Abstract
Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a debilitating illness that is over represented among women and characterized by extreme fatigue and myriad distressing somatic complaints, with no known etiology or putative biomarker, though recent research has shown evidence of immunological abnormalities in CFS/ME. One of the major symptoms of CFS/ME is experiencing unrefreshing sleep or poor subjective sleep quality, which as a construct, can encompass sleep duration, sleep efficiency, sleep latency, and sleep disturbances, among other aspects of sleep quality. The subjective account of poor sleep quality has been consistently shown in CFS/ME, though objective evidence of sleep-related abnormalities by polysomnography or multiple sleep latency tests are inconsistent. Despite evidence of increased fatigue, somatic symptoms, pro-inflammatory cytokines and poor subjective sleep quality in CFS/ME, the association among these variables has not yet been studied extensively in women with CFS/ME, even though the relationship between poor subjective and objective sleep quality and inflammation, fatigue, and symptom severity has been established in other healthy and chronically ill populations. Additionally, CFS/ME patients report increased prevalence of mood disorders such as depression. Depression has been linked to both inflammation and poor sleep quality in other contexts, but not yet in CFS/ME. Due to depression’s known relationship to increased inflammation and poor sleep quality, I hypothesized that the relationship between poor sleep quality and inflammation would be more salient for more depressed CFS/ME women. This study sought to examine the main effects of poor sleep quality on pro and anti-inflammatory cytokines, fatigue severity and interference, symptom severity and frequency in CFS/ME women and also measure the moderating effect of depression on the relationship between poor sleep quality and pro and anti-inflammatory cytokines. In total, 95 women with CFS/ME provided blood samples, as well as self-reported measures of poor sleep quality, depressive symptomatology, CFS/ME somatic symptoms and fatigue. On average patients scored in the clinically elevated range for poor sleep quality on the Pittsburgh Sleep Quality Index (PSQI) global score. Multiple regression analyses showed that worse sleep quality overall (PSQI global score) related to more severe and more frequent CFS (non-sleep) symptoms, more fatigue severity and interference in daily life, and greater levels of inflammation (interleukin-2 [IL-2], IL-6, and tumor necrosis factor-alpha [TNF-α]), when controlling for age and educational level. When the analyses were repeated using sleep quality subscale scores, the poor sleep quality subscale score was positively related to increased pro-inflammatory (IL-2, IL-6, and TNF-α) and anti-inflammatory (IL-10) cytokine levels. Longer sleep latency was positively related to increased pro-inflammatory and sleep regulating cytokines (IL-1β and TNF-α). The sleep disturbance subscale score was positively related to increased pro-inflammatory IL-6, which is known to disrupt sleep at increased concentrations. Shorter sleep duration was positively related to TNF-α. Poor sleep efficiency was not related to any pro or anti-inflammatory cytokine studied. When examining the moderating effect of depression, poor global sleep quality’s relationship to IL-4 and IL-6 was positively moderated by depressive symptom severity such that poorer sleep related to greater IL-4 and IL-6 to a significantly greater degree in women reporting more depressive symptoms. Additionally, sleep duration relationship to IL-4 was also positively moderated by depression symptom status such that the association between shorter sleep duration and IL-4 was significantly greater for more depressed women. Importantly, depression, fatigue severity and interference, and CFS symptom severity and frequency were not related to any cytokine. In conclusion, poorer sleep quality is associated with greater fatigue, CFS symptoms, and inflammation is significant in CFS/ME women, and may be more pronounced in CFS/ME women who are more depressed. These preliminary and novel findings deserve further research using longitudinal study designs to establish the temporality of these associations, and may shed light on the biopsychosocial mechanisms underlying this chronic condition. This work also suggests that subgroups within this heterogeneous population (e.g., depressed women) may respond in distinctive ways to sleep disruptions, which could inform intervention strategies.