The Human Stress Response: Interaction of Life Stress History and Genetic Variation on Behavior, Brain Function, and the (Epi-)Genome

人类压力反应：生活压力史与行为、大脑功能和（表观）基因组遗传变异的相互作用

• 批准号: 0843346
• 负责人: Turhan Canli
• 金额: $ 88.22万
• 依托单位: SUNY at Stony Brook
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-15 至 2013-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0843346&HistoricalAwards=false
• 关键词: Human; Stress; Response; Interaction; Life

Stress is a widespread societal problem that can have dramatic health costs for some vulnerable individuals, which may include damage to the brain and numerous physical and mental health problems. Yet, individual differences make it difficult to predict who is vulnerable to the adverse effects of stress. These individual differences must be generated by brain circuits involved in stress-related behaviors and responses, which can be affected by common variations within genes, individuals' life experiences, and the interaction between gene and environment. How these interactions take place in the human brain is currently unknown. Thus, the field is in critical need of an integrated approach to the study of gene x environment interactions on human behavior, its mediating brain circuits, and its underlying molecular-genetic mechanisms. With support from the National Science Foundation, Dr. Turhan Canli and colleagues at Stony Brook University will examine the interaction between genes, life stress, and stress reactivity. The project involves molecular genotyping of subjects, with focus on three genes thought to be important for neurotransmitter and hormonal cascades involved in stress reactivity. Genetic information will be correlated with behavioral response on a well-characterized social stress task. The genetic information will also be correlated with brain imaging, which will allow the researchers to see how individual differences in the response of specific brain regions are influenced by genetic variation. Because gene x environment interactions are expected, life history will also be a part of the analysis. Lastly, because leading theories of the effects of stress on the brain predict damage in particular brain regions, the research will also involve an analysis of postmortem human brains, from individuals with known life histories and genetic profiles.This project's significance is that it will reveal much about the genetic and environmental factors that affect vulnerability and resilience in healthy, normal individuals. Furthermore, the anticipated findings from this research will have important implications for mood disorders such as post-traumatic stress disorder or depression. This project meets the educational mandate of NSF in several ways: The research broadens participation by underrepresented groups by including students who are female and/or minorities. Moreover, the project presents a unique opportunity for cross-training in genetics and neuroscience.

压力是一个普遍的社会问题，对一些脆弱的个人来说可能会产生巨大的健康成本，这可能包括对大脑的损害和许多身心健康问题。然而，个体差异使得很难预测谁容易受到压力的不利影响。这些个体差异必然是由参与压力相关行为和反应的脑回路产生的，这些脑回路可能受到基因内的常见变异、个体的生活经历以及基因与环境之间的相互作用的影响。这些相互作用是如何在人脑中发生的，目前尚不清楚。因此，该领域迫切需要一种综合的方法来研究基因x环境对人类行为的相互作用，其介导的大脑回路及其潜在的分子遗传机制。在美国国家科学基金会的支持下，斯托尼布鲁克大学的Turhan Canli博士和他的同事们将研究基因、生活压力和压力反应之间的相互作用。该项目涉及受试者的分子基因分型，重点是三个基因，这些基因被认为对参与应激反应的神经递质和激素级联反应很重要。遗传信息将与行为反应的一个很好的特点社会压力任务。遗传信息也将与大脑成像相关，这将使研究人员能够看到特定大脑区域反应的个体差异如何受到遗传变异的影响。由于基因x环境的相互作用是预期的，生活史也将是分析的一部分。最后，由于压力对大脑影响的主要理论预测了特定大脑区域的损伤，因此该研究还将涉及对具有已知生活史和遗传特征的个体的死后大脑的分析。该项目的意义在于，它将揭示许多影响健康正常个体的脆弱性和恢复力的遗传和环境因素。此外，这项研究的预期结果将对创伤后应激障碍或抑郁症等情绪障碍产生重要影响。该项目以几种方式满足了NSF的教育任务：研究通过包括女性和/或少数民族学生来扩大代表性不足的群体的参与。此外，该项目为遗传学和神经科学的交叉培训提供了一个独特的机会。