Wong Chloe C Y, Schumann Gunter
Interdisciplinary Research Group Addiction, MRC-SGDP-Centre, Institute of Psychiatry at King's College, London, 16 De Crespigny Park, London SE5 8AF, UK.
Philos Trans R Soc Lond B Biol Sci. 2008 Oct 12;363(1507):3213-22. doi: 10.1098/rstb.2008.0104.
Addictions are common psychiatric disorders that exert high cost to the individual and to society. Addictions are a result of the interplay of multiple genetic and environmental factors. They are characterized by phenotypic and genetic heterogeneity as well as polygenicity, implying a contribution of different neurobiological mechanisms to the clinical diagnosis. Therefore, treatments for most substance use disorders are often only partially effective, with a substantial proportion of patients failing to respond. To address heterogeneity and polygenicity, strategies have been developed to identify more homogeneous subgroups of patients and to characterize genes contributing to their phenotype. These include genetic linkage and association studies as well as functional genetic analysis using endophenotypes and animal behavioural experimentation. Applying these strategies in a translational context aims at improving therapeutic response by the identification of subgroups of addiction patients for individualized, targeted treatment strategies. This article aims to discuss strategies addressing heterogeneity and polygenicity of substance use disorders by presenting results of recent research on genetic and environmental components of addiction. It will also introduce the European IMAGEN study that aims to integrate methodical approaches discussed in order to identify the genetic and neurobiological basis of behavioural traits relevant to the development of addictions.
成瘾是常见的精神疾病，给个人和社会带来高昂代价。成瘾是多种遗传和环境因素相互作用的结果。它们具有表型和遗传异质性以及多基因性的特点，这意味着不同的神经生物学机制对临床诊断有影响。因此，大多数物质使用障碍的治疗往往仅部分有效，相当一部分患者没有反应。为了解决异质性和多基因性问题，已制定策略来识别更同质的患者亚组，并确定导致其表型的基因。这些策略包括遗传连锁和关联研究，以及使用内表型和动物行为实验的功能基因分析。在转化背景下应用这些策略旨在通过识别成瘾患者亚组以制定个性化、有针对性的治疗策略来改善治疗反应。本文旨在通过介绍成瘾的遗传和环境成分的最新研究结果，讨论应对物质使用障碍异质性和多基因性的策略。它还将介绍欧洲IMAGEN研究，该研究旨在整合所讨论的方法，以确定与成瘾发展相关的行为特征的遗传和神经生物学基础。
