- Author: James Robert Brasic, MD, MPH; Chief Editor: Caroly Pataki, MD more...
Autism spectrum disorder (ASD) manifests in early childhood and is characterized by qualitative abnormalities in social interactions, markedly aberrant communication skills, and restricted repetitive behaviors, interests, and activities (RRBs).
Signs and symptoms
Behavioral and developmental features that suggest autism include the following:
Absence of protodeclarative pointing
Abnormal reactions to environmental stimuli
Abnormal social interactions
Absence of smiling when greeted by parents and other familiar people
Absence of typical responses to pain and physical injury
Language delays and deviations
Susceptibility to infections and febrile illnesses
Absence of symbolic play
Repetitive and stereotyped behavior
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. Siblings of children with autism are at risk for developing traits of autism and even a full-blown diagnosis of autism. Therefore, siblings should also undergo screening not only for autism-related symptoms but also for language delays, learning difficulties, social problems, and anxiety or depressive symptoms.
Having parents fill out the Autism Screening Checklist can identify children who merit further assessment for possible autism. See the image below for a printable version of the checklist.
See Clinical Presentation for more detail.
Examination for patients with suspected autistic spectrum disorder may include the following findings:
Abnormal motor movements (eg, clumsiness, awkward walk, hand flapping, tics)
Dermatologic anomalies (eg, aberrant palmar creases)
Orofacial, extremity, and head/trunk stereotypies (eg, purposeless, repetitive, patterned motions, postures, and sounds)
Self-injurious behaviors (eg, picking at the skin, self-biting, head punching/slapping)
Physical abuse inflicted by others (eg, parents, teachers)
Sexual abuse: External examination of genitalia is appropriate; if bruises and other evidence of trauma are present, pelvic and rectal examinations may be indicated
The definition of ASD in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) encompasses the previous manual's autistic disorder (autism), Asperger's disorder, childhood disintegrative disorder, and pervasive developmental disorder not otherwise specified. ASD is characterized by the following :
Deficits in social communication and social interaction
Restricted repetitive behaviors, interests, and activities (RRBs)
These symptoms are present from early childhood and limit or impair everyday functioning. Both components are required for diagnosis of ASD.
There are no blood studies recommended for the routine assessment of ASD. Although several metabolic abnormalities have been identified in investigations of people with autism (eg, elevated 5-HT, reduced serum biotinidase, abnormal neurotransmitter functions, impaired phenolic amines metabolism), a metabolic workup should be considered on an individual basis. No biologic markers for autism currently exist.
Studies that may be helpful in the evaluation of autistic disorder include the following:
EEG: To exclude seizure disorder, acquired aphasia with convulsive disorder (Landau-Kleffner syndrome), biotin-responsive infantile encephalopathy, related conditions
Psychophysiologic assessment: To show lack of response habituation to repeatedly presented stimuli (in respiratory period, electrodermal activity, vasoconstrictive peripheral pulse amplitude response); auditory overselectivity may be seen
Polysomnography: To identify sleep disorders and to demonstrate seizure discharges
There is currently no clinical evidence to support the role of routine clinical neuroimaging in the diagnostic evaluation of autism, even in the presence of megalencephaly. Although characteristic abnormalities have been identified, no single finding is diagnostic.
The following imaging techniques have yielded inconsistent results in evaluating autism:
MRI with or without diffusion tensor imaging
See Workup for more detail.
The established therapies for autistic disorder are nonpharmacologic and may include individual intensive interventions. Individuals with autism spectrum disorder and unspecified pervasive developmental disorder typically benefit from behaviorally oriented therapeutic programs developed specifically for this population. Autistic children should be placed in these specialized programs as soon as the diagnosis is suspected.
Intensive individual special education
Speech, behavioral, occupational, and physical therapies (eg, assisted communication, auditory integration training, sensory integration therapy, exercise/physical therapy)
No pharmacologic agent is effective in the treatment of the core behavioral manifestations of autistic disorder, but drugs may be effective in treating associated behavioral problems and comorbid disorders (eg, self-injurious behaviors, movement disorders). The possible benefits from pharmacotherapy must be balanced against the likely adverse effects on a case-by-case basis (eg, venlafaxine may increase high-intensity aggression in some adolescents with autism )
Medications used in managing related behavioral problems and comorbid conditions in children with autism include the following:
Second-generation antipsychotics (eg, risperidone, aripiprazole, ziprasidone)
SSRI antidepressants (eg, fluoxetine, citalopram, escitalopram)
Stimulants (eg, methylphenidate)
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. A heterogeneous group of disorders includes the trait of autism.
Motion anomalies are a prominent feature in a subset of individuals and have been reported at birth in some persons with autism. Motion analysis may provide evidence of autism in early infancy, before other manifestations occur.
The motion anomalies demonstrated by children with autism are often highly characteristic and noticeable. 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. (See Presentation.)
Many of the motions of children with autism appear to be attempts to provide themselves with sensory input in a barren environment. Through special education, children may learn to suppress the movements, although these may subsequently be exhibited at times of particular stress or excitement.
Although the etiology of autism is unknown, hypotheses include genetic abnormalities, obstetric complications, exposure to toxic agents, and prenatal, perinatal, and postnatal infections.[8, 9, 10, 11] 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. Approximately 10% of children with a pervasive developmental disorder exhibit a known medical condition. (See Etiology.)
On the other hand, anecdotal reports that autism may be linked with vaccinations (eg, for measles, mumps, and rubella) have not been supported by broader research. Research from the CDC indicates that the number of childhood vaccines administered, either in a single day or during a child's first 2 years, has no effect on the risk of developing an autism spectrum disorder (ASD). According to results of a case-control study of more than 1000 children born between January 1994 and December 1999, exposure to antibody-stimulating proteins or polysaccharides from vaccines between the ages of 3 months and 2 years was not associated with an increased risk of developing an ASD. The study included 256 children with an ASD and 752 healthy controls.[14, 15] Parents should be encouraged to fully immunize their children. (See Etiology.)
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. (See 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 by any other emotional or psychological parental deficits. 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. Administering these tools in a reliable and valid manner requires extensive training and experience. 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. (See the screening checklist below.)
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.
Individualized, intensive behavioral and psychological interventions must be instituted immediately after the diagnosis of autism in order for the patient to achieve an 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 deficits in language and communication are often major impediments to progress in educational, work, and personal settings, patients often benefit from specialized communication devices and training. 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.
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.)
The American Academy of Child and Adolescent Psychiatry's practice guidelines for the assessment and treatment of children and adolescents with ASD include the following recommendations:[18, 19]
Questions about core symptoms of ASD should be a routine part of psychiatric and developmental assessments of young children.
If screening reveals significant ASD symptomatology, a thorough evaluation should be performed and possible comorbid diagnoses should be considered.
Children with ASD should undergo a multidisciplinary assessment, including a physical examination, a hearing screen, communication and psychological tests, and genetic testing.
