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Transl Psychiatry. 2017 Jan 31;7(1):e1019. doi: 10.1038/tp.2016.294.

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

Author information

1
Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
2
Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
3
University of Exeter Medical School, University of Exeter, Exeter, UK.
4
Department of Craniofacial and Stem Cell Biology, MRC Centre for Neurodevelopmental Disorders, King's College London, London, UK.
5
Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
6
School of Biological Sciences, University of Essex, Colchester, UK.

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.

PMID:
28140401
PMCID:
PMC5299396
DOI:
10.1038/tp.2016.294
[Indexed for MEDLINE]
Free PMC Article

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