Healthy, Panic Disorder
Conditions
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.
Interventions
DIETARY_SUPPLEMENTCaffeine
Caffeine capsule 250 mg, oral intake
DRUGPlacebo
Placebo capsule, oral intake
Sponsors
Uppsala University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Intervention model description
The study entails two sessions with a cross-over design. Participants will be randomized to start with either the caffeine condition or the placebo condition. The study includes two arms: (a) participants with Panic Disorder (anticipated n = 50) and (b) Healthy controls (anticipated n = 50). Both arms (Panic Disorder and Healthy controls) will complete both conditions with the two sessions (caffeine and placebo condition) in randomized order.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* 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.
Exclusion criteria
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Task-related BOLD fMRI signal | Session 1 (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 1 (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 1 (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 1 (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 1 (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 1 (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
| Measure | Time frame | Description |
|---|---|---|
| Structural brain data, T1-w sMRI | Session 1 (day 1) | Structural brain changes will be analyzed through T1-weighted sMRI (structural magnetic resonance imaging). |
| Heart rate variability | Session 1 (day 1) | Heart rate variability (HRV) will be assessed by using a 7T MR-compatible heart rate band, during the whole MR scanner time. |
| Respiratory rate | Session 1 (day 1) | Respiratory or breathing rates will be assessed during the whole MR scanner time. |
Countries
Sweden
Contacts
PRINCIPAL_INVESTIGATORAndreas Frick, PhD
Uppsala University, Department of Medical Sciences, Psychiatry
Outcome results
None listed