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药物基因组学:精神医学精准医疗的前行之路。

Pharmacogenomics: A road ahead for precision medicine in psychiatry.

作者信息

Pardiñas Antonio F, Owen Michael J, Walters James T R

机构信息

MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University School of Medicine, Hadyn Ellis Building, Maindy Road, Cardiff CF24 4HQ, UK.

MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University School of Medicine, Hadyn Ellis Building, Maindy Road, Cardiff CF24 4HQ, UK.

出版信息

Neuron. 2021 Dec 15;109(24):3914-3929. doi: 10.1016/j.neuron.2021.09.011. Epub 2021 Oct 6.

Abstract

Psychiatric genomics is providing insights into the nature of psychiatric conditions that in time should identify new drug targets and improve patient care. Less attention has been paid to psychiatric pharmacogenomics research, despite its potential to deliver more rapid change in clinical practice and patient outcomes. The pharmacogenomics of treatment response encapsulates both pharmacokinetic ("what the body does to a drug") and pharmacodynamic ("what the drug does to the body") effects. Despite early optimism and substantial research in both these areas, they have to date made little impact on clinical management in psychiatry. A number of bottlenecks have hampered progress, including a lack of large-scale replication studies, inconsistencies in defining valid treatment outcomes across experiments, a failure to routinely incorporate adverse drug reactions and serum metabolite monitoring in study designs, and inadequate investment in the longitudinal data collections required to demonstrate clinical utility. Nonetheless, advances in genomics and health informatics present distinct opportunities for psychiatric pharmacogenomics to enter a new and productive phase of research discovery and translation.

摘要

精神科基因组学正在为精神疾病的本质提供见解,假以时日,有望识别出新的药物靶点并改善患者护理。尽管精神科药物基因组学研究有潜力在临床实践和患者预后方面带来更迅速的改变,但人们对其关注较少。治疗反应的药物基因组学涵盖了药代动力学(“身体对药物的作用”)和药效动力学(“药物对身体的作用”)效应。尽管在这两个领域早期都抱有乐观态度且进行了大量研究,但迄今为止它们对精神科临床管理几乎没有产生影响。一些瓶颈阻碍了进展,包括缺乏大规模重复研究、各实验中定义有效治疗结果不一致、研究设计中未常规纳入药物不良反应和血清代谢物监测,以及对证明临床效用所需的纵向数据收集投入不足。尽管如此,基因组学和健康信息学的进展为精神科药物基因组学进入一个新的、富有成效的研究发现与转化阶段提供了独特机遇。

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