NEW YORK —
In recent years, scientists have debated based on mixed evidence whether a father’s age is linked to his child’s vulnerability to such individual disorders as autism and schizophrenia. Some studies have found strong associations, while others have found weak ones 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 F. 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 S. Kendler, a professor of psychiatry and human molecular genetics at Virginia Commonwealth University, also urged caution in interpreting the results.
“This is great work from a scientific perspective,” he said. “But it needs to be replicated, and biomedical science needs to get in gear and figure out what accounts for” the mixed findings of previous studies.
The strengths of the new report are size and rigor. The research team, led by Brian M. 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, so the scientists knew the father’s age for each birth and were able to track each child’s medical history over time, as well as that of siblings and other relatives. Among other things, the analysis compared the mental health of siblings born to the same father and found a clear pattern of increased risk with increasing paternal age.
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 likelihood of being diagnosed with 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. Older couples tend to be more stable and have more income — both protective factors that help to temper mental problems — and this was the case in the study. But much of the risk associated with paternal age remained.
“We spent months trying to make the findings go away, looking at the mother’s age, at psychiatric history, doing sub-analyses,” D’Onofrio said. “They wouldn’t go away.”
D’Onofrio had seven coauthors, including Paul Lichtenstein of the Karolinska Institute in Stockholm and Dr. Catarina Almqvist of the Karolinska Institute and Astrid Lindgren Children’s Hospital in nearby Solna, Sweden.
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. Unlike women, who age with a limited number of eggs, men have to replenish their supply of sperm cells. Studies suggest that the cells’ repeated reproductions lead to the accumulation of random errors over time, called de novo mutations.
“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. 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.