Neurobiological Mechanisms of Depression and Antidepressant Therapy

Depression represents a complex mental disorder which results from the contribution of multiple genetic and environmental factors. A depressive state can be characterized by abnormalities in the functions of monoaminergic neurotransmission, hypothalamic-pituitary-adrenocortical system, neurotrophins and cytokines in genetically predisposed individuals that endured the impact of stress or infection. Genetic, epigenetic and ontogenetic factors underlie these abnormalities. Manifestations of the pathology demonstrate associations with specific alleles of candidate genes. Epigenetic mechanisms of DNA methylation, acetylation and methylation of histones and processes of transcription and translation are also involved in the development of depressive symptoms and their amelioration under prolonged treatment with antidepressants. These processes are regulated by transcription factors and specific microRNAs. The search for effective means to affect activity of these intracellular targets with traditional pharmaceutical agents altering intercellular communication performed by neurotransmitters, hormones and tissue factors that provide long-lasting neuronal plasticity would be useful for unraveling the pathophysiological mechanisms of depression and for development of new approaches to its therapy.