Major depressive disorder (MDD) is a common debilitating disorder characterized by impaired spontaneous brain activity, yet little is known about its alterations in dynamic properties and the molecular mechanisms associated with these changes.

Based on the resting-state functional MRI data of 65 first-episode, treatment-naïve patients with MDD and 66 healthy controls, we compared dynamic regional homogeneity (dReHo) of spontaneous brain activity between the two groups, and we investigated gene expression profiles associated with dReHo alterations in MDD by leveraging transcriptional data from the Allen Human Brain Atlas and weighted gene co-expression network analysis.

Compared with healthy controls, patients with MDD consistently showed reduced dReHo in both fusiform gyri and in the right temporal pole and hippocampus. The expression profiles of 16 gene modules were correlated with dReHo alterations in MDD. These gene modules were enriched for various biological process terms, including immune, synaptic signalling, ion channels, mitochondrial function and protein metabolism, and were preferentially expressed in different cell types.

Patients with MDD have reduced dReHo in brain areas associated with emotional and cognitive regulation, and these changes may be related to complex polygenetic and polypathway mechanisms.