Clinicians should help families obtain educational and behavioral interventions, such as applied behavioral analysis (ABA) programs.
Pharmacotherapy should be offered for specific target symptoms or comorbid conditions.
Clinicians should maintain an active role in the planning of long-term treatment.
Families should be asked about the use of alternative/complementary treatments.
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 are present in select divisions of the prefrontal cortex of autopsy specimens of some children with autism, compared with those without autism.
Magnetic resonance imaging (MRI) studies have suggested evidence for differences in neuroanatomy and connectivity in people with autism compared with normal controls. Specifically, these studies have found reduced or atypical connectivity in frontal brain regions, as well as thinning of the corpus callosum in children and adults with autism and related conditions.
In a study that included 17 adults with high-functioning autism and 17 age- and IQ-matched control subjects, functional magnetic resonance imaging (fMRI) of the brain that showed neural representations of social interactions was able to accurately identify individuals with autism. Scans were performed as study subjects thought about a set of social interaction verbs from both an action and a recipient perspective.[21, 22]
Importantly, some of the regional differences in neuroanatomy correlate significantly with the severity of specific autistic symptoms.[23, 24] For example, social and language deficits of people with autism likely are related to dysfunction of the frontal and temporal lobes.
In a study of postmortem brain tissue from 11 children with autism and 11 unaffected controls, researchers found focal disruption of cortical laminar architecture in the cortexes of 10 of the children with autism and 1 of the controls, suggesting that brain irregularities in autism may have prenatal origins. The patches of abnormal neurons were found in the frontal and temporal lobes, regions involved in social, emotional, communication, and language functions. Since the changes were in the form of patches, the researchers believe that early treatment could rewire the brain and improve ASD symptoms.[26, 27]
On MRI scans, the brains of children with autism spectrum disorder demonstrate greater myelination in bilateral medial frontal cortices and less myelination in the left temporoparietal junction. Similarly, region-specific differences in the concentrations of gray matter, made up of neuronal cell bodies, dendrites, unmyelinated axons and glial cells, are also found in the brains of people with autism.
Postmortem specimens of the brains of people with autism demonstrated reductions for gamma-aminobutyric acid–B (GABAB) receptors 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. These findings provide the basis for further investigation of autism and other pervasive developmental disorders.
In animal studies, dysfunction of serotonin and the neuropeptides oxytocin and vasopressin has been associated with abnormalities in affiliative behaviors. Neurophysiologic dysfunction involving 1 or more of these substances may also be present in humans with autism.
Elevations of blood serotonin levels occur in approximately one third of individuals with autistic disorder and are also reported in the parents and siblings of patients. Functional anomalies in other neurotransmitters (eg, acetylcholine, glutamate) have also been identified in some people with autism spectrum disorder.[25, 31]
Serum biotinidase is reduced in some people with autistic disorder. This enzyme is required for the use and recycling of the B vitamin biotin. Deficiency of biotin has been linked with behavioral disorders.
Immunologic studies have identified abnormalities such as decreased plasma concentrations of the C4B complement protein. Such abnormalities may be the source of the increased susceptibility to infection seen in some people with autism.
Diet is a controversial aspect of autism. The greatest attention has been given to gluten- and casein-free diets; anecdotal information suggests that these diets help some children with autism. 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.
Plasma levels of cysteine, glutathione, and methionine
The ratio of S -adenosyl-L-methionine (SAM) to S -adenosyl-L-homocysteine (SAH)
The ratio of reduced to oxidized glutathione
Some children with autism display hyperlacticacidemia as well as evidence of mitochondrial disorders including carnitine deficiency. These abnormalities may reflect disturbed neuronal energy metabolism.
In the 1940s, in his seminal papers that first identified autism, the child psychiatrist Leo Kanner conjectured that infantile autism resulted from rejection of the infant by emotionally cold parents ("refrigerator mothers"). In the 1950s and 1960s, Bruno Bettelheim popularized this idea. Since then, careful family studies have disproved the hypothesis that the development of autistic disorder in children is caused by faulty parenting. Sensitive clinicians communicate to parents that their parenting skills did not cause their child's autism. Repeated communication of this fact will help to minimize the guilt often experienced by parents of autistic children.
The causes of autistic disorder are unknown. Hypotheses include obstetric complications, infection, genetics, and toxic exposures.[37, 38, 39] None of these, however, has been established as a definite etiology.
Many individuals with autism and related conditions experienced untoward events in their prenatal and neonatal periods and during delivery.[8, 9, 10, 40] It is unclear whether the obstetric complications caused autistic disorder or whether autism and obstetric complications resulted from environmental or other problems.
In a large Danish study published in JAMA, maternal use of valproate during pregnancy was associated with a significantly increased risk for autism in offspring. The drug is already not recommended for use in pregnant women due to the risk of congenital malformations and its possible association with low intelligence in children exposed during pregnancy.
Researchers used data on all children born in Denmark between 1996 and 2006. Of the 655,615 children born in the study period, 5437 had autism spectrum disorder, including 2067 with childhood autism. There were 2644 children exposed to antiepileptic drugs during pregnancy, 508 of whom were exposed to valproate. Analysis showed that the children exposed to valproate had a 3-fold increased risk for autism spectrum disorder and a 5-fold increased risk for profound childhood autism compared with unexposed children, even after adjustment for parental psychiatric disease and epilepsy.[41, 42]
The management of women with epilepsy who desire to bear children can be challenging. A woman with an ongoing seizure disorder requires treatment because maternal seizures can result in serious morbidity and mortality for the mother and the fetus. To stop anticonvulsant therapy when a woman with a seizure disorder becomes pregnant to avoid teratologic effects may precipitate uncontrolled seizures that may be fatal to the mother and the fetus. Therefore physicians treating women with child-bearing potential can appropriately initiate frank conversations about future pregnancies. Juvenile myoclonic epilepsy and other seizure disorders typically cause seizures throughout adulthood so pharmacotherapy throughout adulthood is a reasonable treatment plan. While valproate is an excellent agent to control a vast spectrum of seizure disorders, its use in women of child-bearing potential is fraught with danger due to the great risk of producing autism spectrum disorders, spina bifida, and other birth defects. A frank conversation between the physician and the woman of child-bearing potential about the risks and benefits of specific antiepileptic drugs for the mother and the fetus is indicated. Documentation of these conversations is the medical record is needed. This record may be useful in court if legal action is initiated if a child has birth defects.
Exposure of the mother to selective serotonin reuptake inhibitors, particularly during the first trimester, may increase the risk that her offspring will develop an autism spectrum disorder.
Severe, early-gestation maternal hypothyroxinemia is associated with an increased risk of having a child with autism, according to a new study that involved 5100 women and 4039 of their children. Severe maternal hypothyroxinemia early in gestation increased the likelihood of having an autistic child by almost 4-fold. By age 6, children of mothers with severe hypothyroxinemia had higher autistic symptom scores on the Pervasive Developmental Problems subscale of the Child Behavior Checklist and the Social Responsiveness Scale.[44, 45]
An infectious basis for some cases of autistic disorder is suggested by the large number of children with autistic disorder born to women who contracted rubella during pregnancy. This finding supports the hypothesis that this infection triggers a vulnerability to the development of autistic disorder in the fetus.
