Scott Jan, Etain Bruno, Bellivier Frank
Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, United Kingdom.
Centre for Affective Disorders, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
Front Psychiatry. 2018 Aug 21;9:360. doi: 10.3389/fpsyt.2018.00360. eCollection 2018.
Clinical practice guidelines identify lithium as a first line treatment for mood stabilization and reduction of suicidality in bipolar disorders (BD); however, most individuals show sub-optimal response. Identifying biomarkers for lithium response could enable personalization of treatment and refine criteria for stratification of BD cases into treatment-relevant subgroups. Existing systematic reviews identify potential biomarkers of lithium response, but none directly address the conceptual issues that need to be addressed to enhance translation of research into precision prescribing of lithium. For example, although clinical syndrome subtyping of BD has not led to customized individual treatments, we emphasize the importance of assessing clinical response phenotypes in biomarker research. Also, we highlight the need to give greater consideration to the quality of prospective longitudinal monitoring of illness activity and the differentiation of non-response from partial or non-adherence with medication. It is unlikely that there is a single biomarker for lithium response or tolerability, so this review argues that more research should be directed toward the exploration of biosignatures. Importantly, we emphasize that an integrative science approach may improve the likelihood of discovering the optimal combination of clinical factors and multimodal biomarkers (e.g., blood omics, neuroimaging, and actigraphy derived-markers). This strategy could uncover a valid lithium response phenotype and facilitate development of a composite prediction algorithm. Lastly, this narrative review discusses how these strategies could improve eligibility criteria for lithium treatment in BD, and highlights barriers to translation to clinical practice including the often-overlooked issue of the cost-effectiveness of introducing biomarker tests in psychiatry.
临床实践指南将锂盐确定为双相情感障碍（BD）情绪稳定和降低自杀倾向的一线治疗药物；然而，大多数患者的反应并不理想。识别锂盐反应的生物标志物可以实现个性化治疗，并完善将BD病例分层为与治疗相关亚组的标准。现有的系统评价确定了锂盐反应的潜在生物标志物，但没有一项直接解决将研究转化为锂盐精准处方时需要解决的概念性问题。例如，尽管BD的临床综合征亚型分类尚未导致个体化定制治疗，但我们强调在生物标志物研究中评估临床反应表型的重要性。此外，我们强调需要更多地考虑疾病活动前瞻性纵向监测的质量，以及区分无反应与部分反应或药物不依从。不太可能存在单一的锂盐反应或耐受性生物标志物，因此本综述认为应将更多研究导向生物标志物组合的探索。重要的是，我们强调综合科学方法可能会提高发现临床因素和多模式生物标志物（如血液组学、神经影像学和活动记录仪衍生标志物）最佳组合的可能性。这种策略可以揭示有效的锂盐反应表型，并促进复合预测算法的开发。最后，本叙述性综述讨论了这些策略如何改善BD患者锂盐治疗的入选标准，并强调了转化为临床实践的障碍，包括在精神病学中引入生物标志物检测的成本效益这一经常被忽视的问题。
