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Introduction Sleep disruption has profound effects on immune function. Many adolescents do not get adequate amounts of sleep each night, and chronic sleep disturbance has been associated with increased risk of several inflammatory diseases. However, the relationship between sleep disturbances and inflammation during adolescence is not well understood. In this study, we examined the relationship between specific features of sleep disruption and cytokine levels in adolescents. Methods A total of 88 adolescents (18.36 ± 0.51 years, 56.8% female) completed the Pittsburgh Sleep Quality Index (PSQI), a self-reported questionnaire used to assess subjective sleep quality over a 1-month time period. Blood plasma samples were obtained for each participant at the same timepoint to measure levels of pro-inflammatory cytokines (Interleukin (IL)-6, IL-8, tumor-necrosis factor (TNF)-alpha, and interferon (IFN)-gamma), anti-inflammatory cytokine (IL-10), and C-reactive protein (CRP). Samples were assayed using a Meso Scale Discovery multiplex immunoassay. Linear regression models were used to test the effect of PSQI sleep latency, duration, efficiency, quality, disturbance, and total score on each cytokine level, while covarying for sex and body mass index. We corrected for multiple comparisons using a False Discovery Rate (FDR) correction. Results Overall, disruption in sleep was associated with distinct cytokine differences. Worse sleep, reflected by the PSQI total score and greater sleep disturbance, was associated with lower IL-6 levels (p=0.013, p=0.015, respectively), however theses associations were attenuated to a trend after FDR correction (q=0.083, q=0.092, respectively). Longer sleep latency was also associated with lower IL-6 (p=0.028), and IFN (p=0.016) levels, however these effects were also attenuated after FDR correction (q=0.138, q=0.094, respectively). Reduced sleep efficiency was associated with higher TNF (q=0.046) and CRP (q=0.021) levels. Conclusion Our findings show that different components of sleep disruption have varying effects on cytokine release, resulting in an overall blunted immune response. This underscores the significant impact of sleep disturbances on perturbing immune function during this critical developmental period. Support (If Any)

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 (q0.18). 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