Monoamine Contributions to Neurocircuitry in Eating Disorders

Study Overview
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Brief Summary
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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.

Detailed Description
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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).

Official Title
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Monoamine Contributions to Neurocircuitry in Eating Disorders

Conditions
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Eating Disorder

Intervention / Treatment
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* Drug: [11C]raclopride
* Drug: [11C]DASB
* Drug: amphetamine


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: [11C]raclopride, [11C]DASB, amphetamine<br>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. | Drug: [11C]raclopride<br>* 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<br>* Other names: Raclopride, serial number 009;Drug: [11C]DASB<br>* BPND of [11C]DASB.<br>* Other names: DASB, serial number 0011;Drug: amphetamine<br>* The change (Δ) in BPND (the difference between the [11C]raclopride BPND at baseline and post-AMPH treatment normalized to the baseline BPND.<br>* Other names: dextroamphetamine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 5-HT Transporter Binding as Measured During the 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. | 90 minute PET scan | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dopamine D2/D3 Receptor Binding as Measured During the PET Scan After Amphetamine Administration | 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]. | 90 min PET scan |