Resilience as a translational endpoint in the treatment of PTSD

Resilience is a neurobiological entity that shapes an individual's response to trauma. Resilience has been implicated as the principal mediator in the development of mental illness following exposure to trauma. Although animal models have traditionally defined resilience as molecular and behavioral changes in stress responsive circuits following trauma, this concept needs to be further clarified for both research and clinical use. Here, we analyze the construct of resilience from a translational perspective and review optimal measurement methods and models. We also seek to distinguish between resilience, stress vulnerability, and posttraumatic growth. We propose that resilience can be quantified as a multifactorial determinant of physiological parameters, epigenetic modulators, and neurobiological candidate markers. This multifactorial definition can determine PTSD risk before and after trauma exposure. From this perspective, we propose the use of an 'R Factor' analogous to Spearman's g factor for intelligence to denote these multifactorial determinants. In addition, we also propose a novel concept called 'resilience reserve', analogous to Stern's cognitive reserve, to summarize the sum total of physiological processes that protect and compensate for the effect of trauma. We propose the development and application of challenge tasks to measure 'resilience reserve' and guide the assessment and monitoring of 'R Factor' as a biomarker for PTSD.