NEUROBIOLOGY OF INCREASED VULNERABILITY TO SOCIAL STRESSORS DURING ADOLESCENCE

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 利用恒河猴模型，该项目旨在更好地了解社会从属关系带来的心理压力如何影响女性的大脑成熟和情绪发育，以及这种影响是否受到编码5-羟色胺再摄取转运体(5HTT)的基因多态性的影响，5-HTT是正常的5-羟色胺神经传递和情绪性所必需的蛋白质。在本年度，在外地站大型社会团体收容的第一批青少年(n=37)方面取得了重大进展。数据显示，青春期女性对糖皮质激素的阴性反应不那么敏感，这表明她们可能特别容易受到社会从属的压力。 此外，编码5HTT基因的S变异多态的下级青春期女性对新事物的反应更强，反映出更强的情感反应。在这一队列中完成了5HTT和5HT1A受体结合密度的结构MR、DTI和PET成像，数据显示从属和优势女性在边缘皮质环路成分的5HT1A结合和白质完整性方面存在显著差异。 正如预期的那样，这一群体中更具社会支配性的女性已经进入青春期，而从属女性则没有。第二组(n=39)使用路普隆的青春期延迟试验今年仍在继续。行为测试、糖皮质激素评估和神经成像已经在这个队列中开始。这些研究将显示雌激素对女性青春期行为和大脑成熟的重要性。

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. Using a rhesus monkey model, this project is designed to provide a better understanding of how psychosocial stress, imposed by social subordination, affects brain maturation and emotional development in females and whether this is influenced by polymorphisms in the gene that encodes the serotonin re-uptake transporter (5HTT), a protein essential for normal serotonin neurotransmission and emotionality. Significant progress was made during the current year on the first cohort of adolescents (n = 37) that are housed in large social groups at the Field Station. Data show that adolescent females are less sensitivity to glucocorticoid negative, suggesting the may be particularly vulnerable to the stress of social subordination. Furthermore, subordinate adolescent females with the s-variant polymorphism in the gene encoding the 5HTT are more reactive to novel objects, reflecting greater emotional reactivity. Structural MR, DTI, and PET imaging of 5HTT and 5HT 1A receptor binding density were completed on this cohort and data show significant differences in 5HT1A binding and white matter integrity in components of limbic  cortical circuits in subordinate versus dominant females. As expected, the more socially dominant females of this cohort have entered puberty whereas the subordinate females have not. The experimental delay in puberty with Lupron administration for the second cohort (n = 39) was continued this year.. Behavioral testing, glucocorticoid assessments, and neuroimaging have begun on this cohort. These studies will show the importance of estradiol for behavioral and brain maturation during adolescence in females.