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Email Address:Z Kaminsky : zkamins1@jhmi.edu

We gratefully acknowledge the participants of the study and the Grady Trauma Project staff for their assistance with participant recruitment and data collection.

The views expressed in this article are those of the authors and do not necessarily reflect the position or views of the Department of Veterans Affairs or the United States government.

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Research Funding:

This research was supported by the National Institutes of Health Grants MH071537 and MH096764 (KJR), MH085806 (AKS), HD071982 (BB) and DA009897 (WWE).

This work was also supported by a NARSAD YI award (AKS) and the Howard Hughes Medical Institute (KJR), the Behrens-Weise foundation (EBB) and the Russell Military Scholar's Award (ZK).

Epigenetic and genetic variation at SKA2 predict suicidal behavior and post-traumatic stress disorder.

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Journal Title:

Translational Psychiatry

Volume:

Volume 5

Publisher:

, Pages e627-e627

Type of Work:

Article | Final Publisher PDF

Abstract:

Traumatic stress results in hypothalamic pituitary adrenal (HPA) axis abnormalities and an increased risk to both suicidal behaviors and post-traumatic stress disorder (PTSD). Previous work out of our laboratory identified SKA2 DNA methylation associations with suicidal behavior in the blood and brain of multiple cohorts. Interaction of SKA2 with stress predicted suicidal behavior with ~80% accuracy. SKA2 is hypothesized to reduce the ability to suppress cortisol following stress, which is of potentially high relevance in traumatized populations. Our objective was to investigate the interaction of SKA2 and trauma exposure on HPA axis function, suicide attempt and PTSD. SKA2 DNA methylation at Illumina HM450 probe cg13989295 was assessed for association with suicidal behavior and PTSD metrics in the context of Child Trauma Questionnaire (CTQ) scores in 421 blood and 61 saliva samples from the Grady Trauma Project (GTP) cohort. Dexamethasone suppression test (DST) data were evaluated for a subset of 209 GTP subjects. SKA2 methylation interacted with CTQ scores to predict lifetime suicide attempt in saliva and blood with areas under the receiver operator characteristic curve (AUCs) of 0.76 and 0.73 (95% confidence interval (CI): 0.6-0.92, P=0.003, and CI: 0.65-0.78, P<0.0001) and to mediate the suppression of cortisol following DST (β=0.5±0.19, F=1.51, degrees of freedom (df)=12/167, P=0.0096). Cumulatively, the data suggest that epigenetic variation at SKA2 mediates vulnerability to suicidal behaviors and PTSD through dysregulation of the HPA axis in response to stress.

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© 2015 Macmillan Publishers Limited

This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits distribution of derivative works, distribution, public display, and publicly performance, making multiple copies, provided the original work is properly cited. This license requires credit be given to copyright holder and/or author, copyright and license notices be kept intact.

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