Resilience to fear: The role of individual factors in amygdala response to stressors

Abstract

Resilience to stress is an adaptive process that varies individually. Resilience refers to the adaptation, or the ability to maintain or regain mental health, despite being subject to adverse situation. Resilience is a dynamic concept that reflects a combination of internal individual factors, including age and gender interacting with external factors such as social, cultural and environmental factors. In the last decade, we have witnessed an increase in the prevalence of anxiety disorders, including post-traumatic stress disorder. Given that stress in unavoidable, it is of great interest to understand the neurophysiological mechanisms of resilience, the individual factors that may contribute to susceptibility and promote efficacious approaches to improve resilience. Here, we address this complex question, attempting at defining clear and operational definitions that may allow us to improve our analysis of behavior incorporating individuality. We examine how individual perception of the stressor can alter the outcome of an adverse situation using as an example, the fear-conditioning paradigm and discuss how individual differences in the reward system can contribute to resilience. Given the central role of the endocannabinoid system in regulating fear responses and anxiety, we discuss the evidence that polymorphisms in several molecules of this signaling system contribute to different anxiety phenotypes. The endocannabinoid system is highly interconnected with the serotoninergic and dopaminergic modulatory systems, contributing to individual differences in stress perception and coping mechanisms. We review how the individual variability in these modulatory systems can be used towards a multivariable assessment of stress risk. Incorporating individuality in our research will allow us to define biomarkers of anxiety disorders as well as assess prognosis, towards a personalized clinical approach to mental health.