Neurotherapeutics

, Volume 14, Issue 3, pp 677–686 | Cite as

Neural Substrates of Depression and Resilience

Review

Abstract

There is an urgent need for more effective medications to treat major depressive disorder, as fewer than half of depressed patients achieve full remission and many are not responsive with currently available antidepressant medications or psychotherapy. It is known that prolonged stressful events are an important risk factor for major depressive disorder. However, there are prominent individual variations in response to stress: a relatively small proportion of people (10–20%) experiencing prolonged stress develop stress-related psychiatric disorders, including depression (susceptibility to stress), whereas most stress-exposed individuals maintain normal psychological functioning (resilience to stress). There have been growing efforts to investigate the neural basis of susceptibility versus resilience to depression. An accumulating body of evidence is revealing the genetic, epigenetic, and neurophysiological mechanisms that underlie stress susceptibility, as well as the active mechanisms that underlie the resilience phenotype. In this review, we discuss, mainly based on our own work, key pathological mechanisms of susceptibility that are identified as potential therapeutic targets for depression treatment. We also review novel mechanisms that promote natural resilience as an alternative strategy to achieve treatment efficacy. These studies are opening new avenues to develop conceptually novel therapeutic strategies for depression treatment.

Keywords

Major depressive disorder Depression susceptibility Resilience Prefrontal cortex Nucleus accumbens Ventral tegmental area 

Notes

Acknowledgements

This work was supported by grants from the National Institute of Mental Health (M.H.H., R21MH112081; E.J.N., R01MH051399, P50MH096890), the National Institute of Alcohol Abuse and Alcoholism (M.H.H., R01AA022445), the Brain and Behavior Research Foundation (M.H.H., NARSAD), and the Hope for Depression Research Foundation (E.J.N.).

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Supplementary material

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Copyright information

© The American Society for Experimental NeuroTherapeutics, Inc. 2017

Authors and Affiliations

  1. 1.Department of Pharmacological Sciences and Institute for Systems BiomedicineIcahn School of Medicine at Mount SinaiNew YorkUSA
  2. 2.Fishberg Department of Neuroscience and Friedman Brain InstituteIcahn School of Medicine at Mount SinaiNew YorkUSA
  3. 3.Department of PsychiatryIcahn School of Medicine at Mount SinaiNew YorkUSA

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