Sex differences have been observed across many psychiatric diseases, especially mood disorders. For major depression, the most prevalent psychiatric disorder, females show a roughly two-fold greater risk as compared to males. Depression is sexually dimorphic with males and females exhibiting differences in clinical presentation, course, and response to antidepressant treatment. In this review, we first discuss sex differences observed in depressed patients, as well as animal models that reveal potential underlying mechanisms. We then discuss antidepressant treatments including their proposed mechanism of action and sex differences observed in treatment response. We include possible mechanisms underlying these sex differences with particular focus on synaptic transmission.
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We thank Adam Van Dyke for his helpful input. This work was supported by R01MH086828 (S.M.T.) and a NARSAD Young Investigator Award (T.A.L.). S.M.T. and M.D.K. are listed as a co-inventors on a patent application for the use of negative allosteric modulators of GABA-A receptors containing alpha5 subunits as fast-acting antidepressants. They have assigned their patent rights to the University of Maryland Baltimore, but will share a percentage of any royalties that may be received by the University of Maryland Baltimore. S.M.T. and M.D.K. are co-founders of a company, Asulon Therapeutics Inc., developing alpha5-selective GABA-NAMs as fast-acting antidepressants.
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