Monoamine Contributions to Neurocircuitry in Eating Disorders

Overview

This study will use brain imaging technologies to measure several neurotransmitters (serotonin and dopamine) that contribute to our abilities to respond to reward or inhibit our impulses, and which are known to be altered in the brain of people with anorexia nervosa (AN) and bulimia nervosa (BN). Because palatable food stimulates dopamine secretion, we propose to use a challenge with brain imaging that will stimulate dopamine release which we hypothesize will generate anxiety rather than pleasure in AN, and will help explain why AN restrict eating in order to reduce anxiety. This study will help to understand the unique puzzling symptoms in eating disorders and contribute to finding better methods for identifying effective treatments for these often relapsing and sometimes chronic disorders.

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: N/A
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Basic Science
    • Masking: None (Open Label)
  • Study Primary Completion Date: December 31, 2017

Detailed Description

Alterations of serotonin (5-HT) and dopamine (DA) activity may contribute to extremes of appetitive behaviours in anorexia nervosa (AN) and bulimia nervosa (BN), through effects on inhibitory and reward neural pathways. To avoid the confounding effects of malnutrition, and because they have behaviours and neural circuit alterations relevant for this study, we will study 25 recovered (REC) restricting-type AN, 25 REC bulimic-type AN (AN-BN), 25 REC BN, and 25 control women (CW). This 5 year study, of women 18 to 45 years old, will employ positron emission tomography (PET) imaging with radioligands for the 5-HT transporter ([11C]DASB) and DA D2/D3 receptors ([11C]raclopride).

Interventions

  • Drug: [11C]raclopride
    • 1.[11C]raclopride -The change (Δ) in BPND (the difference between the [11C]raclopride BPND at baseline and post-AMPH treatment normalized to the baseline BPND
  • Drug: [11C]DASB
    • BPND of [11C]DASB.
  • Drug: amphetamine
    • The change (Δ) in BPND (the difference between the [11C]raclopride BPND at baseline and post-AMPH treatment normalized to the baseline BPND.

Arms, Groups and Cohorts

  • Experimental: [11C]raclopride, [11C]DASB, amphetamine
    • One time administration of oral amphetamine based on subject’s weight (0.5 mg/kg). One PET scan using [11C]DASB. Two PET scans using [11C]raclopride.

Clinical Trial Outcome Measures

Primary Measures

  • 5-HT Transporter Binding as Measured During the PET Scan
    • Time Frame: 90 minute PET scan
    • Use PET and [11C]DASB to explore 5-HTT receptor binding potential midbrain and striatal regions of interest in eating disorder subtypes. The Binding Potential (BP) was calculated as BP Non Displaceable (ND) = (VT/VND) -1. [VT = distribution volume in tissue; VND = non-displaceable distribution volume]. The binding of the 5-HTT on PET presumably reflects 5-HTT density and/or affinity.

Secondary Measures

  • Dopamine D2/D3 Receptor Binding as Measured During the PET Scan After Amphetamine Administration
    • Time Frame: 90 min PET scan
    • Use PET and [11C]raclopride to explore Dopamine D2/D3 receptor binding potential (BPND) in striatal regions of interest in eating disorder subtypes after amphetamine administration. The Binding Potential (BP) was calculated as BP Non Displaceable (ND) = (VT/VND) -1. [VT = distribution volume in tissue; VND = non-displaceable distribution volume].

Participating in This Clinical Trial

Inclusion

  • history of Diagnostic and Statistical Manual (DSM-IV) diagnosis of anorexia or bulimia. – AN women have history of average body weight (ABW) below 85% for height. – AN-BN subjects have history of ABW below 85% ABW. – AN-BN subjects have history of binging/purging behaviors during a period of low weight. – Subjects must be right-handed. – Subjects have been recovered for 12 months or more. Exclusion – Diagnosis of alcohol or drug abuse or dependence in the 3 months. – Alcohol or substance use within 30 days. – Current diagnosis of an Axis I disorder. – Organic brain syndromes, dementia, psychotic disorders, or mental retardation. – Neurological or medical disorders such as seizure disorder, renal disease, diabetes, thyroid disease, EKG indicative of electrolyte imbalance – BN subjects whose purging methods were the use of laxatives, diuretics – Use of psychoactive medication in the 3 months. – Pregnancy or lactation. – Tobacco use in the 3 months.

Gender Eligibility: Female

Minimum Age: 18 Years

Maximum Age: 45 Years

Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

Investigator Details

  • Lead Sponsor
    • University of California, San Diego
  • Collaborator
    • National Institute of Mental Health (NIMH)
  • Provider of Information About this Clinical Study
    • Principal Investigator: Walter Kaye, MD – University of California, San Diego
  • Overall Official(s)
    • Walter Kaye, MD, Principal Investigator, UCSD
    • Ursula Bailer, MD, Principal Investigator, UCSD

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