mTOR signaling in the neuropathophysiology of depression: current evidence Gislaine Z Réus,1 João Quevedo,1,2 Ana Lúcia S Rodrigues3 1Laboratory of Neurosciences, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, Santa Catarina, Brazil; 2Center for Translational Psychiatry, Department of Psychiatry and Behavioral Sciences, University of Texas Medical School, Houston, TX, USA; 3Laboratory of Neurobiology of Depression, Department of Biochemistry, Center of Biological Sciences, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil Abstract: Despite significant progress in major depressive disorder (MDD) research over the past decades, the mechanisms underlying its pathophysiology and treatment remain to be established. The complexity and heterogeneity of MDD involves multiple causes, such as inflammation, genetic, and environmental factors that could be related to poor effectiveness, variability of response to antidepressant drugs, delay in clinical response, and side effects. Ketamine, an N-methyl-D-aspartate receptor antagonist, has been proposed as a revolutionary antidepressant that acts rapidly and is effective for treatment-resistant MDD. Ketamine stimulates mammalian target of rapamycin (mTOR), which is involved in transcription, survival, and cell proliferation. mTOR is an emerging signaling pathway of interest in MDD pathophysiology and treatment. Thus, this review describes the role of mTOR in the pathophysiology of MDD as well as highlights therapeutic targets that modulate mTOR signaling. Keywords: mTOR, antidepressant, major depressive disorder