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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
DOUBLE
Enrollment
42
National 7T Facility - Lunds universitet
Lund, Sweden
Uppsala University, Department of Medical Sciences, Psychiatry
Uppsala, Sweden
Task-related BOLD fMRI signal
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.
Time frame: Session 1 (day 1)
Task-related BOLD fMRI signal
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.
Time frame: Session 2 (day 2; minimum of 36 hours after session/day 1)
Self-reported anxiety
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).
Time frame: Session 1 (day 1)
Self-reported anxiety
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).
Time frame: Session 2 (day 2; minimum of 36 hours after session/day 1)
Self-reported interoceptive awareness
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).
Time frame: Session 1 (day 1)
Self-reported interoceptive awareness
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).
Time frame: Session 2 (day 2; minimum of 36 hours after session/day 1)
Self-reported interoceptive functional impairment
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).
Time frame: Session 1 (day 1)
Self-reported interoceptive functional impairment
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).
Time frame: Session 2 (day 2; minimum of 36 hours after session/day 1)
Skin conductance responses (SCR)
Skin conductance responses will be used to assess emotional reactivity at the physiological level to emotional stimuli vs neutral stimuli (faces).
Time frame: Session 1 (day 1)
Skin conductance responses (SCR)
Skin conductance responses will be used to assess emotional reactivity at the physiological level to emotional stimuli vs neutral stimuli (faces).
Time frame: Session 2 (day 2; minimum of 36 hours after session/day 1)
Occurrence of panic attacks
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".
Time frame: Session 1 (day 1)
Occurrence of panic attacks
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".
Time frame: Session 2 (day 2; minimum of 36 hours after session/day 1)
Structural brain data, T1-w sMRI
Structural brain changes will be analyzed through T1-weighted sMRI (structural magnetic resonance imaging).
Time frame: Session 1 (day 1)
Structural brain data, T1-w sMRI
Structural brain changes will be analyzed through T1-weighted sMRI (structural magnetic resonance imaging).
Time frame: Session 2 (day 2; minimum of 36 hours after session/day 1)
Heart rate variability
Heart rate variability (HRV) will be assessed by using a 7T MR-compatible heart rate band, during the whole MR scanner time.
Time frame: Session 1 (day 1)
Heart rate variability
Heart rate variability (HRV) will be assessed by using a 7T MR-compatible heart rate band, during the whole MR scanner time.
Time frame: Session 2 (day 2; minimum of 36 hours after session/day 1)
Respiratory rate
Respiratory or breathing rates will be assessed during the whole MR scanner time.
Time frame: Session 1 (day 1)
Respiratory rate
Respiratory or breathing rates will be assessed during the whole MR scanner time.
Time frame: Session 2 (day 2; minimum of 36 hours after session/day 1)
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