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Gene may predict PTSD severity, abnormal brain functions related to emotions, coping

The spindle and kinetochore-associated complex subunit 2 gene may be a predictor of PTSD symptoms and cortical thinning in brain regions that regulate strong emotions and coping with stress, according to study findings in Molecular Psychiatry.

“Building on previous research on [spindle and kinetochore-associated complex subunit 2 (SKA2)], the primary aims of this study were to examine whether SKA2 methylation is associated with alterations in cortical thickness and suicide-related psychiatric symptoms, specifically PTSD and depression. We focused on cortical rather than subcortical structures (for example, hippocampus), based on evidence of reduced expression of SKA2 in prefrontal tissue of suicide patients,” the researchers wrote. “Based on evidence that the SKA2 protein may be involved in mitigating the neurotoxic effects of stress, we hypothesized that greater DNA methylation of the cytosine-guanine site identified by Guintivano, et al would be associated with decreased cortical thickness in prefrontal brain regions.”

For genotyping and methylation analysis, approximately 200 white nonHispanic veterans of recent conflicts in Iraq and Afghanistan, who had been exposed to trauma, underwent clinical assessment and blood sampling. Researchers examined DNA methylation at the cytosine-guanine locus cg13989295 and DNA methylation adjusted for genotype at the methylation-associated single nucleotide polymorphism (rs7208505) in relation to whole-brain cortical thickness, PTSD and depression symptoms.

Three clusters in the prefrontal cortex were associated with genotype-adjusted SKA2 DNA methylation, as identified by whole-brain vertex-wise analyses.

Genotype-adjusted DNA methylation was associated with bilateral reductions of cortical thickness in the frontal pole and superior frontal gyrus. Similar associations were found in the right orbitofrontal cortex and right inferior frontal gyrus.

Researchers found a positive correlation between PTSD symptom severity and genotype-adjusted SKA2 DNA methylation and a negative correlation between PTSD symptom severity and cortical thickness in these regions.

Mediation analyses showed that PTSD had a significant indirect effect on cortical thickness via SKA2 methylation status.

“In summary, findings advance our understanding of stress susceptibility for psychiatric disorders by identifying SKA2 as a potential biomarker of the effects of stress exposure on cortical thickness in psychiatrically relevant brain regions. As a putative molecular measure of cumulative dysregulation in stress response systems, SKA2 epigenetic variation may be a useful blood biomarker for screening military personnel prior to deployment to identify individuals with a high lifetime burden of stress who are at risk for developing PTSD and suicide following exposure to warzone stress,” the researchers concluded. – by Amanda Oldt

Disclosure: The researchers report no relevant financial disclosures.