OBJECTIVE: To characterize changes associated with lactate-induced panic, proton magnetic resonance spectroscopy (MRS) was used to measure brain lactate during intravenous infusion of 0.5-M sodium lactate in panic disorder patients and comparison subjects. METHOD: Eight panic disorder subjects, five medicated and three unmedicated, and eight healthy comparison subjects were studied at baseline, during lactate infusion (5 meq/kg over 20 minutes), and after infusion. Localized proton MRS was used to acquire averaged spectra every 5 minutes from a 27-ml sampling volume in the insular cortex and adjacent regions. Brain lactate levels, quantitatively estimated in relationship to N-acetyl aspartate, were compared to blood lactate levels. RESULTS: The procedure was generally well tolerated; one panic subject requested early termination before lactate infusion. Significant rises in brain lactate levels occurred for all subjects during infusion. The panic patients who responded to lactate (N = 3) had significantly higher brain lactate levels before, during, and after infusion than did the comparison subjects (N = 8) and medicated patients who were lactate nonresponders (N = 4). After infusion the panic patients with lactate- induced panic exhibited a striking dissociation between decreasing blood lactate and further increases in brain lactate levels. CONCLUSIONS: These preliminary observations indicate that brain lactate increases during a standard lactate infusion. Lactate-induced panic is associated with greater increases than in comparison subjects and with prolonged elevations in brain lactate that are decoupled from falling blood lactate levels after completion of lactate infusion. Further investigation is necessary to clarify the mechanism(s) responsible for these findings and establish whether a causal relationship to the occurrence of lactate-induced panic exists.Abstract Teaser