Neural Basis of Meal Related Interoceptive Dysfunction in Anorexia Nervosa

Study Overview
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Brief Summary
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This study aims to identify the brain regions responsible for encoding cardiorespiratory 'interoceptive' sensations and determine whether they are dysfunctional in individuals affected by eating disorders, anxiety, depression, or brain injury. By evaluating the same interoceptive sensations across different human illnesses, the investigators hope to provide convergent evidence resulting in identification of core underlying neural processes, and to discern relative contributions in each condition.

Detailed Description
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The human brain has constant access to a multitude of complex signals, which it must simplify and organize in order to sustain the integrity of the organism. Many of these signals originate from outside of the body, such as lights, sounds, and smells, and much is known about how humans consciously perceive these 'exteroceptive' signals and how the human brain represents them. Comparatively little is known about how the human brain processes 'interoceptive' signals originating from inside of the body, despite the fact that the brain has access to far more of them (for instance, intestinal tension, bladder distension, breath, heartbeat, body temperature, blood pressure, serum osmolality, inflammation, proprioception etc.). The current study study therefore aims to identify the brain regions responsible for encoding cardiorespiratory 'interoceptive' sensations and determine whether they are dysfunctional in individuals affected by eating disorders, anxiety, depression, or brain injury. Participants in this study will receive stimulation of the cardiorespiratory channel of the interoceptive system using bolus intravenous infusions of isoproterenol, a peripherally acting medication similar to adrenaline, and saline. Stimulation will occur during functional magnetic resonance imaging (fMRI) as well as outside of the fMRI scanner. After the scan participants will consume a meal. By evaluating the same interoceptive sensations across different human illnesses, the investigators hope to provide convergent evidence resulting in identification of core underlying neural processes, and to discern relative contributions in each condition.

Official Title
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Neural Basis of Meal Related Interoceptive Dysfunction in Anorexia Nervosa

Conditions
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Anorexia Nervosa, Major Depressive Disorder, Generalized Anxiety Disorder, Panic Disorder, Brain Injury

Intervention / Treatment
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* Drug: Isoproterenol
* Drug: Normal saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnostic and Statistical Manual 5 (DSM 5) criteria for anorexia nervosa and age 18 to 40, or generalized anxiety disorder, or panic disorder, or major depressive disorder, or brain injury caused either by herpes simplex encephalitis or Urbach-Wiethe disease. Exclusion Criteria: DSM 5 diagnosis with any of the following: Schizophrenia spectrum and other psychotic disorders, bipolar and related disorders, antisocial personality disorder, active suicidal ideation with intent or plan Current cardiac arrhythmia Current respiratory disease Seizure disorder MRI contraindications including: cardiac pacemaker, metal fragments in eyes/skin/body (shrapnel), aortic/aneurysm clips, prosthesis, by-pass surgery/coronary artery clips, hearing aid, heart valve replacement, shunt (ventricular or spinal), electrodes, metal plates/pins/screws/ wires, or neuro/bio-stimulators (TENS unit), persons who have ever been a professional metal worker/welder, history of eye surgery/eyes washed out because of metal, vision problems uncorrectable with lenses, inability to lie still on one's back for 60-120 minutes; prior neurosurgery; tattoos or cosmetic makeup with metal dyes, unwillingness to remove body piercings, and pregnancy.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

