Convergent molecular and structural neuroimaging signatures of first-episode depression

Convergent studies have demonstrated morphological abnormalities in various brain regions in depression patients. However, the molecular underpinnings of the structural impairments remain largely unknown, despite a pressing need for treatment targets and mechanisms. Here, we investigated the gray matter volume (GMV) alteration in patients with depression and its underlying molecular architecture. We recruited 195 first-episode, treatment-naïve depression patients and 78 gender-, age-, and education level-matched healthy controls (HCs) who underwent high-resolution T1-weighted magnetic resonance scans. Voxel-based morphometry (VBM) was adopted to calculate the GMV differences between two groups. Then we analyzed the spatial correlation between depression-induced alteration in GMV and density maps of 10 receptors/transporters deriving from prior molecular imaging in healthy people. Compared to HCs, the depression group had significantly increased GMV in the left ventral portions of the ventral medial prefrontal cortex, parahippocampal gyrus, amygdala, the right superior parietal lobule and precuneus while decreased GMV in the bilateral hippocampus extending to the thalamus and cerebellum. The GMV alteration introduced by depression was spatially correlated with serotonin receptors (5-HT1a, 5-HT1b, and 5-HT2a), dopamine receptors (D1 and D2) and GABAergic receptor (GABAa) densities. The conclusions drawn in this study were obtained from a single dataset. This study reveals abnormal GMV alteration and provides a series of neurotransmitters receptors possibly related to GMV alteration in depression, which facilitates an integrative understanding of the molecular mechanism underlying the structural abnormalities in depression and may provide clues to new treatment strategies.