Paternal age as a risk factor for schizophrenia: How important is it?

Torrey, E. Fuller; Buka, Stephen; Cannon, Tyrone D.; Goldstein, Jill M.; Seidman, Larry J.; Liu, Tianli; Hadley, Trevor; Rosso, Isabelle M.; Bearden, Carrie; Yolken, Robert H.

doi:10.1016/j.schres.2009.06.017

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Volume 114, Issue 1 , Pages 1-5, October 2009

Paternal age as a risk factor for schizophrenia: How important is it?

E. Fuller Torrey
- The Stanley Medical Research Institute, 8401 Connecticut Ave., Suite 200, Chevy Chase, MD 20815, USA
- Corresponding author. Tel.: +1 301 571 2078; fax: +1 301 571 0775.
Stephen Buka
- Department of Community Health, Brown University, 121 South Main Street, Providence, RI 02806, USA
Tyrone D. Cannon
- Departments of Psychology and Psychiatry, 1285 Franz Hall, University of California, Los Angeles, Los Angeles, CA 90095, USA
Jill M. Goldstein
- Departments of Psychiatry and Medicine, Harvard Medical School at Brigham and Women's Hospital, One Brigham Circle, Division of Women's Health, 3rd floor, 1620 Tremont St., Boston, MA 02120, USA
Larry J. Seidman
- Harvard Medical School, Department of Psychiatry, Massachusetts Mental Health Center Public Psychiatry Division, Beth Israel Deaconess Medical Center, Boston, MA 02115
- Harvard Medical School, Department of Psychiatry, Massachusetts General Hospital, Boston, MA 02114, USA
Tianli Liu
- Department of Community Health, Brown University, 121 South Main Street, Providence, RI 02806, USA
Trevor Hadley
- Department of Psychiatry, University of Pennsylvania, 3535 Market Street, Philadelphia PA 19104, USA
Isabelle M. Rosso
- McLean Hospital and Harvard Medical School, 115 Mill Street, Belmont, MA 02478, USA
Carrie Bearden
- Departments of Psychology and Psychiatry, 1285 Franz Hall, University of California, Los Angeles, Los Angeles, CA 90095, USA
Robert H. Yolken
- The Stanley Division of Developmental Neurovirology, Johns Hopkins University, 600 N. Wolfe Street, Blalock 1105, Baltimore, MD 21287-4933, USA

Received 12 February 2009; received in revised form 19 June 2009; accepted 23 June 2009. published online 17 August 2009.

Abstract

Advanced paternal age has been widely cited as a risk factor for schizophrenia among offspring and even claimed to account for one-quarter of all cases. We carried out a new study on 25,025 offspring from the Collaborative Perinatal Project (CPP), including 168 diagnosed with psychosis and 88 with narrowly defined schizophrenia. We also conducted a meta-analysis of this and nine other studies for which comparable age-cohort data were available. The mean paternal age for the CPP cases was slightly, but not significantly, higher than the matched controls (p=0.28). Meta-analyses including these new results were conducted to determine the relative risk associated with alternative definitions of advanced paternal age (35, 45 or 55years and older). These yielded pooled odds ratios and 95% confidence intervals of 1.28 (1.10, 1.48), 1.38 (0.95, 2.01) and 2.22 (1.46, 3.37), respectively. Thus, increased paternal age appears to be a risk factor for schizophrenia primarily among offspring of fathers ages 55 and over. In these 10 studies, such fathers accounted for only 0.6% of all births. Compared with other known risk factors for schizophrenia, advanced paternal age appears to be intermediate in magnitude. Advanced paternal age is also known to be a risk factor for some chromosomal and neoplastic diseases in the offspring where the cause is thought to be chromosomal aberrations and mutations of the aging germline. Similar mechanisms may account for the relationship between advanced paternal age and schizophrenia risk.