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将神经精神遗传学和基因组学的见解转化为精准精神病学。

Translating insights from neuropsychiatric genetics and genomics for precision psychiatry.

机构信息

MRC Centre for Neuropsychiatric Genetics and Genomics, Neuroscience and Mental Health Research Institute and Division of Psychological Medicine and Clinical Neuroscience, Cardiff University, Hadyn Ellis Building, Maindy Road, Cardiff, CF24 4HQ, UK.

出版信息

Genome Med. 2020 Apr 29;12(1):43. doi: 10.1186/s13073-020-00734-5.

Abstract

The primary aim of precision medicine is to tailor healthcare more closely to the needs of individual patients. This requires progress in two areas: the development of more precise treatments and the ability to identify patients or groups of patients in the clinic for whom such treatments are likely to be the most effective. There is widespread optimism that advances in genomics will facilitate both of these endeavors. It can be argued that of all medical specialties psychiatry has most to gain in these respects, given its current reliance on syndromic diagnoses, the minimal foundation of existing mechanistic knowledge, and the substantial heritability of psychiatric phenotypes. Here, we review recent advances in psychiatric genomics and assess the likely impact of these findings on attempts to develop precision psychiatry. Emerging findings indicate a high degree of polygenicity and that genetic risk maps poorly onto the diagnostic categories used in the clinic. The highly polygenic and pleiotropic nature of psychiatric genetics will impact attempts to use genomic data for prediction and risk stratification, and also poses substantial challenges for conventional approaches to gaining biological insights from genetic findings. While there are many challenges to overcome, genomics is building an empirical platform upon which psychiatry can now progress towards better understanding of disease mechanisms, better treatments, and better ways of targeting treatments to the patients most likely to benefit, thus paving the way for precision psychiatry.

摘要

精准医学的主要目标是更精确地根据个体患者的需求提供医疗服务。这需要在两个领域取得进展:开发更精确的治疗方法,以及在临床上识别出可能最受益于这些治疗方法的患者或患者群体的能力。人们普遍乐观地认为,基因组学的进步将促进这两个方面的发展。可以说,在所有医学专业中,精神病学在这方面受益最大,因为它目前依赖于综合征诊断,现有的机械知识基础很少,以及精神表型的大量遗传性。在这里,我们回顾了精神病学基因组学的最新进展,并评估了这些发现对开发精准精神病学的可能影响。新出现的研究结果表明,精神疾病具有高度的多基因性,遗传风险与临床上使用的诊断类别相关性较差。精神疾病遗传学的高度多基因性和多效性将影响使用基因组数据进行预测和风险分层的尝试,也对从遗传发现中获得生物学见解的传统方法提出了重大挑战。尽管面临许多挑战,但基因组学正在构建一个经验平台,精神病学现在可以在此基础上更好地理解疾病机制、开发更好的治疗方法,以及更好地将治疗方法针对最有可能受益的患者,从而为精准精神病学铺平道路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25fd/7189552/ea9a709b57b0/13073_2020_734_Fig1_HTML.jpg

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