Recognizing resilience: Learning from the effects of stress on the brain

Abstract

As the central organ of stress and adaptation to stressors, the brain plays a pivotal role in behavioral and physiological responses that may lead to successful adaptation or to pathophysiology and mental and physical disease. In this context, resilience can be defined as “achieving a positive outcome in the face of adversity”. Underlying this deceptively simple statement are several questions; first, to what extent is this ability limited to those environments that have shaped the individual or can it be more flexible; second, when in the life course does the brain develop capacity for flexibility for adapting positively to new challenges; and third, can such flexibility be instated in individuals where early life experiences have limited that capacity? Brain architecture continues to show plasticity throughout adult life and studies of gene expression and epigenetic regulation reveal a dynamic and ever-changing brain. The goal is to recognize those biological changes that underlie flexible adaptability, and to recognize gene pathways, epigenetic factors and structural changes that indicate lack of resilience leading to negative outcomes, particularly when the individual is challenged by new circumstances. Early life experiences determine individual differences in such capabilities via epigenetic pathways and laying down of brain architecture that determine the later capacity for flexible adaptation or the lack thereof. Reactivation of such plasticity in individuals lacking such resilience is a new challenge for research and practical application. Finally, sex differences in the plasticity of the brain are often overlooked and must be more fully investigated.

Origins of heath inequalities: the case for Allostatic Load

“…However, between the lines of the allostasis literature we also encounter considerations pertaining to salutogenetic factors which promote and uphold health. An explicit focus on resilience can be found in recent key publications about allostasis (Ghini et al, 2015;Karatsoreos & McEwen, 2013;McEwen, Gray, & Nasca, 2015). Consequently, we suggest that a metaphorical expression of the fundamental idea of allostasis should involve both detrimental ("draining") and health promoting ("gaining") phenomena (Kirkengen, 2010;Tomasdottir et al, 2014).…”

Profiling coping strategies in male and female rats: Potential neurobehavioral markers of increased resilience to depressive symptoms

“…Flexible copers also had lower levels of glucocorticoid receptor immunoreactivity following chronic stress and cognitive training and testing. Because decreased fear activation, increased neuroplasticity, and higher DHEA levels have been associated with emotional resilience (Charney, 2003; McEwen et al, 2015), the flexible coping rats are viewed as exhibiting enhanced resilience in the current study. Thus, prior association with chronic unpredictable stress exacerbated the beneficial effects of utilizing a more varied, context-dependent coping strategy.…”

“…Because stress and anxiety are closely associated with emotional disorders, effective coping strategies provide an opportunity for animals to gain emotional control in unpredictable, stressful environments (McEwen et al, 2015). Although HPA activation is necessary for survival, especially in the context of acute stressors, hypersecretion of glucocorticoids for extended durations leads to disrupted cellular functioning and eventual physiological dysfunction (Mackin and Young, 2004).…”

Stress dynamically regulates behavior and glutamatergic gene expression in hippocampus by opening a window of epigenetic plasticity

“…The window of epigenetic plasticity offers opportunity for behavioral and pharmacological interventions that can increase resilience by correcting imbalances of excitatory transmission through regulation of gene transcription via histone modifications and related epigenetic alterations. Thereby, this window of epigenetic plasticity can be capitalized by behavioral and pharmacological interventions to reestablish balanced neural circuitry in the hippocampus, prefrontal cortex, and amygdala that become unbalanced in stress-related disorders (3,(35)(36)(37)(38). Pharmacological interventions may include acetyl-Lcarnitine (LAC), a donor of acetyl groups that has been shown to rapidly counteract depressive-like behavior and rectify glutamate dysregulation (18).…”

“…These differential responses, including determining susceptibility versus resilience to stress, contribute to the pathophysiology of debilitating stress-related disorders (2)(3)(4)(5). The hippocampus is a brain region noted for its plasticity in response to stress and sensitivity to adrenal steroid hormones (6).…”