skills on schedule, so early signs may not be apparent and the
condition may not be diagnosed until later childhood. Impairment in social interaction is sometimes not in evidence
until a child attains an age at which these behaviors become important; social disabilities are often first noticed when
children encounter peers in daycare or preschool.[5] Diagnosis is most commonly made between the ages of four
and eleven, and one study suggests that diagnosis cannot be rendered reliably before age four.[5]

Asperger syndrome can be misdiagnosed as a number of other conditions, leading to medications that are
unnecessary or even worsen behavior.[54]

Causes of autism

Asperger described common symptoms among his patients' family members, especially fathers,[5] and research
supports this observation and suggests a genetic contribution to AS.[5][57] Although no specific gene has yet been
identified, multiple factors are believed to play a role in the expression of autism, given the phenotypic variability
seen in this group of children.[57] Evidence for a genetic link is the tendency for AS to run in families and an
observed higher incidence of family members who have behavioral symptoms similar to AS but in a more limited form
(for example, slight difficulties with social interaction, language, or reading).[1] Most research suggests that all
autism spectrum disorders have shared genetic mechanisms, but AS may have a stronger genetic component than
autism.[5] There is probably a common group of genes where particular alleles render an individual vulnerable to
developing AS; if this is the case, the particular combination of alleles would determine the severity and symptoms
for each individual with AS.[1] No gene has been identified for AS, although studies suggest specific genetic
abnormalities: such as various types of chromosomal translocations in chromosomes 1, 5, 11, 13, 14, 15 and 17;
autosomal fragile site, fragile X syndrome, fragile Y, and 21pþ.[5] Anomalies in chromosome 22 were related to the
diagnosis of autism and Asperger syndrome in five children. The distal tip of the long arm of the chromosome 22
contains the SHANK3 gene, which is thought to have a role in the maturation and maintenance of brain synapses.
The deletion of this part of the chromosome (22q13 deletion syndrome) was found in low-functioning autistic
subjects, and its duplication observed in a subject diagnosed with Asperger syndrome.[58]

Environmental factors may interact with genetic influences to play a role in the cause of ASDs, but research has
identified no consistent correlations.[5] There is strong evidence that genetic factors play a major role in the causes
of autism spectrum disorders, while none of the possible environmental causes has been confirmed by scientific
investigation.[59]

Mechanism

Brain imaging techniques have revealed structural and functional differences in specific regions of the brains of AS
children; these are most likely caused by the abnormal migration of embryonic cells during fetal development, which
affects the final structure and connectivity of the brain, resulting in alterations in the neural circuits that control
thought and behavior.[1] Although progress has been made, brain imaging technologies have failed to identify the
specific underpinnings of AS or factors that distinguish it from other ASDs and no clear pathology common to
individuals with AS has emerged.[5] Functional MRI has provided interesting findings, but no convincing evidence
reproducibly indicates differences among AS and other ASDs.[5]

One study reported a reduction of brain activity in the frontal lobe of AS children when they were asked to respond
to tasks that required them to use their judgment. These differences in activity were also seen when children were
asked to respond to facial expressions.[1] Another study, of brain function in adults with AS, revealed abnormal
levels of some proteins and demonstrated a correlation between these levels and obsessive and repetitive
behaviors.[1] Possible differences in AS include:[5] gray tissue anomalies,[60][61] left temporal lobe damage,[62]
and left occipital hypoperfusion.[63] Other possible causative mechanisms include serotonin dysfunction and
cerebellar dysfunction.[64][65] Differences in brain volumes—such as enlarged amygdala and hippocampus—have
been linked to autism;[66] the most robust findings are of the reduced size of the corpus callosum and rapid brain
growth and increased brain volume in early childhood that normalizes in mid-childhood.[67] Other research suggests
abnormal right hemisphere functioning in AS,[68] dysfunction in brain regions affecting social cognition,[69] and
problems with functional connectivity among separate brain regions.[70]

