eMedicine Specialties > Pediatrics: Developmental and Behavioral > Medical Topics

Autism

James Robert Brasic, MD, MPH, Research Associate, Division of Nuclear Medicine, Russell H Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine

Updated: Jul 13, 2009

Introduction

Background

Autism is a condition that manifests in early childhood and is characterized by qualitative abnormalities in social interactions, marked aberrant communication skills, and restricted repetitive and stereotyped behaviors.

Most individuals with autism also manifest mental retardation, typically moderate mental retardation with intelligence quotients (IQs) of 35-50 (approximate numbers). Although often difficult to evaluate with intelligence tests, three fourths of children with autism function in the mentally retarded range. Generally, the lower the IQ, the greater the likelihood of autism. However, the low functioning level hinders assessment for key characteristics of autism in individuals with profound mental retardation and IQs below approximately 20. Thus, diagnostic instruments for autism may give spurious results in children with profound mental retardation.

The diagnosis of autism in a child with profound mental retardation requires an experienced clinician. This article addresses the problems of individuals with mental retardation. For information concerning individuals with autism spectrum disorders and related conditions without mental retardation, please see Pervasive Developmental Disorder: Asperger Syndrome.

Seizure disorders are common in individuals with autism. Movement abnormalities are a prominent feature in a subset of individuals. Motion anomalies have been reported at birth in some individuals. Motion analysis may provide evidence of autism in early infancy before other manifestations occur. Although autistic disorder was initially reported in children of high social class, subsequent research has established that autistic disorder equally afflicts all social classes.

The motion anomalies demonstrated by children with autism are often highly characteristic. Children with autism who exhibit motion anomalies often stand out as odd in crowds because of the motions. An example of a motion typical in autism occurs when the child places a hand with fingers separately outstretched before the eyes and rapidly moves the hand back and forth. This action is described as self-stimulation because it produces a visual sensation of movement. Many of the motions of children with autism appear to be attempts to provide sensory input to themselves in a barren environment. Through special education, children may learn not to perform movements. The movements may then be exhibited at times of particular stress or excitement.

Although the etiology is unknown, hypotheses include genetic abnormalities; obstetric complications; exposure to toxic agents; and prenatal, perinatal, and postnatal infections. Maternal rubella is associated with significantly higher rates of autism and other conditions in children. Additionally, tuberous sclerosis is associated with autism as a comorbid disorder. On the other hand, anecdotal reports that autism may be linked with vaccinations for measles, mumps, and rubella have not been confirmed. Approximately 10% of children with a pervasive developmental disorder exhibit a known medical condition.

Effective treatment of associated behavioral problems includes intensive behavioral, educational, and psychological components. Interventions initiated at the time of diagnosis increase the likelihood of a favorable outcome. Regular screening of infants and toddlers for symptoms and signs of autistic disorder is crucial because it allows for early referral of patients for further evaluation and treatment.

Although psychoanalytic approaches to treatment of children with autism were common in the mid-20th century, these approaches were not found to be effective and are no longer used. The initial clinical descriptions of autism suggested that cold, rejecting parents ("refrigerator mothers") caused autism in offspring; however, careful study of children with autism and their parents has disproved this hypothesis. Autism is not caused by a lack of warmth and affection in parents. Autism is not due to any emotional or psychological deficits in the parents. Blaming parents for the development of autism in their children is inappropriate.

A major problem in the public health of children with autism and other pervasive developmental disorders is the inconsistent diagnosis of autism. Criteria for the diagnosis of autism are included in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR[TM]) and the International Classification of Diseases, Ninth Revision, Clinical Modification, Fourth Edition.1,2 Although the criteria for autism and other pervasive developmental disorders differ between the DSM-IV-TR(TM) and the ICD-9-CM, they are both widely accepted and are used around the world by clinicians and researchers.

A discussion of the differences in the criteria for autism and related conditions in the DSM-IV-TR(TM) and the ICD-9-CM and other nomenclatures is beyond the scope of this article. The key point for pediatricians and other clinicians is that the criteria for autism and related conditions in the DSM-IV-TR(TM) and the ICD-9-CM are presented in an outline form without a discussion of the terms used.

The DSM-IV-TR(TM) and the ICD-9-CM are poor textbooks of child development and child psychopathology; they do not fully describe the concepts incorporated in the criteria for autism and related conditions. Therefore, an inexperienced clinician is likely to incorrectly apply the criteria for autism and related conditions in the DSM-IV-TR(TM) and the ICD-9-CM.

Several instruments have been developed to diagnose autism and other pervasive developmental disorders. To administer tools for the diagnosis of autism and related conditions in a reliable and valid manner, extensive training and experience is needed. Therefore, unless they have vast experience with children with autism and understand the concepts implicit in the diagnostic criteria and rating scales, pediatricians and other clinicians are advised to refer patients with possible autism to experienced clinicians for definitive diagnostic evaluations. One goal of this article is to convey fundamental concepts related to autism and related conditions. Readers of this article must obtain considerable additional training before they can reliably and validly apply diagnostic criteria and rating tools.

Pharmacotherapy is ineffective in treating the core deficits of autism but may be effective in treating associated behavioral problems and comorbid disorders. The possible benefits from pharmacotherapy must be balanced against the likely adverse effects on a case-by-case basis.

Pathophysiology

Neuroanatomic and neuroimaging studies reveal abnormalities of cellular configurations in several regions of the brain, including the frontal and temporal lobes and the cerebellum. Enlargements of the amygdala and the hippocampus are common in childhood. Findings vary in each person. Hughes (2007) has observed the presence of underconnectivity in the brains of children with autism and related conditions.3 This finding provides a basis for further investigation of autism and other pervasive developmental disorders.

Abnormalities in affiliative behaviors of other species, which are associated with dysfunction of serotonin and the neuropeptides, oxytocin, and vasopressin, suggest that there may be a neurophysiological dysfunction involving one or more of these substances in autism in humans.

Elevations of whole blood serotonin occur in one third of patients. Increased levels are also reported in the parents and siblings of patients. Individuals with autistic disorder and their mothers show elevated levels of C-terminally directed beta-endorphin protein immunoreactivity. The basis and importance of these findings is unknown. Test findings suggest that low-functioning children with autism may have impairment in the metabolism of phenolic amines. Therefore, symptoms of autistic disorder are possibly aggravated by the consumption of dairy products, chocolates, corn, sugar, apples, and bananas; however, no large population studies have confirmed this.

Many individuals with autism and related conditions experienced untoward events in the prenatal and neonatal periods and during delivery. The possible role of obstetric complications in the pathogenesis of autism and related conditions is unclear. Brasic and Holland (2006, 2007) and Brasic and colleagues (2003) have reviewed the literature on autism and obstetric complications.4,5,6 In particular Roberts and colleagues (2007) and Samson (2007) have reported an association between exposure to dicofol and endosulfan, organochlorine pesticides, in the first trimester of pregnancy in the Central Valley of California and the subsequent development of autism spectrum disorders in the child.7,8 Potential mothers can wisely be advised to avoid exposure to organochlorine pesticides.

Some children developed autism after immunizations, including inoculations for measles, mumps, and rubella. However, several population studies have demonstrated no association between childhood immunization and the development of autism and related conditions.9 Thompson and colleagues (2007) detected no causal association between exposure to vaccines that contain thimerosal and neuropsychological deficits at age 7-10 years.10 Parents can administer the recommended childhood immunizations without fear of causing autism and related conditions.11

Many other hypotheses, such as the consumption of folic acid in pregnancy, have been proposed as possible causes of autism. None has been established as a definite etiology of autism.

Frequency

United States

Autistic disorder and related conditions affect up to 10-20 individuals per 10,000 population. Estimates of the prevalence of autism suggest that as many as 400,000 individuals in the United States have autism and related conditions. Autism spectrum disorder is one of the most common childhood developmental disabilities. Current epidemiological studies are needed to identify the incidence, prevalence, and distribution of autistic disorder in the United States.

Epidemiological studies of relatively uncommon conditions such as autism spectrum disorders are expensive. A suitable strategy is the performance of multiple screenings on a population, each time identifying more likely subjects for detailed investigation. For example, a checklist such as the Autism Screening Checklist can be distributed to all parents and guardians of a target population. The Autism Screening Checklist identifies those children with characteristics of autism spectrum disorders. It differentiates children with autism spectrum disorders from children with schizophrenia and other psychoses. The higher the score on the Autism Screening Checklist (see Media file 1 for a printable version), the more likely the presence of autism spectrum disorders.

Autism screening checklist.

Autism screening checklist.


International

Autistic disorder and related conditions affect up to 10-15 people per 10,000 population. Studies in Japan report much higher rates.12 Japanese investigators suggest that these findings reflect the careful evaluations performed by Japanese clinicians. Some studies suggest that infectious diseases that are prevalent in parts of Japan may account for higher rates of autistic disorder. Epidemiologic studies are needed to assess the current incidence, prevalence, and distribution of autistic disorder throughout the world. These studies may help focus on causality.

Mortality/Morbidity

The long-term outcome for individuals with autistic disorder is directly proportional to the IQ of individuals. In other words, individuals with autistic disorder and intellectual limitations have poorer outcomes. Individuals with autistic disorder and profound mental retardation may require constant care in a residential treatment facility.

Race

Japanese studies often indicate the more common occurrence of autism in Japan than in other countries.12 The high rates of autism reported in many Japanese studies may reflect higher incidence and prevalence in Japan. Alternatively, because Japanese clinicians are highly skilled to diagnose autism, they may identify cases that are overlooked in other countries. Some studies suggest that some cases of autism in Japan result from GI infections and other infections due to the ingestion of seafood and other aquatic sources of food characteristic of Japan.

Sex

  • The male-to-female ratio is 3-4:1.
  • Autistic disorder is most common in boys who have the 46,XY karyotype (ie, the karyotype of healthy normal boys). In some studies, fragile X is reported in approximately one tenth of males with autistic disorder.13,14,15,16,17,18

Age

  • Autistic disorder manifests in early childhood. Using contemporary criteria, the absence of abnormalities in the first 30 months of life rules out autistic disorder. For information about individuals with later onset of symptoms consistent with autistic disorder, see Pervasive Developmental Disorder: Childhood Disintegration Disorder, Pervasive Developmental Disorder: Rett Syndrome, Pervasive Developmental Disorder: Asperger Syndrome, and Pervasive Developmental Disorder (not otherwise specified).
  • Many parents report normal development in their child until age 2 years before noticing the deficits in social and communicative skills.
  • Individuals with autism spectrum disorder and unspecified pervasive developmental disorder typically benefit from behaviorally oriented therapeutic programs developed specifically for people with autistic disorder. Therefore, children who manifest symptoms of autistic disorder, other pervasive developmental disorders, and other autism spectrum disorders are likely to benefit from the highly specialized intensive intervention programs designed for children with these disorders.
  • Because optimal results occur when intensive interventions are administered early in childhood, autistic children should be placed in specialized programs as soon as the diagnosis is entertained. Delays in placement of a young child in a specialized program for children with autistic disorder may reduce the effectiveness of those interventions. Parents, pediatricians, other health care providers, and educators are advised to seek the assistance of people who are familiar with early intervention programs for children with autistic disorder. The Autism Society of America can help parents obtain appropriate referrals for optimal interventions.

Clinical

History

  • Environmental exposures: Roberts and colleagues (2007) and Samson (2007) have reported that women in the Central Valley of California who were exposed to endosulfan and dicofol, organochlorine pesticides, during the first trimester of pregnancy were more likely to have children with autism spectrum disorders.7,8  Thus, obstetricians and other health workers can wisely advise women who are likely to become pregnant to avoid contact with pesticides and other environmental contaminants.
  • Protodeclarative pointing
    • Protodeclarative pointing is the use of the index finger to indicate an item of interest to another person. Toddlers typically learn to use protodeclarative pointing to communicate their concern for an object to others.
    • The absence of protodeclarative pointing is predictive of the later diagnosis of autism. The presence of protodeclarative pointing can be assessed by interview of the parent or caregiver. As a screening question, Baron-Cohen and colleagues (1992, 1996) have demonstrated that the absence of a positive response to an inquiry about protodeclarative pointing is predictive of the later diagnosis of autism.19,20 Screening questions include "Does your child ever use his or her index finger to point, to indicate interest in something?" The absence of a positive response to this question suggests the need for a specialized assessment for possible pervasive developmental disorder.
  • Environmental stimuli
    • Parents report unusual responses to environmental stimuli, including excessive reaction or an unexpected lack of reaction to sensory input.
    • Sounds, such as vacuum cleaners or motorcycles, may elicit incessant screaming from a child with autistic disorder. Playing a radio, phonograph, or television at a loud level may appear to produce auditory stimulation of a painful magnitude. Sometimes parents must rearrange the family routine so that the child is absent during noisy housekeeping activities.
    • Children with autistic disorder may also display exaggerated responses or rage to everyday sensory stimuli, such as bright lights or touching.
  • Social interactions
    • Separation from parents may elicit a lack of appropriate eye contact and other symptoms that are typically seen in individuals with autism. Media files 5-6 illustrate the apparent indifference of a boy with autistic disorder to the departure and return of his father and his brother.

      The examiner may attempt to establish a sequence of taking turns hitting a plate with a block. The examiner says, "My turn," and then taps the plate. The examiner gives the block to the subject and says, "Your turn." The subject may be physically assisted in the activity if the desired response does not occur.

      The following is a clinical example: A 7-year-old boy with autistic disorder took daily vitamins and no other medications at the time of assessment. The examiner attempted to elicit turn-taking by hitting the plate with a block. The child repeatedly jumps and rotates. He exhibits nonfunctional play with the telephone. He tilts his head and peers out of the corner of his eye. He is interested in the feel of the stick. He exhibits quick hand movements with small toys.

      When his father and his brother leave the room, the child does not acknowledge their departure. When his father returns to the room, he does not run to greet him. He appears indifferent to the departure and the return of his father. He repeatedly touches the surface of the wooden block. He touches the surface of a furlike cloth. He also places this cloth to his mouth to feel the texture on his lips. He is also fascinated with a string of yarn. He moves the string of yarn up and down and back and forth. This is nonfunctional play with ordinary items.

      Video available at http://img.medscape.com/pi/emed/ckb/pediatrics_development/912185-912186-912781-912884.flv.




      The following is a clinical example that continues the segment of Image 5: A 7-year-old boy with autistic disorder took daily vitamins and no other medications at the time of assessment. He appears indifferent to the departure of his brother from the room. He also does not respond with a greeting when his brother returns. He appears interested in his nonfunctional play. He displays minimal acknowledgment of the departure and return of his brother. In particular, he does not respond to his brother's touching him on the shoulder to greet him.

      Instead, he demonstrates inappropriate friendliness with the psychologist who is evaluating the procedures. Although he never saw her before this assessment, he suddenly goes to her to kiss her.

      Video available at http://img.medscape.com/pi/emed/ckb/pediatrics_development/912185-912186-912781-912885.flv.


    • An absence of typical responses to pain and physical injury may also be noted. Rather than crying and running to a parent when cut or bruised, the child may display no change in behavior. Sometimes, parents do not realize that a child with autistic disorder is hurt until they observe the lesion. Parents frequently report that they need to ask the child if something is wrong when a change in the child's mood occurs. When injured, a child may not run to the parent to seek help. The parent may need to examine the surface of the child's body to detect the injury.
    • Difficulties in social interactions are common. Children may have problems making friends and understanding the social intentions of other children. Instead, they may show attachments to objects not normally predicted to be child oriented. Although children with autistic disorder may want to have friendships with other children, their actions may actually drive away other children.
  • Communication: Speech abnormalities are common. They take the form of language delays and deviations. Pronominal reversals are common, including saying "you" instead of "I."
  • Play
    • Baron-Cohen and colleagues (1992, 1996) have demonstrated that the absence of symbolic play in infants and toddlers is highly predictive of the later diagnosis of autism.19,20 Therefore, screening for the presence of symbolic play is a key component of the routine assessment of well babies. The absence of normal pretend play indicates the need for referral of specialized developmental assessment for autism and other developmental disabilities.
    • Odd play may take the form of interest in parts of objects instead of functional uses of the whole object. For example, a child with autistic disorder may enjoy repeatedly spinning a wheel of a car instead of moving the entire car on the ground in a functional manner. The nonfunctional play of a boy with autism is illustrated in Media files 4-6.

      A 7-year-old boy with autistic disorder took daily vitamins and no other medications at the time of assessment. The examiner repeated movements of the telephone receiver and tapping on the telephone receiver initially exhibited by the subject. The examiner repeated the subject's actions several times in an attempt to elicit repetition of the movement by the subject. Instead, the subject does not acknowledge the presence of the examiner. He looks away from the examiner. He turns his back to the examiner. The subject spins by rotating on a central vertical axis in his body. He exhibits nonfunctional play with the telephone. He displays frequent finger wiggling and the other hand stereotypies. He frequently vocalizes indecipherable sounds and briefly rocks. He tilts his head and looks out of the corner of his eye for a few seconds.

      Video available at http://img.medscape.com/pi/emed/ckb/pediatrics_development/912185-912186-912781-912883.flv.




      The examiner may attempt to establish a sequence of taking turns hitting a plate with a block. The examiner says, "My turn," and then taps the plate. The examiner gives the block to the subject and says, "Your turn." The subject may be physically assisted in the activity if the desired response does not occur.

      The following is a clinical example: A 7-year-old boy with autistic disorder took daily vitamins and no other medications at the time of assessment. The examiner attempted to elicit turn-taking by hitting the plate with a block. The child repeatedly jumps and rotates. He exhibits nonfunctional play with the telephone. He tilts his head and peers out of the corner of his eye. He is interested in the feel of the stick. He exhibits quick hand movements with small toys.

      When his father and his brother leave the room, the child does not acknowledge their departure. When his father returns to the room, he does not run to greet him. He appears indifferent to the departure and the return of his father. He repeatedly touches the surface of the wooden block. He touches the surface of a furlike cloth. He also places this cloth to his mouth to feel the texture on his lips. He is also fascinated with a string of yarn. He moves the string of yarn up and down and back and forth. This is nonfunctional play with ordinary items.

      Video available at http://img.medscape.com/pi/emed/ckb/pediatrics_development/912185-912186-912781-912884.flv.




      The following is a clinical example that continues the segment of Image 5: A 7-year-old boy with autistic disorder took daily vitamins and no other medications at the time of assessment. He appears indifferent to the departure of his brother from the room. He also does not respond with a greeting when his brother returns. He appears interested in his nonfunctional play. He displays minimal acknowledgment of the departure and return of his brother. In particular, he does not respond to his brother's touching him on the shoulder to greet him.

