35. Early rearing & genotypic influences on CNS serotonin & behavior in nonhuman primates

Abstract

Length variation in the serotonin transporter gene-linked promoter region (5-HTTLPR), first described by Lesch et al., are related to serotonin functioning, serotonin-related behaviors, and psychopathological disorders. A similar polymorphism, believed to be homologous, also exists in nonhuman primates. We have recently analyzed the relationship between the rhesus macaque serotonin transporter (rh5-HTTLPR) genotypes, CSF 5-HIAA concentrations, and aggression. Our results show that rhesus macaques with the short rh5-HTTLPR allele have low CSF 5-HIAA concentrations, and are highly aggressive. However, the phenotypic expression of this short allele is environmentally-dependent, with the short allele associated with low CSF 5-HIAA concentrations only in subjects reared in age-matched peer groups that lack adult influence. Aggression was shown to be higher in subjects with the short allele than in subjects with the long allele regardless of early rearing experiences. In humans, the 5-HTTLPR is associated with early infant temperament. Similar data for neonatal rhesus monkeys were collected during assessments on days of life 7, 14, 21 and 30. Subjects with the short rh5-HTTLPR variant exhibit diminished orientation, attention, and increased emotional responses. Consistent with our earlier findings, these differences were generally exaggerated by parental deprivation. These findings illustrate the interacting influence of genotype and early rearing experiences on the developing phenotype.