Familial and genetic factors
Familial factors influence the risk for autism spectrum disorders. The rate of autism spectrum disorder in children born into families that already have a child with an autism spectrum disorder is as high as 18.7 %, and the risk is twice as high in children born to families with 2 or more children with an autism spectrum disorder. Girls born to a family that has a child with an autism spectrum disorder have 2.8 times the risk of having such a disorder.
Twin studies have demonstrated a moderate degree of genetic heritability for autism and autism spectrum disorders,[47, 48, 49] with environment making a substantial contribution to the development of these conditions in the study subjects.
Multiple family studies have suggested genetic components in many cases of autism.[50, 40, 51] For example, some asymptomatic first-degree relatives of some probands with autism have abnormalities in serotonin and other chemicals similar to the probands.
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. 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 4-8%, which is comparable to siblings. A focused neurogenetic evaluation of children with autism spectrum disorder yields a genetic disorder in two fifths of the children. For example, mutations in the gene SHANK3 are associated with autism spectrum disorders.
Fragile X syndrome, a condition associated with autism, can be identified through genetic testing. Antagonists to metabotropic glutamate receptors can reverse the symptoms in mouse models of fragile X syndrome. Autism has also been associated with tuberous sclerosis, a disorder with specific genetic mutations.[58, 59]
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.
Roberts et al 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 disorder in children. Potential mothers can wisely be advised to avoid exposure to organochlorine pesticides.
In parts of the world, exposure to specific toxins may influence local autism rates. For example, the high incidence of autism in areas of Japan has been hypothesized to be due to a toxic effect of certain fish. Although toxins may play a role in the development of isolated cases of autism in Japan, they have not been proved to be generally causative of autism there. Another possible explanation for the high autism rates in Japan is the excellent training of Japanese clinicians; low rates elsewhere may reflect the limited abilities of clinicians to diagnose autism.
Some studies have documented associations between autism and air pollution. One, from North Carolina found a link between exposure to traffic-related air pollution, particularly during the third trimester, to the development of autism in offspring. These results add to the evidence already provided by previous studies conducted in California.
Another study of children living in counties in Pennsylvania found that children with autism were 1.4 to two times more likely to have been exposed to higher levels of air pollution, especially the toxins styrene and chromium, during pregnancy and the first 2 years of life than children without the disorder. Cyanide, methylene chloride, methanol, and arsenic were also linked to increased risk of autism.
Meta-analyses of epidemiologic studies have shown that autism risk in offspring increases with advancing age of either parent. Sandin et al reported that, after controlling for paternal age, the adjusted relative risk for autism was 1.52 in the offspring of mothers aged 35 years or older compared with mothers aged 25-29 years. Hultman et al found that, after controlling for maternal age, offspring of men aged 50 years or older were 2.2 times more likely to have autism than offspring of men aged 29 years or younger.
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.[66, 67, 68, 69] } }
Thompson and colleagues detected no causal association between exposure to vaccines that contain thimerosal and neuropsychological deficits at age 7-10 years. 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 it that were "proven to be false."
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.
Reported rates of autism spectrum disorder have been rising in many countries over the past 2 decades.[72, 73] It remains unclear how much of these data represent an actual increase and how much reflect changes in diagnostic definitions and practices, as well as increasing awareness among the general public and within the medical profession.[74, 75, 76] Further epidemiologic studies are needed.
However, such studies of relatively uncommon conditions such as autism spectrum disorder are expensive. A suitable research strategy is the administration of multiple screenings in a population, each time identifying more likely subjects for detailed investigation.
For example, a reporting tool, such as the Autism Screening Checklist, can be distributed to all parents and guardians in a target population. See the image below.
The checklist identifies those children with characteristics of an autism spectrum disorder and differentiates them from children with child-onset schizophrenia. (See History).
Occurrence in the United States
Autism spectrum disorder is one of the most common childhood developmental disabilities. Autistic disorder or related conditions were found to affect 14.7 in 1,000 (1 in 68) children aged 8 years living in 11 communities monitored by the US Centers for Disease Control and Prevention (CDC). However, overall prevalence estimates of autistic spectrum disorder varied widely across the 11 monitored communities (range, 5.7-21.9 in 1,000 children aged 8 years).
In its study, the CDC reported a 29% rise in prevalence from 2008 to 2010 in children aged 8 years, or an increase from 11.3 in 1,000 to 14.7 in 1,000 for the 11 sites that provided data for both surveillance years. From 2002 to 2010, an estimated increase of 123% occurred in children aged 8 years. Estimates of the prevalence of autism suggest that as many as 400,000 individuals in the United States have autism or a related condition.
Autistic disorder and related conditions are estimated to affect up to 10-15 people per 10,000 population worldwide. In a population-based study of all 7- to 12-year-old children (N = 55,266) in a South Korean community, Kim et al estimated that the prevalence of autism spectrum disorders was 2.64%
Studies in Japan report much higher rates than are found in other countries. 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 aquatically derived foods that are characteristic of the Japanese diet.
Estimates of the prevalence of autism spectrum disorder vary widely by sex. Combining data from all 11 Autism and Developmental Disabilities Monitoring (ADDM) Network communities, ASD prevalence was 23.7 per 1,000 (one in 42) boys and 5.3 per 1,000 (one in 189) girls (prevalence ratio: 4.5 for all sites combined). The male-to-female ratio ranged from 3.6 (Alabama and Colorado) to 5.1 (North Carolina).
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 10% males with autistic disorder.[80, 81, 82, 83, 84, 85]
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. Remission of autism has been described in anecdotal case reports.
High-functioning individuals with autistic disorder are similar to people with Asperger syndrome. Please refer to the Medscape Reference article Asperger Syndrome for further information and to learn more about high-functioning autism.
Gastrointestinal disorders, particularly constipation and chronic diarrhea, are more common in children with autism spectrum disorder. The risk of gastrointestinal disorders increases with the severity of autism symptoms.
Because local boards of education may be ignorant about the needs of children with autistic spectrum 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.
People with developmental disabilities, including Asperger syndrome, are vulnerable to sexual abuse, with the most severely disabled being at highest risk. Parents and caregivers need to be aware of this increased risk. Additionally, children with Asperger syndrome must be trained to recognize impending sexual abuse and to develop plans of action to abort it.
Almost half of a sample of more than 1000 children with autism spectrum disorders exhibited elopement, wandering away from home, school, and other safe environments. Parents of children with autism spectrum disorders need to be warned that there is a fair chance that their child, without warning, may walk away from home or school to go to an environment where there is a risk for potential danger. Additionally, parents need to be advised to request that teachers and other caregivers vigilantly watch the child to prevent elopement.
