Asperger Syndrome 

Updated: Feb 13, 2018
Author: James Robert Brasic, MA, MD, MPH, MS; Chief Editor: Caroly Pataki, MD 

Overview

Practice Essentials

Asperger syndrome is a term applied to a condition characterized by persistent impairment in social interactions and by repetitive behavior patterns and restricted interests. Once generally regarded as a discrete disorder, it is categorized as a form of autism spectrum disorder (ASD) in the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5).[1]

Signs and symptoms

In DSM-5, ASD encompasses the following 4 previously separate diagnoses[1] :

  • Autism

  • Asperger disorder

  • Childhood disintegrative disorder

  • Pervasive developmental disorder not otherwise specified

These are now considered forms of a single disorder characterized by different levels of severity in the following 2 core symptom areas, both of which are required for a diagnosis of ASD:

  • Impairments in social communication and social interaction

  • Restricted, repetitive patterns of behavior, interests, or activities

Individual clinical characteristics are denoted through the use of specifiers, as follows:

  • With or without accompanying intellectual impairment

  • With or without accompanying language impairment

  • Associated with a known medical or genetic condition or environmental factor

  • Associated with another neurodevelopmental, mental, or behavioral disorder

  • With catatonia[2, 3, 4, 58, 75]

By the current DSM-5 criteria, individuals previously diagnosed with Asperger syndrome would be diagnosed as having ASD without language or intellectual impairment.

The history is likely to elicit the following:

  • Social problems

  • Communication abnormalities

  • Speech and hearing abnormalities

  • Sensory sensitivity

Typical physical findings in children with Asperger syndrome may include the following:

  • Lax joints (eg, an immature or unusual grasp for handwriting and other fine hand movements)

  • Clumsiness

  • Anomalies of locomotion, balance, manual dexterity, handwriting, rapid movements, rhythm, and imitation of movements

  • Impaired ball-playing skills

Screening for a theory of mind can help identify some of the core behavioral symptoms of Asperger syndrome. Such screening has the following 2 main components:

  • Doll-play paradigm

  • Imagination task

See Presentation for more detail.

Diagnosis

Neuropsychological testing should focus on simple and complex problem-solving tasks, using tests and scales such as the following:

  • Wisconsin Card Sorting Test

  • Trail-Making Test

  • Stanford-Binet Scale

The Autism Screening Checklist (see the image below) is helpful in identifying children with characteristics of autism spectrum disorder (ASD) and in differentiating children with these disorders from children with schizophrenia and other psychoses.

Autism screening checklist. Autism screening checklist.

Magnetic resonance imaging (MRI) is not required for diagnosing Asperger syndrome but may demonstrate the following:

  • Hypoplasia of the inferior precentral gyrus and the anterior portion of the superior temporal gyrus, resulting in a widening of the sylvian fissure and a partial exposure of the insular cortex

  • Hypoplasia of the right temporo-occipital cortex

  • Small gyri of the posterior parietal lobes

  • Enlargement of the right lateral ventricle

  • Diminished size of the midbrain and medulla oblongata

Magnetic resonance spectroscopy (MRS) provides a tool to measure the concentration of chemicals in regions of interest (ROIs) of the brain. Several findings suggest an excitatory/inhibitory imbalance in Asperger syndrome.

Other tests that, though not required for diagnosis, may add useful information are as follows:

  • Event-related brain potential testing via electroencephalography (EEG)

  • Computed tomography (CT) of the head

Genetic tests that may be useful include the following:

  • Chromosomal microarray (CMA), or array comparative genomic hybridization (aCGH)

  • Karyotyping

  • Fragile X (FMR1 molecular studies)

  • Methylation studies

  • Methyl-CpG-binding protein (MECP2) analysis[5]

  • Phosphatase and tensin (PTEN) homolog testing[6]

  • Specific gene sequencing when a particular syndrome is suspected

See Workup for more detail.

Management

Treatment of people with Asperger syndrome consists primarily of instruction and counseling, focusing on the following areas:

  • Reinforcement of appropriate social behaviors[56]

  • Implementation of communication and language strategies[56]

  • Development of social skills[56]

  • Relaxation therapy[57]

  • Encouragement of special skills (eg, music or mathematics)

  • Career counseling and orientation

In addition, any comorbid conditions should be managed as appropriate, including the following:

  • Depression

  • Behavioral disorders

Drugs to treat the core characteristics of Asperger syndrome have not yet been identified. Pharmacologic interventions are used to treat comorbid disorders but should not be prescribed in the absence of an indication. Vigilance for drug toxicity must be maintained.

See Treatment for more detail.

Background

Asperger syndrome (also referred to as Asperger disorder) is a term applied to a form of autism spectrum disorder (ASD)[7, 1] It is characterized by persistent impairment in social interactions and by repetitive behavior patterns and restricted interests. Although in the past this syndrome was commonly considered a separate diagnosis, it is now subsumed under the diagnosis of ASD in the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5).[1]

Asperger syndrome is generally evident in children older than age 3 years and occurs most often in males. (See Etiology and Epidemiology.) Children with this syndrome typically exhibit a limited capacity for spontaneous social interactions, a failure to develop friendships, and a limited number of intense and highly focused interests.

People with Asperger syndrome may have certain communication problems, including poor nonverbal communication and pedantic speech, but many of them have good cognitive and verbal skills. Physical symptoms may include early childhood motor delays, clumsiness, fine motor difficulty, gait anomalies, and odd movements. (See Presentation.)

Standard early childhood development surveillance can identify some children who should receive further testing for Asperger syndrome. An ASD-specific tool should be used at 18 and 24 months.[8] In children with possible developmental issues, screening for a theory of mind (ie, determining whether these children have the ability to impute mental states to themselves and others) is an important process a clinician can use to identify some of the core behavioral symptoms of Asperger syndrome. (See Presentation.)

Individuals with Asperger syndrome have normal, or even superior, intelligence while demonstrating social insensitivity or even apparent indifference toward loved ones. Indeed, individuals with Asperger syndrome have accomplished cutting-edge research in computer science, mathematics, and physics, as well as outstanding creative work in art, film, and music. Many prominent individuals (eg, Albert Einstein) have demonstrated traits suggesting Asperger syndrome.

Additionally, some individuals with Asperger syndrome devote sustained daily concentration to the development of musical, mathematical, and other skills. This may facilitate the refinement of highly specialized tasks that would be beyond reach for many people without the syndrome.

Neuropsychological testing and event potential studies can be used to uncover characteristics of Asperger syndrome. Magnetic resonance imaging (MRI) and positron emission tomography (PET) can reveal brain anomalies associated with the condition. (See Workup.) None of these studies are required for diagnosis, but the results can help guide treatment planning.

