Effects of electroconvulsive therapy on cerebellar-cerebral functional connectivity in patients with treatment-resistant depression and their correlations with gene expression profiles.

Abstract

Aims: Electroconvulsive therapy (ECT) is an effective intervention for treatment-resistant depression (TRD). Although prior studies have identified cerebellar functional alterations following ECT, cerebellar-cerebral functional connectivity (FC) changes remain insufficiently explored.

Methods: Cerebellar seeds were defined based on prior connectivity studies, targeting cerebellar regions functionally coupled with executive, default-mode, and affective-limbic networks. Seed-based cerebellar-cerebral FC analyses were conducted using neuroimaging data from 72 patients with TRD (52 of whom completed post-ECT assessment) and 63 healthy controls (HCs). Correlation analyses assessed clinical associations, and support vector regression was applied to predict treatment response using baseline FC. Neuroimaging-transcriptomic association analyses were conducted to identify gene expression patterns correlated with post-ECT FC alterations.

Results: Compared to HCs, patients with TRD exhibited decreased cerebellar connectivity with the sensorimotor network (SMN) and the default-mode network (DMN). Following ECT, TRD patients showed significant alleviation of depressive symptoms, which was accompanied by a marked increase in cerebellar-DMN connectivity. Enhanced FCs between the left Crus II_Exec2 and the bilateral medial superior frontal gyrus were positively correlated with Hamilton Depression Rating Scale (HAMD) score reduction (r = 0.343, P = 0.026). Additionally, baseline FC of the left Crus II_Exec2 significantly predicted HAMD reduction (r = 0.412, P < 0.001). Neuroimaging-transcription association analysis revealed these FC alterations were associated with normative gene patterns enriched in synaptic signaling, ion channel, and chromatin remodeling.

Conclusions: TRD is associated with reduced cerebellar-SMN and cerebellar-DMN connectivity. ECT may enhance cerebellar-DMN connectivity, potentially contributing to antidepressant effects.