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 and must provide permission for possible interventions. By making a video recording of the process of explaining to the parent the recommended procedures, in addition to the signing of written release forms, the clinician establishes evidence that he/she imparted appropriate information to the correct party. (See the video below.)
Published resources for parents
Recommended readings for parents include the following:
Attwood T. The Complete Guide to Asperger's Syndrome. London, UK: SK Kingsley Publishers; 2006
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
Gaus VL. Cognitive/Behavioural Therapy for Adult Asperger's Syndrome. New York, NY: The Guilford Press; 2007
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
Matthews P, Matthews T. (2012) Charter of Rights for People with Autism: “Reflections” and Personal Experiences. Dublin, Ireland: Original writing; 2012
Offit PA. Autism's false prophets. New York, NY: Columbia University Press; 2008
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
Individuals with autism and related conditions, as well as their advocates, can benefit from the experiences of other individuals and advocates who are dealing with autism. (See the organizations and resources listed below.)
7910 Woodmont Ave, Suite 650
Bethesda, MD 20814-3015
Autism Society of America
25 West 17th St Ground Floor
New York, NY 10011
Autism Society of Canada
2-20 College St
Canada M5G 1K2
National Alliance for Autism Research
414 Wall St
Princeton, NJ 08540
393 City Rd
London EC1V 1NG
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
Autism Research Institute
4182 Adams Ave
San Diego, CA 92116
5455 Wilshire Blvd, Suite 715
Los Angeles, CA 90036
[Guideline] Filipek PA, 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 2000 Aug;55(4):468-79. Reaffirmed July 2010. [Full Text].
Courchesne E, Carper R, Akshoomoff N. Evidence of brain overgrowth in the first year of life in autism. JAMA. 2003 Jul 16. 290(3):337-44. [Medline].
Aylward EH, Minshew NJ, Field K, Sparks BF, Singh N. Effects of age on brain volume and head circumference in autism. Neurology. 2002 Jul 23. 59(2):175-83. [Medline].
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (DSM-V). 5th Edition. Washington, DC: American Psychiatric Association; 2013:
Antshel KM, Polacek C, McMahon M, Dygert K, Spenceley L, Dygert L, et al. Comorbid ADHD and anxiety affect social skills group intervention treatment efficacy in children with autism spectrum disorders. J Dev Behav Pediatr. 2011 Jul-Aug. 32(6):439-46. [Medline].
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. 2003 Apr. 42(4):383-4. [Medline].
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. 1998 Nov 10. 95(23):13982-7. [Medline]. [Full Text].
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:
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:
Brasic JR, Holland JA, Alexander M. The increased likelihood of obstetric complications in autistic disorder [abstract]. Southern Medical Journal. 2003;96 (10 supplement):S34:
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. 2002 Feb. 22(1):25-33. [Medline].
Gutierrez GC, Smalley SL, Tanguay PE. Autism in tuberous sclerosis complex. J Autism Dev Disord. 1998 Apr. 28(2):97-103. [Medline].
Court finds no Vaccines-autism link. Hum Vaccin. 2010 May 14. 6(5):[Medline].
Brauser D. No Evidence Multiple Vaccines Raise Autism Risk, CDC Says. Medscape Medical News. Available at http://www.medscape.com/viewarticle/781670. Accessed: April 3, 2013.
DeStefano F, Price CS, Weintraub ES. Increasing Exposure to Antibody-Stimulating Proteins and Polysaccharides in Vaccines Is Not Associated with Risk of Autism. J Peds. March 2013.
Hammer LD, Curry ES, Harlor AD, Laughlin JJ, Leeds AJ, Lessin HR, et al. Increasing immunization coverage. Pediatrics. 2010 Jun. 125(6):1295-304. [Medline].
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. 2000 Aug 22. 55(4):468-79. [Medline].
Brauser D. New Practice Guidelines for Autism. Medscape Medical News. Available at http://www.medscape.com/viewarticle/819935. Accessed: February 4, 2014.
Volkmar F, Siegel M, Woodbury-Smith M, King B, McCracken J, State M. Practice parameter for the assessment and treatment of children and adolescents with autism spectrum disorder. J Am Acad Child Adolesc Psychiatry. 2014 Feb. 53(2):237-57. [Medline].
Courchesne E, Mouton PR, Calhoun ME, Semendeferi K, Ahrens-Barbeau C, Hallet MJ, et al. Neuron number and size in prefrontal cortex of children with autism. JAMA. 2011 Nov 9. 306(18):2001-10. [Medline].
Davenport L. Measuring thoughts' accurately detects autism. Medscape Medical News. December 3, 2014. [Full Text].
Just MA, Cherkassky VL, Buchweitz A, Keller TA, Mitchell TM. Identifying autism from neural representations of social interactions: neurocognitive markers of autism. PLoS One. 2014. 9(12):e113879. [Medline]. [Full Text].
Hughes JR. Autism: the first firm finding = underconnectivity?. Epilepsy Behav. 2007 Aug. 11(1):20-4. [Medline].
Ecker C, Suckling J, Deoni SC, Lombardo MV, Bullmore ET, Baron-Cohen S, et al. Brain anatomy and its relationship to behavior in adults with autism spectrum disorder: a multicenter magnetic resonance imaging study. Arch Gen Psychiatry. 2012 Feb. 69(2):195-209. [Medline].
Brasic JR, Mohamed M. Human brain imaging of autism spectrum disorders. In: Seeman P, Madras B, Eds. Imaging of the Human Brain in Health and Disease. Neuroscience-Net, LLC, 2012. [Full Text].
NIH press release. Disorganized cortical patches suggest prenatal origin of autism. Available at http://www.nih.gov/news/health/mar2014/nimh-27.htm. Accessed: April 1, 2014.
Stoner R, Chow ML, Boyle MP, Sunkin SM, Mouton PR, Roy S, et al. Patches of disorganization in the neocortex of children with autism. N Engl J Med. 2014 Mar 27. 370(13):1209-19. [Medline].
Carmody DP, Lewis M. Regional white matter development in children with autism spectrum disorders. Dev Psychobiol. 2010 Dec. 52(8):755-63. [Medline].
Cauda F, Geda E, Sacco K, D'Agata F, Duca S, Geminiani G, et al. Grey matter abnormality in autism spectrum disorder: an activation likelihood estimation meta-analysis study. J Neurol Neurosurg Psychiatry. 2011 Dec. 82(12):1304-13. [Medline].
Chugani DC. Neuroimaging and neurochemistry of autism. Pediatr Clin North Am. 2012 Feb. 59(1):63-73, x. [Medline].
Pennesi CM, Klein LC. Effectiveness of the gluten-free, casein-free diet for children diagnosed with autism spectrum disorder: based on parental report. Nutr Neurosci. 2012 Mar. 15(2):85-91. [Medline].
