Cingulum White Matter in Young Women at Risk of Depression: The Effect of Family History and Anhedonia

Background: Altered white matter microstructure in tracts integral to mood regulation networks could underlie vulnerability to major depressive disorder (MDD). Guided by functional magnetic resonance studies, we explored whether a positive family history of MDD (FH+) and anhedonia (reduced capacity for pleasure) were associated with altered white matter microstructure in the cingulum bundles and uncinate fasciculi. Methods: Diffusion tensor magnetic resonance imaging data were acquired on 34 healthy female student volunteers (mean age 22 years). Exclusion criteria included other current or previous psychiatric disorder, current depression, and current psychotropic medication. Family history was determined using established criteria. Fiber tractography was performed for each individual for a priori tracts of interest and a comparison tract. Mean fractional anisotropy (FA), an index of microstructure, was calculated for each tract. Results: Tracts were reconstructed in 18 FH+ individuals and 15 FH-individuals, who did not differ by age or subclinical depressive symptoms. FH+ subjects had 3% to 5% lower FA in the right and left cingulum bundles than FH-individuals (p = .012, p = .059, respectively). Post hoc analysis demonstrated 8% lower FA in the left subgenual cingulate (p = .007). Hedonic tone correlated positively with FA in the right and left cingulum bundles (r = .342, p = .052; r = .477, p = .005, respectively), and the left subgenual cingulum (r = .500, p = .003). Conclusions: Both family history of MDD and subclinical anhedonia are associated with reduced FA in the bilateral cingulum bundles, particularly in the left subgenual cingulum. Altered cingulum white matter architecture is implicated in the etiology of MDD.