The Role of Epigenetic Factors in the Development of Depressive Disorders

Abstract

To determine the molecular mechanisms of the development of depressive disorders, numerous analyses of associations and gene linkage were carried out using the whole-genomic methods of searching for candidate genes. The role of neurotransmitter systems and metabolic pathways in the pathogenesis of depressive disorders as a result of these studies was revealed. A promising direction is the search for epigenetic markers because of the possibility of standardizing diagnostic methods for the effective pharmacological correction of depression. MicroRNAs and long noncoding RNAs regulate neurogenesis and fine tuning of the differentiation of brain regions during their development. Numerous studies have shown that changes in the levels of microRNAs and long noncoding RNAs play an important role in the development of depressive disorders. Stress appears to be the cause of depressive disorders. It is known that stress causes the activation of transposons, which may result in pathological epigenetic regulation of neurotransmitter systems. In this regard, we can suggest the role of transposons in the pathogenesis of depressive disorders. The role of transposons in the development of depression can be confirmed on the basis of association of depression with telomere shortening, since telomerase originated from transposons. Transposons are also important sources of noncoding RNAs, which are associated with depressive disorders. Noncoding RNAs can specifically alter DNA methylation and histone modifications, the epigenetic labels of which also affect the development of depression. Drug therapy directed to only one neurotransmitter system is not effective in all patients, which may be due to the differences in the mechanisms of development of depression in different patients. In order to determine the main molecular pathways of the pathogenesis of depression with an individual approach, the most convenient diagnostic systems are noncoding RNAs. Moreover, noncoding RNAs can be used for targeted therapy of depressive disorders.

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