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
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Anorexia nervosa<br>Intravenous bolus infusions of isoproterenol (up to 4 micrograms per infusion) and normal saline. | Drug: Isoproterenol<br>* Intravenous infusions of isoproterenol, delivered in a randomized double blinded order, in each participant from each group. Participants will rate the experience of heartbeat and breathing sensations as well as anxiety induced by the infusion.<br>* Other names: Isuprel;Drug: Normal saline<br>* Intravenous infusions of normal saline, delivered in a randomized double blinded order, in each participant from each group. Participants will rate the experience of heartbeat and breathing sensations as well as anxiety induced by the infusion.<br>* Other names: Saline;|
| Experimental: Generalized anxiety disorder<br>Intravenous bolus infusions of isoproterenol (up to 4 micrograms per infusion) and normal saline. | Drug: Isoproterenol<br>* Intravenous infusions of isoproterenol, delivered in a randomized double blinded order, in each participant from each group. Participants will rate the experience of heartbeat and breathing sensations as well as anxiety induced by the infusion.<br>* Other names: Isuprel;Drug: Normal saline<br>* Intravenous infusions of normal saline, delivered in a randomized double blinded order, in each participant from each group. Participants will rate the experience of heartbeat and breathing sensations as well as anxiety induced by the infusion.<br>* Other names: Saline;|
| Experimental: Panic disorder<br>Intravenous bolus infusions of isoproterenol (up to 4 micrograms per infusion) and normal saline. | Drug: Isoproterenol<br>* Intravenous infusions of isoproterenol, delivered in a randomized double blinded order, in each participant from each group. Participants will rate the experience of heartbeat and breathing sensations as well as anxiety induced by the infusion.<br>* Other names: Isuprel;Drug: Normal saline<br>* Intravenous infusions of normal saline, delivered in a randomized double blinded order, in each participant from each group. Participants will rate the experience of heartbeat and breathing sensations as well as anxiety induced by the infusion.<br>* Other names: Saline;|
| Experimental: Major depressive disorder<br>Intravenous bolus infusions of isoproterenol (up to 4 micrograms per infusion) and normal saline. | Drug: Isoproterenol<br>* Intravenous infusions of isoproterenol, delivered in a randomized double blinded order, in each participant from each group. Participants will rate the experience of heartbeat and breathing sensations as well as anxiety induced by the infusion.<br>* Other names: Isuprel;Drug: Normal saline<br>* Intravenous infusions of normal saline, delivered in a randomized double blinded order, in each participant from each group. Participants will rate the experience of heartbeat and breathing sensations as well as anxiety induced by the infusion.<br>* Other names: Saline;|
| Experimental: Brain injury<br>Intravenous bolus infusions of isoproterenol (up to 4 micrograms per infusion) and normal saline. | Drug: Isoproterenol<br>* Intravenous infusions of isoproterenol, delivered in a randomized double blinded order, in each participant from each group. Participants will rate the experience of heartbeat and breathing sensations as well as anxiety induced by the infusion.<br>* Other names: Isuprel;Drug: Normal saline<br>* Intravenous infusions of normal saline, delivered in a randomized double blinded order, in each participant from each group. Participants will rate the experience of heartbeat and breathing sensations as well as anxiety induced by the infusion.<br>* Other names: Saline;|
| Active Comparator: Healthy comparison<br>Intravenous bolus infusions of isoproterenol (up to 4 micrograms per infusion) and normal saline. | Drug: Isoproterenol<br>* Intravenous infusions of isoproterenol, delivered in a randomized double blinded order, in each participant from each group. Participants will rate the experience of heartbeat and breathing sensations as well as anxiety induced by the infusion.<br>* Other names: Isuprel;Drug: Normal saline<br>* Intravenous infusions of normal saline, delivered in a randomized double blinded order, in each participant from each group. Participants will rate the experience of heartbeat and breathing sensations as well as anxiety induced by the infusion.<br>* Other names: Saline;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in cardiorespiratory sensation intensity | Visual analogue rating of intensity of heartbeat and breathing sensations (scale: 0 to 10) through study completion (e.g., the day of testing). | Baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in anxiety level | Visual analog rating of level of anxiety (scale: 0 to 10) through study completion, an average of 2 weeks. | Baseline | 
| Generalized anxiety disorder severity (Generalized Anxiety Disorder 7 scale) | 7 questions on anxiety symptoms | Baseline | 
| Panic disorder severity (Panic Disorder Severity scale) | panic symptoms questionnaire | Baseline | 
| Major depressive disorder severity (Patient Health Questionnaire-9 scale) | 9 questions on depression symptoms | Baseline | 
| Eating disorder severity (Eating Disorder Examination scale) | questionnaire about eating disorder symptoms | Baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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heartbeat, respiration, interoception, anxiety, eating