Postulating Traumatic Stress Disorders

Abstract

This special issue of Biological Psychiatry, “Understanding PTSD: From Mind to Molecules,” is focused on neurobiological studies that inform our scientific approach to posttraumatic stress disorder (PTSD). By virtue of the requirement that a lifethreatening stressor precede its onset, PTSD is distinguished from other mental disorders. Although mental health clinicians and researchers acknowledge the contributions (and presumably very complex interactions) of psychological, social, and biological factors in the generation of virtually all mental disorders, only PTSD (and the other trauma and stressorrelated disorders with it shares a chapter in DSM-5) has exposure to a traumatic stressor or stressors as a mandatory antecedent. In other words, PTSD is the quintessential biopsychosocially determined disorder; as such, it demands the efforts of a diverse and eclectic set of researchers and experimental methods to understand its etiology and consider novel approaches to its treatment. Such is the spirit of this special issue, where we have brought together a multitalented group of basic and translational researchers to share their insights into the nature of PTSD and its potential prevention and management. The time frame of inquiry begins very early in development, with Rodgers and Bale (1) describing an intriguing body of preclinical work positing the transgenerational transmission of stress through male germ cells; this work has been echoed in clinical studies demonstrating not only an increase in PTSD among adult offspring of survivors of extreme trauma (i.e., the Holocaust) but also a possible epigenetic reflection of that increased risk in glucocorticoid-relevant genes or their promoters (2). Bock et al. (3) review and insightfully integrate a body of animal and human literature that emphasizes possible molecular bases for prenatal stress exposures adversely affecting emotional and cognitive development of the brain. Zannas et al. (4) provide a comprehensive review of epigenetic studies relevant to PTSD and in so doing forge a path for future research in this area, highlighting opportunities and challenges that lie ahead. Together, these articles paint a picture of the brains of certain individuals being primed in utero to experience stressful life experiences differently than others. How can we begin to tie together these observations with findings of specific genetic vulnerabilities for PTSD that may operate through altering stress responsiveness (e.g., FKBP5 and allele-specific demethylation in association with childhood trauma exposure (5))? What is the physiologic and molecular nature of this altered brain response to stress? There is evidence that exposure of the hippocampus to glucocorticoids after stress results in a PTSD-like set of memory impairments that includes the inability to restrict fear to the appropriate context (i.e., there is an overgeneralization of the fear response (6)). Could it be that the hippocampus of individuals at risk for PTSD is exposed to functionally elevated levels of