GABA System in Depression: Impact on Pathophysiology and Psychopharmacology

Background: The pathophysiology of major depressive disorder (MDD), one of the major causes of worldwide disability, is still largely unclear, despite the increasing data reporting evidence of multiple alterations of different systems. Recently, there was a renewed interest in the signalling of gamma aminobutyric acid (GABA) - the main inhibitory neurotransmitter. Objective: The aim of this study was to review and comment on the available literature about the involvement of GABA in MDD, as well as on novel GABAergic compounds possibly useful as antidepressants. Methods: We carried out a narrative review through Pubmed, Google Scholar and Scopus, by using specific keywords. Results: The results, derived from various research tools, strongly support the presence of a deficiency of the GABA system in MDD, which appears to be restored by common antidepressant treatments. More recent publications would indicate the complex interactions between GABA and all the other processes involved in MDD, such as monoamine neurotransmission, hypothalamus-pituitary adrenal axis functioning, neurotrophism, and immune response. Taken together, all these findings seem to further support the complexity of the pathophysiology of MDD, possibly reflecting the heterogeneity of the clinical pictures. Conclusion: Although further data are necessary to support the specificity of GABA deficiency in MDD, the available findings would suggest that novel GABAergic compounds might constitute innovative therapeutic strategies in MDD.