If Asperger syndrome is diagnosed, social skills training and other psychological interventions may be provided. Although the deficits manifested by people with Asperger syndrome are often debilitating, many of these individuals experience positive outcomes, especially those who excel in areas not dependent on social interaction. (See Treatment.)

Since some people with Asperger syndrome exhibit acute awareness of environments and highly developed adaptive skills, they may escape detection in childhood. Thus, children, adolescents, and adults with Asperger syndrome may never be recognized as having Asperger syndrome. In particular, the ability of women with Asperger syndrome to conform with behavioral expectations of women may result in their integration into society without awareness of their condition. Thus, the reported male predominance in populations of people with Asperger disorder may reflect a high threshold to detect the condition in women. The stress of environmental changes and life events may cause adolescents and adults to seek diagnosis. An unknown number of adults with Asperger syndrome may be undiagnosed for their entire lives. There may exist many individuals with Asperger syndrome who are unaware of their condition.

Diagnostic criteria (DSM-5)

In DSM-5, the diagnosis of ASD encompasses the following 4 previously separate diagnoses[1] :

  • Autism

  • Asperger disorder

  • Childhood disintegrative disorder

  • Pervasive developmental disorder not otherwise specified

This change in nosology reflects a scientific consensus that these are not separate disorders but, rather, forms of a single disorder characterized by different levels of severity with respect to the following 2 core symptom areas, both of which are required for a diagnosis of ASD:

  • Impairments in social communication and social interaction, including all three of the following:

    • Deficits in social-emotional reciprocity

    • Deficits in developing and maintaining relationships

    • Deficits in nonverbal communicative behaviors in social interactions

  • Restricted, repetitive patterns of behavior, interests, or activities, including two or more of the following:

    • Repetitive movement or speech or use of objects

    • Insistence on sameness, unwavering adherence to routines, or ritualized patterns of behavior

    • Highly restricted, fixated interests with abnormal strength or focus

    • Increased or decreased response to sensory input

These symptoms are present from early childhood and limit or impair everyday functioning.

Individual clinical characteristics are denoted through the use of specifiers, as follows:

  • With or without accompanying intellectual impairment

  • With or without accompanying language impairment

  • Associated with a known medical or genetic condition or environmental factor

  • Associated with another neurodevelopmental, mental, or behavioral disorder

  • With catatonia[2, 3, 4, 58]

By the current DSM-5 criteria, individuals previously diagnosed with Asperger syndrome would be diagnosed as having ASD without language or intellectual impairment.[1]

Pathophysiology

In Asperger syndrome, the clinical manifestations presumably reflect alterations in brain development resulting from interactions between multiple genes, epigenetic factors affecting gene expression, and exposure to environmental factors.[9] Gaigg and Bowler hypothesized that impairments in the connections between the amygdala and associated structures of the brain may play a role in the pathogenesis of Asperger symptoms.[10]

People with Asperger syndrome demonstrate problems analyzing configurations. These deficits probably contribute to these individuals’ difficulty with facial recognition.[11] Bowler et al reported that people with Asperger syndrome have fewer memories than healthy control subjects do.[12]

Dyslipidemia may play a role in Asperger syndrome as well. Dziobek et al. reported elevations of total cholesterol and low-density lipoprotein in people with Asperger syndrome.[13]

Etiology

The etiology of Asperger syndrome is unknown. Some individuals with the syndrome have a history of complications in the prenatal and neonatal periods and during delivery,[14, 15, 16, 17, 18] but the relationship between obstetric complications and Asperger syndrome is unclear.[15, 16]

Unfavorable experiences in the prenatal, perinatal, and postnatal periods may increase the likelihood of Asperger syndrome.[14, 15, 16, 19, 20, 17, 18] In a Swedish study, adverse perinatal events were recorded for about two thirds of 100 males with Asperger syndrome, and the mothers experienced infection, vaginal hemorrhage, preeclampsia, and other adverse events during pregnancy at an above-average rate.[18] Whether the syndrome is a consequence or a cause of perinatal complications in such cases is unknown.

Studies have shown that there might be a link between disturbed metabolism of N-acetylaspartate and glutamine in cingulate and Asperger syndrome.[60]

Genetic factors

Reports of families with multiple members meeting the criteria for Asperger syndrome suggest a genetic contribution to development of the disorder. The past few years have seen a flood of research and insight into the underlying genetic contribution to Asperger syndrome, as well as to other forms of ASD. Hundreds of candidate genes and copy number variation (CNV) loci have been associated with ASD (see Genetics of Autism Spectrum Disorders).

The neurobiology and genetics are complicated.[21, 22] Genes involving the neuronal synaptic pathways are under particular investigation. Whereas most genome-wide association studies (GWAS) look at the entire range of ASD, some chromosomal regions have been associated specifically with Asperger syndrome, including 5q21.1, 3p14.2, 3q25, and 3p23.[23]  Also the maternal duplication at the 15q11-13 locus and the deletions or duplications at the 16p11 locus have been observed in 1% to 3% of patients with ASD.[61] It has been reported that reduced expression of α5GABAAreceptors can cause autism-like behavior in mice.[62] In general, more than 15% of all cases of ASD can be explained by genetic causes.[63]

Epidemiology

Because of the divergent diagnostic criteria used, estimates of the prevalence of Asperger syndrome vary widely.[24] In various studies from the United States and Canada, for example, reported rates have ranged from 1 case in 250 children to 1 case in 10,000. Additional epidemiologic studies are needed, using widely accepted criteria and a screening instrument that targets these criteria.

A population study in Sweden estimated the prevalence of Asperger syndrome as 1 case in 300 children.[25] This estimate is convincing for Sweden because complete medical records are available for all citizens in that country and the population is highly homogeneous. However, in other parts of the world, where neither of these factors may apply, prevalence may be quite different.

Like Sweden, other Scandinavian countries keep complete medical records for their populations and thus are uniquely suitable locations for conducting pristine epidemiologic studies. Comparable studies cannot always be readily carried out in other parts of the world. For example, in New York City, many inhabitants are immigrants, and it is not always possible to obtain health records from their country of origin.

To extrapolate from the Swedish study, Asperger syndrome may be more common than clinicians once thought. Pediatricians, family physicians, general practitioners, and other health professionals in North America may underdiagnose this disorder. Family members and friends may have a tendency to ascribe the signs of Asperger syndrome to individual idiosyncrasies.

