RT Journal Article SR Electronic T1 Jetlag Expectations, not Circadian Parameters, Predict Jetlag Symptom Severity in Travelers JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.04.23.441149 DO 10.1101/2021.04.23.441149 A1 Maximilian Ullrich A1 Dorothee Fischer A1 Sebastian Deutsch A1 Karin Meissner A1 Eva C Winnebeck YR 2021 UL http://biorxiv.org/content/early/2021/04/26/2021.04.23.441149.abstract AB After a flight across multiple time zones, most people show a transient state of circadian misalignment causing temporary malaise known as jetlag disorder. The severity of the elicited symptoms is postulated to depend mostly on circadian factors such as the number of time zones crossed and the direction of travel. Here, we examined the influence of prior expectation on symptom severity, compared to said “classic” determinants, in order to gauge potential psychosocial effects in jetlag disorder.To this end, we monitored jetlag symptoms in travel-inexperienced individuals (n=90, 18-37y) via detailed questionnaires twice daily for one week before and after flights crossing >3 time zones. We found pronounced differences in individual symptom load that could be grouped into 4 basic symptom trajectories. Both traditional and newly devised metrics of jetlag symptom intensity and duration (accounting for individual symptom trajectories) recapitulated previous results of jetlag prevalence at about 50-60% as well as general symptom dynamics.Surprisingly, however, regression models showed very low predictive power for any of the jetlag outcomes. The classic circadian determinants, including number of time zones crossed and direction of travel, exhibited little to no link with jetlag symptom intensity and duration. Only expectation emerged as a parameter with systematic, albeit small, predictive value.These results suggest expectation as a relevant factor in jetlag experience - hinting at potential placebo effects and new treatment options. Our findings also caution against jetlag recommendations based on circadian principles but insufficient evidence linking circadian re-synchronization dynamics with ensuing symptom intensity and duration.Significance Statement Jetlag disorder afflicts millions of travelers each year - a nuisance on holiday trips but also a danger in safety and performance-critical operations. For effective prevention and treatment, it is critical to understand what influences jetlag severity, i.e. jetlag symptom intensity and duration. In contrast to what guidelines state, in our study, we did not find that symptom severity could be explained by the number of time zones crossed or travel direction. Rather, travelers’ expectations about how long and strongly they will suffer from jetlag symptoms was the only factor systematically predicting jetlag severity. If this holds true not only for subjective but also objective symptoms, we need to revisit assumptions about how circadian desynchronization relates to experienced jetlag symptoms.Competing Interest StatementThe authors have declared no competing interest.