Background: Certain metabolites of progesterone such as 3alpha,5alpha-tetrahydroprogesterone (3alpha,5alpha-THP; allopregnanolone) and 3alpha,5beta-THP (pregnanolone) are potent, positive allosteric modulators of gamma-aminobutyric acid type A receptors. Although animal studies suggest anxiolytic properties of these endogenous modulators of central nervous excitability, no clinical data indicate whether they are also involved in the pathophysiology of anxiety disorders and panic attacks. Methods: We quantified the concentrations of 3alpha,5alpha-THP, 3alpha,5beta-THP, the isomer 3beta,5alpha-THP, and their precursors in the plasma of 10 patients with panic disorder and matched control subjects during panic attacks induced by means of sodium lactate and cholecystokinin tetrapeptide administration, using a highly sensitive gas chromatography-mass spectrometry analysis. Results: Panic attacks induced by sodium lactate and cholecystokinin tetrapeptide in patients with panic disorder were accompanied by pronounced decreases in the concentrations of 3alpha,5alpha-THP and 3alpha,5beta-THP and a concomitant increase in the concentrations of the functional antagonistic isomer 3beta,5alpha-THP, findings that are compatible with a decreased gamma-aminobutyric acid-ergic tone. No changes in neuroactive steroid concentrations were observed after placebo administration in patients with panic disorder or after placebo, sodium lactate, or cholecystokinin tetrapeptide administration in controls. Conclusions: 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-amino-butyric acid type A receptor modulators suggest that neuroactive steroids may play a role in the pathophysiology of panic attacks in patients with panic disorder.

Strohle, A., Romeo, E., Di Michele, F., Pasini, A., Hermann, B., Gajewsky, G., et al. (2003). Induced panic attacks shift gamma-aminobutyric acid type A receptor modulatory neuroactive steroid composition in patients with panic disorder preliminary results. ARCHIVES OF GENERAL PSYCHIATRY, 60(2), 161-168 [10.1001/archpsyc.60.2.161].

Induced panic attacks shift gamma-aminobutyric acid type A receptor modulatory neuroactive steroid composition in patients with panic disorder preliminary results

ROMEO, ELENA;PASINI, AUGUSTO;
2003-01-01

Abstract

Background: Certain metabolites of progesterone such as 3alpha,5alpha-tetrahydroprogesterone (3alpha,5alpha-THP; allopregnanolone) and 3alpha,5beta-THP (pregnanolone) are potent, positive allosteric modulators of gamma-aminobutyric acid type A receptors. Although animal studies suggest anxiolytic properties of these endogenous modulators of central nervous excitability, no clinical data indicate whether they are also involved in the pathophysiology of anxiety disorders and panic attacks. Methods: We quantified the concentrations of 3alpha,5alpha-THP, 3alpha,5beta-THP, the isomer 3beta,5alpha-THP, and their precursors in the plasma of 10 patients with panic disorder and matched control subjects during panic attacks induced by means of sodium lactate and cholecystokinin tetrapeptide administration, using a highly sensitive gas chromatography-mass spectrometry analysis. Results: Panic attacks induced by sodium lactate and cholecystokinin tetrapeptide in patients with panic disorder were accompanied by pronounced decreases in the concentrations of 3alpha,5alpha-THP and 3alpha,5beta-THP and a concomitant increase in the concentrations of the functional antagonistic isomer 3beta,5alpha-THP, findings that are compatible with a decreased gamma-aminobutyric acid-ergic tone. No changes in neuroactive steroid concentrations were observed after placebo administration in patients with panic disorder or after placebo, sodium lactate, or cholecystokinin tetrapeptide administration in controls. Conclusions: 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-amino-butyric acid type A receptor modulators suggest that neuroactive steroids may play a role in the pathophysiology of panic attacks in patients with panic disorder.
2003
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore BIO/09 - FISIOLOGIA
Settore MED/39 - NEUROPSICHIATRIA INFANTILE
English
Con Impact Factor ISI
3alpha hydroxy 5alpha pregnan 20 one; 4 aminobutyric acid A receptor; eltanolone; lactate sodium; neurosteroid; placebo; progesterone; tetragastrin; adult; anxiety disorder; article; central nervous system; clinical article; clinical trial; concentration response; controlled clinical trial; controlled study; disease association; double blind procedure; excitability; female; gas chromatography; human; male; mass spectrometry; panic; pathophysiology; randomized controlled trial; steroid blood level; tranquilizing activity; Adult; Female; Gas Chromatography-Mass Spectrometry; Gonadal Steroid Hormones; Humans; Male; Middle Aged; Panic Disorder; Placebos; Pregnanolone; Receptors, GABA-A; Sodium Lactate; Tetragastrin
Strohle, A., Romeo, E., Di Michele, F., Pasini, A., Hermann, B., Gajewsky, G., et al. (2003). Induced panic attacks shift gamma-aminobutyric acid type A receptor modulatory neuroactive steroid composition in patients with panic disorder preliminary results. ARCHIVES OF GENERAL PSYCHIATRY, 60(2), 161-168 [10.1001/archpsyc.60.2.161].
Strohle, A; Romeo, E; Di Michele, F; Pasini, A; Hermann, B; Gajewsky, G; Holsboer, F; Rupprecht, R
Articolo su rivista
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/49951
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