Alberti A, Pirrone P, Elia M, Waring RH, Romano C. Sulphation deficit in "low-functioning" autistic children: a pilot study. Biol Psychiatry. 1999 Aug 1. 46(3):420-4. [Medline].
James SJ, Melnyk S, Jernigan S, Cleves MA, Halsted CH, Wong DH, et al. Metabolic endophenotype and related genotypes are associated with oxidative stress in children with autism. Am J Med Genet B Neuropsychiatr Genet. 2006 Dec 5. 141B(8):947-56. [Medline]. [Full Text].
Oliveira G, Diogo L, Grazina M, Garcia P, Ataíde A, Marques C, et al. Mitochondrial dysfunction in autism spectrum disorders: a population-based study. Dev Med Child Neurol. 2005 Mar. 47(3):185-9. [Medline].
Filipek PA, Juranek J, Nguyen MT, Cummings C, Gargus JJ. Relative carnitine deficiency in autism. J Autism Dev Disord. 2004 Dec. 34(6):615-23. [Medline].
Larsson HJ, Eaton WW, Madsen KM, Vestergaard M, Olesen AV, Agerbo E, et al. Risk factors for autism: perinatal factors, parental psychiatric history, and socioeconomic status. Am J Epidemiol. 2005 May 15. 161(10):916-25; discussion 926-8. [Medline].
Lawler CP, Croen LA, Grether JK, Van de Water J. Identifying environmental contributions to autism: provocative clues and false leads. Ment Retard Dev Disabil Res Rev. 2004. 10(4):292-302. [Medline].
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. 2004 Jun. 61(6):618-27. [Medline].
Hughes S. Prenatal Valproate Exposure Linked to Autism. Medscape Medical News. Available at http://www.medscape.com/viewarticle/803034. Accessed: May 2, 2013.
Christensen J, Grønborg TK, Sørensen MJ, Schendel D, Parner ET, Pedersen LH, et al. Prenatal valproate exposure and risk of autism spectrum disorders and childhood autism. JAMA. 2013 Apr 24. 309(16):1696-703. [Medline].
Croen LA, Grether JK, Yoshida CK, Odouli R, Hendrick V. Antidepressant use during pregnancy and childhood autism spectrum disorders. Arch Gen Psychiatry. 2011 Nov. 68(11):1104-12. [Medline].
Brooks M. Autism Risk Linked to Maternal Thyroid Dysfunction. Available at http://www.medscape.com/viewarticle/809718. Accessed: August 27, 2013.
Román GC, Ghassabian A, Bongers-Schokking JJ, Jaddoe VW, Hofman A, de Rijke YB, et al. Association of gestational maternal hypothyroxinemia and increased autism risk. Ann Neurol. 2013 Aug 13. [Medline].
Ozonoff S, Young GS, Carter A, Messinger D, Yirmiya N, Zwaigenbaum L, et al. Recurrence risk for autism spectrum disorders: a Baby Siblings Research Consortium study. Pediatrics. 2011 Sep. 128(3):e488-95. [Medline]. [Full Text].
Abrahams BS, Geschwind DH. Connecting genes to brain in the autism spectrum disorders. Arch Neurol. 2010 Apr. 67(4):395-9. [Medline].
Hallmayer J, Cleveland S, Torres A, Phillips J, Cohen B, Torigoe T, et al. Genetic heritability and shared environmental factors among twin pairs with autism. Arch Gen Psychiatry. 2011 Nov. 68(11):1095-102. [Medline].
Gillberg C, Cederlund M. Asperger syndrome: familial and pre- and perinatal factors. J Autism Dev Disord. 2005 Apr. 35(2):159-66. [Medline].
Merritt JL 2nd, Jalal SM, Barbaresi WJ, Babovic-Vuksanovic D. 14q32.3 deletion syndrome with autism. Am J Med Genet A. 2005 Feb 15. 133A(1):99-100. [Medline].
Liu XQ, Georgiades S, Duku E, Thompson A, Devlin B, Cook EH, et al. Identification of genetic loci underlying the phenotypic constructs of autism spectrum disorders. J Am Acad Child Adolesc Psychiatry. 2011 Jul. 50(7):687-696.e13. [Medline].
Schaefer GB, Lutz RE. Diagnostic yield in the clinical genetic evaluation of autism spectrum disorders. Genet Med. 2006 Sep. 8(9):549-56. [Medline].
Durand CM, Betancur C, Boeckers TM, Bockmann J, Chaste P, Fauchereau F, et al. Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are associated with autism spectrum disorders. Nat Genet. 2007 Jan. 39(1):25-7. [Medline]. [Full Text].
Garber KB, Visootsak J, Warren ST. Fragile X syndrome. Eur J Hum Genet. 2008 Jun. 16(6):666-72. [Medline].
Nakamoto M, Nalavadi V, Epstein MP, Narayanan U, Bassell GJ, Warren ST. Fragile X mental retardation protein deficiency leads to excessive mGluR5-dependent internalization of AMPA receptors. Proc Natl Acad Sci U S A. 2007 Sep 25. 104(39):15537-42. [Medline]. [Full Text].
Curatolo P, Porfirio MC, Benedetti S, Giana G, Manzi B. [Autismo.]. Minerva Pediatr. 2008/10;60(5):846-848:
Curatolo P, Bombardieri R, Jozwiak S. Tuberous sclerosis. Lancet. 2008 Aug 23. 372(9639):657-68. [Medline].
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. Environ Health Perspect. 2007 Oct. 115(10):1482-9. [Medline]. [Full Text].
Samson K. CDC-backed study suggests possible link between autistic disorders, maternal perticide exposure in California. Neurology Today. September 2007;7:7:
Hackethal V. More Evidence Links Autism to Air Pollution. Medscape Medical News. Available at http://www.medscape.com/viewarticle/833653. Accessed: October 24, 2014.
Evelyn Talbott, Lynne Marshall, Judith Rager, Vincent Arena, Ravi Sharma. The Association of National Air Toxics Assessment Exposures and the Risk of Childhood Autism Spectrum Disorder: A Case Control Study. American Association for Aerosol Research. Available at http://aaarabstracts.com/2014/viewabstract.php?pid=599. Accessed: October 24, 2014.
Sandin S, Hultman CM, Kolevzon A, Gross R, MacCabe JH, Reichenberg A. Advancing maternal age is associated with increasing risk for autism: a review and meta-analysis. J Am Acad Child Adolesc Psychiatry. 2012 May. 51(5):477-486.e1. [Medline].
Hultman CM, Sandin S, Levine SZ, Lichtenstein P, Reichenberg A. Advancing paternal age and risk of autism: new evidence from a population-based study and a meta-analysis of epidemiological studies. Mol Psychiatry. 2011 Dec. 16(12):1203-12. [Medline].
Rapin I, Tuchman RF. What is new in autism?. Curr Opin Neurol. 2008 Apr. 21(2):143-9. [Medline].
