Sex Differences in Brain Activity and Connectivity in Late-Life Depression

Background There are notable sex differences in the symptoms and treatment response of late-life depression (LLD); however, the underlying static and dynamic abnormalities in brain function that may drive these disparities remain poorly understood. The aim of this study is to investigate the potential links between sex-specific aberrant brain activity and LLD. Methods In the present study, 75 patients with LLD and 164 healthy controls (HCs) were recruited. Static and dynamic metrics of amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo) and functional connectivity (FC) were compared across four groups (LLD-female, LLD-male, HC-female and HC-male). Correlation and moderation analyses were then used to examine whether sex moderated the associations between brain activity, cognitive impairment, and depressive symptoms. Results First, significant interaction effects between diagnosis (LLD vs. HCs) and sex were found for ALFF in the left paracentral lobule, ReHo in the right superior temporal gyrus, and static FC (sFC) between the right superior temporal gyrus and left middle frontal gyrus. Second, in LLD-females, ReHo (right superior temporal gyrus) and sFC (right superior temporal gyrus–left middle frontal gyrus) correlated with weight, and ALFF (left paracentral lobule) correlated with visuospatial skills. Third, sex significantly moderated the relationships between ReHo (right superior temporal gyrus) and cognition, ALFF (left paracentral lobule) and depressive symptoms, and sFC (right superior temporal gyrus–left middle frontal gyrus) and depressive symptoms in the LLD group. Conclusion Our study highlights sex differences in static brain activity related to cognitive impairment and depressive symptoms in LLD patients, indicating sex-specific neurobiological underpinnings for this disorder.