Glutamate turnover and glucose metabolism in alcoholism

Yale University, New Haven CT

Investigators

Linked publications & trials

Abstract

There is growing evidence that recovery from ethanol dependence is associated with an extended phase of depressed metabolic activity in the frontal cortex, and these metabolic reductions are believed to correspond to reduced glutamate function. The deficits become less diffusely localized during the initial months of sobriety, corresponding with the reduction in risk for relapse to alcoholism during this period and improvements in cognitive function. Reductions in frontal glutamate function may contribute to the complex picture associated with the protracted recovery from ethanol dependence. The overarching hypothesis of this project is that reduced rates of glutamate neurotransmission in the frontal lobe contribute to reduced metabolism, cognitive deficits, and perhaps risk for relapse in recovering alcohol dependent patients. This study will evaluate recently detoxified alcohol-dependent subjects for differences in frontal brain glucose metabolism and glutamate neurotransmitter release compared to healthy control subjects, using novel magnetic resonance spectroscopic techniques. These two rates will be evaluated for correlation with one another to determine if glucose metabolism shows the previously reported 1:1 relationship with glutamate neurotransmission. The rates will be compared with results from cognitive tests to evaluate the hypothesis that lower performance is related to reduced metabolic rates. The relationship of these rates with electrophysiologic measurements of brain activity will also be explored, as will the rate of glutamate neurotransmission with the magnitude of cue-induced craving. In summary, this work will explore the effects of recent abstinence and risk of relapse using a combination of brain imaging, electrophysiology, and cognitive methods to examine the relationship of basic chemistry and neuronal activity to brain function in alcohol dependence.