Asperger syndrome has no apparent racial predilection. The estimated male-to-female ratio is approximately 4:1. However, investigations show that autism should not be considered a male condition; females have different biological characteristics in comparison with males with autism.[64, 65]

The syndrome is commonly diagnosed in the early school years and less frequently identified during early childhood or in adulthood. However, there may exist an unknown number of adults with excellent awareness and adaptation skills who are never diagnosed during their lifetimes. There may be a cohort of women with Asperger syndrome who conform with the behavioral expectations of society and are never diagnosed.

Prognosis

People with Asperger syndrome tend to have a better prognosis when they receive support from family members who are knowledgeable about the disorder. These individuals may be taught specific social guidelines, but the underlying social impairment is believed to be lifelong.

Individuals with Asperger syndrome appear to have a normal lifespan; however, they seem to endure an increased prevalence of comorbid psychiatric maladies (eg, depression, mood disorders, obsessive-compulsive disorder [OCD], and Tourette disorder). Comorbid psychiatric disorders, when present, significantly affect the prognosis.

Depression and hypomania are especially common among adolescents and adults with Asperger syndrome, particularly those with a family history of these conditions. (Caregivers of persons with Asperger syndrome may be prone to depression as well.)

An increased risk of suicide is observed in persons with this syndrome, with risks possibly rising in proportion to the number and severity of comorbid maladies. Asperger syndrome is probably undiagnosed in many suicide cases, both because the level of awareness of the condition is often low and because the tools used to identify it are often ineffective and unreliable. Consequently, people with Asperger syndrome who commit suicide are frequently reported as having other or undiagnosed psychiatric problems.

Patient Education

Individuals with Asperger syndrome and related conditions—as well as their families, teachers, and communities—can benefit from the experiences of other individuals with this disorder and from the experiences of their advocates. The following organizations provide information and advice to persons with Asperger syndrome and related conditions:

  • ASPEN (Asperger Syndrome Education Network, Inc), 9 Aspen Circle, Edison, NJ 08820; 732-321-0880; info@aspennj.org

  • Asperger Norfolk, Old Lion Cottage, Thurne, Great Yarmouth NR29 3AP, United Kingdom; +44 01 692 670 864

  • Polar Communications

  • Jessica Kingsley Publishers, 400 Market Street, Suite 400, Philadelphia, PA 19106; 866-416-1078 (toll-free ordering), 215-922-1161 (main), 215-922-1474 (fax); orders@jkp.com; 116 Pentonville Road, London N1 9JB, United Kingdom; +44 (0)20 7833 2307 (main), +44 (0)20 7837 2917 (fax); post@jkp.com

The organizations above may also be contacted for information about assessment and treatment facilities located near the patient. People with Asperger syndrome and their families benefit from intensive assessments and treatment interventions.

Several other resources have been recorded in a manual entitled A Parent’s Guide to Asperger Syndrome and High-Functioning Autism: How to Meet the Challenges and Help Your Child Thrive.[26] This excellent guide for lay people who encounter people with Asperger syndrome provides practical suggestions for day-to-day life.

People with developmental disabilities, including those with Asperger syndrome, are vulnerable to sexual abuse, and the most severely disabled are at the greatest risk. For this reason, parents and caregivers must be alert to avoid situations inviting sexual abuse. Additionally, children with Asperger syndrome must be trained to recognize impending sexual abuse and to develop plans of action for preventing it.[27]

For patient education information, see the Brain and Nervous System Center, as well as Asperger Syndrome.

 

Presentation

History

Parents should be interviewed about prenatal history and maternal health factors that may have affected the pregnancy. The clinician should conduct a thorough evaluation of social behaviors, language, interests, routines, physical coordination, and sensory sensitivity, starting from birth. The history is likely to elicit the following:

  • Social problems

  • Communication abnormalities

  • Speech and hearing abnormalities

  • Sensory sensitivity

Social problems

Children with Asperger syndrome may have difficulties with peer relations and may be rejected by other children. Adolescents with the syndrome commonly experience depression and loneliness.[19]

Outside the realm of immediate family members, an affected child may exhibit inappropriate attempts to initiate social interaction and to make friends. Whereas children with Asperger syndrome may have great anxiety about demonstrating genuine desires for friendship to peers, they may be taught by family members to express their love for their parents through multiple rehearsals over the years.

Alternatively, an affected child may not display affection to parents or other family members. A lack of bonding and warmth with parents and other guardians may seem apparent, typically resulting from the child’s lack of social skills.

Children with Asperger syndrome exhibit peculiar and narrow interests, excluding other activities. These interests may take precedence over their relationships with their family, school, and community.

Separations from parents because of work and divorce may be particularly stressful for these children. Changing homes, communities, and neighborhoods may also exacerbate anxiety, depression, and other psychological disturbances.

Individuals with Asperger syndrome may have particular difficulty with dating and marriage. Adolescents and men with Asperger syndrome may decide to marry suddenly, without the dating and courtship that typically precede a union. They may be unaware that friendship often precedes courtship and engagement; indeed, they may even approach strangers to propose marriage.

People with Asperger syndrome may appear aloof and uninterested in other people, in most cases probably as a result of perplexity about how to communicate appropriately with others. Individuals with this condition often find it difficult to interpret the responses of others and may find it equally challenging to determine how to make their own optimal responses in particular social situations.

Socially inappropriate behavior and failure to understand social cues may be reported. A child may not understand why people become upset when he or she breaks social rules. An adult may lose employment because his or her impaired comprehension of social norms leads to poor judgment in worksite behavior (eg, speaking inappropriately to colleagues, bosses, or administrators).

Communication abnormalities

Use of gestures is frequently limited in people with Asperger syndrome, and body language or nonverbal communication may be awkward and inappropriate. Facial expressions may be absent or inappropriate. Pragmatic errors are commonly produced by children with Asperger syndrome in response to questions. These children often produce irrelevant responses.[28]

Speech and hearing abnormalities

Children affected by Asperger syndrome demonstrate several abnormalities in speech and language, including pedantic speech and oddities in pitch, intonation, prosody, and rhythm. Miscomprehension of language nuance (eg, literal interpretations of figures of speech) is common.

Individuals often exhibit practical speech problems, including inability to use language in social contexts, insensitivity about interrupting others, and irrelevant commentary. Speech may be unusually formal or used in idiosyncratic ways that others do not understand. Individuals may vocalize their thoughts without censoring. Personal remarks inappropriate to most social environments may be uttered routinely.

The amount of speech may vary widely and may reflect the individual’s current emotional state more than the communication requirements of the social setting. Some individuals may be verbose, others taciturn. Furthermore, the same individual may demonstrate both verbosity and taciturnity at different times.

