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.

该申请获得独立科学家奖（K02）的总体目标是支持持续的 候选人作为独立科学家的发展，并促进候选人的跨学科 研究Progrann旨在更好地理解使用物质的决定因素和后果 疾病（SUD）。但是，遗传对成瘾责任的影响有充分的记录。 遗传因素导致上瘾行为的神经生物学机制仍然很差 理解。候选人的主要理论前提是抑制性自我的遗传传播缺陷 行为的调节构成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的大脑电位（ERP）已经确定了许多可遗传的 然而，行为调节的神经生理学指标有限，电植物的空间分辨率有限 神学方法阻碍了基本神经底物的识别。因此，候选人的 第一个职业目标是通过功能磁共振成像（fMRI）技术获得专业知识 正式的课程工作，动手培训以及与神经成像研究人员一起开发协作项目 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 分析遗传信息丰富的纵向数据的方法，例如潜在生长和潜在类别 过渡建模。研究计划借鉴了候选人对青少年和年轻的持续研究 成人双胞胎。具体研究目的是：1）确定成瘾和成瘾和 建立它们的共同点与特异性以及预测物质使用的能力和 虐待; 2）通过添加功能更好地表征行为抑制性自我调节的神经底物 对PI正在进行的研究和整合遗传，fMRI和ERP数据的神经影像学评估； 3）到 提供对使用组合涉及成瘾脆弱性的遗传变异的功能验证 EEG，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导致更好 了解成瘾的途径并确定预防和治疗工作的目标。 相关性（请参阅Instmctions）： 研究已经记录了遗传因素在成瘾中的作用，但对基因的方式知之甚少 发挥其影响力的复杂行为。研究神经生物学途径和认知 介导遗传影响行为影响的过程将使人们更好地了解通往的途径 成瘾并确定预防和治疗工作的目标。