Neurobehavioral Correlates of Caffeine on Anxiety, Avoidance and Interoception in Healthy Individuals and Panic Disorder.
- Conditions
- Panic DisorderHealthy
- Interventions
- Dietary Supplement: CaffeineDrug: Placebo
- Registration Number
- NCT06145490
- Lead Sponsor
- Uppsala University
- Brief Summary
The current study is a placebo-controlled, double-blind, randomized controlled study using a cross-over design, including Healthy Controls (HC) and participants with Panic Disorder (PD).
The primary aim of the study is to investigate the neural correlates and behavioral effects of caffeine (versus placebo), and its impact on emotional reactivity, decision-making, and interoception, and compare the effects in individuals with PD vs HCs. Subjective anxiety and the occurrence of panic attacks will also be measured. Multimodal neuroimaging methods, such as structural and functional MRI, will be used to address the aims of the study.
Emotional reactivity, emotional decision-making and interoception will be measured with experimental tasks in a 7 Tesla (7T) magnetic resonance (MR) scanner, jointly with measures of skin conductance, heart rate, respiratory rate, and self-reported ratings of anxiety and interoception.
Emotional reactivity will be assessed using emotional and neutral faces. Emotional decision-making will be assessed with an approach-avoidance conflict task. Changes in interoception (bodily sensation, such as pulse and respiration) will be explored using a task in which participants are asked to focus on their breathing or an external stimulus. Caffeine effects on brain resting-state activity will also be assessed. All tasks will be conducted while in the 7T MR scanner.
A secondary aim of the study is to examine the impact of genetic variability in the adenosine A2A receptor (ADORA2A) genotype (e.g., rs5751876 T/T) on the effects of caffeine (vs placebo), as ADORA2A genotype has previously been associated with elevated caffeine-induced anxiety.
- Detailed Description
Given the novelty of the intended study and the lack of previous neuroimaging and emotion-related behavioral studies on caffeine effects in HCs and PD, analyses will be exploratory without directed hypotheses.
It is intended to conduct between-group analyses (HCs vs PD) in the two conditions (caffeine versus placebo), as well as within-group analyses in HCs and PD separately. Between-group analyses will also be conducted between individuals with different ADORA2A genotypes.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 100
- Panic Disorder group (PD): Primary diagnosis of Panic Disorder.
- Healthy control group (HCs): No current or history of psychiatric disorders.
- All participants (PD and HCs): Weekly caffeine consumption ≤ 300 mg.
- Weekly caffeine consumption ≥ 300 mg.
- Thoracic or head surgery, or any other surgery or metallic implanted devices not compatible with the safety standards for 7T MR scanner.
- History of severe psychiatric disorder (e.g., schizophrenia).
- Somatic or neurological conditions (e.g., hypertension and heart condition).
- Ongoing treatment with psychotropic medication or treatment with psychotropic medication which has been discontinued within 2 months.
- Other ongoing treatments that may confound the results.
- Current drug or alcohol abuse/dependency.
- Habitual nicotine use.
- Uncorrected visual or hearing impairment.
- Pregnancy.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Panic Disorder Caffeine Participants will be randomized to start with either the caffeine condition or the placebo condition. Participants will complete session 2 with the other condition (condition not allocated to in session 1). Panic Disorder Placebo Participants will be randomized to start with either the caffeine condition or the placebo condition. Participants will complete session 2 with the other condition (condition not allocated to in session 1). Healthy controls Caffeine Participants will be randomized to start with either the caffeine condition or the placebo condition. Participants will complete session 2 with the other condition (condition not allocated to in session 1). Healthy controls Placebo Participants will be randomized to start with either the caffeine condition or the placebo condition. Participants will complete session 2 with the other condition (condition not allocated to in session 1).
- Primary Outcome Measures
Name Time Method Task-related BOLD fMRI signal Session 2 (day 2; minimum of 36 hours after session/day 1) Task-related BOLD (blood-oxygen-level-dependent) fMRI (functional magnetic resonance imaging) signal will be collected through a 7T MR scanner, starting approximately 30 minutes after oral intake of caffeine or placebo pill. Tasks: Emotional reactivity, Approach-Avoidance Conflict Task, Interoception, Resting-state fMRI.
Self-reported anxiety Session 2 (day 2; minimum of 36 hours after session/day 1) Anxiety will be assessed before capsule intake (either caffeine or placebo), 20 minutes after intake, after each task, and during the interoception task measured with self-reported ratings, on a scale from 0-100 (0= no anxiety - 100= extreme anxiety).
Self-reported interoceptive awareness Session 2 (day 2; minimum of 36 hours after session/day 1) Interoceptive awareness will be assessed before capsule intake (either caffeine or placebo), 20 minutes after intake, after each task in the MR scanner, and during the interoception task, measured with self-reported ratings on a scale from 0-100 (0= no awareness - 100= extreme awareness).
Self-reported interoceptive functional impairment Session 2 (day 2; minimum of 36 hours after session/day 1) Interoceptive functional impairment will be assessed before capsule intake (either caffeine or placebo), 20 minutes after intake, after each task, and during the interoception task, measured with self-reported ratings on a scale from 0-100 (0= no impairment - 100= extreme impairment).
Skin conductance responses (SCR) Session 2 (day 2; minimum of 36 hours after session/day 1) Skin conductance responses will be used to assess emotional reactivity at the physiological level to emotional stimuli vs neutral stimuli (faces).
Occurrence of panic attacks Session 2 (day 2; minimum of 36 hours after session/day 1) The occurrence of panic attacks will be assessed according to the Diagnostic Statistical Manual (DSM-5) criteria for panic attacks and will be coded dichotomous as "present" or "not present".
- Secondary Outcome Measures
Name Time Method Heart rate variability Session 2 (day 2; minimum of 36 hours after session/day 1) Heart rate variability (HRV) will be assessed by using a 7T MR-compatible heart rate band, during the whole MR scanner time.
Structural brain data, T1-w sMRI Session 2 (day 2; minimum of 36 hours after session/day 1) Structural brain changes will be analyzed through T1-weighted sMRI (structural magnetic resonance imaging).
Respiratory rate Session 2 (day 2; minimum of 36 hours after session/day 1) Respiratory or breathing rates will be assessed during the whole MR scanner time.
Trial Locations
- Locations (2)
National 7T Facility - Lunds universitet
🇸🇪Lund, Sweden
Uppsala University, Department of Medical Sciences, Psychiatry
🇸🇪Uppsala, Sweden