Anorexia Nervosa, Major Depressive Disorder, Generalized Anxiety Disorder, Panic Disorder, Brain Injury
Conditions
Keywords
heartbeat, respiration, interoception, anxiety, eating
Brief summary
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
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.
Interventions
DRUGIsoproterenol
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.
DRUGNormal saline
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.
Sponsors
National Institute of Mental Health (NIMH)
Laureate Institute for Brain Research, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in cardiorespiratory sensation intensity | Baseline | Visual analogue rating of intensity of heartbeat and breathing sensations (scale: 0 to 10) through study completion (e.g., the day of testing). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in anxiety level | Baseline | Visual analog rating of level of anxiety (scale: 0 to 10) through study completion, an average of 2 weeks. |
| Generalized anxiety disorder severity (Generalized Anxiety Disorder 7 scale) | Baseline | 7 questions on anxiety symptoms |
| Panic disorder severity (Panic Disorder Severity scale) | Baseline | panic symptoms questionnaire |
| Major depressive disorder severity (Patient Health Questionnaire-9 scale) | Baseline | 9 questions on depression symptoms |
| Eating disorder severity (Eating Disorder Examination scale) | Baseline | questionnaire about eating disorder symptoms |
Other
| Measure | Time frame | Description |
|---|---|---|
| Structural magnetic resonance imaging (cortical thickness in millimeters cubed). | Baseline | Structural MRI measure: cortical thickness. |
| Functional magnetic resonance imaging (Blood Oxygenation Level Dependent i.e. BOLD signal) | Baseline | Functional MRI measure: task based activation change |
| Resting cardiac interoceptive sensitivity (heartbeat tapping task tap latencies (in milliseconds)) | Baseline | subject taps with their finger their own perceived heart beat |
| Change in heart rate | Baseline | Average heart rate change versus pre-infusion baseline |
| Change in breathing pattern | Baseline | Average respiratory volume variability change versus pre-infusion baseline |
| EEG (coherence in alpha, beta, theta, delta, gamma frequencies, in Hertz (Hz)) | Baseline | EEG: global and local coherence. |
| Systolic and diastolic blood pressure (millimeters of mercury; mmHg) during the autonomic task of the valsalva maneuver | Baseline | blood pressure assessed |
| Systolic and diastolic blood pressure (millimeters of mercury; mmHg) during the autonomic handgrip task. | Baseline | blood pressure assessed |
| Systolic and diastolic blood pressure (millimeters of mercury; mmHg) during the autonomic task of mental arithmetic. | Baseline | blood pressure assessed |
| Systolic and diastolic blood pressure (millimeters of mercury; mmHg) during the autonomic cold pressor task. | Baseline | blood pressure assessed |
| Systolic and diastolic blood pressure (millimeters of mercury; mmHg) during the autonomic task of breath holding). | Baseline | blood pressure assessed |
Countries
United States
Outcome results
None listed