Mechanisms of antidepressant action: an integrated dopaminergic perspective

The molecular mechanisms that cause and maintain the major depressive disorder (MDD) are currently unknown. Consistently, antidepressant treatments are characterized by insufficient success rates. This causes high social costs and severe personal sufferings. In the present review we analyze some of the paradigms that are used to explain MDD, particularly from the perspective of the dopaminergic (DA) system. DA has been more classically associated with psychosis and substance abuse disorders, even though a role of DA in MDD has been proposed as well and some antidepressants with DA profile exist. In the present work, we review some of the molecular mechanisms that underpin MDD from the perspective of the dopaminergic system, in the hope of unifying some of the major theories of MDD - the monoaminergic, inflammatory, epigenetics, neurotrophin and anti-apoptotic theories. Several shared components of these theories are highlighted, partially accounted by the functions of the DA system (see supplementary video).