NEUROCOGNITIVE CONSEQUENCES OF ADOLESCENT MARIJUANA USE

青少年吸食大麻的神经认知后果

• 批准号: 9239633
• 负责人: Andrey P. Anokhin
• 金额: $ 60.35万
• 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 2021-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9239633
• 关键词: Abstinence; Accounting; Address; Adolescence; Adolescent; Adolescent and Young Adult; Adolescent marijuana use; Age; Age of Onset; Alcohol or Other Drugs use; Auditory; Behavior; Behavioral; Brain; Characteristics; Chronic; Cognition; Cognitive; Cognitive deficits; Comorbidity; 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; 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; Preventive Intervention; 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; cost; design; deviant; drug of abuse; early onset; epidemiology study; evidence base; illicit drug use; marijuana use; marijuana user; member; neurobiological mechanism; neurophysiology; response; selective attention; sex; 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.

项目摘要（摘要） 拟议的研究的总体目标是描述后果并确定青少年 大麻（MJ）使用联合控制方法的消费。 MJ是最常用的非法 在青少年中典型使用的药物，持续大脑发育并增加的药物 对滥用药物的有害影响的脆弱性。先前的研究已经建立了关联 慢性和/或早期MJ暴露以及脑功能，行为和认知的改变，包括缺陷 行为的自我调节和增加的冲动性，可能会增加过渡到使用的风险 “更难的”药物以及类似于精神分裂症的神经认知功能障碍。然而， 大多数现有研究依赖于病例对照，相关设计排除了强烈的因果推断。它 尚不清楚MJ用户中发现的定义是否代表MJ使用的后果，相反， 现有的MJ使用风险因素。这个未解决的问题代表了知识的关键差距 开发预防，干预和治疗方法，以及基于证据的MJ相关公众 政策。拟议的研究试图通过实施强大的 联合控制设计。在单卵双胞胎双对中，MJ使用历史记录，双胞胎具有相同的程度 遗传责任和共享环境的许多关键方面，但在MJ暴露方面有所不同。那， 非暴露的双胞胎代表了其MJ暴露的联合双胞胎的理想对照。联合控制方法是 因此，一种成本和时间效率的方法可以被视为与纵向研究相称的 需要很大的样本以确保足够的高暴露情况和长时间的表现（约10个 几年）取得了结论性的结果。拟议的研究将使用一组理论驱动的实验 收集神经生理学，行为和认知措施的范例，以利用特定 与（i）冲动性和成瘾风险相关的神经认知成分过程（响应 抑制，错误监测和选择性关注）和/或（ii）增加精神分裂症的风险（感觉和 感觉运动门控，听觉偏差检测）。这些措施将在280个青少年和 有和没有MJ的年轻成人双胞胎使用19-36岁的历史。双胞胎将从现有 PI和共同研究器的流行病学研究，并根据现有数据选择，以确保足够 发病年龄，暴露范围，禁欲的长度和双对一致性的变异性 使用MJ的不一致。具体目标是：1）检查MJ使用之间的关联 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，MJ使用年龄和禁欲的长度以及2） 孤立，使用共晶体控制方法，MJ在脑功能中使用的后果产生的后果 和认知。