Differentiation of Transformed Bipolar Disorder From Unipolar Depression by Resting-State Functional Connectivity Within Reward Circuit

Previous studies have found that neural functional abnormalities detected by functional magnetic resonance imaging (fMRI) in brain regions implicated in reward processing during reward tasks show promise to distinguish bipolar from unipolar depression (UD), but little is known regarding resting-state functional connectivity (rsFC) within the reward circuit. In this study, we investigated neurobiomarkers for early recognition of bipolar disorder (BD) by retrospectively comparing rsFC within the reward circuit between UD and depressed BD. Sixty-six depressed patients were enrolled, none of whom had ever experienced any manic/hypomanic episodes before baseline. Simultaneously, 40 matched healthy controls (HC) were also recruited. Neuroimaging data of each participant were obtained from resting-state fMRI scans. Some patients began to manifest bipolar disorder (tBD) during the follow-up period. All patients were retrospectively divided into two groups (33 tBD and 33 UD) according to the presence or absence of mania/hypomania in the follow-up. rsFC between key regions of the reward circuit was calculated and compared among groups. Results showed decreased rsFC between the left ventral tegmental area (VTA) and left ventral striatum (VS) in the tBD group compared with the UD group, which showed good accuracy in predicting diagnosis (tBD vs. UD) according to receiver operating characteristic (ROC) analysis. No significant different rsFC was found within the reward circuit between any patient group and HC. Our preliminary findings indicated that bipolar disorder, in early depressive stages before onset of mania/hypomania attacks, already differs from UD in the reward circuit of VTA-VS functional synchronicity at the resting state.