Abstract
Bulimia nervosa (BN) and binge eating disorder (BED) are psychiatric disorders characterised by recurrent loss-of-control binge eating behaviour, which is associated with the consumption of an objectively large quantity of food for the circumstances. BN is additionally characterised by recurrent inappropriate compensatory weight control behaviours. Both BN and BED cause significant distress and detract from quality of life in affected individuals. To date, however, current treatments do not support full recovery in a considerable portion of individuals with BN or BED, thus highlighting the need for novel treatment approaches which target critical maintenance factors.The current thesis synthesises current evidence for the maintenance of recurrent binge eating behaviour through neural processes related to reward dysregulation and addiction. Based on previous and original evidence, I will go on to propose a new maintenance model of BN and BED and apply this model to a multi-modal investigation of exogenously-administered intranasal oxytocin in adult women with BN and BED.
Paper 1 presents a narrative review of empirical literature relating to the dysregulation of reward processes in bulimia nervosa and binge eating disorder. Within this paper, I propose a new theoretical maintenance model of recurrent binge eating behaviour: the “addictive appetite” model. Paper 2 presents an additional narrative review of evidence for the novel elements of the addictive appetite model, including evidence for tolerance and withdrawal effects in BN and a central insulin- and dopamine-mediated mechanism underpinning heightened craving. Paper 3 tests hypotheses stemming from the addictive appetite model, which predicts that craving and reward-motivated eating are central to the maintenance of BN and BED. Paper 3 presents a cluster analysis demonstrating that food craving, reward-motivated eating, and eating for coping purposes significantly distinguish women with BN and BED from age- and weight-matched comparison women.
Oxytocin, a neuropeptide and hormone, has previously been found to modulate anxiety and reward processes, which are central components of the addictive appetite model. Paper 4 presents a systematic review and quantitative meta-analysis of the effects of oxytocin on feeding behaviour in both animal and human samples. This meta-analysis demonstrates that a single dose of central or peripheral oxytocin significantly attenuates subsequent feeding in animals, while the effects of oxytocin decrease with chronic administration. The evidence for the effects of oxytocin on feeding in humans is mixed, and moderated by factors including eating disorder status, sex, and food type.
Paper 5 tests the functional significance of exogenous oxytocin in altering palatable food intake, subjective stress, and salivary cortisol in women with BN or BED and healthy comparison women without history of an eating disorder. Contrary to our hypotheses, oxytocin did not significantly affect palatable eating behaviour, 24-hour calorie intake, subjective, stress, or salivary cortisol.
Paper 6 investigates the influence of oxytocin on attentional bias to palatable food images. Contrary to our hypothesis, we found that oxytocin increased vigilance towards palatable, versus neutral, food images. Paper 7 tested the influence of oxytocin on risk-taking behaviours in a computerised task. Contrary to our hypotheses, women with BN and BED did not demonstrate significantly different risk-taking behaviour on the task in the placebo condition. We detected a significant interaction such that oxytocin decreased risk-taking behaviour to a greater degree in women with BN and BED. Paper 8 presents the preliminary outcomes of a study investigating the effect of 40IU intranasal oxytocin on the neural processing of visual and gustatory food stimuli. We did not observe significant differences in neural activation between women with BN or BED, versus healthy control women, in response to the anticipation or receipt of chocolate taste, versus water taste in the brain regions analysed. We did not find a significant effect of 40IU intranasal oxytocin, versus placebo, on BOLD response to the anticipation or receipt of chocolate milk, versus water.
The results of these original experiments testing the influence of oxytocin indicate that a divided 64IU dose of oxytocin was not effective in reducing calorie consumption in women with BN and BED, although there is preliminary evidence that oxytocin may reduce risk-taking and attentional bias to food in women with BN and BED. Future doseresponse studies in women would be helpful in ascertaining whether a different regime of oxytocin treatment may be more effective in treating the symptoms and sequelae of BN and BED. Future research targeting the maintenance factors of BN and BED identified by the addictive appetite model via different treatment methods would be useful to advance treatment for affected individuals and further refine this theoretical model of recurrent binge eating.
| Date of Award | 1 Nov 2019 |
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| Original language | English |
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| Supervisor | Janet Treasure (Supervisor) & Yannis Paloyelis (Supervisor) |