Modeling and analysis of circadian rhythm disorder in women and its connections to autism in babies

The circadian clock is a diurnal timer that regulates the biological processes of hormones in approximately 24-hour cycles. Melatonin, a sleep hormone, has a circadian rhythm, and environmental factors, like night shift work, disrupt the melatonin circadian rhythm, which might cause neurodevelopmental disorders. The maternal circadian rhythm is synchronized with the fetus via melatonin during the prenatal period. This thesis investigates how maternal circadian rhythm disorders affect fetal circadian rhythms and explores their potential impact on the risk of autism spectrum disorder (ASD) in the fetus, which constitutes the hypothesis of the thesis. The thesis established links between autism and circadian rhythm using two models: the steady-state model (protein-protein interaction(PPI)) and the dynamic model (using system dynamics methodology). The dynamic model examines the effects of the disruption of the circadian clock caused by night shift work on ASD. The night shift simulation results indicate that the Malondialdehyde level of the fetus increased by 47%, and the melatonin level decreased by 36% during the night shift which increases the risk of autism in the fetus. In the steady-state model, a PPI network was constructed in the research to understand the pathways between autism and the circadian clock and was evaluated using graph-theoretic analysis. In addition, potential hub proteins and pathways such as ribosome biogenesis, oxidative stress, insulin/IGF pathway, Wnt pathway, and mTOR pathway on the development of ASD were examined. Considering these findings, the impacts of circadian disorders should be examined in more detail, and further clinical studies should be conducted on fetal health.