Evidence for Internal Misalignment of Circadian Rhythms in Youth With Emerging Mood Disorders

J Biol Rhythms. 2025 Jul 15:7487304251349408. doi: 10.1177/07487304251349408. Online ahead of print.

ABSTRACT

Despite evidence for links between circadian dysfunction and mood disorders, previous research has largely reported on single biological markers of circadian alignment. The available evidence on relationships between 2 internal phase markers (e.g., dim light melatonin onset [DLMO] and peak cortisol concentration) suggests these signals may be temporally misaligned in major depressive disorder with greater misalignment associated with more severe depressive symptoms. This study aimed to examine multiple circadian phase markers to determine whether any youth with emerging mood disorders present with clear evidence of internal circadian misalignment, and whether the degree of circadian misalignment is correlated with more severe mood symptoms. Cross-sectional data from 69 youth presenting for mental health care (20.6 ± 3.8 years; 39% male) and 19 healthy controls (24.0 ± 3.6 years; 53% male) included actigraphy monitoring; overnight in-lab measurement of 3 phase markers: DLMO, salivary cortisol peak (CORT), and core body temperature nadir (TEMP); and depressive symptoms (Hamilton Depression Rating Scale). Abnormal phase angles between 2 phase markers were defined as ±2 standard deviations beyond the control mean. In those with emerging mood disorders, earlier TEMP relative to other phase markers (DLMO, CORT, sleep midpoint) was associated with higher depressive symptoms. Sixteen individuals (23%) with emerging mood disorders had abnormal phase angles between at least 1 pair of phase markers, consistent with internal misalignment of the circadian system. The internal misalignment subgroup had later DLMO on average, however presented with a diverse range of individual phase angle abnormalities. Diverse disruptions of circadian alignment occur in youth with mental ill-health. The relative timing of core body temperature and melatonin rhythms may be key circadian features linked to depressive symptoms. Longitudinal research is needed to establish whether correction of circadian misalignment is relevant to treatment of mood syndromes in youth with evidence of disrupted circadian systems.

PMID:40662977 | DOI:10.1177/07487304251349408