Neurobiology of Resilience: Interface Between Mind and Body

Abstract

Stress-related neuropsychiatric disorders, such as major depressive disorder and posttraumatic stress disorder, exact enormous socioeconomic and individual consequences. Resilience, the process of adaptation in the face of adversity, is an important concept that is enabling the field to understand individual differences in stress responses, with the hope of harnessing this information for the development of novel therapeutics that mimic the body's natural resilience mechanisms. This review provides an update on the current state of research of the neurobiological mechanisms of stress resilience. We focus on physiological and transcriptional adaptations of specific brain circuits, the role of cellular and humoral factors of the immune system, the gut microbiota, and changes at the interface between the brain and the periphery, the blood-brain barrier. We propose viewing resilience as a process that requires the integration of multiple central and peripheral systems and that elucidating the underlying neurobiological mechanisms will ultimately lead to novel therapeutic options.

Keywords: Blood-brain barrier; Gut microbiota; Inflammation; Major depressive disorder; Mesolimbic reward circuit; Posttraumatic stress disorder; Resilience; Stress.

Fig. 1.

Stress-resilience, the process of positive adaptation in the face of psychosocial stress, is a complex process that involves both central and peripheral mechanisms. In the central nervous system, several specific brain regions and circuits are crucial in mediating responses to stress (Fig. A-E). In the periphery, cellular and humoral factors of the immune system (Fig. G, H) and changes in gut microbiota composition (Fig. I) contribute to the development of resilience. Recently, the blood-brain barrier has been implicated as an additional factor (Fig. F). Importantly, these compartments interact extensively with each other. Abbreviations: CREB: cAMP response element-binding protein; DA: Dopamine; DHCA: Dihydrocaffeic acid; Mal-gluc: Malvidin-3′-O-glucoside; Dusp6: Dual Specificity Phosphatase 6; Emx1: Empty spiracles homeobox; IL: Interleukin; K⁺: Potassium; LC: Locus coeruleus; LPS: Lipopolysaccharides; MBP: Myelin basic protein; miR: microRNA; mPFC: Medial prefrontal cortex; MSN: Medium spiny neurons; NE: Norepinephrine; NAc: Nucleus accumbens; TNF: Tumor necrosis factor: VTA: Ventral tegmental area; Zfp189: Zinc finger protein 189.