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Author Notes:

Corresponding Author: Naomi Sadeh, National Center for PTSD, Behavioral Science Division, VA Boston Healthcare System, 150 South Huntington Avenue; Boston, MA 02130. ; Email: Naomi.SamimiSadeh@va.gov; (857) 364-5924.

Authors Sadeh, Spielberg, Wolf, Logue, Lusk, Hayes, Sperbeck, Milberg, McGlinchey, Salat, Carter, Stone, Schichman, Humphries, and Miller reported no biomedical financial interests or potential conflicts of interest.

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Research Funding:

This research was supported in part by NIMH grant R21MH102834 “Neuroimaging Genetics of PTSD” and the Translational Research Center for TBI and Stress Disorders (TRACTS), a VA Rehabilitation Research and Development Traumatic Brain Injury Center of Excellence (B9254-C), and the Cooperative Studies Program, Department of Veterans Affairs.

This research is the result of work supported with resources and the use of facilities at the Pharmacogenomics Analysis Laboratory, Research and Development Service, Central Arkansas Veterans Healthcare System, Little Rock, Arkansas.

This work was also supported by a Career Development Award to Erika J. Wolf from the United States (U.S.) Department of Veterans Affairs, Clinical Sciences Research and Development Program.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Biochemistry & Molecular Biology
  • Neurosciences
  • Psychiatry
  • Neurosciences & Neurology
  • GLUCOCORTICOID-RECEPTOR
  • SUICIDE ATTEMPTERS
  • CORTEX
  • STRESS
  • FKBP5
  • GENE
  • BRAIN
  • DYSFUNCTION
  • RESPONSES
  • BEHAVIOR
  • SKA2
  • cortical thickness
  • methylation
  • trauma
  • posttraumatic stress

SKA2 methylation is associated with decreased prefrontal cortical thickness and greater PTSD severity among trauma-exposed veterans

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Journal Title:

Molecular Psychiatry

Volume:

Volume 21, Number 3

Publisher:

, Pages 357-363

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Methylation of the SKA2 (spindle and kinetochore-associated complex subunit 2) gene has recently been identified as a promising biomarker of suicide risk. Based on this finding, we examined associations between SKA2 methylation, cortical thickness and psychiatric phenotypes linked to suicide in trauma-exposed veterans. About 200 trauma-exposed white non-Hispanic veterans of the recent conflicts in Iraq and Afghanistan (91% male) underwent clinical assessment and had blood drawn for genotyping and methylation analysis. Of all, 145 participants also had neuroimaging data available. Based on previous research, we examined DNA methylation at the cytosine-guanine locus cg13989295 as well as DNA methylation adjusted for genotype at the methylation-associated single nucleotide polymorphism (rs7208505) in relationship to whole-brain cortical thickness, posttraumatic stress disorder symptoms (PTSD) and depression symptoms. Whole-brain vertex-wise analyses identified three clusters in prefrontal cortex that were associated with genotype-adjusted SKA2 DNA methylation (methylation adj). Specifically, DNA methylation adj was associated with bilateral reductions of cortical thickness in frontal pole and superior frontal gyrus, and similar effects were found in the right orbitofrontal cortex and right inferior frontal gyrus. PTSD symptom severity was positively correlated with SKA2 DNA methylation adj and negatively correlated with cortical thickness in these regions. Mediation analyses showed a significant indirect effect of PTSD on cortical thickness via SKA2 methylation status. Results suggest that DNA methylation adj of SKA2 in blood indexes stress-related psychiatric phenotypes and neurobiology, pointing to its potential value as a biomarker of stress exposure and susceptibility.

Copyright information:

© 2016 Macmillan Publishers Limited.

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