Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA.
Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA.
J Affect Disord. 2018 Oct 1;238:1-7. doi: 10.1016/j.jad.2018.05.005. Epub 2018 May 26.
Substantial research progress can be achieved if available clinical datasets can be mapped to the National Institute of Mental Health Research-Domain-Criteria (RDoC) constructs. This mapping would allow investigators to both explore more narrowly defined clinical phenotypes and the relationship of these phenotypes to biological markers and clinical outcomes approximating RDoC criteria.
Using expert review and consensus, we defined four major depression phenotypes based on specific RDoC constructs. Having matched these constructs to individual items from the Hamilton Depression Rating Scale and Quick Inventory of Depressive Symptomatology, we identified subjects meeting criteria for each of these phenotypes from two large clinical trials of patients treated for major depression. In a post hoc analysis, we evaluated the overall treatment response based on the phenotypes: Core Depression (CD), Anxiety (ANX), and Neurovegetative Symptoms of Melancholia (NVSM) and Atypical Depression (NVSAD).
The phenotypes were prevalent (range 10.5-52.4%, 50% reduction range 51.9-82.9%) and tracked with overall treatment response. Although the CD phenotype was associated with lower rates of remission in both cohorts, this was mainly driven by baseline symptom severity. However, when controlling for baseline severity, patients with the ANX phenotype had a significantly lower rate of remission.
The lack of replication between the studies of the phenotypes' treatment prediction value reflects important variability across studies that may limit generalizability.
Further work evaluating biological markers associated with these phenotypes is needed for further RDoC concept development.
如果能够将现有的临床数据集映射到国家心理健康研究所研究领域标准（RDoC）的结构中，就可以取得实质性的研究进展。这种映射将使研究人员能够探索更狭义的临床表型，以及这些表型与接近 RDoC 标准的生物标志物和临床结果之间的关系。
我们使用专家审查和共识，根据特定的 RDoC 结构定义了四种主要的抑郁症表型。将这些结构与汉密尔顿抑郁评定量表和抑郁症状快速清单中的各个项目相匹配，我们从两项大型抑郁症患者治疗临床试验中确定了符合这些表型标准的受试者。在事后分析中，我们根据表型评估了整体治疗反应：核心抑郁（CD）、焦虑（ANX）、忧郁的神经植物性症状（NVSM）和非典型抑郁（NVSAD）。
这些表型较为普遍（范围为 10.5-52.4%，50%缓解范围为 51.9-82.9%），并与整体治疗反应相关。虽然 CD 表型与两个队列的缓解率较低相关，但这主要是由基线症状严重程度驱动的。然而，当控制基线严重程度时，具有 ANX 表型的患者缓解率明显较低。
这些表型治疗预测价值的研究之间缺乏复制反映了研究之间的重要变异性，这可能限制了其普遍性。
需要进一步评估与这些表型相关的生物标志物，以进一步发展 RDoC 概念。
