Advanced paternal age effects extend to several psychiatric disorders

By Lucy Piper, Senior medwireNews Reporter

The effect of advanced paternal age at childbearing on the psychiatric morbidity risk of their children extends to several psychiatric disorders and particularly bipolar disorder, findings from a sibling-comparison study show.

The results are in line with those from previous studies, including one recently published on medwireNews.com, and suggest that “[advanced paternal age] represents a risk of numerous public health and societal problems”, say the researchers.

But they also extend the current literature by ruling out the effects of genetic and environmental selection factors shared by siblings and demonstrate an effect that extends across several psychiatric disorders and developmental domains.

And, “perhaps most importantly, the current study suggests that the specific risks associated with [advanced paternal age] follow a dose-response relationship (ie, the increased risk was not solely present in extremely advanced paternal age) and that the magnitude of most of the associations were stronger than previous estimates”, lead researcher Brian D’Onofrio (Indiana University, Bloomington, USA) and colleagues report.

They carried out a population-based cohort study of all individuals born in Sweden between 1973 and 2001, involving 2,615,081 children.

Children born to fathers who were 45 years of age and older had a 24.70-fold increased risk for bipolar disorder, compared with those born to fathers aged 20 to 24 years. This was after all factors shared by siblings had been taken into account.

Similar associations were found for autism (hazard ratio [HR]=3.45), attention deficit hyperactivity disorder (HR=13.13), psychosis (HR=2.07), suicide attempts (HR=2.72) and substance use problems (HR=2.44).

Advanced paternal age also increased the risk of children failing grades and having low educational attainment of less than 10 years, by 59% and 70%, respectively.

Interestingly, the researchers note that the association of advanced paternal age with suicide attempt, substance use and academic problems strengthened after controlling for familial confounding, suggesting that shared factors correlated with advanced paternal age have a protective effect.

They replicated their findings using several family-based, quasi-experimental designs to strengthen both the internal and external validity of the findings.

The team concludes in JAMA Psychiatry that the results support the theory that genetic mutations that occur during spermatogenesis as a man ages influence offspring morbidity.

“If de novo point mutations are important genetic risk factors then molecular genetic studies should involve exome sequencing from both affected individuals and parents; reliance on genome-wide association studies would not identify such genetic factors,” they comment.

Licensed from medwireNews with permission from Springer Healthcare Ltd. ©Springer Healthcare Ltd. All rights reserved. Neither of these parties endorse or recommend any commercial products, services, or equipment.