Some individuals may display selective mutism, speaking not at all to most people and excessively to specific people. Some may choose to talk only to people they like. Thus, speech may reflect the individual’s idiosyncratic interests and preferences.

The form of language chosen may include metaphors that are meaningful only to the speaker. The message meant by the speaker may not be understood by those who hear it, or the message may be meaningful only to a few people who understand the speaker’s private language.

Children often exhibit auditory discrimination and distortion, particularly when encountering 2 or more people speaking simultaneously.

Sensory sensitivity

Children with Asperger syndrome may show abnormal sensitivity to sound, touch, taste, sight, smell, pain, and temperature. For example, they may demonstrate either extreme or diminished sensitivity to pain. They may be particularly sensitive to the texture of foods. Children may also exhibit synesthesia, including a sensory response to an environmental stimulus in a different sensory modality.

Physical Examination

Typical physical findings in children with Asperger syndrome may include the following:

  • Lax joints (eg, an immature or unusual grasp for handwriting and other fine hand movements)

  • Clumsiness

  • Anomalies of locomotion, balance, manual dexterity, handwriting, rapid movements, rhythm, and imitation of movements

  • Impaired ball-playing skills

  • Macrocephaly (in approximately one fourth of children with isolated ASD[66] )

Screening

Only limited screening tools are available for Asperger syndrome, and no recommendations for universal screening have been formulated.[29] Nevertheless, early identification is crucial for intervention, and screening of children during healthcare maintenance visits is done in many clinics.

The American Academy of Pediatrics (AAP) recommends developmental surveillance for all children at 9, 18, and 24 or 30 months at preventive visits and additional screening for Asperger syndrome if any developmental concerns arise. An autism spectrum disorder (ASD)-specific tool should be used at 18 and 24 months.[8]

Of the tools designed for screening the elementary school–aged population, the Childhood Asperger Syndrome Test (CAST) for children aged 5-11 years has demonstrated good accuracy for use in large epidemiologic studies.[30, 31] At present, however, the evidence is insufficient to recommend it for routine screening. In addition, the AAP does not currently recommend universal screening of school-aged children with an ASD-specific tool.[32]

Screening for theory of mind

A theory of mind can be thought of as the ability to understand the mental processes of oneself and others, which allows one to predict other people’s responses to common situations. Accordingly, the lack of this understanding in a person with Asperger syndrome is termed a deficiency in the formation of a theory of mind.[33, 34, 35, 36, 37] Some people with Asperger syndrome appear never to develop a theory of mind.[38]

In children with possible developmental issues, screening for a theory of mind is an important process that a clinician can use to identify some of the core behavioral symptoms of Asperger syndrome. Typical children show evidence of having a theory of the mind before beginning school. Thus, inability of a school-aged child to perform any of the theory of mind screening procedures correctly suggests the need to refer the child for additional evaluation.

Screening for a theory of mind has 2 main components, a doll-play paradigm and an imagination task. It can be performed in offices and other everyday settings and takes only a few minutes.[39]

Doll-play paradigm

For the doll-play paradigm, the clinician and the patient are seated at opposite ends of a table. The clinician shows the patient 2 dolls and names them by saying, “This is Sally. This is Anne.”[40]

The doll-play paradigm involves 2 procedures. In the first, the clinician describes and shows Sally placing a marble in a basket, then removes Sally from the room and closes the door, leaving her outside. Next, the clinician describes and shows Anne removing the marble from the basket and placing it in a box. Finally, the clinician brings Sally back into the room and asks the patient, “Where will Sally look for the marble?”

An individual with a theory of mind will respond that Sally will look for the marble in the basket where she placed it before leaving the room. If this response is elicited, the child passes the doll-play paradigm, and the clinician may then proceed to the imagination task.

A response that Sally will look for the marble in the box signals that the child lacks a theory of mind. Such a response indicates that the patient cannot distinguish Sally’s mind from his or her own and thus does not recognize that Sally was absent and could not have known that the marble was moved from the basket into the box. The child assumes that because he or she knows that the marble is in the box, Sally must also know this.

If the patient does not reply that Sally will look for the marble in the basket, the clinician proceeds with questions to clarify the patient’s understanding of the situation. The clinician asks the patient, “Where is the marble, really?” Both typical and atypical patients usually state that the marble is in the box. The clinician then asks, “Where was the marble in the beginning?” Both typical and atypical patients usually state that the marble was originally in the basket.

In the second procedure, the clinician describes and shows Sally placing a marble in a basket, then removes Sally from the room and closes the door, leaving Sally outside. Next, the clinician describes and shows Anne removing the marble from the basket and placing it in the clinician’s pocket. Finally, the clinician brings Sally back into the room and asks the patient, “Where will Sally look for the marble?”

Typical patients with a theory of mind respond that Sally will look in the basket because that is where Sally last placed the marble. If this response is elicited, the patient passes the doll-play paradigm, and the clinician may proceed to the imagination task. If not, the clinician then asks the patient, “Where is the marble, really?” and “Where was the marble in the beginning?” to confirm the patient’s understanding of the situation.

Imagination task

The imagination task includes 3 parts. In the first, the clinician tells the patient, “Now, I want you to close your eyes and think about a big white teddy bear. Make a picture in your head of a big white teddy bear. Can you see the white teddy?”

A typical patient will report visualizing the image of a big white teddy bear. If the patient does not report visualizing this image, the clinician asks, “What can you see when you close your eyes?” If the patient reports any mental image, the clinician asks, “What are you thinking of?” A typical patient will readily report the visualization of a big white teddy bear.[41]

The next part of the task is a repetition of the first part, with the substitution of a big red balloon for the white teddy bear. A typical patient will readily report the visualization of a big red balloon.

In the third part of the imagination task, the clinician asks the patient to identify the first picture visualized during the task. A typical patient will readily report first imagining a big white teddy bear. Ability to remember an earlier mental image is evidence of a theory of mind; thus, inability to recognize one’s own prior mental images suggests the lack of a theory of mind. Accordingly, if the patient reports that a big red balloon was the first item imagined, this is evidence of a theory-of-mind deficit.

 

DDx

Diagnostic Considerations

Although normal language and cognitive development differentiate Asperger syndrome from other developmental disorders, the social impairment associated with this condition is also a characteristic of the following disorders:

  • Developmental learning disability of the right hemisphere

  • Nonverbal learning disability

  • Schizoid personality disorder

  • Schizotypal personality disorder

  • Semantic-pragmatic processing disorder

  • Social-emotional learning disabilities

The Autism Screening Checklist (see the image below) is helpful in identifying children with characteristics of autism spectrum disorder (ASD) and in differentiating children with these disorders from children with schizophrenia and other psychoses.

