Sex differences in anxiety and depression: circuits and mechanisms

• Published in: Nature reviews. Neuroscience Vol. 22; no. 11; pp. 674 - 684
• Main Authors: Bangasser, Debra A., Cuarenta, Amelia
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.11.2021; Nature Publishing Group
• Subjects: 631/378/1689/1300; 631/378/1689/1414; 631/378/1831; Analysis; Animal Genetics and Genomics; Animals; Anxiety; Anxiety - diagnosis; Anxiety - physiopathology; Anxiety - psychology; Anxiety disorders; Arousal; Behavioral Sciences; Biological Techniques; Biomedical and Life Sciences; Biomedicine; Brain - physiopathology; Depression - diagnosis; Depression - physiopathology; Depression - psychology; Development and progression; Epidemiology; Female; Gender differences; Hedonic response; Humans; Information processing; Learned helplessness; Major depressive disorder; Male; Mental depression; Nerve Net - physiopathology; Neurobiology; Neurosciences; Physiological aspects; Review Article; Risk factors; Sex Characteristics; Sex differences; Sex factors in disease; United States
• ISSN: 1471-003X; 1471-0048; 1471-0048; 1469-3178
• DOI: 10.1038/s41583-021-00513-0

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. 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.