Sex differences in anxiety and depression: circuits and mechanisms

Male-only studies predominate preclinical research on anxiety and depression. In this Review, Bangasser and Cuarenta discuss how, since the inclusion of female subjects, new mechanisms have been identified that underlie vulnerability to these disorders, and that reveal novel targets for treatments. Epidemiological sex differences in anxiety disorders and major depression are well characterized. Yet the circuits and mechanisms that contribute to these differences are understudied, because preclinical studies have historically excluded female rodents. This oversight is beginning to be addressed, and recent studies that include male and female rodents are identifying sex differences in neurobiological processes that underlie features of these disorders, including conflict anxiety, fear processing, arousal, social avoidance, learned helplessness and anhedonia. These findings allow us to conceptualize various types of sex differences in the brain, which in turn have broader implications for considering sex as a biological variable. Importantly, comparing the sexes could aid in the discovery of novel therapeutics.

Automated summary

Male-dominated preclinical studies on anxiety and depression are being addressed to include females, leading to the discovery of new mechanisms and treatment targets. Epidemiological sex differences in these disorders are well-known, but the underlying circuits and mechanisms contributing to these differences still lack attention due to historical exclusion of females in research. Comparing the sexes may help in the discovery of novel therapeutics.