Consensus paper of the WFSBP Task Force on Biological Markers: Criteria for biomarkers and endophenotypes of schizophrenia, part III: Molecular mechanisms

A. Schmitt, D. Martins‐de‐Souza, S. Akbarian, J. Cassoli, H. Ehrenreich, A. Fischer, A. Fonteh, W. Gattaz, M. Gawlik, M. Gerlach, E. Grünblatt, Tobias Halene, A. Hasan, Kenij Hashimoto, Yong-Ku Kim, Sophie-Kathrin Kirchner, J. Kornhuber, Theo F. J. Kraus, B. Malchow, J. Nascimento, M. Rossner, M. Schwarz, J. Steiner, L. Talib, F. Thibaut, P. Riederer, P. Falkai
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引用次数: 33

Abstract

Abstract Objectives: Despite progress in identifying molecular pathophysiological processes in schizophrenia, valid biomarkers are lacking for both the disease and treatment response. Methods: This comprehensive review summarises recent efforts to identify molecular mechanisms on the level of protein and gene expression and epigenetics, including DNA methylation, histone modifications and micro RNA expression. Furthermore, it summarises recent findings of alterations in lipid mediators and highlights inflammatory processes. The potential that this research will identify biomarkers of schizophrenia is discussed. Results: Recent studies have not identified clear biomarkers for schizophrenia. Although several molecular pathways have emerged as potential candidates for future research, a complete understanding of these metabolic pathways is required to reveal better treatment modalities for this disabling condition. Conclusions: Large longitudinal cohort studies are essential that pair a thorough phenotypic and clinical evaluation for example with gene expression and proteome analysis in blood at multiple time points. This approach might identify biomarkers that allow patients to be stratified according to treatment response and ideally also allow treatment response to be predicted. Improved knowledge of molecular pathways and epigenetic mechanisms, including their potential association with environmental influences, will facilitate the discovery of biomarkers that could ultimately be effective tools in clinical practice.
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WFSBP生物标志物工作组共识文件:精神分裂症生物标志物和内表型标准,第三部分:分子机制
摘要目的:尽管在鉴定精神分裂症的分子病理生理过程方面取得了进展,但缺乏有效的生物标志物来识别疾病和治疗反应。方法:本文综述了近年来在蛋白质和基因表达水平以及表观遗传学方面的研究进展,包括DNA甲基化、组蛋白修饰和微RNA表达。此外,它总结了最近的发现在脂质介质的改变,并强调炎症过程。讨论了该研究在识别精神分裂症生物标志物方面的潜力。结果:最近的研究尚未发现明确的精神分裂症生物标志物。尽管一些分子途径已经成为未来研究的潜在候选者,但为了揭示更好的治疗方法,需要对这些代谢途径有一个完整的了解。结论:大型纵向队列研究是必要的配对彻底的表型和临床评估,例如基因表达和蛋白质组分析在多个时间点的血液。这种方法可以识别生物标志物,根据治疗反应对患者进行分层,理想情况下也可以预测治疗反应。对分子途径和表观遗传机制的进一步了解,包括它们与环境影响的潜在关联,将有助于发现生物标志物,这些生物标志物最终可能成为临床实践中的有效工具。
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