Diffusion tensor imaging correlates of early markers of depression in youth at high-familial risk for bipolar disorder

Background: Mood disorders are familial psychiatric diseases, in which patients show reduced white matter (WM) integrity. We sought to determine whether WM integrity was affected in young offspring at high-familial risk of mood disorder before they go on to develop major depressive disorder (MDD). Methods: The Bipolar Family study is a prospective longitudinal study examining young individuals (age 16-25 years) at familial risk of mood disorder on three occasions 2 years apart. This study used baseline imaging data, categorizing groups according to clinical outcome at follow-up. Diffusion tensor MRI data were acquired for 61 controls and 106 high-risk individuals, the latter divided into 78 high-risk subjects who remained well throughout the study ('high-risk well') and 28 individuals who subsequently developed MDD ('high-risk MDD'). Voxel-wise between-group comparison of fractional anisotropy (FA) based on diagnostic status was performed using tract-based spatial statistics (TBSS). Results: Compared to controls, both high-risk groups showed widespread decreases in FA (p(corr) < .05) at baseline. Although FA in the high-risk MDD group negatively correlated with subthreshold depressive symptoms at the time of scanning (p(corr) < .05), there were no statistically significant differences at p-corrected levels between the two high-risk groups. Conclusions: These results suggest that decreased FA is related to the presence of familial risk for mood disorder along with subdiagnostic symptoms at the time of scanning rather than predictive of subsequent diagnosis. Due to the difficulties performing such longitudinal prospective studies, we note, however, that this latter analysis may be underpowered due to sample size within the high-risk MDD group. Further clinical follow-up may clarify these findings.