Docosahexaenoic acid (DHA, 22:6 n-3) is an essential omega-3 fatty acid that is selectively concentrated in the brain. Epidemiologic studies suggest that DHA deficiency is related to affective disorders, while clinical studies suggest that DHA is efficacious in treating depression. DHA has also been shown to be an important second messenger involved in phospholipase A(2)-mediated signal transduction. Although animal studies have provided a wealth of knowledge about the role of DHA in neural function, no method exists of evaluating DHA content or metabolism in the living human brain. Our goal is to establish a quantitative method of examining brain DHA metabolism using PET in healthy humans and to measure regional DHA incorporation from plasma into the brain. Utilizing the data from the pilot phase with healthy volunteers, we will apply the method to study DHA metabolism in alcoholics. Since alcohol consumption depletes brain DHA, we hypothesize that compared to healthy volunteers; alcoholics will have a decreased rate of incorporation of DHA from plasma into brain. Utilizing the method we have established, we anticipate that we will find previously undetectable metabolic abnormalities in alcoholics. We may further find that such abnormalities are correlated with cognitive or behavioral function. Now that the pilot phase of the protocol has been completed, we are proceeding with the main phase of the protocol to study non-smoking chronic alcoholics.