Neurobehavioral Correlates of Caffeine on Anxiety, Avoidance and Interoception in Healthy Individuals and Panic Disorder.

Adenosine Receptors From Genes to Behavior: Neurobehavioral Correlates of Caffeine on Anxiety, Avoidance, Decision-Making and Interoception in Healthy Individuals and Panic Disorder.

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.

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.