A broad-based approach to integrating biochemical, brain imaging and pharmacological studies in the study of affective disorders was implemented during the last year. Highlights of these efforts include: a). Healthy volunteers have been studied using a novel double FDG PET Scan method in conjunction with intravenous idazoxan (IDX), a selective alpha-2 antagonist. Results reveal that acute alpha-2 blockade decreases frontal glucose metabolism and surprisingly increases it in primary visual cortex providing a possibility of measuring central alpha-2 function in humans with affective illness. b.) Based on the metabolic change in primary visual cortex, we measured visual evolved potentials during an infusion with IDX. Our pilot study indicates an increase in P100 suggesting the possibility of a more generally available test of central alpha-2 function. c.) Exploratory studies of idazoxan's effects on functional MRI in volunteers show decreased deoxyhemoglobin content of occipital primary visual cortex; a functional measure of blood flow to the area consistent with the split FDG findings noted above. The exciting possibility that MRI may be applied to investigate central alpha-2 function in psychiatric illness is being further explored. d.) An off-site double blind outpatient trial of idazoxan in bipolar depression was initiated and reveals a positive response in the first 4 out of 6 patients, consistent with our earlier findings here with inpatients.
