Dopamine Receptor Contributions to Prediction Error and Reversal Learning in Anorexia Nervosa

Summary

Anorexia nervosa (AN) is an eating disorder associated with intense fear of weight gain, food refusal, and severe weight loss. AN has the highest mortality rate among the psychiatric disorders; however, little is known about biomarkers, and no medication has been approved for AN. Many individuals only partially recover, and treatment options, especially for the psychological components of the illness, are not very effective, highlighting the need for more effective treatments.

Brain reward pathways have a direct impact on the drive to eat, and a variety of neuroimaging studies have suggested altered reward processing in AN. The neurotransmitter dopamine has a central role in the reward circuitry to drive food approach, and the dynamic interplay between dopamine receptor response and food restriction could have implications for the pathophysiology of AN. Dopamine-related brain function has been studied indirectly using functional magnetic resonance brain imaging (fMRI) and tasks that deliver reward stimuli unexpectedly, that elicit the so-called prediction error (PE) response.

Research in AN showed repeatedly altered PE processing suggesting altered dopamine circuit function in the disorder.

Dopamine and PE response have also been associated with altered reversal learning, which has important treatment implication for AN as reversal learning is impaired in the disorder and modulation of the dopamine system could improve treatment.

Conditions

• Anorexia Nervosa

Interventions

DRUG

amisulpride

Dopamine D2 antagonist to test how it affects brain response and behavior to prediction error and reversal tasks during functional magnetic resonance imaging (fMRI).

DRUG

bromocriptine

Dopamine D2 receptor agonist test how it affects brain response and behavior to prediction error and reversal tasks during functional magnetic resonance imaging (fMRI).

DRUG

Placebo

Placebo pill with no active drug ingredients

Sponsors & Collaborators

• National Institute of Mental Health (NIMH)

  collaborator NIH

• University of California, San Diego

  lead OTHER

Principal Investigators

• Guido Frank, MD · University of California, San Diego

Study Design

Allocation

RANDOMIZED

Purpose

OTHER

Masking

SINGLE

Model

CROSSOVER

Eligibility

Min Age

18 Years

Max Age

29 Years

Sex

FEMALE

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2020-10-20

Primary Completion

2023-09-06

Completion

2025-01-01

FDA Drug

Yes

Countries

• United States

Study Locations