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

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.

摘要 酒精使用和酒精使用障碍（AUD）表现出强烈的年龄相关模式，特别是， 在青春期上升，在成年初期达到高峰使用和流行，随后大幅下降 在年轻的成年期。然而，在这些一般模式的基础上， 的发生、持续和严重程度。这些模式受到大脑中个体差异的影响 结构和功能方面的初始风险和神经成熟的速度，后者是 受到酒精和毒品的影响然而，除了暴露于物质之外，一个人的更广泛的 环境背景包括许多影响神经发育和增加或 降低澳元风险。描述了不同的神经和环境之间的复杂相互作用 影响，有助于出现和持续与停止AUD需要跟踪， 物质使用、神经过程和背景变量之间的共同发展， 使用和持续过去的青年成年后，澳元利率已经达到顶峰，并开始下降。 我们建议通过继续跟踪密歇根纵向研究的两组后代来做到这一点 (MLS)参与纵向神经成像的人MLS是一项高风险家庭研究， 父母一代中物质使用障碍的发病率较高（>60%）。后代有 从3-5岁开始，对个人水平和背景进行密集评估， 每3年评估一次风险因素，并从11岁开始每年评估一次物质使用和风险因素。 MLS参与者（N=340）的纵向神经成像在一到两年的时间间隔开始于儿童时期， （n=130;基线法师=10岁，当前法师=16岁）或年轻成人（n=210;基线法师=20岁， 当前法师= 26岁），包括结构，静息状态和任务相关激活，重点是认知 控制和奖励过程。我们建议在21岁以下的儿童队列中进行额外的纵向扫描， 在年轻的成年人群体中，年龄可达30岁。这将提供对大脑结构的大量评估， 儿童期至青年期（7-30岁）的发育阶段的功能和连接。我们 方法将强调复杂的分析方法，从神经影像中提取最大的信息 数据（例如，专注于使用独立成分分析的基于电路的模式），以绘制规范的大脑 发展，确定AUD的神经生物学风险，并确定酒精使用对大脑的影响 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和大脑发育，重点是与增加相关的生活过渡（性开始， 离开家）或减少（婚姻，父母）饮酒。拟议的研究将是独一无二的， 该领域有可能对AUD与大脑发育之间的联系做出关键发现。