Linking disease symptoms and subtypes with personalized systems-based phenotypes: a proof of concept study.
Linking disease symptoms and subtypes with personalized systems-based phenotypes: a proof of concept study.
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将疾病症状和亚型与个性化的基于系统的表型联系起来：概念研究证明。
DOI：
10.1016/j.bbi.2012.06.002
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发表时间：
2012-10
影响因子：
15.1
通讯作者：
Ben-Zvi, Amos
中科院分区：
文献类型：
--
作者：
Aschbacher, Kirstin;Adam, Emma K.;Crofford, Leslie J.;Kemeny, Margaret E.;Demitrack, Mark A.;Ben-Zvi, Amos
关键词：
使用动态系统模型生成描述 36 名慢性疲劳综合征 (CFS) 和/或纤维肌痛 (FM) 患者和 36 名病例匹配的健康对照样本中下丘脑-垂体-肾上腺 (HPA) 行为表型的参数。神经内分泌功能的改变，特别是与躯体症状和睡眠质量差相关的改变，可能导致这些疾病的病理生理学。 24 小时内每 10 分钟检测一次血浆中的皮质醇和 ACTH。动态模型通过使用三个参数的常微分方程来指定：(1) ACTH 肾上腺信号传导，(2) 抑制反馈，以及 (3) 非 ACTH 影响。该模型是通过根据每个参与者的数据估计一组个性化参数来“个性化”的。白天和夜间参数分别进行评估。两个夜间参数（ACTH-肾上腺信号传导和抑制反馈）将两个患者亚组（仅患有 CFS 的“疲劳为主”患者与患有 FM 和共病慢性疲劳的“疼痛为主”患者）与对照组（allp < .05）显着区分开来，而日间参数和昼夜斜率则没有。相同的夜间参数与患者的躯体症状显着相关（p < .05）。与对照组相比，患者夜间非 ACTH 影响与睡眠质量之间的关联模式存在显着差异 (p < .05)。虽然是推测性的，但当每单位 ACTH 产生更多皮质醇时，患者的躯体症状会减轻，这一发现与皮质醇的抗炎和睡眠调节作用一致。患者的 HPA 系统可以通过促进更快或更持续的皮质醇产生来进行补偿。将压力唤醒系统的“行为表型”映射到症状群上可能有助于理清具有频繁合并症的复杂疾病的病理生理学。
A dynamic systems model was used to generate parameters describing a phenotype of Hypothalamic–Pituitary–Adrenal (HPA) behavior in a sample of 36 patients with chronic fatigue syndrome (CFS) and/ or fibromyalgia (FM) and 36 case-matched healthy controls. Altered neuroendocrine function, particularly in relation to somatic symptoms and poor sleep quality, may contribute to the pathophysiology of these disorders. Blood plasma was assayed for cortisol and ACTH every 10 min for 24 h. The dynamic model was specified with an ordinary differential equation using three parameters: (1) ACTH-adrenal signaling, (2) inhibitory feedback, and (3) non-ACTH influences. The model was ‘‘personalized’’ by estimating an individualized set of parameters from each participant’s data. Day and nighttime parameters were assessed separately. Two nocturnal parameters (ACTH-adrenal signaling and inhibitory feedback) significantly differentiated the two patient subgroups (“fatigue-predominant” patients with CFS only versus ‘‘pain-predominant’’ patients with FM and comorbid chronic fatigue) from controls (allp’s < .05), whereas daytime parameters and diurnal/nocturnal slopes did not. The same nocturnal parameters were significantly associated with somatic symptoms among patients (p’s < .05). There was a significantly different pattern of association between nocturnal non-ACTH influences and sleep quality among patients versus controls (p < .05). Although speculative, the finding that patient somatic symptoms decreased when more cortisol was produced per unit ACTH, is consistent with cortisol’s anti-inflammatory and sleep-modulatory effects. Patients’ HPA systems may compensate by promoting more rapid or sustained cortisol production. Mapping “behavioral phenotypes” of stress–arousal systems onto symptom clusters may help disentangle the pathophysiology of complex disorders with frequent comorbidity.
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