Autism screening checklist. Autism screening checklist.

A score of “yes” on items 1, 3, and 4 of the Autism Screening Checklist occurs in healthy children and in children with ASD (including Asperger syndrome). Some children with ASD demonstrate normal development for the first couple of years or so and then demonstrate a regression with loss of language skills.

Children with ASD may or may not speak; thus, they may score either “no” or “yes” on item 4. Children with Asperger syndrome develop speech at the usual age. They may display oddities of speech characteristic of ASD. A score of “yes” on items 2 and 11 occurs in healthy children, not in children with ASD (including Asperger syndrome and other pervasive developmental disorders).

A score of “no” on items 2 and 11 coupled with a score of “yes” on items 5, 6, 7, 8, 9, 10, 12, and 13 occurs in some children with ASD (including Asperger syndrome). The higher the score for “no” on items 2, 4, and 11 and for “yes” on items 5, 6, 7, 8, 9, 10, 12, and 13, the more likely the presence of ASD (including Asperger syndrome).

A score of “yes” on items 14, 15, 16, 17, 18, and 19 occurs in children with schizophrenia and other disorders but not in children with Asperger syndrome and other forms of ASD. A score of “no” on item 2 and “yes” on item 12 may occur in people with Asperger syndrome.

In making a differential diagnosis, it is important to consider comorbid movement disorders. Appropriate rating scales, when used regularly, help identify and differentiate among various movement disorders. (For more information on instruments for assessing movement in children with Asperger syndrome and related conditions, see Tardive Dyskinesia.)

In addition to the conditions listed in the differential diagnosis, other disorders to consider include the following:

  • Basic phonologic processing disorder

  • Catatonia[2, 3, 4, 58]

  • Dyslexia

  • Hearing impairment

  • Hyperlexia

  • Nonverbal learning disability

  • Personality disorder

  • Physical abuse

  • Pragmatic language disorder

  • Right cerebral hemisphere damage or dysfunction

  • Schizoid personality

  • Semantic-pragmatic processing disorder

  • Sensory integration disorder

  • Triple X syndrome

  • Endocrine disorders

  • Audiovisual disorders

  • Collagen disorders

Differential Diagnoses

 

Workup

Approach Considerations

Neuropsychological testing can be used to uncover characteristics of Asperger syndrome. Audiography is indicated to rule out auditory discrimination deficits. Magnetic resonance imaging (MRI) and positron emission tomography (PET) can reveal brain anomalies associated with the condition. Event-related brain potential testing with electroencephalography (EEG) may demonstrate errors in cortical auditory discrimination. Genetic testing may be helpful.

A neurologist should be consulted for examination and neuropsychological testing. Neuropsychological assessments should focus on simple and complex problem-solving tasks, using tests and scales such as the following:

  • Wisconsin Card Sorting Test

  • Trail-Making Test

  • Stanford-Binet Scale

Such diagnostic measures can demonstrate marked deficits in verbal and nonverbal functioning and intelligence level.

Magnetic Resonance Imaging

Although MRI is not required for diagnosing Asperger syndrome, it can be helpful for identifying cortical defects in the right-central perisylvian area and incomplete formation of the posterior-inferior frontal gyrus (ie, pars opercularis and pars triangularis). However, the results of MRI are inconsistent.

MRI may demonstrate the following:

  • Hypoplasia of the inferior precentral gyrus and the anterior portion of the superior temporal gyrus, resulting in a widening of the sylvian fissure and a partial exposure of the insular cortex

  • Hypoplasia of the right temporo-occipital cortex

  • Small gyri of the posterior parietal lobes

  • Enlargement of the right lateral ventricle

  • Diminished size of the midbrain and medulla oblongata

Functional MRI demonstrates that exposure to facial expressions of fear, disgust, happiness, and sadness yields less activation of the fusiform and extrastriate cortices in people with Asperger syndrome than in healthy, normal control subjects.[42] In response to fearful faces, people with Asperger syndrome demonstrate greater activation in the anterior cingulate gyrus and the superior temporal cortex, whereas control subjects demonstrate greater activation in the left amygdala and the left orbitofrontal cortex.[43]

Herrington et al reported less activity in the inferior, middle, and superior temporal regions in people with Asperger syndrome in response to a task typically interpreted as human movement.[44]

Magnetic Resonance Spectroscopy (MRS)

Magnetic resonance spectroscopy (MRS) provides a tool to measure the concentration of chemicals in regions of interest (ROIs) of the brain. Several findings suggest an excitatory/inhibitory imbalance in Asperger syndrome. In the anterior cingulate cortext of children with Asperger syndrome, reductions of N-acetylaspartate (NAA), total creatine (tCr), total choline-containing compounds (tCho), and myoinositol (ml) were observed in contrast to typically developing children.[67, 76]

Additionally, adults with Asperger syndrome demonstrated reduced NAA, glutamate, and glutamine in the bilateral pregenual anterior cingulate cortices and left cerebellum.[67, 60, 77]

Adolescents with Asperger syndrome demonstrated higher ratios of glutamate (Glu)/creatinine (Cr) and lower ratios of gamma-Aminobutyric acid (GABA)/Glu.[67, 78]

The hyperglutamatergic hypothesis of autism spectrum disorder is supported by the decreased ratio of glutamate and glutamine (Glx)/Cr in the putamen of children with Asperger syndrome.[67, 79, 80]

 

Positron Emission Tomography

Like MRI, PET is not required for diagnosing Asperger syndrome. In some individuals, PET reveals multiple deficits. On scanning with 2-deoxy-2-F-18-fluoro-D-glucose, the anterior rectal gyrus of some people with Asperger syndrome is larger on the left than on the right—the opposite of the asymmetry seen in most people. Other patients exhibit an increased glucose metabolic rate in the right posterior calcarine cortex and a decreased glucose metabolic rate in the left posterior putamen and left medial thalamus. (See PET Scanning in Autism Spectrum Disorders.[67] )

Event-Related Brain Potential Testing

Although not required for diagnosis, event-related brain potential testing (ie, electroencephalographic [EEG] measurement of brain responses to specific sensory, cognitive, or motor events) has identified errors in cortical auditory discrimination in people with Asperger syndrome. Mismatch negativity in event-related brain potentials demonstrates how well a person determines changes in sounds against the other sounds of the environment. People with Asperger syndrome are hypersensitive to changes in sounds.[13, 45]

Behaviorally, people with Asperger syndrome have been shown to process faces differently, and event-related potential studies have demonstrated this difference at a neurologic level. O'Connor et al found that in comparison with healthy control subjects, people with Asperger syndrome are slower to recognize faces.[46]

Computed Tomography

Computed tomography (CT) of the head cannot be used either to diagnose or to rule out Asperger syndrome, because no consistent CT findings are evident in people with this condition. Nevertheless, CT can be valuable for excluding treatable conditions in the differential diagnosis, such as neurologic disorders (eg, tumors). Analysis of head CT scans inconsistently reveals enlargement of the third ventricle and diminution of the caudate nucleus.

