Deconstructing Schizophrenia: Advances in Preclinical Models for Biomarker Identification.

Deconstructing Schizophrenia: Advances in Preclinical Models for Biomarker Identification.
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解构精神分裂症:生物标志物识别的临床前模型的进展。

DOI:
10.1007/7854_2018_48
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发表时间:
2018
影响因子:
--
通讯作者:
Pratt JA
Pratt JA
中科院分区:
--
文献类型:
--
作者:
Pratt JA

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精神分裂症被认为是遗传和环境因素在脆弱的神经发育时期影响脑神经系统和回路的结果,从而导致成年早期出现症状。了解精神分裂症危险因素对脑生物学和行为的影响,有助于确定生物学相关途径,为临床研究和生物标志物开发提供有吸引力的信息。在本章中,我们强调采用互惠的正向和反向翻译方法的重要性,当获得额外的新信息时,迭代更新,无论是临床前还是临床,为发现精神分裂症的诊断、预后和治疗的生物标志物提供了最大的机会。重要的是,识别高危人群的生物标志物可以在精神分裂症发展之前为早期干预策略提供信息。鉴于该方法在该领域的新兴性质,本综述将重点介绍精神分裂症临床前生物标志物的最新研究,这些研究显示最有希望为临床需求提供信息,重点是相关的成像、电生理、认知行为和生化模式。这种相互转化方法的实施首先通过基于谷氨酸功能低下假说,精神分裂症的遗传和环境风险因素(反向翻译)的临床前模型的产生和表征,然后根据临床前发现,最近临床认识到丘脑网状丘脑(TRN)是精神分裂症脑功能障碍的重要位点(正向翻译)。
Schizophrenia is considered to develop as a consequence of genetic and environmental factors impacting on brain neural systems and circuits during vulnerable neurodevelopmental periods, thereby resulting in symptoms in early adulthood. Understanding of the impact of schizophrenia risk factors on brain biology and behaviour can help in identifying biologically relevant pathways that are attractive for informing clinical studies and biomarker development. In this chapter, we emphasize the importance of adopting a reciprocal forward and reverse translation approach that is iteratively updated when additional new information is gained, either preclinically or clinically, for offering the greatest opportunity for discovering panels of biomarkers for the diagnosis, prognosis and treatment of schizophrenia. Importantly, biomarkers for identifying those at risk may inform early intervention strategies prior to the development of schizophrenia.Given the emerging nature of this approach in the field, this review will highlight recent research of preclinical biomarkers in schizophrenia that show the most promise for informing clinical needs with an emphasis on relevant imaging, electrophysiological, cognitive behavioural and biochemical modalities. The implementation of this reciprocal translational approach is exemplified firstly by the production and characterization of preclinical models based on the glutamate hypofunction hypothesis, genetic and environmental risk factors for schizophrenia (reverse translation), and then the recent clinical recognition of the thalamic reticular thalamus (TRN) as an important locus of brain dysfunction in schizophrenia as informed by preclinical findings (forward translation).
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