Neurobiology and systems biology of stress resilience

Stress resilience is the phenomenon that some people maintain their mental health despite exposure to adversity or show only temporary impairments followed by quick recovery. Resilience research attempts to unravel the factors and mechanisms that make resilience possible and to harness its insights for the development of preventative interventions in individuals at risk for acquiring stress-related dysfunctions. Biological resilience research has been lagging behind the psychological and social sciences but has seen a massive surge in recent years. At the same time, progress in this field has been hampered by methodological challenges related to finding suitable operationalizations and study designs, replicating findings, and modeling resilience in animals. We embed a review of behavioral, neuroimaging, neurobiological, and systems biological findings in adults in a critical methods discussion. We find preliminary evidence that hippocampus-based pattern separation and prefrontal-based cognitive control functions protect against the development of pathological fears in the aftermath of singular, event-type stressors [as found in fear-related disorders, including simpler forms of posttraumatic stress disorder (PTSD)] by facilitating the perception of safety. Reward system-based pursuit and savoring of positive reinforcers appear to protect against the development of more generalized dysfunctions of the anxious-depressive spectrum resulting from more severe or longer-lasting stressors (as in depression, generalized or comorbid anxiety, or severe PTSD). Links between preserved functioning of these neural systems under stress and neuroplasticity, immunoregulation, gut microbiome composition, and integrity of the gut barrier and the blood-brain barrier are beginning to emerge. On this basis, avenues for biological interventions are pointed out.