Zike Isaac, Xu Tim, Hong Natalie, Veenstra-VanderWeele Jeremy
Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Neuroscience. 2017 Mar 14;345:256-273. doi: 10.1016/j.neuroscience.2016.09.012. Epub 2016 Sep 16.
Obsessive Compulsive Disorder (OCD) is a common neuropsychiatric disorder with unknown molecular underpinnings. Identification of genetic and non-genetic risk factors has largely been elusive, primarily because of a lack of power. In contrast, neuroimaging has consistently implicated the cortico-striatal-thalamo-cortical circuits in OCD. Pharmacological treatment studies also show specificity, with consistent response of OCD symptoms to chronic treatment with serotonin reuptake inhibitors; although most patients are left with residual impairment. In theory, animal models could provide a bridge from the neuroimaging and pharmacology data to an understanding of pathophysiology at the cellular and molecular level. Several mouse models have been proposed using genetic, immunological, pharmacological, and optogenetic tools. These experimental model systems allow testing of hypotheses about the origins of compulsive behavior. Several models have generated behavior that appears compulsive-like, particularly excessive grooming, and some have demonstrated response to chronic serotonin reuptake inhibitors, establishing both face validity and predictive validity. Construct validity is more difficult to establish in the context of a limited understanding of OCD risk factors. Our current models may help us to dissect the circuits and molecular pathways that can elicit OCD-relevant behavior in rodents. We can hope that this growing understanding, coupled with developing technology, will prepare us when robust OCD risk factors are better understood.
强迫症（OCD）是一种常见的神经精神疾病，其分子基础尚不清楚。遗传和非遗传风险因素的识别在很大程度上一直难以捉摸，主要是因为样本量不足。相比之下，神经影像学一直表明强迫症与皮质-纹状体-丘脑-皮质回路有关。药物治疗研究也显示出特异性，强迫症症状对5-羟色胺再摄取抑制剂的长期治疗有一致的反应；尽管大多数患者仍有残余损伤。理论上，动物模型可以在神经影像学和药理学数据与细胞和分子水平的病理生理学理解之间架起一座桥梁。已经提出了几种使用基因、免疫、药理和光遗传学工具的小鼠模型。这些实验模型系统允许对强迫行为的起源假说进行测试。几种模型产生了类似强迫行为的表现，特别是过度梳理毛发，一些模型还证明了对5-羟色胺再摄取抑制剂的长期治疗有反应，确立了表面效度和预测效度。在对强迫症风险因素了解有限的情况下，构建效度更难确立。我们目前的模型可能有助于我们剖析在啮齿动物中引发与强迫症相关行为的神经回路和分子途径。我们希望，随着对这方面的认识不断加深，再加上技术的不断发展，当我们对强大的强迫症风险因素有更好的了解时，能做好充分准备。
