Circadian rhythm abnormalities and autonomic dysfunction in patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis

Abstract

Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) patients frequently show autonomic symptoms which may be associated with a hypothalamic dysfunction. This study aimed to explore circadian rhythm patterns in rest and activity and distal skin temperature (DST) and their association with self-reported outcome measures, in CFS/ME patients and healthy controls at two different times of year. Ten women who met both the 1994 CDC/Fukuda definition and 2003 Canadian criteria for CFS/ME were included in the study, along with ten healthy controls matched for age, sex and body mass index. Self-reported measures were used to assess fatigue, sleep quality, anxiety and depression, autonomic function and health-related quality of life. The ActTrust actigraph was used to record activity, DST and light intensity, with data intervals of one minute over seven consecutive days. Sleep variables were obtained through actigraphic analysis and from subjective sleep diary. The circadian variables and the spectral analysis of the rhythms were calculated. Linear regression analysis was used to evaluate the relationship between the rhythmic variables and clinical features. Recordings were taken in the same subjects in winter and summer. Results showed no differences in rhythm stability, sleep latency or number of awakenings between groups as measured with the actigraph. However, daily activity, the relative amplitude and the stability of the activity rhythm were lower in CFS/ME patients than in controls. DST was sensitive to environmental temperature and showed lower nocturnal values in CFS/ME patients than controls only in winter. A spectral analysis showed no differences in phase or amplitude of the 24h rhythm, but the power of the second harmonic (12h), revealed differences between groups (controls showed a post-lunch dip in activity and peak in DST, while CFS/ME patients did not) and correlated with clinical features. These findings suggest that circadian regulation and skin vasodilator responses may play a role in CFS/ME.

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1. Mean ± SEM band of the environmental temperature and light intensity to which the subjects were exposed to in winter and summer.

Black bands indicate the values registered for CFS/ME patients and grey bands the values for HCs.

Fig 2. Mean values (± SEM) of self-reported tendency to sleep (A and B) and mood (C and D) for each group in winter and summer.

Overall analysis indicated that sleepiness was higher in CFS/ME patients than in HCs (p = 0.001), while mood is lower in CFS/ME than in HCs (p = 0.009). HCs presented better mood in summer than in winter (p = 0.043). No overall effects of season or time of day were detected.

Fig 3. 24-hour profiles (mean for each group) of activity and temperature for HC and CFS/ME subjects in winter and summer.

A. Mean daily profiles of activity and skin temperature. Dark lines correspond to CFS/ME patients and grey lines to HCs (to aid visualization, SEM is not shown). Asterisks indicate differences between groups at p<0.05 (see text, segments analysis). B. Synthesis of the mean waveform for activity and skin temperature, according to the first two harmonics of the spectrum (see text, spectral analysis subsection).