Expression of genes in the brain associated with depression
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Meta-analysis of genome-wide studies involving thousands of patients and healthy subjects did not reveal significant genetic associations with major depressive disorder (Ripke et al., 2013), which may be due to the heterogeneity of this pathology. To identify the genetic base of depression, it is obviously necessary to assess the contributions of not only the alleles of individual genes but also of the gene complex altering activity of molecular pathways, which are important in the disease manifestation. The range of genes in which variability contributes to a genetic predisposition to depression includes genes inducing activity in neurotransmission systems, stress and immune response, and neurotrophic and apoptotic processes. Impairments of the functions of glutamate, norepinephrine, GABA, serotonin (5-HT), and other neurotransmitters in the brain contribute to the pathology. While the contribution of individual genes of neurotransmitter systems in the pathology can be smallish, the summation of effects of alleles of several genes that contribute to the disease and those of adverse life circumstances may predispose one to develop depression. Stress converts the genetic predisposition into psychopathology via epigenetic regulation of gene activity. Neuroplasticity and inflammatory processes in the brain that depend on the functions of neurotrophins and interleukins contribute significantly to psychopathology. The resistance of brain structure and its cells to damaging genetic and/or environmental factors is an important component for predisposition of an individual to depression state. Neurotrophins activate the expression of proteins, such as anti-apoptotic proteins Bcl-2 and Bcl-xL, which protect cells from death and counteract the effects of pathogenic processes damaging brain structure. Obviously, the interaction of different sets of alleles that predispose or counteract the development of pathology with environmental factors, such as stress, determines individual differences in resistance to the manifestation of depression.
Keywordsdepression gene expression serotonergic system stress system neurotrophins immune system factors cell viability proteins
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