Circadian cortisol, depressive symptoms and neurological impairment in early multiple sclerosis

There is evidence for the existence of a hyperactive hypothalamus-pituitary-adrenal (HPA) axis and its potential role in disease progression in multiple sclerosis (MS). Depressive symptoms are also common in MS. At the same time, depressive symptoms are often associated with an elevated circadian cortisol secretion. So far, little is known about the interplay between depressive symptoms and circadian HPA axis abnormalities in MS.

Here we investigated depressive symptoms, circadian HPA axis function, cortisol awakening response (CAR) and neurological impairment in 32 early stage relapsing-remitting MS (RRMS) patients and 16 age- and sex-matched controls. Saliva cortisol samples were collected in patients' home environment. Depressive symptoms were assessed by self-report measures. Neurological impairment was assessed by the Kurtzke Expanded Disability Status Scale (EDSS).

RRMS patients expressed a significantly higher CAR when compared to healthy controls. After patients were divided into two groups based on their depressive symptom load (Beck Depression Inventory (BDI); median-split), only RRMS patients with moderately elevated depression scores (BDI high) statistically differed in their cortisol release when compared to healthy controls. RRMS patients with low depression scores (BDI low) expressed similar circadian patterns as healthy controls. Neurological impairment (EDSS) was more pronounced in the BDI high group than in the BDI low group.

In summary, there is evidence, that a hyperactive HPA axis is primarily present in MS patients expressing moderately elevated depressive symptoms. MS patients with only few depressive symptoms do not significantly differ in CAR when compared to healthy controls. To the best of our knowledge, this is the first study showing that in early stage MS, a hyperactive HPA axis is primarily present in patients who express moderate depressive symptoms.