This research is designed to determine neuroanatomical and neurochemical correlates of addictive and aggressive/impulsive behavior in human subjects. The principal focus of these studies is the measurement and correlation of regional cerebral glucose metabolic activity, using positron emission tomography (PET), cerebrospinal fluid metabolites, and measures of impulsive/aggressive behavior and excessive alcohol consumption. Past studies have correlated decreasing cerebrospinal fluid (CSF) levels of 5-hydroxy-indoleacetic acid (5-HIAA) with increasing lifetime histories of aggression. During the past year we have found that male alcoholic with a history of violence have lower glucose metabolism in the right orbital cortex than male controls without a history of violence. Male alcoholics in general (i.e., with or without a history of violence) also have lower glucose metabolism in the right orbital cortex, but, in addition, show increased glucose metabolism in the left middle temporal gyrus compared to male controls. Since the during the PET scan subjects performed an auditory discrimination task, the increase in glucose utilization in auditory association cortex observed among alcoholics may reflect an inefficiency in the way in which alcoholics performed the task. We also found that low CSF 5-HIAA (in both controls and alcoholics) was associated with increased glucose utilization in the right orbital cortex. Finally, we found large decreases in glucose metabolism throughout the frontal lobes of female compared to male alcoholics. Such differences were not present when male and female controls were compared. Subject accrual continues. We particularly need to recruit more female control subjects.
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