Honda H, Shimizu Y, Rutter M. No effect of MMR withdrawal on the incidence of autism: a total population study. J Child Psychol Psychiatry. 2005 Jun. 46(6):572-9. [Medline].
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. 1999 Jun 12. 353(9169):2026-9. [Medline].
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. 2007 Sep 27. 357(13):1281-92. [Medline].
Retraction--Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children. Lancet. 2010 Feb 6. 375(9713):445. [Medline].
Dobbs M. What the autism studies show isn't reflected in what the candidates say. The Washington Post. April 22, 2008;A: A8:
Newschaffer CJ, Falb MD, Gurney JG. National autism prevalence trends from United States special education data. Pediatrics. 2005 Mar. 115(3):e277-82. [Medline].
Barbaresi WJ, Katusic SK, Colligan RC, Weaver AL, Jacobsen SJ. The incidence of autism in Olmsted County, Minnesota, 1976-1997: results from a population-based study. Arch Pediatr Adolesc Med. 2005 Jan. 159(1):37-44. [Medline].
Rutter M. Aetiology of autism: findings and questions. J Intellect Disabil Res. 2005 Apr. 49:231-8. [Medline].
Rutter M. Incidence of autism spectrum disorders: changes over time and their meaning. Acta Paediatr. 2005 Jan. 94(1):2-15. [Medline].
Developmental Disabilities Monitoring Network Surveillance Year 2010 Principal Investigators, Centers for Disease Control and Prevention (CDC). Prevalence of autism spectrum disorder among children aged 8 years - autism and developmental disabilities monitoring network, 11 sites, United States, 2010. MMWR Surveill Summ. 2014 Mar 28. 63 (2):1-21. [Medline].
Kim YS, Leventhal BL, Koh YJ, Fombonne E, Laska E, Lim EC, et al. Prevalence of autism spectrum disorders in a total population sample. Am J Psychiatry. 2011 Sep. 168(9):904-12. [Medline].
Kurita H. [Current status of autism studies]. Seishin Shinkeigaku Zasshi. 2001. 103(1):64-75. [Medline].
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. 1993 Jul. 34(5):673-88. [Medline].
Chudley AE, Hagerman RJ. Fragile X syndrome. J Pediatr. 1987 Jun. 110(6):821-31. [Medline].
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. 1991 Feb. 48(2):195-202. [Medline]. [Full Text].
Einfeld SL. Autism and the fragile X syndrome. Am J Med Genet. 1988 May-Jun. 30(1-2):237-8. [Medline].
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. 1988 May-Jun. 30(1-2):655-63. [Medline].
Reiss AL, Freund L. Fragile X syndrome, DSM-III-R, and autism. J Am Acad Child Adolesc Psychiatry. 1990 Nov. 29(6):885-91. [Medline].
Wang LW, Tancredi DJ, Thomas DW. The prevalence of gastrointestinal problems in children across the United States with autism spectrum disorders from families with multiple affected members. J Dev Behav Pediatr. 2011 Jun. 32(5):351-60. [Medline].
Mahoney A, Poling A. Sexual Abuse Prevention for People with Severe Developmental Disabilities. J of Developmental and Physical Disabilities. May 2011;23(4):369-76:
Anderson C, Law JK, Daniels A, Rice C, Mandell DS, Hagopian L, et al. Occurrence and family impact of elopement in children with autism spectrum disorders. Pediatrics. 2012 Nov. 130(5):870-7. [Medline].
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].
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. 1996 Feb. 168(2):158-63. [Medline].
Lee MS, Kim JI, Ernst E. Massage therapy for children with autism spectrum disorders: a systematic review. J Clin Psychiatry. 2011 Mar. 72(3):406-11. [Medline].
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. 1994 Oct. 24(5):659-85. [Medline].
Liptak GS, Kennedy JA, Dosa NP. Social Participation in a Nationally Representative Sample of Older Youth and Young Adults With Autism. J Dev Behav Pediatr. 2011 Apr 15. [Medline].
Allison C, Auyeung B, Baron-Cohen S. Toward brief "Red Flags" for autism screening: The Short Autism Spectrum Quotient and the Short Quantitative Checklist for Autism in toddlers in 1,000 cases and 3,000 controls [corrected]. J Am Acad Child Adolesc Psychiatry. 2012 Feb. 51(2):202-212.e7. [Medline].
Allison C, Baron-Cohen S, Wheelwright S, Charman T, Richler J, Pasco G, et al. The Q-CHAT (Quantitative CHecklist for Autism in Toddlers): a normally distributed quantitative measure of autistic traits at 18-24 months of age: preliminary report. J Autism Dev Disord. 2008 Sep. 38(8):1414-25. [Medline].
Auyeung B, Baron-Cohen S, Wheelwright S, Allison C. The Autism Spectrum Quotient: Children's Version (AQ-Child). J Autism Dev Disord. 2008 Aug. 38(7):1230-40. [Medline].
Baron-Cohen S, Hoekstra RA, Knickmeyer R, Wheelwright S. The Autism-Spectrum Quotient (AQ)--adolescent version. J Autism Dev Disord. 2006 Apr. 36(3):343-50. [Medline].
Baron-Cohen S, Wheelwright S, Skinner R, Martin J, Clubley E. The autism-spectrum quotient (AQ): evidence from Asperger syndrome/high-functioning autism, males and females, scientists and mathematicians. J Autism Dev Disord. 2001 Feb. 31(1):5-17. [Medline].
Fombonne E, Rogé B, Claverie J, Courty S, Frémolle J. Microcephaly and macrocephaly in autism. J Autism Dev Disord. 1999 Apr. 29(2):113-9. [Medline].
National Center for Health Statistics. International Classification of Diseases (ICD-9-CM), 9th Revision, Clinical Modification. 4th Edition. Los Angeles, CA: Practice Management Information Corporation (PMIC); 1993:
Canal-Bedia R, García-Primo P, Martín-Cilleros MV, Santos-Borbujo J, Guisuraga-Fernández Z, Herráez-García L, et al. Modified checklist for autism in toddlers: cross-cultural adaptation and validation in Spain. J Autism Dev Disord. 2011 Oct. 41(10):1342-51. [Medline].
[Guideline] Cincinnati Children's Hospital Medical Center. Best evidence statement (BESt). Use of motor and self-care assessment tools for children with autism spectrum disorder (ASD). 2009 Jul. [Full Text].
Cincinnati Children's Hospital Medical Center. Best evidence statement (BESt). Use of sensory assessment tools with children diagnosed with autism spectrum disorder (ASD). 2009 Mar. [Full Text].
[Guideline] New York State Department of Health, Division of Family Health, Bureau of Early Intervention. Clinical Practice Guideline: Quick Reference Guide. Autism/Pervasive Developmental Disorders, Assessment and Intervention for Young Children (Age 0-3 Years). Reprinted 2009. [Full Text].
Lord C, Petkova E, Hus V, Gan W, Lu F, Martin DM, et al. A multisite study of the clinical diagnosis of different autism spectrum disorders. Arch Gen Psychiatry. 2012 Mar. 69(3):306-13. [Medline].
