0619 The Relationship Between Sleep Disturbance and Inflammatory Markers in Individuals with 22q11.2 Copy Number Variations

Abstract

Abstract Introduction The 22q11.2 locus contains genes critical for brain development. Individuals with copy number variations (i.e. a deletion or duplication; CNV) at this locus have greatly increased risk of developmental neuropsychiatric disorders, as well as immune dysfunction and sleep problems. However, it remains unknown if sleep disturbance and immune dysfunction are related to each other in this population, as they are in typically developing individuals. Methods We examined the relationship between self-reported sleep disturbance and blood cytokine levels in 22q11.2 deletion (22qDel; n= 40, Mage = 17.5±8.4 years, 45% males) and duplication (22qDup; n=28, Mage =16.8±12.9 years, 45% males) carriers. Blood plasma samples were obtained to measure interlukein-6 (IL-6), interlukein-10 (IL-10), interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF) and interferon-gamma (IFN) using a MesoScale Discovery multiplex immunoassay. We also measured levels of C-reactive protein (CRP) using an ELISA. Subjects were classified as either good or poor sleepers based on the sleep disturbance score on the Structured Interview of Psychosis-Risk Symptoms (SIPS). Linear regression models were used to test the effect of sleep disturbance, subject group (22qDel vs. 22qDup), and a group-by-sleep interaction on each cytokine level while controlling age, sex, body mass index, and collection time. We corrected for multiple comparisons using False Discovery Rate (FDR) correction. Results Overall, 22qDup carriers had higher levels of IL-8 (q<0.001) and TNF (q<0.001) relative to 22qDel. Across CNV groups, poor sleepers had higher levels of IL-8 (p=0.046) and IFN (p=0.028), but these effects did not survive FDR correction (q>0.18). There was a group-by-sleep interaction for IL-8 (p=0.013), TNF (p=0.048), and IFN (p=0.034) such that sleep disturbance had a greater effect on cytokine levels in the 22qDel group, but only the interaction for IL-8 survived as a trend towards significance after FDR correction (q=0.076). Conclusion Our findings suggest that poor sleep may contribute to immune dysfunction in 22q11.2 CNV carriers. Further, there may be differential impacts of sleep on immune function, depending on gene dosage at the 22q11.2 locus. Future research in larger samples is required to determine if immune disruption and sleep problems are related to elevated psychiatric symptoms in 22q11.2 CNV carriers. Support (If Any) RO1MH085953; U01MH10171