Developmental Continuity Of Individual Differences In Re

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. This past year a new experimental procedure was developed to monitor rhesus monkey maternal and fetal heart rate and blood pressure from the second trimester of pregnancy to parturition; the procedure involves surgically implanting indwelling catheters in both mother and fetus and recording data online via a tethering device that does not impede any locomotor or exploratory activity on the part of the mother. The initial pregnancy tested resulted in a successful birth and normal postnatal infant development. Preliminary analyses of the prenatal data revealed patterns of maternal and fetal heart rate and blood pressure changes that became increasingly synchronous with approaching parturition. Additional pregnancies are presently being followed. This past year we also completed a study evaluating relative heritability of various components of the LCE?s standard neurobehavioral assessment battery for rhesus monkey infants throughout the first 30 days of life. The analyses revealed significant heritability for the Orientation, State Control, and Activity (but not Motor Maturity) clusters at 14 days of age. By 30 days heritabilities had increased for the Orientation and Motor Maturity clusters, remained stable for the State Control cluster, and declined for the Activity cluster, suggesting that there were marked changes in relative heritabilities during the infants? initial month of life. Significant gender and early rearing condition components were also detected for 3 of the 4 clusters, and these components tended to increase in relative magnitude over the first month. A collaborative study with NIAAA and NIMH researchers employed PET imaging methodology to investigate possible differences in brain serotonin transporter receptor distribution and affinity for rhesus monkey juveniles who had been either reared by their biological mothers in small social groups or nursery-reared with same-age peers during their first 7 months of life. Analyses of serotonin transporter ligand binding potential and cerebral blood flow revealed significant deficits in raphe, thalamus, striatum, frontal, and parietal regions among peer-reared juveniles relative to their mother-reared counterparts, thereby demonstrating long-term effects of variation in early rearing at the level of brain structure and function. Several ongoing studies have focused on possible interactions between a polymorphism (due to length variation in the promoter region) in 5-HTT, a candidate gene for impaired serotonergic function, and differential early social experience. This past year we published a report of a specific gene-environment interaction in rhesus monkey HPA responsiveness to short-term social separation at 7 months of age: monkeys with the ?short? (LS) allele exhibited excessive ACTH responsiveness relative to those with the ?long? (LL) allele, but only if they had been nursery-peer-reared. In contrast, LS monkeys reared by their biological mother did not differ in ACTH responsiveness from mother-reared LL subjects, suggesting a ?buffering? effect of maternal rearing. This gene-environment interaction was significantly greater in female than in male monkeys. A parallel pattern of gene-environment interaction involving a polymorphism in the MAO-A gene was found for levels of aggressive behavior exhibited by mother- and peer-reared rhesus monkey juveniles. We are now in the process of determining whether these and other specific polymorphisms are associated with speecific gene-environment interactions with respect to a variety of behavioral and biological measures obtained throughout development in our rhesus monkey population. Rhesus monkeys are notoriously aggressive as a species, relative to other macaques (indeed, relative to most other primates). Last year we were able to genotype blood samples obtained from 6 other species of macaques (Barbary, crab-eating, pigtail, stumptail, Tibetan, and Tonkean macaques) with respect to the 5-HTT gene and, unlike the case for rhesus monkeys, we found no polymorphisms for this gene in any of these macaque species. Moreover, there was an apparent inverse relationship between the relative length of the promoter region in the 5-HTT gene and the relative level of aggression that has been reported from field observations of each species. For example, all of the Barbary macaques sampled had an "extra long" (XL) allele (a form found in less than 2% of our rhesus monkeys genotyped to date); this species is notably nonaggressive in both naturalistic and captive settings. All of the crab-eating, pigtail, stumptail, and Tonkean macaques sampled had the LL allele; these species are generally considered to be less aggressive than rhesus macaques. Finally, all of the Tibetan macaques had an "extra short" (XS) allele not seen in any of the other species; recent field data suggest that these monkeys may be even more aggressive than most rhesus monkeys. Subsequent comparisons of potential polymorphisms in three other "candidate" genes among these 7 macaque species revealed an intriguing pattern: as was the case with the 5-HTT gene, rhesus monkeys were the only species to exhibit polymorphisms in any of these genes. Rhesus monkeys also differ from these other macaque species in terms of their overall natural populations and the range of physical, social, and climatic environments in which they reside in nature, suggesting that their relative "success" as species may be somehow related to their genetic variability, at least with respect to these specific genes.