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GABRA 2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。它将测试是否有基因已被经验联系到物质依赖，并测量额叶脑功能（即，自发脑电图中的快速β功率和额叶P300 a振幅），也增加了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与100名成功维持戒断的患者和50名非物质依赖对照的基因型是否不同;（二）重复我们先前的研究结果，即与维持戒断和健康的患者相比，恢复使用药物的患者的脑电图快速β活动增强，额叶P300 a振幅降低。非物质依赖性控制;（3）GABRA 2和COMT基因多态性是否分别与EEG快β功率和额叶P300 a波幅的表型变异相关;（4）确定遗传标志物是否改善复发的预测，超过用EEG快速β功率和额叶P300 a振幅获得的预测准确性，与其他已知的风险因素组合，包括依赖的严重性/慢性性，年龄，物质依赖和反社会人格障碍

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.