Neurobehavioral Liabilities of Precursive Risk for SUDS in Children

儿童 SUDS 前期风险的神经行为倾向

• 批准号: 9196347
• 负责人: C EMILY DURBIN
• 金额: $ 55.27万
• 依托单位: MICHIGAN STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-04-01 至 2020-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9196347
• 关键词: 7 year old; Adolescence; Adult; Age; Alcohol or Other Drugs use; Alcohols; Behavior; Behavioral; Brain; Child; Child Behavior; Childhood; Chronology; Databases; Depressed mood; Development; Early Intervention; Environment; Etiology; Expectancy; Family; Family Study; Feedback; Fright; Generations; Heritability; Interview; Laboratories; Link; Longitudinal Studies; Measures; Mediating; Methods; Michigan; Modeling; Nature; Neurobiology; Parents; Participant; Pathway interactions; Personality; Pharmaceutical Preparations; Phenotype; Process; Psychometrics; Psychopathology; Questionnaires; Recruitment Activity; Reporter; Reporting; Rewards; Risk; Risk Factors; Sampling; Science; Structure; Substance Use Disorder; Sum; Temperament; Testing; aged; anti social; anxious; base; cohort; design; disorder risk; early adolescence; early childhood; early onset; follow up assessment; follow-up; high reward; high risk; indexing; informant; innovation; insight; middle childhood; neurobehavioral; neurophysiology; novel; offspring; peer; prevent; prospective; public health relevance; trait; transmission process

 DESCRIPTION (provided by applicant): Behaviors in children as young as age 3 predict substance use and substance use disorders (SUDs) in adolescence and adulthood. Little is known, however, about the neurobiological processes that underlie this risk. We will test a neurobehavioral model of SUDs that accounts for their familial transmission and characterizes putative externalizing (antisocial) and internalizing (anxious and depressed) pathways to SUDs via the neurobehavioral constructs of effortful control (EC), reward responsiveness (RR), and fear proneness (FP). Our hypothesis is that this "Big 3" represents heritable, early emerging neurobehavioral processes that underlie non-specific risk for SUDs. To test this model, we will integrate brain science with a longitudinal-family design of two cohorts of children (aged 3-7 and 8-12) and their parents. Even more unique is that the parents have already been studied since early childhood as part of an ongoing family study, the Michigan Longitudinal Study (MLS). The original MLS parents (generation 1 [G1]) have high rates of SUDs (60%), and the original offspring participants (G2) are now adults, who also have high rates of SUDs, and many are now raising children of their own (G3). We will recruit the G3 families (N =259 children) to complete a comprehensive assessment of each neurobehavioral liability that includes neurophysiological (error-related negativity [ERN] for EC, feedback-related negativity [FRN] for RR, and fear-potentiated startle for FP), laboratory-based objective tasks, interview, and questionnaire approaches. We have three specific aims. (1) Examine the family transmission of the Big 3. The multigenerational structure of the sample also allows for especially unique comparisons such as the similarity between G2 parents and their G3 children using measures taken at the same chronological ages. (2) Test the unique, additive, and interactive effects of the Big 3 on risk for SUDs in the G3 offspring and their relationship to SUDs in G2 parents. We predict that different profiles of high and low levels of the Big 3 will differentiate externalizin and internalizing pathways to SUDs. We will also test whether the family transmission of the Big 3 mediates the associations between parent and child indices of SUDs. (3) Conduct a follow-up assessment of each child cohort 3 years after baseline to test whether the Big 3 have prospective and concurrent associations with intermediate phenotypes for SUD risk assessed at follow-up (e.g., substance initiation, externalizing problems). Delineating the mechanisms of early emerging neurobehavioral risk and the nature of the family transmission of risk will have a significant impact in regards to understanding etiological processes that will inform early intervention efforts to prevent the emergence and long-term impact of SUDs.

 描述（由申请人提供）：3 岁儿童的行为可以预测青春期和成年期的物质使用和物质使用障碍 (SUD)。然而，人们对造成这种风险的神经生物学过程知之甚少。我们将测试 SUD 的神经行为模型，该模型解释了 SUD 的家族传播，并通过努力控制（EC）、奖励反应性（RR）和恐惧倾向（FP）的神经行为结构来表征假定的 SUD 外化（反社会）和内化（焦虑和抑郁）途径。我们的假设是，这“三大”代表了可遗传的、早期出现的神经行为过程，这些过程是 SUD 非特异性风险的基础。 为了测试这个模型，我们将脑科学与两组儿童（3-7 岁和 8-12 岁）及其父母的纵向家庭设计相结合。更独特的是，作为正在进行的家庭研究——密歇根纵向研究（MLS）的一部分，父母从幼儿时期就开始接受研究。最初的 MLS 父母（第 1 代 [G1]）具有很高的 SUD 发生率（60%），最初的后代参与者 (G2) 现在已经是成年人，他们的 SUD 发生率也很高，而且许多人现在正在抚养自己的孩子 (G3)。 我们将招募 G3 家庭（N = 259 名儿童）来完成对每种神经行为倾向的全面评估，包括神经生理学（EC 的错误相关消极性 [ERN]、RR 的反馈相关消极性 [FRN] 和 FP 的恐惧强化惊吓）、基于实验室的客观任务、访谈和问卷方法。我们有三个具体目标。 (1) 检查“三巨头”的家庭传承。样本的多代结构还允许进行特别独特的比较，例如使用相同年龄采取的措施，G2 父母与其 G3 孩子之间的相似性。 (2) 测试三大因素对 G3 后代 SUD 风险的独特、累加和交互影响及其与 G2 父母 SUD 的关系。我们预测，三巨头高水平和低水平的不同特征将区分 SUD 的外化途径和内化途径。我们还将测试三巨头的家庭传播是否介导 SUD 的父指数和子指数之间的关联。 (3) 在基线后 3 年对每个儿童队列进行随访评估，以测试三大因素是否与随访时评估的 SUD 风险的中间表型具有前瞻性和同时的关联（例如，物质启动、外化问题）。描述早期出现的神经行为风险的机制和风险家庭传播的性质将对理解病因学过程产生重大影响，这将为早期干预工作提供信息，以防止 SUD 的出现和长期影响。