Associations Between Thalamic Gray Matter Volume and Psychomotor Symptoms in Major Depressive Disorder: A Voxel-Based Morphometry Study

Abstract

Background Major depressive disorder (MDD) is a heterogeneous disorder with diverse symptom profiles and treatment responses. Psychomotor retardation and agitation represent clinically relevant dimensions of MDD heterogeneity, but their neurobiological basis remains unclear. Given the role of the thalamus in motor regulation and affective processing, this study examined thalamic gray matter volume (GMV) differences among patients with MDD with predominant psychomotor retardation (MDD-R), patients with MDD with predominant psychomotor agitation (MDD-A), and healthy controls (HCs). Methods Structural MRI data from the REST-meta-MDD consortium included 54 patients with MDD-A, 123 with MDD-R, and 122 HCs. Total, hemispheric, and 30 subregional thalamic GMV measures were extracted using voxel-based morphometry and the AAL3v1 atlas. ComBat harmonization was applied before analysis. Group differences were tested with analysis of covariance controlling for sex, age, education, and total gray matter volume. Exploratory partial Spearman correlations examined associations with psychomotor symptoms, HAMD(adj), and anxiety symptoms. Results After FDR correction, significant group effects were limited to the bilateral ventral anterior nucleus (VA). Patients with MDD-R had greater bilateral VA GMV than HCs, whereas MDD-A did not differ from HCs. No direct MDD-A vs MDD-R difference survived FDR correction; only the left inferior pulvinar showed a nominal difference. Exploratory correlations linked several thalamic nuclei, including the reuniens nucleus, ventral posterolateral nucleus, lateral geniculate nucleus, and anteroventral nucleus, to psychomotor, depressive, or anxiety symptoms. Conclusion MDD-R was associated with selective bilateral VA structural differences rather than widespread thalamic abnormalities. No direct thalamic GMV difference between MDD-A and MDD-R survived FDR correction. The exploratory symptom associations suggest that thalamic structure may relate to multidimensional clinical heterogeneity in MDD. These findings require replication given the cross-sectional design, unequal subgroup sizes, and incomplete medication data.