Cerebral Glucose Metabolism, CSF 5-HIAA Levels, and Aggressive Behavior in Rhesus Monkeys

Doudet, Doris PhD
Hommer, Daniel MD
Higley, Dee J. PhD
Andreason, Paul J. MD
Moneman, Reza PhD
Suomi, Stephen J. PhD
Linnoila, Markku MD, PhD

Received Feb. 13, 1995; revision received June 21, 1995; accepted June 23, 1995. From the Laboratory of Cerebral Metabolism, NIMH, Bethesda, Md.; the Laboratory of Clinical Studies, National Institute on Alcohol Abuse and Alcoholism; and the Laboratory of Comparative Ethology, National Institute of Child Health and Human Development, Bethesda, Md. Address reprint requests to Dr. Linnoila, Laboratory of Clinical Studies, National Institute on Alcohol Abuse and Alcoholism, NIH Bldg. 10, Room 3C103, 10 Center Dr. MSC 1256, Bethesda, MD 20892.

American Journal of Psychiatry 152(12):p 1782-1787, December 1995.

Objective

Considerable evidence suggests that low concentrations of 5-hydroxyindoleacetic acid (5-HIAA) in CSF are associated with a history of aggressive behavior in both human and nonhuman primates. The purpose of this investigation was to examine the relationships among CSF 5-HIAA concentration, history of aggressive behavior, and cerebral glucose metabolism in a group of nonhuman primates whose CSF 5-HIAA had been sampled several times over the preceding 2 years and whose social behavior had been observed since birth. Method: The subjects were nine adult male rhesus monkeys studied under isoflurane anesthesia. Cerebral glucose utilization was measured by [sup 18 F]fluorodeoxyglucose positron emission tomography. Aggressiveness ratings were made by a primatologist who had had frequent contact with the animals over several years. Results: There was a significant negative correlation between ratings of aggressive behavior and CSF 5-HIAA concentrations. There was also a negative correlation between the dose of pentobarbital required to induce anesthesia and level of CSF 5-HIAA. Moreover, there were significant negative correlations between CSF 5-HIAA levels and both whole brain glucose utilization and regional glucose utilization in the orbital-frontal cortex. Conclusions: These results suggest that both increased aggressiveness and low concentrations of CSF 5-HIAA are associated with higher brain glucose metabolism in rhesus monkeys under standardized anesthesia. Aggressive nonhuman primates with low CSF 5-HIAA concentrations may have ``innate'' tolerance toward functional gamma -aminobutyric acid A receptor agonists such as pentobarbital, isoflurane, and possibly alcohol.

(Am J Psychiatry 1995; 152:1782-1787)