Overview Type 1 and II personality correlates of excessive alcohol consumption, such as differential social adjustment, risk taking, violence, as well as differential survival, are studied in free-ranging field settings, where subjects engage in species-typical behaviors with minimal human interference. This naturalistic population is large, with over 5000 rhesus monkeys, offering a unique opportunity to investigate a large variety of phenotypes. These research subjects are also studied developmentally using a longitudinal design. Real world outcomes can be studied in these subjects, placing the phenotypes in the natural environments from which the traits evolved. I. Studies of Females with Low CSF 5-HIAA concentrations in Feral Environments To date our naturalistic studies of the phenotypic expression of low concentrations of CSF 5-HIAA have focused mainly on males. There is reason to think that while females with low CSF 5-HIAA concentrations would show some temperamental similarities to males, given their differences in life history patterns, when compared to males, behavioral differences would be present as well. Unlike males, who live much of their lives independent of family relationships females live in closely bonded, extended families. Therefore we hypothesized that females would be buffered from many of the psychopathological effects of impoverished CNS serotonin. To assess the phenotype in females, four years ago, we began to gather a sample of young female macaques with varying levels of CSF 5-HIAA. Like the ostracized males with low CSF 5-HIAA concentrations, females with low CSF 5-HIAA concentrations seldom engaged in affiliative social interactions. They were more likely to act in a bully-like fashion by """"""""kidnapping"""""""" other females' infants. Of the first 7 females who died, they were more likely to possess low CSF 5-HIAA concentrations than subjects who survived. This finding replicates earlier data from males showing premature mortality in males with low CSF 5-HIAA concentrations. Thus, like males, adolescent and young adult females with low CSF 5-HIAA concentrations were antisocial and more likely to die at an early age. Unlike males, however, premature death was not just a result of violence. In the laboratory, premature deaths of female monkeys with low CSF 5-HIAA concentrations are typically the result of chronic diarrhea, suggesting that they are at risk for serious gastrointestinal illness, as well as traumatic violence. II. Genotype Comparisons Over the last year Dr. Newman has been expanding his research interest with the MAOA gene promoter polymorphism by examining the evolution of the gene across a broad taxonomic sampling of primates. To date, he has found extensive variation in the MAOA repeat polymorphism in Old World Monkeys and in apes, whereas New World Monkeys and prosimians so far appear to not to possess the polymorphism. Because the polymorphism is functional in both humans and rhesus, imparting a modulatory effect on transcriptional efficiency, the implication is that this variant is under selection in higher primates generally. This new avenue of research offers the intriging potential to understand how a gene becomes linked to alcoholism and to understand how the environment plays a role in the phenotypic expression of a genotype (gene X environment interaction) with the MAOA gene and alcohol consumption in our rhesus in an evolutionary framework hitherto not possible. III. Fear Anxiety and HPA output It is well established that anxiety and the HPA response to stress are predictors of excessive alcohol intake. In a study performed in collaboration with Drs. Stefan Tiefenbacher and Melinda Novak at the New England Regional Primate Research Center, we examined continuity and change in emotional reactivity as assessed by hypothalamic-pituitary-adrenal (HPA) activity in rhesus monkeys. Plasma samples were obtained from mother-peer-reared and parentally-deprived surrogate-peer-reared monkeys and assayed the samples for cortisol concentrations at 5 time points in infancy. Both plasma and saliva samples were collected for cortisol assay from the same monkeys as 1-, 2-, and 3-year-old juveniles. We found that plasma cortisol concentrations increased during the first 5 months of life and decreased from 1 to 3 years of age. Females consistently had higher plasma cortisol concentrations than males. Plasma cortisol concentrations were lower in surrogate-peer reared than mother-peer reared monkeys during the first month of life. Juvenile plasma cortisol concentrations were significantly correlated with infant cortisol levels at all but the earliest time point. Analysis of salivary cortisol from a subset of animals showed a similar age-related decline and the presence of a significant rearing effect, with lower concentrations in surrogate-peer-reared juveniles, but no sex difference. Salivary and plasma cortisol concentrations in these animals were highly correlated.
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