      Instead, he demonstrates inappropriate friendliness with the psychologist who is evaluating the procedures. Although he never saw her before this assessment, he suddenly goes to her to kiss her.

      Video available at http://img.medscape.com/pi/emed/ckb/pediatrics_development/912185-912186-912781-912885.flv.


    • Children with autistic disorder may enjoy repeatedly lining up or dropping objects from a particular height.
    • Children may be fascinated with items that are not typical toys, such as pieces of string. Media file 5 illustrates the fascination of a boy with autism with a string of yarn. They may enjoy hoarding rubber bands, paper clips, and pieces of paper. They may spend hours watching traffic lights, fans, and running water.

      The examiner may attempt to establish a sequence of taking turns hitting a plate with a block. The examiner says, "My turn," and then taps the plate. The examiner gives the block to the subject and says, "Your turn." The subject may be physically assisted in the activity if the desired response does not occur.

      The following is a clinical example: A 7-year-old boy with autistic disorder took daily vitamins and no other medications at the time of assessment. The examiner attempted to elicit turn-taking by hitting the plate with a block. The child repeatedly jumps and rotates. He exhibits nonfunctional play with the telephone. He tilts his head and peers out of the corner of his eye. He is interested in the feel of the stick. He exhibits quick hand movements with small toys.

      When his father and his brother leave the room, the child does not acknowledge their departure. When his father returns to the room, he does not run to greet him. He appears indifferent to the departure and the return of his father. He repeatedly touches the surface of the wooden block. He touches the surface of a furlike cloth. He also places this cloth to his mouth to feel the texture on his lips. He is also fascinated with a string of yarn. He moves the string of yarn up and down and back and forth. This is nonfunctional play with ordinary items.

      Video available at http://img.medscape.com/pi/emed/ckb/pediatrics_development/912185-912186-912781-912884.flv.


    • Some parents report that they must lock the bathroom door to prevent a child from flushing the toilet all day long.
  • Response to febrile illnesses
    • Children with autistic disorder may show a decrease in their odd behaviors during a febrile illness. Parents may report that when their autistic child has a fever, the child's behavior appears to be improved. Parents may say, "When he is suddenly an angel, I know that he has an ear infection." Some behavioral abnormalities that plague the parents when their autistic child is well, such as self-injurious behaviors, aggression toward others, property destruction, temper tantrums, and hyperactivity, may diminish and resolve temporarily during a febrile illness. Children who typically display uncontrollable behavior at school and at home may seem more manageable and obedient.
    • This inhibition of negative behaviors may occur with various febrile illnesses, including ear infections, upper respiratory tract infections, and childhood illnesses. The recovery of the child from the febrile illness may be accompanied by an abrupt return of the child's usual problem behaviors.

Physical

Screening well babies for signs predictive of autistic disorder is important. Baron-Cohen and colleagues (1992, 1996) observed that abnormalities in gaze monitoring, protodeclarative pointing, and pretend play noted in toddlers during well child visits in the United Kingdom was useful in predicting the later diagnosis of autistic disorder.19,20 Baron-Cohen and colleagues (1992, 1996) developed the Checklist for Autism in Toddlers (CHAT) to screen newborns and toddlers to rule out autism.19,20

  • CHAT screening
    • Although the CHAT has been reported to identify infants and toddlers in Britain who develop autism, the reliability and the validity of the CHAT have not been confirmed by other investigators with other populations. In particular, an item on the CHAT about pretending to pour tea from a toy teapot into a toy teacup is not likely to be meaningful to minority North American children because the cultural connotations may not be relevant to children outside the United Kingdom. However, a tea party with toy teacups and a toy teapot involves symbolic play. Because children with autism spectrum disorders may be unable to engage in symbolic play as other children, an item to assess the ability to participate in a tea party is useful in cultures in which a tea party is widely understood. The possible cultural biases of the CHAT limit its usefulness outside the United Kingdom. For this reason, direct application of the full CHAT is not recommended. Additionally, the specificity and sensitivity of the CHAT remain tobe ascertained in various cultures.
    • The items of the CHAT that are highly correlated with the diagnosis of autistic disorder are recommended. This discussion is limited to those items. Instead of asking the child to pretend to pour tea from a toy teapot into a toy teacup, the child is asked to pretend to drive a miniature car. Driving a car is important to minority North American children, whereas pouring tea is not. Although pretending to drive a car is not tantamount to pretending to pour tea, it is a good screen for minority North American children. The failure of a minority North American child to pretend to drive a miniature car constitutes a definite deficit in pretend play. Other make-believe play may be substituted based on cultural relevance. A child who does not respond appropriately to a pretend activity compared to most other children of the same culture merits referral for a specialized assessment to rule out autism and other developmental disabilities.
    • The assessment of normal gaze monitoring, suggested by Baron-Cohen and colleagues (1992, 1996), is composed of the following steps: The clinician calls the child's name, points to a toy on the other side of the room, and says, "Oh look! There's a [name a toy]!"19,20 If the child looks across the room to look at the item indicated by the clinician, then a joint attention is established, indicating normal gaze monitoring. The absence of a normal response merits referral for specialized assessment to rule out autism and other developmental disabilities.
    • Baron-Cohen and colleagues (1992, 1996) have established a protocol to assess for the presence of protodeclarative pointing in the evaluation of well babies as follows: "Say to the child, 'Where's the light?' or 'Show me the light.' Does the child point with his or her index finger at the light?"19,20 If the child does not respond appropriately to the light, the procedure may be repeated with a teddy bear or any other unreachable object. The child must look up at the clinician's face at the time of pointing to establish a normal response for this item. Absence of the expected response merits specialized clinical evaluation to rule out autism and other developmental disorders.
    • Unlike many other children with mental retardation, children with autistic disorder are typically physically normal in appearance, without dysmorphic features. Thus, among children with developmental disorders, children with autistic disorder and other pervasive developmental disorders may be remarkable for their pulchritude. For this reason children with autistic disorder and other pervasive developmental disorders may be vulnerable to sexual and physical abuse. Since children with autistic disorder and other pervasive developmental disorders may be unable to report abuse to authorities, parents and guardians must examine their children for evidence of abuse especially when behavioral changes are present.
  • Body movement
    • Some children with autistic disorder display choreoathetotic movements that resemble the movements seen in Sydenham chorea and other movement disorders. Stereotypies (patterned repetitive movements, postures, and utterances) constitute a common finding in many individuals with autistic disorder.
    • Common abnormal motor movements that occur in children with autism include hand flapping, a motion in which the upper extremity is rapidly raised and lowered using a flaccid wrist so that the hands flap like flags in the wind.
    • Hand flapping typically occurs when the child is happy or excited. Hand flapping may occur in combination with movement of the entire body, such as bouncing (ie, jumping up and down) and rotating (ie, constantly spinning around a vertical axis in the midline of the body).
    • Children with autistic disorder also often display motor tics and are unable to remain still. Because children with autistic disorder are often mentally retarded and nonverbal, expressing subjective experiences associated with the movement is often impossible for them. Because the verbalization of the subjective desire to be in motion is necessary for the diagnosis of akathisia, akathisia cannot be diagnosed in individuals without the ability to express those subjective experiences in words. The high activity level and apparent lack of ability to remain still, resembling akathisia, has been termed pseudoakathisia when the individual cannot verbally express a sensation of inner restlessness and an urge to move.
  • Head features
    • The head circumference is increased in a subgroup of children with autistic disorder without known comorbid conditions. Increased head circumference is more common in boys and is associated with poor adaptive behavior. The increase in head circumference becomes pronounced in the first few years of life. The head circumference may then return to normal in adolescence.
    • Aberrant palmar creases and other dermatoglyphic anomalies are more common in children with autistic disorder.
  • Rating procedures
    • Patients with autistic disorder merit a careful assessment of movements (see Body movement).
    • The caregiver and clinicians may be asked to look for any motions in the mouth, face, hands, or feet of the patient and, if so, may be asked to describe them and how they bother the patient. The patient may be asked to sit on the chair with legs slightly apart, feet flat on the floor, and hands hanging supported between the legs or hanging over the knees. The patient may be asked to open his or her mouth and then twice to stick out the tongue. If the subject does not perform the requested action, the examiner then repeatedly performs the actions in the direct view of the subject to demonstrate the desired actions. For additional information about the rating of movement disorders, please see Tardive Dyskinesia.
    • The patient may be asked to sit, stand, and lie on a sheet on the floor for 2 minutes in each position. The patient is asked to remain motionless in each posture. In each position, the patient is asked, "Do you have a sensation of inner restlessness?" and "Do you have the urge to move?" These questions require an appropriate developmental level for a useful response. Therefore, most children with autism cannot respond appropriately. In the absence of a clear verbal response, the subjective items are not rated. Nevertheless, the objective behavior of the child can be observed and rated. For additional information about the rating of movement disorders, please see Tardive Dyskinesia.
    • Because the verbalization of inner restlessness and an urge to move are required for the diagnosis of akathisia, the observation of the movements typical of akathisia in an individual who does not verbalize the subjective experience of akathisia merits the diagnosis of pseudoakathisia or probable objective akathisia. For additional information about the rating of movement disorders, please see Tardive Dyskinesia.
  • Assessing stereotypies
    • Movements observed in individuals with autistic disorder are frequently classified as stereotypies (eg, purposeless, repetitive, patterned motions, postures, and sounds). Stereotypies are divided into the following 3 topological classes:
      1. Oro-facial (eg, tongue, mouth, and facial movements; smelling; sniffing; and other sounds)
      2. Extremity (eg, hand, finger, toe, leg)
      3. Head and trunk (eg, rolling, tilting, or banging of the head; rocking the body)
    • Stereotypies occur in nonautistic infants and children with mental retardation. Regularly assessing stereotypies is a valuable practice because stereotypies may bother other people and interfere with performance at school, work, and home. Routine assessment of stereotypies before, during, and after treatment is valuable in determining the effects of interventions.
    • Stereotypies are assessed for clinical purposes through regular use of the Timed Stereotypies Rating Scale. For this procedure, the occurrence of stereotypies is noted during 30-second intervals over a 10-minute duration. For additional information about the rating of stereotypies, please see Tardive Dyskinesia.
  • Self-injurious behaviors
    • A particularly serious form of stereotypy is self-injurious behavior. Self-injury may take the form of skin picking; self-biting; head punching and slapping; head-to-object and body-to-object banging; body punching and slapping; poking the eye, the anus, and other body parts; lip chewing; removal of hair and nails; and teeth banging.
    • Self-injury can result in morbidity and mortality. For example, eye poking and head banging may cause retinal detachments resulting in blindness. Although only a minority of the population of children with autism manifest self-injury, they constitute some of the most challenging patients in developmental pediatrics.
  • Clinical examples
    • A 6-year-old boy with autistic disorder who is treated with 75 mg clomipramine (Anafranil) by mouth daily at bedtime exhibits nonstop stereotypies. He frequently peers out of the corner of his eye, tilting his head. He often twiddles his fingers, moving an action figure in a nonfunctional manner. He occasionally grimaces. He repeatedly touches the slits of the blinds at the corner of the window. He rubs his fingers on the blinds, the cabinet drawer, and the chair. At 8:30 pm he rocks briefly and utters indeterminable vocalizations. He may be falling asleep.
    • A 7-year-old boy with autistic disorder took daily vitamins and no other medications at the time of assessment. The examiner repeated movements of the telephone receiver and tapping on the telephone receiver initially exhibited by the subject. The examiner repeated the subject's actions several times in an attempt to elicit repetition of the movement by the subject. Instead, the subject does not acknowledge the presence of the examiner. The subject spins by rotating on a central vertical axis in his body. He exhibits nonfunctional play with the telephone. He displays frequent finger wiggling and the other hand stereotypies. He frequently vocalizes indecipherable sounds and rocks briefly (see Media file 4).

      A 7-year-old boy with autistic disorder took daily vitamins and no other medications at the time of assessment. The examiner repeated movements of the telephone receiver and tapping on the telephone receiver initially exhibited by the subject. The examiner repeated the subject's actions several times in an attempt to elicit repetition of the movement by the subject. Instead, the subject does not acknowledge the presence of the examiner. He looks away from the examiner. He turns his back to the examiner. The subject spins by rotating on a central vertical axis in his body. He exhibits nonfunctional play with the telephone. He displays frequent finger wiggling and the other hand stereotypies. He frequently vocalizes indecipherable sounds and briefly rocks. He tilts his head and looks out of the corner of his eye for a few seconds.

      Video available at http://img.medscape.com/pi/emed/ckb/pediatrics_development/912185-912186-912781-912883.flv.


    • The examiner may attempt to establish a sequence of taking turns hitting a plate with a block. The examiner says, "My turn," and then taps the plate. The examiner gives the block to the subject and says, "Your turn." The subject may be physically assisted in the activity if the desired response does not occur. The following is a clinical example: A 7-year-old boy with autistic disorder took daily vitamins and no other medications at the time of assessment. The examiner attempted to elicit turn-taking by hitting the plate with a block. The child repeatedly jumps and rotates. He exhibits nonfunctional play with the telephone. He tilts his head and peers out of the corner of his eye. He is interested in the feel of the stick. He exhibits quick hand movements with small toys (see Media file 5).

      The examiner may attempt to establish a sequence of taking turns hitting a plate with a block. The examiner says, "My turn," and then taps the plate. The examiner gives the block to the subject and says, "Your turn." The subject may be physically assisted in the activity if the desired response does not occur.

      The following is a clinical example: A 7-year-old boy with autistic disorder took daily vitamins and no other medications at the time of assessment. The examiner attempted to elicit turn-taking by hitting the plate with a block. The child repeatedly jumps and rotates. He exhibits nonfunctional play with the telephone. He tilts his head and peers out of the corner of his eye. He is interested in the feel of the stick. He exhibits quick hand movements with small toys.

      When his father and his brother leave the room, the child does not acknowledge their departure. When his father returns to the room, he does not run to greet him. He appears indifferent to the departure and the return of his father. He repeatedly touches the surface of the wooden block. He touches the surface of a furlike cloth. He also places this cloth to his mouth to feel the texture on his lips. He is also fascinated with a string of yarn. He moves the string of yarn up and down and back and forth. This is nonfunctional play with ordinary items.

      Video available at http://img.medscape.com/pi/emed/ckb/pediatrics_development/912185-912186-912781-912884.flv.


Causes

Decades ago, researchers conjectured that infantile autism resulted from rejection of the infant by cold parents ("refrigerator mothers") who were blamed for the occurrence of the social deviations of their young children. Careful family studies have disproved the hypothesis that the development of autistic disorder in children is due to faulty parenting. Communicating repeatedly to the parents of the autistic child that they are not responsible is important. For additional information for parents and people with autism and related conditions, please visit the Autism Society of America.

The causes of autistic disorder are unknown. Hypotheses include obstetric complications, infection, genetics, and toxic exposures.

  • Obstetric complications are associated with an increased risk of autistic disorder. Whether obstetric complications caused autistic disorder or whether autism and obstetric complications resulted from another problem is unclear.
  • An infectious basis for autistic disorder in some individuals is suggested by the large number of children with autistic disorder born to women who were infected in the rubella epidemic. This finding supports the hypothesis that this infection triggers a vulnerability to develop autistic disorder in the fetus.
  • A genetic contribution to the development of autism has been hypothesized.
    • Multiple family studies have suggested genetic components to many cases of autism. For example, many studies have demonstrated that some asymptomatic first-degree relatives of some probands with autism have abnormalities in serotonin and other chemicals similar to the probands with autism. However, a particular individual with autistic disorder may not exhibit familial traits seen in populations.
    • Finding genetic bases for autism is a promising research goal. However, the clinical usefulness of the assessment of families of individuals with autism has not been established.
  • Toxic exposures have been hypothesized to cause autism.
    • Exposures to toxins, chemicals, poisons, and other substances have been hypothesized to cause autism. Although anecdotal case reports suggest that exposures to toxins and other substances may play a role in isolated cases of autistic disorder, a causative role for toxins in the development of autism in general has not been demonstrated. Local regions may have toxic exposures that exert a geographical influence. For example, the high incidence of autism in portions of Japan has been hypothesized to be due to a toxic effect of fish. Although toxins may play a role in the development of isolated cases of autism in Japan, toxins have not been proved to be causative of autism in Japan in general. Another possible explanation for the high rates of autism in Japan is the excellent training of Japanese clinicians. Low rates of autism in countries outside Japan may reflect the limited abilities of clinicians to make the diagnosis of autism.
    • In particular, the development of autism after immunization to measles, mumps, and rubella led to the hypothesis that autism was caused by immunization. Careful research has not demonstrated an association between immunization for measles, mumps, and rubella and the subsequent development of autism and related conditions in the general population. General immunization for measles, mumps, and rubella is recommended. Immunization for the general population is highly recommended. The rate of autism in children who receive immunizations does not appear to be increased.

Differential Diagnoses

Acanthocytosis
Down Syndrome
Anxiety Disorder: Obsessive-Compulsive Disorder
Eating Disorder: Pica
Anxiety Disorder: Trichotillomania
Fragile X Syndrome
Biotin Deficiency
Gaucher Disease
Child Abuse & Neglect: Dissociative Identity Disorder
Hearing Impairment
Child Abuse & Neglect: Failure to Thrive
Human Immunodeficiency Virus Infection
Child Abuse & Neglect: Physical Abuse
Hypomelanosis of Ito
Child Abuse & Neglect: Psychosocial Dwarfism
Learning Disorder: Reading
Child Abuse & Neglect: Reactive Attachment Disorder
Toxicity, Lead
Cognitive Deficits
Tuberous Sclerosis
Cornelia De Lange Syndrome
Cri-du-chat Syndrome

Other Problems to Be Considered

44,XXX karyotype
47 chromosomes
(7;20) balanced chromosomal translocation
Angelman syndrome
Deletion 1p35
Duplication of bands 15q11-13
Extra bisatellite marker chromosome
Habit disorder
Hydrocephalus, infantile
Interstitial deletion of (17)(p11.2)
Inv Dup (15)(pter->q13)
Language disorder: mixed
Language disorder: phonology
Language disorder: receptive
Language disorder: stuttering
Long Y chromosome
Minamata disease
Moebius syndrome
Nonketotic hyperglycinemia (NKH)
Partial 6p trisomy
Seizures
Seizures, frontal lobe
Spasms, infantile
Tourette disorder
Trisomy 22

Workup

Laboratory Studies

  • Whole-blood serotonin is elevated in approximately one third of individuals with autistic disorder. Elevations of whole-blood serotonin occur in parents and siblings of individuals with autistic disorder.
  • Serum biotinidase is reduced in some individuals with autistic disorder.
  • Immunologic studies are helpful to identify abnormalities, such as decreased plasma concentrations of the C4B complement protein.
  • Elevations of C-terminally directed beta-endorphin protein immunoreactivity is common in individuals with autistic disorder and their mothers.

