Data from: Cortisol awakening response is linked to disease course and progression in multiple sclerosis

OBJECTIVES: 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. METHODS: 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. RESULTS: 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 (R² = 67 %) for RRMS patients. CONCLUSIONS: 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.研究目的：多发性硬化（multiple sclerosis, MS）患者下丘脑-垂体-肾上腺（hypothalamus-pituitary-adrenal, HPA）轴功能失调已有诸多报道。截至目前，针对MS患者HPA轴功能的研究多采用药物刺激范式，该方法存在一系列方法学局限性。目前学界对MS患者的皮质醇昼夜节律及皮质醇觉醒反应（cortisol awakening response, CAR）的认知仍较为有限。 研究方法：本研究共纳入77例MS患者（其中复发缓解型多发性硬化（relapsing-remitting MS, RRMS）55例、继发进展型多发性硬化（secondary-progressive MS, SPMS）22例）及34例健康对照（healthy control, HC）受试者。采用重复唾液皮质醇采样检测受试者的昼夜皮质醇分泌水平。采用库尔特泽克扩展残疾状态量表（Kurtzke’s Expanded Disability Status Scale, EDSS）评估神经功能残疾程度。采用自评量表评估抑郁症状与感知压力水平。 研究结果：复发缓解型多发性硬化患者而非继发进展型多发性硬化患者的昼夜皮质醇分泌模式与健康对照者存在显著差异，且该差异仅局限于皮质醇觉醒反应层面。接受治疗与未接受治疗的RRMS患者的皮质醇觉醒反应并无显著差异。在一项为期9个月的RRMS随访队列中，基线EDSS评分进展≥0.5分的患者，其皮质醇觉醒反应显著高于HC受试者；而EDSS评分稳定的RRMS患者与HC受试者无显著差异。RRMS患者的皮质醇觉醒反应与抑郁症状及感知压力水平均无相关性。逐步回归分析显示，对于RRMS患者，基线EDSS评分与CAR可预测随访期的EDSS评分（R²=67%）。 研究结论：昼夜皮质醇分泌模式，尤其是CAR，在MS中呈现疾病亚型特异性特征，其中RRMS患者的皮质醇分泌最为显著。同时有证据表明，出现EDSS评分进展的RRMS患者，其CAR水平更高。据此推测，CAR或可用于预测RRMS患者的神经功能残疾进展。本研究还进一步探讨了神经内分泌-免疫交互作用在MS发病机制中的潜在作用。