Simon Baron-Cohen proposes a model for Asperger's[71] that extends the extreme male brain theory, which
hypothesizes that autism is an extreme case of the male brain, defined psycho-metrically as individuals in whom
systemizing is better than empathizing.[72] Hyper-systemizing hypothesizes that autistic individuals can systematize—
that is, they can develop internal rules of operation to handle internal events—but are less effective at empathizing
by handling events generated by other agents.[73] This in turn is related to the earlier theory of mind, which
hypothesizes that autistic behavior arises from an inability to ascribe mental states to oneself and others.[74] Two
studies showed that Asperger subjects had a second-order theory of mind; compared to younger or more impaired
autistic individuals, they were able to understand problems of the type "Peter thinks that Jane thinks that ..."
although their explanationns of their solutions did not use mental states.[75] There is some evidence that the mind-
reading capacity of children in the higher-functioning range of the autistic spectrum are intact.[76]

Autism therapies

The goal of treatment is the development of age-appropriate social, communication and vocational abilities, and the
successful management of distressing symptoms, aiming to teach through explicit instruction the skills that are not
naturally acquired during development.[5] Intervention should be tailored to the needs of the individual child, based
on multidisciplinary assessment.[77] Although progress has been made, data supporting the efficacy of particular
interventions are limited.[5]

The ideal treatment for AS coordinates therapies that address the three core symptoms of the disorder: poor
communication skills, obsessive or repetitive routines, and physical clumsiness. While most professionals agree that
the earlier the intervention, the better, there is no single best treatment package.[1] AS treatment resembles that of
other high-functioning ASDs, except that it takes into account the linguistic capabilities, verbal strengths, and
nonverbal vulnerabilities of individuals with AS.[5] A typical treatment program generally includes:[1]

* the training of social skills for more effective interpersonal interactions;
* cognitive behavioral therapy to improve the management of anxiety or explosive emotions, and to reduce the
prevalence of obsessive interests and repetitive routines;
* medication, for coexisting conditions such as depression and anxiety;
* occupational or physical therapy to assist with poor sensory integration and motor coordination;
* specialized speech therapy, to help with the pragmatics of the "give and take" of normal conversation;
* the training and support of parents, particularly in behavioral techniques to use in the home.

There have been many studies on psychologically based early intervention programs; most of these are case
studies of up to five participants.[78] These studies typically examine non-core autistic problem behaviors such as
self-injury, aggression, noncompliance, stereotypies and spontaneous language.[78] Despite the widespread
application of social skills training, its effectiveness is not firmly established.[79] A randomized controlled study of a
model for training parents in problem behaviors in their children with AS showed that parents attending a 1-day
workshop or six individual lessons reported fewer behavioral problems, while parents receiving the individual lessons
reported less intense behavioral problems in their AS children.[80] Vocational training is important to teach job
interview etiquette and workplace behavior to older children and adults with AS, and organization software and
personal data assistants to improve the work and life management of people with AS are useful.[5]

No medications specifically target AS[4] or directly treat the core symptoms of autism spectrum disorders; research
into the efficacy of pharmaceutical intervention for AS is limited.[5] However, it is essential to diagnose and treat
comorbid conditions;[4] medication can be effective in combination with behavioral interventions and environmental
accommodations in treating comorbid symptoms such as anxiety, depression, inattention and aggression.[5] The
atypical neuroleptic medications risperidone and olanzapine have been shown to reduce the associated symptoms
of AS;[5] risperidone can reduce repetitive and self-injurious behaviors, aggressive outbursts and impulsivity, and
improve stereotypical patterns of behavior and social relatedness. The selective serotonin reuptake inhibitors
(SSRIs) fluoxetine, fluvoxamine and sertraline have been effective in treating repetitive behaviors and restricted
interests.[4][57][5]

