The Modifying Role of Cortisol in the Sex-Specific Associations of Social Jetlag with Neurobehavioral Problems Among Adolescents: The Shanghai Adolescent Cohort Study.

PURPOSE: Social-jetlag is linked to adverse mental health outcomes, though longitudinal evidence in adolescents remains insufficient. The neuroendocrine mechanism underlying this association, particularly the modifying role of cortisol and sex difference, remains uncharacterized.

PATIENTS AND

METHODS

Data were collected from the Shanghai Adolescent Cohort Study (2017-2021), involving 609 students investigated from grade 6 to 9. Levels of neurobehavioral symptoms were evaluated using the Youth Self-Report (YSR). Social-jetlag was assessed using structured questionnaire. Cortisol levels in fingernail samples were measured using liquid-chromatography-tandem-mass-spectrometry (LC-MS/MS). Two distinct social-jetlag trajectories (the consistently low-level and relatively high-level social-jetlag trajectories across 4 years) were identified by the Latent-class-mixture-modeling (LCMM). Negative binomial generalized linear models were employed to analyze the longitudinal associations between social-jetlag trajectories with adolescent neurobehavioral problems under low and high cortisol levels.

RESULTS

Among the 418 middle-school students with complete 4-year follow-up data, 38.52% experienced high-level social-jetlag (at least 1 hour) trajectory. After adjusting for related confounders, female students with high-level social-jetlag trajectory were significantly associated with increased neurobehavioral problems (vs. low-level trajectory, for the domains of social problems, attention problems, aggressive problems, externalizing problems and total problems, IRR: 1.482-1.547, P-values<0.05; P sex-interaction-values<0.2), especially among girls with high baseline cortisol levels (vs. girls with low-level baseline cortisol, for the domains of internalizing problems, externalizing problems, total problems, attention problems, somatic complaints, aggressive behavior and social problems: IRR: 4.418-15.997, P-values<0.05, P high/low-cortisol-interaction-values<0.2). Nevertheless, no significant associations between social-jetlag trajectories and neurobehavioral symptoms were detected in male adolescents regardless of baseline cortisol levels, as well as in female adolescents with low baseline cortisol levels (P-values>0.05).

CONCLUSION

The association between persistently high social-jetlag levels and neurobehavioral problems was most pronounced among adolescent girls with relatively high baseline cortisol, a pattern that, if replicated, could guide targeted prevention.