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

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.

• Authors: Yota Fujimura, Fumihiko Yasuno, Amanda Farris, Jeih-San Liow, Marilla Geraci, Wayne Drevets, Daniel S Pine, Subroto Ghose, Alicja Lerner, Richard Hargreaves, H Donald Burns, Cheryl Morse, Victor W Pike, Robert B Innis
• Journal: Biological psychiatry (Biol Psychiatry) Vol. 66 Issue 1 Pg. 94-7 (Jul 01 2009) ISSN: 1873-2402 [Electronic] United States
• PMID: 19200949 (Publication Type: Journal Article, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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