Poster Sessions

IMAG -9

Yota Fujimura

Y. Fujimura, F. Yasuno, A. Farris, J.-S. Liow, M. Geraci, W. Drevets Drevets, D. S. Pine, S. Ghose, A. Lerner, R. Hargreaves, H. D. Burns, C. Morse, V. W. Pike, R. Innis

Decreased Neurokinin-1 (Substance P) Receptor Binding in Patients with Panic Disorder: Positron Emission Tomography Study with [18F]SPA-RQ

Introduction: Studies in animals have shown that pain and stress cause the release of the peptide neurotransmitter substance P, which binds to and causes the internalization of neurokinin-1 (NK1) receptors. For example, NK1 receptor internalization occurs in rat dorsal horn of the spinal cord after exposure to pain and in several forebrain regions after forced swim stress. Positron emission tomography (PET) can localize and quantify NK1 receptors in humans using the nonpeptide antagonist [18F]SPA-RQ. Using this radioligand, we sought to determine if receptor internalization also occurs in patients with panic disorder after induction of a panic attack. We imaged patients and healthy subjects twice: at baseline and after injection of doxapram, a respiratory stimulant known to induce panic attacks. We predicted that internalization would be evidenced by a decrease of radioligand binding after doxapram in comparison to the baseline scan. Materials and Methods: One or two PET scans with [18F]SPA-RQ were performed in a total of 14 patients with panic disorder and 14 healthy subjects. Of these two groups, 7 patients and 10 healthy subjects were scanned twice, at baseline and after injection of doxapram (0.5 mg / kg). After injection of 317 ± 52 MBq [18F]SPA-RQ, subjects were scanned for a total of ~4 h, with two breaks of 1 h each after 2h. The cerebellum was used as a reference region, and receptor binding was quantified as BPND – i.e., the ratio at equilibrium of specific binding to nondisplaceable uptake. Results: 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. However, the binding at baseline in patients (n=14) compared to healthy subjects (n=14) showed widespread and statistically significant decreases. For example, in patients with panic disorder, most neocortical regions were decreased ~15-20% (P<0.007). Conclusion: Induction of a panic attack had no significant effect on NK1 receptor binding in brain, suggesting that any released substance P neither displaced the radioligand nor caused internalization of the receptor. We unexpectedly found that, in comparison to healthy subjects, patients with panic disorder have widespread reduction in NK1 receptor binding in the brain. Although the acute stress of a panic attack had no effect on radioligand binding, these data suggest that the recurrent and long-standing stress in patients with panic disorder can decrease or internalize NK1 receptors in brain.