Linking Genetics, Brain, and Behavior to Understand Addiiction Vulnerability

将遗传学、大脑和行为联系起来以了解成瘾脆弱性

• 批准号: 8474737
• 负责人: Andrey P. Anokhin
• 金额: $ 11.77万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-15 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8474737
• 关键词: Addictive Behavior; Adolescence; Adolescent; Age; Alcohol or Other Drugs use; Alleles; Anterior; Attention; Basal Ganglia; Behavior; Behavior Control; Behavioral; Brain; Characteristics; Cognitive; Complex; Conflict (Psychology); DNA; Data; Decision Making; Development; Diagnostic; Disease; Disinhibition; Electroencephalography; Electrophysiology (science); Epidemiology; Etiology; Evaluation; Event; Frequencies; Functional Magnetic Resonance Imaging; Functional disorder; Funding; Genes; Genetic; Genetic Polymorphism; Genetic Risk; Genetic Structures; Genotype; Goals; Growth; Heritability; Imaging Techniques; Independent Scientist Award; Individual; Individual Differences; Informal Social Control; Interdisciplinary Study; Knowledge; Label; Lateral; Lead; Link; Maintenance; Measures; Mediating; Methods; Modeling; Monitor; National Institute of Drug Abuse; Neural Pathways; Neurobiology; Neurocognitive; Neuropsychological Tests; Neurosciences Research; Outcome; Participant; Pathway interactions; Pattern; Phenotype; Prefrontal Cortex; Prevention; Process; Psychopathology; Punishment; Regulation; Research; Research Personnel; Resolution; Rewards; Risk; Risk Factors; Role; Sampling; Scientist; Specificity; Structural Models; Substance Addiction; Substance Use Disorder; Substance abuse problem; System; Testing; Time; Training; Twin Multiple Birth; Twin Studies; Universities; Validation; Washington; addiction; base; brain behavior; career; cingulate cortex; cognitive control; cognitive neuroscience; computerized data processing; design; developmental genetics; early adolescence; endophenotype; follow-up; genetic association; genetic linkage; genetic variant; independent component analysis; indexing; neurobiological mechanism; neuroimaging; neuromechanism; neurophysiology; neuropsychological; prospective; relating to nervous system; response; young adult

The overall goal of this application for an Independent Scientist Award (K02) is to support the continuing development of the candidate as an independent scientist and facilitate the candidate's interdisciplinary research progrann aimed at a better understanding the determinants and consequences of substance use disorders (SUD). Genetic influences on the liability to addiction are well documented, however, neurobiological mechanisms by which genetic factors contribute to addictive behaviors remain poorly understood. The candidate's major theoretical premise is that genetically transmitted deficits in inhibitory self- regulation of behavior constitute a core component of addiction vulnerability. The candidate's research using quantitative EEG and event-related brain potentials (ERPs) has identified a number of heritable neurophysiological indicators of behavioral regulation, however, limited spatial resolution of electrophy- siology methods impedes the identification of the underlying neural substrates. Accordingly, the candidate's first career objective is to gain expertise in functional magnetic resonance imaging (fMRI) techniques through formal coursework, hands-on training, and developing collaborative projects with neuroimaging researchers at Washington University. The second career objective is to increase the candidate's expertise in advanced methods for the analysis of genetically informative longitudinal data such as latent growth and latent class transition modeling. The research plan draws upon the candidate's ongoing studies of adolescent and young adult twins. Specific research aims are: 1) to identify neurocognitive endophenotypes for addiction and establish their commonality versus specificity and their ability to prospectively predict substance use and abuse; 2) to better characterize neural substrates of inhibitory self-regulation of behavior by adding functional neuroimaging assessments to the Pi's ongoing studies and integrating genetic, fMRI, and ERP data; 3) to provide a functional validation of genetic variants implicated in addiction vulnerability using a combination EEG, ERPs, functional MRI, neuropsychological testing, and diagnostic assessments. In the long run, establishing the links between genes, brain function, and inhibitory control of behavior will lead to a better understanding of the pathways to addiction and identify targets for prevention and treatment efforts. RELEVANCE (See instmctions): Research has documented the role of genetic factors in addictions, but very little is known about how genes exert their influence'on complex behaviors. Investigating the neurobiological pathways and cognitive processes mediating genetic influences on behavior will lead to a better understanding of the pathways to addiction and identify targets for prevention and treatment efforts.

本次独立科学家奖（K02）申请的总体目标是支持持续的 培养候选人作为独立科学家并促进候选人的跨学科能力 研究计划旨在更好地了解物质使用的决定因素和后果 疾病（SUD）。然而，遗传对成瘾倾向的影响已有充分记录， 遗传因素导致成瘾行为的神经生物学机制仍然很差 明白了。候选人的主要理论前提是，遗传性的自我抑制缺陷 行为调节是成瘾脆弱性的核心组成部分。候选人的研究使用 定量脑电图和事件相关脑电位 (ERP) 已确定了许多可遗传的 然而，行为调节的神经生理学指标限制了电生理的空间分辨率 生物学方法阻碍了潜在神经基质的识别。据此，候选人的 第一个职业目标是通过以下方式获得功能磁共振成像 (fMRI) 技术的专业知识 正式课程、实践培训以及与神经影像研究人员开发合作项目 在华盛顿大学。第二个职业目标是提高候选人的高级专业知识 分析遗传信息纵向数据（例如潜在生长和潜在类别）的方法 过渡建模。该研究计划借鉴了候选人正在进行的青少年和青年研究 成年双胞胎。具体研究目标是：1）确定成瘾和成瘾的神经认知内表型 确定其共性与特异性以及前瞻性预测物质使用的能力和 虐待; 2）通过添加功能来更好地表征行为抑制性自我调节的神经基质 对 Pi 正在进行的研究进行神经影像评估，并整合遗传、功能磁共振成像和 ERP 数据； 3）到 使用组合提供与成瘾脆弱性相关的遗传变异的功能验证 脑电图、ERP、功能性 MRI、神经心理学测试和诊断评估。从长远来看， 建立基因、大脑功能和行为抑制控制之间的联系将带来更好的结果 了解成瘾的途径并确定预防和治疗工作的目标。 相关性（参见说明）： 研究已经记录了遗传因素在成瘾中的作用，但人们对基因如何影响成瘾知之甚少。 对复杂行为施加影响。研究神经生物学途径和认知 介导遗传对行为影响的过程将有助于更好地理解 成瘾并确定预防和治疗工作的目标。