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Neurobiological mechanisms of perceived stress and their modification through behavioral intervention

感知压力的神经生物学机制及其通过行为干预的修改

基本信息

批准号：
10597643
负责人：
Daniel W Grupe
金额：
$ 12.47万
依托单位：
UNIVERSITY OF WISCONSIN-MADISON
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-04-01 至 2024-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10597643
关键词：
Acute Adult Atlases Award Axon Behavior Behavior Therapy Behavioral Assay Behavioral Mechanisms Brain Brain imaging Chronic Clinical Research Clinical Trials Cognitive Communities Control Groups Dendrites Development Diffusion Diffusion Magnetic Resonance Imaging Discrimination Disease Event Exposure to Foundations Fright Funding Future Grain Hippocampus Individual Individual Differences Intervention Intervention Studies Investigation K-Series Research Career Programs Knowledge Laboratories Life Link Measurable Measures Medial Mediating Mediator Mental Depression Mentors Methodology Methods Minority Groups Modeling Modification Neurites Neurobiology Parahippocampal Gyrus Participant Patient Self-Report Pattern Perception Post-Traumatic Stress Disorders Prefrontal Cortex Process Psychopathology Public Health Randomized Reporting Research Resolution Resources Risk Risk Factors Sampling Stress Stressful Event Structure Testing Training Translational Research Trier Social Stress Test United States National Institutes of Health Veterans Waiting Lists Work anxiety symptoms density dentate gyrus emotion regulation high risk population imaging facilities imaging modality improved indexing insight mindfulness intervention mindfulness-based stress reduction multi-atlas segmentation negative affect neurobiological mechanism neuroimaging novel perceived stress prevent promote resilience psychological outcomes psychosocial resilience response stress related disorder stress resilience stressor structural imaging therapy development white matter

项目摘要

PROJECT SUMMARY Subjective perceptions of stress mediate the effects of acute and chronic stressors on long-term psychological outcomes, and thus represent an important risk factor for disorders such as PTSD and depression. The proposed project will fill a knowledge gap by identifying novel putative brain mechanisms of perceived stress, thus allowing for better identification of at-risk individuals and the development of treatment targets for interventions that seek to enhance stress resilience. This Career Development Award will provide the candidate with training in advanced structural and diffusion-weighted MRI methods and didactic and mentored training in the fundamentals of clinical trials research. This new training will be leveraged to test novel hypotheses regarding hippocampal contributions to perceived stress, and modification of these mechanisms by a mindfulness intervention. In a sample of 300 individuals from the community, Study 1 will investigate relationships between perceived stress and pattern separation behavior, a hippocampal-dependent process that allows for fine-grained discrimination of safe vs. threatening contexts, and which has been theoretically linked to over-generalization of fear and negative affect. Using high-resolution structural imaging and multi-atlas segmentation of the hippocampus, Aim 1 will investigate relationships between pattern separation behavior, hippocampal subfield volumes, and perceptions of daily life stressors and acute laboratory stressors. In Aim 2, advanced diffusion-weighted imaging methods will be used to gain insight into the density and orientation of hippocampal neurites (axons and dendrites). This will allow for a novel investigation of the microstructural correlates of subjectively perceived stress, hypothesized to include reduced neurite density within the hippocampus and less coherent orientation of white matter tracts linking the hippocampus and medial prefrontal cortex. In Study 2, 80 participants will be randomized to a wait-list control group or mindfulness-based stress reduction (MBSR), which is known to reduce subjective perceptions of stress. Aim 3 will test whether MBSR participants demonstrate improvements in pattern separation behavior, hippocampal volume, and hippocampal microstructure, and whether these hippocampal changes are associated with expected reductions in perceived stress. Aims 1-2 will be facilitated by new training in advanced structural imaging of the hippocampus and advanced diffusion-weighted imaging methods, supported by a training team with extensive expertise in these domains and made possible by the rich resources of a world-class brain imaging center. Aim 3 will be supported by didactic, experiential, and mentored training in the fundamentals of clinical research through the NIH-funded Institute for Clinical and Translational Research (ICTR). Collectively, the research and training aims of this project seek to illuminate novel neurobiological mechanisms of perceived stress and provide new training in advanced neuroimaging methods and clinical trials methodology. This award will enable the candidate to conduct future intervention studies aimed at preventing the development of stress-related disorders by engaging these neurobiological targets.

项目概要对压力的主观感知介导急性和慢性压力源对长期心理的影响结果，因此是创伤后应激障碍（PTSD）和抑郁症等疾病的重要危险因素。拟议的该项目将通过识别感知压力的新的假定大脑机制来填补知识空白，从而允许更好地识别高危人群并制定干预措施的治疗目标以增强抗压能力。该职业发展奖将为候选人提供以下方面的培训：先进的结构和扩散加权 MRI 方法以及基础知识的教学和指导培训的临床试验研究。这项新的训练将用于测试有关海马体的新假设对感知压力的贡献，以及通过正念干预修改这些机制。在一个研究 1 以社区中 300 名个体为样本，调查感知压力之间的关系和模式分离行为，这是一种依赖海马的过程，可以进行细粒度的辨别安全与威胁环境的区别，理论上与恐惧和恐惧的过度概括有关负面影响。利用海马体的高分辨率结构成像和多图谱分割，Aim 1 将研究模式分离行为、海马亚区体积和对日常生活压力源和急性实验室压力源的看法。在目标 2 中，先进的扩散加权成像方法将用于深入了解海马神经突（轴突和轴突）的密度和方向树突）。这将允许对主观感知的微观结构相关性进行新颖的研究压力，假设包括海马内神经突密度减少和神经元方向不连贯连接海马体和内侧前额皮质的白质束。在研究 2 中，80 名参与者将随机分配到等候名单对照组或基于正念的减压（MBSR）组，众所周知，这可以减少对压力的主观感受。目标 3 将测试 MBSR 参与者是否表现出模式方面的改进分离行为、海马体积和海马微观结构，以及这些海马是否变化与感知压力的预期减少有关。新的培训将促进目标 1-2 在先进的海马结构成像和先进的扩散加权成像方法中，由在这些领域拥有丰富专业知识的培训团队提供支持，并通过丰富的资源实现世界一流的脑成像中心。目标 3 将得到教学、体验和指导培训的支持通过 NIH 资助的临床和转化研究所了解临床研究的基础知识（卢旺达问题国际法庭）。总的来说，该项目的研究和培训目标旨在阐明新颖的神经生物学感知压力的机制，并提供先进神经影像方法和临床试验的新培训方法论。该奖项将使候选人能够开展未来的干预研究，旨在预防通过参与这些神经生物学目标来发展与压力相关的疾病。