Bipolar Mood State Reflected in Functional Connectivity of the Hate Circuit: A Resting-State Functional Magnetic Resonance Imaging Study

BACKGROUND: Previous studies suggested bipolar disorder caused an aberrant alteration in the insular, putamen, and left superior frontal gyrus, which are the main components of the hate circuit. However, the relationship between the hate circuit and the pathophysiologic substrate underlying different phases of bipolar disorder remain unclear. In this study, we aimed to identify group differences of resting-state functional connectivity within the hate circuit in healthy controls (HCs) and bipolar patients in different mood states. METHODS: Resting-state functional magnetic resonance imaging of the brain were acquired from 54 HCs and 81 patients with bipolar disorder including 20 with bipolar mania (BM), 35 with bipolar depression (BD), and 26 with bipolar euthymia (BE). We selected bilateral insula (L.INS and R.INS), bilateral putamen (L.PUT and R.PUT), and left superior frontal gyrus (L.SFGd) as seed regions, and conducted the seed-based functional connectivity analysis to identify group differences of connectivity strength within the hate circuit. Spearman correlations were performed to evaluate the relationship between the hate circuit and manic/depressive symptoms. RESULTS: Significant group differences of connectivity strength within the hate circuit were found in links of the R.INS-L.SFGd, R.PUT-L.SFGd, and L.INS- R.PUT after false discovery rate was corrected. The BM group showed an opposite hate circuit pattern to BD, BE, and HCs. The BD group showed decreased hate circuit connectivity in the L.INS-R.PUT compared with the BE group. No significant difference was detected among BD, BE, and HCs. Furthermore, functional connectivity of the R.INS-L.SFGd and R.PUT-L.SFGd were positively correlated with manic symptoms, while the L.INS- R.PUT was negatively correlated with depressive symptoms. CONCLUSIONS: Our preliminary findings suggest that altered functional connectivity of the hate circuit in different mood phases may be related to state markers and underpin the neuropathological basis of bipolar disorder.