Genetic Testing

Patients with autism spectrum disorder (ASD), intellectual disability, or both may benefit from chromosomal microarray (CMA), or array comparative genomic hybridization (aCGH), testing to look for duplication or deletion of genomic material (otherwise known as copy number variants [CNVs] or genomic dosage anomalies).[47] Genetic testing is more likely to yield results if the patient has dysmorphic features or has a family history of fragile X syndrome.

Depending on the patient's clinical presentation, other recommended genetic tests may include any of the following:

  • Karyotyping

  • Fragile X (FMR1 molecular studies)[81]

  • Methylation studies

  • Methyl-CpG-binding protein (MECP2) analysis[5, 82]

  • Phosphatase and tensin (PTEN) homolog testing[6]

  • Specific gene sequencing when a particular syndrome is suspected

Advances in genetic testing have resulted in the development of next-generation sequencing panels that allow simultaneous analysis of as many as 62 genes associated with genetic syndromes that have autism or autistic features as part of their clinical profile. However, although microarray testing has provided many families with diagnoses, it cannot detect single point mutations in a gene.

 

Treatment

Approach Considerations

Treatment of people with Asperger syndrome consists of instruction and counseling to ameliorate the social disabilities that are features of the disorder, along with encouragement of special skills that can take advantage of these individuals’ capacity for narrowly focused and sustained concentration. Teachers provide an important resource for school-age children with Asperger syndrome.

For children and youths, specific interventions that may be provided include communication and language strategies and social skills training. For youths and adults, interventions may include relaxation training and career counseling and orientation.

Depression is a common comorbidity, and depressed patients may benefit from specific treatment. People with Asperger syndrome can also have other neuropsychiatric disorders, including Tourette syndrome, anorexia nervosa, and schizophrenia; treating such comorbid disorders may be beneficial.

Drugs to treat the core characteristics of Asperger syndrome have not yet been identified.[48, 49] Pharmacologic interventions are used to treat comorbid disorders, including attention problems and mood disorders (eg, dysthymia and bipolar disorder), but should not be prescribed in the absence of an indication. Regularly assessing the patient by administering the Psychoactive Medication Quality Assurance Rating Survey[50, 51, 52, 53, 54] helps determine the need for psychoactive medications. Vigilance for drug toxicity must be maintained.

Reinforcement of Appropriate Social Behaviors

Teachers have many opportunities to help children develop appropriate social behaviors. For instance, they can model socially appropriate behavior and encourage cooperative games in the classroom. They can explain appropriate means of seeking help when the child demonstrates problematic social behaviors in the classroom. They may identify suitable friends for children and encourage prospective friendships. They may also help children in challenging social situations by supervising breaks between classes and lunchroom and playground activities.

Children may benefit from a full-time, trained, 1-on-1 teacher’s aide. The aide can shadow the child in the classroom and coach appropriate behavior. Videotapes may facilitate self-monitoring of adherence to classroom rules.[55] Children can learn to watch other children for social cues and for behaviors to imitate. Because changes in schools, classrooms, and teachers may exacerbate symptoms, efforts should be made to minimize alterations to the patient’s schedule and educational environment.

There is some evidence that early intensive behavioral intervention benefits patients with austism spectrum disorders.[68] However, it has been specifically worked on due to positive prognosis.[69]

For complete information on these topics, see Pervasive Developmental Disorder and Autism Spectrum Disorder.

Implementation of Communication and Language Strategies

Children with Asperger syndrome can be taught to memorize phrases for specific purposes (eg, to open conversations). They can also learn to seek clarification by asking people to rephrase confusing expressions. They should be encouraged to ask that confusing instructions be repeated, simplified, clarified, and written down, as well as to admit, when appropriate, that they do not know an answer.

Caregivers, through modeling, can teach affected children how to interpret others’ conversational cues to reply, interrupt, or change topics. Because interpretation of metaphors and figures of speech is often difficult, caregivers should explain these language subtleties when they arise. When communicating a series of instructions to a child with Asperger syndrome, caregivers should pause between each separate statement.

Role-playing may help children with Asperger syndrome learn to understand the perspectives and thoughts of other people. Affected children should be encouraged to stop and think how another person will feel before acting or speaking. They can be taught to refrain from vocalizing every thought.

Some children with Asperger syndrome may have good visual thinking abilities. These children may be encouraged to visualize by using diagrams and visual analogues.

Additionally, participation in the activities of Toastmasters International may help individuals with asperger syndrome to develop outstanding abilities in communication and leadership.

Development of Social Skills

Children with Asperger syndrome may benefit from participation in an organized club, chaperoned by adult leaders who provide advance preparation and a discussion forum. Children, adolescents, and adults with Asperger syndrome typically benefit from a weekly, therapist-guided, social skills group that includes peers.[68] Auditory integration training helps some children with social interactions.

Parents can help children to learn appropriate play by modeling and rehearsing such skills as flexibility, cooperation, and sharing. Parents should encourage an affected child to invite a friend to their home. Only 6 hours of parent training, including group sessions, would benefit the child's social communicative behavior.[70, 71]

To assist people with Asperger syndrome in social encounters, it may be helpful to provide social skills training, including role modeling and role playing. Attwood described techniques for parents to use with children with Asperger syndrome.[56]

The ability to communicate with groups of people can be developed. Toastmasters International is an organization of local clubs that promote communication and leadership skills (eg, public speaking); these clubs are found around the world. Some individuals with Asperger syndrome may develop special skills, such as interpretive reading and storytelling, by participating in the activities of Toastmasters.

Psychotherapy can often help people with Asperger syndrome recognize their deficits in social skills. Group psychotherapy may facilitate the development of appropriate social skills. Individual psychotherapy may help the person with Asperger syndrome identify and address particular personal issues.