Imaging Studies

  • MRI
    • Studies are inconsistent but reveal some findings, including enlargement of the total brain, the total brain tissue, and the lateral and fourth ventricles, along with reductions in size of the midbrain, the medulla oblongata, the cerebellar hemispheres, and vermal lobules VI and VII.
    • Although vermal hypoplasia is found in some individuals with autism, vermal hyperplasia is identified in others.
    • People with autistic disorder who exhibit head banging may present enlargement of the diploic space in the parietal and occipital bones, with loss of gray matter adjacent to the bony changes. These findings resemble those of professional boxers who exhibit encephalopathy (dementia pugilistica).
  • CT scanning: Studies of the head are inconsistent but can reveal deficits, including enlargement of the ventricles, hydrocephalus, parenchymal lesions, and reduction in size of the caudate nucleus.
  • Positron emission tomography
    • Positron emission tomography (PET) reveals multiple deficits. No finding has characterized all people with autism and the results vary with each individual.
    • With fluorine-18 fluoro-2-deoxyglucose, the anterior rectal gyrus is found larger on the left than the right in some people, a finding opposite the asymmetry seen in typical individuals.
    • Some individuals also exhibit increased glucose metabolic rate in the right posterior calcarine cortex and decreased glucose metabolic rate in the left posterior putamen and the left medial thalamus.
    • See PET Scanning in Autism Spectrum Disorders for further information including the PET scan of the boy with autism in Media files 4-6.
  • Single-photon emission computed tomography (SPECT) measurements: Tests of regional cerebral blood flow with 133 Xe reveal hypometabolism of the left hemisphere in some individuals.
  • Electroencephalography
    • Electroencephalography rules out seizure disorder, acquired aphasia with convulsive disorder (Landau-Kleffner syndrome), biotin-responsive infantile encephalopathy, and related conditions. Consultation with an electroencephalographer may help determine appropriate procedures for individual cases.
    • A single normal electroencephalogram does not rule out a paroxysmal abnormality, such as a seizure disorder.
    • When a routine electroencephalogram does not reveal unequivocal evidence of a seizure disorder in a patient with a possible seizure disorder, such as a partial seizure with complex symptomatology, specialized procedures may help to clarify the diagnosis. Measurements of electroencephalographic activity after sleep deprivation and after stimulation with light, noise, and tactile sensations using nasopharyngeal leads and simultaneous video monitoring along with electroencephalogram may then be helpful.
    • Admission to a specialized unit for simultaneous 24-hour videotape monitoring of electroencephalography and movement of the patient for a few days of assessment may facilitate the establishment of or the exclusion of diagnosis of a paroxysmal disorder.
    • See PET Scanning in Autism Spectrum Disorders for further information including the electroencephalogram of the boy with autism in Media file 4-6.
  • Radioisotope brain imaging: Regional cerebral blood flow (rCBF) assessed with technetium-99m labeled to hexamethylpropyleneamine oxide (HMPAO), a lipophilic substance, in children with autistic disorder exhibits variable anomalies including reductions in the vermis, the cerebellar hemispheres, the thalami, the basal ganglia, and the parietal and temporal lobes. These findings suggest that no single abnormality characterizes all individuals with autistic disorder. Biological classes may have specific types of rCBF dysfunction.

Other Tests

  • Lead poisoning should be ruled out through appropriate testing.
  • Psychophysiological assessment is indicated.
    • Children are not likely to show the response habituation in respiratory period, electrodermal activity, and the vasoconstrictive peripheral pulse amplitude response to repeatedly presented stimuli seen in typical children.
    • Children with autism may demonstrate auditory overselectivity.

Treatment

Medical Care

Individual intensive interventions, including behavioral, educational, and psychological components, are the most effective treatments of autistic disorder. Beginning the treatment early in infancy results in the most favorable outcome. Diagnosis in the first months of life is crucial.

Many treatments help individuals with autistic disorder. Various interventions, including chiropractic manipulations, are reported to help individuals with autism. The results of individual case reports cannot be generalized to the population. However, scientific research is needed to investigate whether treatments are generally helpful. Adverse effects of interventions must be balanced against potential benefits. In particular, venlafaxine may increase high-intensity aggression in some adolescents with autism.

Secretin, which is supplied by the Repligen Corporation, is being considered by the US Food and Drug Administration (FDA) for the treatment of autism. Several anecdotal reports suggest that secretin helps some children with autism; however, the efficacy of secretin for the treatment of autism remains to be established and confirmed independently through clinical trials. Thus, secretin is currently an experimental agent being studied for the treatment of autism. Currently, no agents have been approved by the FDA for the treatment of autism.

Rossignol (2006) and Rossignol and Rossignol (2006) have reported beneficial effects of hyperbaric oxygen therapy in 6 patients with autism.21,22 The risks of this procedure must be weighed against the benefits for individual patients. Controlled clinical trials and other studies are needed to confirm the potential value of this intervention.

  • Available speech, behavior, and physical therapies include the following:
    • Therapy includes facilitated communication, the use of keyboards, letter boards, word boards, and other devices, with the assistance of a facilitator.
    • Auditory integration training, a procedure in which the individual listens to specially prepared sounds through headphones, is reported to help some individuals.
    • Sensory integration therapy, a treatment for motor and sensory motor problems typically administered by occupational therapists, is reported to help some patients.
    • Exercise and physical therapy are reported to help some people with autistic disorder.
  • The effective treatment for autistic disorder is special education. Although parents may choose to use various experimental treatments, including medication, they should concurrently use intensive individual special education by an educator familiar with instructing children who have autistic disorder and related conditions. Intensive behavioral interventions, instituted as early as possible, are indicated for every child in whom autistic disorder is suspected.

Consultations

  • Metabolic consultation may help identify any deficiencies.
  • Immunologic consultation may be useful to rule out immune abnormalities. The possible benefits must be weighed against the risks of experimental treatments such as intravenous (IV) immunoglobulin therapy.
  • Otolaryngologic consultation may be indicated to rule out deficits in the auditory apparatus. Additionally, audiography is indicated to rule out hearing deficits.
  • Ophthalmologic consultation may be indicated to rule out a treatable visual deficit. Special lenses are reported to help some individuals with autistic disorder.
  • Neurologic consultation with a movement disorder specialist is indicated to evaluate tics and other movement disorders when present.
  • Neuropsychological consultation can be helpful to assess intelligence. Deficits in simple and complex problem-solving tasks, both verbal and nonverbal, are likely to be demonstrated on the Wisconsin Card Sorting Test, the Trail Making Test, and the Stanford-Binet Intelligence Test.
  • Infectious disease consultation may be helpful to rule out bacterial or fungal infections.

Diet

  • Individuals with autistic disorder and related conditions need 3 well-balanced meals a day.
  • Dietary consultation may be useful to evaluate the benefits of special diets, including those lacking gluten and casein.
  • Vitamin B-6 and magnesium are among the vitamins and minerals hypothesized to help some persons with autistic disorder and related conditions.

Activity

  • Exercise is often therapeutic for individuals with autistic disorder.
  • A regular program of activity prescribed by a physical therapist may be helpful.

Medication

The established therapies for autistic disorder are nonpharmacologic. These therapies may include behavioral, educational, and psychological treatment.

Although serotonergic drugs and opioid antagonists, including naltrexone and secretin, are reportedly beneficial, no pharmacologic agent is effective in the treatment of the core behavioral manifestations of autistic disorder. Although 6 controlled clinical trials of secretin have demonstrated no effect, the FDA is permitting the study of secretin for autism. Beneficial effects of secretin for autism have not been demonstrated.

Children with autistic disorder appear sensitive to medication and may experience serious adverse effects that outweigh any beneficial effects. For example, children may develop catatonia when treated with haloperidol and other traditional neuroleptics. Additionally, Kem et al noted priapism in an adolescent with autism who was treated with trazodone.23

Medication may be effective to treat comorbid disorders of individuals with autistic disorder, including self-injurious behaviors and movement disorders. Ziprasidone may help to control aggression, irritability, and agitation. Risperidone has recently been approved by the FDA for irritability associated with autistic disorder. Hyperactivity often improves with methylphenidate therapy. Additionally, treatments are indicated for the underlying condition. For example, children with biotin-responsive infantile encephalopathy improve with the addition of biotin.

Selective serotonin reuptake inhibitors (SSRIs) are widely prescribed for children with autism and related conditions. A multicenter trial by King et al studied 149 children with autism spectrum disorders. The participants were randomized to receive an SSRI, liquid citalopram (n=73), or placebo (n=76) daily for 12 weeks. The mean maximum daily dose was 16.5 mg (maximum 20 mg). No difference was noted between the groups in children rated in the much improved or the very much improved categories. Nearly all the citalopram recipients reported adverse effects (eg, impulsiveness, hyperactivity, diarrhea). Compared with placebo, citalopram did not show beneficial effect for children with autism and autism spectrum disorders.24

Children with autistic disorder are at risk to develop a serotonin syndrome when treated with serotonergic agents. Therefore, children who are treated with serotonergic agents should be evaluated at baseline before beginning treatment and then regularly evaluated for symptoms of a serotonin syndrome using the Serotonin Syndrome Checklist (see Media file 2 for a printable version).

Serotonin syndrome checklist.

Serotonin syndrome checklist.


Antipsychotic Agent

Risperidone was recently approved by the US Food and Drug Administration for irritability associated with autistic disorders.


Risperidone (Risperdol)

Atypical antipsychotic agent. Binds to dopamine D2-receptor with 20 times lower affinity than for 5-HT2-receptor affinity. Improves negative symptoms of psychoses. Reduces incidence of extrapyramidal adverse effects compared to conventional antipsychotics. Indicated for treatment of irritability associated with autistic disorder in children and adolescents aged 6-16 years.

Dosing

Adult

Not established

Pediatric

<5 years: Not established
5-16 years:
<20 kg: 0.25 mg PO qd; may increase by 0.25-0.5 mg/d at intervals >2 wk; target dose is 0.5 mg/d (dose range may vary between 0.5-3 mg/d)
>20 kg: 0.5 mg PO qd; may increase by 0.25-0.5 mg/d at intervals >2 wk; target dose is 1 mg/d (dose range may vary between 0.5-3 mg/d)

Interactions

Coadministration with carbamazepine may decrease effects; risperidone may inhibit effects of levodopa; clozapine may increase risperidone levels; oral solution not compatible with cola or tea

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

May cause extrapyramidal reactions, hypotension, tachycardia, and arrhythmias; hyperglycemia may occur and in some cases be extreme, resulting in ketoacidosis, hyperosmolar coma, or death; do not split or chew oral disintegrating tablets; lower dose and slower titration may be required in elderly or debilitated patients, those with severe renal or hepatic impairment, or individuals predisposed to hypotension; elderly patients with dementia-related psychosis treated with atypical antipsychotic drugs have increased risk of death compared to placebo

Follow-up

Further Outpatient Care

  • Rossignol (2007) has proposed the hypothesis that several symptoms and signs of autism may be alleviated through the administration of hyperbaric oxygen therapy.25 Rossignol and colleagues (2007) have reported improvements in motivation, speech, and cognitive awareness in a small group of children with autism treated with 40 sessions of hyperbaric treatments.26 These promising results merit confirmation by controlled clinical trials. Confirmation of the beneficial effects of hyperbaric oxygen therapy for children with autism by rigorous studies with larger samples of children in other locations is needed.

Complications

  • Physical abuse
    • Children with autism and related conditions are at risk for physical abuse. They may persist incessantly with repetitive behaviors that annoy others, despite instructions to cease. Children with autism spectrum disorders typically do not benefit from spanking and other forms of traditional discipline.
    • By contrast, the behavioral interventions of an educator specially trained to handle the challenging behaviors of children with autism are deliberate applications of psychological interventions to modify the child's behavior. Parents, teachers, and others benefit from training in effective approaches to dealing with challenging behaviors from a special educator or a behavioral psychologist.
    • Because parents understandably become exhausted by the relentless performance of challenging behaviors by a child with autism spectrum disorders, alternatives are needed. Parents frequently benefit from temporary respite from the child.
    • Parents, teachers, and others may eventually lose control and inflict physical injury on the child. For this reason, children with autism spectrum disorders are at high risk for physical abuse; therefore, vigilant regular physical examinations by pediatricians and other health care providers are mandatory. Because the child may not report physical abuse, health care providers must maintain a high level of suspicion for the possibility of physical abuse when assessing children with autism spectrum disorders.
  • Sexual abuse
    • Children with autism spectrum disorders are at risk for sexual abuse. They may be attractive children and, thus, may attract the interests of those who are sexually aroused by children.
    • Children with autism spectrum disorders may lack ability to communicate inappropriate sexual contact to responsible authorities. Thus, parents, teachers, health care providers, and others must maintain a high level of suspicion for the possibility of sexual abuse when assessing children with autism spectrum disorders.

Prognosis

  • The IQ is highly correlated with the prognosis.
  • Low-functioning patients may never live independently; they typically need home or residential care for the rest of their lives.
  • High-functioning patients may live independently, hold jobs successfully, and even marry and have children.
  • High-functioning individuals with autistic disorder are similar to people with Asperger syndrome. Please refer to Pervasive Developmental Disorder: Asperger Syndrome for further information and to learn more about high-functioning autism.

Patient Education

  • Individualized, intensive behavioral and psychological interventions must be instituted immediately after diagnosis in order to attain the optimal outcome.
  • Although controversy surrounds the appropriate form of special education, some evidence suggests that an individual educational program must be developed by a special educator familiar with autistic disorder and related conditions.
  • Because local boards of education may be ignorant about the needs of children with autistic disorder and related conditions, pediatricians and parents should seek advice from knowledgeable sources such as The Autism Society of America, which maintains a Web site and offers a toll-free hotline at 1-800-3-AUTISM, providing information and referral services to the public.
  • Legal assistance may be necessary to influence a board of education to fund appropriate education for a child with autistic disorder and related conditions.
  • Because deficits in language and communication are often major impediments to progress in educational, work, and personal settings, specialized communication devices and training are often helpful.
  • Persons experienced in the needs and treatment of individuals with serious communication handicaps may help the person to maximize communication skills (speech and language specialists).
  • Because of the continued deficits of people with autism in social settings, research is needed to develop the communication and social skills of those with autism and related conditions throughout childhood, adolescence, and adulthood.
  • For excellent patient education resources, visit eMedicine's Brain and Nervous System Center. Also, see eMedicine's patient education articles Autism and Asperger Syndrome.

Miscellaneous

Medicolegal Pitfalls

  • Delayed diagnosis
    • Delayed diagnosis of autistic disorder and related conditions is a serious problem for pediatricians. Parents repeatedly report raising concerns about the patient's development in the first months and years to pediatricians and hearing only that the child will outgrow it.
    • Procedures are available for diagnostic screening by practicing pediatricians, including the CHAT.
      • Although the CHAT has been reported by Baron-Cohen and colleagues (1992, 1996) to identify autistic disorder in a British population, the reliability and validity of this instrument has not been demonstrated in other populations.19,20
      • Some items of the CHAT appear to have strong cultural biases that rule out the direct application of the CHAT to populations outside the United Kingdom.
      • The 3 items of the CHAT that are highly predictive of the development of autistic disorder (ie, protodeclarative pointing, gaze monitoring, pretend play) can be quickly assessed by clinicians during well-baby visits (see Clinical section for detailed descriptions of screening procedures). The direct use of the full CHAT outside the United Kingdom is not recommended due to the apparent cultural biases of some items of the CHAT. Pediatricians can facilitate early diagnosis of autistic disorder and related conditions by performing a screening procedure at every visit, including well-baby check-ups, school examinations, and immunizations appointments.
  • Treatment issues
    • The effective treatment for autistic disorder is special education. Although parents may choose to use various experimental treatments including medication, they should concurrently use intensive individual special education by an educator familiar with instructing children with autistic disorder and related conditions.
    • Intensive behavioral interventions, instituted as early as possible, are indicated for every child in whom autistic disorder is suspected.
    • The Education for All Handicapped Children Act of 1975 requires free and appropriate public education for all children, regardless of the extent and severity of their handicaps.
    • Amendments to the Education of the Handicapped Act of 1986 extended the requirement for free and appropriate education to children aged 3-5 years. These requirements for free appropriate public education apply even if the local board of education lacks specialized programs.
    • Pediatricians and parents cannot assume that the community school will provide satisfactory education for a child with autistic disorder and related conditions. The Individuals with Disabilities Education Act authorized states to determine how to provide educational services to children younger than 3 years. Pediatricians and parents need to determine the best way to proceed with local agencies.
    • The Autism Society of America maintains a Web site and offers a toll-free hotline (1-800-3-AUTISM). This resource provides information and referral services to the public.
    • Legal assistance may be necessary to influence a board of education to fund appropriate education for a child with autistic disorder and related conditions.
  • Obtaining informed consent
    • People with autism are identified as a highly vulnerable population because of the presence of cognitive, social, and mental impairments. Regulatory agencies have expressed particular concern that the rights of children with autistic disorder and related conditions be carefully protected. Some have suggested that parents may not be impartial guardians and that third parties be used instead of parents to provide informed consent for clinical and research purposes. However, parents are generally excellent advocates seeking the best for their children. Nevertheless, clinicians must take particular care to ensure that informed consent is obtained in order to prevent misinterpretations and eventual medicolegal problems.
    • Except in emergencies, patients, parents, guardians, and surrogates must be aware of the diagnostic and treatment possibilities. They must provide permission for possible interventions. By recording on videotape the process of explaining to the parent the recommended procedures, in addition to the signing written release forms, clinicians establish evidence of the informing process.
    • Clinicians should videotape the process of verbally explaining the protocol and answering questions. Permission must be explicitly given to perform the procedure and cannot continue until the parents agree. Parents are asked to give permission to complete this protocol. The entire process is videotaped. Occasionally parents decline to give consent, and then the procedure must cease (see Media file 3).

      Clinicians are advised to videotape the process of verbally explaining the protocol and answering questions. Permission must be explicitly given to perform the procedure and cannot continue until the parents agree. Parents are asked to give permission to complete this protocol. The entire process is videotaped. In this segment, the mother of a healthy, normal control child gives informed consent to participate as a volunteer in a research study of autism. Occasionally, parents decline to give consent, and the procedure must cease. An earlier version of this videotape is in the New York University Medical Library, New York, New York.

