Background
Autism is a condition that manifests in early childhood and is characterized by qualitative abnormalities in social interactions, markedly 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 approximately 35-50. Although children with autism are often difficult to evaluate with intelligence tests, three fourths of autistic children 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. A small portion of those with autism never develop spoken language. Thus, diagnostic instruments for autism may give spurious results in children with profound mental retardation.
This article addresses autism in individuals with mental retardation. For information concerning individuals with autism spectrum disorders and related conditions without mental retardation, please see Asperger Syndrome and Pervasive Developmental Disorder.
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.[1] 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 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. A similar experience results from moving up and down while gazing through the slats of Venetian blinds. 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 to suppress the 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 (see Etiology).[2, 3, 4, 5] 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.[6] Approximately 10% of children with a pervasive developmental disorder exhibit a known medical condition.
On the other hand, anecdotal reports that autism may be linked with vaccinations for measles, mumps, and rubella have not been confirmed.[7] Parents should be encouraged to fully immunize their children.[8]
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 (see Treatment).[9] 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.
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, nor to any other emotional or psychological deficits in the parents. Blaming parents for the development of autism in their children is inappropriate.
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 wide 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.
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. 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 (see Treatment).
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.
Pathophysiology
In patients with autism, 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. Markedly more neurons (nerve cells) are present in the prefrontal cortex of autopsy specimens of some children with autism.[10] Findings vary in each person. Hughes has observed the presence of underconnectivity in the brains of children with autism and related conditions.[11]
Children with autism spectrum disorders on magnetic resonance imaging (MRI) demonstrate greater myelination in bilateral medial frontal cortices and less myelination in the left temporoparietal junction.[12]
Postmortem specimens of the brains of people with autism demonstrated reductions for type B receptors for gamma-aminobutyric acid (GABAB) in the cingulate cortex, a key region for the evaluation of social relationships, emotions, and cognition, and in the fusiform gyrus, a crucial region to evaluate faces and facial expressions.[13] These findings provide the 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.[2, 3, 4]
Roberts and colleagues and Samson have reported an association between exposure to the organochlorine pesticides dicofol and endosulfan during the first trimester of pregnancy and the subsequent development of autism spectrum disorders in the child.[14, 15] Potential mothers can wisely be advised to avoid exposure to organochlorine pesticides.
Some children have 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.[16, 17, 18]
Thompson and colleagues detected no causal association between exposure to vaccines that contain thimerosal and neuropsychological deficits at age 7-10 years.[19] In fact, in early 2010, the Lancet retracted the 1998 article by Wakefield et al that originally linked autism with measles-mumps-rubella (MMR) vaccination, citing flaws in the study and 2 claims in the paper that were "proven to be false."[20] Parents can permit the recommended childhood immunizations without fear of causing autism and related conditions.[21]
Many other hypotheses, such as folic acid supplementation in pregnancy, have been proposed as possible causes of autism. None has been established as a definite etiology of autism.
Etiology
Decades ago, researchers conjectured that infantile autism resulted from rejection of the infant by cold parents ("refrigerator mothers"). 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.
The causes of autistic disorder are unknown. Hypotheses include obstetric complications, infection, genetics, and toxic exposures.[22, 23]
Obstetric complications are associated with an increased risk of autistic disorder.[3, 4] Whether obstetric complications caused autistic disorder, or autism and obstetric complications resulted from another problem, is unclear. Exposure of the mother to selective serotonin-reuptake inhibitors, particularly during the first trimester, may increase the risk of the development of autism spectrum disorders.[24]
An infectious basis for some cases of autistic disorder 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.
Familial influences increase the likelihood that certain families will produce children with autism spectrum disorders. The presence of one child with an autism spectrum disorder increases the likelihood that subsequent siblings will develop an autism spectrum disorder. Children born into families with a child with an autism spectrum disorder have a risk of also developing an autism spectrum disorder, at a rate of as high as 18.7 %.[25] Female infants born to families with a child with an autism spectrum disorder have 2.8 times the risk of developing an autism spectrum disorder.[25] Children born to families with 2 or more children with autism spectrum disorders have twice the risk of developing an autism spectrum disorder compared with children with one sibling with an autism spectrum disorder.[25]
Twin studies have demonstrated a moderate degree of genetic heritability for autism and autism spectrum disorders.[26, 27, 28] The environment shared by twins provides a substantial contribution to the heritability of autism and autism spectrum disorders.[28] Multiple family studies have suggested genetic components in many cases of autism.[29, 30, 31] For example, some asymptomatic first-degree relatives of some probands with autism have abnormalities in serotonin and other chemicals similar to the probands. 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. Factor analysis of datasets from the Autism Genome Project has suggested linkage of a joint attention factor with 11q23 and of a repetitive sensory-motor behavior factor with 19q13.[32] However, the clinical usefulness of the assessment of families of individuals with autism has not been established.
