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dc.contributor.author
Krug, Axel
dc.contributor.author
Wöhr, Markus
dc.contributor.author
Seffer, Dominik
dc.contributor.author
Rippberger, Henrike
dc.contributor.author
Sungur, A. Özge
dc.contributor.author
Dietsche, Bruno
dc.contributor.author
Stein, Frederike
dc.contributor.author
Sivalingam, Sugirthan
dc.contributor.author
Forstner, Andreas J.
dc.contributor.author
Witt, Stephanie H.
dc.contributor.author
Dukal, Helene
dc.contributor.author
Streit, Fabian
dc.contributor.author
Maaser, Anna
dc.contributor.author
Heilmann-Heimbach, Stefanie
dc.contributor.author
Andlauer, Till F.M.
dc.contributor.author
Herms, Stefan
dc.contributor.author
Hoffmann, Per
dc.contributor.author
Rietschel, Marcella
dc.contributor.author
Nöthen, Markus M.
dc.contributor.author
Lackinger, Martin
dc.contributor.author
Lackinger, Martin
dc.contributor.author
Koch, Michael
dc.contributor.author
Schwarting, Rainer K.W.
dc.contributor.author
Kircher, Tilo
dc.date.accessioned
2020-07-07T09:03:30Z
dc.date.available
2020-07-04T02:58:02Z
dc.date.available
2020-07-07T09:03:30Z
dc.date.issued
2020
dc.identifier.issn
2040-2392
dc.identifier.other
10.1186/s13229-020-00345-2
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/424381
dc.identifier.doi
10.3929/ethz-b-000424381
dc.description.abstract
Advanced paternal age (APA) is a risk factor for several neurodevelopmental disorders, including autism and schizophrenia. The potential mechanisms conferring this risk are poorly understood. Here, we show that the personality traits schizotypy and neuroticism correlated with paternal age in healthy subjects (N = 677). Paternal age was further positively associated with gray matter volume (VBM, N = 342) in the right prefrontal and the right medial temporal cortex. The integrity of fiber tracts (DTI, N = 222) connecting these two areas correlated positively with paternal age. Genome-wide methylation analysis in humans showed differential methylation in APA individuals, linking APA to epigenetic mechanisms. A corresponding phenotype was obtained in our rat model. APA rats displayed social-communication deficits and emitted fewer pro-social ultrasonic vocalizations compared to controls. They further showed repetitive and stereotyped patterns of behavior, together with higher anxiety during early development. At the neurobiological level, microRNAs miR-132 and miR-134 were both differentially regulated in rats and humans depending on APA. This study demonstrates associations between APA and social behaviors across species. They might be driven by changes in the expression of microRNAs and/or epigenetic changes regulating neuronal plasticity, leading to brain morphological changes and fronto-hippocampal connectivity, a network which has been implicated in social interaction.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
PubMed Central
en_US
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.title
Advanced paternal age as a risk factor for neurodevelopmental disorders: a translational study
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 4.0 International
dc.date.published
2020-06-23
ethz.journal.title
Molecular Autism
ethz.journal.volume
11
en_US
ethz.journal.issue
1
en_US
ethz.journal.abbreviated
Mol. Autism
ethz.pages.start
54
en_US
ethz.size
19 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.wos
ethz.identifier.scopus
ethz.publication.place
London
en_US
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02070 - Dep. Gesundheitswiss. und Technologie / Dep. of Health Sciences and Technology::02542 - Institut für Neurowissenschaften / Institute for Neuroscience::09498 - Schratt, Gerhard / Schratt, Gerhard
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02070 - Dep. Gesundheitswiss. und Technologie / Dep. of Health Sciences and Technology::02542 - Institut für Neurowissenschaften / Institute for Neuroscience::09498 - Schratt, Gerhard / Schratt, Gerhard
ethz.date.deposited
2020-07-04T02:58:43Z
ethz.source
SCOPUS
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2020-07-07T09:04:00Z
ethz.rosetta.lastUpdated
2024-02-02T11:22:21Z
ethz.rosetta.versionExported
true
ethz.COinS
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