Alcohol dependence and gene x environment interaction in emotion regulation: Is serotonin the link?
Alcohol dependence and gene x environment interaction in emotion regulation: Is serotonin the link?
复制标题
DOI：
10.1016/j.ejphar.2005.09.027
复制
发表时间：
2005-12-05
影响因子：
5
通讯作者：
Lesch, KP
中科院分区：
文献类型：
--
作者：
Lesch, KP
酒精依赖的特征是频繁、强迫和不受控制地饮酒，并伴有适应不良和破坏行为。它是一种病因和临床异质性综合征，中度至高度遗传，由基因和环境的相互作用引起。酒精依赖通过常见的神经生物学途径与其他精神疾病相关，包括调节奖赏、行为控制以及焦虑和应激反应的神经生物学途径。酒精诱导大脑功能的适应性变化，为耐受、渴望、戒断和情绪障碍提供基础。因此，反映神经生物学过程的成瘾行为的心理生物学特征的分化对于解剖酒精依赖的复杂遗传易感性具有特别重要的意义。中枢5-羟色胺（5-HT）缺乏被认为通过调节动机行为、神经适应过程和由此产生的情绪障碍参与酒精依赖的发病机制。5-HT相关的冲动、攻击和自杀行为与易受酒精依赖影响的原始人格有关。尽管编码5-HT系统的受体、酶和转运蛋白的许多基因的变异已被测试为酒精依赖的危险因素，但酒精依赖中5-HT信号传导的遗传分析主要集中在5-HT转运蛋白（5-HTT）基因上。由于5-HTT的调节变异体在调节多巴胺能神经传递中的核心作用，其与焦虑相关的性状相关，不仅是抑郁症病因学中基因x环境相互作用的神经生物学机制的关键参与者，而且还有助于发展具有反社会行为和自杀倾向的酒精依赖的风险。5-HTT功能的等位基因变异对边缘回路对情绪刺激的反应具有调节作用的证据表明，基因型-内表型相关性可能适用于大脑的分子功能成像。这些新的发展对我们理解酒精依赖的遗传脆弱性如何表现在大脑对情绪刺激的反应中具有广泛的意义。(c)2005 Elsevier B. V.保留所有权利。
Alcohol dependence is characterized by frequent, compulsive and uncontrolled consumption of alcohol associated with behavior of maladaption and destruction. It is an etiologically and clinically heterogeneous syndrome, moderately to highly heritable, and caused by interaction of genes and environment. Alcohol dependence is related to other psychiatric diseases by common Deurobiological pathways, including those that modulate reward, behavioral control as well as anxiety and stress response. Alcohol induces adaptive changes in brain function providing the basis for tolerance, craving, withdrawal, and emotional disturbance. The differentiation of psychobiological traits of addictive behavior reflecting neurobiological processes is therefore of particular importance for the dissection of the complex genetic susceptibility to alcohol dependence. A central serotonin (5-HT) deficit is thought to be involved in the pathogenesis of alcohol dependence by modulating motivational behavior, neuroadaptive processes, and resulting emotional disturbance. 5-HT-related impulsive, aggressive, and suicidal behavior has been linked to a primordial personality that is susceptible to alcohol dependence. Although variations in many of the genes that encode receptors, enzymes, and transporters of the 5-HT system have been tested as risk factors for alcohol dependence, genetic analyses of 5-HT signaling in alcohol dependence have mainly been focused on the 5-HT transporter (5-HTT) gene. Due to its central role in the fine-tuning serotonergic neurotransmission, a regulatory variant of the 5-HTT, which is associated with anxiety related traits, is not only a key player in the neurobiological mechanism of gene x environment interaction in the etiology of depression, but also contributes to the risk to develop alcohol dependence with antisocial behavior and suicidality. Evidence for a modulatory effect of allelic variation of 5-HTT function on limbic circuit responses to emotional stimuli suggests that genotype-endophenotype correlations may be accessible to molecular functional imaging of the brain. These new developments have broad implications for our understanding how genetic vulnerability to alcohol dependence is manifested in the brain's response to emotional stimuli. (c) 2005 Elsevier B.V. All rights reserved.