Abnormal white matter properties in adolescent girls with anorexia nervosa

Abstract

Anorexia nervosa (AN) is a serious eating disorder that typically emerges during adolescence and occurs most frequently in females. To date, very few studies have investigated the possible impact of AN on white matter tissue properties during adolescence, when white matter is still developing. The present study evaluated white matter tissue properties in adolescent girls with AN using diffusion MRI with tractography and T1 relaxometry to measure R1 (1/T1), an index of myelin content. Fifteen adolescent girls with AN (mean age = 16.6 years ± 1.4) were compared to fifteen age-matched girls with normal weight and eating behaviors (mean age = 17.1 years ± 1.3). We identified and segmented 9 bilateral cerebral tracts (18) and 8 callosal fiber tracts in each participant's brain (26 total). Tract profiles were generated by computing measures for fractional anisotropy (FA) and R1 along the trajectory of each tract. Compared to controls, FA in the AN group was significantly decreased in 4 of 26 white matter tracts and significantly increased in 2 of 26 white matter tracts. R1 was significantly decreased in the AN group compared to controls in 11 of 26 white matter tracts. Reduced FA in combination with reduced R1 suggests that the observed white matter differences in AN are likely due to reductions in myelin content. For the majority of tracts, group differences in FA and R1 did not occur within the same tract. The present findings have important implications for understanding the neurobiological factors underlying white matter changes associated with AN and invite further investigations examining associations between white matter properties and specific physiological, cognitive, social, or emotional functions affected in AN.

Keywords: Adolescents; Anorexia-nervosa; Diffusion; Quantitative MRI; White matter.

Fig. 1

Tractography of 26 major cerebral and callosal white matter tracts. Left hemisphere cerebral tracts are displayed on mid-sagittal T1 images from a representative control subject (a–c). Right hemisphere tract renderings not shown. Panel a illustrates the following cerebral white matter tracts: arcuate fasciculus (Arc) = yellow; corticospinal tract (CST) = blue; uncinate fasciculus (UF) = purple; fimbria-fornix (F-F) = red. Panel b illustrates the following cerebral white matter tracts: anterior thalamic radiation (ATR) = light blue; cingulum (Cing) = pink; inferior fronto-occipital fasciculus (IFOF) = orange; inferior longitudinal fasciculus (ILF) = green; anterior superior longitudinal fasciculus (aSLF) = lavender. Panel c illustrates 8 subdivisions of the corpus callosum: orbitofrontal (Orb Frontal) = dark red; anterior frontal (Ant. Frontal) = green; superior frontal (Sup. Frontal) = purple; motor = yellow; superior parietal (Sup. Parietal) = blue; posterior (Post. Parietal) = orange; temporal = brown; occipital = teal. Dashed lines represent the location of the regions of interest (ROIs) used to isolate each cerebral tract; ROI 1, white; ROI 2, black. ROIs are not indicated for F-F (red lettering) as this tract was segmented manually.

Fig. 2

FA and R1 tract profiles for the AN and control group for 18 cerebral white matter pathways. Mean FA (a1–a18) and Mean R1 (b1–b18) tract profiles are shown for each of the cerebral tracts depicted in Fig. 1a,b for the AN group (solid purple line) and the control group (solid green line). Group Mean FA and Mean R1 values are plotted for 100 equidistant nodes between the two ROIs used to isolate the core of each tract. Vertical bars along FA and R1 tract profiles indicate ± 1 standard error of the mean. Tracts demonstrating significant group differences (p < 0.05, uncorrected) are indicated with a single *. Tracts demonstrating group differences that were significant (p < 0.05) after correcting for along tract comparisons are indicated with two **. Tracts demonstrating group differences that were significant (p < 0.05) after correcting for between and along tract comparisons are indicated with three ***. ATR = anterior thalamic radiations; Cing = cingulate; CST = corticospinal tract; IFOF = inferior fronto-occipital fasciculus; ILF = inferior longitudinal fasciculus; aSLF = anterior superior longitudinal fasciculus; ARC = arcuate fasciculus; UF = uncinate fasciculus; F-F = fimbria-fornix; L = left; R = right.

Fig. 3

FA and R1 tract profiles for the AN and control group for 8 subdivisions of the corpus callosum. Mean FA (a1–a8) and Mean R1 (b1–b8) tract profiles are shown for each of the cerebral tracts depicted in Fig. 1c for the AN group (solid purple line) and the control group (solid green line). Group Mean FA and Mean R1 values are plotted for 100 equidistant nodes between the two ROIs used to isolate the core of each tract. Vertical bars along FA and R1 tract profiles indicate ± 1 standard error of the mean. Tracts demonstrating group differences that were significant (p < 0.05) after correcting for along tract comparisons are indicated with two **. Tracts demonstrating group differences that were significant (p < 0.05) after correcting for between and along tract comparisons are indicated with three ***. Ant = anterior; Orb = orbital; Sup = superior; Post = posterior.