Children of men age 40 and older have a significantly increased risk of having autism spectrum disorders compared with those whose fathers are younger than 30 years, according to an article in the September issue of Archives of General Psychiatry, one of the JAMA/Archives journals.
Autism is characterized by social and language abnormalities and repetitive patterns of behavior, according to background information in the article. Autism and related conditions, known collectively as autism spectrum disorders, have become increasingly common, affecting 50 in every 10,000 children as compared with five in 10,000 two decades ago. This increase is partially due to higher levels of awareness and changes in diagnosis processes, but could also reflect an increase in incidence of autism, according to the authors. Older parental age has previously been linked to abnormalities in the brain development of children; however, few studies have effectively examined the effect of mothers' and especially fathers' ages on autism.
Abraham Reichenberg, Ph.D., of the Mount Sinai School of Medicine, New York, and Institute of Psychiatry, King's College London, and colleagues evaluated this association in children born during the 1980s in Israel. All men and three-fourths of the women born in these years were assessed by the draft board at age 17, during which time any psychiatric disorders were recorded. Dr. Reichenberg and colleagues obtained draft board information and the age of the father for 318,506 individuals; age of the mother was available for 132,271 of those.
Two hundred and eight individuals in the larger group (a rate of 6.5 per 10,000) and 110 in the group with both maternal and paternal ages (8.3 per 10,000) had a diagnosis of autism spectrum disorder, according to the information in the draft board registry. Among the paternal age groups of 15 to 29 years, 30 to 39 years, 40 to 49 years and older than 50 years, there were 34 cases, 62 cases, 13 cases and one case, respectively, of autism spectrum disorders. Advancing age among fathers was associated with increased risk of autism. This association persisted after the researchers controlled for year of birth, socioeconomic status and the mother's age, such that the odds of autism spectrum disorder were nearly six times greater among children of men age 40 and older than those of men 29 years and younger. Older age among mothers was not associated with autism after researchers factored in the effect of the father's age.
The authors discuss several possible genetic mechanisms for the paternal age effect, including spontaneous mutations in sperm-producing cells or alterations in genetic "imprinting," which affects gene expression. "It is important to keep in mind, however, that age at paternity is influenced by the sociocultural environment and varies across societies and over time," they continue. "In a given population, a change in the sociocultural environment could produce a change in paternal age at birth. In theory, it could thereby lead to a change in the incidence of genetic causes of autism."
"Although further work is necessary to confirm this interpretation, we believe that our study provides the first convincing evidence that advanced paternal age is a risk factor for autism spectrum disorder," they conclude.
(Arch Gen Psychiatry. 2006;63:1026-1032. Available pre-embargo to the media at www.jamamedia.org.)
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