      Video available at http://img.medscape.com/pi/emed/ckb/pediatrics_development/912185-912186-912781-912882.flv.


Special Concerns

Children with autism and related conditions typically benefit from intensive, thorough evaluations performed by experienced professionals. Intensive diagnostic evaluation and treatment are accomplished quickly and effectively by well-staffed and well-trained clinicians. Valuable resources include the following:

  • Division of Developmental and Behavioral Pediatrics
    Pediatric Ambulatory Center
    University of Maryland Medical Center
    700 West Lombard St
    Baltimore, MD
    Phone: 410-328-5437
  • Developmental Disabilities Clinic
    Child Study Center
    Yale University School of Medicine
    230 South Frontage Rd
    PO Box 207900
    New Haven, CT 06520-7900
    Phone: 203-785-2510 (For appointments, call 203-785-2874.)
    Fax: 203-737-4197
  • Developmental Disorders Clinic
    The Harris Center for Developmental Studies
    Section of Child and Adolescent Psychiatry
    Department of Psychiatry
    The University of Chicago
    5841 South Maryland Ave MC3077
    Chicago, IL 60637
  • Seaver Autism Research Center
    Department of Psychiatry
    Mount Sinai School of Medicine, Box 1230
    One Gustave L Levy Place
    New York, NY 10029-6574
    Phone: 212-241-2994
  • Bellevue Hospital Center
    462 First Ave
    New York, NY 10016-9103
    Phone: 212-562-4504
  • Center for Autism and Related Disorders
    Kennedy Krieger Institute
    Pierce Building, Third Floor
    3825 Greenspring Avenue
    Baltimore, MD 21211
    Phone: 410-404-6252
    Fax: 443-923-7695
  • Division of Child Psychiatry
    New York State Psychiatric Institute, Room 2521
    722 West 168th St
    New York, NY 10032
    Phone: 212-543-5280, 212-543-6782, 212-579-5557
    Fax: 212-543-5966
  • Division of Child and Adolescent Psychiatry
    Department of Psychiatry
    University of California at Los Angeles
    760 Westwood Plaza, Room 48-270
    Los Angeles, CA 90095
    Phone: 310-825-0470
    Fax: 310-206-4446
  • Medical Investigation of Neurodevelopmental Disorders (MIND) Institute
    University of California Davis Medical Center
    4860 Y Street, Room 3020
    Sacramento, CA 95817
    Phone (toll-free): 888-883-0961
    Phone: 916-734-5153
  • Strong Center for Developmental Disabilities
    Department of Pediatrics
    Children's Hospital at Strong
    University of Rochester Medical Center
    601 Elmwood Ave
    Rochester, NY 14642
    Phone: 716-275-2100

Individuals with autism and related conditions and their advocates can benefit from the experiences of the following individuals and advocates with similar situations:

  • Autism Society of America
    7910 Woodmont Ave Suite 650
    Bethesda, MD 20814-3015
    Phone: 1-800-328-8476
  • Autism Society of America, Manhattan Chapter
    25 West 17th St Ground Floor
    New York, NY 10011
  • Autism Society of Canada
    2-20 College St
    Toronto, Ontario
    Canada M5G 1K2
  • National Alliance for Autism Research
    Research Park
    414 Wall St
    Princeton, NJ 08540
    Phone: 888-777-NAAR
  • The National Autistic Society
    393 City Rd
    London EC1V 1NG
    UK
    Phone: +44 (0)20 7833 2299
  • Asperger Syndrome Coalition of the United States (ASC-US) Inc
    PO Box 49267
    Jacksonville FL 32240-9267
  • LADDERS
    65 Walnut St
    Wellesley MA 02481
    Phone: 781-449-6074
  • Autism Research Institute
    4182 Adams Ave
    San Diego, CA 92116
    Fax: 619-563-6840
  • Cure Autism Now (CAN) Foundation
    5455 Wilshire Blvd, Suite 715
    Los Angeles, CA 90036
    Phone: 323-549-0500

Multimedia

Autism screening checklist.

Media file 1: Autism screening checklist.

Serotonin syndrome checklist.

Media file 2: Serotonin syndrome checklist.

Media file 3: Clinicians are advised to videotape the process of verbally explaining the protocol and answering questions. Permission must be explicitly given to perform the procedure and cannot continue until the parents agree. Parents are asked to give permission to complete this protocol. The entire process is videotaped. In this segment, the mother of a healthy, normal control child gives informed consent to participate as a volunteer in a research study of autism. Occasionally, parents decline to give consent, and the procedure must cease. An earlier version of this videotape is in the New York University Medical Library, New York, New York.

Video available at http://img.medscape.com/pi/emed/ckb/pediatrics_development/912185-912186-912781-912882.flv.

Media file 4: A 7-year-old boy with autistic disorder took daily vitamins and no other medications at the time of assessment. The examiner repeated movements of the telephone receiver and tapping on the telephone receiver initially exhibited by the subject. The examiner repeated the subject's actions several times in an attempt to elicit repetition of the movement by the subject. Instead, the subject does not acknowledge the presence of the examiner. He looks away from the examiner. He turns his back to the examiner. The subject spins by rotating on a central vertical axis in his body. He exhibits nonfunctional play with the telephone. He displays frequent finger wiggling and the other hand stereotypies. He frequently vocalizes indecipherable sounds and briefly rocks. He tilts his head and looks out of the corner of his eye for a few seconds.

Video available at http://img.medscape.com/pi/emed/ckb/pediatrics_development/912185-912186-912781-912883.flv.

Media file 5: The examiner may attempt to establish a sequence of taking turns hitting a plate with a block. The examiner says, "My turn," and then taps the plate. The examiner gives the block to the subject and says, "Your turn." The subject may be physically assisted in the activity if the desired response does not occur.

The following is a clinical example: A 7-year-old boy with autistic disorder took daily vitamins and no other medications at the time of assessment. The examiner attempted to elicit turn-taking by hitting the plate with a block. The child repeatedly jumps and rotates. He exhibits nonfunctional play with the telephone. He tilts his head and peers out of the corner of his eye. He is interested in the feel of the stick. He exhibits quick hand movements with small toys.

When his father and his brother leave the room, the child does not acknowledge their departure. When his father returns to the room, he does not run to greet him. He appears indifferent to the departure and the return of his father. He repeatedly touches the surface of the wooden block. He touches the surface of a furlike cloth. He also places this cloth to his mouth to feel the texture on his lips. He is also fascinated with a string of yarn. He moves the string of yarn up and down and back and forth. This is nonfunctional play with ordinary items.

Video available at http://img.medscape.com/pi/emed/ckb/pediatrics_development/912185-912186-912781-912884.flv.

Media file 6: The following is a clinical example that continues the segment of Image 5: A 7-year-old boy with autistic disorder took daily vitamins and no other medications at the time of assessment. He appears indifferent to the departure of his brother from the room. He also does not respond with a greeting when his brother returns. He appears interested in his nonfunctional play. He displays minimal acknowledgment of the departure and return of his brother. In particular, he does not respond to his brother's touching him on the shoulder to greet him.

Instead, he demonstrates inappropriate friendliness with the psychologist who is evaluating the procedures. Although he never saw her before this assessment, he suddenly goes to her to kiss her.

Video available at http://img.medscape.com/pi/emed/ckb/pediatrics_development/912185-912186-912781-912885.flv.

References

  1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR)(TM), Text Revision. 4th Edition. Washington, DC: American Psychiatric Association; 2000.

  2. National Center for Health Statistics. International Classification of Diseases (ICD-9-CM), 9th Revision, Clinical Modification. 4th Edition. Practice Management Information Corporation (PMIC), Los Angeles, CA; 1993.

  3. Hughes JR. Autism: the first firm finding = underconnectivity?. Epilepsy Behav. Aug 2007;11(1):20-4. [Medline].

  4. Brasic JR, Holland JA. Reliable classification of case-control studies of autistic disorder and obstetric complications. Journal of Developmental and Physical Disabilities. 2006;18:355-381.

  5. Brasic JR, Holland JA. A qualitative and quantitative review of obstetric complications and autistic disorder. Journal of Developmental and Physical Disabilities. 2007;19:337-364.

  6. Brasic JR, Holland JA, Alexander M. The increased likelihood of obstetric complications in autistic disorder [abstract]. Southern Medical Journal. 2003;96 (10 supplement):S34.

  7. Roberts EM, English PB, Grether JK, Windham GC, Somberg L, Wolff C. Maternal residence near agricultural pesticide applications and autism spectrum disorders among children in the California Central Valley. Environmental health perspectives [serial online]. 2007;Accessed 20 Sep 2007. Available at http://www.ehponline.org/members/2007/10168/10168.pdf.

  8. Samson K. CDC-backed study suggests possible link between autistic disorders, maternal perticide exposure in California. Neurology Today. September 2007;7:7.

  9. Rapin I, Tuchman RF. What is new in autism?. Curr Opin Neurol. Apr 2008;21(2):143-149. [Medline].

  10. Thompson WW, Price C, Goodson B, Shay DK, Benson P, Hinrichsen VL, et al. Early thimerosal exposure and neuropsychological outcomes at 7 to 10 years. N Engl J Med. Sep 27 2007;357(13):1281-92. [Medline].

  11. Dobbs M. What the autism studies show isn't reflected in what the candidates say. The Washington Post. April 22, 2008;AAutismBrain and Nervous System Centerhttp://www.emedicinehealth.com/collections/SU294.aspAutism Overviewhttp://www.emedicinehealth.com/Articles/29544-1.aspAutism Causeshttp://www.emedicinehealth.com/articles/29544-2.aspAutism Symptomshttp://www.emedicinehealth.com/articles/29544-3.aspAutism Treatmenthttp://www.emedicinehealth.com/articles/29544-6.aspAsperger Syndrome Overviewhttp://www.emedicinehealth.com/articles/54056-1.asp: A8.

  12. Kurita H. [Current status of autism studies]. Seishin Shinkeigaku Zasshi. 2001;103(1):64-75. [Medline].

  13. Bailey A, Bolton P, Butler L, Le Couteur A, Murphy M, Scott S, et al. Prevalence of the fragile X anomaly amongst autistic twins and singletons. J Child Psychol Psychiatry. Jul 1993;34(5):673-88. [Medline].

  14. Chudley AE, Hagerman RJ. Fragile X syndrome. J Pediatr. Jun 1987;110(6):821-31. [Medline].

  15. Cohen IL, Sudhalter V, Pfadt A, Jenkins EC, Brown WT, Vietze PM. Why are autism and the fragile-X syndrome associated? Conceptual and methodological issues. Am J Hum Genet. Feb 1991;48(2):195-202. [Medline].

  16. Einfeld SL. Autism and the fragile X syndrome. Am J Med Genet. May-Jun 1988;30(1-2):237-8. [Medline].

  17. Fisch GS, Cohen IL, Jenkins EC, Brown WT. Screening developmentally disabled male populations for fragile X: the effect of sample size. Am J Med Genet. May-Jun 1988;30(1-2):655-63. [Medline].

  18. Reiss AL, Freund L. Fragile X syndrome, DSM-III-R, and autism. J Am Acad Child Adolesc Psychiatry. Nov 1990;29(6):885-91. [Medline].

  19. Baron-Cohen S, Allen J, Gillberg C. Can autism be detected at 18 months? The needle, the haystack, and the CHAT. Br J Psychiatry. Dec 1992;161:839-43. [Medline].

  20. Baron-Cohen S, Cox A, Baird G, Swettenham J, Nightingale N, Morgan K, et al. Psychological markers in the detection of autism in infancy in a large population. Br J Psychiatry. Feb 1996;168(2):158-63. [Medline].

  21. Rossignol DA. Hyperbaric oxygen therapy might improve certain pathophysiological findings in autism. Med Hypotheses. 2007;68(6):1208-27. Epub 2006 Dec 4. [Medline].

  22. Rossignol DA, Rossignol LW. Hyperbaric oxygen therapy may improve symptoms in autistic children. Med Hypotheses. 2006;67(2):216-28. [Medline].

  23. Kem DL, Posey DJ, McDougle CJ. Priapism associated with trazodone in an adolescent with autism. J Am Acad Child Adolesc Psychiatry. Jul 2002;41(7):758. [Medline].

  24. King BH, Hollander E, Sikich L, McCracken JT, Scahill L, Bregman JD, et al. Lack of efficacy of citalopram in children with autism spectrum disorders and high levels of repetitive behavior: citalopram ineffective in children with autism. Arch Gen Psychiatry. Jun 2009;66(6):583-90. [Medline].

  25. Rossignol DA. Hyperbaric oxygen therapy might improve certain pathophysiological findings in autism. Med Hypotheses. 2007;68(6):1208-27. [Medline].

  26. Rossignol DA, Rossignol LW, James SJ, Melnyk S, Mumper E. The effects of hyperbaric oxygen therapy on oxidative stress, inflammation, and symptoms in children with autism: an open-label pilot study. BMC Pediatr. Nov 16 2007;7:36. [Medline].

  27. Adrien JL, Barthelemy C, Perrot A, et al. Validity and reliability of the infant behavioral summarized evaluation (IBSE): a rating scale for the assessment of young children with autism and developmental disorders. J Autism Dev Disord. Sep 1992;22(3):375-94. [Medline].

  28. Adrien JL, Faure M, Perrot A, Hameury L, Garreau B, Barthelemy C, et al. Autism and family home movies: preliminary findings. J Autism Dev Disord. Mar 1991;21(1):43-9. [Medline].

  29. Allen DA, Rapin I, Wiznitzer M. Communication disorders of preschool children: the physician's responsibility. J Dev Behav Pediatr. Jun 1988;9(3):164-70. [Medline].

  30. Anderson LT, Campbell M, Adams P, Small AM, Perry R, Shell J. The effects of haloperidol on discrimination learning and behavioral symptoms in autistic children. J Autism Dev Disord. Jun 1989;19(2):227-39. [Medline].

  31. Anderson LT, Campbell M, Grega DM, Perry R, Small AM, Green WH. Haloperidol in the treatment of infantile autism: effects on learning and behavioral symptoms. Am J Psychiatry. Oct 1984;141(10):1195-202. [Medline].

  32. Arnold LE, Aman MG, Martin A, Collier-Crespin A, Vitiello B, Tierney E, et al. Assessment in multisite randomized clinical trials of patients with autistic disorder: the Autism RUPP Network. Research Units on Pediatric Psychopharmacology. J Autism Dev Disord. Apr 2000;30(2):99-111. [Medline].

  33. Aronowitz BR, Decaria C, Allen A. The neuropsychiatry of autism and Asperger's disorder: review of the literature and case reports. CNS Spectrums. 1997;2(5):43-55.

  34. Aylward EH, Minshew NJ, Field K, Sparks BF, Singh N. Effects of age on brain volume and head circumference in autism. Neurology. Jul 23 2002;59(2):175-83. [Medline].

  35. Bailey A, Le Couteur A, Gottesman I, Bolton P, Simonoff E, Yuzda E, et al. Autism as a strongly genetic disorder: evidence from a British twin study. Psychol Med. Jan 1995;25(1):63-77. [Medline].

  36. Bailey AJ. The biology of autism. Psychol Med. Feb 1993;23(1):7-11. [Medline].

  37. Baker P, Piven J, Sato Y. Autism and tuberous sclerosis complex: prevalence and clinical features. J Autism Dev Disord. Aug 1998;28(4):279-85. [Medline].

  38. Barbaresi WJ, Katusic SK, Colligan RC, Weaver AL, Jacobsen SJ. The incidence of autism in Olmsted County, Minnesota, 1976-1997: results froma population-based study. Arch Pediatr Adolesc Med. Jan 2005;159(1):37-44. [Medline].

  39. Barthelemy C, Adrien JL, Tanguay P, Garreau B, Fermanian J, Roux S, et al. The Behavioral Summarized Evaluation: validity and reliability of a scale for the assessment of autistic behaviors. J Autism Dev Disord. Jun 1990;20(2):189-204. [Medline].

  40. Bauman M, Kemper TL. Histoanatomic observations of the brain in early infantile autism. Neurology. Jun 1985;35(6):866-74. [Medline].

  41. Berument SK, Starr E, Pickles A, Tomlins M, Papanikolauou K, Lord C, et al. Pre-Linguistic Autism Diagnostic Observation Schedule Adapted for Older Individualswith Severe to Profound Mental Retardation: A Pilot Study. J Autism Dev Disord. Dec 2005;35(6):821-9. [Medline].

  42. Bettelheim B. The Empty Fortress. In: Infantile Autism and the Birth of the Self. New York, NY: Free Press; 1977.

  43. Birmaher B, Quintana H, Greenhill LL. Methylphenidate treatment of hyperactive autistic children. J Am Acad Child Adolesc Psychiatry. Mar 1988;27(2):248-51. [Medline].

  44. Blaxill MF. Concerns continue over mercury and autism. Am J Prev Med. Jan 2004;26(1):91; reply 91-2. [Medline].

  45. Blaxill MF. Study fails to establish diagnostic substitution as a factor in increased rate of autism. Pharmacotherapy. Jun 2004;24(6):812-3; author reply 813-5. [Medline].

  46. Blaxill MF. What's going on? The question of time trends in autism. Public Health Rep. Nov-Dec 2004;119(6):536-51. [Medline].

  47. Blaxill MF, Redwood L, Bernard S. Thimerosal and autism? A plausible hypothesis that should not be dismissed. Med Hypotheses. 2004;62(5):788-94. [Medline].

  48. Bodfish JW, Symons FJ, Parker DE, Lewis MH. Varieties of repetitive behavior in autism: comparisons to mental retardation. J Autism Dev Disord. Jun 2000;30(3):237-43. [Medline].

  49. Bodner RA, Lynch T, Lewis L, Kahn D. Serotonin syndrome. Neurology. Feb 1995;45(2):219-23. [Medline].

  50. Bolton PF, Pickles A, Murphy M, Rutter M. Autism, affective and other psychiatric disorders: patterns of familial aggregation. Psychol Med. Mar 1998;28(2):385-95. [Medline].

