Isolating biomarkers for symptomatic states: considering symptom-substrate chronometry.
Isolating biomarkers for symptomatic states: considering symptom-substrate chronometry.
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DOI：
10.1038/mp.2016.83
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发表时间：
2016-09
影响因子：
11
通讯作者：
Leonard, C. V.
中科院分区：
文献类型：
--
作者：
Treadway, M. T.;Leonard, C. V.
精神病理学研究的一个长期目标是开发症状状态的客观标记物，但进展远远慢于预期。虽然以前的综述将这种情况归因于诊断的异质性、症状共病和表型复杂性，但很少有人注意到个体内症状动态和相互关联对生物标记物研究设计的影响。在这篇关键的综述中，我们考虑了短期症状波动对广泛使用的研究设计的影响，这些研究设计将给定症状的“平均水平”与在单个时间点收集的生物学数据进行回归，并总结了来自动态评估研究的结果，表明这种设计可能是检测症状-基质关系的次优设计。虽然这种设计在促进我们对与更稳定、更长期的变化(例如，抑郁发作期间灰质变薄)相关的生物底物的理解方面发挥了关键作用，但它们可能不太适合检测表现出高频波动的症状、容易受到常见报告偏差的影响，或可能受到其他症状的存在的严重影响。我们建议，更多地强调个体内症状计时法可能有助于识别具有共同的近端病理指标的患者亚组。综上所述，症状概念化和测量领域的这三个最新发展为未来试图在精神病学中识别可靠的生物标记物的研究提出了重要的考虑。
A long-standing goal of psychopathology research is to develop objective markers of symptomatic states, yet progress has been far slower than expected. While prior reviews have attributed this state of affairs to diagnostic heterogeneity, symptom comorbidity, and phenotypic complexity, little attention has been paid to the implications of intra-individual symptom dynamics and inter-relatedness for biomarker study designs. In this critical review, we consider the impact of short-term symptom fluctuations on widely-used study designs that regress the “average level” of a given symptom against biological data collected at a single time-point, and summarize findings from ambulatory assessment studies suggesting that such designs may be sub-optimal to detect symptom-substrate relationships. While such designs play a crucial role in advancing our understanding of biological substrates related to more stable, longer-term changes (e.g., grey matter thinning during a depressive episode), they may be less optimal for the detection of symptoms that exhibit show high frequency fluctuations, are susceptible to common reporting biases, or may be heavily influenced by the presence of other symptoms. We propose that a greater emphasis on intra-individual symptom chronometry may be useful for identifying subgroups of patients with a common, proximal pathological indicators. Taken together, these three recent developments in the areas of symptom conceptualization and measurement raise important considerations for future studies attempting to identify reliable biomarkers in psychiatry.
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