Establishing Interhemispheric Interaction assessed by resting state fMRI as an Intermediate Phenotype of Schizophrenia Risk Genes

建立通过静息态功能磁共振成像评估的半球间相互作用作为精神分裂症风险基因的中间表型

• 批准号: 212170118
• 负责人: Professorin Dr. Sophia Stöcklein
• 金额: --
• 依托单位: Buckner Laboratory
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2012
• 资助国家: 德国
• 起止时间: 2011-12-31 至 无数据
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/212170118?language=en
• 关键词: Establishing; Interhemispheric; Interaction; assessed; resting

Genetic factors account for more than 80% of the variance in schizophrenia susceptibility, therefore understanding the genetic underpinning is crucial for developing new treatment strategies. Imaging genetics, which uses brain activity patterns as intermediate phenotypes, provides a unique tool to investigate the impact of polymorphisms on brain function. These intermediate phenotypes are suggested to be closer to the genetic substrate than are heterogeneous clinical symptoms. We propose to establish a new intermediate phenotype based on interhemispheric interaction that leads to brain lateralization. Imaging studies consistently demonstrated that schizophrenia is associated with altered lateralization which is further correlated with the symptom severity. Our groups preliminary data indicate that functional laterality could be unraveled by hemispheric interaction measured by resting state fMRI. The overall aim of this project is to construct a task-independent imaging biomarker based on intrinsic hemispheric interaction, which could serve as an intermediate phenotype of schizophrenia risk genes.Aim 1: Develop an image score based on intrinsic hemispheric interaction in a patient/control cohort. Aim 2: Demonstrate genetic underpinnings of the proposed imaging biomarker.Subaim 2A: Compute a polygenetic score that best predicts the imaging score in 2000 healthy control subjects.Subaim 2B: Test the polygenetic risk score in an independent patient/control cohort to determine its association with pathology.The result of this project will be a reliable and widely applicable intermediate phenotype for schizophrenia risk genes that can be rapidly acquired in large cohorts of subjects without task constraints such as language capacity and task compliance. We also anticipate that this task-independent imaging biomarker will provide greater statistical power in genetic association studies than traditional task induced activation.

遗传因素占精神分裂症易感性差异的 80% 以上，因此了解遗传基础对于制定新的治疗策略至关重要。成像遗传学使用大脑活动模式作为中间表型，为研究多态性对大脑功能的影响提供了独特的工具。这些中间表型被认为比异质临床症状更接近遗传底物。我们建议建立一种基于半球间相互作用的新中间表型，从而导致大脑偏侧化。影像学研究一致表明，精神分裂症与偏侧化改变有关，而侧化改变又与症状严重程度进一步相关。我们小组的初步数据表明，功能偏侧性可以通过静息态功能磁共振成像测量的半球相互作用来解释。该项目的总体目标是构建一种基于内在半球相互作用的独立于任务的成像生物标志物，它可以作为精神分裂症风险基因的中间表型。目标 1：在患者/对照队列中开发基于内在半球相互作用的图像评分。目标 2：展示所提出的成像生物标志物的遗传基础。Subaim 2A：计算最能预测 2000 名健康对照受试者的成像评分的多基因评分。Subaim 2B：在独立患者/对照队列中测试多基因风险评分，以确定其与病理学的关联。该项目的结果将是可以快速获取的可靠且广泛适用的精神分裂症风险基因的中间表型 在没有语言能力和任务依从性等任务限制的大量受试者中。我们还预计，与传统的任务诱导激活相比，这种独立于任务的成像生物标志物将在遗传关联研究中提供更大的统计能力。