Overall emotionl recognition skills can be improved in children with ASD by proper interventions.[72, 73]

Relaxation Therapy

People with Asperger syndrome are frequently misunderstood by family, friends, neighbors, and the general public. They may encounter harsh, unreasonable criticism from teachers, parents, supervisors, and others. Such experiences, together with their difficulties in understanding social situations, may result in anxiety, panic attacks, and other psychological disturbances. Chronic stress may cause hypertension.

For coping with stress, the practice of relaxation techniques is often beneficial.[57] Additional effects of relaxation training may include lowering blood pressure and maintaining and improving health.

Relaxation constitutes a major effect of yoga and meditation. For some people, practices such as these have a religious aspect; however, Benson and Klipper showed that the crucial parts of a relaxation session have a purely physiologic basis, and they developed a compendium of the essential aspects of relaxation that are suitable for practice by the general public.[57] According to Benson and Klipper, the necessary features of relaxation training include the following:

  • Quiet environment

  • Mental device

  • Passive attitude

  • Comfortable position

To establish the desired environment, the person sets aside periods of 10–20 minutes for relaxation sessions twice a day, before breakfast and before dinner. He or she sits in a comfortable chair with eyes closed or open; lying down is not recommended, because sleep may result. Pagers and cell phones should be shut off, and internal and external stimuli should be shut out.

The mental device is a focusing aid that consists of the silent or spoken repetition of a sound, word, or passage. A nonsense syllable or a neutral word is suitable. Benson and Klipper suggest the repetition of the word “one.” This is equivalent to a mantra, such as is used in some meditation techniques. Attending to the pattern of breathing is also a mental device. Alternatively, the person may focus on a picture, image, symbol, or other visual stimulus as the item of attention.

During the session, thoughts are allowed to come and go. Whatever thoughts come should be disregarded. Attention is paid to the chosen mental device. The thoughts are passively allowed to enter awareness and are then passed from awareness. Perceptions are allowed to pass. At the end of the 20 minutes, gradual movement of the hands, feet, and body allow the individual to return to full alertness.

Acute anxiety may take the form of rapid respirations, rapid heartbeat, and a sense of impending doom. Acute relaxation training may relieve the panic to facilitate the ability to continue in the situation. Guided imagery can be provided by clinicians as well as family members, friends, and neighbors.

Encouragement of Special Skills

Individuals with Asperger syndrome can often concentrate on activities for hours without interruption and continue this concentration daily for years. For example, although many children might refuse to practice a musical instrument for even a few minutes a day, a child with Asperger syndrome may enjoy hours of daily practice.

With proper instruction, the talents of people with Asperger syndrome can be developed enormously. Accordingly, it is beneficial to identify and nurture their particular interests and abilities (eg, music or mathematics) at an early age. These talents may also help the child to earn respect from classmates.

Parents and teachers should take creative approaches to uncovering the skills, abilities, and talents of children with Asperger syndrome. Skilled instruction is necessary to develop such talents fully.

Career Counseling and Orientation

Career choice is especially crucial for persons with Asperger syndrome, in that social impairment limits their success in many occupations. Careers in technology, especially the Internet, are often particularly suitable for people with this syndrome. Computer science, engineering, and natural sciences are common career choices. Other special interests may be developed into careers.

Individuals may need special help to prepare for job interviews and to maintain an appropriate demeanor in a work environment. Otherwise, their impaired comprehension of social norms may lead to poor judgment in worksite behavior.

Management of Comorbid Conditions

Depression

Clinicians must be aware of the risk of depression associated with Asperger syndrome and institute prompt interventions when major depression occurs. Unlike other progressive mental disorders, depression typically resolves entirely without treatment; however, treatment likely hastens the onset of recovery.

Even with appropriate management, a person with depression may be convinced that he or she will never recover. This conviction may be a result of the temporary feeling of hopelessness common in depression. The belief that recovery is impossible may lead to suicide. Accordingly, the clinician must continually emphasize to the patient that the depression will probably resolve completely, explaining that sometimes people’s minds play tricks on them and that regardless of how things may seem, full recovery is the most likely outcome.

People who are depressed may need assistance with obtaining help from mental health professionals. If they are suicidal, their caregivers (or they themselves) can call emergency services (eg, 911) to ask for an ambulance for a person with a mental disorder. People who are a danger to themselves may be committed to a mental hospital for treatment to protect them from self-injury.

Behavioral disorders

Many pharmacologic agents (eg, antipsychotics, selective serotonin reuptake inhibitors [SSRIs], clonidine, and naltrexone) have been tried in attempts to improve some of the symptoms associated with Asperger syndrome and related conditions, such as stereotyped movements, self-injury, hyperactivity, and aggression.

Studies suggest that SSRIs help treat repetitive behaviors, impulsivity, irritability, and aggression. However, controlled clinical trials, based on well-diagnosed populations, are needed to confirm the impressions that SSRIs and atypical antipsychotic agents may alleviate core symptoms of Asperger syndrome and related conditions.

A randomized controlled trial found that the SSRI citalopram lacks efficacy in treating repetitive behavior in children diagnosed with autism spectrum disorder (ASD), including Asperger syndrome.[8] Specifically, citalopram did not significantly improve dimensional scores on repetitive behavior, scores on a parent-rated repetitive behavior scale, or the rate of positive global response in comparison with placebo.

Stimulants may be effective as adjunctive therapy for attention-deficit/hyperactivity disorder (ADHD) associated with Asperger syndrome. Patients with Asperger syndrome who have inattention and distractibility may respond to second-line agents for ADHD. Atomoxetine may be effective as adjunctive therapy for comorbid ADHD. Guanfacine has been used off label to reduce hyperactivity in children with Asperger syndrome.[22]

Activity

Patients should be observed walking and running. Adult patients may model appropriate motions to improve the coordination of their upper and lower extremities. Helping patients learn to catch and throw balls proficiently can facilitate their ability to participate in team sports and thereby enhance their social skills.

Wearing sunglasses and avoiding intense light may help children with Asperger syndrome who exhibit photosensitivity. Using earplugs may also help children who exhibit extreme intolerance or sensitivity to sound.

Remedial exercises may improve handwriting. Printing in block capital letters may also facilitate written communication. Alternatively, use of assistive technology (eg, a laptop computer) often helps.

Consultations

A neurologist should be consulted for examination and neuropsychological testing. Consultation with an otolaryngologist, an audiologist, and a speech pathologist is appropriate for excluding treatable auditory and vocal system anomalies. Speech testing helps assess children with developmental disabilities, and speech therapy is often helpful.

Consultation with physical and occupational therapists may be helpful; such therapy often improves the handwriting and other fine motor activities of patients with lax joints and unusual grasps. Sensory integration therapy reportedly helps some individuals.

