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。我们研究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。我们报道了这种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ELS在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额外纵向数据。 研究结果证实，ELS在其中许多系统中具有持久的影响，包括增加情绪反应和社交行为问题，青春期前后身体发育延迟，睡眠障碍，以及青春期和成年期炎症标记物(例如血清C反应蛋白)水平升高。我们还使用[18F]-氟代脱氧葡萄糖正电子发射断层扫描(FDG-PET)在轻度应激测试期间检查了ELS对大脑新陈代谢的长期影响。这些研究的结果显示，尽管在行为、自主神经或神经内分泌测量方面没有发现组间差异，但ELS动物在大脑区域，如颞上沟、壳核、丘脑、颞下皮质、海马体和眶前皮质的代谢活动显著增加，这表明大脑代谢的差异不受这些系统的不同反应的影响。这些发现表明，成年后，有ELS病史的猴子在负责处理和调节来自多种方式的感觉信息的大脑区域表现出多动症。 综上所述，结果表明ELS对灵长类动物有持续的影响，导致青春期和成年期早期情绪反应、社会行为、动态平衡系统和大脑感觉处理的改变，这与ELS患者表现出的人类精神障碍的特征是一致的。

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.