Paternal age and sporadic schizophrenia: Evidence for de novo mutations

Authors

  • Dolores Malaspina,

    Corresponding author
    1. Columbia University Department of Psychiatry/New York State Psychiatric Institute, Mailman School of Public Health, Columbia University, New York, New York
    • New York State Psychiatric Institute, 1051 Riverside Drive, New York, NY 10032.
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  • Cheryl Corcoran,

    1. Columbia University Department of Psychiatry/New York State Psychiatric Institute, Mailman School of Public Health, Columbia University, New York, New York
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  • Cherine Fahim,

    1. Columbia University Department of Psychiatry/New York State Psychiatric Institute, Mailman School of Public Health, Columbia University, New York, New York
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  • Ariela Berman,

    1. Columbia University Department of Psychiatry/New York State Psychiatric Institute, Mailman School of Public Health, Columbia University, New York, New York
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  • Jill Harkavy-Friedman,

    1. Columbia University Department of Psychiatry/New York State Psychiatric Institute, Mailman School of Public Health, Columbia University, New York, New York
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  • Scott Yale,

    1. Columbia University Department of Psychiatry/New York State Psychiatric Institute, Mailman School of Public Health, Columbia University, New York, New York
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  • Deborah Goetz,

    1. Columbia University Department of Psychiatry/New York State Psychiatric Institute, Mailman School of Public Health, Columbia University, New York, New York
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  • Raymond Goetz,

    1. Columbia University Department of Psychiatry/New York State Psychiatric Institute, Mailman School of Public Health, Columbia University, New York, New York
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  • Susan Harlap,

    1. Department of OBGYN, New York University School of Medicine, New York, New York
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  • Jack Gorman

    1. Columbia University Department of Psychiatry/New York State Psychiatric Institute, Mailman School of Public Health, Columbia University, New York, New York
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Abstract

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. © 2002 Wiley-Liss, Inc.

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