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. The goal of this project is to study the developmental effects of early life stress (ELS) using a nonhuman primate animal model. For this, 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 previously reported that 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 more longitudinal data of ELS effects on emotional behavior, sleep, physical growth, metabolism, immune and neuroendocrine function during puberty, adolescence and adulthood. Our findings indicated enduring effects of the ELS in many of these systems. For example, the animals showed increased anxiety and social alterations during puberty, as well as exaggerated stress responses as adolescents and adults, even after habituation to the paradigms. ELS also caused delayed physical growth and skeletal maturation around puberty, both deficits being associated with reduced bone mineral content. However, the animals with ELS caught up with the controls at later ages, suggesting a potential recovery if the stress is not chronically sustained. We have also detected sleep disturbances in the maternally separated animals during adolescence (they sleep less, and the sleep is more restless and less efficient). The animals with ELS also exhibited increased levels of inflammatory markers (c-reactive protein) during adolescence and adulthood. Altogether, these findings suggest that ELS had persistent effects on primates, leading to increased anxiety and alterations in social behavior, sleep and endocrine function, as well as delayed physical growth and maturation and increased risk for inflammatory disorders throughout puberty, adolescence and the early adulthood periods, which are consistent with features of human psychiatric disorders.
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