NEUROBIOLOGY OF INCREASED VULNERABILITY TO SOCIAL STRESSORS DURING ADOLESCENCE

青少年时期对社会压力的脆弱性增加的神经生物学

• 批准号: 8357485
• 负责人: Mark E Wilson
• 金额: $ 4.12万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357485
• 关键词: Adolescence; Adolescent; Affect; Behavioral; Binding; Brain; Data; Development; Emotional; Enantone; Estradiol; Female; Female Adolescents; Funding; Genes; Genetic Polymorphism; Glucocorticoids; Grant; Housing; Macaca mulatta; Modeling; National Center for Research Resources; Neurobiology; Positron-Emission Tomography; Primates; Principal Investigator; Proteins; Psychosocial Stress; Puberty; Research; Research Infrastructure; Resources; Serotonin; Source; United States National Institutes of Health; Variant; behavior test; cohort; cost; density; design; neuroimaging; neurotransmission; novel; receptor binding; social; social group; social stress; stressor; uptake; white matter

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.

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。 使用恒河猴模型，这个项目的目的是提供一个更好的理解如何心理社会压力，施加社会从属地位，影响大脑成熟和情感发展的女性，这是否是受多态性的基因编码的血清素再摄取转运蛋白（5 HTT），蛋白质的正常血清素神经传递和情绪。 今年，在外地站大型社会团体中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阴性的敏感性较低，这表明她们可能特别容易受到社会从属关系的压力。 此外，在编码5 HTT的基因中具有S-变异多态性的下属青少年女性对新物体的反应更强烈，反映出更大的情绪反应。 在该队列中完成了5 HTT和5 HT 1A受体结合密度的结构MR、DTI和PET成像，数据显示边缘系统组分中5 HT 1A结合和白色物质完整性的显著差异。  在从属和主导女性中的皮层回路。 正如预期的那样，这个群体中社会地位较高的女性已经进入青春期，而从属女性则没有。 第二个队列（n = 39）中Lupron给药的青春期延迟实验今年继续进行。 行为测试、糖皮质激素评估和神经影像学已开始对该队列进行。 这些研究将显示雌二醇对女性青春期行为和大脑成熟的重要性。