[TheMercenary]

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


Updated: Sep 10, 2008

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

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

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

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

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

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

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

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

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

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

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

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

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


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

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

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

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

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

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