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[酒精依赖的遗传因素]

[Genetic factors of alcohol-dependence].

作者信息

Pinto E, Ansseau M

机构信息

Service de Psychiatrie et de Psychologie Médicale, Université de Liège, CHU Sart-Tilman, BP 35, 4000 Liège, Belgique.

出版信息

Encephale. 2009 Oct;35(5):461-9. doi: 10.1016/j.encep.2008.03.008. Epub 2008 Oct 23.

Abstract

INTRODUCTION

Alcohol dependence is a complex and multifactorial disease resulting both from neurobiological mechanisms and environmental factors. It is frequently associated with comorbid psychiatric disorders or with specific personality or behavioral features. Although action can be taken on the environment in order to decrease the risk of the illness, current methods used to prevent or to treat this pathology show moderate efficacy: problematic consumption of ethanol in the general population as well as relapse rates under treatment in dependent patients remain indeed very high.

LITERATURE FINDINGS

It is therefore of major importance to broaden our knowledge of alcohol dependence and its comorbidities so as to improve both their prevention and treatment. In this perspective, recent progress in the field of neurosciences may contribute to achieve this goal. Precisely, genetics is a promising way benefiting from many advances in genetic epidemiology, cellular and molecular biology, neuroimaging and pharmacology. In parallel with a better understanding of the neurobiology of addictions and associated behaviors, these techniques led to the identification of brain mechanisms in which a genetic variation may influence the individual vulnerability towards alcohol dependence. Moreover, there is growing evidence that alcoholism results from the interaction of genetic and environmental factors influencing both its expression and its course. Given the fact that alcohol-dependence seems highly heritable (50 to 60% of the variance in both men and women), this review assesses the role of some of the genomic regions linked with the disease, as well as the principal variants of candidate genes identified as specifically involved in the predisposition. Polymorphisms of genes influencing alcohol metabolism, GABAergic, dopaminergic and serotonergic neurotransmission seem, indeed, at stake in the development of alcohol-dependence and its related features such as personality, behavior, impulse control or craving. In the future, a better characterization of the links between genotypes and phenotypes will probably increase our ability to treat alcoholic patients.

摘要

引言

酒精依赖是一种复杂的多因素疾病,由神经生物学机制和环境因素共同导致。它常与共病性精神障碍或特定的人格或行为特征相关。尽管可以针对环境采取行动以降低患病风险,但目前用于预防或治疗这种病症的方法疗效中等:普通人群中乙醇的问题性消费以及依赖患者治疗中的复发率仍然非常高。

文献研究结果

因此,拓宽我们对酒精依赖及其共病的认识对于改善其预防和治疗至关重要。从这个角度来看,神经科学领域的最新进展可能有助于实现这一目标。确切地说,遗传学是一条有前景的途径,受益于遗传流行病学、细胞与分子生物学、神经影像学和药理学等多方面的进展。在更好地理解成瘾神经生物学及相关行为的同时,这些技术促使人们识别出一些脑机制,其中基因变异可能影响个体对酒精依赖的易感性。此外,越来越多的证据表明,酒精中毒是由影响其表达和病程的遗传与环境因素相互作用导致的。鉴于酒精依赖似乎具有高度遗传性(男性和女性的方差均为50%至60%),本综述评估了一些与该疾病相关的基因组区域的作用,以及被确定为特别参与易感性的候选基因的主要变体。影响酒精代谢、γ-氨基丁酸能、多巴胺能和5-羟色胺能神经传递的基因多态性似乎确实与酒精依赖及其相关特征(如人格、行为、冲动控制或渴望)的发展有关。未来,对基因型与表型之间联系的更深入了解可能会提高我们治疗酒精性患者的能力。

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