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

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 本项目的目标是利用非人灵长类动物模型研究早期生活应激(ELS)对发育的影响。为此，我们调查了在婴儿猕猴发育的关键时期(3-6个月大)重复母体分离的短期和长期影响。我们之前曾报道，这种ELS使婴儿的应激反应敏化，特别是在女性和具有低功能5-羟色胺转运体基因的婴儿中。在青少年时期，与母亲分离的受试者表现出更强的焦虑(惊吓反应)，皮质醇昼夜节律平缓，以及压力生理上的其他变化。 在过去的一年里，我们收集了更多关于ELS在青春期、青春期和成年期对情绪行为、睡眠、身体发育、新陈代谢、免疫和神经内分泌功能影响的纵向数据。我们的发现表明ELS在许多这样的系统中都有持久的影响。例如，这些动物在青春期表现出更多的焦虑和社交变化，以及在青少年和成年时夸大的压力反应，即使在习惯于这些范例之后也是如此。ELS还导致青春期前后身体发育和骨骼成熟延迟，这两种缺陷都与骨骼矿物质含量减少有关。然而，患有ELS的动物在较晚的年龄赶上了对照组，这表明如果压力不是长期持续的，可能会恢复。 我们还检测到在青春期与母亲分开的动物的睡眠障碍(它们睡得更少，睡眠更不安宁，效率更低)。患有ELS的动物在青春期和成年期也表现出炎症标志物(C-反应蛋白)水平的增加。综上所述，这些发现表明ELS对灵长类动物有持续的影响，导致焦虑增加，社会行为、睡眠和内分泌功能改变，身体发育和成熟延迟，在青春期、青春期和成年早期患炎症性疾病的风险增加，这与人类精神疾病的特征一致。

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.