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Investigating the role of early childhood abuse and HPA axis genes in suicide attempters with bipolar disorder

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Genes and the environment both play a major role in the risk for attempted suicide, and environments harboring stressors, such as early childhood abuse, have been linked to suicidal behavior. Such environments also disrupt the hypothalamic–pituitary–adrenal (HPA) axis pathway, which has been hypothesized to play a role in suicidal behavior. We investigated whether the risk for attempted suicide was attributable in part to the interaction between childhood physical and/or sexual abuse and genetic variation in 19 genes (±5 kb) integral to the HPA axis pathway.

Materials and methods

Using the Genetic Association Information Network Bipolar Disorder and Translational Genomics Research Institute cohorts, we implemented PLINK’s logistic regression-based ‘interaction’ approach to search for evidence of an interaction between 235 genotyped HPA axis single-nucleotide polymorphisms and early childhood abuse. Our study included 631 bipolar disorder suicide attempters and 657 bipolar disorder nonattempters with information on abuse.


After correction for multiple testing, no significant interaction between the 235 HPA axis single-nucleotide polymorphisms and early childhood abuse was found. In our study, the strongest interaction was found with rs2664008 in the corticotropin-releasing hormone receptor 1 (CRHR1) gene, with a nominal interaction P-value of 1.22×10−2 and an interaction odds ratio of 0.47.


Our findings suggest that further work and larger sample sizes are required to elucidate the link between early childhood abuse and the HPA axis in suicidal behavior.
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Keywords: bipolar disorder; early childhood abuse; gene-by-environment; suicidal behavior

Document Type: Research Article

Affiliations: 1: Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, Iowa 2: Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine

Publication date: June 1, 2015

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