Care must be taken in the management of pharmacotherapy; abnormalities in metabolism, cardiac conduction times,
and an increased risk of type 2 diabetes have been raised as concerns with these medications[81][82] and
unintended side effects have largely been ignored in the literature.[78] SSRIs can lead to manifestations of
behavioral activation such as increased impulsivity, aggression and sleep disturbance.[57] Weight gain and fatigue
are commonly reported side effects of risperidone, which may also lead to increased risk for extrapyramidal
symptoms such as restlessness and dystonia[57] and increased serum prolactin levels.[83] Sedation and weight
gain are more common with olanzapine,[82] which has also been linked with diabetes.[81] Sedative side-effects in
school-age children[84] have ramifications for classroom learning. Individuals with AS may be unable to identify and
communicate their internal moods and emotions or to tolerate side effects that for most people would not be
problematic.[12]

Prognosis

As of 2006, no studies addressing the long-term outcome of individuals with AS are available and there are no
systematic long-term follow-up studies of children with AS.[6] Individuals with AS appear to have normal life
expectancy but have an increased prevalence of comorbid psychiatric conditions such as depression, mood
disorders, and obsessive-compulsive disorder that may significantly affect prognosis. Although the social impairment
is believed to be lifelong,[2] outcome is generally more positive than with individuals with lower functioning autism
spectrum disorders.[5][90]

Children with AS are vulnerable to being teased and victimized; some may require special education services
because of their social and behavioral difficulties although many attend regular education classes.[6] Adolescents
with AS may exhibit ongoing difficulty with self-care, organization and disturbances in social and romantic
relationships;[91] despite high cognitive potential, most remain at home, although some do marry and work
independently.[5][92] The "different-ness" adolescents experience can be traumatic.[24] Although the deficits
associated with AS are often debilitating, many individuals experience positive outcomes—particularly those who are
able to excel in areas less dependent on social interaction, such as mathematics, music, and the sciences. Reports
suggest that many people with AS are highly creative and accomplish innovative research in fields such as computer
science, mathematics, and physics.[2] Baron-Cohen reports a link between AS and high-achieving mathematicians,
physicists and computer scientists that shows that the condition need not be an obstacle to achievement.[93] The
symptoms of AS can at some point "fade to normal" and people with AS can become valued workers as adults
because of the "intensity of interest and volume of knowledge" that they may bring to idiosyncratic subjects,[24] but
they may lose employment if impaired understanding of social norms leads to poor judgment in work site behavior.[2]

Education of families is critical in developing strategies for understanding strengths and weaknesses;[4] prognosis is
improved when individuals with AS have supportive families who are knowledgeable about Asperger's.[2] Prognosis
may be improved by diagnosis at a younger age that allows for early interventions, while interventions in adulthood
are valuable but less beneficial.[4] There are legal implications for individuals with AS as they run the risk of
exploitation by others and may be unable to comprehend the societal implications of their actions.[4] The hypothesis
that the combination of intact intellectual and linguistic ability with limited empathy and social understanding may
predispose individuals with AS to violent or criminal behavior has been investigated and found to be unsupported by
data.[5][94]

Epidemiology

The incidence of AS is not well established, but conservative estimates using the DSM-IV criteria indicate that two to
three of every 10,000 children have the condition, making it rarer than autistic disorder itself.[1][95] A computerized
registry in Denmark indicates an annual incidence of 1.4 per 10,000 for AS.[4] Advocacy and parent support
organizations have proliferated around the concept of AS, and there are indications that this has resulted in more
frequent diagnoses of AS, which may be given as a "residual diagnosis" to children of normal intelligence who do not
meet diagnostic criteria for autism but have some social difficulties.[6]

A 2003 review of epidemiological studies[96] found prevalence rates ranging from .03 to 4.8 per 1,000; the authors
suggested a working rate of .26 per 1,000.[5] A 1993 Sweden study found the prevalence of AS was 3.6 per 1,000
among school-aged children aged 7–16 using Gillberg's criteria, rising to 7.1 per 1,000 if suspected cases are
included.[19] The estimate is convincing for Sweden, but the findings may not apply elsewhere because they are
based on a homogeneous population.[2]

