title: Advanced paternal age effects in neurodevelopmental disorders-review of potential underlying mechanisms.
abstract: Multiple epidemiological studies suggest a relationship between advanced paternal age (APA) at conception and adverse neurodevelopmental outcomes in offspring, particularly with regard to increased risk for autism and schizophrenia. Conclusive evidence about how age-related changes in paternal gametes, or age-independent behavioral traits affect neural development is still lacking. Recent evidence suggests that the origins of APA effects are likely to be multidimensional, involving both inherited predisposition and de novo events. Here we provide a review of the epidemiological and molecular findings to date. Focusing on the latter, we present the evidence for genetic and epigenetic mechanisms underpinning the association between late fatherhood and disorder in offspring. We also discuss the limitations of the APA literature. We propose that different hypotheses relating to the origins of the APA effects are not mutually exclusive. Instead, multiple mechanisms likely contribute, reflecting the etiological complexity of neurodevelopmental disorders.
authors.affiliation: Social, Genetic and Developmental Psychiatry Centre, 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: M
authors.initials: M
authors.lastname: Janecka
authors.affiliation: Social, Genetic and Developmental Psychiatry 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: Department of Craniofacial and Stem Cell Biology, MRC Centre for Neurodevelopmental Disorders, King's College London, London, UK.
authors.forename: M A
authors.initials: MA
authors.lastname: Basson
authors.affiliation: Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
authors.forename: A
authors.initials: A
authors.lastname: Goriely
authors.affiliation: University of Exeter Medical School, University of Exeter, Exeter, UK.
authors.forename: H
authors.initials: H
authors.lastname: Spiers
authors.affiliation: 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: School of Biological Sciences, University of Essex, Colchester, UK.
authors.forename: L
authors.initials: L
authors.lastname: Schalkwyk
authors.affiliation: Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
authors.forename: C
authors.initials: C
authors.lastname: Fernandes
mesh_terms: D000367:Age Factors; D001321:Autistic Disorder / Q000453:epidemiology* / Q000235:genetics; D044127:Epigenesis, Genetic; D006801:Humans; D065886:Neurodevelopmental Disorders / Q000453:epidemiology* / Q000235:genetics; D010331:Paternal Age; D012307:Risk Factors; D012559:Schizophrenia / Q000453:epidemiology* / Q000235:genetics