Abstract

Background: Stress is a common reaction to an environmental adversity, but a dysregulation of the stress response can lead to psychiatric illnesses such as major depressive disorder (MDD), post-traumatic stress disorder (PTSD), and anxiety disorders. Yet, not all individuals exposed to stress will develop psychiatric disorders; those with enhanced stress resilience mechanisms have the ability to adapt successfully to stress without developing persistent psychopathology. Notably, the potential to enhance stress resilience in at-risk populations may prevent the onset of stress-induced psychiatric disorders. This novel idea has prompted a number of studies probing the mechanisms of stress resilience and how it can be manipulated.

Methods: Here, we review the neurobiological factors underlying stress resilience, with particular focus on the serotoninergic (5-HT), glutamatergic, and γ-Aminobutyric acid (GABA) systems, as well as the hypothalamic-pituitary axis (HPA) in rodents and in humans. Finally, we discuss stress resiliency in the context of aging, as the likelihood of mood disorders increases in older adults.

Results: Interestingly, increased resiliency has been shown to slow aging and improved overall health and quality of life. Research in the neurobiology of stress resilience, particularly throughout the aging process, is a nascent, yet, burgeoning field.

Conclusion: Overall, we consider the possible methods that may be used to induce resilient phenotypes, prophylactically in at-risk populations, such as in military personnel or in older MDD patients. Research in the mechanisms of stress resilience may not only elucidate novel targets for antidepressant treatments, but also provide novel insight about how to prevent these debilitating disorders from developing.

Keywords: Stress, resilience, aging, serotonin, glutamate, γ-aminobutyric acid, hypothalamic–pituitary–adrenal axis.

Graphical Abstract