A gene linked in previous research, appears to predict more severe post-traumatic stress disorder (PTSD) symptoms as well as a thinner cortex in regions of the brain critical for regulating strong emotions and coping with stressful experiences. This study is believed to be the first to show that the spindle and kinetochore-associated complex subunit 2 (SKA2) gene may play a role in the development of PTSD.
Led by researchers at Boston University School of Medicine (BUSM), the National Center for PTSD and the Translational Research Center for TBI and Stress Disorders at VA Boston Healthcare System, the study appears online in the journal Molecular Psychiatry.
PTSD is prevalent among veterans. Eleven to 20 percent of veterans who served in Operations Iraqi Freedom and Enduring Freedom have experienced PTSD in a given year. Studies suggest that warzone trauma, PTSD symptoms and other post-deployment mental health problems put veterans at heightened risk for suicide relative to the general population.
The researchers performed MRI brain scans and collected blood samples from 200 veterans returning from the recent conflicts in Iraq and Afghanistan. They looked at whether a chemical change (methylation) in the function of the SKA2 gene measured in blood predicted the thickness of brain cortex (a measure of neuronal health) and psychological symptoms, specifically PTSD and depression.
“Our findings showed that an in increase in methylation of the SKA2 gene is associated with decreased cortical thickness in the prefrontal cortex, which may play a role in the development of PTSD and may explain why this gene predicts risk for mental health problems, like PTSD and suicide,” explained lead and corresponding author Naomi Samimi Sadeh, PhD, assistant professor of psychiatry at BUSM and a psychologist in the National Center for PTSD at VA Boston.
According to the researchers the implications of this study are significant since it is difficult to predict who will develop PTSD following traumatic events. “These findings suggest that in the future it may be possible to use a genetic blood test to identify military personnel at risk for developing PTSD in response to warzone stressors. We hope these findings will ultimately enhance our ability to identify individuals who are at risk for this disorder by using information about biology to improve diagnosis,” Sadeh concluded.
About this genetics and PTSD research
Funding: This research was supported in part by the NIMH grant R21MH102834 ‘Neuroimaging Genetics of PTSD’ Mark Miller, PhD, 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 theuse 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 EJW from the United States Department of Veterans Affairs, Clinical Sciences Research and Development Program.
Source: Kristen Perfetuo – Boston University Medical Center Image Source: The image is in the public domain Original Research:Abstract for “SKA2 methylation is associated with decreased prefrontal cortical thickness and greater PTSD severity among trauma-exposed veterans” by N Sadeh, J M Spielberg, M W Logue, E J Wolf, A K Smith, J Lusk, J P Hayes, E Sperbeck, W P Milberg, R E McGlinchey, D H Salat, W C Carter, A Stone, S A Schichman, D E Humphries and M W Miller in Molecular Psychiatry. Published online September 1 2015 doi:10.1038/mp.2015.134
SKA2 methylation is associated with decreased prefrontal cortical thickness and greater PTSD severity among trauma-exposed veterans
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 (methylationadj). Specifically, DNA methylationadj 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 methylationadj 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 methylationadj of SKA2 in blood indexes stress-related psychiatric phenotypes and neurobiology, pointing to its potential value as a biomarker of stress exposure and susceptibility.
“SKA2 methylation is associated with decreased prefrontal cortical thickness and greater PTSD severity among trauma-exposed veterans” by N Sadeh, J M Spielberg, M W Logue, E J Wolf, A K Smith, J Lusk, J P Hayes, E Sperbeck, W P Milberg, R E McGlinchey, D H Salat, W C Carter, A Stone, S A Schichman, D E Humphries and M W Miller in Molecular Psychiatry. Published online September 1 2015 doi:10.1038/mp.2015.134