• The Influence of Oxytocin on Eating Behaviours and Stress in Women with Bulimia Nervosa and Binge Eating Disorder

      Leslie, Monica; Leppanen, Jenni; Paloyelis, Yannis; Treasure, Janet; King's College London (Elsevier, 2018-12-21)
      The current study aimed to test the influence of oxytocin on palatable food intake, 24-hour caloric consumption, and stress in women with bulimia nervosa and binge eating disorder. We recruited 25 women with DSM-5 bulimia nervosa or binge eating disorder, and 27 weight-matched comparison women without history of an eating disorder. We employed a double-blind, placebo-controlled crossover design in which each participant attended the lab for two experimental sessions, receiving a divided dose of 64IU intranasal oxytocin in one session and equivalent volume of placebo nasal spray in the opposite session. The order of administration was pseudo-randomised across participants. We hypothesised that a divided dose of 64IU intranasal oxytocin administration would reduce subjective hunger, the immediate consumption of palatable food, 24-hour calorie consumption, and the incidence of binge eating when compared to placebo. We also hypothesised that oxytocin administration would be associated with lower levels of stress and salivary cortisol, and that there would be an interaction with participant group such that oxytocin would reduce eating behaviour and stress to a greater degree in women with bulimia nervosa or binge eating disorder, compared to women without history of an eating disorder. We did not find a significant effect of oxytocin on any of the measurements of eating behaviour, subjective stress, or salivary cortisol. We recommend that future studies test the dose-response effect of oxytocin on eating behaviours and stress in human populations with eating disorders to further clarify the moderating factors for oxytocin’s effect on eating.
    • The Influence of Oxytocin on Risk-Taking in the Balloon Analogue Risk Task Among Women with Bulimia Nervosa and Binge Eating Disorder

      Leslie, Monica; Leppanen, Jenni; Paloyelis, Yannis; Nazar, Bruno; Treasure, Janet; King's College London; Federal University of Rio de Janeiro
      Previous theoretical models of bulimia nervosa (BN) and binge eating disorder (BED) have implicated cross-domain risk-taking behaviour as a significant maintenance factor in both disorders. The current study sought to test this hypothesis by administering the Balloon Analogue Risk Task (BART) to 25 women with BN or BED and 27 healthy comparison women without history of an eating disorder. Furthermore, we tested the effect of a divided dose of 64IU oxytocin on risk-taking behaviour in the BART. Contrary to our hypothesis, women with BN or BED did not exhibit baseline differences in performance on the BART in the placebo condition (t = 1.42, df = 50, p = .161, d = 0.39). Oxytocin did not have a main effect on performance in the BART (F = 0.01, df = 1, p = .907, η2partial < .001); however, there was an interaction such that participants in the BN/BED participant group, compared to the healthy comparison group, demonstrated safer behaviour on the BART specifically in the oxytocin condition, but not in the placebo condition (F = 4.29, df = 1, p = .044, η2partial = .082). These findings cast doubt on the common assumption that individuals with BN and BED exhibit greater risk-taking behaviour in all domains and add to evidence that oxytocin plays a functional role in modulating behaviours which entail trade-offs between reward approach and risk in humans. We recommend that future dose-response studies further investigate the effect of oxytocin on reward approach behaviour in women with recurrent binge eating behaviour and the clinical significance of this effect.
    • Investigating resting brain perfusion abnormalities and disease target-engagement by intranasal oxytocin in women with bulimia nervosa and binge-eating disorder and healthy controls

      Martins, Daniel; Leslie, Monica; Rodan, Sarah; Zelaya, Fernando; Treasure, Janet; Paloyelis, Yannis; King's College London; University College London (Springer, 2020-06-08)
      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 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 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 minutes) 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.
    • A Pilot Study Investigating the Influence of Oxytocin on Attentional Bias to Food Images in Women with Bulimia Nervosa or Binge Eating Disorder

      Leslie, Monica; Leppanen, Jenni; Paloyelis, Yannis; Treasure, Janet; King's College London
      Background: Previous research has found that exogenous oxytocin administration has the potential to modulate attentional biases in women with anorexia nervosa. Recent work has indicated that attentional biases to food may reinforce the recurrent binge eating behaviour which characterises bulimia nervosa and binge eating disorder. To date, however, no study has yet investigated the effect of oxytocin on attentional biases to palatable food in women with bulimia nervosa and binge eating disorder. Methods: This study employed a single-session crossover design to test the hypothesis that a divided dose of 64IU intranasal oxytocin, administered as one intranasal dose of 40IU oxytocin followed by a top-up of 24IU oxytocin 80 minutes later, versus placebo administration administered in the same dosing schedule, would reduce attentional biases towards food images in a dot probe task. We hypothesised that oxytocin administration would reduce vigilance towards food to a greater degree in women with bulimia nervosa or binge eating disorder, versus healthy comparison women. Twenty-five women with bulimia nervosa or binge eating disorder and 27 comparison women without history of an eating disorder were recruited to take part in the study. Results: Contrary to our hypothesis, there was no main effect of diagnosis on attentional bias to food (fixed effect = 5.70, p = .363), nor a significant interaction between diagnosis and drug condition (fixed effect = -14.80, p = .645). There was a main effect of drug condition, such that oxytocin increased vigilance towards food, versus neutral, images in the dot probe task (fixed effect = 10.42, p = .044). A correlation analysis revealed that this effect was moderated by attentional bias in the placebo condition, such that greater avoidance of food stimuli in the placebo condition was associated with a greater increase in vigilance induced by oxytocin. Conclusion: The current findings add to a mixed body of literature investigating the therapeutic effects of oxytocin in women. Future research would benefit from dose-response studies investigating the optimal dose of oxytocin for modulating the attentional processing of palatable food in populations with eating disorders.
    • A systematic review and quantitative meta-analysis of the effects of oxytocin on feeding

      Leslie, Monica; Silva, Paulo; Paloyelis, Yannis; Blevins, James; Treasure, Janet; King's College London; Department of Veterans Affairs Medical Center; University of Washington School of Medicine
      The anorexigenic effects of oxytocin have been widely documented and accepted; however, no study has yet used the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines to compile previous findings in a single systematic review and quantitative meta-analysis. The present review aimed to identify published and unpublished studies examining the effects of oxytocin on energy intake in animals and humans, as well as the factors that moderate this effect. Web of Science, Pub Med and Ovid were searched for published and unpublished studies reporting the effects of oxytocin on energy intake in wild-type animals and in humans when administered in the absence of other active drugs or surgery. Two thousand and forty-nine articles were identified through the original systematic literature search, from which 54 articles were identified as being relevant for inclusion in the present review. An additional 3 relevant articles were identified in a later update of the literature search. Overall, a single dose of oxytocin was found to reduce feeding in animals. Despite several individual studies reporting that this effect persists to the end of the third week of chronic administration in rodent models, overall, this anorexigenic effect did not hold in the meta-analyses testing the effects of chronic administration. There was no overall effect of oxytocin on energy intake in humans, although a trend was identified for oxytocin to reduce the consumption of solid foods. Oxytocin reduces energy intake when administered as a single dose. Oxytocin can inhibit feeding over 2- to 3-week periods in rodent models. These effects typically do not persist beyond the third week of treatment. The anorexigenic effect of oxytocin is moderated by pregnant status, dose, method of administration and diet composition.