Advancing paternal age is associated with deficits in social and exploratory behaviors in the offspring: a mouse model

• Published in: PloS one Vol. 4; no. 12; p. e8456
• Main Authors: Smith, Rebecca G, Kember, Rachel L, Mill, Jonathan, Fernandes, Cathy, Schalkwyk, Leonard C, Buxbaum, Joseph D, Reichenberg, Abraham
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 30.12.2009; Public Library of Science (PLoS)
• Subjects: Age; Analysis; Animals; Autism; Behavior; Bipolar disorder; Breeding; Epidemiology; Epigenetic inheritance; Epigenetics; Exploratory behavior; Exploratory Behavior - physiology; Female; Group dynamics; Male; Medical research; Mental disorders; Mental Health/Child and Adolescent Psychiatry; Mental Health/Neuropsychiatric Disorders; Mental Health/Schizophrenia and Other Psychoses; Mice; Mice, Inbred C57BL; Models, Animal; Motor activity; Mutation; Neuroscience/Animal Cognition; Offspring; Paternal Age; Rodents; Schizophrenia; Social Behavior; United Kingdom > UK; New York; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0008456

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. 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. 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. 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.