0148 Toxoplasma Gondii Serointensity and Plasma Kynurenine Metabolites Are Associated with Sleep Dysregulation

Abstract Introduction Suicidal self-directed violence (SSDV) has been previously associated with Toxoplasma gondii (T. gondii) IgG positivity and intensity, blood levels of quinolinic acid (QUIN, positively), picolinic acid (PIC, negatively) and kynurenic acid (KYNA, negatively), and sleep disturbance (insomnia, daytime sleepiness, positively). We examined associations between T. gondii IgG serointensity, excitotoxic and neuroprotective kynurenines and their ratios, and sleep disturbance in U.S. Veterans enrolled in mental health treatment. Methods Veterans from three Veterans Affairs Medical Centers participated in the study (N=407, mean age = 45.6 ± 11.6 years; 74.7% men). Of these, 203 had a history of SSDV, while 204 had no history of self-directed violence (SDV). T. gondii IgG was measured with ELISAs. QUIN and PIC were analyzed with GC-MS, KYNA with UPLC-MS/MS. Sleep disturbance was estimated using Pittsburgh Sleep Quality index (PSQI). Statistics included ANCOVAs and logistic regressions. Results High T. gondii serointensity (classified as high-top quartile) was significantly associated with daytime dysfunction due to sleepiness (p < 0.05) in SSDV positive Veterans. This relationship remained significant after adjusting for socioeconomic factors status. T. gondii seropositivity was significantly associated with QUIN positively and PIC/QUIN, and KYNA/QUIN negatively (p< 0.05). In turn, QUIN was positively associated with daytime dysfunction due to sleepiness (p=0.007) and KYNA/QUIN and PIC/QUIN ratios were negatively associated with sleep disturbance, sleep latency, daytime dysfunction, and PSQI total score (p< 0.05). Conclusion Limitations include the cross-sectional design, low seropositivity, lack of data on sleep apnea and actual recording of sleep, and multiple comparisons. Sleep- wake dysregulation was positively associated with T. gondii serointensity and QUIN, and negatively with neuroprotective kynurenine ratios. These findings warrant replication in larger, longitudinal studies with direct measuring of sleep parameters. Support (if any) Veteran Administration CSR&D Merit Award (grant number 1 I01CX001310–01), PI Postolache, with local PIs Duncan (Atlanta, GA), Brenner (Aurora, CO) and Postolache (Baltimore, MD).