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

Breen, Marie E.a,*; Seifuddin, Fayazb,*; Zandi, Peter P.b,c; Potash, James B.a; Willour, Virginia L.a

doi: 10.1097/YPG.0000000000000082

Objective 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.

Results 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.

Conclusion 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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aDepartment of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, Iowa

bDepartment of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine

cDepartment of Mental Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA

* Marie E. Breen and Fayaz Seifuddin contributed equally to the writing of this article.

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Correspondence to Virginia L. Willour, PhD, Department of Psychiatry, University of Iowa Carver College of Medicine, B002J Medical Labs, 25 South Grand Avenue, Iowa City, Iowa 52242, USA Tel: +1 319 335 7140; fax: +1 319 353 4568; e-mail:

Received July 9, 2014

Received in revised form December 13, 2014

Accepted January 20, 2015

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