Abstract
Advances 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 with healthy controls and investigate whether 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 randomized, 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 (40 IU) or placebo over 18–26 min post dosing, as we have previously shown robust OT-induced changes in resting rCBF in men in a similar time-window (15–36 min 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 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 intranasal OT on perfusion abnormalities in these patients, at least for the specific dose (40 IU) and post-dosing interval (18–26 min) examined. 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. They also highlight the need for a comprehensive investigation of intranasal OT pharmacodynamics in women before we can fully ascertain its therapeutic value in disorders affecting predominantly this gender, such as BN/BED.
Highlights
Bulimia nervosa (BN) and binge-eating disorder (BED)are psychiatric disorders characterized by recurrent binge eating[1]
We have previously shown that arterial spin labelling (ASL) captures OT-induced changes as early as 15–36 min post dosing in resting regional cerebral blood flow (rCBF) after a single acute intranasal administration (40 IU) in both healthy men[48,49] and men at clinical high-risk for psychosis (CHR-P)[50]
Our choice of OT dose and post dosing interval was driven by our previous work, whereby we have shown that 40 IU intranasal OT induce robust changes in rCBF in both healthy men[48,49] and men at CHR-P50
Summary
Bulimia nervosa (BN) and binge-eating disorder (BED)are psychiatric disorders characterized by recurrent binge eating[1]. BN/BED have been conceptualized as impulsive/compulsive eating disorders[4] with altered reward sensitivity[5] and food-related attentional biases[6] Consistent with this model of BN/BED, neuroimaging studies in these patients. All with small sample sizes, used singlephoton emission computerized tomography (SPECT) to measure regional cerebral blood flow (rCBF), which provides a proxy of brain metabolism and neural activity[15]. These studies reported rCBF increases in the temporal lobes and/or the frontal cortex of patients with BN and BED in response to anticipation or exposure to food/body shape-related stimuli[16,17,18]. SPECT is a high-cost technique that requires the injection of a radionuclide tracer, making it suboptimal as a routine screening tool in non-specialized centres or for evaluating short-term responses[19]
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