The Role of Intrinsic Brain Functional Connectivity in Vulnerability and Resilience to Bipolar Disorder

Objective: Bipolar disorder is a heritable disorder characterized by mood dysregulation associated with brain functional dysconnectivity. Previous research has focused on the detection of risk-and disease-associated dysconnectivity in individuals with bipolar disorder and their first-degree relatives. The present study seeks to identify adaptive brain connectivity features associatedwith resilience, defined here as avoidance of illness or delayed illness onset in unaffected siblings of patients with bipolar disorder. Method: Graph theoretical methods were used to examine global and regional brain network topology in head-motioncorrected resting-state functional MRI data acquired from 78 patients with bipolar disorder, 64 unaffected siblings, and 41 healthy volunteers. Results: Global network propertieswere preserved in patients and their siblings while both groups showed reductions in the cohesiveness of the sensorimotor network. In the patient group, these sensorimotor network abnormalities were coupled with reduced integration of core default mode network regions in the ventromedial cortex and hippocampus. Conversely, integrationof thedefaultmodenetworkwas increased in the sibling group comparedwith both the patient group and the healthy volunteer group. Conclusions: Theauthors foundthat trait-related vulnerability to bipolar disorder was associated with reduced resting-state cohesiveness of the sensorimotor network in patients with bipolar disorder. However, integration of the default mode network emerged as a key feature differentiating disease expression and resilience between the patients and their siblings. This is indicative of the presence of neural mechanisms that may promote resilience, or at least delay illness onset.