Julia Sacher & Rachel G Zsido | Leveraging knowledge of sex-steroid hormones towards improved clinical translation in depression

Pharmacological treatment options for depression work well in some patients, but more than half the people who take antidepressants experience limited efficacy. Depression is a debilitating disorder that affects approximately 20% of the world’s population and is the leading contributor to years lost to disability. Every year, nearly twice as many women as men develop a depressive illness. While this suggests that sex hormones play a key role in depression, it is not understood in depression, nor in health, how these hormones affect mood. Preclinical and animal models of depression do exist, but our understanding of depression may be hampered by the fact that many studies do not stratify their data by sex or sex hormone status. Women are particularly susceptible to depression during the postpartum and perimenopausal stages across their lifespan. In order to build a better model of depression, it is necessary to leverage our knowledge of these sex and life stage differences in disease vulnerability. Accumulating evidence also encourages that sex differences be considered for treatment efficacy, as they may be critical for optimal tailoring of precision medicine. Here, we develop a neurobiological model of postpartum blues, argue for a broad spectrum-approach for treatment of postpartum mood disorders, present current research strategies to identify the neurochemical mechanisms underlying premenstrual dysphoric disorder (PMDD), and discuss sex differences in visceral fat accumulation and structural brain networks across the lifespan. In summary, our data highlight why the inclusion of biological sex and sex hormone manipulations are imperative for building a better translational model of depression.

Poster