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.

抽象的 饮酒和酒精使用障碍 (AUD) 表现出强烈的年龄相关模式，特别是开始和饮酒 青春期使用率上升，成年初期使用率和流行率达到峰值，随后大幅下降 在年轻的成年时期。然而，在这些一般模式的基础上，在 AUD 的发作、持续时间和严重程度。这些模式受到大脑个体差异的影响 初始风险和神经成熟率方面的结构和功能，后者是 受酒精和药物使用的影响。然而，除了接触物质之外，一个人的更广泛的 环境背景包括许多影响神经发育并增加或增加的影响 降低澳元风险。描绘不同神经和环境之间复杂的相互作用 有助于澳元出现​​、持续与消亡的影响需要跟踪 在开始之前物质使用、神经过程和情境变量之间的共同发展 使用并持续到成年后，之后澳元汇率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）一直参与纵向神经影像学。 MLS 是一项高风险家庭研究 父母一代物质使用障碍的患病率很高（>60%）。后代有 从 3-5 岁开始对个人水平和背景进行深入评估 从 11 岁开始，每 3 年进行一次危险因素评估，并对物质使用和危险因素进行年度评估。 MLS 参与者 (N = 340) 每隔一到两年进行一次纵向神经影像学检查，从童年开始 （n=130；基线法师=10岁，当前法师=16岁）或青年期（n=210；基线法师=20岁， 当前法师 = 26 岁），包括结构、静息状态和专注于认知的任务相关激活 控制和奖励过程。我们建议对儿童队列中 21 岁以下的儿童进行额外的纵向扫描，并且 年轻人群体中的年龄最大为 30 岁。这将提供大量的大脑结构评估， 儿童到成年早期（7-30 岁）整个发育阶段的功能和连接性。我们的 该方法将强调复杂的分析方法，以从神经影像中提取最大的信息 数据（例如，使用独立组件分析关注基于电路的模式）来绘制规范的大脑图 开发，识别 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 和大脑发育，重点是与增加相关的生活转变（性开始、 离开家）或减少（结婚、为人父母）饮酒。拟议的研究将是独一无二的 该领域有潜力就 AUD 与大脑发育之间的联系做出重要发现。