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Abstract

Objective:

Greater paternal age is associated with increased risk of schizophrenia, and it has been hypothesized that de novo mutations in paternal germ cells are responsible for this association. An alternative hypothesis is that selection into late fatherhood accompanies a predisposition to schizophrenia. However, direct evidence of either hypothesis is lacking. If de novo mutations are responsible, greater paternal age at conception should increase the risk of schizophrenia. Conversely, if selection into late fatherhood is responsible for the association, greater age at which the father had his first child should increase the risk of schizophrenia. The authors aimed to distinguish between these two measures of paternal age.

Method:

A total of 2.2 million people born in Denmark between 1955 and 1992 were followed up until first diagnosis with schizophrenia. Incidence rate ratios were estimated in a Cox regression.

Results:

Among second- or later-born children, greater paternal age increased the risk of schizophrenia. However, when paternal age at the time of the father's first child was accounted for, the risk of schizophrenia did not depend on paternal age at the birth of later children. In contrast, the risk of schizophrenia increased significantly with increasing paternal age at the time of the father's first child.

Conclusions:

Factors related to greater paternal age when the father's first child was born, and not the father's age at conception of later children, are responsible for the association between paternal age and the risk of schizophrenia. These findings do not support the de novo mutation hypothesis.

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Information

Published In

Go to American Journal of Psychiatry
Go to American Journal of Psychiatry
American Journal of Psychiatry
Pages: 82 - 88
PubMed: 20952457

History

Received: 18 February 2010
Revision received: 15 June 2010
Accepted: 15 July 2010
Published online: 1 January 2011
Published in print: January 2011

Authors

Details

Liselotte Petersen, M.Sc., Ph.D.
From the National Centre for Register-Based Research, Aarhus University.
Preben Bo Mortensen, M.D., D.M.Sc.
From the National Centre for Register-Based Research, Aarhus University.
Carsten Bøcker Pedersen, M.Sc., D.M.Sc.
From the National Centre for Register-Based Research, Aarhus University.

Notes

Address correspondence and reprint requests to Dr. Petersen, National Centre for Register-Based Research, Aarhus University, Taasingegade 1, DK-8000 Aarhus C, Denmark; [email protected] (e-mail).

Funding Information

All authors report no financial relationships with commercial interests.Supported by the Stanley Medical Research Institute.

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