Serotonin Role on Brain Circuits Involved in Food Avoidance in Anorexia Nervosa

Study Overview
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Brief Summary
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Serotoninergic activity in brain structures involved in food control and avoidance, such as the basal ganglia, is poorly understood in Anorexia Nervosa.

Detailed Description
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A simultaneous positron emission tomography (PET)- functional magnetic resonance imaging (fMRI) approach and testing of food preferences and choices will provide further insight into the link between potential abnormalities in serotoninergic transmission and the specific food restriction disorder for Anorexia Nervosa. These Data can pave the way for new therapeutic avenues.

Official Title
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Serotonin Role on Brain Circuits Involved in Food Avoidance in Anorexia Nervosa : Study of Gaze Control and Multimodal Brain Imaging

Conditions
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Anorexia Nervosa

Intervention / Treatment
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* Other: PET imaging using [11C]DASB radioligand.
* Behavioral: Eye Tracker


Participation Criteria
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Eligibility Criteria
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Common Criteria for inclusion : Signature of written consent Subject affiliated or entitled to a social security scheme Inclusion Criteria: Patients with restrictive anorexia nervosa (30 subjects). Anorexia nervosa common features : fear of weight gain, dysmorphophobia, BMI < 17.5 kg/ m², amenorrhea Absence of food compulsions and purges Subgroup 1 (15 subjects) : STAI Y2 anxiety score > 61 Subgroup 2 (15 subjects) : STAI Y2 anxiety score < 51 Inclusion criteria - Female control subjects (15 subjects) BMI between 18.5 and 25 kg/ m² Absence of a psychological profile of eating disorder or other psychiatric disorders. Exclusion Criteria: Subjects with an oral contraception and breastfeeding woman Subject with heart failure Subject treated during the last three months with neuroleptics, and antiparkinsonian drugs, monoamine oxidase (MAO)-A or monoamine oxidase (MOA)-B inhibitors, tricyclic antidepressants, 5HT reuptake inhibitors, thymo regulators (lithium), antiepileptic dugs, codeine derivatives, morphinics, tramadol-containing products (Topalgic, …),dopaminergic drugs. Subjects with suspected pregnancy; Test β human chorionic gonadotropin (HCG) positive prior to examination. Subjects for whom MRI is contraindicated (pacemaker, intracerebral clips, prosthesis made of ferromagnetic material or claustrophobia). Subjects unable to sign written consent for participation in the study. Subject deprived of liberty by a judicial or administrative decision

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 35 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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Pathophysiological comparative study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Anorexia Nervosa patients<br>30 patients with anorexia nervosa = 15 with moderate to high anxiety (STAI YB anxiety (STAI YB > 51) and 15 with low anxiety (STAI YB<51). A TOBII eye tracker will be realised at Day 1. PET and MRI scans will be acquired at Day 2. | Other: PET imaging using [11C]DASB radioligand.<br>* Subjects will be asked to complete a food choice task in PET/MRI. During the task, PET and MRI scans will be acquired simultaneously. This will allow us to see in real time during food choices the brain activations of the subjects. For imaging we will inject the DASB tracer intravenously. This radio ligand is a tracer that allows us to see the cerebral serotoninergic transmission by positron emission tomography.<br>Behavioral: Eye Tracker<br>* The second technique used is the eye tracker that will allow us to analyze food avoidance behaviors through the eyes. With a TOBII eye tracker we wil be able to follow the gaze of the subjects during the food preference task. It is a non-invasive approach.<br>|
| Placebo Comparator: Controls<br>15 healthy volunteers (control group) and a low level of anxiety trait (< 51) A TOBII eye tracker will be realised at Day 1. PET and MRI scans will be acquired at Day 2. | Other: PET imaging using [11C]DASB radioligand.<br>* Subjects will be asked to complete a food choice task in PET/MRI. During the task, PET and MRI scans will be acquired simultaneously. This will allow us to see in real time during food choices the brain activations of the subjects. For imaging we will inject the DASB tracer intravenously. This radio ligand is a tracer that allows us to see the cerebral serotoninergic transmission by positron emission tomography.<br>Behavioral: Eye Tracker<br>* The second technique used is the eye tracker that will allow us to analyze food avoidance behaviors through the eyes. With a TOBII eye tracker we wil be able to follow the gaze of the subjects during the food preference task. It is a non-invasive approach.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| difference between the two groups of the study for serotonin binding potential | The difference in serotonin binding potential is measured by PET scan of the brain networks between anorexic and control subjects. | Day 2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| correlation between abnormalities in serotonin binding potential and abnormalities in brain activity in resting state | serotonin binding potential is measured with [11C]DASB PET. abnormalities in brain activity is measured on fMRI. correlation between abnormalities in serotonin binding potential and abnormalities in brain activity is quantified by change in the resting state | Day 2 | 
| correlation between abnormalities in serotonin binding potential and abnormalities in brain activity during the food choice tasks. | serotonin binding potential is measured with [11C]DASB PET. abnormalities in brain activity is measured on fMRI. correlation between abnormalities in serotonin binding potential and abnormalities in brain activity is quantified by change during the food choice tasks. | Day 2 | 
| correlation between anxiety profile and brain activity | brain activity is measured on fMRI and anxiety is measured by the score STAI YB. STAI YB > 51 = Moderate to high anxiety STAI YB<51 = Low anxiety | Day 2 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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anorexia nervosa, serotonin, PET-MRI, eating disorders