Using human brain imaging studies as a guide toward animal models of schizophrenia.
Using human brain imaging studies as a guide toward animal models of schizophrenia.
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DOI：
10.1016/j.neuroscience.2015.05.055
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发表时间：
2016-05-03
期刊：
影响因子：
3.3
通讯作者：
Kellendonk C
中科院分区：
文献类型：
--
作者：
Bolkan SS;Carvalho Poyraz F;Kellendonk C
精神分裂症是一种异质性的和知之甚少的精神障碍，目前仅通过其行为症状来定义。然而，在过去的半个世纪中，遗传学、流行病学和脑成像技术的进步极大地促进了我们对这种疾病的潜在生物学的理解。尽管取得了这些进展，临床研究在建立病因学与病理生理学和症状之间的因果关系方面的能力仍然有限。在这种情况下，动物模型提供了一个重要的工具，因果检验假设的生物过程被破坏的障碍。虽然动物模型可以利用各种切入点对精神分裂症的研究，在这里，我们描述了一种方法，旨在密切接近脑成像技术在患者中观察到的功能改变。通过在动物中模拟这些中间的病理生理学改变，这种方法提供了一个机会：（1）将单一的功能性脑异常与其行为后果紧密联系起来，（2）确定单一的病理生理学是否可以在患者中描述的其他脑区域中因果地产生改变。在这篇综述中，我们首先总结了精神分裂症文献中描述的复制良好的生物学异常的选择。然后，我们提供了动物模型的例子，在患者的成像结果描述增强纹状体多巴胺D2受体功能，丘脑-前额叶回路功能的改变，海马代谢功能亢进的背景下进行了研究。最后，我们讨论了这些动物模型的研究结果对我们目前对精神分裂症的理解的影响，并考虑了未来在动物模型和人类患者中进行研究的关键问题。
Schizophrenia is a heterogeneous and poorly understood mental disorder that is presently defined solely by its behavioral symptoms. Advances in genetic, epidemiological and brain imaging techniques in the past half century, however, have significantly advanced our understanding of the underlying biology of the disorder. In spite of these advances clinical research remains limited in its power to establish the causal relationships that link etiology with pathophysiology and symptoms. In this context, animal models provide an important tool for causally testing hypotheses about biological processes postulated to be disrupted in the disorder. While animal models can exploit a variety of entry points towards the study of schizophrenia, here we describe an approach that seeks to closely approximate functional alterations observed with brain imaging techniques in patients. By modeling these intermediate pathophysiological alterations in animals, this approach offers an opportunity to (1) tightly link a single functional brain abnormality with its behavioral consequences, and (2) to determine whether a single pathophysiology can causally produce alterations in other brain areas that have been described in patients. In this review we first summarize a selection of well-replicated biological abnormalities described in the schizophrenia literature. We then provide examples of animal models that were studied in the context of patient imaging findings describing enhanced striatal dopamine D2 receptor function, alterations in thalamo-prefrontal circuit function, and metabolic hyperfunction of the hippocampus. Lastly, we discuss the implications of findings from these animal models for our present understanding of schizophrenia, and consider key unanswered questions for future research in animal models and human patients.