Paternal Age at Birth of First Child and Risk of Schizophrenia.

Am J Psychiatry. 2010 Oct 15. [Epub ahead of print]




Paternal Age at Birth of First Child and Risk of Schizophrenia.

Petersen L, Mortensen PB, Pedersen CB.



National Centre for Register-Based Research, Aarhus University.



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 fi rst 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 fi rst 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 fi rst 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 fi rst 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 fi ndings do not support the de novo mutation hypothesis.



http://www.ncbi.nlm.nih.gov/pubmed/20952457