Expanding Our Understanding of Neurobiological Mechanisms of Resilience by Using Animal Models

Abstract

The original conceptualization of stress and the stress response has been developed based on the understanding that certain environmental exposures and life events can be both detrimental to individual's health and wellbeing, and also promote physiological responses that can be adaptive. Interestingly, until recently, the majority of translational research focused on neurobiological processes involved in the abnormal or altered stress response, on the vulnerability to stress, or the negative consequences of stress. Only recently the field started focusing on the concept of resilience, exploring the possibility that, similarly to stress vulnerability, there could be unique mechanisms involved in resilience to stress. Defining resilience has not been easy and within clinical research, resilience often refers to the ability of an organism to deal with, or adapt to, the pathological effects of stress. This seemingly subtle shift in research focus actually has immediate and substantial implications to stress research, as it suggests that some individuals are particularly adept to dealing with stressful situations, and if we examine this subgroup of individuals, we are likely to find different or compensatory changes, or changes in biological processes that are diametrically opposed to those found in stress-vulnerable individuals.It has long been known that significant individual variability in vulnerability to severe stress or trauma exists with respect to the development of psychiatric consequences like post-traumatic stress disorder (PTSD), however, the resilience perspective might suggest that this can be accounted for by individual variability in resilience. Insofar as the mechanisms of vulnerability and resilience do not overlap completely, the study of the neurobiology of resilience is not simply a mirror of the study of stress vulnerability, but it could offer new perspectives on pathophysiology or treatment of stress-induced anxiety disorders such as PTSD and depression. Together with the study of stress vulnerability, understanding the neurobiology of resilience could provide a more comprehensive picture in the service of understanding pathophysiology, development of new treatments for stress-induced psychiatric disorders, and identifying markers for primary and secondary prevention. More importantly, if individuals who have low levels of resilience can be treated in such a manner so as to increase their levels of resilience, this could greatly reduce the incidence of stress-induced psychiatric disorders.Understanding the neurobiology of resilience in clinical research can be hindered by ethical constraints, but can be readily explored by employing animal models of stress and trauma. One promising approach for studying the neurobiology of resilience is the use of the cut-off behavioral criteria (CBC), as proposed by Cohen et al. This method, here applied to predator-odor-exposed animals that are later tested for startle and anxiety behavior, allows for identification of not only vulnerable groups (extreme be...

A conceptual framework for the neurobiological study of resilience

“…Resilience researchers are not interested in pathophysiology; instead of investigating the mechanisms that lead to stress-related illness, they investigate the mechanisms that prevent illness. The topic has become increasingly popular over the last 10 years and, though initially proposed by psychologists and clinicians (Werner 1993), has in the meantime even motivated neurobiological research in animal models (Feder et al 2011;Franklin et al 2012;Friedman et al 2014;Liberzon & Knox 2012;Russo et al 2012;Scharf & Schmidt 2012;Southwick & Charney 2012). Many resilience researchers make the basic assumption that resilience is not simply the result of an absence of disease processes but also reflects the work of active adaptation mechanisms that have a biological basis (Friedman et al 2014;Russo et al 2012).…”

Resilience as a translational endpoint in the treatment of PTSD

“…This may represent differences in resilience phenotypes. In some animal models of PTSD, 30 to 40 percent of C57/BL6 mice exposed to the trauma paradigm escape any effects of the trauma exposure and are called unsusceptible (86,89). Studies using the social defeat stress paradigm find that a certain percentage of rodents exposed to the paradigm do not exhibit social avoidance typically induced by exposure to social defeat (90,91).…”

When pain gets stuck: the evolution of pain chronification and treatment resistance

“…Thus, drugs that perform a ‘good balancing act’ including buprenorphine [123] or nalbuphine [225] may have protective effects because of the receptors they target and by implication the circuits they modify. Thus, there are underlying unique responses to stress in individuals that can markedly change the manner in which an individual adapts to later stress [165] including specific clinical conditions such as pain.…”