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Epigenetic and genetic variation at SKA2 predict suicidal behavior and post-traumatic stress disorder
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 bra...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4564560/ https://www.ncbi.nlm.nih.gov/pubmed/26305478 http://dx.doi.org/10.1038/tp.2015.105 |
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author | Kaminsky, Z Wilcox, H C Eaton, W W Van Eck, K Kilaru, V Jovanovic, T Klengel, T Bradley, B Binder, E B Ressler, K J Smith, A K |
author_facet | Kaminsky, Z Wilcox, H C Eaton, W W Van Eck, K Kilaru, V Jovanovic, T Klengel, T Bradley, B Binder, E B Ressler, K J Smith, A K |
author_sort | Kaminsky, Z |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4564560 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-45645602015-09-18 Epigenetic and genetic variation at SKA2 predict suicidal behavior and post-traumatic stress disorder Kaminsky, Z Wilcox, H C Eaton, W W Van Eck, K Kilaru, V Jovanovic, T Klengel, T Bradley, B Binder, E B Ressler, K J Smith, A K Transl Psychiatry Original Article 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. Nature Publishing Group 2015-08 2015-08-25 /pmc/articles/PMC4564560/ /pubmed/26305478 http://dx.doi.org/10.1038/tp.2015.105 Text en Copyright © 2015 Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Original Article Kaminsky, Z Wilcox, H C Eaton, W W Van Eck, K Kilaru, V Jovanovic, T Klengel, T Bradley, B Binder, E B Ressler, K J Smith, A K Epigenetic and genetic variation at SKA2 predict suicidal behavior and post-traumatic stress disorder |
title | Epigenetic and genetic variation at SKA2 predict suicidal behavior and post-traumatic stress disorder |
title_full | Epigenetic and genetic variation at SKA2 predict suicidal behavior and post-traumatic stress disorder |
title_fullStr | Epigenetic and genetic variation at SKA2 predict suicidal behavior and post-traumatic stress disorder |
title_full_unstemmed | Epigenetic and genetic variation at SKA2 predict suicidal behavior and post-traumatic stress disorder |
title_short | Epigenetic and genetic variation at SKA2 predict suicidal behavior and post-traumatic stress disorder |
title_sort | epigenetic and genetic variation at ska2 predict suicidal behavior and post-traumatic stress disorder |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4564560/ https://www.ncbi.nlm.nih.gov/pubmed/26305478 http://dx.doi.org/10.1038/tp.2015.105 |
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