Brain-based Sex Differences in Depression: A Systematic Review of Neuroimaging Studies

Major depressive disorder (MDD) is a common psychiatric illness with a wide range of symptoms such as mood decline, loss of interest, and feelings of guilt and worthlessness. Women develop depression more often than men, and the diagnostic criteria for depression mainly rely on female patients' symptoms. By contrast, male depression usually manifests as anger attacks, aggression, substance use, and risk-taking behaviors. Various studies have focused on the neuroimaging findings in psychiatric disorders for a better understanding of their underlying mechanisms. With this review, we aimed to summarize the existing literature on the neuroimaging findings in depression, separated by male and female subjects. A search was conducted on PubMed and Scopus for magnetic resonance imaging (MRI), functional MRI (fMRI), and diffusion tensor imaging (DTI) studies of depression. After screening the search results, 15 MRI, 12 fMRI, and 4 DTI studies were included. Sex differences were mainly reflected in the following regions: 1) total brain, hippocampus, amygdala, habenula, anterior cingulate cortex, and corpus callosum volumes, 2) frontal and temporal gyri functions, along with functions of the caudate nucleus and prefrontal cortex, and 3) frontal fasciculi and frontal projections of corpus callosum microstructural alterations. Our review faces limitations such as small sample sizes and heterogeneity in populations and modalities. But in conclusion, it reflects the possible roles of sex-based hormonal and social factors in the depression pathophysiology.