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Induced Panic Attacks Shift  -Aminobutyric Acid Type A Receptor Modulatory Neuroactive Steroid Composition in Patients With Panic Disorder
Preliminary Results
Andreas Ströhle, MD;
Elena Romeo, MD;
Flavia di Michele, MD;
Augusto Pasini, MD;
Bettina Hermann, PhD;
Gisela Gajewsky;
Florian Holsboer, MD, PhD;
Rainer Rupprecht, MD
Arch Gen Psychiatry. 2003;60:161-168.
Background Certain metabolites of progesterone such as 3 ,5-tetrahydroprogesterone (3,5-THP; allopregnanolone) and 3,5 -THP (pregnanolone) are potent, positive allosteric modulators of  -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 3,5-THP, 3,5-THP, the isomer 3,5-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 3,5-THP and 3,5-THP and a concomitant increase in the concentrations of the functional antagonistic isomer 3,5-THP, findings that are compatible with a decreased -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 -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.
From the Max Planck Institute of Psychiatry, Munich, Germany (Drs Ströhle, Hermann, Holsboer, and Rupprecht and Ms Gajewsky); and Tor Vergata University, IRCCS Santa Lucia, Rome, Italy (Drs Romeo, di Michele, and Pasini). Dr Ströhle is now with the Department of Psychiatry and Psychotherapy, Charité Hospital, Humboldt University at Berlin, Berlin, Germany.
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