Connectome architecture modulates the gray matter atrophy in major depression disorder patients with diverse suicidal ideations.

Gray matter (GM) atrophy is well documented in patients with major depressive disorder (MDD), but its underlying mechanism remains unknown. This study aimed to examine the GM atrophy in MDD patients with diverse suicidal ideations (SIs) and to explore whether those alterations were driven by connections. GM volume was estimated in 163 patients with recurrent MDD (comprising 122 with SI [MDDSI] and 41 without SI [MDDNSI]) and 134 health controls (HCs). A two-sample t-test was used to identify GM volume abnormalities in MDD patients and their subgroups. Functional connectivity was computed between pairs of aberrant GM in both patients and HCs, which were further compared with the connectivity of random brain regions. A permutation test was performed to assess its significance. Propensity score matching (PSM) was further performed to validate the main results. Compared with HCs, the MDDNSI group exhibited GM atrophy in 24 regions, with the largest effect sizes found in the frontal and parietal lobes, while the MDDSI group exhibited more widespread GM atrophy involving 49 regions, with the largest effect sizes in the frontal lobe, parietal lobe, temporal lobe, and the limbic system. Furthermore, patients and HCs exhibited significantly increased functional connectivity between regions with GM atrophy compared with randomly selected regions (p < 0.05). PSM analysis presented similar results to the main analysis. MDD patients had diverse GM atrophy features according to their SI tendency. Moreover, connectome architecture modulates the GM atrophy in MDD patients, implying the possibility that connections drive these pathological changes.