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Abstract

Humans exhibit a remarkable degree of resilience in the face of extreme stress, with most resisting the development of neuropsychiatric disorders. Over the past 5 years, there has been increasing interest in the active, adaptive coping mechanisms of resilience; however, in humans, most published work focuses on correlative neuroendocrine markers that are associated with a resilient phenotype. In this review, we highlight a growing literature in rodents that is starting to complement the human work by identifying the active behavioral, neural, molecular and hormonal basis of resilience. The therapeutic implications of these findings are important and can pave the way for an innovative approach to drug development for a range of stress-related syndromes.

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Ordinary magic. Resilience processes in development.

A. S. Masten (2001)

The study of resilience in development has overturned many negative assumptions and deficit-focused models about children growing up under the threat of disadvantage and adversity. The most surprising conclusion emerging from studies of these children is the ordinariness of resilience. An examination of converging findings from variable-focused and person-focused investigations of these phenomena suggests that resilience is common and that it usually arises from the normative functions of human adaptational systems, with the greatest threats to human development being those that compromise these protective systems. The conclusion that resilience is made of ordinary rather than extraordinary processes offers a more positive outlook on human development and adaptation, as well as direction for policy and practice aimed at enhancing the development of children at risk for problems and psychopathology.

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Essential role of BDNF in the mesolimbic dopamine pathway in social defeat stress.

Olivier Berton, Colleen A. McClung, Ralph J Dileone … (2006)

Mice experiencing repeated aggression develop a long-lasting aversion to social contact, which can be normalized by chronic, but not acute, administration of antidepressant. Using viral-mediated, mesolimbic dopamine pathway-specific knockdown of brain-derived neurotrophic factor (BDNF), we showed that BDNF is required for the development of this experience-dependent social aversion. Gene profiling in the nucleus accumbens indicates that local knockdown of BDNF obliterates most of the effects of repeated aggression on gene expression within this circuit, with similar effects being produced by chronic treatment with antidepressant. These results establish an essential role for BDNF in mediating long-term neural and behavioral plasticity in response to aversive social experiences.

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The link between childhood trauma and depression: insights from HPA axis studies in humans.

Christine Heim, D Newport, Tanja M. Mletzko … (2008)

Childhood trauma is a potent risk factor for developing depression in adulthood, particularly in response to additional stress. We here summarize results from a series of clinical studies suggesting that childhood trauma in humans is associated with sensitization of the neuroendocrine stress response, glucocorticoid resistance, increased central corticotropin-releasing factor (CRF) activity, immune activation, and reduced hippocampal volume, closely paralleling several of the neuroendocrine features of depression. Neuroendocrine changes secondary to early-life stress likely reflect risk to develop depression in response to stress, potentially due to failure of a connected neural circuitry implicated in emotional, neuroendocrine and autonomic control to compensate in response to challenge. However, not all of depression is related to childhood trauma and our results suggest the existence of biologically distinguishable subtypes of depression as a function of childhood trauma that are also responsive to differential treatment. Other risk factors, such as female gender and genetic dispositions, interfere with components of the stress response and further increase vulnerability for depression. Similar associations apply to a spectrum of other psychiatric and medical disorders that frequently coincide with depression and are aggravated by stress. Taken together, this line of evidence demonstrates that psychoneuroendocrine research may ultimately promote optimized clinical care and help prevent the adverse outcomes of childhood trauma.

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PubMed ID:: 23064380

PMC ID:: 3580862

DOI:: 10.1038/nn.3234

ScienceOpen disciplines: Chemistry

Keywords: Animals,Brain,pathology,Dehydroepiandrosterone,metabolism,Disease Models, Animal,Early Growth Response Transcription Factors,Humans,Hypothalamo-Hypophyseal System,physiopathology,Neurobiology,Neuropeptide Y,Pituitary-Adrenal System,Resilience, Psychological,Stress, Psychological,genetics,psychology,Testosterone

Neurobiology of resilience.

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A Sustainable Future

Most cited references 80

Ordinary magic. Resilience processes in development.

Essential role of BDNF in the mesolimbic dopamine pathway in social defeat stress.

The link between childhood trauma and depression: insights from HPA axis studies in humans.

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