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这一重要的临床问题联系起来。它将测试与物质依赖和额叶大脑功能指标(即自发脑电中的快速β功率和额叶P300a波幅)相关的基因是否也会增加这些疾病的复发风险。该项目的具体目标是：(1)检查100名在研究登记后4个月内重新吸食毒品的可卡因、海洛因或多药依赖患者的基因型别是否与100名成功维持戒酒的患者和50名非物质依赖对照组的不同；(2)复制我们之前的发现，即与维持戒毒的患者和健康的非物质依赖对照组相比，重新吸食药物的患者的脑电快速β活动增强，额叶P300a波幅降低；(3)确定GABRA2和COMT基因的多态性是否分别与脑电快速β功率和额叶P300a波幅的表型变异有关；(4)确定遗传标记是否可以提高复发预测的准确性，超过脑电快速β功率和额叶P300a波幅的预测精度，并结合其他已知的危险因素，包括依赖的严重程度/慢性、年龄、物质依赖类型和反社会人格障碍。

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.