Altered fimbria-fornix white matter integrity in anorexia nervosa predicts harm avoidance

Abstract

The eating disorder anorexia nervosa (AN) is associated with high anxiety. The brain mechanisms that drive those behaviors are unknown. In this study we wanted to test whether brain WM integrity is altered in AN, and related to heightened anxiety. Sixteen adult women with AN (mean age 24±7 years) and 17 healthy control women (CW, mean age 25±4 years) underwent diffusion tensor imaging (DTI) of the brain. The DTI brain images were used to calculate the fractional anisotropy (FA) of WM tracts, which is a measure for WM integrity. AN individuals compared to CW showed clusters of significantly reduced FA (p<0.05, corrected) in the bilateral fimbriafornix, fronto-occipital fasciculus, as well as posterior cingulum WM. In the AN group, Harm Avoidance was predicted by left (F=5.8, Beta=−0.54, p<0.03) and right (F=6.0, Beta=−0.55, p<0.03) fimbria-fornix FA. Those findings were not due to WM volume deficits in AN. This study indicates that WM integrity is abnormal in AN in limbic and association pathways, which could contribute to disturbed feeding, emotion processing and body perception in AN. The prediction of Harm Avoidance in AN by fimbria-fornix WM integrity suggests that this pathway may be mechanistically involved in high anxiety in AN.

Abnormal White Matter Properties in Adolescent Girls With Anorexia Nervosa

“…Consistent with our initial predictions, measures for R1 also demonstrated significant decreases in the AN as compared to the control group within cerebral white matter tracts previously found to have altered white matter microstructure during adulthood and adolescence (Frank et al, 2013;Frieling et al, 2012;Kazlouski et al, 2011). In addition to these pathways, we observed evidence for significantly decreased R1 in bilateral segments of the arcuate fasciculus and medial and posterior subdivisions of the corpus callosum.…”

“…Consistent with our initial predictions, measures for FA were found to be significantly decreased in the AN as compared to the control group within cerebral white matter tracts previously found to have decreased FA during adulthood and adolescence (Frank et al, 2013;Frieling et al, 2012;Kazlouski et al, 2011), including bilateral segments of the fimbria-fornix and the right aSLF. Evidence for decreased FA in adolescents with AN suggests that structural differences within these pathways are already present after a relatively short duration of illness.…”

“…These estimates are comparable to a previous dMRI study of AN in which significant FA differences were observed for these pathways (Frieling et al, 2012). However, a study with a sample only slightly larger than the present study was able to detect evidence for significant group differences in FA of the inferior fronto-occipital fasciculus and cingulate (Kazlouski et al, 2011).…”

“…Lack of significant group differences within the cingulate and inferior fronto-occipital fasciculus tracts may also be explained by methodological differences between tractography versus voxel-based studies of AN (Frank et al, 2013;Frieling et al, 2012;Kazlouski et al, 2011). Studies that use whole brain voxel-based methods are susceptible to error based on challenges in the co-registration and normalization process that might result in subtle but significant differences in the composition of voxels in terms of cerebral spinal fluid, gray matter and white matter (Jones and Cercignani, 2010).…”

“…Regions for decreased FA have been observed in distributed cortical white matter brain areas, including the bilateral fimbria-fornix, fronto-occipital fasciculus, posterior cingulate (Frank et al, 2013;Kazlouski et al, 2011), superior and posterior corona radiata (Frank et al, 2013;Frieling et al, 2012), optic radiations (Frieling et al, 2012), and the superior longitudinal fasciculus (Frieling et al, 2012;Via et al, 2014). However, not all studies of AN observe changes in FA (Yau et al, 2013).…”