Deep gray matter substructure volumes and depressive symptoms in a large multiple sclerosis cohort

Background: Consistent findings on underlying brain features or specific structural atrophy patterns contributing to depression in multiple sclerosis (MS) are limited. Objective: To investigate how deep gray matter (DGM) features predict depressive symptom trajectories in MS patients. Methods: We used data from the MS Partners Advancing Technology and Health Solutions (MS PATHS) network in which standardized patient information and outcomes are collected. We performed whole-brain segmentation using SLANT-CRUISE. We assessed if DGM structures were associated with elevated depressive symptoms over follow-up and with depressive symptom phenotypes. Results: We included 3844 participants (average age: 46.05 ± 11.83 years; 72.7% female) of whom 1905 (49.5%) experienced ⩾1 periods of elevated depressive symptoms over 2.6 ± 0.9 years mean follow-up. Higher caudate, putamen, accumbens, ventral diencephalon, thalamus, and amygdala volumes were associated with lower odds of elevated depressive symptoms over follow-up (odds ratio (OR) range per 1 SD (standard deviation) increase in volume: 0.88–0.94). For example, a 1 SD increase in accumbens or caudate volume was associated with 12% or 10% respective lower odds of having a period of elevated depressive symptoms over follow-up (for accumbens: OR: 0.88; 95% confidence interval (CI): 0.83–0.93; p < 0.001; for caudate: OR: 0.90; 95% CI: 0.85–0.96; p = 0.003). Conclusion: Lower DGM volumes were associated with depressive symptom trajectories in MS.