Problem paternity: older men seem more apt to have autistic kids.

Children born to fathers who are age 40 or older have an increased risk of developing autism, a new study suggests.

Autism is marked by poor verbal skills, repetitive behavior patterns, and social detachment. It shows a hereditary component; someone with an autistic sibling has an increased risk of being autistic. But no single gene mutation or alteration appears to explain most cases of the disease. "There are probably many genes that might contribute to it" says Abraham Reichenberg, a neuro-psychologist at Mount Sinai School of Medicine in New York City.

The incidence of autism rose roughly tenfold in the United States between 1975 and 1995. While some of the increase might have resulted from greater awareness and diagnosis of the condition, scientists have sought other explanations. Some have focused on paternal age, which appears to be increasing in industrialized countries.

Reichenberg and his colleagues tapped into a database of Israeli young people, who are required to register with a draft board at age 17. Records of more than 300,000 youths revealed that children fathered by men age 40 or older were nearly six times as likely to be autistic as those with fathers under 30. In a separate calculation, the team found that fathers in their 30s were no more likely than younger men to have autistic children. The findings appear in the September Archives of General Psychiatry. Previous studies attempting to link advanced paternal age to autism risk had shown mixed results.

Scientists are speculating about how advanced paternal age might impart autism risk. The fault could lie in genetic changes that accumulate in a man's sperm-producing cells as they regenerate over the years, Reichenberg says. "These are spontaneous mutations in the germ line, and they just stay there," he says. An older man would have more mutations that might lead to autism to pass on to his children.

Another proposed explanation evokes gene imprinting. Children get two copies of every gene, one apiece from the mother and father. Some genes arrive from a parent with chemical groups--or imprints--that influence whether that copy will be activated or silenced in the offspring. Studies have linked a loss of imprinting to some diseases, including cancer.

It isn't known whether paternal age disrupts this system of imprinting, but some imprinted genes play a role in brain development, says behavioral geneticist Lawrence Wilkinson of Cardiff University in Wales. "Abnormalities in genomic imprinting could lead to abnormal gene [activation] in the brain--perhaps during critical stages of development--that could increase the risk for autism," he says.

A third possibility rests on past reports that parents of some autistic children are themselves prone to social awkwardness, potentially reflecting autism's genetic underpinnings. "We and others wonder if, in families with autism, there might be [others] with problems of social interaction, or speech problems, or shyness," says Richard Schroer, a geneticist and pediatrician at the Florence, S.C., branch of the Greenwood Genetic Center, a nonprofit research-and-diagnostic institute. The connection found in this study, he says, "might be that some men, because of social-interaction problems, may have taken longer to marry and to have children."