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Sex differences in anxiety and depression: circuits and mechanisms

Abstract

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.

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Fig. 1: Different types of sex differences in brain circuits.
Fig. 2: Sex-biased receptor signalling.
Fig. 3: Brain regions and circuits that bias male or female anxiety-like and/or depression-like behaviour.

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Acknowledgements

This work was supported by National Science Foundation (NSF) CAREER grant IOS-1552416 (D.A.B.), NSF grant IOS-1929829 (D.A.B.) and US National Institutes of Health (NIH) DA049837 (D.A.B. with supplement to A.C.).

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Glossary

Anhedonia

A loss of or inability to feel pleasure.

Dioestrus

A period of the oestrous cycle immediately preceding pro-oestrus in which female subjects are not sexually receptive and there are relatively low levels of oestrogens and progesterone.

Extinction

A weakening of a conditioned response that yields a decrease in behaviour.

Monetary incentive delay task

An imaging paradigm used to study the neural activity of anticipatory incentive processing.

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Bangasser, D.A., Cuarenta, A. Sex differences in anxiety and depression: circuits and mechanisms. Nat Rev Neurosci 22, 674–684 (2021). https://doi.org/10.1038/s41583-021-00513-0

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