In vivo proton magnetic resonance spectroscopic examination of benzodiazepine action in humans

In an examination of the effect of benzodiazepines on brain chemistry, 44 healthy controls underwent a short echo-time proton magnetic resonance spectroscopy (1H MRS) session after induced sedation with intravenous midazolam (0.03 mg/kg) plus fentanyl (2 μg/kg). The regions of interest were the anterior cingulate cortex, right basal ganglia, right frontal lobe, and right hippocampus. Twenty-five of these subjects underwent the second 1H MRS session while awake. The measured 1H MRS metabolites included N-acetyl-aspartate, creatine-containing compounds (PCr+Cr), choline-containing compounds, myo-inositol, and glutamate plus glutamine, which were quantified both as absolute values and metabolite/PCr+Cr ratios. The results were analyzed using independent group t tests and repeated measures analysis of variance (ANOVA, with alpha values set at 0.025 to minimize the risk of false-positive findings arising from multiple comparisons. No significant difference between subjects under midazolam plus fentanyl induced sedation and awake could be detected with unpaired analyses. Paired comparisons by ANOVA with repeated measures found that neither drug (midazolam plus fentanyl) nor the drug by time (interval between two scan times) interaction had a significant effect on the quantified metabolites. These findings encourage utilization of benzodiazepine-induced brief sedation during in vivo 1H MRS experiments of the brain, and may help with elucidation of state-dependent neurochemical alterations during the course of bipolar and schizoaffective disorders.