Neural Basis of Meal Related Interoceptive Dysfunction in Anorexia Nervosa

Laureate Institute for Brain Research (LIBR)

Status: Completed

Conditions: Major Depressive Disorder; Brain Injury; Panic Disorder; Generalized Anxiety Disorder; Anorexia Nervosa

Treatments: Drug: Isoproterenol; Drug: Normal saline

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT02615119

2017-002

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 97 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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97 participants in 6 patient groups

Anorexia nervosa

Experimental group

Description:

Intravenous bolus infusions of isoproterenol (up to 4 micrograms per infusion) and normal saline.

Treatment:

Drug: Normal saline

Drug: Isoproterenol

Generalized anxiety disorder

Experimental group

Description:

Intravenous bolus infusions of isoproterenol (up to 4 micrograms per infusion) and normal saline.

Treatment:

Drug: Normal saline

Drug: Isoproterenol

Panic disorder

Experimental group

Description:

Intravenous bolus infusions of isoproterenol (up to 4 micrograms per infusion) and normal saline.

Treatment:

Drug: Normal saline

Drug: Isoproterenol

Major depressive disorder

Experimental group

Description:

Intravenous bolus infusions of isoproterenol (up to 4 micrograms per infusion) and normal saline.

Treatment:

Drug: Normal saline

Drug: Isoproterenol

Brain injury

Experimental group

Description:

Intravenous bolus infusions of isoproterenol (up to 4 micrograms per infusion) and normal saline.

Treatment:

Drug: Normal saline

Drug: Isoproterenol

Healthy comparison

Active Comparator group

Description:

Intravenous bolus infusions of isoproterenol (up to 4 micrograms per infusion) and normal saline.

Treatment:

Drug: Normal saline

Drug: Isoproterenol