Social jetlag (SJL), defined as a mismatch in midsleep timing between school or workdays and free days, has been associated with adverse mental health, cognitive, and brain outcomes in adults. However, its effects in youth remain insufficiently studied. We investigated the effects of SJL on these factors and on tryptophan metabolites implicated in sleep, fatigue, and social function. Based on SJL assessed using the Munich ChronoType Questionnaire, 89 healthy youths aged 6-17 years were classified into high-SJL (≥ 1 h; n = 25) or low-SJL (< 1 h; n = 64) groups. Fatigue, chronotype, Trail Making Test (TMT) performance, urinary tryptophan and 5-hydroxyindoleacetic acid (5-HIAA) levels, gray matter volume (GMV), and resting-state functional connectivity (FC) were evaluated. Compared with the low-SJL group, the high-SJL group exhibited greater fatigue (p-FDR = 0.034), a later chronotype (p-FDR = 0.00003), and higher urinary tryptophan levels (p-FDR = 0.014). Moreover, the high-SJL group showed smaller GMV in the left inferior occipital/fusiform region (p-FWE = 0.002), right inferior temporal region (p-FWE = 0.006), right angular gyrus (p-FWE = 0.012), left temporal pole (p-FWE = 0.013), and left superior parietal lobule (p-FWE = 0.024). However, TMT performance, urinary 5-HIAA levels, and FC did not differ between groups. An SJL of ≥ 1 h was associated with elevated tryptophan levels and structural vulnerability in temporal pole, ventral occipitotemporal regions, and parietal regions. These findings suggest that higher SJL may contribute to molecular and region-specific structural disadvantages relevant to socioemotional and higher-order cognitive processes in youth.
