Structural covariance network of inhibition and shifting in major depressive disorder

Executive function impairments, particularly in inhibition and cognitive flexibility/shifting, are core features of major depressive disorder (MDD) yet marked interindividual heterogeneity has hindered the identification of reliable brain-based biomarkers. This study aimed to use individualized structural covariance networks (SCNs) analysis, a novel approach reflecting interregional covariation within subjects to characterize the individual differences in brain architecture related to inhibition and shifting ability in first-episode drug-naïve (FEDN) MDD patients. Individualized SCNs were constructed for 283 patients and 81 healthy controls (HCs) using the Brainnetome Atlas, combining probability density estimation and Kullback-Leibler divergence based on regional gray matter volumes. Global and nodal topological properties were estimated. In both MDD and HCs, inhibition-shifting was significantly associated with global and local efficiency and small-worldness. In MDD group, the betweenness centrality of middle frontal gyrus, precentral gyrus, and inferior temporal gyrus were associated with poorer inhibition-shifting, and those of thalamus, cingulate gyrus and inferior frontal gyrus were associated with better inhibition-shifting function. No significant associations between inhibition-shifting and nodal centrality were observed in HCs. These results suggest recruitment of thalamo-cingulate regions in compensation for frontal-temporal organizations affecting inhibition-shifting in FEDN MDD. The individual SCNs may help identify biomarkers for specific executive function in MDD.