New research links SKA2 gene methylation to more severe PTSD symptoms and reduced cortical thickness in brain regions that regulate emotion and stress response. This study is among the first to identify a potential role for the spindle and kinetochore-associated complex subunit 2 (SKA2) gene in the development and severity of post-traumatic stress disorder (PTSD).
The study was led by investigators at Boston University School of Medicine, the National Center for PTSD, and the Translational Research Center for TBI and Stress Disorders at VA Boston Healthcare System. The findings were published in the journal Molecular Psychiatry.
PTSD is common among military personnel who have experienced combat. Estimates indicate that between 11 and 20 percent of veterans who served in Operations Iraqi Freedom and Enduring Freedom experience PTSD in a given year. Research also shows that exposure to warzone trauma, ongoing PTSD symptoms, and other post-deployment mental health challenges increase suicide risk compared with the general population.
For this study, researchers collected MRI brain scans and blood samples from roughly 200 veterans who served in the recent conflicts in Iraq and Afghanistan. The team examined whether methylation—a chemical modification that can alter gene expression—of the SKA2 gene in blood was associated with cortical thickness, a neuroimaging measure of neuronal health, and with psychiatric symptoms, focusing on PTSD and depression.
“We found that increased methylation of SKA2 corresponds with reduced cortical thickness in the prefrontal cortex,” said Naomi Sadeh, PhD, lead and corresponding author, assistant professor of psychiatry at Boston University School of Medicine and a psychologist at the National Center for PTSD at VA Boston. “These brain regions are critical for regulating intense emotions and coping with stress, which suggests a potential mechanism through which SKA2 methylation could influence PTSD risk and severity, and possibly related suicide risk.”
The researchers emphasize that these results may have practical implications. If validated in further studies, a blood-based measure of SKA2 methylation might help identify service members at elevated risk for PTSD following trauma exposure. Such a biomarker could complement clinical assessment and improve early identification of individuals who would benefit from preventive or targeted interventions.
Funding: This work received support from multiple sources, including the NIMH grant R21MH102834 “Neuroimaging Genetics of PTSD,” the Translational Research Center for TBI and Stress Disorders (TRACTS), a VA Traumatic Brain Injury Center of Excellence, and resources at the Pharmacogenomics Analysis Laboratory, Research and Development Service, Central Arkansas Veterans Healthcare System. Additional support included 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: Public domain image
Original Research: Abstract for “SKA2 methylation is associated with decreased prefrontal cortical thickness and greater PTSD severity among trauma-exposed veterans,” published in Molecular Psychiatry on September 1, 2015. DOI: 10.1038/mp.2015.134
Abstract
SKA2 methylation is associated with decreased prefrontal cortical thickness and greater PTSD severity among trauma-exposed veterans
Previous research identified methylation of the SKA2 gene as a potential biomarker for suicide risk. Building on that work, this study investigated the relationship between SKA2 methylation, cortical thickness, and psychiatric symptoms related to suicide risk in trauma-exposed veterans. Approximately 200 predominantly male, white non-Hispanic veterans who served in Iraq and Afghanistan underwent clinical assessment and provided blood samples for genotyping and methylation analysis; 145 of these participants also completed neuroimaging.
The team focused on DNA methylation at the cytosine–guanine locus cg13989295 and on methylation measures adjusted for genotype at the methylation-associated single nucleotide polymorphism rs7208505. Whole-brain vertex-wise analyses revealed three prefrontal cortex clusters where genotype-adjusted SKA2 methylation was linked to reduced cortical thickness. Associations were observed bilaterally in the frontal pole and superior frontal gyrus, and in the right orbitofrontal cortex and right inferior frontal gyrus. Greater PTSD symptom severity correlated positively with genotype-adjusted SKA2 methylation and negatively with cortical thickness in these regions. Mediation analyses indicated a significant indirect effect of PTSD symptoms on cortical thickness through SKA2 methylation status.
Overall, these results suggest that SKA2 DNA methylation in blood indexes stress-related psychiatric phenotypes and neurobiology. The findings point to the potential value of SKA2 methylation as a blood-based biomarker for stress exposure and vulnerability to stress-related psychiatric outcomes, including PTSD.