Psychological, cardiovascular and neurochemical reactions to CCK [indice] 4 challenge in panic disorder patients and healthy subjects

Abstract

Panic disorder (PD) is an anxiety disorder that affects about 2% of the general population. Many cognitive-behavioral and biomedical theories attempting to explain its etiology have been proposed. One of the most studied theories is the noradrenergic hypothesis. It suggests that panic disorder is due to a dysregulation of the catecholaminergic systems, the noradrenergic system in particular. Despite the biological plausibility of this hypothesis, the evidence is often inconsistent and contradictory. The present study investigated the peripheral monoaminergic systems using a panic provocation paradigm. Cholecystokinin tetrapeptide (CCK₄), a neuropeptide that seems to be implicated in anxiety and panic in addition to providing a valid human and animal model of panic attacks, was used as a challenge agent. In this double-blind, randomized, cross-over study, 16 emotionally and physically healthy subjects (HS) and 12 PD patients received injections of both 25 µg of CCK₄ and placebo (0.9% NaCl) on two separate occasions. The effects of both CCK₄ and placebo on psychological (state-anxiety, number, intensity and duration of symptoms), cardiovascular (heart rate and blood pressure) and neurochemical (plasma and platelet norepinephrine, epinephrine, dopamine; and serotonin) parameters were assessed. Baseline measures were taken before the administration of the substance and compared to post-injection values. Overall, it appears that PD patients and healthy subjects have similar patterns of psychological and cardiovascular reactions to CCK₄. However, the reactions of PD patients seems to be more pronounced with a slower return to pre-injection values. In terms of CCK₄-induced effects on the peripheral catecholaminergic systems, the reactivity of PD patients appears to be blunted. While in HS we observed significant CCK₄-induced changes in catecholamine concentrations, the modifications found in PD patients are limited, erratic, and suggestive of reduced plasticity of the catecholaminergic systems in this population. Based on our results, it appears that, in healthy subjects, panic-like anxiety is mediated, at least in part, by the catecholaminergic systems. Despite the obvious modification of catecholaminergic activity in PD patients (baseline differences in EPI and DA levels in both blood compartments), and notwithstanding possible influences of catecholamines on other systems, our results suggest that the actual immediate mechanism(s) of panic attacks in PD patients are not solely attributable to increases in catecholamine concentrations.