The genetic basis of addictive disorders.
The genetic basis of addictive disorders.
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DOI：
10.1016/j.psc.2012.03.010
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发表时间：
2012-06
影响因子：
1.7
通讯作者：
Goldman, David
中科院分区：
文献类型：
--
作者：
Ducci, Francesca;Goldman, David
成瘾，包括物质使用障碍（SUD），是多步骤的条件，根据定义，需要暴露于成瘾剂。成瘾剂的种类繁多，包括药物、食物、性、视频游戏和赌博。这些药物中的任何一种都可能通过与精神活性物质成瘾相关的神经生物学途径部分重叠而导致“成瘾状态”。1每年有数百万人接触成瘾剂，例如，在治疗疼痛的医疗过程中。绝大多数人不会上瘾，即使引起暂时的耐受性和依赖性。初始使用的概率和向病理性使用模式进展的概率受内在因素的影响（例如，基因型、性别、年龄、首次使用年龄、既存成瘾性障碍或其他精神疾病）、外在因素（例如，药物的可获得性、同伴影响、社会支持、童年逆境、父母教养方式、社会经济地位）和成瘾剂的性质（例如，精神活性、药代动力学、使用或给药方式）。这些因素的相对重要性在整个生命周期和成瘾的不同阶段有所不同。例如，同龄人的影响和家庭环境是最重要的接触和最初的使用模式，而遗传因素和精神病理学在过渡到有问题的使用中发挥了更突出的作用。2在易成瘾的个体中，反复暴露于药物会诱导持久的神经适应性变化，进一步促进药物寻求行为，最终导致持续和不受控制的使用模式，构成成瘾。这些神经适应性变化是容忍、渴望和退缩的基础，并导致动机的转变。3.吸毒行为的动机最初是由冲动和正性奖励驱动的。相反，强迫性和消极情绪在病理学的晚期占主导地位。从某种意义上说，成瘾是“末期”诊断，因为在诊断的时候，潜在的不可逆的神经适应性变化已经发生了，这些变化在疾病发展的早期是可以预防的。
Addictions, including substance use disorders (SUDs), are multistep conditions that, by definition, require exposure to an addictive agent. The wide variety of addictive agents encompasses drugs, foods, sex, video-gaming, and gambling. Any of these agents may lead to an “addicted state” through neurobiologic pathways partially overlapping with those involved in addiction to psychoactive substances. 1 Millions of people are exposed to addictive agents each year, for instance, in the course of medical care for treatment of pain. The vast majority do not become addicted, even if temporary tolerance and dependence are elicited. The probability of initial use and the probability of progression toward a pathologic pattern of use are influenced by intrinsic factors (eg, genotype, sex, age, age at first use, preexisting addictive disorder, or other mental illness), extrinsic factors (eg, drug availability, peer influences social support, childhood adversity, parenting style, socioeconomic status), and the nature of the addictive agent (eg, psychoactive properties, pharmacokinetics, mode of use or administration). The relative importance of these factors varies across the lifespan and at different stages of addiction. For example, peer influences and family environment are most important for exposure and initial pattern of use, whereas genetic factors and psychopathology play a more salient role in the transition to problematic use. 2In individuals who are vulnerable to addiction, repetitive exposure to the agent induces longlasting neuroadaptative changes that further promote drug-seeking behaviors and ultimately lead to persistent and uncontrolled patterns of use that constitute addiction. These neuroadaptive changes are the bases for tolerance, craving, and withdrawal and lead to a motivational shift. 3 Motivation to drug-seeking behavior is initially driven by impulsivity and positive reward. In contrast, compulsivity and negative affect dominate the terminal stages of the pathology. Addictions are in a sense “end-stage” diagnoses because at the time diagnosis is made potentially irreversible neuroadaptative change have occurred—changes that were preventable at an early point of the trajectory of the illness.
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