Neurobiology of resilience

Russo, Scott J.; Murrough, James W.; Han, Ming–Hu; Charney, Dennis S.; Nestler, Eric J.

doi:10.1038/nn.3234

Cited by 947 publications

(746 citation statements)

References 102 publications

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“…As noted in the Introduction, for CSD behavioural effects the major focus to-date has been on passive avoidance by CSD mice of mice from the dominant aggressor CD-1 strain in a social proximity test (Berton et al, 2006;Haque et al, 2012;Krishnan et al, 2007;Savignac et al, 2011a). In terms of helplessness theory, this effect constitutes increased emotional reactivity to the specific stimulus that induced the CSD (Russo et al, 2012). In some studies, passive avoidance of CD-1 mice has been reported to occur in about 50% of CSD mice with the other 50% not avoiding the dominant aggressor strain (Krishnan et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

“…Bite wounds are common in the standard CSD protocol (Golden et al, 2011), somewhat impacting on its aetiological validity as an emotional psychosocial stressor. Readout tests of CSD effects have focussed on passive avoidance of the 5 aggressor mouse strain in a social proximity test (Krishnan et al, 2007;Savignac et al, 2011b); that is, on increased emotional reactivity to the specific learned uncontrollable social stimulus (Russo et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

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Mouse social stress induces increased fear conditioning, helplessness and fatigue to physical challenge together with markers of altered immune and dopamine function

et al. 2014

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In neuropsychiatry, animal studies demonstrating causal effects of environmental manipulations relevant to human aetiology on behaviours relevant to human psychopathologies are valuable. Such valid models can improve understanding of aetio-pathophysiology and preclinical discovery and development of new treatments. In depression, specific uncontrollable stressful life events are major aetiological factors, and subsequent generalized increases in fearfulness, helplessness and fatigue are core symptoms or features. Here we exposed adult male C57BL/6 mice to 15-day psychosocial stress with loss of social control but minimal physical wounding. One cohort was assessed in a 3-day test paradigm of motor activity, fear conditioning and 2-way avoid-escape behaviour on days 16-18, and a second cohort was assessed in a treadmill fatigue paradigm on days 19 and 29, followed by the 3-day paradigm on days 30-32. All tests used a physical aversive stimulus, namely mild, brief electroshocks. Socially stressed mice displayed decreased motor activity, increased fear acquisition, decreased 2-way avoid-escape responding (increased helplessness) and increased fatigue. They also displayed increased plasma TNF and spleen hypertrophy, and adrenal hypertrophy without hyper-corticoidism. In a third cohort, psychosocial stress effects on brain gene expression were assessed using next generation sequencing. Gene expression was altered in pathways of inflammation and G-protein coupled receptors in prefrontal cortex and amygdala; in the latter, expression of genes important in dopamine function were de-regulated including down-regulated Drd2, Adora2a and Darpp-32. This model can be applied to identify targets for treating psychopathologies such as helplessness or fatigue, and to screen compounds/biologics developed to act at these targets. AbstractIn neuropsychiatric research, animal studies that demonstrate causal effects of environmental manipulations relevant to human aetiological factors on emotional and cognitive behaviours relevant to human psychopathologies are valuable. Such valid animal models can be useful for improved understanding of aetio-pathophysiology and preclinical discovery and development of new treatments. In depression, specific uncontrollable stressful life events are major aetiological factors, and subsequent generalized increases in fearfulness, helplessness and fatigue are core psychopathology symptoms or features. In the present study we exposed adult male C57BL/6 mice to an environmental manipulation of 15-day psychosocial stress with loss of social control but with minimal physical wounding. One cohort of stressed and control mice was assessed in a novel 3-day test paradigm of motor activity, fear conditioning and 2-way avoid-escape behaviour on days 16-18, and a second cohort was assessed in a treadmill fatigue paradigm on days 19 and 29, followed by the 3-day paradigm on days 30-32. All tests used a physical aversive stimulus, namely mild, brief electroshocks. The socially stressed mice displayed dec...

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Mouse social stress induces increased fear conditioning, helplessness and fatigue to physical challenge together with markers of altered immune and dopamine function

et al. 2014

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“…Higher DHEA-s level is likely to have some beneficial effects on improving attention 12) and lowering perceived stress. 13,14) Some studies suggests that higher DHEA-s and DHEA may counteract the neurotoxic effects due to high cortisolemia in depression. 15,16) Some conflicting results concerning associations between MDD and mediating factors including DHEA-s bring us to reconsider methodological issues in research.…”

Section: Introductionmentioning

confidence: 99%

Dehydroepiandrosterone sulfate level varies nonlinearly with symptom severity in major depressive disorder

Kim¹,

Yi²,

Kim³

2016

European Neuropsychopharmacology

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“…A range of human genes and polymorphisms associated with NPY, HPA axis, noradrenergic, dopaminergic and serotonergic systems, and BDNF have been linked to resilient phenotypes (Table 1) (Feder et al, 2009;Russo et al, 2012).…”

Section: Genetic Factors In Resiliencementioning

confidence: 99%

“…Resilience is the capacity and dynamic process of adaptively overcoming stress and adversity while maintaining normal psychological and physical functioning (Russo et al, 2012;Rutter, 2012b;Southwick and Charney, 2012). Every individual experiences stressful events and the majority are exposed to trauma at some point during life.…”

Section: Introductionmentioning

confidence: 99%

Understanding Resilience

Building Resilience for Success

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Resilience is the ability to adapt successfully in the face of stress and adversity. Stressful life events, trauma, and chronic adversity can have a substantial impact on brain function and structure, and can result in the development of posttraumatic stress disorder (PTSD), depression and other psychiatric disorders. However, most individuals do not develop such illnesses after experiencing stressful life events, and are thus thought to be resilient. Resilience as successful adaptation relies on effective responses to environmental challenges and ultimate resistance to the deleterious effects of stress, therefore a greater understanding of the factors that promote such effects is of great relevance. This review focuses on recent findings regarding genetic, epigenetic, developmental, psychosocial, and neurochemical factors that are considered essential contributors to the development of resilience. Neural circuits and pathways involved in mediating resilience are also discussed. The growing understanding of resilience factors will hopefully lead to the development of new pharmacological and psychological interventions for enhancing resilience and mitigating the untoward consequences.

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Neurobiology of resilience

Cited by 947 publications

References 102 publications

Mouse social stress induces increased fear conditioning, helplessness and fatigue to physical challenge together with markers of altered immune and dopamine function

Mouse social stress induces increased fear conditioning, helplessness and fatigue to physical challenge together with markers of altered immune and dopamine function

Dehydroepiandrosterone sulfate level varies nonlinearly with symptom severity in major depressive disorder

Understanding Resilience

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