The interplay between inflammation, oxidative stress, DNA damage, DNA repair and mitochondrial dysfunction in depression

A growing body of evidence suggests that inflammation, mitochondrial dysfunction and oxidant-antioxidant imbalance may play a significant role in the development and progression of depression. Elevated levels of reactive oxygen and nitrogen species – a result of oxidant-antioxidant imbalance – may lead to increased damage of biomolecules, including DNA. This was confirmed in depressed patients in a research study conducted by our team and other scientists. 8-oxoguanine – a marker of oxidative DNA damage – was found in the patients' lymphocytes, urine and serum. These results were confirmed using a comet assay on lymphocytes. Furthermore, it was shown that the patients' cells repaired peroxide-induced DNA damage less efficiently than controls' cells and that some single nucleotide polymorphisms (SNP) of the genes involved in oxidative DNA damage repair may modulate the risk of depression. Lastly, less efficient DNA damage repair observed in the patients can be, at least partly, attributed to the presence of specific SNP variants, as it was revealed through a genotype-phenotype analysis. In conclusion, the available literature shows that both oxidative stress and less efficient DNA damage repair may lead to increased DNA damage in depressed patients. A similar mechanism may result in mitochondrial dysfunction, which is observed in depression. •Molecular aspects of depression pathophysiology are discussed.•Inflammation and oxidative stress are well-known factors accompanying depression.•Increased DNA damage and impairments in its repair are also present.•There are evidence of mitochondrial dysfunction in the disease.•Usefulness of these processes as markers of depression, are yet to be elucidated.