Longitudinal differences in white matter integrity in youth at high familial risk for bipolar disorder

Previous neuroimaging studies have reported abnormalities in white matter (WM) pathways in subjects at high familial risk of mood disorders. In the current study, we examined the trajectory of these abnormalities during the early stages of illness development using longitudinal diffusion tensor imaging (DTI) data.Subjects (16-28 years old) were recruited in the Scottish Bipolar Family Study, a prospective longitudinal study that has examined individuals at familial risk of mood disorder on three occasions, 2 years apart. The current study concerns imaging data from the first and second assessments. We analysed DTI data for 43 controls and 69 high-risk individuals who were further subdivided into a group of 53 high-risk subjects who remained well (high-risk well) and 16 who met diagnostic criteria for major depressive disorder (high-risk MDD) at follow-up. Longitudinal differences in fractional anisotropy (FA) between groups based on diagnostic status were investigated using the tract-based spatial statistics technique (TBSS).We found a significant reduction in FA (Pcorr <.05) across widespread brain regions over 2 years in all three groups. The trajectory of FA reduction did not differ significantly between groups.These results suggest that there are similar trajectories of FA reductions for controls and high-risk young adults, despite high-risk individuals being at a disadvantaged starting point considering their reduced WM integrity detected at baseline in previous studies. Difference in WM integrity between high-risk individuals and controls could therefore occur in earlier childhood and be a necessary but not sufficient condition to develop future mood disorders.