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.