title: Induced panic attacks shift gamma-aminobutyric acid type A receptor modulatory neuroactive steroid composition in patients with panic disorder: preliminary results.
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-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.
authors.affiliation: Max Planck Institute of Psychiatry, Munich, Germany. andreas.stroehle@charite.de
authors.forename: Andreas
authors.initials: A
authors.lastname: Ströhle
authors.forename: Elena
authors.initials: E
authors.lastname: Romeo
authors.forename: Flavia
authors.initials: F
authors.lastname: di Michele
authors.forename: Augusto
authors.initials: A
authors.lastname: Pasini
authors.forename: Bettina
authors.initials: B
authors.lastname: Hermann
authors.forename: Gisela
authors.initials: G
authors.lastname: Gajewsky
authors.forename: Florian
authors.initials: F
authors.lastname: Holsboer
authors.forename: Rainer
authors.initials: R
authors.lastname: Rupprecht
mesh_terms: D000328:Adult; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D012739:Gonadal Steroid Hormones / Q000097:blood* / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D016584:Panic Disorder / Q000097:blood* / Q000139:chemically induced* / Q000503:physiopathology; D010919:Placebos; D011280:Pregnanolone / Q000097:blood* / Q000502:physiology; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000502:physiology; D019354:Sodium Lactate / Q000008:administration & dosage; D013758:Tetragastrin / Q000008:administration & dosage
chemical_list: D012739:Gonadal Steroid Hormones; D010919:Placebos; D011963:Receptors, GABA-A; D013758:Tetragastrin; D011280:Pregnanolone; D019354:Sodium Lactate