Paternal age older than 25 years and younger than 20 years were both associated with earlier onset among familial schizophrenia patients, according to a study led by Prof. Wei J. Chen with his postdoc fellow Dr. Shi-Heng Wang at National Taiwan University. This study has been published online on March 10 in Psychological Medicine.

“Advanced paternal age is associated with increased risk of schizophrenia,” said Dr. Wang, the first-author of the paper and now a postdoc at U.S. Food and Drug Administration. “However, what remains rarely explored is whether older paternal age could be associated with earlier onset among co-affected schizophrenia sib-pairs with the same familial predisposition.”

Based on a total of 1297 patients with schizophrenia from 630 families, which were ascertained to have at least two siblings affected, throughout Taiwan were interviewed using Diagnostic Interview for Genetic Studies. Both inter-family comparisons, a hierarchical regression model allowing for familial dependence and adjusting for confounders, and within-family comparisons, examining the consistency between onset order and birth order, were performed.

One major finding is that “an inverted U-shape was observed between paternal age and onset of schizophrenia,” said Dr. Wang. Affected offspring with paternal age of 20-24 had the oldest onset. As paternal age increased over 25, older paternal age exhibited a linear decrease in the onset of schizophrenia. On average, the onset was lowered by 1.5 years for paternal age of 25-29 and by 5.5 years for paternal age 30-50, with a p-value of 0.04 for the trend test. The proportion of younger siblings with earlier onset (58 percent) was larger than that of older siblings with earlier onset (42 percent), with a p-value of 0.0002.

Prof. Chen and his colleagues conclude “the associations of advanced paternal age with both increased susceptibility to schizophrenia and earlier onset of schizophrenia are consistent with the rate of increases in spontaneous mutations in sperm as men age.”