Chronic graft-versus-host-disease (cGVHD) is a common complication of hematopoietic stem cell transplantation that involves alloegeneic and autoimmune dysregulation affecting multiple organ systems. We hypothesized that disrupted circadian rest-activity rhythms and inflammation contribute to co-occurring behavioral symptoms in this population. Adults with cGVHD (N = 55) wore a wrist actigraph for 7 days, provided a blood sample, completed self-report measures of depression (IDAS), fatigue (FSI), and cognition (PROMIS), and underwent clinical evaluation. Rest-activity indices (mesor, amplitude, acrophase) were derived from actigraphy. Cytokines and chemokines relevant to cGVHD (IL-6, IL-8, TNFα, MIF, MCP-1, MIP-1 alpha) were measured with multiplex detection. After covarying for disease severity and age, participants with less optimal rest-activity patterns, including less overall activity (mesor) and less distinction between daytime and nighttime activity (amplitude), reported more severe depression (β = −.372, −.296), fatigue (β = -.237, −.314), and cognitive dysfunction (β = .331, .440) and had poorer physician-rated performance status (β = .340, .383); all p < .05. Higher circulating IL-8 and MIP-1 alpha were associated with greater depression (β=.304, .282), IL-8 and MIF were associated with greater fatigue (β = .350, .283), and IL-6, IL-8, and MCP-1 were indicative of poorer performance status (β = −.229 to −.320); all p < .05. Unexpectedly, those with higher IL-6 and TNFα had better cognition (β = .285, .355, p < .05). Findings provide evidence for biobehavioral pathways by which disrupted circadian rhythms and dysregulated immune processes may contribute to depression, fatigue, and disability among individuals with cGVHD.

Sleep-wake disturbance, pain, fatigue, and depression are common and persistent issues among gynecologic cancer patients. There is evidence from other populations that sleep-wake difficulties contribute to a pain, fatigue, and depression symptom cluster. The current longitudinal study examined how sleep-wake disturbance contributed to pain, fatigue, and depression in endometrial cancer patients over a 4-month post-surgical recovery period. Sixty patients completed actigraphic assessment and self-report measures of insomnia, pain, fatigue, and depression at 1 week/T1, 1 month/T2, and 4 months/T3 post-surgery. Actigraphy was analyzed with a cosinor approach, providing the rest-activity indices of mesor (mean activity level) and amplitude (height of rhythm). Latent growth curve modeling evaluated the influence of insomnia severity and rest-activity indices (both T1 values and change/slope (T1-T3)) on T3 pain, fatigue, and depression. All analyses adjusted for BMI and invasiveness of surgery and T1 pain, fatigue, or depressive symptoms. Results revealed that more severe T1 insomnia predicted greater T3 pain intensity (b=.22;p=.002), pain interference (b=.27;p=.001), fatigue intensity (b=.65;p<.001), fatigue interference (b=.25;p<.001), and depressive symptoms (b=.99;p=.001). Results also indicated that less improvement in mesor and amplitude across recovery predicted greater T3 pain intensity (b=-.05;p=.019 and b=-1.42;p<.001, respectively). Less increase in mesor across recovery also predicted greater T3 fatigue interference (b=-.06;p=.001). Endometrial cancer patients with more severe post-surgery insomnia experience greater pain, fatigue, and depressive symptoms 4 months later compared to women reporting less insomnia symptoms. Furthermore, patients with less robust improvement in objective mean activity level and differentiation in the rest-activity pattern experience greater pain and fatigue 4 months post-surgery. Results indicate that insomnia severity and lack of improvement in objective rest-activity patterns during surgical recovery are risk factors for poorer quality of life and suggest a potential intervention target for improving recovery in this understudied cancer population. This research was supported by grants from NCI (K07 CA136966 and P30CA014520 (UW Carbone Cancer Center)). The UW Center for Sleep Medicine and Research also provided actigraphic devices for this research.