Abstract

Depression is a common mental disorder being one of the main causes of disability and mortality worldwide. Despite an intensive research during the past decades, the etiology of depressive disorders (DDs) remains incompletely understood; however, genetic factors are significantly involved in the liability to depression. The present review is focused on the studies based on a candidate gene approach, genome-wide association studies (GWAS) and whole exome sequencing (WES), which previously demonstrated associations between gene polymorphisms and DDs. According to the first approach, DD development is affected by serotonergic (TPH1, TPH2, HTR1A, HTR2A, and SLC6A4), dopaminergic (DRD4, SLC6A3) and noradrenergic (SLC6A2) system genes, and genes of enzymatic degradation (MAOA, COMT). In addition, there is evidence of the involvement of HPA-axis genes (OXTR, AVPR1A, and AVPR1B), sex hormone receptors genes (ESR1, ESR2, and AR), neurotrophin (BDNF) and methylenetetrahydrofolate reductase (MTHFR) genes, neuronal apoptosis (CASP3, BCL-XL, BAX, NPY, APP, and GRIN1) and inflammatory system (TNF, CRP, IL6, IL1B, PSMB4, PSMD9, and STAT3) genes in DD development. The results of the second approach (GWAS and WES) revealed that the PCLO, SIRT1, GNL3, GLT8D1, ITIH3, MTNR1A, BMP5, FHIT, KSR2, PCDH9, and AUTS2 genes predominantly responsible for neurogenesis and cell adhesion are involved in liability to depression. Therefore, the findings discussed suggest that genetic liability to DD is a complex process, which assumes simultaneous functioning of multiple genes including those reported previously, and requires future research in this field.

Highlights

  • Депрессия – это распространенное психическое расстройство, которое является одной из ведущих причин нетрудоспособности и смертности в мире

  • Inroduction According to the World Health Organization (WHO), unstable social, economic and ecological factors in the modern society result in the constant increase in the distribution frequency of socially significant diseases with a specific attention given to depressive disorders (DDs)

  • The most common validated scales for DDs diagnostics include the Hospital Anxiety and Depression Scale (HADS), Hamilton Depression Rating Scale (HAM-D), Beck Depression Inventory (BDI), Montgomery-Asberg Depression Rating Scale (MADRS), which are used in clinical practice by psychiatrists for the assignment of treatment strategy (Cusin et al, 2010)

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Summary

Genetic basis of depressive disorders

Yu.D. Davydova , R.F. Enikeeva, A.V. Kazantseva, R.N. Mustafin , A.R. Romanova, S.B. Malykh, E.K. Khusnutdinova . Despite an intensive research during the past decades, the etiology of depressive disorders (DDs) remains incompletely understood; genetic factors are significantly involved in the liability to depression. The present review is focused on the studies based on a candidate gene approach, genome-wide association studies (GWAS) and whole exome sequencing (WES), which previously demonstrated associations between gene polymorphisms and DDs. According to the first approach, DD development is affected by serotonergic (TPH1, TPH2, HTR1A, HTR2A, and SLC6A4), dopaminergic (DRD4, SLC6A3) and noradrenergic (SLC6A2) system genes, and genes of enzymatic degradation (MAOA, COMT). For citation: Davydova Yu.D., Enikeeva R.F., Kazantseva A.V., Mustafin R.N., Romanova A.R., Malykh S.B., Khusnutdinova E.K. Genetic basis of depressive disorders.

Генетические основы предрасположенности к депрессивным расстройствам
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