NEUROCOGNITIVE CONSEQUENCES OF ADOLESCENT MARIJUANA USE

青少年吸食大麻的神经认知后果

• 批准号: 10057378
• 负责人: Andrey P. Anokhin
• 金额: $ 58.2万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-02-15 至 2022-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10057378
• 关键词: Abstinence; Accounting; Address; Adolescence; Adolescent; Adolescent and Young Adult; Adolescent marijuana use; Age; Age of Onset; Auditory; Behavior; Behavioral; Brain; Characteristics; Chronic; Cognition; Cognitive; Cognitive deficits; Consumption; Data; Data Analyses; Deltastab; Detection; Development; Dose; Elderly; Ensure; Environment; Epidemiology; Ethnic Origin; Etiology; Family; Frequencies; Functional disorder; Gender; Genetic; Goals; Impaired cognition; Impairment; Impulsivity; Individual; Informal Social Control; Intervention; Knowledge; Length; Link; Long-Term Effects; Longitudinal Studies; Marijuana; Marijuana Abuse; Measures; Mediating; Methods; Monitor; Monozygotic twins; Neighborhoods; Neurocognitive; Neurocognitive Deficit; Neurophysiology - biologic function; Pharmaceutical Preparations; Predisposition; Prevention; Process; Psychopathology; Psychotic Disorders; Public Policy; Recording of previous events; Reporting; Research Personnel; Residual state; Risk; Risk Factors; Sampling; Schizophrenia; Sensory; Severities; Socioeconomic Status; Testing; Time; Twin Multiple Birth; Twin Studies; addiction; aged; base; brain behavior; case control; comorbidity; cost; design; deviant; drug of abuse; early onset; epidemiology study; evidence base; illicit drug use; marijuana use; marijuana user; member; neurobiological mechanism; neurophysiology; response; schizophrenia risk; selective attention; sex; substance use; theories

Project Summary (Abstract) The overall goal of the proposed study is to delineate consequences and determinants of adolescent marijuana (MJ) consumption using the co-twin control approach. MJ is the most commonly used illicit drug with a typical onset of use in adolescence, a period of continued brain development and increased vulnerability to detrimental effects of drugs of abuse. Previous studies have established associations between chronic and/or early MJ exposure and alterations in brain function, behavior, and cognition, including deficits in self-regulation of behavior and increased impulsivity that may increase the risk for transition to the use of “harder” drugs, as well as neurocognitive dysfunctions that resemble those seen in schizophrenia. However, most existing studies relied on case-control, correlational designs precluding strong causal inferences. It remains unclear whether deficits found in MJ users represent the consequences of MJ use or, conversely, pre- existing factors of risk for MJ use. This unresolved issue represents a critical gap in knowledge that hinders the development of prevention, intervention, and treatment methods, as well as evidence-based MJ related public policy. The proposed study seeks to address this gap in knowledge through the implementation of the powerful co-twin control design. In monozygotic twin pairs discordant for MJ use history, twins have the same degree of genetic liability and share many critical aspects of environment but differ with respect to MJ exposure. Thus, the non-exposed twins represent ideal controls for their MJ-exposed co-twins. The co-twin control method is thus a cost- and time-efficient approach that can be viewed as complimentary to longitudinal studies that require very large samples to ensure sufficient representation of high-exposure cases and long time (about 10 years) to achieve conclusive results. The proposed study will use a set of theory-driven experimental paradigms to collect neurophysiological, behavioral, and cognitive measures that tap into specific neurocognitive component processes that have been linked to (i) impulsivity and addiction risk (response inhibition, error monitoring, and selective attention) and/or (ii) increased risk for schizophrenia (sensory and sensorimotor gating, auditory deviance detection). These measures will be assessed in 280 adolescent and young adult twins with and without MJ use history aged 19-36. The twins will be drawn from existing epidemiological studies of the PI and co-investigators and selected, based on existing data, to ensure sufficient variability in the age of onset, extent of exposure, length of abstinence, and twin pair concordance versus discordance for MJ use. Specific aims will be: 1) To examine associations between MJ use and neurocognitive functioning in adolescents and young adults and to determine the extent to which these associations depend on severity of exposure, age of onset of MJ use, and length of abstinence and 2) To isolate, using co-twin control approach, consequences of MJ use from pre-existing alterations in brain function and cognition.

项目概要（摘要） 拟议研究的总体目标是描述青少年的后果和决定因素 使用共同孪生控制方法控制大麻 (MJ) 消费是最常用的非法行为。 药物通常在青春期开始使用，这是大脑持续发育和增加的时期 先前的研究已经确定了滥用药物造成的痛苦影响之间的关联。 慢性和/或早期 MJ 暴露以及大脑功能、行为和认知的改变，包括功能缺陷 行为的自我调节和冲动的增加可能会增加过渡到使用 “更难”的药物，以及类似于精神分裂症的神经认知功能障碍。 大多数现有研究依赖于病例对照和相关设计，排除了强烈的因果推论。 目前尚不清楚 MJ 用户中发现的缺陷是否代表 MJ 使用的后果，或者相反，是预 MJ 使用的现有风险因素这一尚未解决的问题代表了阻碍 MJ 使用的关键知识差距。 制定预防、干预和治疗方法，以及基于证据的 MJ 相关公众 拟议的研究旨在通过实施强有力的政策来解决这一知识差距。 在 MJ 使用历史不一致的同卵双胞胎中，双胞胎具有相同的程度。 遗传倾向和环境的许多关键方面有共同之处，但在 MJ 暴露方面有所不同。 未暴露的双胞胎代表其 MJ 暴露的双胞胎的理想控制。共同双胞胎控制方法是。 因此，一种具有成本效益和时间效率的方法可以被视为对纵向研究的补充， 需要非常大的样本，以确保充分代表高暴露情况和长时间（约 10 年）以取得结论性的结果。拟议的研究将使用一组理论驱动的实验。 收集神经生理学、行为和认知测量的范式，这些测量利用特定的 与 (i) 冲动和成瘾风险（反应 抑制、错误监控和选择性注意）和/或（ii）精神分裂症风险增加（感觉和 这些措施将在 280 名青少年和青少年中进行评估。 年龄在 19 至 36 岁之间、有或没有 MJ 使用史的年轻成年双胞胎将从现有双胞胎中抽取。 PI 和共同研究者的流行病学研究，并根据现有数据进行选择，以确保足够的 发病年龄、暴露程度、戒断时间长度以及双胞胎一致性的变异性 MJ 使用的不一致具体目标是： 1）检查 MJ 使用和之间的关联。 青少年和年轻人的神经认知功能，并确定这些功能的程度 关联取决于暴露的严重程度、开始使用 MJ 的年龄以及禁欲的时间长短，并且 2) 使用双生控制方法，将使用 MJ 的后果与先前存在的大脑功能改变分开 和认知。