NEUROBIOLOGY OF ADVERSE CARE IN RHESUS INFANTS: BUILDING TRANSLATIONAL BRIDGE

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 我们使用了NHP模型的早期生活压力（ELS）的形式，不利的早期护理，研究其神经发育的影响，使用的方法，不能用于非常年幼的儿童。目标发育期为出生至18个月，相当于人类的幼儿期。这个发育期涉及大脑的快速发育，据信易受ELS的影响。 我们收集了项目中提出的所有纵向措施，到目前为止出生的恒河猴婴儿（n = 24）在2周和3，6，12和18个月大。我们研究了ELS对情绪反应的影响，并有初步数据表明，恒河猴婴儿，得到穷人的母亲照顾更情绪化的反应，并表现出赤字的认知功能控制的前额叶边缘电路。从社会群体和实验室挑战（LabTAB和人类入侵者测试）的观察中检测到增加的情绪反应。我们还研究了ELS对应激生理学的影响，通过测量皮质醇和促肾上腺皮质激素血浆水平，以及CSF水平的应激神经肽（CRF，AVP）和单胺能功能，但分析待定。当检查与ELS婴儿的应激反应系统的敏感性相关的发育维度时，母亲的排斥似乎是婴儿发育不良结局的最强预测因子。还使用神经成像方法（结构磁共振成像（MRI）和扩散张量成像（DTI））评估了介导ELS对情绪行为、应激系统和认知功能影响的潜在神经发育改变;数据有待分析。

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.