The relationship between biological rhythm disturbances and mixed features in major depressive episodes: a multicenter cross-sectional study

Major depressive episodes (MDEs) with mixed features are associated with greater clinical complexity and may represent an important indicator of bipolarity. Biological rhythm disturbances have been implicated in mood disorders, but their relationship with mixed features during MDE remains insufficiently understood. This study aimed to investigate the association between biological rhythm disturbances and mixed features in patients experiencing MDE. A multicenter cross-sectional study was conducted across four hospitals in China, including 294 patients with mood disorders experiencing MDE. Biological rhythm disturbances were assessed using the Chinese version of the Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN-C), while mixed features, depressive symptoms, manic symptoms, and anxiety were assessed using validated instruments. Multivariable logistic regression was performed to identify factors independently associated with mixed features, with adjustment for age, sex, diagnosis, and antidepressant use. Overall, 61.9% of participants exhibited mixed features. Compared with patients without mixed features, those with mixed features had significantly higher BRIAN total scores and higher sleep, social, and eating rhythm scores, whereas no significant difference was observed in activity rhythm scores. In multivariable logistic regression, eating rhythm disturbances were independently associated with mixed features (OR = 1.14, 95% CI: 1.04–1.25, P = 0.006). Higher Altman Self-Rating Mania Scale (ASRM) scores, excessive screen time, and suicidal ideation were also independently associated with mixed features. The model demonstrated good fit (Hosmer–Lemeshow P = 0.701) and discrimination (AUC = 0.803, 95% CI: 0.753–0.853). Biological rhythm disturbances, particularly eating rhythm disturbances, were independently associated with mixed features in patients experiencing MDE. These findings support the potential value of assessing biological rhythms, especially eating rhythms, in the clinical evaluation of patients with mixed features. Longitudinal studies incorporating detailed pharmacotherapy data and objective measures of biological rhythms are warranted to clarify the temporal relationships between biological rhythm disturbances and mixed features. Not applicable.