ATROPHY CORRECTED BRAIN DOCOSAHEXAENOIC ACID INCORPORATION AND BLOOD FLOW ARE INCREASED IN CHRONIC ALCOHOLICS In animal models, excessive alcohol consumption is reported to reduce brain docosahexaenoic acid (DHA) concentration, suggesting disturbed brain DHA metabolism. We hypothesized that brain DHA metabolism and regional cerebral blood flow (rCBF) also are abnormal in chronic alcoholics. We compared 15 non-smoking chronic alcoholics, studied within 7 days of their last drink, with 22 non-smoking healthy controls. Using our published neuroimaging methods with PET, we measured regional coefficients (K*) and rates (Jin) of DHA incorporation from plasma into the brain of each group using 1-11CDHA, and regional cerebral blood flow (rCBF) using 15Owater. Data were partial volume error corrected for brain atrophy. Plasma unesterified DHA concentration was quantified. Mean K* for DHA was significantly and widely elevated by 10-20%, and rCBF was elevated by 7%-34%, in alcoholics compared with controls. Unesterified plasma DHA did not differ significantly between groups nor did whole brain Jin, the product of K* and unesterified plasma DHA concentration. Significantly higher values of K* in alcoholics indicate increased brain avidity for DHA, thus a brain DHA metabolic deficit vis--vis plasma DHA availability. Higher rCBF in alcoholics suggests increased energy consumption. These changes may reflect a hypermetabolic state related to early alcohol withdrawal, or a general brain metabolic change in chronic alcoholics. (1) 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.
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