Increased plasma levels of circulating cell-free mitochondrial DNA in medication-free suicide attempters – associations with HPA-axis hyperactivity

Abstract

Data suggest that chronic stress may cause cellular damage and mitochondrial dysfunction[1-3], potentially leading to the release of mitochondrial DNA (mtDNA) into the bloodstream. Major Depressive Disorder has been associated with an increased amount of mtDNA in leukocytes from saliva samples and blood[4, 5], but no previous studies have measured plasma levels of free-circulating mtDNA in a clinical psychiatric sample. In this study, free circulating mtDNA was quantified in plasma samples from 37 suicide attempters, who had undergone a dexamethasone suppression test (DST), and 37 healthy controls. We hypothesized that free circulating mtDNA would be elevated in the suicide attempters and associated with HPA-axis hyperactivity. Suicide attempters had significantly higher plasma levels of free-circulating mtDNA compared to healthy controls at different time points (pre- and post-DST) (all p-values <2.98E-12, Cohen’s d ranging from 2.55-4.01). Pre-DST plasma levels of mtDNA were positively correlated with post-DST cortisol levels (rho=0.49, p<0.003). Suicide attempters may have elevated plasma levels of free-circulating mtDNA, which are related to impaired HPA-axis negative feedback. This peripheral index is consistent with increased cellular or mitochondrial damage. Future studies are needed to understand the relevance of increased free-circulating mtDNA in relation to the pathophysiology underlying suicidal behavior and depression.