Center for Clinical Neuroscience, MS Center, Department of Neurology, University Hospital Carl Gustav Carus at the Technische Universität Dresden, Dresden, Germany.
PLoS One. 2013 Apr 16;8(4):e60647. doi: 10.1371/journal.pone.0060647. Print 2013.
Dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis has frequently been reported in multiple sclerosis (MS). So far, HPA axis function in MS has predominantly been studied under pharmacological stimulation which is associated with a series of methodological caveats. Knowledge of circadian cortisol patterns and cortisol awakening response (CAR) is still limited.
A total of 77 MS patients (55 relapsing-remitting MS (RRMS)/22 secondary-progressive MS (SPMS)) as well as 34 healthy control (HC) subjects were enrolled. Diurnal cortisol release was assessed by repeated salivary cortisol sampling. Neurological disability was rated by the Kurtzke's Expanded Disability Status Scale (EDSS). Depressive symptoms and perceived stress were assessed by self-report measures.
RRMS but not SPMS patients differed in circadian cortisol release from HC subjects. Differences in cortisol release were restricted to CAR. Treated and treatment naïve RRMS patients did not differ in CAR. In a RRMS follow-up cohort (nine months follow-up), RRMS patients with EDSS progression (≥0.5) expressed a significantly greater CAR compared to HC subjects. RRMS patients with a stable EDSS did not differ from HC subjects. Neither depressive symptoms nor perceived stress ratings were associated with CAR in RRMS patients. In a step-wise regression analysis, EDSS at baseline and CAR were predictive of EDSS at follow-up (R(2) = 67%) for RRMS patients.
Circadian cortisol release, in particular CAR, shows a course specific pattern with most pronounced release in RRMS. There is also some evidence for greater CAR in RRMS patients with EDSS progression. As a consequence, CAR might be of predictive value in terms of neurological disability in RRMS patients. The possible role of neuroendocrine-immune interactions in MS pathogenesis is further discussed.
下丘脑-垂体-肾上腺（HPA）轴失调在多发性硬化症（MS）中经常被报道。到目前为止，MS 中的 HPA 轴功能主要是在药理学刺激下进行研究的，这与一系列方法上的局限性有关。关于皮质醇昼夜节律模式和皮质醇觉醒反应（CAR）的知识仍然有限。
共纳入 77 名 MS 患者（55 名复发缓解型 MS（RRMS）/22 名继发进展型 MS（SPMS））和 34 名健康对照（HC）受试者。通过多次唾液皮质醇采样评估日间皮质醇释放。神经功能缺损由 Kurtzke 的扩展残疾状况量表（EDSS）评定。抑郁症状和感知压力通过自我报告量表评估。
RRMS 患者而非 SPMS 患者的昼夜皮质醇释放与 HC 受试者不同。皮质醇释放的差异仅限于 CAR。接受治疗和未接受治疗的 RRMS 患者的 CAR 无差异。在 RRMS 随访队列（九个月随访）中，EDSS 进展（≥0.5）的 RRMS 患者的 CAR 明显高于 HC 受试者。EDSS 稳定的 RRMS 患者与 HC 受试者无差异。RRMS 患者的抑郁症状和感知压力评分与 CAR 无关。在逐步回归分析中，RRMS 患者的基线 EDSS 和 CAR 可预测随访时的 EDSS（RRMS 患者的 R²=67%）。
昼夜皮质醇释放，特别是 CAR，在 RRMS 中表现出特定的病程模式，RRMS 患者的释放最为明显。EDSS 进展的 RRMS 患者的 CAR 也有增加的迹象。因此，CAR 可能对 RRMS 患者的神经功能缺损具有预测价值。进一步讨论了神经内分泌-免疫相互作用在 MS 发病机制中的可能作用。
