Mental Illness Risk Higher for Children of Older Fathers, Study Finds

Mental Illness Risk Higher for Children of Older Fathers, Study Finds

By BENEDICT CAREYFEB. 26, 2014

Children born to middle-aged men are more likely than those born to younger fathers to develop any of a range of mental difficulties, including attention deficits, bipolar disorder, autism and schizophrenia, according to the most comprehensive study to date of paternal age and offspring mental health.

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 on Wednesday in the journal JAMA Psychiatry.

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“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 about 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, aged 20 to 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. 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,” Dr. D’Onofrio said. “They wouldn’t go away.”

Dr. D’Onofrio had seven co-authors, 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.

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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. Most such mutations are harmless, geneticists say, but some have been linked to mental disorders.

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RECENT COMMENTS

Krish 58 minutes ago

I couldn't tell from this article at what age this problem develops or they are diagnosed for the late born children.I would be very...

JK 58 minutes ago

Why is there - reading some reader comment - such joy "Ha! Those men are subject to aging too. not only us, sisters?"

wedge1 58 minutes ago

I am 57.Sarah 35.She is due in April.The midwife who has delivered 300 Amish babies says things are perfect. I believe her.Andy my 19 year...

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“It’s a plausible hypothesis at this point,” Dr. Sullivan said.

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Experts say the numbers in the study look more alarming than they probably are. For example, Dr. 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 one in 300, or even lower. A threefold increase would put the odds at about one 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,” Dr. 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.

“The question we now need to ask,” Dr. Kendler said, “is what else is going on with respect to older and younger siblings that could cause these differences.”

A version of this article appears in print on February 27, 2014, on page A6 of the New York edition with the headline: Mental Health Risks Seen for Children of Older Fathers . Order Reprints|Today's Paper|Subscribe