Global hippocampus functional connectivity as a predictive neural marker for conversion to future mood disorder in unaffected offspring of bipolar disorder parents

Objectives: Hippocampus-related functional alteration in genetically at-risk individuals may reflect an endo-phenotype of a mood disorder. Herein, we performed a prospective study to investigate whether baseline hip-pocampus functional connectivity (FC) in offspring of patients with bipolar disorder (BD) would predict subsequent conversion to mood disorder.Methods: Eighty bipolar offspring and 40 matched normal controls (NC) underwent resting state functional MRI (rsfMRI) scanning on a 3.0 Tesla MR scanner. The offspring were subdivided into asymptomatic offspring (AO) (n = 41) and symptomatic offspring (SO) (n = 39) according to whether they manifested subthreshold mood symptoms. After identifying the different hippocampus FCs between the AO and SO, a logistic regression analysis was conducted to investigate whether the baseline hippocampus FCs predicted a future mood disorder during a 6-year follow-up.Results: We identified seven baseline para/hippocampus FCs that showed differences between AO and SO, which were entered as predictive features in the logistic regressive model. Of the 80 bipolar offspring entering the analysis, the FCs between left hippocampus and left precuneus, and between right hippocampus and left pos-terior cingulate, showed a discriminative capacity for predicting future mood disorder (area-under-curve, or AUC=75.76 % and 75.00 % respectively), and for predicting BD onset (AUC=77.46 % and 81.63 %, respectively).Conclusions: The present findings revealed high predictive utility of the hippocampus resting state FCs for future mood disorder and BD onset in individuals at familial risk. These neural markers can potentially improve early detection of individuals carrying particularly high risk for future mood disorder.