Hippocampal cingulum white matter increases over time in young people at high genetic risk for bipolar disorder

Background: Bipolar disorder (BD) is a strongly familial psychiatric disorder associated with white matter (WM) brain abnormalities. It is unclear whether such abnormalities are present in relatives without BD, and little is known about WM trajectories in those at increased genetic risk.Methods: Diffusion magnetic resonance imaging (dMRI) data were acquired at baseline and after two years in 91 unaffected individuals with a first-degree relative with bipolar disorder (HR), and 85 individuals with no family history of mental illness (CON). All participants were aged between 12 and 30 years at baseline. We examined longitudinal change in Fractional Anisotropy (FA) using tract-based spatial statistics (TBSS).Results: Compared to the CON group, HR participants showed a significant increase in FA in the right cingulum (hippocampus) (CGH) over a two-year period (p < .05, FDR corrected). This effect was more pronounced in HR individuals without a lifetime diagnosis of a mood disorder than those with a mood disorder.Limitations: While our study is well powered to achieve the primary objectives, our sub-group analyses were under powered. Conclusions: In one of the very few longitudinal neuroimaging studies of young people at high risk for BD, this study reports novel evidence of atypical white matter development in HR individuals in a key cortico-limbic tract involved in emotion regulation. Our findings also suggest that this different white matter developmental tra-jectory may be stronger in HR individuals without affective psychopathology. As such, increases in FA in the right CGH of HR participants may be a biomarker of resilience to mood disorders.

Automated summary

This study found that individuals with first-degree relatives with bipolar disorder have white matter abnormalities in a key cortico-limbic tract, with this effect being more pronounced in individuals without a mood disorder diagnosis.