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Louis J. Sheehan

Children born to older fathers might have an increased risk of developing bipolar disorder, Swedish researchers report in the September Archives of General Psychiatry.

The finding is a statistical association drawn from a large population survey. But it falls in line with earlier studies suggesting that children sired by older men face a greater-than-average risk of being stillborn, miscarried or having schizophrenia, cancer or autism.

The theory linking paternal age with an offspring’s health rests on the genetics of aging sperm. Spontaneous mutations can accumulate in the genes of a man’s sperm cells as he ages. These cells divide as many as 660 times by the time a man reaches 40, by some estimates. Each division increases the risk of acquiring a harmful mutation from erroneous gene copying, the theory holds.

Women don’t face this risk since the number of eggs a woman carries is set at birth, each having divided 23 times at that point and no more. But older women do face a higher risk of having a child with Down syndrome.

In the new study, epidemiologist Emma Frans of the Karolinska Institute in Stockholm and her colleagues used a national registry to identify 13,428 people who had been diagnosed with bipolar disorder during at least two hospital admissions. For comparison purposes, each of these individuals was matched with five randomly selected people of the same gender and year of birth.

People fathered by men 55 or older had a 37 percent greater risk of being bipolar than those sired by men age 20 through 24. If the father was age 30 through 54, he imparted only a modestly increased risk. Being sired by a father age 25 through 29 did not add a risk. The researchers accounted for education level, age of the mother, family history of psychotic disorders and the number of children the mother had.

For people diagnosed with bipolar disorder before age 20, the late paternity effect was even more pronounced. Researchers found that people born to men over age 40 seemed to incur double the risk of being bipolar in youth as those fathered by men in their early 20s.

Other studies have suggested that having a close, personal relative with bipolar disorder increases a person’s risk of developing the condition. That association’s increase is much greater than any risk from merely having an older father, Frans says.

Bipolar disorder appears to have a clear genetic component, particularly when the condition shows up in youth, says epidemiologist Ronald Kessler of Harvard Medical School in Boston. But this study may not catch all men with bipolar disorder, and many bipolar men go through multiple marriages and often father children as they go along, he says.

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“I wonder whether men who have more severe bipolar disorder are just more likely to have kids at 40 or 50?” he asks. If so, that would exaggerate any risk seemingly imparted by aging itself, he says. The explanation “may be a psychosocial one,” he says.

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