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Developmental Continuity Of Individual Differences In Re

$0Z01FY2002HDNIH

Child Health And Human Development

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Abstract

This project investigates primate biobehavioral development through comparative longitudinal studies of rhesus macaques and other monkey species, with special emphasis on characterizing individual patterns of differential behavioral and physiological responses to environmental novelty and challenge and on determining long-term developmental consequences for individuals of different genetic backgrounds reared in different physical and social environments. Several studies completed this year focused on possible interactions between a polymorphism in 5-HTT, a candidate gene for impaired serotonergic function, and differential early social experience. We published the first report of a specific gene-environment interaction in a nonhuman primate species: rhesus monkeys with the "short" (LS) allele exhibited deficits in central serotonin metabolism relative to those with the "long" (LL) allele, but only if they had been nursery-reared; in contrast, LS monkeys reared by their biological mother had normal serotonin metabolism, suggesting a "buffering" effect of maternal rearing. We reported a similar buffering effect of maternal rearing for measures of state control and visual orienting obtained during infancy. Rhesus monkeys are notoriously aggressive as a species, relative to other macaques (indeed, relative to most other primates); by contrast, Barbary macaques are unusual in their relatively low levels of aggression. This past year we were able to genotype members of a group of free-ranging Barbary macaques with respect to the 5-HTT gene and, unlike the case for rhesus monkeys, we found no individuals with either the LS or the LL allele. Instead, all of the Barbary macaques sampled had an "extra long" (XL) allele, a form found in less than 2% of the rhesus monkeys genotyped to date. This past year we also characterized a polymorphism in the MAO-A receptor gene, demonstrated functional differences among the different alleles, genotyped the LCE rhesus monkey colony with respect to this polymorphism, and began analyzing a variety of behavioral and physiological measures as a function of genetic status and early rearing history. Our initial analysis revealed a significant allele x rearing history interaction for aggressive behavior during the juvenile years: whereas as mother-reared monkeys with the "7" allele initiated more bouts of aggression than those with the "5" or "6" allele, the reverse was found for nursery-reared monkeys. We also completed a study investigating the relationship between serotonin metabolism and measures of impulsive and aggressive behavior in adult female rhesus monkeys living in free-ranging naturalistic social groups. Previous work had demonstrated that low cerebrospinal fluid (CSF) concentrations of 5-HIAA, the primary central serotonin metabolite, were associated with a relatively high incidence of risky, impulsive behavior and socially inappropriate, violent aggression (but not with low-level, socially appropriate dominance behavior) in free-ranging adult males and in both adult male and female rhesus monkeys reared in captivity. Our analyses revealed that low CSF 5-HIAA concentrations in these free-ranging females were also associated with excessive risky, impulsive behavior but not with violent aggression; instead a significant negative correlation was found between CSF 5-HIAA and socially appropriate dominance behavior. Finally, we published a study examining the biobehavioral consequences of adding a long-chain essential fatty acid supplement to the standard diet of nursery-reared rhesus monkey infants, which effectively raised their serum levels to those characteristic of infants raised (and nursed) by their biological mothers. Nursery-reared infants receiving dietary supplements exhibited accelerated motor maturation and enhanced visual orientation capabilities during their first month of life relative to infants fed the standard formula, more closely resembling the patterns normally seen in mother-reared infants. A follow-up study examined heart rate variability in these monkeys when they were 3 years of age. Monkeys who had received the formula supplement exhibited significantly greater heart rate variability than their counterparts who had received the standard formula during infancy, despite the fact that both groups had been maintained on a supplemented diet following weaning.

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