In recent years, scientists have debated based on mixed evidence whether a father's age is linked to his child's vulnerability to individual disorders like autism and schizophrenia. Some studies have found strong associations, while others have found weak associations or none at all.
The new report, which looked at many mental disorders in Sweden, should inflame the debate, if not settle it, experts said. Men have a biological clock of sorts because of random mutations in sperm over time, the report suggests, and the risks associated with later fatherhood may be higher than previously thought.
The findings were published Wednesday in the journal JAMA Psychiatry.
"This is the best paper I've seen on this topic, and it suggests several lines of inquiry into mental illness," said Dr. Patrick Sullivan, a professor of genetics at the University of North Carolina, who was not involved in the research. "But the last thing people should do is read this and say, 'Oh no, I had a kid at 43, the kid's doomed.' The vast majority of kids born to older dads will be just fine."
Dr. Kenneth Kendler, a professor of psychiatry and human molecular genetics at Virginia Commonwealth University, also urged caution in interpreting the results.
The research team, led by Brian D'Onofrio of Indiana University, analyzed medical and public records of some 2.6 million people born in Sweden from 1973 to 2001. Like many European countries, Sweden has centralized medical care and keeps detailed records.
Compared with the children of young fathers, ages 20-24, those born to men age 45 and older had about twice the risk of developing psychosis, the signature symptom of schizophrenia; more than three times the likelihood of receiving a diagnosis of autism; and about 13 times the chance of having a diagnosis of attention deficit disorder. Children born to older fathers also tended to struggle more with academics and substance abuse.
The researchers controlled for every factor they could think of, including parents' education and income. The researchers say that any increased risk due solely to paternal age is most likely a result of the accumulation of genetic mutations in sperm cells.
"It's a plausible hypothesis at this point," Sullivan said.
Experts say the numbers in the study look more alarming than they probably are. For example, Sullivan said, the overall prevalence of autism is 0.5 percent to 1 percent of the population, depending on the estimate and the location.
But for the children of healthy parents in their 20s, the rate is perhaps 1 in 300, or even lower. A threefold increase would put the odds at about 1 in 100, still very low.
The same goes for the risk of psychosis. The baseline rate is tiny for the children of young, healthy parents, and remains quite low even when doubled.
The researchers found much larger increases in risk for attention deficits (13-fold) and bipolar disorder (25-fold) associated with late fatherhood.
"I don't know what to do with those numbers," Sullivan said, noting that two recent genetic studies found that the contribution of de novo mutations to the risk of mental disorders was "probably pretty low" compared with other factors.