Brain Deviation Preceding Substance Use: An Offspring of Co-Twin Control Study

药物使用之前的大脑偏差：双胞胎控制研究的后代

• 批准号: 8821159
• 负责人: Sylia Wilson
• 金额: $ 15.27万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-03-15 至 2020-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8821159
• 关键词: 11 year old; Address; Affect; Age; Alcohol abuse; Alcohol or Other Drugs use; Behavioral Genetics; Brain; Characteristics; Child; Childhood; Confounding Factors (Epidemiology); Controlled Study; Data; Data Set; Dependence; Development; Diffusion Magnetic Resonance Imaging; Disease; Drug abuse; Ensure; Environment; Environmental Exposure; Environmental Risk Factor; Etiology; Exposure to; Family; Family Research; Female; Fostering; Genes; Genetic; Genetic Risk; Health; Heritability; Impairment; Individual; Investigation; K-Series Research Career Programs; Literature; Magnetic Resonance Imaging; Mediating; Mentors; Minnesota; Monozygotic Twinning; Monozygotic twins; Natural experiment; Nature; Neurobiology; Neurocognitive Deficit; Outcome; Parents; Preventive Intervention; Public Health; Recruitment Activity; Relative (related person); Research; Research Design; Rest; Risk; Role; Sampling; Scientist; Siblings; Structure; Substance Use Disorder; Techniques; Temperament; Testing; Time; Training; Twin Multiple Birth; Twin Studies; base; career; cohort; cost effective; design; deviant; experience; high risk; innovation; middle age; mortality; neuroimaging; neurotoxic; offspring; physical conditioning; population based; preadolescence; psychosocial; public health relevance; trait

DESCRIPTION (provided by applicant): Substance use disorders (SUDs; alcohol and drug abuse and dependence) are associated with substantial negative outcomes and significant impairment in multiple domains of functioning, including physical health and mortality, psychiatric health, psychosocial functioning, and neurocognitive deficits. SUDs are also associated with structural and functional brain deviations. However, the primarily cross-sectional nature of the vast majority of existing research means that the causal basis of these associations remains unclear: substance misuse appears to have neurotoxic effects on the brain, but it is also plausible that premorbid brain deviations that precede substance use influence the development of both SUDs and related impairment. The aims of the proposed career development award are twofold: (1) to train the candidate in pediatric neuroimaging techniques, including magnetic resonance imaging (MRI), diffusion tensor imaging (DTI), and resting state connectivity MRI, for assessing brain structure and functioning during key developmental periods; and (2) to use this training to examine brain structure in young children at high and low risk for the development of problematic substance use using an innovative and powerful offspring of monozygotic (MZ) co- twin control study design that disentangles genetic and environmental effects on the developing brain. The candidate will receive training essential for her development as an independent research scientist under the guidance of an outstanding team of mentors with extensive expertise in substance use, brain development, pediatric neuroimaging, and behavioral genetics (Drs. William Iacono, Kathleen Thomas, Matt McGue, Irving Gottesman). This training builds upon the candidate's already strong scientific background and will ensure that she is well situated to launch an independent research career and make substantive contributions to the substance use literature. The research will be conducted at the Minnesota Center for Twin and Family Research (MCTFR), which offers unparalleled opportunities for applying genetically informative study designs to examine genetic and environmental influences on substance use in several large, population-based cohorts of twins, prospectively assessed from preadolescence into middle age. Two specific aims will be addressed in a sample of 120 7- to 11-year-old offspring of these twins: (1) examine brain structure in offspring at high and low risk for SUDs with the aim of identifying premorbid brain deviations associated with risk; and (2) determine whether brain deviations reflect preexisting liability for substance misuse or instead reflect offspring exposure to a rearing environment associated with having a SUDs-affected parent. Results of the proposed project have great potential to further understanding of the etiology and consequences of SUDs, and, in turn, guide needed prevention and intervention efforts to reduce the tremendous negative public health and personal implications of substance misuse.

描述（由申请人提供）：物质使用障碍（SUD;酒精和药物滥用和依赖）与多个功能领域的实质性负面结果和显著损害相关，包括身体健康和死亡率、精神健康、心理社会功能和神经认知缺陷。SUD还与结构和功能性脑偏差相关。然而，绝大多数现有研究的主要横截面性质意味着这些关联的因果基础仍然不清楚：物质滥用似乎对大脑有神经毒性作用，但在物质使用之前的病前大脑偏差也可能影响SUD和相关损伤的发展。拟议的职业发展奖有两个目的：（1）培训候选人的儿科神经成像技术，包括磁共振成像（MRI），扩散张量成像（DTI）和静息状态连接MRI，用于评估关键发育时期的大脑结构和功能;和（2）使用这种训练来检查幼儿的大脑结构，在高风险和低风险的发展有问题的物质使用的创新和强大的后代的同卵（MZ）共-双胞胎对照研究设计，解开遗传和环境对大脑发育的影响。候选人将接受培训，她的发展是一个独立的研究科学家的指导下，具有广泛的专业知识，在物质使用，大脑发育，儿科神经影像学和行为遗传学（威廉Iacono博士，凯瑟琳托马斯，马特McGue，欧文Gottesman）的优秀导师团队的指导下必不可少的。这种培训建立在候选人已经很强的科学背景之上，将确保她能够很好地开展独立的研究生涯，并为物质使用文献做出实质性贡献。这项研究将在明尼苏达州双胞胎和家庭研究中心（MCTFR）进行，该中心提供了无与伦比的机会，可以应用遗传信息研究设计来研究遗传和环境对几个大型，基于人口的双胞胎队列中物质使用的影响，从青春期前到中年进行前瞻性评估。两个具体目标将在120个7 - 11岁的双胞胎后代的样本中进行：（1）检查SUD高风险和低风险后代的大脑结构，目的是识别与风险相关的发病前大脑偏差;以及（2）确定大脑的偏差是否反映了预先存在的物质滥用的责任，或者反映了后代暴露于与药物滥用相关的养育环境，有一个受SUDS影响的父母。拟议项目的结果有很大的潜力，以进一步了解SUD的病因和后果，并反过来，指导所需的预防和干预工作，以减少巨大的负面公共卫生和物质滥用的个人影响。