Localized Brain Volume and White Matter Integrity Alterations in Adolescent Anorexia Nervosa

Abstract

Objective The neurobiological underpinnings of anorexia nervosa (AN) are poorly understood. In this study we tested whether brain gray matter (GM) and white matter (WM) in adolescents with AN would show alterations comparable to adults. Method We used magnetic resonance imaging to study GM and WM volume, and diffusion tensor imaging to assess fractional anisotropy for WM integrity in 19 adolescents with AN and 22 controls. Results Individuals with AN showed greater left orbitofrontal, right insular, and bilateral temporal cortex GM, as well as temporal lobe WM volumes compared to controls. WM integrity in adolescents with AN was lower (lower fractional anisotropy) in fornix, posterior frontal, and parietal areas, but higher in anterior frontal, orbitofrontal, and temporal lobes. In individuals with AN, orbitofrontal GM volume correlated negatively with sweet taste pleasantness. An additional comparison of this study cohort with adult individuals with AN and healthy controls supported greater orbitofrontal cortex and insula volumes in AN across age groups. Conclusions This study indicates larger orbitofrontal and insular GM volumes, as well as lower fornix WM integrity in adolescents with AN, similar to adults. The pattern of larger anteroventral GM and WM volume as well as WM integrity, but lower WM integrity in posterior frontal and parietal regions may indicate that developmental factors such as GM pruning and WM growth could contribute to brain alterations in AN. The negative correlation between taste pleasantness and orbitofrontal cortex volume in individuals with AN could contribute to food avoidance in this disorder.

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.…”

“…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).…”

“…Failure to find group differences may be related to the biology of AN, such as stage of recovery following treatment (Yau et al, 2013), but may also reflect limitations in voxel-based methods for analyzing dMRI data (Jones and Cercignani, 2010), or difficulty detecting group FA differences with small sample sizes (De Santis et al, 2014). To our knowledge, only a single study has examined diffusion property changes associated with AN during adolescence (Frank et al, 2013). We require further studies of adolescents with AN to gain deeper understanding for whether changes in white matter properties during adulthood reflect persistent structural differences inherent to AN neuropathology beginning in adolescence, late alterations in tissue microstructure during adulthood, compensatory processes secondary to physiological manifestations of AN, or a combination of these possibilities.…”