Cannabis Use, Abuse and Dependence: Exploring Phenotypes

描述(由申请人提供)： 尽管大麻被广泛使用，但在遗传信息研究设计中探索使用、滥用和依赖的模式和相关性的研究相对较少。这项研究将补充正在进行的两项关于男性(DA 12540，Pi Madden)和女性(AA 09022 Pi Heath)双胞胎的研究的现有数据，收集关于双胞胎18-30岁(预计n=1,600)的完整兄弟姐妹的大麻使用模式、使用升级和相关危害的综合信息。将这三个来源的数据结合起来，将确保有足够的统计能力来解决以下问题： 目的1：通过评估大麻使用障碍发展的时间和开始阶段，确定大麻使用进展的哪些阶段首先出现遗传影响，这些阶段包括：第一次接触/使用机会；实验、增加使用、使用量、第一次滥用/依赖症状的经历以及滥用或依赖的开始。 目的2：评估对大麻的主观反应，这种反应在多大程度上受到遗传因素的影响，这种反应可能在多大程度上与发生大麻使用障碍的风险相关，以及与对大麻的主观反应有关的遗传和环境影响与与大麻使用障碍的易感性有关的遗传和环境影响的重叠程度。 目的3：检查与大麻使用/依赖有关的共病精神病理学(包括其他物质使用/依赖)的模式，以及在多大程度上可以根据共病精神病理学确定大麻使用/依赖的定性不同的遗传亚型。 目的4：在遗传信息性研究设计的背景下，评估大麻使用障碍(滥用、依赖)的心理测量学特性，并检查个别滥用/依赖症状的遗传协方差结构。 目的5：在这些分析的基础上，建立一个模型，揭示基因对大麻转变的影响和依赖症状的出现。

DESCRIPTION (provided by applicant): Despite the widespread use of cannabis, there has been relatively little research exploring patterns and correlates of use, abuse and dependence within genetically informative research designs. This study will supplement existing data from two ongoing studies of male (DA 12540, PI Madden) and female (AA 09022 PI Heath) twins by collecting comprehensive information on patterns of cannabis use, escalation in use and related harm from the twins' full siblings aged 18-30 (projected n =1,600). Combining data from these three sources will ensure adequate statistical power to address the following issues: AIM 1: To determine at what stages in the progression of cannabis use heritable influences first arise, by assessing the timing and onset of stages in the development of cannabis use disorders including: first exposure/opportunity to use; experimentation, escalating use, quantity used, the experience of first abuse/ dependence symptom and the onset of abuse or dependence. AIM 2: To assess subjective reactions to cannabis, the extent to which such responses are influenced by heritable factors, the extent to which such reactions may be correlated with risks for the development of cannabis use disorders and the extent of overlap in the genetic and environmental influences associated with subjective reactions to cannabis and those associated with liability to cannabis use disorders. AIM 3: To examine patterns of comorbid psychopathology (including other substance use/ dependence) associated with cannabis use/dependence and the extent to which qualitatively distinct heritable subtypes of cannabis use/dependence can be identified on the basis of comorbid psychopathology. AIM 4: To assess the psychometric properties of an assessment of cannabis use disorders (abuse, dependence) within the context of a genetically informative research design, and examine the genetic covariance structure of individual symptoms of abuse/dependence. AIM 5: Based on these analyses, to formulate a model for unfolding of genetic influences on transitions in cannabis and the emergence of dependence symptoms.