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dc.contributor.authorSteine, Iris Mulders
dc.contributor.authorZayats, Tetyana
dc.contributor.authorStansberg, Christine
dc.contributor.authorPallesen, Ståle
dc.contributor.authorMrdalj, Jelena
dc.contributor.authorHåvik, Bjarte
dc.contributor.authorSoule, Jonathan
dc.contributor.authorHaavik, Jan
dc.contributor.authorMilde, Anne Marita
dc.contributor.authorSkrede, Silje
dc.contributor.authorMurison, Robert
dc.contributor.authorKrystal, John H
dc.contributor.authorGrønli, Janne
dc.date.accessioned2017-05-02T11:38:52Z
dc.date.available2017-05-02T11:38:52Z
dc.date.issued2016-12-13
dc.PublishedSteine IM, Zayats T, Stansberg C, Pallesen S, Mrdalj J, Håvik B, Soule J, Haavik J, Milde AMM, Skrede S, Murison R, Krystal JH, Grønli J. Implication of NOTCH1 Gene in Susceptibility to Anxiety and Depression among Sexual Abuse Victims. Translational psychiatry. 2016;6:e977eng
dc.identifier.issn2158-3188
dc.identifier.urihttps://hdl.handle.net/1956/15766
dc.description.abstractSexual abuse contributes to the development of multiple forms of psychopathology, including anxiety and depression, but the extent to which genetics contributes to these disorders among sexual abuse victims remains unclear. In this translational study, we first examined gene expression in the brains of rodents exposed to different early-life conditions (long, brief or no maternal separation). Hypothesizing that genes revealing changes in expression may have relevance for psychiatric symptoms later in life, we examined possible association of those genes with symptoms of anxiety and depression in a human sample of sexual abuse victims. Changes in rodent brain gene expression were evaluated by means of correspondence and significance analyses of microarrays by comparing brains of rodents exposed to different early-life conditions. Tag single-nucleotide polymorphisms (SNPs) of resulting candidate genes were genotyped and tested for their association with symptoms of anxiety and depression (Hospital Anxiety and Depression Scale) in a sample of 361 sexual abuse victims, using multinomial logistic regression. False discovery rate was applied to account for multiple testing in the genetic association study, with q-value of 0.05 accepted as significant. We identified four genes showing differential expression among animals subjected to different early-life conditions as well as having potential relevance to neural development or disorders: Notch1, Gabrr1, Plk5 and Zfp644. In the human sample, significant associations were observed for two NOTCH1 tag SNPs: rs11145770 (OR=2.21, q=0.043) and rs3013302 (OR=2.15, q=0.043). Our overall findings provide preliminary evidence that NOTCH1 may be implicated in the susceptibility to anxiety and depression among sexual abuse victims. The study also underscores the potential importance of animal models for future studies on the health consequences of early-life stress and the mechanisms underlying increased risk for psychiatric disorders.en_US
dc.language.isoengeng
dc.publisherNature Publishing Groupeng
dc.rightsAttribution CC BYeng
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/eng
dc.titleImplication of NOTCH1 Gene in Susceptibility to Anxiety and Depression among Sexual Abuse Victimseng
dc.typePeer reviewed
dc.typeJournal article
dc.date.updated2017-02-01T16:31:51Z
dc.description.versionpublishedVersion
dc.rights.holderCopyright 2016 The Author(s)eng
dc.identifier.doihttps://doi.org/10.1038/tp.2016.248
dc.identifier.cristin1419352
dc.source.journalTranslational psychiatry


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