Brain structural and functional correlates of resilience to Bipolar Disorder

Background: Resilient adaptation can be construed in different ways, but as used here it refers to adaptive brain responses associated with avoidance of psychopathology despite expressed genetic predisposition to Bipolar Disorder (BD). Although family history of BD is associated with elevated risk of affective morbidity a significant proportion of first-degree relatives remain free of psychopathology. Examination of brain structure and function in these individuals may inform on adaptive responses that pre-empt disease expression. Methods: Data presented here are derived from the Vulnerability to Bipolar Disorders Study (VIBES) which includes BD patients, asymptomatic relatives and controls. Participants underwent extensive investigations including brain structural (sMRI) and functional magnetic resonance imaging (fMRI). We present results from sMRI voxel-based-morphometry and from conventional and connectivity analyses of fMRI data obtained during the Stroop Colour Word Test (SCWT), a task of cognitive control during conflict resolution. All analyses were implemented using Statistical Parametric Mapping software version 5 (SPM5). Resilience in relatives was operationalized as the lifetime absence of clinical-range symptoms. Results: Resilient relatives of BD patients expressed structural, functional, and connectivity changes reflecting the effect of genetic risk on the brain. These included increased insular volume, decreased activation within the posterior and inferior parietal regions involved in selective attention during the SCWT, and reduced fronto-insular and fronto-cingulate connectivity. Resilience was associated with increased cerebellar vermal volume and enhanced functional coupling between the dorsal and the ventral prefrontal cortex during the SCWT. Conclusions: Our findings suggests the presence of biological mechanisms associated with resilient adaptation of brain networks and pave the way for the identification of outcome-specific trajectories given a bipolar genotype.