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Neurotherapeutics. 2017 Jul;14(3):677-686. doi: 10.1007/s13311-017-0527-x.

Neural Substrates of Depression and Resilience.

Han MH1,2, Nestler EJ3,4,5.

Author information

1
Department of Pharmacological Sciences and Institute for Systems Biomedicine, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA. ming-hu.han@mssm.edu.
2
Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA. ming-hu.han@mssm.edu.
3
Department of Pharmacological Sciences and Institute for Systems Biomedicine, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA. eric.nestler@mssm.edu.
4
Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA. eric.nestler@mssm.edu.
5
Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA. eric.nestler@mssm.edu.

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:

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

PMID:
28397115
PMCID:
PMC5509625
DOI:
10.1007/s13311-017-0527-x
[Indexed for MEDLINE]
Free PMC Article

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