Genetic Versus Phenotypic Markers of Relapse Risk

描述（由申请人提供）：拟议工作的总体目标是测试一种理论，该理论将COMT和GABRA2基因与中间表型联系起来，进而与药物滥用复发的重要临床问题联系起来。它将测试与物质依赖和额叶脑功能测量（即自发性脑电图中的快速β功率和额叶P300a振幅）相关的基因是否也会增加这些疾病复发的风险。该项目的具体目标是：(1)检查100名可卡因、海洛因或多种药物依赖患者在研究入组后4个月内恢复物质使用的基因型是否与100名成功保持戒断的患者和50名非物质依赖对照者的基因型不同；(2)重复我们之前的研究结果，即与保持戒断的患者和健康的非物质依赖对照相比，恢复物质使用的患者的脑电图快β活性增强，额叶P300a振幅降低；(3)确定GABRA2和COMT基因多态性是否分别与脑电快β功率和额叶P300a振幅表型变异相关；(4)结合其他已知的危险因素，包括依赖的严重程度/慢性程度、年龄、物质依赖类型和反社会人格障碍，确定遗传标记是否能提高预测复发的准确度，超过脑电图快速β功率和额叶P300a振幅所达到的预测精度。

DESCRIPTION (provided by applicant): The general goal of the proposed work is to test a theory that links the COMT and GABRA2 genes to intermediate phenotypes, and, in turn, to the important clinical problem of relapse to substance abuse. It will test whether genes that have been empirically linked to substance dependence, and to measures of frontal brain function (viz., fast beta power in the spontaneous electroencephalogram and frontal P300a amplitude), also confer an increased risk for relapse to these disorders. The specific goals of the project are: (1) to examine whether the genotypes of 100 cocaine-, heroin, or polydrug-dependent patients who return to substance use within 4 months after study enrollment are different from those of 100 patients who successfully maintain abstinence and 50 non-substance-dependent controls; (2) to replicate our previous findings of enhanced electroencephalographic fast beta activity and reduced frontal P300a amplitude in patients who return to substance use in comparison to patients who maintain abstinence and to healthy non-substance-dependent controls; (3) to determine if polymorphisms in GABRA2 and COMT genes are respectively associated with phenotypic variation in EEG fast beta power and frontal P300a amplitude; (4) to determine if genetic markers improve the prediction of relapse beyond the predictive accuracy attained with EEG fast beta power and frontal P300a amplitude, in combination with other known risk factors, including severity/chronicity of dependence, age, type of substance dependence, and Antisocial Personality Disorder.