Paternal age and sporadic schizophrenia: evidence for de novo mutations.
Schizophrenia is an etiologically heterogeneous syndrome. It has a strong genetic component and exists in clinically indistinguishable familial and nonfamilial (sporadic) forms. A significant role for de novo genetic mutations in genetic schizophrenia vulnerability is suggested by a strong monotonic increase in schizophrenia risk with advancing paternal age. However, an alternative explanation for the paternal age effect in schizophrenia is that childbearing is delayed in fathers who themselves have genetic schizophrenia vulnerability. In this study, we compared paternal birth ages between patient groups with familial (n = 35) and sporadic (n = 68) patients with DSM-IV schizophrenia from an inpatient schizophrenia research unit. If later age of fathering children is related to having some genetic schizophrenia vulnerability, then paternal birth age should be later in familial schizophrenia cases than in sporadic cases, and any association of father's age and schizophrenia risk in offspring would be a spurious finding, unrelated to etiology. However, if de novo mutations cause sporadic schizophrenia, then patients without a family history of schizophrenia would have older fathers than familial patients. We found that patients without a family history of schizophrenia had significantly older fathers (4.7 years) than familial patients; so later childbirth was not attributable to parental psychiatric illness. These findings support the hypothesis that de novo mutations contribute to the risk for sporadic schizophrenia.
Malaspina
Dolores
D
Columbia University Department of Psychiatry/New York State Psychiatric Institute, Mailman School of Public Health, Columbia University, New York, New York 10032, USA. dm9@Columbia.edu
Corcoran
Cheryl
C
Fahim
Cherine
C
Berman
Ariela
A
Harkavy-Friedman
Jill
J
Yale
Scott
S
Goetz
Deborah
D
Goetz
Raymond
R
Harlap
Susan
S
Gorman
Jack
J
D000367:Age Factors; D000704:Analysis of Variance; D005192:Family Health; D005260:Female; D006801:Humans; D008297:Male; D008423:Maternal Age; D010331:Paternal Age; D012307:Risk Factors; D012559:Schizophrenia / Q000209:etiology / Q000235:genetics*