@article{826e4d53653d4bda826e400a20ad4333,
title = "Epigenetic and genetic variation at SKA2 predict suicidal behavior and post-traumatic stress disorder",
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): 0.60.92, P = 0.003, and CI: 0.650.78, 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.",
author = "Z. Kaminsky and Wilcox, {H. C.} and Eaton, {W. W.} and {Van Eck}, K. and V. Kilaru and T. Jovanovic and T. Klengel and B. Bradley and Binder, {E. B.} and Ressler, {K. J.} and Smith, {A. K.}",
note = "Funding Information: ZK is an inventor on patent applications for DNA methylation biomarker-based prediction of PPD, suicide and PTSD. ZK received consultant fees from Janssen Research and Development, LLC. BB receives grant support or has received awards from AFSP and the American Psychoanalytic Association Psychoanalytic Research Fund. KJR has received funding from the Burroughs Wellcome Fund, NIH, and he has an unrelated role as the cofounder of Extinction Pharmaceuticals for development of N-methyl-D-aspartate-based therapeutics. EBB receives grant support from the 7th framework program of the European Community (ERC starting grant, the German Federal Ministry of Education and Research, ERANet-Neuron and NIH. EBB is inventor on patent applications related to using FKBP5 and ABCB1 genotypes in the prediction of antidepressant response and genetic predictors of treatment emergent suicidal ideation. AKS receives or has received research support from the American Foundation for Suicide Prevention, Schering Plough Pharmaceuticals, NARSAD, the Conquer Cancer Foundation and NIH. The remaining authors declare no conflict of interest. Funding Information: We gratefully acknowledge the participants of the study and the Grady Trauma Project staff for their assistance with participant recruitment and data collection. 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{\textquoteright}s Award (ZK).",
year = "2015",
month = aug,
day = "25",
doi = "10.1038/tp.2015.105",
language = "English (US)",
volume = "5",
journal = "Translational Psychiatry",
issn = "2158-3188",
publisher = "Nature Publishing Group",
number = "8",
}