PhD PROPOSAL: Can genomics enhance care and quality of life in psychosis?

精神病是影响3%人口的严重精神疾病（Bogren et al. 2009）。英国每年精神病的经济负担为90亿英镑，欧洲为930亿英镑，包括直接医疗保健和社会间接成本（McCrone et al. 2008, Olesen et al. 2012）。超过20种药物已被证明对治疗精神病有效（联合处方委员会2018）。药物选择和剂量调整是经验性的，患者需要多次更换药物是很常见的（Taylor et al. 2018）。然而，有令人信服的证据表明，遗传因素会影响反应和药物不良反应（van der woden et al. 2017）。对于大约200种药物，包括一些抗精神病药物，有临床指南和美国食品和药物管理局或欧洲药品管理局的标签，建议根据基因谱调整剂量（临床药物遗传学实施联盟2017，Stingl等人2016，Swen等人2011，美国食品和药物管理局2015）。在精神病护理方面，我们面临两大挑战：首先，多达60%的人停止服药，这增加了复发的风险（Velligan et al. 2020, Velligan et al. 2017）；其次，存在多种用药的主要问题（Broekema et al. 2007, Young et al. 2015）， 20-40%的人使用与国家健康与护理卓越研究所指南（NICE 2014）相反的药物组合治疗。公众现在可以以负担得起的费用进行基因检测，10万和500万基因组项目正在以前所未有的方式改变我们的医疗保健服务（Genomics England， 2020年12月）。最近的研究表明，使用基因数据来指导药物选择可以节省成本（Verbelen et al. 2017）。在丹麦进行的唯一一项基因指导的抗精神病治疗试验显示，在精神卫生和初级保健方面，直接医疗保健费用都有显著节省（Herbild et al. 2013, Jurgens et al. 2020）。然而，在英国的心理健康实践中，我们还没有使用药物基因组学测试，因为其益处和成本效益的证据不足（Just et al. 2017, Walden et al. 2015）。

Psychotic disorders are severe mental illnesses affecting 3% of the population (Bogren et al. 2009). The annual economic burden of psychosis is £9 billion in England and 93 billion in Europe, including both direct healthcare as well as indirect costs to society (McCrone et al. 2008, Olesen et al. 2012). More than 20 medications have demonstrated efficacy to treat psychosis (Joint Formulary Committee 2018). Drug choices and dose adjustments are empirical and it is common for patients to need several medication changes (Taylor et al. 2018). However, there is compelling evidence that genetic factors influence response and adverse drug reactions (van der Wouden et al. 2017). For about 200 medications, including some antipsychotics, there are clinical guidelines and Food and Drug Administration or European Medicines Agency labels recommending dose adjustments based on genetic profile (Clinical Pharmacogenetics Implementation Consortium 2017, Stingl et al. 2016, Swen et al. 2011, U.S. Food and Drug Administration 2015). In psychosis care we face two major challenges: Firstly, as many as 60% of people stop taking their medication, which increases risk of relapsing (Velligan et al. 2020, Velligan et al. 2017); Secondly, there is a major problem of polypharmacy (Broekema et al. 2007, Young et al. 2015), with 20-40% of people treated with drug combinations contrary to National Institute for Health and Care Excellence guidelines (NICE 2014). Genetic testing is now available to the general public for affordable fees and the 100,000 and the 5 million Genomes Projects are transforming our healthcare services in an unprecedented way (Genomics England December 2020). Recent studies indicate that using genetic data to guide medication choices is cost-saving (Verbelen et al. 2017). The only trial of genetic-guided antipsychotic treatment run in Denmark revealed significant savings in direct healthcare costs both in mental health and primary care (Herbild et al. 2013, Jurgens et al. 2020). However, in UK mental health practice we do not use pharmacogenomics testing yet, due to insufficient evidence of its benefits and of its cost-effectiveness (Just et al. 2017, Walden et al. 2015).