  51. Brasic JR. Documentation of demographic data. Psychol Rep. Aug 2003;93(1):151-2. [Medline].

  52. Brasic JR. Documentation of ethnicity. Psychol Rep. Dec 2004;95(3 Pt 1):859-61. [Medline].

  53. Brasic JR. Movements in autistic disorder. Med Hypotheses. Jul 1999;53(1):48-9. [Medline].

  54. Brasic JR. Obtaining funding for new researchers in psychology. Psychol Rep. Aug 2003;93(1):276-8. [Medline].

  55. Brasic JR, Barnett JY. Hyperkinesias in a prepubertal boy with autistic disorder treated with haloperidol and valproic acid. Psychol Rep. Feb 1997;80(1):163-70. [Medline].

  56. Brasic JR, Barnett JY, Ahn SC, Nadrich RH, Will MV, Clair A. Clinical assessment of self-injurious behavior. Psychol Rep. Feb 1997;80(1):155-60. [Medline].

  57. Brasic JR, Barnett JY, Aisemberg P, et al. Dyskinesias subside off all medication in a boy with autistic disorder and severe mental retardation. Psychol Rep. Dec 1997;81(3 Pt 1):755-67. [Medline].

  58. Brasic JR, Barnett JY, Kaplan D, Sheitman BB, Aisemberg P, Lafargue RT, et al. Clomipramine ameliorates adventitious movements and compulsions in prepubertal boys with autistic disorder and severe mental retardation. Neurology. Jul 1994;44(7):1309-12. [Medline].

  59. Brasic JR, Barnett JY, Kowalik S, Tsaltas MO, Ahmad R. Neurobehavioral assessment of children and adolescents attending a developmental disabilities clinic. Psychol Rep. Dec 2004;95(3 Pt 2):1079-86. [Medline].

  60. Brasic JR, Barnett JY, Lafargue RT. The classification of stereotypies and other movement disorders in persons with autism. In: Presented at: 4th Conference of the International Federation of Classification Societies. Paris: 1993.

  61. Brasic JR, Barnett JY, Sheitman BB. Behavioral effects of clomipramine on prepubertal boys with autistic disorder and severe mental retardation. CNS Spectrums. 1998;3:39-46.

  62. Brasic JR, Barnett JY, Sheitman BB, Lafargue RT, Ahn SC. Clinical assessment of adventitious movements. Psychol Rep. Dec 1998;83(3 Pt 1):739-50. [Medline].

  63. Brasic JR, Barnett JY, Sheitman BB, Lafargue RT, Ahn SC. Clinical assessment of adventitious movements. Psychol Rep. Dec 1998;83(3 Pt 1):739-50. [Medline].

  64. Brasic JR, Barnett JY, Sheitman BB, Tsaltas MO. Adverse effects of clomipramine. J Am Acad Child Adolesc Psychiatry. Sep 1997;36(9):1165-6. [Medline].

  65. Brasic JR, Gianutsos JG. Neuromotor assessment and autistic disorder. Autism. In: The International Journal of Research and Practice. Vol 4. 2000:287-298.

  66. Brasic JR, Morgan RH. Suicide is probably more common in untreated youths than in those receiving treatment: the need for a retrospective epidemiological study. Med Hypotheses. 2005;65(6):1204-5. [Medline].

  67. Brasic JR, Will MV, Ahn SC, Nadrich RH, McNally G. A review of the literature and a preliminary study of family compliance in a developmental disabilities clinic. Psychol Rep. Feb 1998;82(1):275-86. [Medline].

  68. Brasic JR, Zagzag D, Kowalik S, et al. Progressive catatonia. Psychol Rep. Feb 1999;84(1):239-46. [Medline].

  69. Buchsbaum MS, Siegel BV Jr, Wu JC, Hazlett E, Sicotte N, Haier R, et al. Brief report: attention performance in autism and regional brain metabolic rate assessed by positron emission tomography. J Autism Dev Disord. Mar 1992;22(1):115-25. [Medline].

  70. Burd L, Fisher W, Kerbeshian J. Pervasive disintegrative disorder: are Rett syndrome and Heller dementia infantilis subtypes?. Dev Med Child Neurol. Oct 1989;31(5):609-16. [Medline].

  71. Burd L, Kerbeshian J. Psychogenic and neurodevelopmental factors in autism. J Am Acad Child Adolesc Psychiatry. Mar 1988;27(2):252-3. [Medline].

  72. Burd L, Severud R, Kerbeshian J, Klug MG. Prenatal and perinatal risk factors for autism. J Perinat Med. 1999;27(6):441-50. [Medline].

  73. Campbell M, Locascio JJ, Choroco MC, Spencer EK, Malone RP, Kafantaris V, et al. Stereotypies and tardive dyskinesia: abnormal movements in autistic children. Psychopharmacol Bull. 1990;26(2):260-6. [Medline].

  74. Campbell M, Overall JE. Diagnostic criteria and behavior patterns in infantile autism. Psychopharmacol Bull. 1989;25(2):194-7. [Medline].

  75. Campbell M, Palij M. Behavioral and cognitive measures used in psychopharmacological studies of infantile autism. Psychopharmacol Bull. 1985;21(3):1047-53. [Medline].

  76. Carmagnat-Dubois F, Desombre H, Perrot A, Roux S, Le Noir P, Sauvage D, et al. [Rett syndrome and autism. Early comparative evaluation for signs of autism using family movies]. Encephale. Jul-Aug 1997;23(4):273-9. [Medline].

  77. Carracedo A, Martin Murcia F, García Penas JJ, Ramos J, Cassinello E, Calvo MD. [Autistic syndrome associated with refractory temporal epilepsy]. Rev Neurol. Nov-Dec 1995;23(124):1239-41. [Medline].

  78. Casanova MF, Buxhoeveden DP, Switala AE, Roy E. Minicolumnar pathology in autism. Neurology. Feb 12 2002;58(3):428-32. [Medline].

  79. Casey BJ, Gordon CT, Mannheim GB, Rumsey JM. Dysfunctional attention in autistic savants. J Clin Exp Neuropsychol. Nov 1993;15(6):933-46. [Medline].

  80. Caston J, Yon E, Mellier D, Godfrey HP, Delhaye-bouchaud N, Mariani J. An animal model of autism: behavioural studies in the GS guinea-pig. Eur J Neurosci. Aug 1998;10(8):2677-84. [Medline].

  81. Cederlund M, Gillberg C. One hundred males with Asperger syndrome: a clinical study of background andassociated factors. Dev Med Child Neurol. Oct 2004;46(10):652-60. [Medline].

  82. Centofanti M. Rat model could yield clues in autism. Johns Hopkins Magazine. 2001;53 (2):42-43.

  83. Chez MG, Buchanan CP, Bagan BT, Hammer MS, McCarthy KS, Ovrutskaya I, et al. Secretin and autism: a two-part clinical investigation. J Autism Dev Disord. Apr 2000;30(2):87-94. [Medline].

  84. Chiron C, Leboyer M, Leon F, Jambaque I, Nuttin C, Syrota A. SPECT of the brain in childhood autism: evidence for a lack of normal hemispheric asymmetry. Dev Med Child Neurol. Oct 1995;37(10):849-60. [Medline].

  85. Cohen IL, Brown WT, Jenkins EC, Krawczun MS, French JH, Raguthu S, et al. Fragile X syndrome in females with autism. Am J Med Genet. Oct 1989;34(2):302-3. [Medline].

  86. Cohen S. Targeting Autism. Berkeley: University of California Press; 1998.

  87. Comings DE, Comings BG. Clinical and genetic relationships between autism-pervasive developmental disorder and Tourette syndrome: a study of 19 cases. Am J Med Genet. May 1 1991;39(2):180-91. [Medline].

  88. Cook EH. Autism: review of neurochemical investigation. Synapse. 1990;6(3):292-308. [Medline].

  89. Cook EH Jr. Genetics of autism. Mental Retardation and Developmental Disabilities Research Reviews. 1998;4:113-120.

  90. Courchesne E, Akshoomoff NA, Townsend J, Saitoh O. A model system for the study of attention and the cerebellum: infantile autism. Electroencephalogr Clin Neurophysiol Suppl. 1995;44:315-25. [Medline].

  91. Courchesne E, Saitoh O, Townsend JP, Yeung-Courchesne R, Press GA, Lincoln AJ, et al. Cerebellar hypoplasia and hyperplasia in infantile autism. Lancet. Jan 1 1994;343(8888):63-4. [Medline].

  92. Courchesne E, Saitoh O, Yeung-Courchesne R, Press GA, Lincoln AJ, Haas RH, et al. Abnormality of cerebellar vermian lobules VI and VII in patients with infantileautism: identification of hypoplastic and hyperplastic subgroups with MR imaging. AJR Am J Roentgenol. Jan 1994;162(1):123-30. [Medline].

  93. Courchesne E, Townsend J, Saitoh O. The brain in infantile autism: posterior fossa structures are abnormal. Neurology. Feb 1994;44(2):214-23. [Medline].

  94. Courchesne E, Townsend J, Saitoh O. The cerebellum and autism. Neurology. 1995;45:399-402.

  95. Courchesne E, Yeung-Courchesne R, Egaas B. Methodology in neuroanatomic measurement. Neurology. Feb 1994;44(2):203-8. [Medline].

  96. Cox RD, Schopler E. Aggression and self-injurious behaviors in persons with autism--the TEACCH (Treatment and Education of Autistic and related Communications Handicapped Children) approach. Acta Paedopsychiatr. 1993;56(2):85-90. [Medline].

  97. Croen LA, Grether JK, Yoshida CK, Odouli R, Van de Water J. Maternal autoimmune diseases, asthma and allergies, and childhood autism spectrumdisorders: a case-control study. Arch Pediatr Adolesc Med. Feb 2005;159(2):151-7. [Medline].

  98. Croen LA, Yoshida CK, Odouli R, Newman TB. Neonatal hyperbilirubinemia and risk of autism spectrum disorders. Pediatrics. Feb 2005;115(2):e135-8. [Medline].

  99. Dahlgren Sandberg A, Ehlers S, Hagberg B. The Rett syndrome complex: communicative functions in relation to developmental level and autistic features. Autism. In: The International Journal of Research and Practice. Vol 4. 2000:249-267.

  100. Dahlgren SO, Gillberg C. Symptoms in the first two years of life. A preliminary population study of infantile autism. Eur Arch Psychiatry Neurol Sci. 1989;238(3):169-74. [Medline].

  101. Davidovitch M, Patterson B, Gartside P. Head circumference measurements in children with autism. J Child Neurol. Sep 1996;11(5):389-93. [Medline].

  102. Dawson G, Klinger LG, Panagiotides H, Lewy A, Castelloe P. Subgroups of autistic children based on social behavior display distinct patterns of brain activity. J Abnorm Child Psychol. Oct 1995;23(5):569-83. [Medline].

  103. DelGiudice-Asch G, Simon L, Schmeidler J, Cunningham-Rundles C, Hollander E. Brief report: a pilot open clinical trial of intravenous immunoglobulin in childhood autism. J Autism Dev Disord. Apr 1999;29(2):157-60. [Medline].

  104. Deonna TW. Acquired epileptiform aphasia in children (Landau-Kleffner syndrome). J Clin Neurophysiol. Jul 1991;8(3):288-98. [Medline].

  105. DeStefano F, Chen RT. Negative association between MMR and autism. Lancet. Jun 12 1999;353(9169):1987-8. [Medline].

  106. DiLavore PC, Lord C, Rutter M. The pre-linguistic autism diagnostic observation schedule. J Autism Dev Disord. Aug 1995;25(4):355-79. [Medline].

  107. Dura JR, Mulick JA, Rasnake LK. Prevalence of stereotypy among institutionalized nonambulatory profoundly mentally retarded people. Am J Ment Defic. Mar 1987;91(5):548-9. [Medline].

  108. Egaas B, Courchesne E, Saitoh O. Reduced size of corpus callosum in autism. Arch Neurol. Aug 1995;52(8):794-801. [Medline].

  109. Elia M, Musumeci SA, Ferri R, Bergonzi P. Clinical and neurophysiological aspects of epilepsy in subjects with autism and mental retardation. Am J Ment Retard. Jul 1995;100(1):6-16. [Medline].

  110. Esquembre J. Su mejor maestro, un delfin: un delfinario de Alicante ensaya con exito terapias para que los ninos autistas aprendan a comunicarse [Your main teacher, a dolphin: a dolphinarium in Alicante teaches with results therpies for autistic children to learn to. El Pais [Madrid]. 1994;26.

  111. Fatemi SH. The role of Reelin in pathology of autism. Mol Psychiatry. 2002;7(9):919-20. [Medline].

  112. Fatemi SH, Earle J, Kanodia R, Kist D, Emamian ES, Patterson PH, et al. Prenatal viral infection leads to pyramidal cell atrophy and macrocephaly in adulthood: implications for genesis of autism and schizophrenia. Cell Mol Neurobiol. Feb 2002;22(1):25-33. [Medline].

  113. Fatemi SH, Halt AR, Realmuto G, Earle J, Kist DA, Thuras P, et al. Purkinje cell size is reduced in cerebellum of patients with autism. Cell Mol Neurobiol. Apr 2002;22(2):171-5. [Medline].

  114. Fatemi SH, Halt AR, Stary JM, Kanodia R, Schulz SC, Realmuto GR. Glutamic acid decarboxylase 65 and 67 kDa proteins are reduced in autistic parietal and cerebellar cortices. Biol Psychiatry. Oct 15 2002;52(8):805-10. [Medline].

  115. Fatemi SH, Stary JM, Egan EA. Reduced blood levels of reelin as a vulnerability factor in pathophysiology of autistic disorder. Cell Mol Neurobiol. Apr 2002;22(2):139-52. [Medline].

  116. Filipek PA. Quantitative magnetic resonance imaging in autism: the cerebellar vermis. Curr Opin Neurol. Apr 1995;8(2):134-8. [Medline].

  117. Filipek PA, Accardo PJ, Ashwal S, Baranek GT, Cook EH Jr, Dawson G, et al. Practice parameter: screening and diagnosis of autism: report of the Quality Standards Subcommittee of the American Academy of Neurology and the Child Neurology Society. Neurology. Aug 22 2000;55(4):468-79. [Medline].

  118. FitzGerald PM, Jankovic J, Glaze DG, Schultz R, Percy AK. Extrapyramidal involvement in Rett's syndrome. Neurology. Feb 1990;40(2):293-5. [Medline].

  119. FitzGerald PM, Jankovic J, Percy AK. Rett syndrome and associated movement disorders. Mov Disord. 1990;5(3):195-202. [Medline].

  120. Fleischhacker WW, Bergmann KJ, Perovich R, Pestreich LK, Borenstein M, Lieberman JA, et al. The Hillside Akathisia Scale: a new rating scale for neuroleptic-induced akathisia. Psychopharmacology Bulletin. 1989;25:222-226. [Medline].

  121. Folstein SE, Bisson E, Santangelo SL, Piven J. Finding specific genes that cause autism: a combination of approaches will be needed to maximize power. J Autism Dev Disord. Oct 1998;28(5):439-45. [Medline].

  122. Freeman BJ, Ritvo ER, Needleman R, Yokota A. The stability of cognitive and linguistic parameters in autism: a five- year prospective study. J Am Acad Child Psychiatry. Jul 1985;24(4):459-64. [Medline].

  123. Freeman BJ, Ritvo ER, Schroth PC. Behavior assessment of the syndrome of autism: behavior observation system. J Am Acad Child Psychiatry. Sep 1984;23(5):588-94. [Medline].

  124. Freeman BJ, Ritvo ER, Yokota A, Ritvo A. A scale for rating symptoms of patients with the syndrome of autism in real life settings. J Am Acad Child Psychiatry. Jan 1986;25(1):130-6. [Medline].

  125. Frith U. Autism and Asperger Syndrome. United Kingdom: Cambridge University Press; 1991.

  126. Frith U, Morton J, Leslie AM. The cognitive basis of a biological disorder: autism. Trends Neurosci. Oct 1991;14(10):433-8. [Medline].

  127. Garber HJ, McGonigle JJ, Slomka GT, Monteverde E. Clomipramine treatment of stereotypic behaviors and self-injury in patients with developmental disabilities. J Am Acad Child Adolesc Psychiatry. Nov 1992;31(6):1157-60. [Medline].

  128. Garber HJ, Ritvo ER. Magnetic resonance imaging of the posterior fossa in autistic adults. Am J Psychiatry. Feb 1992;149(2):245-7. [Medline].

  129. Garfin DG, McCallon D, Cox R. Validity and reliability of the Childhood Autism Rating Scale with autistic adolescents. J Autism Dev Disord. Sep 1988;18(3):367-78. [Medline].

  130. Gedye A. Frontal lobe seizures in autism. Med Hypotheses. Feb 1991;34(2):174-82. [Medline].

  131. Gillberg C. Chromosomal disorders and autism. J Autism Dev Disord. Oct 1998;28(5):415-25. [Medline].

  132. Gillberg C. Endogenous opioids and opiate antagonists in autism: brief review of empirical findings and implications for clinicians. Dev Med Child Neurol. Mar 1995;37(3):239-45. [Medline].

  133. Gillberg C. Neuropsychiatric disorders. Curr Opin Neurol. Apr 1998;11(2):109-14. [Medline].

  134. Gillberg C. The treatment of epilepsy in autism. J Autism Dev Disord. Mar 1991;21(1):61-77. [Medline].

  135. Gillberg C, Cederlund M. Asperger syndrome: familial and pre- and perinatal factors. J Autism Dev Disord. Apr 2005;35(2):159-66. [Medline].

  136. Gillberg C, Coleman M. The biology of the autistic syndromes. In: Clinics in Developmental Medicine. 3rd ed. London, United Kingdom: Mac Keith Press; 2000.

  137. Gillberg C, Schaumann H, Gillberg IC. Autism in immigrants: children born in Sweden to mothers born in Uganda. J Intellect Disabil Res. Apr 1995;39 (Pt 2):141-4. [Medline].

  138. Glasson EJ, Bower C, Petterson B, de Klerk N, Chaney G, Hallmayer JF. Perinatal factors and the development of autism: a population study. Arch Gen Psychiatry. Jun 2004;61(6):618-27. [Medline].

  139. Glasson EJ, Wray J. Obtaining consent affects the value of the Western Australian autism register. Med J Aust. Nov 1 2004;181(9):514-5. [Medline].

  140. Gleberzon BJ, Rosenberg-Gleberzon AL. On autism: its prevalence, diagnosis, causes, and treatment. Topics in Clinical Chiropractic. 2001;8:42-57.

  141. Goldberg D. MMR, autism, and adam. BMJ. Feb 5 2000;320(7231):389. [Medline].

  142. Goleman D. New treatments for autism arouse hope and skepticism. New York Times: July 13, 1993:C1, C11.

  143. Gordon CT, Rapoport JL, Hamburger SD, State RC, Mannheim GB. Differential response of seven subjects with autistic disorder to clomipramine and desipramine. Am J Psychiatry. Mar 1992;149(3):363-6. [Medline].

