Neural Response to Catecholamine Depletion in Subjects Suffering From Bulimia Nervosa in Their Past and Healthy Controls

Summary

Bulimia nervosa is a severe psychiatric disorder characterized by recurrent binge eating episodes followed by inappropriate compensatory behavior to prevent weight gain such as self-induced vomiting. With this project, the investigators want to investigate the role of the neurotransmitter dopamine in bulimia nervosa. Dopamine is reported to have an important influence on the neural reward system and is involved in the processing of gains and losses. The reward system is functionally connected to the individual perception of rewards in the environment. A previous study revealed that under catecholamine depletion including dopamine depletion women suffering from bulimia nervosa in their past reported mild bulimic symptoms and their reward processing became dysfunctional: their ability to use rewarding stimuli for task solving was diminished.

The aim of this study is to investigate the role of reduced dopamine availability in the development or maintaining of bulimia nervosa and in the dysfunctional processing of rewarding stimuli and negative visual information. Therefore, the investigators hypothesize that catecholamine depletion achieved by oral administration of alpha-methyl-paratyrosine (AMPT) will induce mild bulimic symptoms in females suffering from bulimia nervosa in their past. In addition, they will reveal dysfunctions in reward and emotional processing under catecholamine depletion. Using functional magnetic resonance imaging, the investigators propose that a reduced activation of the nucleus accumbens, a neural structure of the reward system, will be the neural correlate of this dysfunctional reward processing. Furthermore, the amygdala, a neural structure that is involved in emotional processing, will show a higher activation under catecholamine depletion. Genetic factors additionally have an influence on the dopaminergic system. Therefore, the investigators hypothesize that genetic factors, for example the COMT val-158-met polymorphism may have an effect on the behavioral and neural response to catecholamine depletion. In sum, this investigation may help to understand which changes in reward and emotional processing may lead to a reoccurrence of bulimic symptoms.

In future, the findings of this study may help to develop individual pharmacological and psychotherapeutical interventions to enhance the outcome of treatment.

Conditions

• Bulimia Nervosa
• Eating Disorders
• Dopamine
• Reward
• Catechol-O-methyltransferase

Interventions

DRUG

AMPT/ Demser

alpha-methyl-paratyrosine (AMPT, trade name: Demser) body-weight adjusted dosage (40 mg/kg body weight, maximum 4000mg) at 4 medication intake time points over 24 hours

DRUG

Diphenhydramine

Diphenhydramine (25mg) at the first medication intake time point

DRUG

Placebo

Placebo at the second, third and fourth medication intake time point

Sponsors & Collaborators

• Insel Gruppe AG, University Hospital Bern

  collaborator OTHER

• University of Zurich

  collaborator OTHER

• University of Bern

  lead OTHER

Principal Investigators

• Gregor Hasler, Prof. Dr. med · University Hospital of Psychiatry, University of Bern

Study Design

Allocation

RANDOMIZED

Purpose

DIAGNOSTIC

Masking

DOUBLE

Model

CROSSOVER

Eligibility

Min Age

18 Years

Max Age

60 Years

Sex

FEMALE

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2012-02-20

Primary Completion

2019-05-31

Completion

2022-05-31

Countries

• Switzerland

Study Locations