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Increased Bipolar Risk Linked to Father's Age

Older men are more likely than younger men to father children with autism, schizophrenia, or early-onset bipolar disorder.

Fathering a child later in life seems to increase its risk of having autism or schizophrenia, research has shown. And now it seems to increase a child's risk of having bipolar disorder as well, a new study suggests.

The study was headed by Emma Frans, a doctoral student in epidemiology at the Karolinska Institute in Stockholm. Results were published in the September Archives of General Psychiatry.

Sweden's Multigeneration Register, as well as Sweden's National Hospital Discharge Register, made this new investigation possible. The former, which has been in existence since 1947, gives demographic information about all people living in Sweden as well as about their parents. The latter, which has been in existence since 1973, lists all people living in Sweden who have been hospitalized for various conditions.

Using the hospital discharge register, the researchers identified more than 13,000 persons who had been hospitalized for bipolar disorder at least twice since 1973 when the hospital discharge register was started. Using the Multigeneration Register, the researchers picked out five healthy individuals who matched each of the 13,000 persons on gender and date of birth. In other words, some 13,000 persons with bipolar disorder served as subjects, and 67,000 other individuals served as controls.

The researchers then used the Multigeneration Register to determine the age of each subject's father and of each control's father at the time of the subject's or control's birth. Finally, the researchers used this data to determine whether there was any link between paternal age at the time of birth and an offspring's chances of having bipolar disorder.

A link was found. Even when some possibly confounding factors such as socioeconomic status, family history of mental disorders, or maternal age at time of birth were considered, the offspring of men aged 55 or older were significantly more likely—1.37 times more likely—to have bipolar disorder than were the offspring of men aged 20 to 24. And for early-onset bipolar disorder (defined as occurring before age 20), the impact of paternal age was even more pronounced: the offspring of men aged 50 or older were 2.63 times more likely to have bipolar disorder than were the offspring of men aged 20 to 24.

Thus, paternal age seems to be "an independent risk factor for bipolar disorder," Frans and her colleagues concluded in their study report. "Furthermore, our results indicate that the paternal age effect might be most evident in patients with an early onset of the disorder."

Why older men are more at risk of fathering children with bipolar disorder, or autism or schizophrenia, than younger men are is not known. However, Frans and her team suspect that it is genetic, especially since they found a strong link between older paternal age and early-onset bipolar disorder, which has shown greater heritability than bipolar disorder that occurs later in life.

Furthermore, Frans and her group speculated in their report, older men's genetic proneness to father children with bipolar disorder may be due to the fact that "spermatogonial cells replicate every 16th day, resulting in approximately 200 divisions by the age of 20 years and 660 divisions by the age of 40 years [and even more divisions as a man grows older. Thus] disorders associated with advancing paternal age could partially result from de novo mutations."

Women, in contrast, they explained, "are born with their full supply of eggs that have gone through only 23 replications, a number that does not change as they age. Therefore DNA copy errors should not increase in number with maternal age."

The study had no outside funding.

An abstract of "Advancing Paternal Age and Bipolar Disorder" is posted at <http://archpsyc.ama-assn.org/cgi/content/abstract/65/9/1034>.

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