  144. Gordon CT, State RC, Nelson JE, Hamburger SD, Rapoport JL. A double-blind comparison of clomipramine, desipramine, and placebo in the treatment of autistic disorder. Arch Gen Psychiatry. Jun 1993;50(6):441-7. [Medline].

  145. Grandin T. My mind is a web browser: how people with autism think. Cerebrum. 2000;2(1):14-22.

  146. Gray C, Dutkiexicz M, Fleck C. The social story book. Jenison, Mich: Jenison Public Schools; 1993.

  147. Gray C, Garand J. Social stories: improving responses of students with autism with accurate social information. Focus on Autistic Behavior. 1993;8:1-10.

  148. Greenspan S, Wieder S. A functional developmental approach to autism spectrum disorders. JASH. 1999;24:147-161.

  149. Grether J, Croen L, Theis C, Blaxill M, Haley B, Holmes A. Baby hair, mercury toxicity and autism. Int J Toxicol. Jul-Aug 2004;23(4):275-6. [Medline].

  150. Griffith EM, Pennington BF, Wehner EA, Rogers SJ. Executive functions in young children with autism. Child Dev. Jul-Aug 1999;70(4):817-32. [Medline].

  151. Gringas P. Practical paediatric psychopharmacological prescribing in autism: the potential and the pitfalls. Autism: The International Journal of Research and Practice. Vol 4. 2000:229-247.

  152. Gross J. As autistic children grow, so does social gap. 154(53,137). The New York Times: Feburary 26 2005:A1, A8.

  153. Guerin P, Lyon G, Barthelemy C, Sostak E, Chevrollier V, Garreau B, et al. Neuropathological study of a case of autistic syndrome with severe mental retardation. Dev Med Child Neurol. Mar 1996;38(3):203-11. [Medline].

  154. Gutierrez GC, Smalley SL, Tanguay PE. Autism in tuberous sclerosis complex. J Autism Dev Disord. Apr 1998;28(2):97-103. [Medline].

  155. Hadwin J, Baron-Cohen S, Howlin P, Hill K. Does teaching theory of mind have an effect on the ability to develop conversation in children with autism?. J Autism Dev Disord. Oct 1997;27(5):519-37. [Medline].

  156. Hallett JJ, Kiessling LS. Infection-triggered OCD. J Am Acad Child Adolesc Psychiatry. Oct 1997;36(10):1320-2. [Medline].

  157. Hallett JJ, Kiessling LS. Neuroimmunology of tics and other childhood hyperkinesias. Neurol Clin. May 1997;15(2):333-44. [Medline].

  158. Hameury L, Roux S, Barthelemy C, Adrien JL, Desombre H, Sauvage D, et al. Quantified multidimensional assessment of autism and other pervasive developmental disorders. Application for bioclinical research. Eur Child Adolesc Psychiatry. Apr 1995;4(2):123-35. [Medline].

  159. Hardan AY, Minshew NJ, Keshavan MS. Corpus callosum size in autism. Neurology. Oct 10 2000;55(7):1033-6. [Medline].

  160. Harris JC. Developmental Neuropsychiatry: Assessment, Diagnosis, and Treatment. Vol 2. Oxford University Press; 1995.

  161. Harris JC. Developmental Neuropsychiatry: Fundamentals. Vol 1. Oxford University Press; 1995.

  162. Harris S, Weiss M. Right from the Start: Behavioral Intervention for Young Children with Autism. Bethesda, Md: Woodbine House; 1998.

  163. Harris SR, MacKay LL, Osborn JA. Autistic behaviors in offspring of mothers abusing alcohol and other drugs: a series of case reports. Alcohol Clin Exp Res. Jun 1995;19(3):660-5. [Medline].

  164. Harrison DW, Demaree HA, Shenal BV, Everhart DE. QEEG assisted neuropsychological evaluation of autism. Int J Neurosci. Feb 1998;93(1-2):133-40. [Medline].

  165. Hart CA. A Parent's Guide to Autism. NY: Pocket Books; 1993.

  166. Hashimoto T, Tayama M, Miyazaki M, Murakawa K, Shimakawa S, Yoneda Y, et al. Brainstem involvement in high functioning autistic children. Acta Neurol Scand. Aug 1993;88(2):123-8. [Medline].

  167. Hashimoto T, Tayama M, Murakawa K, Yoshimoto T, Miyazaki M, et al. Development of the brainstem and cerebellum in autistic patients. J Autism Dev Disord. Feb 1995;25(1):1-18. [Medline].

  168. Haznedar MM, Buchsbaum MS, Wei TC, Hof PR, Cartwright C, Bienstock CA, et al. Limbic circuitry in patients with autism spectrum disorders studied with positron emission tomography and magnetic resonance imaging. Am J Psychiatry. Dec 2000;157(12):1994-2001. [Medline].

  169. Heh CW, Smith R, Wu J, Hazlett E, Russell A, Asarnow R, et al. Positron emission tomography of the cerebellum in autism. Am J Psychiatry. Feb 1989;146(2):242-5. [Medline].

  170. Heimann M, Nelson KE, Tjus T, Gillberg C. Increasing reading and communication skills in children with autism through an interactive multimedia computer program. J Autism Dev Disord. Oct 1995;25(5):459-80. [Medline].

  171. Heinen F, Petersen H, Fietzek U, Mall V, Schulte-Monting J, Korinthenberg R. Transcranial magnetic stimulation in patients with Rett syndrome: preliminary results. Eur Child Adolesc Psychiatry. 1997;6 Suppl 1:61-3. [Medline].

  172. Hertzig ME, Snow ME, Sherman M. Affect and cognition in autism. J Am Acad Child Adolesc Psychiatry. Mar 1989;28(2):195-9. [Medline].

  173. Hippler K, Klicpera C. A retrospective analysis of the clinical case records of 'autistic psychopaths'diagnosed by Hans Asperger and his team at the University Children's Hospital, Vienna. Philos Trans R Soc Lond B Biol Sci. Feb 28 2003;358(1430):291-301. [Medline].

  174. Hobson RP, Ouston J, Lee A. What's in a face? The case of autism. Br J Psychol. Nov 1988;79 (Pt 4):441-53. [Medline].

  175. Hodgdon L. Visual strategies for improving communication. Troy, Mich: Quirk Roberts Publishing; 1995.

  176. Hofman KJ, Harris EL, Bryan RN, Denckla MB. Neurofibromatosis type 1: the cognitive phenotype. J Pediatr. Apr 1994;124(4):S1-8. [Medline].

  177. Hollander E. 24 of the Medical Psychiatry Series. In: Autism Spectrum Disorders. New York: Marcel Dekker, Inc; 2003:[Full Text].

  178. Hollander E, Cartwright C, Wong CM. A dimensional approach to the autism spectrum. CNS Spectrums. 1998;3(3):22-39.

  179. Hollander E, DelGiudice-Asch G, Simon L, Schmeidler J, Cartwright C, DeCaria CM, et al. B lymphocyte antigen D8/17 and repetitive behaviors in autism. Am J Psychiatry. Feb 1999;156(2):317-20. [Medline].

  180. Hollander E, Kaplan A, Cartwright C, Reichman D. Venlafaxine in children, adolescents, and young adults with autism spectrum disorders: an open retrospective clinical report. J Child Neurol. Feb 2000;15(2):132-5. [Medline].

  181. Hollander E, Novotny S, Allen A, Aronowitz B, Cartwright C, DeCaria C. The relationship between repetitive behaviors and growth hormone response to sumatriptan challenge in adult autistic disorder. Neuropsychopharmacology. Feb 2000;22(2):163-7. [Medline].

  182. Holmes DL. Autism Through the Lifespan. In: the Eden Model. Woodbine House: Bethesda, Md; 1998.

  183. Honda H, Shimizu Y, Rutter M. No effect of MMR withdrawal on the incidence of autism: a total populationstudy. J Child Psychol Psychiatry. Jun 2005;46(6):572-9. [Medline].

  184. Horrigan JP, Barnhill LJ. Risperidone and explosive aggressive autism. J Autism Dev Disord. Jun 1997;27(3):313-23. [Medline].

  185. Horrigan JP, Barnhill LJ, Courvoisie HE. Olanzapine in PDD. J Am Acad Child Adolesc Psychiatry. Sep 1997;36(9):1166-7. [Medline].

  186. Horvath K, Papadimitriou JC, Rabsztyn A, Drachenberg C, Tildon JT. Gastrointestinal abnormalities in children with autistic disorder. J Pediatr. Nov 1999;135(5):559-63. [Medline].

  187. Horvath K, Stefanatos G, Sokolski KN, Wachtel R, Nabors L, Tildon JT. Improved social and language skills after secretin administration in patients with autistic spectrum disorders. J Assoc Acad Minor Phys. 1998;9(1):9-15. [Medline].

  188. Hoshino Y, Kaneko M, Yashima Y, Kumashiro H, Volkmar FR, Cohen DJ. Clinical features of autistic children with setback course in their infancy. Jpn J Psychiatry Neurol. Jun 1987;41(2):237-45. [Medline].

  189. Howlin P. Behavioural techniques to reduce self-injurious behaviour in children with autism. Acta Paedopsychiatr. 1993;56(2):75-84. [Medline].

  190. Howlin P. Prognosis in autism: do specialist treatments affect long-term outcome?. Eur Child Adolesc Psychiatry. Jun 1997;6(2):55-72. [Medline].

  191. Hughes C, Soares-Boucaud I, Hochmann J, Frith U. Social behaviour in pervasive developmental disorders: effects of informant, group and "theory-of-mind". Eur Child Adolesc Psychiatry. Dec 1997;6(4):191-8. [Medline].

  192. Hughes R. Living with 'the look': how passersby see my autistic son's antics is making me change the way I see myself. Newsweek: 1997:20-21.

  193. Hultman CM, Sparen P, Cnattingius S. Perinatal risk factors for infantile autism. Epidemiology. Jul 2002;13(4):417-23. [Medline].

  194. Hultman CM, Sparen P. Autism--prenatal insults or an epiphenomenon of a strongly genetic disorder?. Lancet. Aug 7-13 2004;364(9433):485-7. [Medline].

  195. Insel TR, O'Brien DJ, Leckman JF. Oxytocin, vasopressin, and autism: is there a connection?. Biol Psychiatry. Jan 15 1999;45(2):145-57. [Medline].

  196. Insel TR, Winslow JT. Serotonin and neuropeptides in affiliative behaviors. Biol Psychiatry. Aug 1 1998;44(3):207-19. [Medline].

  197. James G. Autistic teen-ager arraigned in death of his infant nephew. New York Times. December 20, 1994:B2.

  198. Jan JE, Abroms IF, Freeman RD, Brown GM, Espezel H, Connolly MB. Rapid cycling in severely multidisabled children: a form of bipolar affective disorder?. Pediatr Neurol. Feb 1994;10(1):34-9. [Medline].

  199. Jick H, Kaye JA. Autism and DPT vaccination in the United Kingdom. N Engl J Med. Jun 24 2004;350(26):2722-3. [Medline].

  200. Jick H, Kaye JA. Epidemiology and possible causes of autism. Pharmacotherapy. Dec 2003;23(12):1524-30. [Medline].

  201. Jick H, Kaye JA. Study fails to establish diagnostic substitution as a factor in increased rate of autism. Authors' reply. Pharmacotherapy. 2004;24:813-815.

  202. Jick H, Kaye JA, Black C. Changes in risk of autism in the U.K. for birth cohorts 1990-1998. Epidemiology. Sep 2003;14(5):630-2. [Medline].

  203. Jinnah HA, Harris JC, Reich SC. The motor disorder of Lesch-Nyhan disease. Mov Disord. 1998;13 (Suppl 2):98.

  204. Johnson LA. N.J. town might have unique cluster of autism. USA Today; January 20, 1999:10A.

  205. Johnson MH, Siddons F, Frith U, Morton J. Can autism be predicted on the basis of infant screening tests?. Dev Med Child Neurol. Apr 1992;34(4):316-20. [Medline].

  206. Juul-Dam N, Townsend J, Courchesne E. Prenatal, perinatal, and neonatal factors in autism, pervasive developmentaldisorder-not otherwise specified, and the general population. Pediatrics. Apr 2001;107(4):E63. [Medline].

  207. Kano Y, Ohta M, Nagai Y, Yokota K, Shimizu Y. Tourette's disorder coupled with infantile autism: a prospective study of two boys. Jpn J Psychiatry Neurol. Mar 1988;42(1):49-57. [Medline].

  208. Kawasaki Y, Yokota K, Shinomiya M, Shimizu Y, Niwa S. Brief report: electroencephalographic paroxysmal activities in the frontal area emerged in middle childhood and during adolescence in a follow-up study of autism. J Autism Dev Disord. Oct 1997;27(5):605-20. [Medline].

  209. Keenan M, Kerr KP, Dillenburger K, eds. Parents' Education as Autism Therapists. In: Applied Behaviour Analysis in Context. Philadelphia, Pa: Jessica Kingsley Publisher; 1999.

  210. Kemner C, Verbaten MN, Cuperus JM, Camfferman G, van Engeland H. Auditory event-related brain potentials in autistic children and three different control groups. Biol Psychiatry. Aug 1 1995;38(3):150-65. [Medline].

  211. Kerbeshian J, Burd L. Epidemiology and comorbidity. The North Dakota prevalence studies of Tourette syndrome and other developmental disorders. Adv Neurol. 1992;58:67-74. [Medline].

  212. Klee BJ, Back S, Green WH. Tricyclic antidepressants in child and adolescent psychiatry: indications, use, and safety. Primary Psychiatry. 1998;5(7):86-90.

  213. Klin A, Volkmar FR, Sparrow SS. Asperger Syndrome. NY: Guilford Publications; 2000.

  214. Koegel L, Koegel R, Harrower J. Pivotal response intervention I: Overview. JASH. 1999;24:174-185.

  215. Koegel RL, Koegel LK. Teaching children with autism: strategies for initiating positive interactions and improving learning opportunities. Baltimore, Md: Brookes; 1995.

  216. Koegel RL, Mentis M. Motivation in childhood autism: can they or won't they?. J Child Psychol Psychiatry. Mar 1985;ID - MH28210/MH/NIMH(2):185-91. [Medline].

  217. Krug DA, Arick J, Almond P. Behavior checklist for identifying severely handicapped individuals with high levels of autistic behavior. J Child Psychol Psychiatry. Jul 1980;21(3):221-9. [Medline].

  218. Kurlan R. Diagnostic criteria for genetic studies of Tourette syndrome. Arch Neurol. May 1997;54(5):517-8. [Medline].

  219. Kurlan R. Future direction of research in Tourette syndrome. Neurol Clin. May 1997;15(2):451-6. [Medline].

  220. Kurlan R. Tourette syndrome. Treatment of tics. Neurol Clin. May 1997;15(2):403-9. [Medline].

  221. Lafargue T, Brasic J. Neurodevelopmental hypothesis of schizophrenia: a central sensory disturbance. Med Hypotheses. Oct 2000;55(4):314-8. [Medline].

  222. Lainhart JE, Folstein SE. Affective disorders in people with autism: a review of published cases. J Autism Dev Disord. Oct 1994;24(5):587-601. [Medline].

  223. Lainhart JE, Piven J. Diagnosis, treatment, and neurobiology of autism in children. Curr Opin Pediatr. Aug 1995;7(4):392-400. [Medline].

  224. Lamb JA, Moore J, Bailey A, Monaco AP. Autism: recent molecular genetic advances. Hum Mol Genet. Apr 12 2000;9(6):861-8. [Medline].

  225. Lanier JL, Grandin T, Green RD, Avery D, McGee K. The relationship between reaction to sudden, intermittent movements and sounds and temperament. J Anim Sci. Jun 2000;78(6):1467-74. [Medline].

  226. Larsen FW, Mouridsen SE. The outcome in children with childhood autism and Asperger syndrome originally diagnosed as psychotic. A 30-year follow-up study of subjects hospitalized as children. Eur Child Adolesc Psychiatry. Dec 1997;6(4):181-90. [Medline].

  227. [Best Evidence] Larsson HJ, Eaton WW, Madsen KM, Vestergaard M, Olesen AV, Agerbo E, et al. Risk factors for autism: perinatal factors, parental psychiatric history, andsocioeconomic status. Am J Epidemiol. May 15 2005;161(10):916-25; discussion 926-8. [Medline].

  228. Lawler CP, Croen LA, Grether JK, Van de Water J. Identifying environmental contributions to autism: provocative clues and falseleads. Ment Retard Dev Disabil Res Rev. 2004;10(4):292-302. [Medline].

  229. Le Couteur A. Autism: current understanding and management. Br J Hosp Med. Jun 1990;43(6):448-52. [Medline].

  230. Le Couteur A, Rutter M, Lord C, Rios P, Robertson S, Holdgrafer M, et al. Autism diagnostic interview: a standardized investigator-based instrument. J Autism Dev Disord. Sep 1989;19(3):363-87. [Medline].

  231. Leary MR, Hill DA. Moving on: autism and movement disturbance. Ment Retard. Feb 1996;34(1):39-53. [Medline].

  232. Leboyer M, Philippe A, Bouvard M, Guilloud-Bataille M, Bondoux D, Tabuteau F, et al. Whole blood serotonin and plasma beta-endorphin in autistic probands and their first-degree relatives. Biol Psychiatry. Jan 15 1999;45(2):158-63. [Medline].

  233. Lewis RB. Assistive technology and learning disabilities: today's realities and tomorrow's promises. J Learn Disabil. Jan-Feb 1998;31(1):16-26, 54. [Medline].

  234. Lincoln AJ, Courchesne E, Harms L, Allen M. Sensory modulation of auditory stimuli in children with autism and receptive developmental language disorder: event-related brain potential evidence. J Autism Dev Disord. Oct 1995;25(5):521-39. [Medline].

  235. Lomia M, Daraselia M. Metoclopramide and naloxone in treatment of tics. Mov Disord. 1998;13 (Suppl 2):203.

  236. London E, Johnson C. The neuropathology of autism: what we know and don't know. Narrative: Newsletter of the National Alliance for Autism Research. 1998:1, 16-20.

  237. Lord C. Follow-up of two-year-olds referred for possible autism. J Child Psychol Psychiatry. Nov 1995;36(8):1365-82. [Medline].

