Biological Sex Differences in Depression: A Systematic Review

Depression is the leading cause of disability worldwide, and its prevalence is 2 times higher in women than in men. There is, however, a lack of data on sex-specific pathophysiology of this disorder. The purpose of this systematic review is to identify the biological sex differences found in major depressive disorder (MDD) in studies published in the last 10 years. We conducted a literature search using the Medline, PsycInfo, PubMed, and Web of Science databases, selecting English-language studies that included physiological measures compared by sex in addition to MDD. We identified 20 relevant studies, which consisted primarily of mixed methodology and samples. The reported physiological measures comprised a variety of serum biomarkers, gene mRNA expression, and brain activity. Findings suggest different biological patterns in those with MDD depending on sex. Specifically, women presented higher levels of inflammatory, neurotrophic, and serotonergic markers and a stronger correlation between levels of some inflammatory and neurotrophic factors and the severity of symptoms. This review provides information about possible different biological patterns for women and men with depressive disorder and may have important implications for treatment. Future research should include homogeneous samples; make comparisons based on sex, control sex hormone fluctuations and pharmacological treatment; and use consistent criteria for evaluating psychobiological changes in MDD.