IMAGING NEUROINFLAMMATION IN BIPOLAR DISORDER WITH RADIOLABELED ARACHIDONIC ACID: We reported that brain uptake of radiolabeled arachidonic acid (1-14CAA) could be used to assess neuroinflammation in different animal models, and confirmed using PET and the positron-emitting isotope 1-11CAA the presence of upregulated AA incorporation as a marker of neuroinflammation in Alzheimer disease (AD) patients (Esposito et al., J Nucl Medicine. 2008 49:1414-21). Based on this work, in collaboration with researchers at the at Weill Cornell Medical College and the New York Psychiatric Institute, we are conducting a NIH-grant supported protocol to extend this observation and to neuroimage neuroinflammation with 1-11CAA using PET in patients with bipolar disorder. This research is based in part on our report that the postmortem brain from bipolar disorder patients demonstrated increased markers of neuroinflammation, in association with increased markers of upregulated arachidonic acid (AA) metabolism. Taken in the context of our findings that mood stabilizers used in BD downregulate rat brain AA metabolism, Dr. Elizabeth Sublette at New York Psychiatric Institute has initiated a NIH Grant-supported collaborative clinical protocol to image brain AA metabolism, using our PET method in depressed patients with BD, compared to healthy controls. IMAGING FAILING SYNAPTIC INTEGRITY WITH PROGRESSIVE BRAIN DISEASE. We published blood flow changes in the human brain, using 15O-H20 PET, in response to visual flash stimulation at different frequencies. We showed progressive synaptic failure in Alzheimer disease patients in relation to dementia severity (Mentis et al. Am J Psychiatry 155, 785, 1998). We are planning a collaboration with Professor Elliot Hong, at the University of Maryland School of Medicine, to map brain regional evoked responses (event related potentials) using electroencephalography, in response to the same visual flash stimulation paradigm, in control and schizophrenic patients, as a potential marker of synaptic changes in schizophrenia. Synaptic changes may underlie cognitive deficits, and might be identified using ERP and our flash stimulation paradigm. We plan to extend the method using fMRI in a later collaboration.