Are Anti-Inflammatory Cytokines Associated with Cognitive Impairment in Patients with Insomnia Comorbid with Depression? A Pilot Study

BACKGROUND: To distinguish insomnia comorbid with depression (ICD) from chronic insomnia disorder (CID) by exploring the relationship between serum levels of frequently overlooked anti-inflammatory cytokines and cognitive function. METHODS: A total of 42 ICD patients, 63 CID patients, and 42 healthy control subjects were enrolled in the study. The Pittsburgh Sleep Quality Index and Hamilton Depression Rating Scale were used to assess sleep quality and depression severity, respectively. The Chinese-Beijing version of Montreal Cognitive Assessment scale (MoCA-C) and Nine-Box Maze Test (NBMT) were used to assess cognitive function. Serum levels of anti-inflammatory interleukins (IL-1RA, IL-4, IL-5, IL-10, IL-13, and IL-28A), transforming growth factor (TGF)-β1, granulocyte-macrophage colony-stimulating factor, interferon-γ, and the chemokine regulated upon activation, normal T cell expressed and secreted (RANTES) were measured by enzyme-linked immunosorbent assay. RESULTS: The ICD group had significantly more errors in the spatial reference task (H=2.55, P(s)=0.03) and spatial working memory task (H=5.67, P(s)<0.01) of the NBMT, as well as lower levels of IL-1RA (H=−2.85, P(s)=0.01), IL-4 (H=−3.28, P(s)<0.01), IL-5 (H=−3.35, P(s)<0.01), IL-10 (H=−4.46, P(s)<0.01), and IL-28A (H=−2.75, P(s)=0.02) than control subjects. Compared with the CID group, the ICD group had significantly more errors in the spatial reference memory task (H=−2.84, P(s)=0.01) of the NBMT, and lower levels of IL-5 (H=3.41, P(s)<0.01), IL-10 (H=5.30, P(s)<0.01), IL-13 (H=3.89, P(s)<0.01), and GM-CSF (H=2.72, P(s)=0.02). A partial correlation analysis showed that the level of one or more of IL-4, IL-5, IL-10, IL-13, and TGF-β1 was positively correlated with cognitive function (MoCA-C score and/or performance in spatial memory task) in ICD patients. CONCLUSION: ICD is a distinct condition that can be distinguished from CID based on immune dysfunction and specific types of cognitive dysfunction.