Brain Endophenotypes Modulating Drug Abuse Risk

调节药物滥用风险的大脑内表型

基本信息

项目摘要

This project examines the intermediate neural systems that mediate the gene-behavior relationships involv- ed in risk for development of substance use disorders (SUDs) with special focus on alcohol, cannabis, and nicotine. We will characterize this circuitry, study its interaction with two intermediate behavioral phenotypes (behavioral undercontrol and negative affectivity), and examine the contribution of selected genetic variants, and early-life stress on the neural correlates of impulsivity and negative emotionality in children with varying risk for development of SUDs in adulthood [G2 sample of the Michigan Longitudinal Study(MLS)]. We will examine these correlates during childhood and begin to characterize changes that occur during adolesc- ence. The general hypothesis is that dysregulation of the brain networks involved in processing and regula- tion of behavior and affect during childhood underlies a heightened predisposition to develop SUDs at a later age. Both behavioral undercontrol and affective dysregulation at an early age are strong predictors of SUDs later in life, and these processes are regulated by complex neuronal circuits. We will use fMRI to investigate these neural systems in a sample of 8-10 year old boys & girls (n=129) from the ongoing MLS in a longitud- inal design in which scanning occurs at 2-year intervals. It is expected that children at high risk for develop- ment of SUDs based on the risk conferred by behavioral phenotypes (measured initially as externalizing and internalizing behavior and later by developmental trajectory classes), will demonstrate alterations in the functional responses of neuronal circuitry involved in impulse control and emotional regulation. It is also ex- pected that this effect will be modified by genes and early-life stress. Changes in brain functional responses over time are expected to be influenced by risk conferred by genetic variants and early stress. As models of gene-trait-environment interaction over time are developed in the MLS, we will investigate the relationship between brain responses and these developmental phenotypes. As substance abuse problems develop in this sample, this information will be available during subsequent funding periods to determine dysfunctions in neural circuitry associated with the early development of SUDs during adolescence. RELEVANCE (See instructions): This project will provide in-depth understanding about the intermediate neural pathways underlying susceptibility to drug use disorders, their genetic basis, and the possible interactive role of the social environment in producing variations in risk over time. Findings will have direct implications for early identific- ation, prevention, and early treatment of at-risk individuals as well as those in early stages of drug addiction.
该项目研究了中间神经系统,这些神经系统介导了基因行为关系的参与 有可能出现毒品使用障碍(SUD)的风险,特别关注酒精,大麻和 尼古丁。我们将表征该电路,研究其与两个中间行为表型的相互作用 (行为范围内的控制和负面情感),并检查选定的遗传变异的贡献, 以及对脉冲和消极情绪的神经相关性的早期生活压力变化 成年后的SUD的风险[密歇根州纵向研究(MLS)的G2样本]。我们将 检查这些在童年时期的相关性,并开始表征在青少年期间发生的变化 ence。一般的假设是,与处理和调节有关的大脑网络失调 童年时期的行为和影响是较晚的倾向的增强的倾向 年龄。企业范围内的行为不足和幼年的情感失调都是SUD的强烈预测指标 在生活的后期,这些过程受复杂的神经元回路调节。我们将使用fMRI调查 这些神经系统来自纵向MLS的8-10岁男孩和女孩(n = 129) 扫描以2年间隔进行的扫描。可以预期,发育高风险的儿童 - 基于行为表型赋予的风险(最初以外部化和外在化和 内部化行为,后来按发展轨迹类别),将证明 神经元电路的功能响应涉及脉冲控制和情绪调节。这也是 发现这种效果将通过基因和早期应激来改变。大脑功能反应的变化 随着时间的流逝,预计将受到遗传变异和早期压力赋予的风险的影响。作为模型 随着时间的流逝,基因特征 - 环境相互作用在MLS中发展,我们将研究这种关系 在大脑反应与这些发育表型之间。随着药物滥用问题的发展 该样本,此信息将在随后的资金期间可用以确定功能障碍 在与青春期早期发育有关的神经回路中。 相关性(请参阅说明): 该项目将提供有关中间神经途径的深入了解 对药物使用障碍的敏感性,其遗传基础以及社会的可能互动作用 随着时间的推移产生风险变化的环境。调查结果将对早期识别产生直接影响 - 处于危险中的个体以及在药物成瘾的早期阶段的预防,预防和早期治疗。

项目成果

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ROBERT ALPERT ZUCKER其他文献

ROBERT ALPERT ZUCKER的其他文献

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{{ truncateString('ROBERT ALPERT ZUCKER', 18)}}的其他基金

Archiving parent-child, marital, and family social Interaction videotapes from a 33 year prospective study of the development of risk and resilience in a high risk population
归档 33 年高风险人群风险和复原力发展的前瞻性研究中的亲子、婚姻和家庭社交互动录像
  • 批准号:
    10380109
  • 财政年份:
    2021
  • 资助金额:
    $ 78.56万
  • 项目类别:
Capacity Building for Lifespan Focused Substance Use Disorder Research in Ukraine
乌克兰以寿命为中心的药物使用障碍研究能力建设
  • 批准号:
    8334872
  • 财政年份:
    2012
  • 资助金额:
    $ 78.56万
  • 项目类别:
Capacity Building for Lifespan Focused Substance Use Disorder Research in Ukraine
乌克兰以寿命为中心的药物使用障碍研究能力建设
  • 批准号:
    8652331
  • 财政年份:
    2012
  • 资助金额:
    $ 78.56万
  • 项目类别:
Capacity Building for Lifespan Focused Substance Use Disorder Research in Ukraine
乌克兰以寿命为中心的药物使用障碍研究能力建设
  • 批准号:
    8507820
  • 财政年份:
    2012
  • 资助金额:
    $ 78.56万
  • 项目类别:
Brain Endophenotypes Modulating Drug Abuse Risk
调节药物滥用风险的大脑内表型
  • 批准号:
    8049243
  • 财政年份:
    2009
  • 资助金额:
    $ 78.56万
  • 项目类别:
Brain Endophenotypes Modulating Drug Abuse Risk
调节药物滥用风险的大脑内表型
  • 批准号:
    7752750
  • 财政年份:
    2009
  • 资助金额:
    $ 78.56万
  • 项目类别:
Brain Endophenotypes Modulating Drug Abuse Risk
调节药物滥用风险的大脑内表型
  • 批准号:
    7792309
  • 财政年份:
    2009
  • 资助金额:
    $ 78.56万
  • 项目类别:
Brain Endophenotypes Modulating Drug Abuse Risk
调节药物滥用风险的大脑内表型
  • 批准号:
    8447114
  • 财政年份:
    2009
  • 资助金额:
    $ 78.56万
  • 项目类别:
Brain Endophenotypes Modulating Drug Abuse Risk
调节药物滥用风险的大脑内表型
  • 批准号:
    8245909
  • 财政年份:
    2009
  • 资助金额:
    $ 78.56万
  • 项目类别:
International Substance Abuse Research Program
国际药物滥用研究计划
  • 批准号:
    6640013
  • 财政年份:
    2001
  • 资助金额:
    $ 78.56万
  • 项目类别:

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