Sleep Disturbances and Inflammatory Biomarkers in Schizophrenia: Focus on Sex Differences

Objectives: Persons with schizophrenia, and women in particular, are at high risk for sleep disturbances and inflammatory activation. The sleep-inflammation link has been reported to be stronger in women within the general population. This study sought to examine the sleep-inflammation link in persons with schizophrenia and its relationship with demographic, clinical and cognitive variables. Design: Cross-sectional case-control study. Participants: Community-dwelling outpatients with schizophrenia (N=144, 46% women) and non-psychiatric comparison (NC) participants (N=134, 52% women), age 26-65 years. Measurements: Reported sleep disturbances (sleep quality and duration), and mental and physical health were assessed. Cognitive assessments included executive functioning (Delis-Kaplan Executive Function System) and global cognitive functioning (Telephone Interview for Cognitive Status modified.) Inflammatory biomarkers included pro-inflammatory cytokines [high sensitivity C-Reactive Protein (hs-CRP), Interleukin (IL)-6, Tumor Necrosis Factor-alpha (TNF-alpha)] and an anti-inflammatory cytokine (IL-10). Results: The schizophrenia group had longer sleep duration, worse sleep quality, and increased levels of hs-CRP, IL-6, and TNF-alpha compared to NCs. Women with schizophrenia were less likely to have good sleep quality and had elevated levels of hs-CRP and IL-6 compared to men with schizophrenia. In the schizophrenia group, worse sleep quality and global cognitive functioning were associated with higher hs-CRP and IL-6 levels. Female sex and younger age were also associated with higher hs-CRP levels. Conclusions: Sleep disturbances and increased inflammation, which were common in schizophrenia, were associated in persons with schizophrenia. Moreover, women with schizophrenia had worse sleep quality and inflammation than men. Further examination of the sleep-inflammation links, their contribution to clinical outcomes, and sex-specific factors is warranted.