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)表现出强烈的与年龄相关的模式，具体地说，开始和 青春期升级、使用高峰期和成年初期流行率，随后大幅下降 在年轻的成年期。然而，在这些一般模式的背后，存在着很大的差异 AUD的发病、持续和严重程度。这些模式受到大脑中个体差异的影响 在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，除了接触物质外，一个人的更广泛的 环境背景包括一些影响神经发育和增加或 降低澳元的风险。描绘不同神经和环境之间复杂的相互作用 有助于澳元出现和持续而不是持续的影响需要跟踪 物质使用、神经过程和上下文变量在启动之前的共同发展 使用和继续使用过了年轻的成年期，之后澳元使用率达到顶峰，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)，他们一直参与纵向神经成像。MLS是一项高风险的家庭研究， 物质使用障碍在父母一代中的高流行率(&gt；60%)。后代有了 从3-5岁开始跟踪调查，对个人层面和背景进行密集评估 每隔3年对危险因素进行一次评估，并从11岁开始对药物使用情况和危险因素进行年度评估。 MLS参与者(N=340)每隔一到两年就开始进行纵向神经成像 (n=130；基线MAGE=10岁，当前MAGE=16岁)或青壮年(n=210；基线MAGE=20岁， 当前MAGE=26岁)，包括结构、休息状态和任务相关的激活，侧重于认知 控制和奖励流程。我们建议在21岁以下的儿童队列中进行额外的纵向扫描，并且 在青壮年队列中，年龄在30岁以下。这将提供大量对大脑结构的评估， 从儿童到成年(7-30岁)整个发育阶段的功能和连接性。我们的 方法将强调复杂的分析方法，以从神经成像中提取最大信息 数据(例如，使用独立分量分析专注于基于电路的模式)以绘制标准大脑 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结合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命过渡(性启动， 离家出走)或减少(婚姻、为人父母)饮酒。拟议的研究将在 该领域有可能在AUD和大脑发育之间的联系上取得关键发现。