Aberrant functional gradient of thalamo-cortical circuitry in major depressive disorder and generalized anxiety disorder

Background: Functional gradient analysis provides insights into the brain's macroscale organization; however, the differences in thalamo-cortical gradients between major depressive disorder (MDD) and generalized anxiety disorder (GAD) remain unclear. Investigating these heterogeneities may uncover disorder-specific neural mechanisms and enhance diagnostic precision, addressing the distinct yet overlapping features of these affective disorders. Methods: Resting-state functional MRI data were acquired from 88 healthy controls, 53 patients with MDD, and 28 patients with GAD. Functional gradient analysis was conducted to investigate differences in the spatial organization of the Thalamo-Cortical circuitry among three groups. The eccentricity index was computed to quantify the segregation of thalamic voxels in a two-dimensional gradient space. Results: Abnormal functional gradients in MDD and GAD were prrdominantly related to connectivity between the thalamus and the dorsal attention (DorsAttn) and somatomotor (SomMot) networks. Compared to HCs, both MDD and GAD patients showed decreased global eccentricity, with significant reductions observed only in the MDD group. Moreover, abnormal gradient organization significantly correlated with clinical symptoms and gene expressions in patient cohorts. In addition, using the eccentricity of Thalamo-Cortical circuitry as features, patients with MDD and GAD could be distinguished with over 72 % accuracy. Conclusion: Our findings indicate significant alterations in the gradient organization of the Thalamo-DorsAttn and Thalamo-SomMot connectivity in these two patient populations, suggesting potential contributions to the etiology and diagnosis of MDD and GAD.