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 children with AS. 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 ASDs. 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 behavior. Several theories of mechanism are available; none are likely to provide a complete explanation.
The underconnectivity theory hypothesizes underfunctioning 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 hypothesizes 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 behavior 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.
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, the DSM-IV-TR criteria also required significant impairment in day-to-day functioning; DSM-5 eliminated AS as a separate diagnosis in 2013, and folded it into the umbrella of autism spectrum disorders. 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 "gold standard" in diagnosing ASDs combines clinical judgment with the Autism Diagnostic Interview-Revised (ADI-R)—a semistructured parent interview—and the Autism Diagnostic Observation Schedule (ADOS)—a conversation and play-based interview with the child. 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, bipolar disorder, and social-cognitive deficits due to brain damage from alcohol abuse.
Underdiagnosis and overdiagnosis are problems in marginal cases. The cost and difficulty of screening and assessment can 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 are not autistic but have social difficulties.
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.
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 pediatrician 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 Autism Spectrum Test (CAST) (previously called the Childhood Asperger Syndrome Test), 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.
Management
Asperger syndrome treatment attempts to manage distressing symptoms and to teach age-appropriate social, communication and vocational skills that are not naturally acquired during development, with intervention tailored to the needs of the individual based on multidisciplinary assessment. Although progress has been made, data supporting the efficacy of particular interventions are limited.
Therapies
The ideal treatment for AS coordinates therapies that address core symptoms of the disorder, including poor communication skills and obsessive or repetitive routines. While most professionals agree that the earlier the intervention, the better, there is no single best treatment package. 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. A typical program generally includes:
• An applied behavior analysis (ABA) technique called social skills training for more effective interpersonal interactions;
• Cognitive behavioral therapy to improve stress management relating to anxiety or explosive emotions and to cut back on obsessive interests and repetitive routines;
• Medication, for coexisting conditions such as major depressive disorder and anxiety disorder;
• Occupational or physical therapy to assist with poor sensory processing and motor coordination;
• Social communication intervention, which is specialized speech therapy to help with the pragmatics of the give and take of normal conversation;
• An ABA procedure known as positive behavior support includes training and support of parents and school faculty in behavior management strategies to use in the home and school.
Of the many studies on behavior-based early intervention programs, most are case reports of up to five participants and typically examine a few problem behaviors such as self-injury, aggression, noncompliance, stereotypies, or spontaneous language; unintended side effects are largely ignored. Despite the popularity of social skills training, its effectiveness is not firmly established. A randomized controlled study of a model for training parents in problem behaviors in their children with AS showed that parents attending a one-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. 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 can improve the work and life management of people with AS.
Medications
No medications directly treat the core symptoms of AS. Although research into the efficacy of pharmaceutical intervention for AS is limited, it is essential to diagnose and treat comorbid conditions. Deficits in self-identifying emotions or in observing effects of one's behavior on others can make it difficult for individuals with AS to see why medication may be appropriate. Medication can be effective in combination with behavioral interventions and environmental accommodations in treating comorbid symptoms such as anxiety disorder, major depressive disorder, inattention and aggression. The atypical antipsychotic medications risperidone and olanzapine have been shown to reduce the associated symptoms of AS; 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 restricted and repetitive interests and behaviors.
Care must be taken with medications, as side effects may be more common and harder to evaluate in individuals with AS, and tests of drugs' effectiveness against comorbid conditions routinely exclude individuals from the autism spectrum. Abnormalities in metabolism, cardiac conduction times, and an increased risk of type 2 diabetes have been raised as concerns with these medications, along with serious long-term neurological side effects. SSRIs can lead to manifestations of behavioral activation such as increased impulsivity, aggression, and sleep disturbance. 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 and increased serum prolactin levels. Sedation and weight gain are more common with olanzapine, which has also been linked with diabetes. Sedative side-effects in school-age children 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.
Prognosis
There is some evidence that children with AS may see a lessening of symptoms; up to 20% of children may no longer meet the diagnostic criteria as adults, although social and communication difficulties may persist. As of 2006, no studies addressing the long-term outcome of individuals with Asperger syndrome are available and there are no systematic long-term follow-up studies of children with AS. Individuals with AS appear to have normal life expectancy, but have an increased prevalence of comorbid psychiatric conditions, such as major depressive disorder and anxiety disorder that may significantly affect prognosis. Although social impairment may be lifelong, the outcome is generally more positive than with individuals with lower functioning autism spectrum disorders; for example, ASD symptoms are more likely to diminish with time in children with AS or HFA. Most students with AS/HFA have average mathematical ability and test slightly worse in mathematics than in general intelligence, but some are gifted in mathematics and AS has not prevented some adults from major accomplishments, such as Vernon L. Smith winning the Nobel Memorial Prize in Economic Sciences.
Although many attend regular education classes, some children with AS may utilize special education services because of their social and behavioral difficulties. Adolescents with AS may exhibit ongoing difficulty with self care or organization, and disturbances in social and romantic relationships. Despite high cognitive potential, most young adults with AS remain at home, yet some do marry and work independently.
The "different-ness" adolescents experience can be traumatic. Anxiety may stem from preoccupation over possible violations of routines and rituals, from being placed in a situation without a clear schedule or expectations, or from concern with failing in social encounters; the resulting stress may manifest as inattention, withdrawal, reliance on obsessions, hyperactivity, or aggressive or oppositional behavior. Depression is often the result of chronic frustration from repeated failure to engage others socially, and mood disorders requiring treatment may develop. Clinical experience suggests the rate of suicide may be higher among those with AS, but this has not been confirmed by systematic empirical studies.
Education of families is critical in developing strategies for understanding strengths and weaknesses; helping the family to cope improves outcomes in children. Prognosis may be improved by diagnosis at a younger age that allows for early interventions, while interventions in adulthood are valuable but less beneficial. 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.