NEUROCOGNITIVE CONSEQUENCES OF ADOLESCENT MARIJUANA USE

项目摘要(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 使用同卵双胞胎控制方法的大麻(MJ)消费。MJ是最常用的违禁药 典型的药物使用开始于青春期，这一时期大脑持续发育并增加 易受滥用药物有害影响的影响。以前的研究已经建立了 慢性和/或早期MJ暴露以及脑功能、行为和认知的改变，包括 对行为的自律和增加的冲动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障碍。然而， 大多数现有的研究依赖于病例对照、相关设计，排除了很强的因果推断。它 目前尚不清楚在MJ使用者中发现的缺陷是否代表MJ使用的后果，或者相反，在MJ使用之前 存在使用MJ的风险因素。这一悬而未决的问题代表着知识上的严重差距，阻碍了 预防、干预和治疗方法的发展，以及与MJ相关的循证公众 政策。拟议的研究试图通过实施强大的 同卵双生控制设计。在MJ使用史不一致的同卵双胞胎中，双胞胎具有相同程度的 遗传风险和环境有许多共同的关键方面，但在MJ暴露方面有所不同。因此， 未接触MJ的双胞胎是他们接触MJ的同卵双胞胎的理想对照。同双胞胎控制方法是 因此，一种成本和时间高效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病例和长时间(约10 几年来)取得了决定性的成果。拟议的研究将使用一套理论驱动的实验 收集神经生理、行为和认知测量的范例，以利用特定的 神经认知成分过程与(I)冲动和成瘾风险(反应 抑制、错误监测和选择性注意)和/或(Ii)增加精神分裂症的风险(感觉性和 感觉运动门控、听觉异常检测)。这些措施将在280名青少年和 有和没有MJ使用史的年轻成年双胞胎年龄在19-36岁之间。这对双胞胎将从现有的 对独立调查员和联合调查员进行流行病学研究，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、禁欲持续时间和双胞胎的一致性与 MJ使用的不和谐。具体目标将是：1)检查MJ使用和 青少年和年轻人的神经认知功能，并确定这些 相关性取决于接触的严重程度、开始使用MJ的年龄和戒酒时间，以及2) 使用同卵双胞胎对照方法，将MJ使用的后果与先前存在的脑功能变化隔离开来 和认知力。

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.