Decreased neurokinin-1 (substance P) receptor binding in patients with panic disorder: positron emission tomographic study with [18F]SPA-RQ.
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.
Fujimura
Yota
Y
Molecular Imaging Branch, National Institute of Mental Health, Bethesda, Maryland 20892, USA. FujimuraY@mail.nih.gov
Yasuno
Fumihiko
F
Farris
Amanda
A
Liow
Jeih-San
JS
Geraci
Marilla
M
Drevets
Wayne
W
Pine
Daniel S
DS
Ghose
Subroto
S
Lerner
Alicja
A
Hargreaves
Richard
R
Burns
H Donald
HD
Morse
Cheryl
C
Pike
Victor W
VW
Innis
Robert B
RB
D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology; D001931:Brain Mapping; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016584:Panic Disorder / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D010880:Piperidines; D049268:Positron-Emission Tomography; D011485:Protein Binding / Q000502:physiology; D018040:Receptors, Neurokinin-1 / Q000378:metabolism*; D013777:Tetrazoles
C517420:(2-fluoromethoxy-5-(5-trifluoromethyltetrazol-1-yl)benzyl)(2-phenylpiperidin-3-yl)amine; D010880:Piperidines; D018040:Receptors, Neurokinin-1; D013777:Tetrazoles