The role of mTOR in depression and antidepressant responses

The aim of this study was to characterize the mTOR signaling cascade in depression and the actions that antidepressant drugs have on this pathway. Herein, a literature review was performed by verification and comparison of textbooks and journal articles that describe the characterization of the mTOR signaling cascade and its relationship to depression and antidepressant drugs, especially ketamine. Postmortem studies have shown robust deficits in the mammalian target of rapamycin (mTOR) signaling in the prefrontal cortex of subjects diagnosed with major depressive disorder. However, besides the mTOR signaling pathway having an antidepressant response to various drugs, this seems to be more associated with antidepressant N-methyl-d-aspartate (NMDA) receptor antagonists, such as ketamine. The characterization of the mTOR signaling pathway in depression and its action in response to antidepressants show great potential for the identification of new therapeutic targets for the development of antidepressant drugs.

Graphical abstractRole of mTOR signaling cascade and its relationship to depression and antidepressant drugs, especially ketamine. Ketamine stimulates mTOR synaptogenesis. Ketamine stimulates glutamate transmission resulting in an activation of AKT and ERK signaling, which in turn stimulates mTOR synaptogenesis and increases CREB, BDNF, TrkB and Wnt levels carrying out the protein transcription leading to neuroprotection, neurogenesis and neuroplasticity.Figure optionsDownload full-size imageDownload high-quality image (86 K)Download as PowerPoint slide