  238. Lord C, Risi S, Lambrecht L, Cook EH Jr, Leventhal BL, DiLavore PC, et al. The autism diagnostic observation schedule-generic: a standard measure of social and communication deficits associated with the spectrum of autism. J Autism Dev Disord. Jun 2000;30(3):205-23. [Medline].

  239. Lord C, Rutter M, Goode S, Heemsbergen J, Jordan H, Mawhood L, et al. Autism diagnostic observation schedule: a standardized observation of communicative and social behavior. J Autism Dev Disord. Jun 1989;19(2):185-212. [Medline].

  240. Lord C, Rutter M, Le Couteur A. Autism Diagnostic Interview-Revised: a revised version of a diagnostic interview for caregivers of individuals with possible pervasive developmental disorders. J Autism Dev Disord. Oct 1994;24(5):659-85. [Medline].

  241. Lord C, Schopler E. Stability of assessment results of autistic and non-autistic language- impaired children from preschool years to early school age. J Child Psychol Psychiatry. Jul 1989;30(4):575-90. [Medline].

  242. Lord C, Schopler E. The role of age at assessment, developmental level, and test in the stability of intelligence scores in young autistic children. J Autism Dev Disord. Dec 1989;19(4):483-99. [Medline].

  243. Lord C, Storoschuk S, Rutter M. Using the ADI-R to diagnose autism in preschool children. Infant Mental Health Journal. Fall 1993;14 (3):234-252.

  244. Lovaas OI. Behavioral treatment and normal educational and intellectual functioning in young autistic children. J Consult Clin Psychol. Feb 1987;55(1):3-9. [Medline].

  245. Mahoney WJ, Szatmari P, MacLean JE, Bryson SE, Bartolucci G, Walter SD, et al. Reliability and accuracy of differentiating pervasive developmental disorder subtypes. J Am Acad Child Adolesc Psychiatry. Mar 1998;37(3):278-85. [Medline].

  246. Marshall BL, Napolitano DA, McAdam DB, Dunleavy III JJ, Tessing JL, Varrell J. Venlafaxine and increased aggression in a female with autism. J Am Acad Child Adolesc Psychiatry. Apr 2003;42(4):383-4. [Medline].

  247. Matese M, Matson JL, Sevin J. Comparison of psychotic and autistic children using behavioral observation. J Autism Dev Disord. Feb 1994;24(1):83-94. [Medline].

  248. Matthews J, Williams J. The self-help guide for special kids and their parents. Philadelphia, Pa: Jessica Kingsley Publisher; 2000.

  249. McCracken JT, McGough J, Shah B, Cronin P, Hong D, Aman MG, et al. Risperidone in children with autism and serious behavioral problems. N Engl J Med. Aug 1 2002;347(5):314-21. [Medline].

  250. McDougle CJ, Kem DL, Posey DJ. Case series: use of ziprasidone for maladaptive symptoms in youths with autism. J Am Acad Child Adolesc Psychiatry. Aug 2002;41(8):921-7. [Medline].

  251. McDougle CJ, Price LH, Goodman WK. Fluvoxamine treatment of coincident autistic disorder and obsessive- compulsive disorder: a case report. J Autism Dev Disord. Dec 1990;20(4):537-43. [Medline].

  252. McDougle CJ, Price LH, Volkmar FR. Recent advances in the pharmacotherapy of autism and related conditions. Child Adolesc Psychiatr Clin N Am. 1994;3:71-89.

  253. McDougle CJ, Price LH, Volkmar FR, Goodman WK, Ward-O'Brien D, Nielsen J, et al. Clomipramine in autism: preliminary evidence of efficacy. J Am Acad Child Adolesc Psychiatry. Jul 1992;31(4):746-50. [Medline].

  254. McDougle CJ, Scahill L, McCracken JT, Aman MG, Tierney E, Arnold LE, et al. Research Units on Pediatric Psychopharmacology (RUPP) Autism Network. Background and rationale for an initial controlled study of risperidone. Child Adolesc Psychiatr Clin N Am. Jan 2000;9(1):201-24. [Medline].

  255. McGee G, Morrier M, Daly T. An incidental teaching approach to early intervention for toddlers with autism. JASH. 1999;24:133-146.

  256. McInnes LA, González PJ, Manghi ER, Esquivel M, Monge S, Delgado MF, et al. A genetic study of autism in Costa Rica: multiple variables affecting IQ scoresobserved in a preliminary sample of autistic cases. BMC Psychiatry. Mar 21 2005;5(1):15. [Medline].

  257. McLennan JD, Lord C, Schopler E. Sex differences in higher functioning people with autism. J Autism Dev Disord. Jun 1993;23(2):217-27. [Medline].

  258. McManus IC, Murray B, Doyle K, Baron-Cohen S. Handedness in childhood autism shows a dissociation of skill and preference. Cortex. Sep 1992;28(3):373-81. [Medline].

  259. Mendez MF, Mirea A. Adult head-banging and stereotypic movement disorders. Mov Disord. Sep 1998;13(5):825-8. [Medline].

  260. Merritt JL 2nd, Jalal SM, Barbaresi WJ, Babovic-Vuksanovic D. 14q32.3 deletion syndrome with autism. Am J Med Genet A. Feb 15 2005;133(1):99-100. [Medline].

  261. Mesibov GB. Social skills training with verbal autistic adolescents and adults: a program model. J Autism Dev Disord. Dec 1984;14(4):395-404. [Medline].

  262. Miller MT, Strömland K, Gillberg C, Johansson M, Nilsson EW. The puzzle of autism: an ophthalmologic contribution. Trans Am Ophthalmol Soc. 1998;96:369-85; discussion 385-7. [Medline].

  263. Minderaa RB, Anderson GM, Volkmar FR, Akkerhuis GW, Cohen DJ. Noradrenergic and adrenergic functioning in autism. Biol Psychiatry. Aug 15 1994;36(4):237-41. [Medline].

  264. Minshew NJ, Meyer J, Goldstein G. Abstract reasoning in autism: a dissociation between concept formation and concept identification. Neuropsychology. Jul 2002;16(3):327-34. [Medline].

  265. Minshew NJ, Sweeney J, Luna B. Autism as a selective disorder of complex information processing and underdevelopment of neocortical systems. Mol Psychiatry. 2002;7 Suppl 2:S14-5. [Medline].

  266. MJ Powers & Co. Secretin update. Child and Adolescent Psychiatry Alerts. 2000;Available at: http://www.alertpubs.com. [Full Text].

  267. MJ Powers & Co. Transdermal secretin. Child and Adolescent Psychiatry Alerts. 2000;Available at: http://www.alertpubs.com. [Full Text].

  268. Modahl C, Green L, Fein D, Morris M, Waterhouse L, Feinstein C, et al. Plasma oxytocin levels in autistic children. Biol Psychiatry. Feb 15 1998;43(4):270-7. [Medline].

  269. Mudford O. Auditory integration training: recent UK study. Autism: The International Journal of Research and Practice. Vol 4. 2000:337-338.

  270. Mudford OC, Cross BA, Breen S, Cullen C, Reeves D, Gould J, et al. Auditory integration training for children with autism: no behavioral benefits detected. Am J Ment Retard. Mar 2000;105(2):118-29. [Medline].

  271. Muller RA, Courchesne E. Autism's home in the brain. Neurology. 2000;54:270.

  272. Murakami JW, Courchesne E, Press GA, Yeung-Courchesne R, Hesselink JR. Reduced cerebellar hemisphere size and its relationship to vermal hypoplasia in autism. Arch Neurol. Jun 1989;46(6):689-94. [Medline].

  273. Nally B, Houlton B, Ralph S. The management of television and video by parents of children with autism. Autism: The International Journal of Research and Practice. Vol 4. 2000:331-337.

  274. Navarro F, Gomez-Ferrer C, Canteras M. Fluctuating asymmetry and obstetric complications in autism. 1. Revista de Psiquiatria Infanto-Juvenil; 1996:6-13.

  275. Nelson KB. The neurologically impaired child and alleged malpractice at birth. Neurol Clin. May 1999;17(2):283-93. [Medline].

  276. Nelson KB, Grether JK, Croen LA. Neuropeptides and neurotrophins in neonatal blood of children with autism, mental retrdation, or cerebral palsy. Neurology. 2000;54 (Suppl3):A247.

  277. Neville BG, Harkness WF, Cross JH, Cass HC, Burch VC, Lees JA, et al. Surgical treatment of severe autistic regression in childhood epilepsy. Pediatr Neurol. Feb 1997;16(2):137-40. [Medline].

  278. Newschaffer CJ, Cole SR. Risk factors for autism---perinatal factors, parental psychiatric history, and socioeconomic status. American Journal of Epidemiology. 2005;161:926-928.

  279. Newschaffer CJ, Falb MD, Gurney JG. National autism prevalence trends from United States special education data. Pediatrics. Mar 2005;115(3):e277-82. [Medline].

  280. Nicolson R, Awad G, Sloman L. An open trial of risperidone in young autistic children. J Am Acad Child Adolesc Psychiatry. Apr 1998;37(4):372-6. [Medline].

  281. Novotny S, Hollander E, Allen A, Mosovich S, Aronowitz B, Cartwright C, et al. Increased growth hormone response to sumatriptan challenge in adult autistic disorders. Psychiatry Res. May 15 2000;94(2):173-7. [Medline].

  282. Ornitz EM, Atwell CW, Kaplan AR, Westlake JR. Brain-stem dysfunction in autism. Results of vestibular stimulation. Arch Gen Psychiatry. Oct 1985;42(10):1018-25. [Medline].

  283. Overall JE, Campbell M. Behavioral assessment of psychopathology in children: infantile autism. J Clin Psychol. Sep 1988;44(5):708-16. [Medline].

  284. Owley T, Cook EH, Jr., Volkmar F. The current status of secretin in autistic disorder. AACAP (American Acadmay of Child and Adolescent Psychiatry) News. May/June 2002;33 (3):108-109.

  285. Owley T, Steele E, Corsello C, Risi S, McKaig K, Lord C, et al. A Double-Blind, Placebo-Controlled Trial of Secretin for the Treatment of Autistic Disorder. MedGenMed. Oct 6 1999;E2. [Medline].

  286. Panksepp J. A neurochemical theory of autism. Trends in Neurosciences. 1979;2:174-179.

  287. Park RJ, Bolton PF. Pervasive developmental disorder and obstetric complications in children andadolescents with tuberous sclerosis. Autism. Sep 2001;5(3):237-48. [Medline].

  288. Pennington BF, Ozonoff S. Executive functions and developmental psychopathology. J Child Psychol Psychiatry. Jan 1996;37(1):51-87. [Medline].

  289. Percy A, Gillberg C, Hagberg B, Witt-Engerstrom I. Rett syndrome and the autistic disorders. Neurol Clin. Aug 1990;8(3):659-76. [Medline].

  290. Perez-Pena R. Autistic youth is charged in death of baby. New York Times: December 19, 1994:B1, B3.

  291. Piven J, Arndt S. The cerebellum and autism. Neurology. Feb 1995;45(2):398-402. [Medline].

  292. Piven J, Arndt S, Bailey J, Havercamp S, Andreasen NC, Palmer P. An MRI study of brain size in autism. Am J Psychiatry. Aug 1995;152(8):1145-9. [Medline].

  293. Piven J, Bailey J, Ranson BJ, Arndt S. No difference in hippocampus volume detected on magnetic resonance imaging in autistic individuals. J Autism Dev Disord. Apr 1998;28(2):105-10. [Medline].

  294. Plioplys AV. Autism: electroencephalogram abnormalities and clinical improvement with valproic acid. Arch Pediatr Adolesc Med. Feb 1994;148(2):220-2. [Medline].

  295. Potenza MN, Holmes JP, Kanes SJ, McDougle CJ. Olanzapine treatment of children, adolescents, and adults with pervasive developmental disorders: an open-label pilot study. J Clin Psychopharmacol. Feb 1999;19(1):37-44. [Medline].

  296. Potenza MN, McDougle CJ. The role of serotonin in autism-spectrum disorders. CNS Spectrums. 1997;2 (5):25-42.

  297. Poustka F, Lisch S. Autistic behaviour domains and their relation to self-injurious behaviour. Acta Paedopsychiatr. 1993;56(2):69-73. [Medline].

  298. Poustka F, Lisch S, Rühl D, Sacher A, Schmötzer G, Werner K. The standardized diagnosis of autism, Autism Diagnostic Interview- Revised: interrater reliability of the German form of the interview. Psychopathology. 1996;29(3):145-53. [Medline].

  299. Quill K. Teaching children with autism: strategies to enhance communication with socialization. Albany, NY: Delmar Publisher; 1995.

  300. Quinn B, Malone A. Pervasive developmental disorder. An altered perspective. Philadelphia, Pa: Jessica Kingsley Publisher; 2000.

  301. Rankin K. Growing up severely autistic. They call me Gabriel. Philadelphia, Pa: Jessica Kingsley Publisher; 2000.

  302. Rapin I. Autism in search of a home in the brain. Neurology. Mar 23 1999;52(5):902-4. [Medline].

  303. Rapin I. Disorders of higher cerebral function in preschool children. Second of two parts. Am J Dis Child. Nov 1988;142(11):1178-82. [Medline].

  304. Richer J. Syndromes of acquired autism. Association for Child Psychology and Psychiatry Newsletter. 1989;11(2):33-34.

  305. Richman S. Raising a child with autism. A guide to applied behavior analysis for parents. Philadelphia, Pa: Jessica Kingsley Publisher; 2000.

  306. Riddle MA, Bernstein GA, Cook EH, Leonard HL, March JS, Swanson JM. Anxiolytics, adrenergic agents, and naltrexone. J Am Acad Child Adolesc Psychiatry. May 1999;38(5):546-56. [Medline].

  307. Rimland B. Comments on "Secretin and autism: a two-part clinical investigation" by M.G. Chez et al. J Autism Dev Disord. Apr 2000;30(2):95; discussion 97-8. [Medline].

  308. Rimland B. Secretin treatment for autism. N Engl J Med. Apr 20 2000;342(16):1216-7; discussion 1218. [Medline].

  309. Rimland B. Secretin: real therapeutic potential (response). J Pediatr Gastroenterol Nutr. Feb 2000;30(2):113; discussion 113-4. [Medline].

  310. Ritvo ER, Freeman BJ, Scheibel AB, Duong T, Robinson H, Guthrie D, et al. Lower Purkinje cell counts in the cerebella of four autistic subjects: initial findings of the UCLA-NSAC Autopsy Research Report. Am J Psychiatry. Jul 1986;143(7):862-6. [Medline].

  311. Ritvo ER, Mason-Brothers A, Freeman BJ, Pingree C, Jenson WR, McMahon WM, et al. The UCLA-University of Utah epidemiologic survey of autism: the etiologic role of rare diseases. Am J Psychiatry. Dec 1990;147(12):1614-21. [Medline].

  312. Roazen P. The rise and fall of Bruno Bettelheim. Psychohist Rev. Spring 1992;20(3):221-50. [Medline].

  313. Rogers SJ, Bennetto L, McEvoy R, Pennington BF. Imitation and pantomime in high-functioning adolescents with autism spectrum disorders. Child Dev. Oct 1996;67(5):2060-73. [Medline].

  314. Rogers SJ, DiLalla DL. Age of symptom onset in young children with pervasive developmental disorders. J Am Acad Child Adolesc Psychiatry. Nov 1990;29(6):863-72. [Medline].

  315. Rojahn J, Tasse MJ, Sturmey P. The Stereotyped Behavior Scale for adolescents and adults with mental retardation. Am J Ment Retard. Sep 1997;102(2):137-46. [Medline].

  316. Rossi PG, Parmeggiani A, Bach V, Santucci M, Visconti P. EEG features and epilepsy in patients with autism. Brain Dev. May-Jun 1995;17(3):169-74. [Medline].

  317. Rothenberger A. Psychopharmacological treatment of self-injurious behavior in individuals with autism. Acta Paedopsychiatr. 1993;56(2):99-104. [Medline].

  318. Rothenberger A. Self-injurious behaviour (SIB)--from definition to human rights. Acta Paedopsychiatr. 1993;56(2):65-7. [Medline].

  319. Roux S, Bruneau N, Garreau B, Guérin P, Adrien JL, Dansart P, et al. Bioclinical profiles of autism and other developmental disorders using a multivariate statistical approach. Biol Psychiatry. Dec 15 1997;42(12):1148-56. [Medline].

  320. Rumsey JM, Ernst M. Functional neuroimaging of autistic disorders. Ment Retard Dev Disabil Res Rev. 2000;6(3):171-9. [Medline].

  321. Rutter M. Aetiology of autism: findings and questions. J Intellect Disabil Res. Apr 2005;49(Pt 4):231-8. [Medline].

  322. Rutter M. Autism research: lessons from the past and prospects for the future. J Autism Dev Disord. Apr 2005;35(2):241-57. [Medline].

  323. Rutter M. Incidence of autism spectrum disorders: changes over time and their meaning. Acta Paediatr. Jan 2005;94(1):2-15. [Medline].

  324. Sahota PK, Miles JH, Wang CH. Sleep disorders in children with autism. Neurology. 1997;48 (3):A258.

  325. Saitoh O, Courchesne E, Egaas B, Lincoln AJ, Schreibman L. Cross-sectional area of the posterior hippocampus in autistic patients with cerebellar and corpus callosum abnormalities. Neurology. Feb 1995;45(2):317-24. [Medline].

  326. Sallustro F, Atwell CW. Body rocking, head banging, and head rolling in normal children. J Pediatr. Oct 1978;93(4):704-8. [Medline].

  327. Samson K. New studies shed light on brain changes in early autism. Neurology Today. 2002;2 (8):1, 18, 19.

  328. Sanchez LE, Campbell M, Small AM, Cueva JE, Armenteros JL, Adams PB. A pilot study of clomipramine in young autistic children. J Am Acad Child Adolesc Psychiatry. Apr 1996;35(4):537-44. [Medline].

  329. Sandler AD, Bodfish JW. Placebo effects in autism: lessons from secretin. J Dev Behav Pediatr. Oct 2000;21(5):347-50. [Medline].

  330. Sandler AD, Sutton KA, DeWeese J, Girardi MA, Sheppard V, Bodfish JW. Lack of benefit of a single dose of synthetic human secretin in the treatment of autism and pervasive developmental disorder. N Engl J Med. Dec 9 1999;341(24):1801-6. [Medline].

  331. Schifter T, Hoffman JM, Hatten HP Jr, Hanson MW, Coleman RE, DeLong GR. Neuroimaging in infantile autism. J Child Neurol. Apr 1994;9(2):155-61. [Medline].

