Abstract
ObjectivesDysregulation 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.MethodsA 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.ResultsRRMS 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.ConclusionsCircadian 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.
Highlights
The cortisol awakening response (CAR) is a well described phenomenon which is characterized by a pronounced increase of cortisol within 20 to 30 minutes after awakening [1,2]
Circadian Cortisol Release and Disease Course Groups were sex-matched (Chi2 test: p.0.05) but SPMS patients were significantly older than RRMS patients (ANOVA, post-hoc: p = 0.03) and healthy control (HC) subjects (ANOVA, post-hoc: p = 0.01)
SPMS patients, but not RRMS patients showed a positive association between AUCawakening and Expanded Disability Status Scale (EDSS) ratings
Summary
The cortisol awakening response (CAR) is a well described phenomenon which is characterized by a pronounced increase of cortisol within 20 to 30 minutes after awakening [1,2]. While the precise mechanisms are still not entirely understood, CAR seems to be controlled by limbic regions [3,4]. It is further modulated by various factors such as genetic polymorphisms [5], stressful experience [5,6,7], affective symptoms [6,8] and inflammatory states [9]. Of the underlying modulating mechanisms, an elevated CAR indicates a hyperactive hypothalamuspituitary-adrenal (HPA) axis with an increased diurnal cortisol release. A series of most recent studies indicates a complex interaction between depressive symptoms and diurnal cortisol release patterns in MS [16,17]
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