Decreased neurokinin-1 (substance P) receptor binding in patients with panic disorder: positron emission tomographic study with [18F]SPA-RQ

Biol Psychiatry. 2009 Jul 1;66(1):94-7. doi: 10.1016/j.biopsych.2008.12.027. Epub 2009 Feb 7.

Abstract

Background: Positron emission tomography (PET) can localize and quantify neurokinin-1 (NK(1)) receptors in brain using the nonpeptide antagonist radioligand, [(18)F]SPA-RQ. We sought to determine if patients with panic disorder have altered density of NK(1) receptors in brain because of their history of recurrent panic attacks. We also sought to determine if a drug-induced panic attack releases substance P in brain, as measured by decreased binding of [(18)F]SPA-RQ.

Methods: Positron emission tomography scans with [(18)F]SPA-RQ were performed in 14 patients with panic disorder and 14 healthy subjects. Of these two groups, 7 patients and 10 healthy subjects were scanned twice, once at baseline and once after injection of doxapram, a drug that induces panic attacks.

Results: NK(1) receptor binding in patients (n = 14) compared with that in healthy subjects (n = 14) was significantly decreased by 12% to 21% in all brain regions. Doxapram effectively produced panic attacks in 6 of 7 patients with panic disorder but only 2 of 10 healthy subjects. Doxapram caused no significant change of [(18)F]SPA-RQ binding in either patients or healthy subjects.

Conclusions: Although induction of a panic attack has no significant effect on [(18)F]SPA-RQ binding to NK(1) receptors, patients with panic disorder have widespread reduction of NK(1) receptor binding in brain.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Brain / diagnostic imaging
  • Brain / metabolism*
  • Brain / physiopathology
  • Brain Mapping
  • Female
  • Humans
  • Male
  • Middle Aged
  • Panic Disorder / diagnostic imaging
  • Panic Disorder / metabolism*
  • Panic Disorder / pathology
  • Panic Disorder / physiopathology
  • Piperidines*
  • Positron-Emission Tomography
  • Protein Binding / physiology
  • Receptors, Neurokinin-1 / metabolism*
  • Tetrazoles*

Substances

  • (2-fluoromethoxy-5-(5-trifluoromethyltetrazol-1-yl)benzyl)(2-phenylpiperidin-3-yl)amine
  • Piperidines
  • Receptors, Neurokinin-1
  • Tetrazoles