Prefrontal-limbic-striatum dysconnectivity associated with negative emotional endophenotypes in bipolar disorder during depressive episodes

Background: The prefrontal-limbic-subcortical network has been suggested as an important circuitry in the pathophysiology underlying bipolar disorder during depressive episodes (BDD). However, the relationships between disrupted prefrontal-limbic-subcortical connection and the emotional endophenotypes in BDD patients remain largely unclear. Methods: Forty-three BDD patients and 63 matched healthy controls (HCs) underwent the resting-state functional magnetic resonance imaging scan. The altered clusters were first identified by using a spatial pairwise clustering method and then were extracted as regions of interest to calculate the functional connectivity (FC). Group comparisons were conducted to identify the abnormal FCs. Classification analysis was employed to examine whether the altered FCs could distinguish BDD from HCs. The relationships between FC alterations and the emotional endophenotypes as measured by the Affective Neuroscience Personality Scales (ANPS) were further detected in BDD. Results: Compared with HCs, BDD patients showed abnormal FCs in the prefrontal-limbic-striatum circuit. Importantly, the altered FCs yielded 84.91% accuracy (p< 1/5000) with 93.65% sensitivity and 72.09% specificity in differentiating between BDD and HCs. Moreover, the decreased FCs in the prefrontal-striatum and prefrontal-limbic systems were positively correlated with negative emotional endophenotypes of Sadness and Fear scores. Conclusions: The findings demonstrated that prefrontal-limbic-striatum disconnection may be identified as a potential effective biomarker for BDD, which could help further explain the neurobiological mechanisms underlying BDD.

Automated summary

The study identified abnormal functional connectivity in the prefrontal-limbic-striatum circuit in patients with bipolar disorder during depressive episodes, which could serve as a potential effective biomarker for distinguishing patients from healthy controls and was positively correlated with negative emotional endophenotypes such as Sadness and Fear.