Single-voxel 1H-MRS investigation of brain metabolic changes during lactate-induced panic

Intravenous sodium lactate infusion is a robust laboratory technique for eliciting panic in susceptible individuals. The objective for this study was to replicate previous work which found differential brain lactate rises among lactate-sensitive panic subjects relative to control subjects using single-voxel 1H-magnetic resonance spectroscopy (MRS). Single-voxel 1H-MRS was used to measure brain lactate changes in the insular cortex region among 13 panic disorder subjects and 10 healthy control subjects during the infusion. One panic subject prematurely terminated the study due to a panic response during lactate infusion. Data from two additional control subjects and one panic subject were lost due to technical problems. Four panic subjects were reinfused with lactate while panic-free under treatment with fluoxetine (20 mg/day). At the time of initial infusion, all subjects were medication-free for at least 1 month. Ten panic subjects, but no control subjects, panicked during lactate infusion. In comparison to control subjects, panic subjects demonstrated significantly greater and prolonged brain lactate rises in the insular cortex region. Three of four medicated panic subjects experienced blockage of panic symptoms during lactate reinfusion but all exhibited persistent excesses in brain lactate rise. Consistent with our prior observations, greater and prolonged lactate rises in the insular brain region occur during and following lactate infusion among panic subjects compared to control subjects. This differential brain metabolic response did not appear to normalize when a small subset of panic patients were reinfused following resolution of panic symptoms during treatment over 3-4 months with fluoxetine.