Dataset Information

Implication of NOTCH1 gene in susceptibility to anxiety and depression among sexual abuse victims.

ABSTRACT: Sexual 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.

SUBMITTER: Steine IM

PROVIDER: S-EPMC5290341 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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Implication of NOTCH1 gene in susceptibility to anxiety and depression among sexual abuse victims.

Steine I M IM Zayats T T Stansberg C C Pallesen S S Mrdalj J J Håvik B B Soulé J J Haavik J J Milde A M AM Skrede S S Murison R R Krystal J J Grønli J J

Translational psychiatry 20161213 12

Sexual 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 lat ...[more]

PMID: 27959334

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Project description:The term "apostate" describes the term used by the religious to describe individuals raised within religious families who once identified as religious, but who have ceased to believe in the existence of God, gods or follow their religious belief, and now identify as non-religious. Given the strong feelings families can have about the rejection of their shared faith, and the difficulty that police forces may have in identifying and understanding the complexities of violence toward the apostate, this study sought to examine the possibility that apostates represent a hidden population of abuse victims within religious households. We recruited 228 persons (102 males, 119 females) from an online survey with the support of "Faith to Faithless"-a service within Humanists UK, which supports people that leave their religious faith. Individuals were screened using a modified version of the Conflict Tactics Scale to quantify their experience of assault and negotiation. It was found that persons who identified as apostates experienced more assault (i.e., harmful violence) than non-religious persons. Within this sample, Muslim apostates were significantly more likely to be victimized than Christian apostates. Disclosure of being abused for identifying as an apostate within a religious household to law enforcement was extremely uncommon, thereby preventing detection or prosecution of abusive acts committed by family members and limiting public awareness of this issue. These results are discussed in the context of the broader culture of honor-based (izzat) violence, which occurs across the Eastern Mediterranean, Middle East, and North Africa, and is also seen in some Protestant Christian subcultures, and common to all Abrahamic religions, rather than Islam alone. This study highlights that within a multicultural society, there remain hidden populations of abuse victims who are vulnerable due to religious, cultural, and traditional constraints made by abusive family members.

Project description:Background: Suicide is moderately heritable and also more common in those who report childhood abuse. Previously, it was found that allele A of GABRG2 (GABA A receptor subunit gamma2) polymorphism rs211034 was protective in a suicide attempt (SA). Hence, it was proposed that rs211034 may interact with childhood trauma to influence cognitive deficits related to SA or depression risk. Genetic variants may predict the benefits of certain cognitive treatments. Methods: A total of 52 individuals who had attempted suicide, 59 individuals with major depressive disorder (MDD) or bipolar depression who had not previously attempted suicide, and 90 healthy volunteers were subjected to the modified Suicide Stroop task and were clinically assessed using the Childhood Trauma Questionnaire (CTQ) and Hamilton Depression Scale-24 items (HAMD-24). rs211034 was genotyped using Sanger sequencing. Results: After correcting for covariates, depressed participants displayed longer reaction times for all emotional conditions, including suicide-related words, compared with healthy controls. Depressed suicide attempters displayed longer reaction times for negative words than depressed non-attempters. Depressed non-attempters displayed higher interference scores for negative words compared with healthy controls. There was an interaction between rs211034 risk allele and the effects of reported childhood sexual abuse (CSA) on reaction time for all emotional words and suicide-related words. Carriers of the rs211034 risk allele A exhibited shorter reaction times, but the protective effects of this allele were eliminated in those exposed to reported CSA. Conclusion: Only limited results were found regarding effects of a past suicide attempt on response times to emotional and suicide-related words, but there was an overall effect of major depression on slower response time. Protective genetic effects of the rs211034 A allele on this slowing were eliminated in those with a history of sexual abuse during childhood. Further research is needed to better characterize the mechanisms underlying the effects of childhood trauma on these genetic effects.

Dataset Information

Implication of NOTCH1 gene in susceptibility to anxiety and depression among sexual abuse victims.

Publications

Implication of NOTCH1 gene in susceptibility to anxiety and depression among sexual abuse victims.

Similar Datasets

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