Genetic variants in major depressive disorder: From pathophysiology to therapy

Publication date: Available online 4 September 2018Source: Pharmacology & TherapeuticsAuthor(s): Xenia Gonda, Peter Petschner, Nora Eszlari, Daniel Baksa, Andrea Edes, Peter Antal, Gabriella Juhasz, Gyorgy BagdyAbstractIn spite of promising preclinical results there is a decreasing number of new registered medications in major depression. The main reason behind this fact is the lack of confirmation in clinical studies for the assumed, and in animals confirmed, therapeutic results. This suggests low predictive value of animal studies for central nervous system disorders. One solution for identifying new possible targets is the application of genetics and genomics, which may pinpoint new targets based on the effect of genetic variants in humans. The present review summarizes such research focusing on depression and its therapy. The inconsistency between most genetic studies in depression suggests, first of all, a significant role of environmental stress. Furthermore, effect of individual genes and polymorphisms is weak, therefore gene x gene interactions or complete biochemical pathways should be analyzed. Even genes encoding target proteins of currently used antidepressants remain non-significant in genome-wide case control investigations suggesting no main effect in depression, but rather an interaction with stress. The few significant genes in GWASs are related to neurogenesis, neuronal synapse, cell contact and DNA transcription and as being nonspecific for depression are d...
Source: Pharmacology and Therapeutics - Category: Drugs & Pharmacology Source Type: research