Molecular Signatures of Major Depression: Current Biology

Adversity particularly in early life, can cause illness. Clues to the responsible
mechanisms may lie with the discovery of molecular signatures of stress,
some of which include alterations to an individual’s somatic genome.
Here, using genome sequences from 11,670 women, we observed a highly
significant association between a stress-related disease, major
depression, and the amount of mitochondrial DNA (p = 9.00 × 10−42, odds ratio 1.33 [95% confidence interval [CI] = 1.29–1.37]) and telomere length (p = 2.84 × 10−14,
odds ratio 0.85 [95% CI = 0.81–0.89]). While both telomere length and mitochondrial DNA amount were associated with adverse life events, conditional
regression analyses showed the molecular changes were contingent on the
depressed state. We tested this hypothesis with experiments in mice,
demonstrating that stress causes both molecular changes, which are
partly reversible and can be elicited by the administration of
corticosterone. Together, these results demonstrate that changes in the
amount of mitochondrial DNA and telomere length are consequences of stress and
entering a depressed state. These findings identify increased amounts of
mtDNA as a molecular marker of MD and have important implications for
understanding how stress causes the disease.

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