Advanced paternal age effects in neurodevelopmental disorders—review of potential underlying mechanisms

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 gamet...

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Bibliographic Details
Published in:Translational psychiatry Vol. 7; no. 1; p. e1019
Main Authors: Janecka, M, Mill, J, Basson, M A, Goriely, A, Spiers, H, Reichenberg, A, Schalkwyk, L, Fernandes, C
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 31.01.2017
Nature Publishing Group
Subjects:
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38/23
631/208/2489
631/477/2811
Age Factors
Autistic Disorder - epidemiology
Autistic Disorder - genetics
Behavioral Sciences
Biological Psychology
Epigenesis, Genetic
Humans
Medicine
Medicine & Public Health
Neurodevelopmental disorders
Neurodevelopmental Disorders - epidemiology
Neurodevelopmental Disorders - genetics
Neurosciences
Paternal Age
Pharmacotherapy
Psychiatry
Review
Risk Factors
Schizophrenia - epidemiology
Schizophrenia - genetics
ISSN:2158-3188, 2158-3188
Online Access:Get full text
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Summary: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.
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These authors contributed equally to this work.
ISSN:2158-3188
2158-3188
DOI:10.1038/tp.2016.294