Abstract
Objectives. The aim of this paper is to elucidate the role of oxidative stress as well as DNA damage and repair in pathogenesis of depression, using the available literature.
Literature review. Depression is accompanied by activation of proinflammatory pathways, dysfunction of mitochondria, increase of oxidative stress markers and decrease of antioxidative defense. Last two factors can cause damage to biomolecules, including nucleic acids. Research carried out by our team and others confirmed that hypothesis. Higher oxidative DNA damage was found in depressed patients. Our results also indicate the presence of impairments in efficiency of such DNA damage repair in nuclei. Additionally, single nucleotide polymorphisms of genes encoding proteins involved in base excision repair (BER) – the main pathway removing oxidative DNA damage – can modulate the risk of depression and influence efficiency of DNA damage repair. These results may reflect the state of mitochondrial DNA.
Conclusion. Available literature confirms that oxidative stress and impaired efficiency of DNA damage repair together are responsible for elevated levels of nuclear DNA damage observed in depression. Similar processes can occur in mitochondria and may lead to mitochondrial DNA damage and dysfunction of these organelles. This, in turn, increases production of reactive oxidative species and may trigger vicious cycle. There is a need for further studies concerning the role of nuclear and mitochondrial DNA damage and repair in pathogenesis of depressive disorders, which could lead to the development of more efficient and personalized therapies.