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. This project studied the developmental effects of early life stress (ELS) using a nonhuman primate animal model. We have investigated the short- and long-term effects of repeated maternal separation during a critical period of infant macaque development (3-6 months of age). We reported this ELS sensitized the infants' stress responses, particularly in females and infants with low functional serotonin transporter genes. As juveniles, maternally-separated subjects exhibited enhanced anxiety (startle reactivity), flattened cortisol diurnal rhythms and other alterations in stress physiology. During the last year we collected additional longitudinal data of ELS effects on emotional behavior, sleep, physical growth, metabolism, immune and neuroendocrine function during adolescence and adulthood. Findings confirmed enduring effects of the ELS in many of these systems with increased emotional reactivity and problems in social behavior, delayed physical growth around puberty, sleep disturbances and elevated levels of inflammatory markers (e.g. serum c-reactive protein) during adolescence and adulthood. We also examined the long-term effects of the ELS on brain metabolism, using [18F]-fluoro-deoxy-glucose Positron Emission Tomography (FDG-PET) during a mildly stressful test session. Results from these studies showed significantly greater metabolic activity in animals with ELS in brain regions such as superior temporal sulcus, putamen, thalamus, inferotemporal cortex, hippocampus and orbitofrontal cortex, despite no group differences detected in behavioral, autonomic or neuroendocrine measures, suggesting that differences in brain metabolism were not influenced by differential reactions of these systems. These findings suggest that, as adults, monkeys with histories of ELS exhibited hyperactivity in brain regions involved in attending to and regulating sensory information from multiple modalities. Altogether, results suggest that ELS had persistent effects on primates, leading to increased emotional reactivity, alterations in social behavior, homeostatic systems and brain sensory processing during adolescence and early adulthood, which are consistent with features of human psychiatric disorders exhibited by individuals with ELS.