While a third of monozygotic twins are concordant for autism, dizygotic twins are concordant for autism at rates of 4%[33] to 8%, which is comparable to siblings. A focused neurogenetic evaluation of children with autism spectrum disorders yields a genetic disorder in two fifths of the children.[34] For example, mutations in the gene SHANK3 are associated with autism spectrum disorders.[35]
A mouse model of Rett syndrome, an autism spectrum disorder caused by mutations of the methyl-CpG binding protein 2 (MeCP2),[36] has demonstrated beneficial effects when treated with insulinlike growth factor 1 (IGF-1).[37]
Fragile X syndrome, a condition associated with autism, can be identified through genetic testing.[38] Antagonists to metabotropic glutamate receptors can reverse the symptoms of mice with models of fragile X syndrome.[39] Autism[40] has been associated with tuberous sclerosis, a disorder with specific genetic mutations.[41]
Exposures to toxins, chemicals, poisons, and other substances have been hypothesized to cause autism. Although anecdotal case reports suggest that such exposures 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.
In certain parts of the world, exposure to specific toxins may influence local autism rates. 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.
On the other hand, another possible explanation for the high rates of autism in Japan is the excellent training of Japanese clinicians. Low rates of autism in other countries may reflect the limited abilities of clinicians to diagnose autism.
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.
The rate of autism in children who receive immunizations does not appear to be increased. In fact, in early 2010, the Lancet retracted the 1998 article by Wakefield et al that originally linked autism with measles-mumps-rubella (MMR) vaccination, citing flaws in the study and 2 claims in the paper that were "proven to be false."[20] Parents can permit the recommended childhood immunizations without fear of causing autism and related conditions. Adherence to recommended immunization schedules, including immunization for measles, mumps, and rubella, is highly recommended.[21]
Epidemiology
Reported rates of autism spectrum disorder have been rising in many countries over the past 2 decades.[42, 43] It remains unclear how much of these data may represent an actual increase and how much reflect changes in diagnostic definitions and practices and increasing awareness among the general public as well as the medical profession.[44, 45, 46] Current epidemiological studies are needed to identify the incidence, prevalence, and distribution of autistic disorder.
United States statistics
Autism spectrum disorder is one of the most common childhood developmental disabilities. Autistic disorder and related conditions affect up to 10-20 individuals per 10,000 population.[47] Estimates of the prevalence of autism suggest that as many as 400,000 individuals in the United States have autism and related conditions.
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 psychoses other and schizophrenia. (See History).
International statistics
Autistic disorder and related conditions are estimated to affect up to 10-15 people per 10,000 population worldwide. Studies in Japan report much higher rates than in other countries.[48]
Japanese investigators suggest that these findings reflect the careful evaluations performed by Japanese clinicians, which may identify cases that would be overlooked in other countries. Alternatively, autism may be more common in Japan because of gastrointestinal and other infections transmitted through the ingestion of seafood and other aquatic food characteristic of Japan.
Sex- and age-related demographics
The male-to-female ratio is 3-4:1. Autistic disorder is most common in boys who have the 46,XY karyotype (ie, the normal male karyotype). In some studies, fragile X is reported in approximately one tenth of males with autistic disorder.[49, 50, 51, 52, 53, 54]
Autistic disorder manifests in early childhood. By 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 the following articles:
Many parents report normal development in their child until age 2 years before noticing the deficits in social and communicative skills.
Comorbid disorders
Gastrointestinal disorders, particularly constipation and chronic diarrhea, are more common in children with autism spectrum disorders. The risk of gastrointestinal disorders increases with the severity of the symptoms of autism.[55]
Prognosis
The prognosis in patients with autism is highly correlated with their IQ. 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 Asperger Syndrome for further information and to learn more about high-functioning autism.
Remission is reported in anecdotal case reports.
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 (ie, speech and language specialists) may help the patient to maximize communication skills.
People with developmental disabilities, including Asperger syndrome, are vulnerable to sexual abuse. The most severely disabled are at highest risk for sexual abuse. For this reason, parents and caregivers must be alert to avoid situations inviting sexual abuse. Additionally, children with Asperger syndrome must be trained to recognize impending sexual abuse and to develop plans of action to abort possible sexual abuse.[56]
For patient education information, see the Brain and Nervous System Center, as well as Autism and Asperger Syndrome.
Recommended reading resources for parents
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
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 of 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 the video below).
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.Other resources
Individuals with autism and related conditions and their advocates can benefit from the experiences of the individuals and advocates with similar situations who are listed below.
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
393 City Rd
London EC1V 1NG
United Kingdom
Phone: +44 (0)20 7833 2299
National Institutes of Health
Asperger Syndrome Coalition of the United States (ASC-US) Inc
PO Box 49267
Jacksonville FL 32240-9267
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
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