Washington University in St. Louis
St. Louis, MO
Dr. Smith’s Research
Role of Transcriptomic Circadian Rhythms in Postoperative Delirium
Delirium is a potentially preventable disorder characterized by transient fluctuating disturbances in attention, consciousness, and cognition. It is a common complication in older adults following major surgery under general anesthesia and is associated with poor postoperative trajectories with costs upwards of $32 billion annually. Circadian rhythm disruptions are thought to contribute to adverse perioperative outcomes including postoperative delirium, but little is known about their perioperative trajectories at the molecular level. The objective of this proposal is to characterize transcriptomic circadian rhythm changes across the perioperative continuum and to elucidate their relationship to postoperative delirium. We will utilize an externally validated transcriptomic algorithm to directly measure internal circadian phase across the perioperative continuum. We hypothesize that changes will be observed in internal circadian phase following the acute event of general anesthesia and major cardiac surgery. Furthermore, we anticipate that the degree of these changes will be associated with postoperative delirium severity, as measured by serial Confusion Assessment Method (CAM) assessments. The significance of this work is two-fold: First, it would provide the first transcriptomic characterization of circadian rhythms during the perioperative period for future therapeutics. Second, it would allow for the discovery of biomarkers that may predict clinical trajectories leading to better outcomes in this vulnerable patient population.
Validation of blood-based transcriptomic circadian phenotyping in older adults
S Kendall Smith, Peter Tran, Katherine A Madden, Jill Boyd, Rosemary Braun, Erik S Musiek, and Yo-El S Ju
Circadian rhythms govern interorgan coordination and harmonize internal function with the external environment. Age-related changes in circadian rhythms are associated with a diverse array of diseases including neurological disorders . Moreover, circadian dysfunction occurs prior to symptoms in some conditions such as Alzheimer disease, suggesting a potential target for intervention.