Stress: A deadly weapon

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Science Translational Medicine  21 Dec 2016:
Vol. 8, Issue 370, pp. 370ec204
DOI: 10.1126/scitranslmed.aal3703

Mitochondria are the main generators for the cell’s energy grid, but even these powerhouses are susceptible to stress. Each mitochondrion houses its own genome—known as mitochondrial DNA (mtDNA)—which contains 37 genes essential for its energy-liberating purpose. As a response to stress, our bodies release glucocorticoids, vital hormones involved in an array of physiological processes that help us cope with the stressful event. When elevated glucocorticoids levels are sustained over time, as with chronic stress, stress-damaged mitochondria are thought to promote the release of mtDNA into the circulation. In a recent study, Lindqvist and collaborators found that freely circulating mtDNA was elevated in the blood of individuals who had attempted suicide, a population that is typically exposed to prolonged stress. Further, these elevated mtDNA levels in blood correlated with hyperactivity of the body’s stress response system.

The authors measured free mtDNA in blood samples from 37 subjects who had attempted suicide and from 37 matched controls (average age, 39 years). All patients were assessed for depression status and went through a drug washout period to remove any trace of medication from their system. In addition, all patients had undergone the dexamethasone suppression test (DST), a test in which blood levels of cortisol—the most common glucocorticoid—are measured after an injection of dexamethasone, as a way to assess activity of the hypothalamic-pituitary-adrenal (HPA) axis, our physiological stress response system. Dexamethasone is a synthetic glucocorticoid similar to cortisol. In a person with a normally functional stress-response system, natural cortisol levels would be reduced as the man-made molecule takes its place. A failure to reduce blood cortisol levels would indicate a dysfunctional hyperactivity of the HPA axis and, therefore, an altered stress response.

The researchers observed that the increased mtDNA blood levels in suicidal subjects were associated with increased activity of the HPA axis but not with the severity of depression (as measured with the Montgomery-Asberg Depression Rating Scale), repetitive suicide attempts, or violence of the attempted suicide method. Elevated free mtDNA in blood has been found in other disorders such as cancer, cardiovascular disease, and diabetes; therefore, it is not a biomarker specific for attempters of suicide. However, the current findings might spur future studies that test whether elevated mtDNA is a signature of other psychiatric disorders with concomitant stress exposure and investigate longitudinally potential variation in the marker as the patient's symptoms improve by pharmacological or other types of interventions.

D. Lindqvist et al., Increased plasma levels of circulating cell-free mitochondrial DNA in suicide attempters: Associations with HPA-axis hyperactivity. Transl. Psychiatry 6, e971 (2016). [Full Text]

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