Developmental neurobiological and contextual influences on alcohol use disorder

发育神经生物学和背景对酒精使用障碍的影响

• 批准号: 10197735
• 负责人: BRIAN M HICKS
• 金额: $ 55.04万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-10 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10197735
• 关键词: 21 year old; 5 year old; Adolescence; Affect; Age; Alcohol consumption; Back; Brain; Child; Childhood; Complex; Data; Data Analytics; Deterioration; Development; Drug usage; Education; Environmental Risk Factor; Exhibits; Exposure to; Family; Family Study; Generations; Growth; Height; High Prevalence; Home; Image; Individual; Individual Differences; Joints; Life; Link; Longitudinal Studies; Marriage; Measurement; Measures; Mediating; Michigan; Modeling; Neurobiology; Neurologic; Neurophysiology - biologic function; Parents; Participant; Pattern; Persons; Positioning Attribute; Prevalence; Process; Psychopathology; Psychosocial Assessment and Care; Rest; Rewards; Risk; Risk Factors; Risk Marker; Role; Sampling; Scanning; Schools; Severities; Structure; Substance Use Disorder; Testing; Variant; Weight; Work; age related; alcohol effect; alcohol reward; alcohol risk; alcohol use disorder; analytical method; anti social; base; cognitive control; cohort; contextual factors; emerging adulthood; experience; financial incentive; high risk; independent component analysis; maltreatment; multimodal data; neurodevelopment; neuroimaging; neurotoxic; offspring; peer; prospective; relating to nervous system; satisfaction; sexual debut; substance use; young adult; 21 year old; 5 year old; Adolescence; Affect; Age; Alcohol consumption; Back; Brain; Child; Childhood; Complex; Data; Data Analytics; Deterioration; Development; Drug usage; Education; Environmental Risk Factor; Exhibits; Exposure to; Family; Family Study; Generations; Growth; Height; High Prevalence; Home; Image; Individual; Individual Differences; Joints; Life; Link; Longitudinal Studies; Marriage; Measurement; Measures; Mediating; Michigan; Modeling; Neurobiology; Neurologic; Neurophysiology - biologic function; Parents; Participant; Pattern; Persons; Positioning Attribute; Prevalence; Process; Psychopathology; Psychosocial Assessment and Care; Rest; Rewards; Risk; Risk Factors; Risk Marker; Role; Sampling; Scanning; Schools; Severities; Structure; Substance Use Disorder; Testing; Variant; Weight; Work; age related; alcohol effect; alcohol reward; alcohol risk; alcohol use disorder; analytical method; anti social; base; cognitive control; cohort; contextual factors; emerging adulthood; experience; financial incentive; high risk; independent component analysis; maltreatment; multimodal data; neurodevelopment; neuroimaging; neurotoxic; offspring; peer; prospective; relating to nervous system; satisfaction; sexual debut; substance use; young adult

Abstract Alcohol use and alcohol use disorder (AUD) exhibits strong age-related patterns, specifically, initiation and escalation in adolescence, peak use and prevalence in emerging adulthood, followed by a substantial decline in young adulthood. Underlying these general patterns, however, there is substantial variation in terms of the onset, persistence, and severity of AUD. These patterns are influenced by individual differences in brain structure and function both in terms of initial risk and the rate of neurological maturation, the latter of which is affected by alcohol and drug use. In addition to exposure to substances, however, a person's broader environmental context includes a number of influences that impact neural development and increase or decrease risk for AUD. Delineating the complex interplay among the different neural and environmental influences that contribute to the emergence and persistence versus desistence of AUD requires tracking the co-development between substance use, neural processes, and contextual variables prior to the initiation of use and continuing past young adulthood after which AUD rates have peaked and begun to decline. We propose to do so by continuing to follow two cohorts of offspring from the Michigan Longitudinal Study (MLS) who have been participating in longitudinal neuroimaging. The MLS is a high-risk family study with a high prevalence of substance use disorders in the parental generation (>60%). The offspring generation has been followed beginning at ages 3-5 years old with intensive assessments of individual-level and contextual risk factors at 3-year intervals and annual assessments of substance use and risk factors beginning at age 11. Longitudinal neuroimaging of MLS participants (N=340) at one- to two-year intervals began in either childhood (n=130; baseline Mage=10 years, current Mage=16 years) or young adulthood (n=210; baseline Mage=20 years, current Mage = 26 years) including structure, resting state, and task-related activation focused on cognitive control and reward processes. We propose additional longitudinal scans, up to age 21 in the child cohort, and up to age 30 in the young adult cohort. This will provide a dense number of assessments of brain structure, function and connectivity across the developmental period of childhood to young adulthood (ages 7-30). Our approach will emphasize sophisticated analytic methods to extract maximal information from the neuroimaging data (e.g., focus on circuit-based patterns using independent components analysis) to chart normative brain development, identify neurobiological risk for AUD, and determine the impact of alcohol use on brain development. We will also use longitudinal models to incorporate the role of environmental influences on both AUD and brain development with an emphasis on life transitions associated with increases (sexual initiation, leaving home) or decreases (marriage, parenthood) in alcohol use. The proposed study will be unique in the field with the potential to make key findings on the link between AUD and brain development.

抽象的 饮酒和酒精使用障碍（AUD）表现出与年龄相关的强大模式，特别是起始和 青春期的升级，新兴成年期的高峰使用和流行率，随后大幅下降 成年。然而，基于这些一般模式，就 AUD的发作，持久性和严重性。这些模式受大脑个体差异的影响 在初始风险和神经系统成熟率方面的结构和功能，后者是 受酒精和吸毒的影响。除了暴露于物质外，一个人的广泛 环境环境包括影响神经发展并增加或增加或 降低AUD的风险。描绘不同神经和环境之间的复合物相互作用 影响出现的影响和持久性与拒绝的影响需要跟踪 在启动之前 使用和持续过去的成年后，AUD率达到顶峰并开始下降。 我们建议通过继续跟随密歇根州纵向研究的两个后代来做到这一点 （MLS）参加了纵向神经影像学。 MLS是一项高风险家庭研究 父母生成中物质使用障碍的高流行率（> 60％）。后代一代有 紧随其后的是3-5岁，对个人级别和上下文进行了深入评估 危险因素以3年间隔和对物质使用和危险因素的年度评估从11岁开始。 MLS参与者的纵向神经影像学（n = 340）以一到两年的间隔在任何一个童年开始 （n = 130;基线法师= 10年，当前法师= 16岁）或成年（n = 210;基线法师= 20岁， 当前法师= 26年），包括结构，静止状态和与任务相关的激活。 控制和奖励流程。我们提出了其他纵向扫描，在儿童队列中最多21岁， 在年轻的成人队列中，最高30岁。这将为大脑结构提供密集的评估， 整个儿童发展期至年轻人的功能和连通性（7-30岁）。我们的 方法将强调复杂的分析方法，以从神经影像中提取最大信息 数据（例如，使用独立组件分析专注于基于电路的模式）以绘制规范性大脑 开发，确定AUD的神经生物学风险，并确定饮酒对大脑的影响 发展。我们还将使用纵向模型来纳入环境影响对两者的作用 aud和大脑的发展，重点是与增加有关的生活转变（性启动， 离开家中）或减少酒精饮酒的（婚姻，育儿）。拟议的研究将在 有可能在AUD与大脑发育之间的联系上做出关键发现。