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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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:
38
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
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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.
AbstractList 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.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.
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.
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.
Author Janecka, M
Reichenberg, A
Schalkwyk, L
Fernandes, C
Mill, J
Goriely, A
Spiers, H
Basson, M A
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  organization: Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King’s College London
BackLink https://www.ncbi.nlm.nih.gov/pubmed/28140401$$D View this record in MEDLINE/PubMed
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PMID 28140401
PQID 1869323563
PQPubID 2041978
ParticipantIDs pubmedcentral_primary_oai_pubmedcentral_nih_gov_5299396
proquest_miscellaneous_1863220537
proquest_journals_1869323563
pubmed_primary_28140401
crossref_citationtrail_10_1038_tp_2016_294
crossref_primary_10_1038_tp_2016_294
springer_journals_10_1038_tp_2016_294
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PublicationDate 2017-01-31
PublicationDateYYYYMMDD 2017-01-31
PublicationDate_xml – month: 01
  year: 2017
  text: 2017-01-31
  day: 31
PublicationDecade 2010
PublicationPlace London
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PublicationTitle Translational psychiatry
PublicationTitleAbbrev Transl Psychiatry
PublicationTitleAlternate Transl Psychiatry
PublicationYear 2017
Publisher Nature Publishing Group UK
Nature Publishing Group
Publisher_xml – name: Nature Publishing Group UK
– name: Nature Publishing Group
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Snippet Multiple epidemiological studies suggest a relationship between advanced paternal age (APA) at conception and adverse neurodevelopmental outcomes in offspring,...
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springer
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StartPage e1019
SubjectTerms 38
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
Title Advanced paternal age effects in neurodevelopmental disorders—review of potential underlying mechanisms
URI https://link.springer.com/article/10.1038/tp.2016.294
https://www.ncbi.nlm.nih.gov/pubmed/28140401
https://www.proquest.com/docview/1869323563
https://www.proquest.com/docview/1863220537
https://pubmed.ncbi.nlm.nih.gov/PMC5299396
Volume 7
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