title: Effects of advanced paternal age on trajectories of social behavior in offspring.
abstract: Our study is the first investigation of the effects of advanced paternal age (APA) on the developmental trajectory of social behavior in rodent offspring. Given the strong epidemiological association between APA and sexually dimorphic neurodevelopmental disorders that are characterized by abnormalities in social behavior (autism, schizophrenia), we assessed sociability in male and female inbred mice (C57BL/6J) across postnatal development (N = 104) in relation to paternal age. We found differences in early social behavior in both male and female offspring of older breeders, with differences in this social domain persisting into adulthood in males only. We showed that these social deficits were not present in the fathers of these offspring, confirming a de novo origin of an altered social trajectory in the offspring generation. Our results, highly novel in rodent research, support the epidemiological observations in humans and provide evidence for a causal link between APA, age-related changes in the paternal sperm DNA and neurodevelopmental disorders in their offspring.
authors.affiliation: Social, Genetic and Developmental Psychiatry MRC Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
authors.forename: M
authors.identifier: http://orcid.org/0000-0001-7406-0776
authors.initials: M
authors.lastname: Janecka
authors.affiliation: Department of Science, Roma Tre University, Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Manduca
authors.affiliation: Department of Science, Roma Tre University, Rome, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Servadio
authors.affiliation: Department of Science, Roma Tre University, Rome, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Trezza
authors.affiliation: Social, Genetic and Developmental Psychiatry MRC Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
authors.forename: R
authors.initials: R
authors.lastname: Smith
authors.affiliation: Social, Genetic and Developmental Psychiatry MRC Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.|University of Exeter Medical School, University of Exeter, Exeter, UK.
authors.forename: J
authors.initials: J
authors.lastname: Mill
authors.affiliation: Social, Genetic and Developmental Psychiatry MRC Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.|School of Biological Sciences, University of Essex, Colchester, UK.
authors.forename: L C
authors.initials: LC
authors.lastname: Schalkwyk
authors.affiliation: Department of Child and Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.|Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: A
authors.initials: A
authors.lastname: Reichenberg
authors.affiliation: Social, Genetic and Developmental Psychiatry MRC Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
authors.forename: C
authors.initials: C
authors.lastname: Fernandes
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D010290:Parents; D010331:Paternal Age; D012098:Reproduction / Q000502:physiology; D012919:Social Behavior
keywords: de novo mutations; environmental effects; epidemiology; mouse models; neurodevelopment autism; neuroligin; paternal age effects; psychiatry; schizophrenia; social behavior