Sahota PK, Miles JH, Wang CH. Sleep disorders in children with autism. Neurology. 1997;48 (3):A258:
Hashimoto T, Tayama M, Miyazaki M, Murakawa K, Shimakawa S, Yoneda Y, et al. Brainstem involvement in high functioning autistic children. Acta Neurol Scand. 1993 Aug. 88(2):123-8. [Medline].
Hashimoto T, Tayama M, Murakawa K, Yoshimoto T, Miyazaki M, Harada M, et al. Development of the brainstem and cerebellum in autistic patients. J Autism Dev Disord. 1995 Feb. 25(1):1-18. [Medline].
Filipek PA. Quantitative magnetic resonance imaging in autism: the cerebellar vermis. Curr Opin Neurol. 1995 Apr. 8(2):134-8. [Medline].
Via E, Radua J, Cardoner N, Happé F, Mataix-Cols D. Meta-analysis of gray matter abnormalities in autism spectrum disorder: should Asperger disorder be subsumed under a broader umbrella of autistic spectrum disorder?. Arch Gen Psychiatry. 2011 Apr. 68(4):409-18. [Medline].
Eyler LT, Pierce K, Courchesne E. A failure of left temporal cortex to specialize for language is an early emerging and fundamental property of autism. Brain. 2012 Mar. 135:949-60. [Medline]. [Full Text].
Barnea-Goraly N, Lotspeich LJ, Reiss AL. Similar white matter aberrations in children with autism and their unaffected siblings: a diffusion tensor imaging study using tract-based spatial statistics. Arch Gen Psychiatry. 2010 Oct. 67(10):1052-60. [Medline].
Jou RJ, Mateljevic N, Kaiser MD, Sugrue DR, Volkmar FR, Pelphrey KA. Structural neural phenotype of autism: preliminary evidence from a diffusion tensor imaging study using tract-based spatial statistics. AJNR Am J Neuroradiol. 2011 Oct. 32(9):1607-13. [Medline].
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. 1989 Feb. 146(2):242-5. [Medline].
Chiron C, Leboyer M, Leon F, Jambaqué I, Nuttin C, Syrota A. SPECT of the brain in childhood autism: evidence for a lack of normal hemispheric asymmetry. Dev Med Child Neurol. 1995 Oct. 37(10):849-60. [Medline].
McGuire K, Erickson C, Gabriels RL, Kaplan D, Mazefsky C, McGonigle J, et al. Psychiatric Hospitalization of Children With Autism or Intellectual Disability: Consensus Statements on Best Practices. J Am Acad Child Adolesc Psychiatry. 2015 Dec. 54 (12):969-71. [Medline].
[Guideline] Luiselli JK, Bass JD, Whitcomb SA. Teaching applied behavior analysis knowledge competencies to direct-care service providers: outcome assessment and social validation of a training program. Behav Modif. 2010 Sep. 34(5):403-14. [Medline].
[Guideline] Carr JE, Fox EJ. Using video technology to disseminate behavioral procedures: a review of Functional Analysis: a Guide for Understanding Challenging Behavior (DVD). J Appl Behav Anal. 2009 Winter. 42(4):919-23. [Medline]. [Full Text].
Ganz JB, Davis JL, Lund EM, Goodwyn FD, Simpson RL. Meta-analysis of PECS with individuals with ASD: investigation of targeted versus non-targeted outcomes, participant characteristics, and implementation phase. Res Dev Disabil. 2012 Mar-Apr. 33(2):406-18. [Medline].
Dawson G, Rogers S, Munson J, Smith M, Winter J, Greenson J, et al. Randomized, controlled trial of an intervention for toddlers with autism: the Early Start Denver Model. Pediatrics. 2010 Jan. 125(1):e17-23. [Medline].
Dawson G, Jones EJ, Merkle K, Venema K, Lowy R, Faja S, et al. Early behavioral intervention is associated with normalized brain activity in young children with autism. J Am Acad Child Adolesc Psychiatry. 2012 Nov. 51(11):1150-9. [Medline].
Rogers SJ, Estes A, Lord C, Vismara L, Winter J, Fitzpatrick A, et al. Effects of a Brief Early Start Denver Model (ESDM)-Based Parent Intervention on Toddlers at Risk for Autism Spectrum Disorders: A Randomized Controlled Trial. J Am Acad Child Adolesc Psychiatry. 2012 Oct. 51(10):1052-65. [Medline]. [Full Text].
Brooks M. GI Troubles Common, Linked to Negative Behaviors in Autism. Medscape Medical News. Available at http://www.medscape.com/viewarticle/814364.. Accessed: November 26, 2013.
Chaidez V, Hansen RL, Hertz-Picciotto I. Gastrointestinal Problems in Children with Autism, Developmental Delays or Typical Development. J Autism Dev Disord. 2013 Nov 6. [Medline].
Mousain-Bosc M, Roche M, Polge A, Pradal-Prat D, Rapin J, Bali JP. Improvement of neurobehavioral disorders in children supplemented with magnesium-vitamin B6. II. Pervasive developmental disorder-autism. Magnes Res. 2006 Mar. 19(1):53-62. [Medline].
Adams JB, Audhya T, McDonough-Means S, Rubin RA, Quig D, Geis E, et al. Effect of a vitamin/mineral supplement on children and adults with autism. BMC Pediatr. 2011 Dec 12. 11:111. [Medline]. [Full Text].
Oswald DP, Sonenklar NA. Medication use among children with autism spectrum disorders. J Child Adolesc Psychopharmacol. 2007 Jun. 17(3):348-55. [Medline].
Spencer D, Marshall J, Post B, Kulakodlu M, Newschaffer C, Dennen T, et al. Psychotropic medication use and polypharmacy in children with autism spectrum disorders. Pediatrics. 2013 Nov. 132(5):833-40. [Medline].
Brauser D. Psychotropics Still Commonly Prescribed for Autism. Medscape [serial online]. Available at http://www.medscape.com/viewarticle/812982. Accessed: November 2, 2013.
McPheeters ML, Warren Z, Sathe N, Bruzek JL, Krishnaswami S, Jerome RN, et al. A systematic review of medical treatments for children with autism spectrum disorders. Pediatrics. 2011 May. 127(5):e1312-21. [Medline].
McDougle CJ, Kem DL, Posey DJ. Case series: use of ziprasidone for maladaptive symptoms in youths with autism. J Am Acad Child Adolesc Psychiatry. 2002 Aug. 41(8):921-7. [Medline].
Hollander E, Phillips A, Chaplin W, Zagursky K, Novotny S, Wasserman S, et al. A placebo controlled crossover trial of liquid fluoxetine on repetitive behaviors in childhood and adolescent autism. Neuropsychopharmacology. 2005 Mar. 30(3):582-9. [Medline].
