Pentagastrin-induced release of free fatty acids in healthy volunteers and patients with panic disorder:: effect of pretreatment with ethinyl estradiol

Objective: The primary objective of this study was to assess whether pentagastrin-induced panic symptoms are associated with release of free fatty acids (FFAs) in a manner that could explain the mechanism of correlations observed between serum cholesterol levels and frequency and severity of panic attacks in patients with panic disorder (PD). A secondary objective was to assess whether pretreatment with ethinyl estradiol (EE) attenuates pentagastrin-induced release of FFAs. Methods: A double-blind, crossover, placebo-controlled study was conducted in which patients with PD and healthy volunteers received 2 injections of pentagastrin, 7-10 days apart, with randomization of the order of pretreatment with placebo and EE. Results: We found a statistically significant, time-dependent release of FFAs in response to pentagastrin challenge. However, this release of FFAs was not attenuated by pretreatment with EE. Conclusions: These results support the hypothesis that release of FFAs in association with panic attacks occurs in a manner similar to the stress-induced lipolysis model. This suggests a possible mechanism for the elevated serum cholesterol levels observed in patients with PD. However, the occurrence of a delayed increase in low-density lipoprotein (LDL) cholesterol following induction of a panic attack remains to be tested in studies incorporating a placebo injection visit and timed measurements of LDL cholesterol.