Investigating resting brain perfusion abnormalities and target-engagement by intranasal oxytocin in women with bulimia nervosa and binge-eating disorder and healthy controls

Abstract

ABSTRACTAdvances in the treatment of bulimia nervosa and binge eating disorder (BN/BED) have been marred by our limited understanding of the underpinning neurobiology. Here we measured regional cerebral blood flow (rCBF) to map resting perfusion abnormalities in women with BN/BED compared to healthy controls and investigate if intranasal oxytocin (OT), proposed as a potential treatment, can restore perfusion in disorder-related brain circuits. Twenty-four women with BN/BED and 23 healthy women participated in a randomised, double-blind, crossover, placebo-controlled study. We used arterial spin labelling MRI to measure rCBF and the effects of an acute dose of intranasal OT (40IU) or placebo over 18-26 minutes post-dosing, as we have previously shown robust OT-induced changes in resting rCBF in men 15-36min post-dosing. We tested for effects of treatment, diagnosis and their interaction on extracted rCBF values in anatomical regions-of-interest previously implicated in BN/BED by other neuroimaging modalities, and conducted exploratory whole-brain analyses to investigate previously unidentified brain regions. We demonstrated that women with BN/BED presented increased resting rCBF in key neural circuits previously implicated in BN/BED pathophysiology, namely the medial prefrontal and orbitofrontal cortices, anterior cingulate gyrus, posterior insula and middle/inferior temporal gyri bilaterally. Hyperperfusion in these areas specifically correlated with eating symptoms severity in patients. Our data did not support a normalizing effect of 40IU intranasal OT on perfusion abnormalities in these patients 18-26 minutes post-dosing. Our findings enhance our understanding of resting brain abnormalities in BN/BED and identify resting rCBF as a non-invasive potential biomarker for disease-related changes and treatment monitoring.