Owley T, Walton L, Salt J, Guter SJ Jr, Winnega M, Leventhal BL, et al. An open-label trial of escitalopram in pervasive developmental disorders. J Am Acad Child Adolesc Psychiatry. 2005 Apr. 44(4):343-8. [Medline].
Namerow LB, Thomas P, Bostic JQ, Prince J, Monuteaux MC. Use of citalopram in pervasive developmental disorders. J Dev Behav Pediatr. 2003 Apr. 24(2):104-8. [Medline].
Couturier JL, Nicolson R. A retrospective assessment of citalopram in children and adolescents with pervasive developmental disorders. J Child Adolesc Psychopharmacol. 2002 Fall. 12(3):243-8. [Medline].
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. 2009 Jun. 66(6):583-90. [Medline].
Brasic JR, Zagzag D, Kowalik S, Prichep L, John ER, Barnett JY, et al. Clinical manifestations of progressive catatonia. Ger J Psychiatr. 2000. 3 (2):13-24. [Full Text].
Brasic JR, Zagzag D, Kowalik S, Prichep L, John ER, Liang HG, et al. Progressive catatonia. Psychol Rep. 1999. 84 (1):239-46.
Kem DL, Posey DJ, McDougle CJ. Priapism associated with trazodone in an adolescent with autism. J Am Acad Child Adolesc Psychiatry. 2002 Jul. 41(7):758. [Medline].
[Guideline] American Academy of Pediatrics. Management of Children With Autism Spectrum Disorder. Pediatrics. 2007 Nov;120(5):1183-1215. Available at http://pediatrics.aappublications.org/content/120/5/1162.full.
Rossignol DA. Hyperbaric oxygen therapy might improve certain pathophysiological findings in autism. Med Hypotheses. 2007. 68(6):1208-27. [Medline].
Rossignol DA, Rossignol LW. Hyperbaric oxygen therapy may improve symptoms in autistic children. Med Hypotheses. 2006. 67(2):216-28. [Medline].
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. 2007 Nov 16. 7:36. [Medline]. [Full Text].
Williams K, Wray JA, Wheeler DM. Intravenous secretin for autism spectrum disorders (ASD). Cochrane Database Syst Rev. 2012 Apr 18. 4:CD003495. [Medline].
Cassels C. Oxytocin 'Normalizes' Social Deficits in Kids With Autism. Medscape Medical News. Available at http://www.medscape.com/viewarticle/817552. Accessed: December 16, 2013.
Gordon I, Vander Wyk BC, Bennett RH, Cordeaux C, Lucas MV, Eilbott JA, et al. Oxytocin enhances brain function in children with autism. Proc Natl Acad Sci U S A. 2013 Dec 2. [Medline].
Celexa (citalopram hydrobromide) [package insert]. St. Louis, Missouri: Forest Pharmaceuticals, Inc; August, 2011. [Full Text].
US Food and Drug Administration. Celexa (citalopram hydrobromide): Drug safety communication – abnormal heart rhythms associated with high doses. Available at http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm269481.htm. Accessed: October 24, 2012.
A Message From APA President Dilip Jeste, M.D., on DSM-5. Available at http://www.psychnews.org/files/DSM-message.pdf. Accessed: December 1, 2012.
American Psychiatric Association. DSM-5 Development, Autism Spectrum Disorder. Proposed Revision. Available at http://www.dsm5.org/ProposedRevisions/Pages/proposedrevision.aspx?rid=94. Accessed: December 22, 2011.
APA. Autism Spectrum Disorder. Available at http://www.dsm5.org/Documents/Autism%20Spectrum%20Disorder%20Fact%20Sheet.pdf.. Accessed: July 1, 2013.
Brauser D. Abnormal Placentas May Signal Autism Risk. Medscape Medical News. Available at http://www.medscape.com/viewarticle/803331. Accessed: May 14, 2013.
Brauser D. Developmental Delays Detectable in High-risk 1-Year-Olds. Medscape Medical News. Available at http://www.medscape.com/viewarticle/821851. Accessed: March 17, 2014.
Brauser D. Routine Ultrasound Scans May Detect Autism in Utero. Medscape Medical News. Available at http://www.medscape.com/viewarticle/827333. Accessed: July 2, 2014.
Brauser D. Some kids 'age out' of autism. Medscape Medical News. January 23, 2013. Available at http://www.medscape.com/viewarticle/778061. Accessed: January 29, 2013.
Corrigan NM, Shaw DW, Estes AM, Richards TL, Munson J, Friedman SD, et al. Atypical Developmental Patterns of Brain Chemistry in Children With Autism Spectrum Disorder. JAMA Psychiatry. 2013 Jul 31. [Medline].
Frazier TW, Youngstrom EA, Speer L, Embacher R, Law P, Constantino J, et al. Validation of proposed DSM-5 criteria for autism spectrum disorder. J Am Acad Child Adolesc Psychiatry. 2012 Jan. 51(1):28-40.e3. [Medline]. [Full Text].
Harrison P. Novel Drug Modifies Core Autism Symptoms in Adults. Medscape Medical News. May 27 2014. [Full Text].
Huerta M, Bishop SL, Duncan A, Hus V, Lord C. Application of DSM-5 Criteria for Autism Spectrum Disorder to Three Samples of Children With DSM-IV Diagnoses of Pervasive Developmental Disorders. . Am J Psychiatry 2012;169:1056-1064. [Full Text].
Mandy WP, Charman T, Skuse DH. Testing the construct validity of proposed criteria for DSM-5 autism spectrum disorder. J Am Acad Child Adolesc Psychiatry. 2012 Jan. 51(1):41-50. [Medline].
Marcus RN, Owen R, Kamen L, Manos G, McQuade RD, Carson WH, et al. A placebo-controlled, fixed-dose study of aripiprazole in children and adolescents with irritability associated with autistic disorder. J Am Acad Child Adolesc Psychiatry. 2009 Nov. 48(11):1110-9. [Medline].
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. 2002 Aug 1. 347(5):314-21. [Medline].
Owen R, Sikich L, Marcus RN, Corey-Lisle P, Manos G, McQuade RD, et al. Aripiprazole in the treatment of irritability in children and adolescents with autistic disorder. Pediatrics. 2009 Dec. 124(6):1533-40. [Medline].
Ozonoff S, Young GS, Belding A, et al. The Broader Autism Phenotype in Infancy: When Does It Emerge?. J American Academy Child Adolesc Psychiatry. 2014 Jan 23. [Epub ahead of print].
Stetka B, Correll, C. A Guide to DSM-5: Autism Spectrum Disorders. Medscape Medical News. Available at http://www.medscape.com/viewarticle/803884_4. Accessed: July 1, 2013.
Walker CK, Anderson KW, Milano KM, Ye S, Tancredi DJ, Pessah IN, et al. Trophoblast Inclusions Are Significantly Increased in the Placentas of Children in Families at Risk for Autism. Biol Psychiatry. 2013 Apr 22. [Medline].