Alcohol, stress, and glucocorticoids: From risk to dependence and relapse in alcohol use disorders.
Alcohol, stress, and glucocorticoids: From risk to dependence and relapse in alcohol use disorders.
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DOI：
10.1016/j.neuropharm.2017.01.037
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发表时间：
2017-08-01
影响因子：
4.7
通讯作者：
Sinha R
中科院分区：
文献类型：
--
作者：
Blaine SK;Sinha R
在这篇综述中，我们详细介绍了在轻到中度酒精使用障碍(AUDS)的发展过程中，心理和生理压力在酒精消费工具动机中的作用，以及在重度、慢性、复发性AUDS中出现的强迫性、习惯性酒精消费中的作用的临床证据。传统上，对AUDS的研究主要集中在酒精对纹状体多巴胺能通路的直接和间接影响，以及它们在酒精强化效应中的作用。然而，越来越多的证据也表明，酒精直接刺激下丘脑垂体肾上腺(HPA)轴，并影响下丘脑外、边缘前脑和内侧前额叶(PFC)回路中的糖皮质激素受体，这有助于AUDS的发生及其严重程度、慢性化和复发风险的进展。有证据表明，重度AUDS患者在长期戒断和高觉醒条件下，HPA轴、糖皮质激素和PFC功能障碍，新的证据也显示，酗酒/酗酒与非依赖者的酒精动机有关。具体地说，酒精引起的HPA轴对压力和酒精提示反应的改变可能作为内感生理信号，促进影响酒精动机的条件反射机制。因此，这种功能障碍可能成为潜在的风险和复发的生物标志物。基于这些新出现的数据，我们概念化并提出了治疗靶点的早期证据，这些靶点可能改善PFC功能和/或使HPA轴功能正常化，并可能对AUDS的治疗和复发预防有益。最后，我们认为这些回路中与酒精相关的病理生理学的个体差异可能调节治疗和康复反应，从而支持建立个性化药物算法来理解和治疗AUDS的需要。
In this review, we detail the clinical evidence supporting the role of psychological and physiological stress in instrumental motivation for alcohol consumption during the development of mild to moderate alcohol use disorders (AUDs) and in the compulsive, habitual alcohol consumption seen in severe, chronic, relapsing AUDs. Traditionally, the study of AUDs has focused on the direct and indirect effects of alcohol on striatal dopaminergic pathways and their role in the reinforcing effects of alcohol. However, growing evidence also suggests that alcohol directly stimulates the hypothalamic pituitary adrenal (HPA) axis and has effects on glucocorticoid receptors in extrahypothalamic, limbic forebrain, and medial Prefrontal Cortex (PFC) circuits, which contribute to the development of AUDs and their progression in severity, chronicity, and relapse risk. Evidence indicates HPA axis, glucocorticoid, and PFC dysfunction during protracted withdrawal and under high arousal conditions in those with severe AUDs, and novel evidence is also emerging to suggest HPA axis dysfunction with binge/heavy drinking, which is associated with motivation for alcohol in non-dependent individuals. Specifically, alcohol-associated alterations in HPA axis responses to stress and alcohol cues may serve as interoceptive physiological signals and facilitate conditioning mechanisms to influence alcohol motivation. Thus, this dysfunction may serve as a potential biomarker of both risk and of relapse. Based on this emerging data, we conceptualize and present early evidence for treatment targets that may improve PFC function and/or normalize HPA axis functioning and may be beneficial in the treatment and relapse prevention of AUDs. Finally, we suggest that individual differences in alcohol-related pathophysiology in these circuits may modulate treatment and recovery response, thereby supporting the need for building personalized medicine algorithms to understand and treat AUDs.