Sex-specific mechanisms for responding to stress.

Posttraumatic stress disorder and major depression share stress as an etiological contributor and are more common in women than in men. Traditionally, preclinical studies investigating the neurobiological underpinnings of stress vulnerability have used only male rodents; however, recent studies that include females are finding sex-specific mechanisms for responding to stress. This Mini-Review examines recent literature using a framework developed by McCarthy and colleagues (2012; J Neurosci 32:2241-2247) that highlights different types of sex differences. First, we detail how learned fear responses in rats are sexually dimorphic. Then, we contrast this finding with fear extinction, which is similar in males and females at the behavioral level but at the circuitry level is associated with sex-specific cellular changes and, thus, exemplifies a sex convergence. Next, sex differences in stress hormones are detailed. Finally, the effects of stress on learning, attention, and arousal are used to highlight the concept of a sex divergence in which the behavior of males and females is similar at baseline but diverges following stressor exposure. We argue that appreciating and investigating the diversity of sex differences in stress response systems will improve our understanding of vulnerability and resilience to stress-related psychiatric disorders and likely lead to the development of novel therapeutics for better treatment of these disorders in both men and women.