Neuroimaging Markers of Risk, Disease Expression, and Resilience to Bipolar Disorder

Familial predisposition to bipolar disorder is associated with increased risk of affective morbidity in the first-degree relatives of patients. Nevertheless, a substantial proportion of relatives remain free of psychopathology throughout their lifetime. A series of studies reviewed here were designed to test whether resilience in these high-risk individuals is associated with adaptive brain plasticity.

The findings presented here derive from structural and functional magnetic resonance imaging data obtained from patients, their resilient first-degree relatives, and healthy individuals. Patients and relatives showed similar abnormalities in activation and connectivity while performing tasks of interference control and facial affect recognition and in the resting-state connectivity of sensory and motor regions. Resilient relatives manifested unique neuroimaging features that differentiated them from patients and healthy individuals. Specifically, they had larger cerebellar vermis volume, enhanced prefrontal connectivity during task performance, and enhanced functional integration of the default mode network in task-free conditions. Resilience to bipolar disorder is not the reverse of risk but is associated with adaptive brain changes indicative of increased neural reserve. This line of research may open new avenues in preventing and treating bipolar disorder.