Decoupling of Gray and White Matter Functional Networks in Medication-Naïve Patients With Major Depressive Disorder

Abstract

Background: Major depressive disorder (MDD) has been increasingly conceptualized as a disconnection syndrome. However, most studies have only focused on functional connectivity (FC) alterations in gray matter (GM), and the functional alterations in white matter (WM) remain largely unknown in MDD.

Purpose: To investigate WM functional alterations and the functional interaction between GM and WM networks in medication-naïve MDD.

Study type: Prospective.

Subjects: Sixty-eight patients with MDD and 66 age- and sex-matched healthy controls (HCs).

Field strength/sequence: Resting state-functional MRI (fMRI) using a gradient-echo imaging sequence and T₁ -weighted images were acquired at 3.0T.

Assessment: Functional GM and WM networks, based on resting-state blood oxygenation level-dependent (BOLD) signals, were identified by the K-means clustering algorithm, and FC matrices were obtained for each subject.

Statistical tests: Two-sample t-tests, Pearson chi-square test, and Pearson correlation analysis.

Results: Both the GM and WM of the visual network (GM1 and WM11) showed reduced FC with the sensorimotor network (WM5 and GM8), lateral temporal network (GM5 and WM6), cingulo-opercular network (GM9), and dorsal attention network (GM7) in MDD patients compared to controls (P < 0.05, false discovery rate [FDR]-corrected). Reduced FC between the anterior cingulum network (WM3) and the lateral temporal network (GM5 and WM6) and temporal pole network (GM13) and between GM13 and the medial temporal network (GM4) and medial prefrontal-subcortical network (GM10) were also observed in MDD patients (P < 0.05, FDR-corrected). In addition, the WM BOLD signal in the sensorimotor network was negatively correlated with illness duration (r = -0.286, P = 0.018).

Data conclusion: Disconnectivity between the GM and WM networks in the perception-motor system may be the foundation of extensively disrupted connections in MDD. Furthermore, the observed decoupling between subsystems of the default mode network may help explain previous findings of persistent negative rumination and theory of mind deficits in depression.

Level of evidence: 3.

Technical efficacy: Stage 3.

Keywords: functional connectivity (FC); gray matter network; major depressive disorder (MDD); resting-state fMRI; white matter network.