Dysfunctional connectivity between raphe nucleus and subcortical regions presented opposite differences in bipolar disorder and major depressive disorder

Abstract

As the source of most serotonergic neurons projecting throughout the brain, the raphe nucleus has been repeatedly implicated in bipolar disorder (BD) and major depressive disorder (MDD). However, whether the functional connectivity (FC) of the raphe nucleus is altered differently in BD and MDD patients is not well understood. In the current study, we aimed to find the difference in altered FC of the raphe nucleus in BD and MDD patients. Resting-state functional magnetic resonance imaging data from 40 BD patients, 54 MDD patients and 44 matched healthy controls (HCs) were collected. Seed-based FC of the raphe nucleus was calculated in three groups and compared using statistical tests. Results showed that BD patients mainly presented increased FC in cortical regions and decreased FC in subcortical regions. MDD patients presented overall decreased FC. The overlapping abnormalities found in BD and MDD patients were very low. Functional connections of subcortical regions such as the thalamus, putamen and hippocampus connected to the raphe nucleus presented opposite differences in BD and MDD patients compared with HCs. In MDD patients, these differences were correlated with the total scores of the Beck Hopelessness Scale. Thus, BD and MDD patients presented opposite differences in altered FC of the raphe nucleus mainly in subcortical regions. Altered functional connectivity of subcortical regions connected to the raphe nucleus played different roles in the physiological mechanisms between BD and MDD and could help us understand specific pathogenesis between BD and MDD patients.

Keywords: Depression; Functional connectivity; Raphe nucleus; Serotonin.