Paternal Age at Birth of First Child and Risk of Schizophrenia

• Published in: The American journal of psychiatry Vol. 168; no. 1; pp. 82 - 88
• Main Authors: Petersen, Liselotte, Mortensen, Preben Bo, Pedersen, Carsten Bøcker
• Format: Journal Article
• Language: English
• Published: Arlington, VA American Psychiatric Publishing 01.01.2011; American Psychiatric Association
• Subjects: Adolescent; Adult; Adult and adolescent clinical studies; Age Factors; Aged; Biological and medical sciences; Birth Order; Breast cancer; Child; Denmark; Female; Genetic Predisposition to Disease - epidemiology; Health risk assessment; Humans; Incidence; Male; Maternal Age; Medical sciences; Middle Aged; Mutation; Parturition; Paternal Age; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychoses; Risk Factors; Schizophrenia; Schizophrenia - epidemiology; Schizophrenia - etiology; Schizophrenia - genetics; Siblings; Denmark; Human; Psychosis; Schizophrenia; Paternal age; Child; Risk factor
• ISSN: 0002-953X; 1535-7228; 1535-7228
• DOI: 10.1176/appi.ajp.2010.10020252

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.