Heilig Markus, Sommer Wolfgang H, Spanagel Rainer
Center for Social and Affective Neuroscience, Department of Clinical and Experimental Medicine, Linköping University, SE-58183, Linköping, Sweden.
Institute of Psychopharmacology, Central Institute of Mental Health, Faculty of Medicine Mannheim, University of Heidelberg, Heidelberg, Germany.
Curr Top Behav Neurosci. 2016;28:151-71. doi: 10.1007/7854_2015_5006.
Over the past two decades, major advances have been made in the basic neuroscience of alcohol addiction. However, few of these have been translated into clinically useful treatments, which remain limited. In the past decade, psychiatric drug development in general has been stalled, with many preclinically validated mechanisms failing in clinical development. Despite the existence of appealing preclinical models in the area of addictive disorders, drug development for these conditions has been impacted by the exodus of major pharma from psychiatric neuroscience. Here, we discuss translational biomarker strategies that may help turn this tide. Following an approach patterned on an endophenotype approach to complex behavioral traits, we hypothesize that relatively simple biological measures should be sought that can be obtained both in experimental animals and in humans, and that may be responsive to alcoholism medications. These biomarkers have to be tailored to the specific mechanism targeted by candidate medications and may in fact also help identify biologically more homogeneous subpopulations of patients. We introduce as examples alcohol-induced dopamine (DA) release, measures of central glutamate levels, and network connectivity, and discuss our experience to date with these biomarker strategies.
在过去二十年里，酒精成瘾的基础神经科学取得了重大进展。然而，其中很少有转化为临床可用的治疗方法，目前的治疗方法仍然有限。在过去十年中，精神科药物研发总体上陷入停滞，许多临床前验证的机制在临床开发中失败。尽管成瘾性疾病领域存在有吸引力的临床前模型，但这些疾病的药物开发受到大型制药公司退出精神神经科学领域的影响。在此，我们讨论可能有助于扭转这一局面的转化生物标志物策略。遵循一种基于复杂行为特征的内表型方法的模式，我们假设应该寻找相对简单的生物学测量方法，这些方法可以在实验动物和人类身上获得，并且可能对酒精中毒药物有反应。这些生物标志物必须针对候选药物靶向的特定机制进行定制，实际上也可能有助于识别生物学上更同质的患者亚群。我们以酒精诱导的多巴胺（DA）释放、中枢谷氨酸水平测量和网络连接性为例进行介绍，并讨论我们迄今为止在这些生物标志物策略方面的经验。
