Older Fathers' Offspring More Likely Bipolar

The children of older aged fathers may have an increased risk of
bipolar disorder (BPD), according to a report released on September 1,
2008 in the Archives of General Psychiatry, one of
the JAMA/Archives journals.



A common and intense mood disorder, people who are bipolar often
experience episodes of mania and depression. There are few previously
identified risk factors for bipolar disorder, one of which is a family
history of psychotic disorders. Even so, many people with BPD have no
relatives also suffering from the disease. As a result of its
heterogenicity, many attempts have been made to classify BPD, for
instance by age of onset.



According to the article, previously, other complex neurodevelopmental
disorders, such as schizophrenia and autism, have been associated with
an older paternal age. To determine if paternal age was associated with
BPD,  Emma M. Frans, M.Med.Sc., of the Karolinska Institute,
Stockholm, Sweden, and colleagues examined Swedish registers with a
diagnosis of bipolar disorder. Pinpointing 13,428 diseased subjects,
five controls were selected for each of the same sex and same
birth-year without BPD.



In comparison, as the age of one's father became higher, it became more
likely that one was bipolar. When controlling for the age of the
mother, those participants whose fathers were older than 29 years had
an increased risk of BPD. The authors controlled for many variables
through with the association held. "After controlling for parity
[number of children], maternal age,
socioeconomic status and family history of psychotic disorders, the
offspring of men 55 years and older were 1.37 times more likely to be
diagnosed as having bipolar disorder than the offspring of men aged 20
to 24 years,"they say. While having an older mother also was associate
with increased risk, this was not as strong an association as the
paternal effect. If the bipolar disorder was diagnosed before the age
of 20, this early onset BPD was much more strongly associated with the
father's age and not associated with that of the mother.



The authors note that this association has often been attributed to the
personality traits of older fathers. They continue, "However, the
mental disorders associated with increasing paternal age are under
considerable genetic influence." This indicates that a genetic link may
exist between the age of a father and the diagnosis of bipolar or other
disorders in his children.



The authors suggest a mechanism for this association: "As men
age, successive germ cell replications occur, and de novo [new,
not passed from parent to offspring] mutations accumulate monotonously
as a result of DNA copy errors," they say. "Women 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. Consistent
with this notion, we found smaller effects of increased maternal age on
the risk of bipolar disorder in the offspring."



Advancing Paternal Age and Bipolar Disorder

Emma M. Frans; Sven Sandin; Abraham Reichenberg; Paul Lichtenstein;
Niklas Langstrom; Christina M. Hultman

Arch Gen Psychiatry. 2008;65(9):1034-1040.

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Written by Anna Sophia McKenney