June 1996

Excessive Mortality in Young Free-Ranging Male Nonhuman Primates With Low Cerebrospinal Fluid 5-Hydroxyindoleacetic Acid Concentrations

Author Affiliations

From the Section on Neurochemistry and Neuroendocrinology, Laboratory of Clinical Studies, Division of Intramural and Clinical Biological Research, National Institute of Alcohol Abuse and Alcoholism (Drs J. D. Higley and Linnoila and Mr Lindell), and Laboratory of Comparative Ethology, National Institute of Child Health and Human Development (Ms S. B. Higley and Dr Suomi), Bethesda, Md; Laboratory Animal Breeders and Services Inc, Yemassee, SC (Drs Mehlman and Taub and Ms Fernald); and the Food and Drug Administration, Bethesda (Dr Vickers).

Arch Gen Psychiatry. 1996;53(6):537-543. doi:10.1001/archpsyc.1996.01830060083011

Background:  The purpose of this study was to assess the impact of central serotonin turnover rate on survival to adulthood among nonhuman primates living in a large, free-ranging colony.

Methods:  The rate of mortality was ascertained over a 4-year period after obtaining blood and cisternal cerebrospinal fluid (CSF) samples from 49 free-ranging, 2-year-old prepubertal male rhesus monkeys. Cerebrospinal fluid was assayed for 5-hydroxyindoleacetic acid (5-HIAA), norepinephrine, 3-methoxy-4-hydroxyphenylgycol, and homovanillic acid. Blood plasma was assayed for adrenocorticotropic hormone, cortisol, and testosterone. Following the sampling of body fluids, records of scars and wounds and aggressive encounters were used to rank the subjects from low to high in aggressiveness. Direct observations of aggressive behavior were collected from 27 of the subjects over a 3-month period.

Results:  Four years later, 6 of the 49 subjects were known to be dead and an additional 5 had been missing for more than 2 years and were presumed dead. The CSF 5-HIAA concentrations were predictive of which subjects died, with 46% of the subjects with low CSF 5-HIAA concentrations dead or presumed dead. None of the subjects from the highest CSF 5-HIAA concentration quartile were dead or missing. Indeed, 91% of the dead subjects came from the 2 lowest quartiles of CSF 5-HIAA concentrations. Direct observations of aggressive behavior showed that dead or missing subjects had initiated escalated aggression, a measure of unrestrained aggression that has a high probability of trauma or injury, at a higher rate than subjects that were known to be alive. The cause of death could be ascertained for 6 of the 11 missing subjects. The 4 subjects that were known to die as a consequence of aggressive encounters came from the lowest quartile of CSF 5-HIAA concentrations and had been rated as more aggressive during their initial capture. Subjects captured more than once possessed lower CSF 5-HIAA concentrations, were rated as more aggressive, and were more likely to suffer early death than those captured only once.

Conclusion:  These findings suggest that low CSF 5-HIAA concentrations quantified early in life is a powerful biological predictor of future excessive aggression, risk taking, and premature death among nonhuman primate males.