Myo-Inositol Levels in the Dorsal Anterior Cingulate Cortex Are Associated With Anxiety-to-Eat in Anorexia Nervosa.

While substantial research has focused on general anxiety in anorexia nervosa (AN), eating-related anxiety is insufficiently understood and less is known about its underlying neurobiological mechanisms. We integrated behavioral and magnetic resonance spectroscopy (MRS) methods to characterize anxiety-to-eat and to identify its neurometabolic correlates in females with AN (n = 16) and in healthy weight females without a lifetime history of an eating disorder (healthy controls; HC; n = 16). Anxiety-to-eat was assessed via a computer-based task in which participants rated their level of anxiety-to-eat on a visual analogue scale in response to images of a standard serving of higher (HED) and lower energy density (LED) foods. Levels of nine neurometabolites in the dorsal anterior cingulate cortex (dACC), a brain region putatively involved in modulating anxiety-related responses, were assessed using edited MRS. The AN group reported greater anxiety-to-eat in response to HED and LED foods relative to the HC group. Both groups reported greater anxiety-to-eat in response to HED relative to LED foods. The neurometabolite myo-inositol (myo-I), a carbocyclic sugar and precursor molecule to phosphatidyl-inositol species in second-messenger systems shown to be dysregulated in AN (e.g., adrenergic, serotonergic, glutamatergic), was lower in the dACC in AN relative to HC. Additionally, in the AN group only, myo-I levels negatively predicted anxiety-to-eat in response to HED but not LED foods independent of body mass index, duration of illness, and general anxiety. These findings raise the possibility that lower myo-I in the dACC and its relationship with anxiety-to-eat responses in AN reflect a distinct biological and behavioral phenotype of AN pathology. To understand the clinical implications of these findings, future studies should investigate the effect of treatment on myo-I levels or directly manipulate myo-I levels in the diet and assess resulting changes in anxiety-to-eat.