Topologic but not volumetric differences diversify sex effects on thalamic nuclei in drug-naive patients with major...

The thalamus is a crucial subcortical structure in etiological models of major depressive disorder (MDD). Given the well-documented sex differences in MDD prevalence and clinical manifestations, it remains unclear whether these differences are linked to structural characteristics of thalamus. This study aimed to investigate the divergent sex effects on thalamus nuclei in drug-naive patients with MDD.

High-resolution 3D T1-weighted and diffusion tensor imaging images were obtained for 174 drug-naive patients with MDD and 118 age-, sex-, education years- and handedness-matched healthy controls (HCs). The thalamus was segmented into 22 nuclei using FreeSurfer. A general linear model (GLM) was used to test sex-by-diagnosis interactions for volumes of whole thalamus and individual nuclei between groups. We also performed a graph theory analysis of the structural covariance network (SCN) of thalamic nuclei in females and males with MDD, compared to their sex-matched HCs, respectively.

There were no significant sex-by-diagnosis interactions in whole thalamus or nuclei volumes. The disruptions of SCN were observed in females with MDD, including lower nodal degree in left lateral posterior (LP) nucleus, lower betweenness centrality across several nuclei in the left intralaminar and bilateral antero-lateral nuclei group, and higher betweenness and closeness centrality in right pulvinar lateral nucleus, compared to female HCs. Males with MDD displayed lower nodal degree in left ventral anterior magnocellular and right medial ventral reuniens nuclei and higher betweenness centrality in left mediodorsal lateral parvocellular nucleus relative to male HCs. Moreover, male HCs exhibited higher closeness centrality in the right LP nucleus than female HCs.

These findings represent the first evidence of sex-specific alterations in the topological properties rather than the volumes of thalamic nuclei in early untreated patients with MDD, indicating the structural reorganization of SCN of thalamic nuclei may represent a potential neuro-mechanism underlying sex differences in MDD.