Induced Panic Attacks Shift γ-Aminobutyric Acid Type A Receptor Modulatory Neuroactive Steroid Composition in Patients With Panic Disorder

Abstract

The association between changes in plasma neuroactive steroid concentrations and experimentally induced panic attacks and the well-documented pharmacological properties of these compounds as gamma-aminobutyric acid type A receptor modulators suggest that neuroactive steroids may play a role in the pathophysiology of panic attacks in patients with panic disorder.

A quantitiative LC-MS/MS method for the measurement of arachidonic acid, prostanoids, endocannabinoids, N-acylethanolamines and steroids in human plasma

“…Different studies have reported levels of THDOC and THP in human and rodent plasma using gas chromatography chemical ionization mass spectrometry (GC-MS) or radioimmunassays [50][51][52][53][54][55]. Using our LC-MS/MS, we were unable to detect these analytes.…”

Panic Induction with Cholecystokinin-Tetrapeptide (CCK-4) Increases Plasma Concentrations of the Neuroactive Steroid 3α, 5α Tetrahydrodeoxycorticosterone (3α, 5α-THDOC) in Healthy Volunteers

“…In contrast, no changes in neuroactive steroid concentrations could be observed during experimental panic induction with sodium lactate or CCK-4 in healthy controls (Strohle et al, 2003). However, panic induction with 25 mg CCK-4 was far less pronounced in healthy controls than in patients with panic disorder (Strohle et al, 2003).…”

“…However, panic induction with 25 mg CCK-4 was far less pronounced in healthy controls than in patients with panic disorder (Strohle et al, 2003). To rule out the possibility that the difference in neuroactive steroid Online publication: 18 August 2004 at http://www.acnp.org/citations/ Npp08180404061/default.pdf composition between patients with panic disorder and controls just reflects the level of anxiety, 3a, 5a-THP, 3a, 5b-THP, and 3b, 5a-THP were analyzed in a follow-up study in healthy volunteers after panic induction with 50 mg CCK-4, which yields the same level of anxiety as 25 mg CCK-4 in patients with panic disorder (Zwanzger et al, 2004).…”

“…Blood samples were quantified for levels of 3a, 5a-THDOC by means of a highly sensitive and specific combined GC/MS analysis extraction with ethyl acetate as described previously (Strohle et al, 2000(Strohle et al, , 2003. A Finningham Trace GC/MS equipped with a capillary column was used to analyze the derivatized steroids in the negative ion chemical ionization mode.…”

“…However, during panic induction with sodium lactate or 25 mg cholecystokinin-tetrapeptide (CCK-4), a marked decrease in plasma levels of the 3a-reduced GABA agonistic neuroactive steroids 3a, 5a-THP and 3a, 5b-THP was found, which was accompanied by a pronounced increase in the functional antagonistic isomer 3b, 5a-THP in patients with panic disorder (Strohle et al, 2003).…”