Advancing Paternal Age Is Associated with Deficits in Social and Exploratory Behaviors in the Offspring: A Mouse Model

Background: Accumulating evidence from epidemiological research has demonstrated an association between advanced paternal age and risk for several psychiatric disorders including autism, schizophrenia and early-onset bipolar disorder. In order to establish causality, this study used an animal model to investigate the effects of advanced paternal age on behavioural deficits in the offspring. Methods: C57BL/6J offspring (n=12 per group) were bred from fathers of two different ages, 2 months (young) and 10 months (old), and mothers aged 2 months (n= 6 breeding pairs per group). Social and exploratory behaviors were examined in the offspring. Principal Findings: The offspring of older fathers were found to engage in significantly less social (p=0.02) and exploratory (p= 0.02) behaviors than the offspring of younger fathers. There were no significant differences in measures of motor activity. Conclusions: Given the well-controlled nature of this study, this provides the strongest evidence for deleterious effects of advancing paternal age on social and exploratory behavior. De-novo chromosomal changes and/or inherited epigenetic changes are the most plausible explanatory factors. © 2009 Smith et al.