Mindfulness

Mindfulness is a technique to relieve stress and to promote effective living. Mindfulness has been a component of martial arts and meditation.

Mindfulness in martial arts

Mindfulness has been a component of martial arts for centuries. Practitioners of martial arts learn to maintain a water face, a sense of calmness reflected in the unbroken surface of a pool. Practitioners of martial arts are also taught to develop a moon face, an awareness of every item surrounding the practitioner as if illuminated by the light of the moon. Awareness of surroundings are needed when walking outside in settings where assailants may appear from all sides. Practitioners of martial arts are also taught to develop mirror face, concentration on exactly the task at hand. Concentration is necessary to effectively and correctly execute the movements of martial arts.

Mindfulness-based stress reduction

People with Asperger syndrome can learn to apply this tool with beneficial results. Extensive training in mindfulness includes classes with regular homework. Individuals with Asperger syndrome may benefit from participating in organized classes, group meditations, and study of texts.[74] Mindfulness practice is based on seven principles as follows: non-judging, patience, beginner’s mind, trust, non-striving, acceptance, and letting go.[74] A key component to mindfulness is the regular practice of meditation and yoga exercises. A full discussion of mindfulness is beyond the scope of this article. Nevertheless, readers may benefit from practicing meditation for 20 minutes or so daily by performing simple breathing exercises. People with and without Asperger may benefit from practicing meditation with breathing for 20 minutes daily. If a person experiences pain or stress with the exercises, then by all means stop. The experience of meditation is not supposed to be harmful or upsetting.

With regular practice of meditation, individuals learn the techniques so that they can provide the cues for a meditation without the guidance of an instructor. While people are learning the techniques, listening to the instructions of a leader in person or on recording facilitates the performance of a meditation. For this reason we provide the text for the spoken instructions for a meditation to focus on the breathing. If the listener encounters increased anxiety or pain during the playing of the sound track, then the person should discontinue the practice with the tape. People who have negative experiences listening to the spoken meditation practice should seek consultation with an experienced teacher instead of practicing with the recorded meditation guidance.

 

Medication

Medication Summary

Drugs to cure the core characteristics of Asperger syndrome have not yet been identified. Pharmacologic interventions are used to treat comorbid disorders, including attention problems and mood disorders (eg, dysthymia, bipolar disorder). Such interventions should not be prescribed in the absence of an indication. Agents that may be considered include the following:

  • Second-generation antipsychotics

  • Selective serotonin reuptake inhibitors (SSRIs)

  • Other psychiatric medications (eg, atomoxetine and guanfacine)

Antipsychotics, 2nd Generation

Class Summary

Antipsychotic medications may help reduce aggressive behavior.

Risperidone (Risperdal, Risperdal Consta, Risperdal M-tab)

Risperidone is an atypical antipsychotic agent that is indicated for irritability associated with autistic spectrum disorder (ASD) in children and adolescents aged 5-16 years. It has high affinity for serotonin 5-HT2 receptors and binds to dopamine D2 receptors with 20 times lower affinity than that for 5-HT2 receptors. Risperidone alleviates negative symptoms of psychoses and has a lower incidence of extrapyramidal adverse effects than conventional antipsychotics do.

Paliperidone (Invega, Invega Sustenna)

Paliperidone is the major active metabolite of risperidone and was the first oral agent to allow once-daily dosing. Its mechanism of action not completely understood but is thought to involve mediation of central antagonism of dopamine D2 and serotonin 5HT-2A receptors. Paliperidone also elicits antagonist activity at adrenergic alpha1 and alpha2 receptors and histamine H1 receptors. Paliperidone is available in an osmotic delivery capsule.

Aripiprazole (Abilify, Abilify Discmelt)

The mechanism of action of aripiprazole is unknown but is hypothesized to differ from those of other antipsychotics. Aripiprazole is thought to be a partial dopamine D2 and serotonin 5-HT1A agonist and an antagonist of serotonin 5-HT2A. No QTc interval prolongation has been noted in clinical trials.

Selective Serotonin Reuptake Inhibitors

Class Summary

SSRIs may hasten recovery from depression in people with Asperger syndrome.

Fluvoxamine (Luvox CR)

Fluvoxamine elicits its effects through inhibition of neuronal uptake of serotonin in the central nervous system (CNS). It is indicated for the treatment of obsessive-compulsive behavior in children and adolescents aged 8-17 years. Gender differences should be considered in pediatric patients; therapeutic effects may be achieved at lower doses in girls.

Fluoxetine (Prozac)

The mechanism of action of fluoxetine involves inhibition of CNS neuronal uptake of serotonin, with minimal reuptake of norepinephrine or dopamine.

Sertraline (Zoloft)

The mechanism of action of sertraline is linked to inhibition of CNS neuronal uptake of serotonin, with very weak effects on norepinephrine and dopamine neuronal reuptake.

Paroxetine (Paxil, Pexeva)

Paroxetine is a potent selective inhibitor of neuronal serotonin reuptake. It also has a weak effect on norepinephrine and dopamine neuronal reuptake. For maintenance, the dosing should be adjusted so as to maintain the patient on the lowest effective dosage, and the patient should be periodically reassessed to determine the need for continued treatment.

Citalopram (Celexa)

Citalopram enhances serotonin activity through selective reuptake inhibition at the neuronal membrane. No head-to-head comparisons of SSRIs have been done; however, on the basis of metabolism and adverse effects, citalopram is considered the SSRI of choice for patients with head injury.

Escitalopram (Lexapro)

Escitalopram is an SSRI and an S-enantiomer of citalopram. It is used for the treatment of depression. Its mechanism of action is thought to be potentiation of serotonergic activity in the CNS, resulting from inhibition of CNS neuronal reuptake of serotonin. The onset of depression relief may be obtained after 1-2 weeks—sooner than is possible with other antidepressants.

Psychiatric Agents, Other

Class Summary

Patients with Asperger syndrome who have inattention and distractibility may respond to second-line agents for attention-deficit/hyperactivity disorder (ADHD).

Atomoxetine (Strattera)

Atomoxetine is a selective norepinephrine reuptake inhibitor (SNRI). It is not a stimulant but may be effective as adjunctive therapy for the comorbid ADHD associated with Asperger syndrome.

Guanfacine (Intuniv, Tenex)

Guanfacine, an alpha2 agonist, may preferentially bind postsynaptic alpha2A adrenoreceptors in the prefrontal cortex, and this preferential binding may improve delay-related firing of prefrontal cortex neurons. As a result, guanfacine may affect behavioral inhibition. It has been used off label to reduce hyperactivity in children with Asperger syndrome.