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Neural Substrates of Depression and Resilience.

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.

SUBMITTER: Han MH

PROVIDER: S-EPMC5509625 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Neural Substrates of Depression and Resilience.

Han Ming-Hu MH Nestler Eric J EJ

Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics 20170701 3

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 prolong ...[more]

PMID: 28397115

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Project description:BackgroundStress and stressful life events have repeatedly been shown as causally related to depression. The Chronic Mild Stress rat model is a valid model of stress-induced depression. Like humans, rats display great heterogeneity in their response to stress and adversity. Hence some individuals are stress-sensitive and prone to develop depression-like behaviour in response to modest stressors, while others are stress-resilient and remain essentially symptom free.ObjectivesCompared to the large body of research, which describes stress-induced maladaptive neurobiological changes, relatively little attention has been devoted to understand resiliency to stress. The aim of the present study was to identify changes in neuronal activity, associated with stress-resilient and stress-susceptible chronic mild stress endophenotypes, by examining c-Fos expression in 13 different brain areas. Changes in c-Fos expression have been reported as associated to stressful conditions.MethodsStress-induced modulation of neuronal activation patterns in response to the chronic mild stress paradigm was mapped using the immediate early gene expression c-Fos as a marker. Quantification of the c-Fos-like immunoreactivity responses was done by semi-automated profile counting procedures and design-based stereology.ResultsExposure to chronic mild stress significantly altered c-Fos expression in a total of 6 out of 13 investigated areas. Chronic mild stress was found to suppress the c-Fos response within the magnocellular ventral lateral geniculate nucleus of both stress subgroups. In the the lateral and ventral orbital cortices of stress-resilient rats, the c-Fos like immunoreactivity response was also repressed by stress exposure. On the contrary the c-Fos response within the amygdala, medial habenula, and infralimbic cortex was increased selectively for the stress-susceptible rats.ConclusionsThe study was initiated to characterize neuronal substrates associated with stress-coping mechanisms. Six areas, all of which represents limbic structures, were found to be sensitive to stress exposure. The effects within these areas associate to the hedonic status of the rats. Hence, these areas might be associated to stress-coping mechanisms underlying the chronic mild stress induced segregation into stress-susceptible and stress-resilient endophenotypes.

Dataset Information

Neural Substrates of Depression and Resilience.

Publications

Neural Substrates of Depression and Resilience.

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