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 (NK₁) receptors in brain using the nonpeptide antagonist radioligand, [¹⁸F]SPA-RQ. We sought to determine if patients with panic disorder have altered density of NK₁ 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 [¹⁸F]SPA-RQ. Methods: Positron emission tomography scans with [¹⁸F]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: NK₁ 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 [¹⁸F]SPA-RQ binding in either patients or healthy subjects. Conclusions: Although induction of a panic attack has no significant effect on [¹⁸F]SPA-RQ binding to NK₁ receptors, patients with panic disorder have widespread reduction of NK₁ receptor binding in brain.