Prevalence estimates vary according to the diagnostic criteria employed. An epidemiological study of 5,484 eight-
year-old children in Finland found 2.9 children per 1,000 met the ICD-10 criteria for an AS diagnosis, 2.7 per 1,000
for Gillberg and Gillberg criteria, 2.5 for DSM-IV and 1.6 for Szatmari et al. The number of children diagnosed as
having AS according to any of the four criteria was 4.3 per 1,000.[55] Leekam et al. documented significant
differences between Gillberg's criteria and the ICD-10 criteria.[97]

Like other autism spectrum disorders, AS prevalence estimates for males are higher than for females.[1] The
Sweden study found a 4:1 male to female ratio in subjects meeting Gillberg's criteria for AS, but a lower 2.3:1 ratio
when suspected or borderline cases were included.[19] The Finland study found a "somewhat surprising" male-to-
female ratio according to DSM-IV criteria of 0.8:1; Gillberg and Gillberg criteria yielded a 2:1 ratio and the ratio when
including children diagnosed per any of the four sets of diagnostic criteria was 1.7:1. Females with AS may not be
recognized in studies as they tend to be superficially more sociable than boys, although closer examination reveals
problems in social interaction.[55]

Comorbidities

Most patients presenting in clinical settings with AS have other comorbid psychiatric disorders; children are likely to
present with attention-deficit hyperactivity disorder (ADHD), while depression is a common diagnosis in adolescents
and adults.[98] Many children with AS are initially misdiagnosed with ADHD.[5] Individuals with AS may also be
diagnosed with oppositional defiant disorder, antisocial personality disorder, tic disorders and Tourette syndrome,
general anxiety disorder, bipolar disorder, obsessive compulsive disorder or obsessive-compulsive personality
disorder.[99]

The conditions most commonly seen are depression and anxiety; comorbidity of these in persons with AS is
estimated at 65%. Anxiety may stem from preoccupation over possible violations of routines and rituals or result
from being placed in a situation without a clear schedule or expectations. Social anxiety (concern with failing in social
encounters) may also manifest. Depression is often the result of chronic frustration from repeated failure to engage
others socially, and mood disorders requiring treatment may develop.[5]

The particularly high comorbidity with anxiety often requires special attention; one study reported that about 84% of
individuals with a pervasive developmental disorder also met the criteria for anxiety disorder.[100] Because of the
social differences experienced by those with AS, such as trouble initiating or maintaining a conversation or
adherence to strict rituals or schedules, additional stress to any of these activities may result in feelings of anxiety,
which can negatively affect multiple areas of one's life, including school, family, and work. Anxiety disorders can be
treated with medication or individual and group cognitive behavioral therapy, where relaxation or distraction-type
activities may be used along with other techniques to diffuse the feelings of anxiety.[101]

Psychosocial factors may contribute to poor adjustment or psychiatric issues. An Internet survey of middle-class
mothers of children with AS and nonverbal learning disorders found peer and sibling victimization of the children was
common; 94% of mothers reported peer victimization of their children. According to the mothers, in the year leading
up to the study, almost three-quarters of the children had been hit by peers or siblings and 75% had been
emotionally bullied. More seriously, 10% of the children were attacked by a gang and 15% were victims of nonsexual
assaults to the genitals. Many of the children ate alone at lunch or were picked last for sports teams, and a third had
not been invited to a birthday party in the past year.[102]

Reports have associated AS with medical conditions such as aminoaciduria and ligamentous laxity, but these have
been case reports or small studies and no factors have been associated with AS across studies.[5] An increased
rate of epilepsy is reported in individuals with AS, and there is a high rate (51%) of non-verbal learning disability.
[103]

* References provided upon request.