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::
Acknowledgments
The Center for Translational Psychiatry (USA) is funded by the Department of Psychiatry and Behavioral Sciences, The University of Texas Medical School at Houston. Laboratory of Neurosciences (Brazil) is one of the centers of the National Institute for Molecular Medicine (INCT-MM). Laboratory of Neurobiology of Depression and Laboratory of Neurosciences (Brazil) are members of the Center of Excellence in Applied Neurosciences of Santa Catarina (NENASC). Work in the authors’ laboratories has been funded by grants from CNPq, CAPES, FAPESC, Instituto Cérebro e Mente, and UNESC, Brazil. JQ and ALSR are CNPq Research Fellows.
Disclosure
The authors report no conflicts of interest in this work.