EMORY CONTE CENTER FOR THE NEUROSCIENCE OF MENTAL DISORDERS: PRIMATE CORE

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Emory Conte Center for the Neuroscience of Mental Disorders - Primate Core. The major goal of this project has been to produce and characterize a non-human primate epigenetic early life stress model in rhesus monkeys. We have imposed a schedule of repeated mother-infant separations in rhesus macaques during a critical period of development (3-6 months of age). The purpose of the Primate Core is to provide, maintain and characterize phenotypes of monkeys with an early developmental stress for the Emory Center for the Neuroscience of Mental Disorders. We have investigated the short-term and long-term effects of repeated maternal separation on emotional behavior and HPA axis function of the animals. We previously reported that repeated maternal separations sensitized the infants' HPA axis responses to stress, particularly in females and infants with the short allele of the promoter region of the serotonin transporter gene (rh5-HTTLPR). As juveniles, maternally-separated subjects exhibited enhanced startle reactivity, flattened cortisol diurnal rhythms and alterations in pituitary-adrenal function detected with CRF and ACTH pharmacological challenges. Last year we collected more data for longitudinal analyses of: (a) HPA and HPT axes function at later ages (juvenile-adolescence-early adulthood periods), and detected sensitized cortisol responses to stress after habituation paradigms; (b) CSF levels of monoamine metabolites and CRF; (c) Physical growth and metabolism: every 6 months we collected measures of height (crown-rump, crown-heel length), body weight, BMI, bone maturity (rated from radiographs), as well as plasma samples for measures of growth hormone, leptin, ghrelin, etc; so far we have detected delayed physical growth and maturation around puberty, in parallel with increased BMI and fat mass, in maternally-separated monkeys that need to be compared with additional metabolic measures (such as fasting serum glucose, insulin, leptin, and lipid levels to define levels of metabolic syndrome caused by the early life stress); (d) Sleep and activity: using activity-based sleep monitoring (actigraphy) we have detected sleep disturbances in the maternally separated animals during adolescence (less time asleep, reduced sleep efficiency, more sleep fragmentation, higher activity during the night); (e) Social behavior. These recent findings suggest that early life stress has persistent effects on nonhuman primates, leading to alterations in endocrine function, delayed physical growth and maturation, and alterations in sleep and metabolism in peri-pubertal and adolescent monkeys.