Infant inhibited temperament in primates predicts adult behavior, is heritable, and is associated with anxiety-relevant genetic variation.

An anxious or inhibited temperament (IT) early in life is a major risk factor for the later development of stress-related psychopathology. Starting in infancy, nonhuman primates, like humans, begin to reveal their temperament when exposed to novel situations. Here, in Study 1 we demonstrate this infant IT predicts adult behavior. Specifically, in over 600 monkeys, we found that individuals scored as inhibited during infancy were more likely to refuse treats offered by potentially-threatening human experimenters as adults. In Study 2, using a sample of over 4000 monkeys from a large multi-generational family pedigree, we demonstrate that infant IT is partially heritable. The data revealed infant IT to reflect a co-inherited substrate that manifests across multiple latent variables. Finally, in Study 3 we performed whole-genome sequencing in 106 monkeys to identify IT-associated single-nucleotide variations (SNVs). Results demonstrated a genome-wide significant SNV near CTNNA2, suggesting a molecular target worthy of additional investigation. Moreover, we observed lower p values in genes implicated in human association studies of neuroticism and depression. Together, these data demonstrate the utility of our model of infant inhibited temperament in the rhesus monkey to facilitate discovery of genes that are relevant to the long-term inherited risk to develop anxiety and depressive disorders.

Effect of Indoor Compared with Outdoor Location during Gestation on the Incidence of Diarrhea in Indoor-Reared Rhesus Macaques (Macaca mulatta).

Behavior and health, including the incidence of chronic idiopathic diarrhea, can vary widely among NHP reared indoors. We hypothesized that factors during gestation account for some of the variability in chronic diarrhea risk that cannot be explained by postnatal environment, genes, or known physiologic deficits. We hypothesized that, among macaques reared indoors postnatally, outdoor housing during gestation (when the dam engaged with a large, species-typical social group) would be protective against diarrhea as compared with gestation experienced in an indoor setting. We also hypothesized that exposure to routine husbandry and veterinary care in utero would increase diarrhea rates in offspring. We built models to test the influence of specific events during pregnancy as well as their interactions with anxiety-related genotype as a way of understanding gene×environment interaction on the development of diarrhea in indoor-reared rhesus macaques. Although previous reports have suggested that rearing by the mother in an indoor environment is preferable to nursery rearing, we found that whether gestation occurred indoors (in single or pair housing) or outdoors (in a large social group) better explained the variability in diarrhea rate in our study population of indoor-reared macaques. Furthermore, the diarrhea incidence was associated with nervous temperament and serotonin transporter promoter genotype. Several significant interactions indicated that some of these effects were specific to subsets of animals. Our results demonstrate that the prenatal environment can have unexpected lasting health consequences.