BACKGROUND The temporal dynamics of cortisol may be altered in depression. Optimally studying these dynamics in daily life requires specific analytical methods. We used a continuous-time multilevel process model to study set point (rhythm-corrected mean), variability around this set point, and regulation strength (speed with which cortisol levels regulate back to the set point after any perturbation). We examined the generalizability of the parameters across two data sets with different sampling and assay methods, and the hypothesis that regulation strength, but not set point or variability thereof, would be altered in depressed, compared to non-depressed individuals. METHODS The first data set is a general population sample of female twins (n = 523), of which 21 were depressed, with saliva samples collected 10 times a day for 5 days. The second data set consists of pair-matched clinically depressed and non-depressed individuals (n = 30), who collected saliva samples 3 times a day for 30 days. Set point, regulation strength and variability were examined using a Bayesian multilevel Ornstein-Uhlenbeck (OU) process model. They were first compared between samples, and thereafter assessed within samples in relation to depression. RESULTS Set point and variability of salivary cortisol were twice as high in the female twin sample, compared to the pair-matched sample. The ratio between set point and variability, as well as regulation strength, which are relative measures and therefore less affected by the specific assay method, were similar across samples. The average regulation strength was high; after an increase in cortisol, cortisol levels would decrease by 63 % after 10 min, and by 95 % after 30 min, but depressed individuals of the pair-matched sample displayed an even faster regulation strength. CONCLUSIONS The OU process model recovered similar cortisol dynamics for the relative parameters of the two data sets. The results suggest that regulation strength is increased in depressed individuals. We recommend the presented methodology for future studies and call for replications with more diverse depressed populations.

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抑郁症的皮质醇动力学：连续时间过程模型的应用

背景皮质醇的时间动态可能在抑郁症中发生改变。最佳地研究日常生活中的这些动态需要特定的分析方法。我们使用连续时间多级过程模型来研究设定点（节律校正平均值）、围绕该设定点的可变性和调节强度（皮质醇水平在任何扰​​动后调节回设定点的速度）。我们用不同的采样和测定方法检查了两个数据集的参数的普遍性，以及与非抑郁个体相比，调节强度而不是设定点或其变异性会在抑郁中改变的假设。方法 第一个数据集是女性双胞胎的一般人群样本（n = 523），其中 21 人患有抑郁症，唾液样本每天收集 10 次，持续 5 天。第二个数据集由配对的临床抑郁和非抑郁个体（n = 30）组成，他们每天收集 3 次唾液样本，持续 30 天。使用贝叶斯多级 Ornstein-Uhlenbeck (OU) 过程模型检查设定点、调节强度和可变性。他们首先在样本之间进行比较，然后在样本内评估与抑郁症的关系。结果 与配对样本相比，雌性双胞胎样本中唾液皮质醇的设定点和变异性高两倍。设定点和变异性之间的比率以及调节强度（它们是相对测量值，因此受特定测定方法的影响较小）在样本之间相似。平均调节强度高；皮质醇增加后，皮质醇水平将在 10 分钟后下降 63%，30 分钟后增加 95%，但配对样本中抑郁的个体表现出更快的调节强度。结论 OU 过程模型为两个数据集的相关参数恢复了类似的皮质醇动力学。结果表明，抑郁个体的调节强度增加。我们为未来的研究推荐所提出的方法，并呼吁对更多样化的抑郁人群进行复制。