Causes

Hans Asperger described common symptoms among his patients' family members, especially fathers, and research supports this observation and suggests a genetic contribution to Asperger syndrome. 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. Evidence for a genetic link is the tendency for AS to run in families and an observed higher incidence of family members who have behavioural symptoms similar to AS but in a more limited form (for example, slight difficulties with social interaction, language, or reading). Most research suggests that all autism spectrum disorders have shared genetic mechanisms, but AS may have a stronger genetic component than autism. 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.

A few ASD cases have been linked to exposure to teratogens (agents that cause birth defects) during the first eight weeks from conception. Although this does not exclude the possibility that ASD can be initiated or affected later, it is strong evidence that it arises very early in development. Many environmental factors have been hypothesized to act after birth, but none has been confirmed by scientific investigation.

Mechanism

Asperger syndrome appears to result from developmental factors that affect many or all functional brain systems, as opposed to localized effects.] Although the specific underpinnings of AS or factors that distinguish it from other ASDs are unknown, and no clear pathology common to individuals with AS has emerged, it is still possible that AS's mechanism is separate from other ASD. Neuroanatomical studies and the associations with teratogens strongly suggest that the mechanism includes alteration of brain development soon after conception. Abnormal migration of embryonic cells during fetal development may affect the final structure and connectivity of the brain, resulting in alterations in the neural circuits that control thought and behaviour. Several theories of mechanism are available; none is likely to provide a complete explanation.

Functional magnetic resonance imaging provides some evidence for both under connectivity and mirror neuron theories. The under connectivity theory hypothesizes under functioning high-level neural connections and synchronization, along with an excess of low-level processes. It maps well to general-processing theories such as weak central coherence theory, which hypothesizes that a limited ability to see the big picture underlies the central disturbance in ASD. A related theory—enhanced perceptual functioning—focuses more on the superiority of locally oriented and perceptual operations in autistic individuals.

The mirror neuron system (MNS) theory hypothesises that alterations to the development of the MNS interfere with imitation and lead to Asperger's core feature of social impairment. For example, one study found that activation is delayed in the core circuit for imitation in individuals with AS. This theory maps well to social cognition theories like the theory of mind, which hypothesizes that autistic behaviour arises from impairments in ascribing mental states to oneself and others, or hyper-systemizing, which hypothesizes that autistic individuals can systematize internal operation to handle internal events but are less effective at empathizing by handling events generated by other agents.

Other possible mechanisms include serotonin dysfunction and cerebellar dysfunction.

Screening

Parents of children with Asperger syndrome can typically trace differences in their children's development to as early as 30 months of age. Developmental screening during a routine check-up by a general practitioner or paediatrician may identify signs that warrant further investigation. The diagnosis of AS is complicated by the use of several different screening instruments, including the Asperger Syndrome Diagnostic Scale (ASDS), Autism Spectrum Screening Questionnaire (ASSQ), Childhood Asperger Syndrome Test (CAST), Gilliam Asperger's Disorder Scale (GADS), Krug Asperger's Disorder Index (KADI), and the Autism Spectrum Quotient (AQ; with versions for children, adolescents and adults). None have been shown to reliably differentiate between AS and other ASDs.

Diagnosis

Standard diagnostic criteria require impairment in social interaction, and repetitive and stereotyped patterns of behaviour, activities and interests, without significant delay in language or cognitive development. Unlike the international standard,[8] U.S. criteria also require significant impairment in day-to-day functioning. Other sets of diagnostic criteria have been proposed by Szatmari et al.and by Gillberg and Gillberg.

Diagnosis is most commonly made between the ages of four and eleven. A comprehensive assessment involves a multidisciplinary team that observes across multiple settings, and includes neurological and genetic assessment as well as tests for cognition, psychomotor function, verbal and nonverbal strengths and weaknesses, style of learning, and skills for independent living. The current "gold standard" in diagnosing ASDs combines clinical judgment with the Autism Diagnostic Interview-Revised (ADI-R)—a semi structured parent interview—and the Autism Diagnostic Observation Schedule (ADOS)—a conversation and play-based interview with the child.[4] Delayed or mistaken diagnosis can be traumatic for individuals and families; for example, misdiagnosis can lead to medications that worsen behaviour. Many children with AS are initially misdiagnosed with attention-deficit hyperactivity disorder (ADHD). Diagnosing adults is more challenging, as standard diagnostic criteria are designed for children and the expression of AS changes with age; adult diagnosis requires painstaking clinical examination and thorough medical history gained from both the individual and other people who know the person, focusing on childhood behaviour. Conditions that must be considered in a differential diagnosis include other ASDs, the schizophrenia spectrum, ADHD, obsessive compulsive disorder, major depressive disorder, semantic pragmatic disorder, nonverbal learning disorder, Tourette syndrome, stereotypic movement disorder and bipolar disorder.

Under diagnosis and over diagnosis are problems in marginal cases. The cost of screening and diagnosis and the challenge of obtaining payment can inhibit or delay diagnosis. Conversely, the increasing popularity of drug treatment options and the expansion of benefits has motivated providers to over diagnose ASD. There are indications AS has been diagnosed more frequently in recent years, partly as a residual diagnosis for children of normal intelligence who do not have autism but have social difficulties. In 2006, it was reported to be the fastest-growing psychiatric diagnosis in Silicon Valley children; also, there is a predilection for adults to self-diagnose it. There are questions about the external validity of the AS diagnosis. That is, it is unclear whether there is a practical benefit in distinguishing AS from HFA and from PDD-NOS; the same child can receive different diagnoses depending on the screening tool. The debate about distinguishing AS from HFA is partly due to a tautological dilemma where disorders are defined based on severity of impairment, so that studies that appear to confirm differences based on severity are to be expected.