  332. Schopler E, Mesibov GB. Social behavior in autism. NY: Plenum; 1992.

  333. Schopler E, Van Bourgondien ME, Bristol MM. Preschool Issues in Autism. NY: Plenum Press; 1993.

  334. Schreibman L. Diagnostic features of autism. J Child Neurol. 1988;3 Suppl:S57-64. [Medline].

  335. Schutt CE. Seretin and autism: a clue but not a cure. National Alliance for Autism Research Newsletter. 1998;21-25.

  336. Siegel B, Pliner C, Eschler J, Elliott GR. How children with autism are diagnosed: difficulties in identification of children with multiple developmental delays. J Dev Behav Pediatr. Aug 1988;9(4):199-204. [Medline].

  337. Siegel BV Jr, Asarnow R, Tanguay P, Call JD, Abel L, Ho A, et al. Regional cerebral glucose metabolism and attention in adults with a history of childhood autism. J Neuropsychiatry Clin Neurosci. Fall 1992;4(4):406-14. [Medline].

  338. Siegel BV Jr, Nuechterlein KH, Abel L, Wu JC, Buchsbaum MS. Glucose metabolic correlates of continuous performance test performance in adults with a history of infantile autism, schizophrenics, and controls. Schizophr Res. Sep 1995;17(1):85-94. [Medline].

  339. Silva RR, Malone RP, Anderson LT, Shay J, Campbell M. Haloperidol withdrawal and weight changes in autistic children. Psychopharmacol Bull. 1993;29(2):287-91. [Medline].

  340. Simon N. Autism's home in the brain. Neurology. Jan 11 2000;54(1):269-70. [Medline].

  341. Singer HS. Pediatric movement disorders: new developments. Mov Disord. 1998;13 (Suppl 2):17.

  342. Skjeldal OH, Sponheim E, Ganes T, Jellum E, Bakke S. Childhood autism: the need for physical investigations. Brain Dev. Jun 1998;20(4):227-33. [Medline].

  343. Smith B, Chung MC, Vostanis P. The path to care in autism: is it better now?. J Autism Dev Disord. Oct 1994;24(5):551-63. [Medline].

  344. Smith DC. Assistive technology: funding options and strategies. Mental and Physical Disabilities Law Report. 1998;22 (1):115-123.

  345. Smith DE, Miller SD, Stewart M, Walter TL, McConnell JV. Conductive hearing loss in autistic, learning-disabled, and normal children. J Autism Dev Disord. Mar 1988;18(1):53-65. [Medline].

  346. Smith MD. Treatment of pica in an adult disabled by autism by differential reinforcement of incompatible behavior. J Behav Ther Exp Psychiatry. Sep 1987;18(3):285-8. [Medline].

  347. Sobesky WE, Taylor AK, Pennington BF, Bennetto L, Porter D, Riddle J, et al. Molecular/clinical correlations in females with fragile X. Am J Med Genet. Aug 9 1996;64(2):340-5. [Medline].

  348. Sparks BF, Friedman SD, Shaw DW, Aylward EH, Echelard D, Artru AA, et al. Brain structural abnormalities in young children with autism spectrum disorder. Neurology. Jul 23 2002;59(2):184-92. [Medline].

  349. Sponheim E, Skjeldal O. Autism and related disorders: epidemiological findings in a Norwegian study using ICD-10 diagnostic criteria. J Autism Dev Disord. Jun 1998;28(3):217-27. [Medline].

  350. Starr EM, Berument SK, Tomlins M, Papanikolaou K, Rutter M. Brief Report: Autism in Individuals with Down Syndrome. J Autism Dev Disord. Oct 2005;35(5):665-73. [Medline].

  351. Steffenburg S, Gillberg CL, Steffenburg U, Kyllerman M. Autism in Angelman syndrome: a population-based study. Pediatr Neurol. Feb 1996;14(2):131-6. [Medline].

  352. Steffenburg S, Steffenburg U, Gillberg C. Autism spectrum disorders in children with active epilepsy and learning disability: comorbidity, pre- and perinatal background, and seizure characteristics. Dev Med Child Neurol. Nov 2003;45(11):724-30. [Medline].

  353. Stein DJ, Hollander E. Obsessive-compulsive spectrum disorders. J Clin Psychiatry. Jun 1995;56(6):265-6. [Medline].

  354. Stern JS, Robertson MM. Tics associated with autistic and pervasive developmental disorders. Neurol Clin. May 1997;15(2):345-55. [Medline].

  355. Stone WL, Hoffman EL, Lewis SE, Ousley OY. Early recognition of autism. Parental reports vs clinical observation. Arch Pediatr Adolesc Med. Feb 1994;148(2):174-9. [Medline].

  356. Stone WL, Lemanek KL, Fishel PT, Fernandez MC, Altemeier WA. Play and imitation skills in the diagnosis of autism in young children. Pediatrics. Aug 1990;86(2):267-72. [Medline].

  357. Sturmey P. Assessing the functions of aberrant behaviors: a review of psychometric instruments. J Autism Dev Disord. Jun 1994;24(3):293-304. [Medline].

  358. Sussman F. More than words: helping parents promote communication and social skills in children with autism spectrum disorder. Ontario, Canada: The Hanen Centre; 1999.

  359. Sverd J. Tourette syndrome and autistic disorder: a significant relationship. Am J Med Genet. May 1 1991;39(2):173-9. [Medline].

  360. Sverd J, Montero G, Gurevich N. Brief report: cases for an association between Tourette syndrome, autistic disorder, and schizophrenia-like disorder. J Autism Dev Disord. Jun 1993;23(2):407-13. [Medline].

  361. Sweeten TL, Posey DJ, Shekhar A, McDougle CJ. The amygdala and related structures in the pathophysiology of autism. Pharmacol Biochem Behav. Mar 2002;71(3):449-55. [Medline].

  362. Szatmari P, Archer L, Fisman S, Streiner DL. Parent and teacher agreement in the assessment of pervasive developmental disorders. J Autism Dev Disord. Dec 1994;24(6):703-17. [Medline].

  363. Tallal P, Miller SL, Bedi G, Byma G, Wang X, Nagarajan SS, et al. Language comprehension in language-learning impaired children improved with acoustically modified speech. Science. Jan 5 1996;271(5245):81-4. [Medline].

  364. Tanguay PE, Robertson J, Derrick A. A dimensional classification of autism spectrum disorder by social communication domains. J Am Acad Child Adolesc Psychiatry. Mar 1998;37(3):271-7. [Medline].

  365. Taylor B, Miller E, Farrington CP, Petropoulos MC, Favot-Mayaud I, Li J, et al. Autism and measles, mumps, and rubella vaccine: no epidemiological evidence for a causal association. Lancet. Jun 12 1999;353(9169):2026-9. [Medline].

  366. Teitelbaum P, Teitelbaum O, Nye J, Fryman J, Maurer RG. Movement analysis in infancy may be useful for early diagnosis of autism. Proc Natl Acad Sci U S A. Nov 10 1998;95(23):13982-7. [Medline].

  367. Tourette Syndrome Classification Study Group. Definitions and classification of tic disorders. Arch Neurol. Oct 1993;50(10):1013-6. [Medline].

  368. Tranebjaerg L, Kure P. Prevalence of fra(X) and other specific diagnoses in autistic individuals in a Danish county. American Journal of Medical Genetics. 1991;39:212-214. [Medline].

  369. Treffert DA. The savant syndrome and autistic disorder. CNS Spectrums. 1999;12 (4):57-60.

  370. Trevarthen C, Aitken K, Papoudi D. Children with Autism. 2nd ed. Philadelphia, Pa: Jessica Kingsley Publisher; 1998.

  371. Tuchman RF. Acquired epileptiform aphasia. Semin Pediatr Neurol. Jun 1997;4(2):93-101. [Medline].

  372. Tuchman RF. [Language disorders: is EEG clinically useful?]. Rev Neurol. May 1997;25(141):744-9. [Medline].

  373. Tuchman RF, Rapin I. Regression in pervasive developmental disorders: seizures and epileptiform electroencephalogram correlates. Pediatrics. Apr 1997;99(4):560-6. [Medline].

  374. Turner RA, Altemus M, Enos T, Cooper B, McGuinness T. Preliminary research on plasma oxytocin in normal cycling women: investigating emotion and interpersonal distress. Psychiatry. Summer 1999;62(2):97-113. [Medline].

  375. Verdoux H. Perinatal risk factors for schizophrenia: how specific are they?. Curr Psychiatry Rep. Jun 2004;6(3):162-7. [Medline].

  376. Vermeulen P. I am special. Introducing children and young people to their autistic spectrum disorder. Philadelphia, Pa: Jessica Kingsley Publisher; 2000.

  377. Volkmar FR, Cicchetti DV, Dykens E, Sparrow SS, Leckman JF, Cohen DJ. An evaluation of the Autism Behavior Checklist. J Autism Dev Disord. Mar 1988;18(1):81-97. [Medline].

  378. Volkmar FR, Klin A, Siegel B, Szatmari P, Lord C, Campbell M, et al. Field trial for autistic disorder in DSM-IV. Am J Psychiatry. Sep 1994;151(9):1361-7. [Medline].

  379. Vostanis P, Nicholls J, Harrington R. Maternal expressed emotion in conduct and emotional disorders of childhood. J Child Psychol Psychiatry. Feb 1994;35(2):365-76. [Medline].

  380. Vostanis P, Smith B, Chung MC, Corbett J. Early detection of childhood autism: a review of screening instruments and rating scales. Child Care Health Dev. May-Jun 1994;20(3):165-77. [Medline].

  381. Wade N. First gene for social behavior identified whiskery mice. C4. New York Times: September 9, 1997.

  382. Wahlstrom J, Steffenburg S, Hellgren L, Gillberg C. Chromosome findings in twins with early-onset autistic disorder. Am J Med Genet. Jan 1989;32(1):19-21. [Medline].

  383. Walker HA. A dermatoglyphic study of autistic patients. J Autism Child Schizophr. Mar 1977;7(1):11-21. [Medline].

  384. Wang Z, Yu G, Cascio C, Liu Y, Gingrich B, Insel TR. Dopamine D2 receptor-mediated regulation of partner preferences in female prairie voles (Microtus ochrogaster): a mechanism for pair bonding?. Behav Neurosci. Jun 1999;113(3):602-11. [Medline].

  385. Warren RP, Singh VK. Elevated serotonin levels in autism: association with the major histocompatibility complex. Neuropsychobiology. 1996;34(2):72-5. [Medline].

  386. Webb EV, Lobo S, Hervas A, Scourfield J, Fraser WI. The changing prevalence of autistic disorder in a Welsh health district. Dev Med Child Neurol. Mar 1997;39(3):150-2. [Medline].

  387. Wenar C, Ruttenberg BA, Kalish-Weiss B, Wolf EG. The development of normal and autistic children: a comparative study. J Autism Dev Disord. Sep 1986;16(3):317-33. [Medline].

  388. Wenstrom KD, Descartes M, Franklin J, Cliver SP. A five-year experience with fragile X screening of high-risk gravid women. Am J Obstet Gynecol. Oct 1999;181(4):789-92. [Medline].

  389. Werner E, Dawson G, Osterling J, Dinno N. Brief report: Recognition of autism spectrum disorder before one year of age: a retrospective study based on home videotapes. J Autism Dev Disord. Apr 2000;30(2):157-62. [Medline].

  390. Wilkerson DS, Volpe AG, Dean RS, Titus JB. Perinatal complications as predictors of infantile autism. Int J Neurosci. Sep 2002;112(9):1085-98. [Medline].

  391. Williams G, King J, Cunningham M. Fetal valproate syndrome and autism: additional evidence of an association. Developmental Medicine and Child Neurology. 2001;43:202-206.

  392. Wisniewski KE, Segan SM, Miezejeski CM, Sersen EA, Rudelli RD. The Fra(X) syndrome: neurological, electrophysiological, and neuropathological abnormalities. Am J Med Genet. Feb-Mar 1991;38(2-3):476-80. [Medline].

  393. Yirmiya N, Sigman M, Freeman BJ. Comparison between diagnostic instruments for identifying high- functioning children with autism. J Autism Dev Disord. Jun 1994;24(3):281-91. [Medline].

  394. Young LJ, Nilsen R, Waymire KG, MacGregor GR, Insel TR. Increased affiliative response to vasopressin in mice expressing the V1a receptor from a monogamous vole. Nature. Aug 19 1999;400(6746):766-8. [Medline].

  395. Zwaigenbaum L, Szatmari P, Jones MB. Decreased obstetric optimality in autism is a function of genetic liability to the broader autism phenotype. J Dev Behav Pediatr. 1999;20 (5):398-399.

  396. Zwaigenbaum L, Szatmari P, Jones MB. Pregnancy and birth complications in autism and liability to the broader autismphenotype. J Am Acad Child Adolesc Psychiatry. May 2002;41(5):572-9. [Medline].

Keywords

autism, autistic disorder, infantile autism, Kanner syndrome, Kanner's syndrome, movement abnormalities, motion anomalies, communication abnormalities, social interaction abnormalities, mental retardation, autism spectrum disorder, unspecified pervasive developmental disorder, autistic spectrum disorder, rubella, measles, mumps, Rett syndrome, Asperger syndrome, childhood disintegration disorder, Sydenham chorea, akathisia, pseudoakathisia

Contributor Information and Disclosures

Author

James Robert Brasic, MD, MPH, Research Associate, Division of Nuclear Medicine, Russell H Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine
James Robert Brasic, MD, MPH is a member of the following medical societies: American Academy of Child and Adolescent Psychiatry, American Academy of Neurology, and Movement Disorders Society
Disclosure: Taylor and Francis Royalty Independent contractor; Wolters Kluver/Lippincott Williams & Wilkins Royalty Independent contractor

Medical Editor

Carol Diane Berkowitz, MD, Executive Vice Chair, Department of Pediatrics, Professor, Harbor-University of California at Los Angeles Medical Center
Carol Diane Berkowitz, MD is a member of the following medical societies: Alpha Omega Alpha, Ambulatory Pediatric Association, American Academy of Pediatrics, American College of Emergency Physicians, American Medical Association, American Pediatric Society, and North American Society for Pediatric and Adolescent Gynecology
Disclosure: Nothing to disclose.

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Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
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CME Editor

Carrie Sylvester, MD, MPH, Director of Education in Child and Adolescent Psychiatry, Professor, Departments of Psychiatry and Pediatrics, Northwestern University Medical School
Carrie Sylvester, MD, MPH is a member of the following medical societies: American Academy of Child and Adolescent Psychiatry, American Academy of Pediatrics, American Medical Women's Association, American Psychiatric Association, and American Society for Adolescent Psychiatry
Disclosure: Nothing to disclose.

Chief Editor

Caroly Pataki, MD, Professor of Clinical Psychiatry and Behavioral Sciences, Department of Psychiatry, Division Chair, Child and Adolescent Psychiatry, Director of Training, Child and Adolescent Psychiatry Residency Program, University of Southern California Keck School of Medicine
Caroly Pataki, MD is a member of the following medical societies: American Academy of Child and Adolescent Psychiatry, New York Academy of Sciences, and Physicians for Social Responsibility
Disclosure: Nothing to disclose.

Acknowledgments

This research is supported by the Essel Foundation, the National Alliance for Research on Schizophrenia and Depression (NARSAD), the Tourette Syndrome Association Inc, the National Institutes of Health, the Department of Psychiatry of Bellevue Hospital Center, and the New York University School of Medicine. The cooperation of the Health and Hospitals Corporation of the City of New York is gratefully acknowledged.

The author also gratefully acknowledges the technical assistance in the preparation of the video portions of this article of the Digital Media Center at the Skirball Institute of Biomolecular Medicine at the New York University Medical Center.

Further Reading

Recommended readings for parents include the following:

  • Baron-Cohen S, Howlin P. Teaching Children with Autism to Mind-read: a Practical Guide for Teachers and Parents. New York, NY: Wiley; 1998.
  • Cohen S. Targeting Autism. Berkeley, CA: University of California Press; 1998.
  • Hart CA. A Parent's Guide to Autism. New York, NY: Pocket Books; 1993.
  • Hollander E. Autism Spectrum Disorders. Volume 24 of the Medical Psychiatry Series. New York, NY: Marcel Dekker; 2003.
  • Lovaas I. The Autistic Child: Language Development through Behavior Modification. New York, NY: Irvington Press; 1977.
  • Powers M. Children with Autism: A Parents' Guide. Bethesda, Md: Woodbine House; 2000.
  • Quill K. Teaching Children with Autism: Strategies to Enhance Communication and Socialization. Albany, NY: Delmar Publishers; 1995.
  • Wing L. The Autistic Spectrum: A Parent's Guide to Understanding and Helping Your Child. London, England: Ulysses Press; 2001.

Key general references include the following:

  • Bettelheim B. The Empty Fortress: Infantile Autism and the Birth of the Self. New York, NY: The Free Press; 1977.
  • Cohen DJ, Volkmar FR. Handbook of Autism and Pervasive Developmental Disorders. New York, NY: Wiley; 1996.
  • DeMyer MK. Parents and Children in Autism. Washington, DC: Winston; 1979.
  • Filipek PA, Accardo PJ, Ashwal SL. Practice parameter: screening and diagnosis of autism: report of the Quality Standards Subcommittee of the American Academy of Neurology and the Child Neurology Society. Neurology. 2000 August 22;55(4):468-479.
  • Gillberg C, Coleman M. The Biology of the Autistic Syndromes, 3rd ed. London, England: Mac Keith Press. Clinics in Developmental Medicine Number 153/4; 2000.
  • Harris JC. Developmental Neuropsychiatry: Fundamentals. Vol 1. Oxford, England: Oxford University Press; 1995.
  • Harris JC. Developmental Neuropsychiatry: Assessment, Diagnosis, and Treatment. Vol 2. Oxford, England: Oxford University Press; 1995.
  • Hollander E. Autism Spectrum Disorders. Volume 24 of the Medical Psychiatry Series. New York, NY: Marcel Dekker; 2003.
  • Klin A, Volkmar FR, Sparrow SS. Asperger Syndrome. New York, NY: Guilford Publications, Inc; 2000.
  • Lovaas OI. Behavioral treatment and normal educational and intellectual functioning in young autistic children. J Consult Clin Psychol. 1987 Feb;55(1):3-9.
  • Schreibman L. Diagnostic features of autism. J Child Neurol. 1988;3(suppl)l:S57-S64.

Additional resources on autism are available at Medscape's Autism Spectrum Disorders Resource Center.

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