NEUROBIOLOGY OF ADVERSE CARE IN RHESUS INFANTS: BUILDING TRANSLATIONAL BRIDGE

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. We used a NHP model of early life stress (ELS) in the form of adverse early care to study its neurodevelopmental impact using methods that cannot be used with very young children. The targeted developmental period is birth through 18 mos, equivalent to early childhood in humans. This developmental period involves rapid brain development believed to be vulnerable to ELS impact. We collected all longitudinal measures proposed in the project for the rhesus infants born so far (n=24) at 2 weeks and 3, 6, 12 and 18 months of age. We examined the effects of ELS on emotional reactivity and have preliminary data suggesting that rhesus infants that received poor maternal care are more emotionally reactive and show deficits in cognitive functions controlled by prefrontal-limbic circuits. The increased emotional reactivity was detected from observations in the social groups and laboratory challenges (LabTAB and Human Intruder tests). We also studied the effects of ELS on the stress physiology via measurements of cortisol and ACTH plasma levels, as well as CSF levels of stress neuropeptides (CRF, AVP) and monoaminergic function, but assays are pending. When examining the caregiving dimensions associated with ELS-infants' sensitization of stress-response systems, maternal rejection seems the strongest predictor of poor infant developmental outcomes. The underlying neurodevelopmental alterations that mediate the effects of ELS on emotional behavior, stress systems and cognitive function was also assessed using neuroimaging methods (structural magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI)); data are pending analysis.