Sex differences in depression: Insights from clinical and preclinical studies

Depression represents a global mental health concern, and disproportionally affects women as they are twice more likely to be diagnosed than men. In this review, we provide a summary of evidence to support the notion that differences in depression between men and women span multiple facets of the disease, including epidemiology, symptomology, treatment, and pathophysiology. Through a lens of biological sex, we overview depression-related transcriptional patterns, changes in neuroanatomy and neuroplasticity, and immune signatures. We acknowledge the unique physiological and behavioral demands of pregnancy and motherhood by devoting special attention to depression occurring in the peripartum period. Specifically, we discuss issues surrounding the presentation, time course, treatment, and neurobiology of peripartum depression. We write this review with the intention of highlighting the encouraging advancements in our understanding of sex differences in depression, while underscoring the gaps that remain. A more systematic consideration of biological sex as a variable in depression research will be critical in the discovery and development of pharmacotherapies that are efficacious for both men and women.