Sexual dimorphism in pre-clinical studies of depression

Although there is a sex bias in the pathological mechanisms exhibited by brain disorders, investigation of the female brain in biomedical science has long been neglected. Use of the male model has generally been the preferred option as the female animal model exhibits both biological variability and hormonal fluctuations. Existing studies that compare behavioral and/or molecular alterations in animal models of brain diseases are generally underrepresented, and most utilize the male model. Nevertheless, in recent years there has been a trend toward the increased inclusion of females in brain studies. However, current knowledge regarding sex-based differences in depression and stress-related disorders is limited. This can be improved by reviewing preclinical studies that highlight sex differences in depression. This paper therefore presents a review of sex-based preclinical studies of depression. These shed light on the discrepancies between males and females regarding the biological mechanisms that underpin mechanistic alterations in the diseased brain. This review also highlights the conclusions drawn by preclinical studies to advance our understanding of mood disorders, encouraging researchers to promote ways of investigating and managing sexually dimorphic disorders.