Circadian cortisol and fatigue severity in relapsing-remitting multiple sclerosis

Cortisol is a key regulator of the immune system, energy metabolism, and stress, yet its relevance to fatigue experienced by people with relapsing-remitting multiple sclerosis (RRMS) remains uncertain. We examined cortisol secretory activity in RRMS and its association with fatigue severity between-individuals and within-individuals (day-to-day) using a case-control ecological momentary assessment design. Whilst undergoing usual daily routines, 38 people with RRMS and 38 healthy control participants provided saliva samples at strategic time-points over 4 consecutive weekdays to measure the cortisol awakening response (CAR; 0, 30 ,and 45 min after awakening) and the diurnal cortisol slope (DCS; 6 quasi-random samples provided between 1000h and 2000h). Recalled fatigue was measured at baseline, and daily fatigue was measured as the mean average of momentary fatigue ratings provided alongside each DCS sample. Multilevel modelling found CAR output was greater in RRMS than controls, and recalled fatigue in RRMS was associated with both lower waking cortisol level and larger awakening response. Day-to-day, the CAR was not associated with same-day fatigue levels in RRMS. Cortisol appears to have a role in fatigue experienced in RRMS, but whether it is a causal factor remains unclear.