Stress and Neurofeedback in Anorexia Nervosa

Study Overview
=================
Brief Summary
-----------------
Anorexia nervosa (AN) and atypical AN (AAN) are severe psychiatric illnesses associated with high disease burden including high treatment costs and excessive mortality rates. Primary characteristics of AN and AAN are food restriction, associated fear of weight gain, and a disturbance in how one's body weight or shape is experienced.The underlying neural mechanisms for the core illness behaviors of food restriction and body size overestimation in anorexia nervosa and atypical anorexia nervosa are not well understood. This project will use neurofeedback and advanced psychophysical methods to assess and moderate the neural and behavioral responses to stress and relate those results to the naturalistic environment. The results will guide the development of novel interventions.

Detailed Description
-----------------
The overall strategy is a cross-sectional study, involving 3 subject groups, each subject studied on two study days (one negative and one neutral affect day, randomized), one week apart; on both study days subjects will undergo functional magnetic resonance imaging (fMRI) during which they complete tasks for 1) neurofeedback-reward learning and 2) body size estimation. Before and after each scan, and in the week between scans, subjects will be assessed for positive and negative affect and how it affects food intake.

Official Title
-----------------
Neural Mechanisms of Negative Affect and Neurofeedback in Anorexia Nervosa

Conditions
-----------------
Anorexia Nervosa, Atypical Anorexia Nervosa

Intervention / Treatment
-----------------
* Behavioral: Negative Affect Task


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy Controls (HC) Individuals aged 18-45 years Healthy body weight between 90 and 110 % average body weight since puberty. Regular monthly menstrual cycle (if applicable) Edinburgh Handedness Inventory Revised (EHI-R) LQ* score > +200 All ethnic backgrounds English is primary language spoken Anorexia Nervosa (AN) Age 18-45 years old Edinburgh Handedness Inventory Revised (EHI-R) LQ* score > +200 All ethnic backgrounds Current diagnosis of anorexia nervosa, including being underweight, will have a severe fear of weight gain, body image distortion and absence of the menstrual cycle over three consecutive months. English is primary language spoken Atypical Anorexia Nervosa (AAN) Age 18-45 years old Edinburgh Handedness Inventory Revised (EHI-R) LQ* score > +200 All ethnic backgrounds Meets the criteria for anorexia nervosa except despite significant weight loss, the individual's weight is within or above the normal range English is primary language spoken Exclusion Criteria: Healthy Controls (HC) Current pregnancy or breast feeding within last 3 months First degree relative with current or past eating disorder Psychiatric Medication use such as selective serotonin reuptake inhibitors (SSRIs), atypical antipsychotics, etc. Past or present Axis I psychiatric disorder including substance or alcohol use disorder as determined through structured clinical interview History of significant head trauma Indication of intellectual disability or autism spectrum disorder Major Medical illness that requires medication or have significant impact on subject's life such as: diabetes, Alzheimer's disease or dementia, stroke, learning disability, mobility disorders, cancer, high blood pressure, etc. (to be determined through biological screening form and interview with principal investigator (PI) Recent history of suspected substance abuse or a lifetime history of psychostimulant abuse and/or dependence Contraindications to magnetic resonance imaging (MRI) including metal implants or braces (as determined through fMRI screening form) Anorexia Nervosa (AN) Pregnancy or breast feeding within last 3 months Lifetime history of bipolar I disorder or psychosis Current substance abuse or dependence in the past 3 months Psychotic illness/other organic brain syndromes, dementia, somatization disorders or conversion disorders Physical conditions (e.g., diabetes mellitus, pregnancy) known to influence eating or weight History of significant head trauma Indication of intellectual disability or autism spectrum disorder Electrolyte, blood count or kidney or liver function abnormalities Contraindications to MRI including metal implants or braces (as determined through fMRI screening form) Atypical Anorexia Nervosa (AAN) Pregnancy or breast feeding within last 3 months Lifetime history of bipolar disorder or psychosis Current substance abuse or dependence in the past 3 months Psychotic illness/other organic brain syndromes, dementia, somatization disorders or conversion disorders Physical conditions (e.g., diabetes mellitus, pregnancy) known to influence eating or weight History of significant head trauma Indication of intellectual disability or autism spectrum disorder Electrolyte, blood count or kidney or liver function abnormalities Contraindications to MRI including metal implants or braces (as determined through fMRI screening form)

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Behavioral<br>Negative Affect Task | Behavioral: Negative Affect Task<br>* fMRI stress task<br>* Other names: Functional Magnetic Resonance Brain Imaging Stress Task;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Functional Magnetic Resonance Imaging (fMRI) brain activation in response to stress during a taste reward task | Activation in the brain during a taste reward task will be measured using functional MRI (fMRI) after a neutral and stressful task. | Difference in brain response between the neutral and stress condition, up to 9 days | 
| Functional Magnetic Resonance Imaging (fMRI) brain activation in response to stress during a body size estimation task | Activation in the brain during a body size estimation task will be measured using functional MRI (fMRI) after a neutral and stressful task. | Difference in brain response between the neutral and stress condition, up to 9 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ecological Momentary Assessment (EMA) | Ecological Momentary Assessment (EMA) will be used to test food restriction and body size estimation in the natural environment and in relation to daily stress. | Up to 9 days |