Resilience and vulnerability: physiological and neural contexts
Studying the neurobiology of resilience and vulnerability is a difficult task that requires considering myriad systems that are involved in both maintaining homeostasis (those factors necessary for life) as well as systems that mediate “allostasis”, or physiological changes that occur in response to environmental perturbations [2-5]. A useful, though sometimes misunderstood, concept to explore these systems is “stress”. While Hans Selye initially borrowed the term in the 1930s from the field of engineering, it is an appropriate concept when discussing resilience and vulnerability. Engineering defines stress as a measure of the internal forces acting within a deformable body – an apt definition when considered in the context of the “bend but not break” metaphor of resilience. In Selye's interpretation, stress was the result of an organism's failed attempts to appropriately cope with a physical challenge [6], and since then the definition of stress has expanded to contain ideation or anticipation of impending threats [7]. The concept of stress has had enormous impact both on pop culture as well as modern neuroscience. As Richard Schweder suggested in a 1997 New York Times Op Ed piece, the word “stress” is America's latest export in a stressed-out world, and is “just as useful as a Visa card, and as satisfying as a Coke.”
When an organism experiences a perturbation in the environment, allostatic responses are mobilized in order to provide stability through active intervention. In many cases, this mobilization includes the activation of the “stress response”. Though “stress” carries with it a negative connotation, it is important to note that the allostatic responses play important roles in ensuring an organism can appropriately adapt to a changing environment, and do not represent purely negative responses (See Table 1; though the concept of “toxic stress” is an important one, it falls outside the scope of this paper). Allostatic responses are inherently brain-body responses, with the brain detecting threats, and then engaging both neural and peripheral responses. The concept of allostasis focuses on mediators that allow adaptation, with cortisol being perhaps one of the best studied, but it also includes metabolic hormones, immune mediators, and autonomic nervous system outflows. A key aspect of allostasis is that these mediators serve in the short term to help promote adaptation, but these same mediators can result in pathophysiologic responses when they are dysregulated or become overused [8]. In keeping with the brain-body theme, a good example of this pathophysiology is the inflammatory response. The sympathetic and parasympathetic nervous systems modulate inflammatory cytokines, with the former stimulating their production, and the latter inhibiting them (reviewed in [9,10]). In addition, inflammatory cytokines may stimulate cortisol production, which in turn can lead to inhibition of the inflammatory response. As such, should these complementary systems become unbalanced, e.g. if corticosteroid levels are too high, appropriate inflammatory responses may be inhibited during immune challenge, but on the other hand, if the levels are too low, “normal” immune responses become uncontained, and rampant inflammation out of scale with the initial challenge can result.
Table 1.  Concepts and definitions of stress     But how does the concept of allostasis relate to resilience and vulnerability? Any new experiences result in neural activity that drives adaptive plasticity, and these responses are mediated by systemic hormone, endogenous excitatory amino acids, and neurotrophic factors to name but a few. Changes in how such mediators and processes respond to new experiences could possibly explain differences in resilience and vulnerability, both mental and physical, to environmental and psychological stressors.