The Boston Circulatory Arrest Study - Antecedents and Correlates of Well-Being in Adults with Congenital Heart Disease

项目摘要 以前致命的，严重的先天性心脏病（CHD）现在可以有效地治疗手术，导管， 和医疗干预。由此带来的预期寿命的大幅提高带来了重大的 人口结构的变化，使成人冠心病患者现在超过儿童冠心病，即使是复杂的， 条件成年幸存者焦虑、抑郁、社交困难、教育水平较低的风险增加。 成就和就业不足。这些心理社会疾病可能与以下缺陷有关： 执行功能（EF）和其他神经认知能力，在儿童和青少年中普遍存在， 冠心病EF的缺陷，以抑制控制、工作记忆、认知灵活性和 决策，高度依赖于皮层和皮层下神经网络的完整性， 发展到成年早期，并可能对自我调节和管理产生重大不利影响。的 我们建议的目标是弥合儿童时期已知的执行功能缺陷之间的知识差距差距 CHD与成人健康我们建议通过研究现在年龄在24-28岁的受试者来实现我们的目标， 婴儿时期参加波士顿循环停止研究， 在1岁、2.5岁、4岁、8岁和16岁时的神经心理和发育功能，以及脑部MRI 16岁的时候在目标1中，我们将探讨EFs与成人幸福感主要维度的关系。 我们假设，较低的性能EF将与较差的整体福祉。成果 确定幸福感的测量将是生活质量，神经心理功能（例如社会认知， 记忆技能），心理健康诊断和功能（例如焦虑，抑郁），社会关系，学术 成就和成人独立性（例如就业状况、医疗随访）。在目标2中，我们 确定EF与MRI衍生的大脑结构，功能和 连通性。我们假设EF的较低性能将与较低的全局效率相关 （集成）和更高的模块化（隔离）。我们将使用全局白色测量脑部MRI结果 物质连接，区域皮质灰质厚度，灰质连接测量， 皮质厚度的区域间相关性和静息状态功能性定义的功能连接性 磁共振成像在目标3中，我们将使用纵向模型来分析 成年人的幸福与早期的EF和其他神经认知和心理健康变量的措施， 以及早期临床变量和青少年神经影像学。我们将分析成年人 幸福维度与儿童和青少年EF，心理健康和认知的其他措施 功能，青少年大脑MRI表现和临床变量。我们的最终目标是尽早发现， 成人表现的风险因素，以指导设计有针对性的治疗策略， 成就，就业能力和生活质量的迅速增长的成年人与CHD的人口。

PROJECT SUMMARY Previously lethal, critical congenital heart disease (CHD) can now be treated effectively with surgical, catheter, and medical interventions. The resulting dramatic improvement in life expectancy has brought a major demographic shift, so that adult patients with CHD now outnumber children with CHD, even for complex conditions. Adult survivors are at increased risk of anxiety, depression, social difficulties, lower educational attainment, and underemployment. These psychosocial morbidities may be associated with deficits in executive functions (EFs) and other neurocognitive abilities that are prevalent in children and adolescents with CHD. Deficits in EFs, represented by measures of inhibitory control, working memory, cognitive flexibility, and decision-making, are highly dependent on the integrity of cortical and subcortical neural networks that continue to develop into early adulthood and can have a major adverse impact on self-regulation and management. The goal of our proposal is to bridge the gap in knowledge between known executive function deficits in childhood CHD and adult well-being. We propose to accomplish our goal by studying subjects, now age 24-28 years, who were enrolled as infants in the Boston Circulatory Arrest Study and then studied with respect to neurolopsychological and developmental function at ages 1, 2.5, 4, 8, and 16 years, as well as with brain MRI at 16 years. In Aim 1, we will explore the relationship of EFs to major dimensions of adult well-being. We hypothesize that lower performance on EFs will be related to poorer overall well-being. The outcomes measured to determine well-being will be quality of life, neuropsychological function (e.g. social cognition, memory skills), mental health diagnosis and function (e.g. anxiety, depression), social relatedness, academic achievement, and adult independence (e.g. employment status, medical follow up). In Aim 2, we will determine the relationship of EFs to MRI-derived measures of brain structure, function, and connectivity. We hypothesize that lower performance on EFs will be associated with lower global efficiency (integration) and higher modularity (segregation). We will measure the brain MRI outcomes using global white matter connectivity, regional cortical gray matter thickness, gray matter connectivity measured from interregional correlation in cortical thickness, and functional connectivity as defined by resting state functional magnetic resonance imaging. In Aim 3, we will use longitudinal models to analyze the association of adult well-being with earlier measures of EFs and other neurocognitive and mental health variables, as well as with earlier clinical variables and adolescent neuroimaging. We will analyze associations of adult well-being dimensions with childhood and adolescent EFs, other measures of mental health and cognitive function, adolescent brain MRI findings, and clinical variables. Our ultimate goal is to identify early, modifiable risk factors for adult performance to guide the design of targeted treatment strategies that optimize educational achievement, employability, and quality of life in the burgeoning population of adults with CHD.