Peripheral and Central Nervous System Contributions to the Subjective Experience of Emotions

Panic attacks (PA) are unexpected periods of intense fear concomitant with both
strong physiological arousal and subjective symptoms. It is unclear whether
this physiological arousal is necessary for the subjective experience of PAs,
or whether these symptoms are an epiphenomenon of central processes. The
(nor)adrenergic system is involved in emotion-related processes in the brain
and in the peripheral nervous system (e.g. in the increase in heart rate, which
is related to arousing emotions). PAs are most commonly associated with panic
disorder (PD), but can occur in any mental disorder. These unexpected,
recurrent attacks severely impact patients* quality of life and lead to immense
health care costs to society.
Beta blockers are drugs that inhibit the activation of the (nor)adrenergic
system. Beta blockers either selectively block beta receptors in the periphery,
or both in the central and peripheral nervous system. This distinction in beta
blockers can be used to study a fundamental, yet unanswered, question about the
processes related to an intense emotion like panic: namely, what the relative
contributions of central and peripheral processes are to the subjective
experience of panic.

The primary objective of this study is to identify the distinct roles of the
peripheral and central nervous system in the subjective experience of panic.

A double-blind, randomized, placebo-controlled within-subject design will be
used.

In 3 different sessions, participants will undergo one 35% CO2 inhalation per
session, preceded by oral administration of atenolol, metoprolol or a placebo.
Each participant will receive each condition, in a randomised order.

Atenolol and metoprolol are registered medicines with a good safety and side
effects profile (e.g., low likelihood of fatigue, dizziness). In the current
study, we will only use single oral dosages of the drugs, with concentrations
below the clinically allowed maximum dosage, and therefore we expect no or only
minor and short lasting side effects. CO2 inhalations are associated with
short-lasting discomfort and potentially minor adverse events such as
headaches. Participants will visit the laboratory on four occasions: 1)
screening visit (checking eligibility, including a physical and psychological
exam, CO2 test with brief questionnaires assessing fear, discomfort and panic
symptoms), 2-4) testing days: CO2 test with brief questionnaires assessing
fear, discomfort and panic symptoms, after oral administration of atenolol,
metoprolol or placebo. Physiological parameters will be recorded during the
whole session, and with more precision during the CO2 inhalation. The testing
days will be planned about one week apart, each session will last about 2.5
hours. Assessments are non-invasive and do not harbour any risks. Given that
the results of this study could lead to an (improved) intervention for PAs, the
burden and risks are deemed to be justifiable.