BACKGROUND: Depression persists as a substantial contributor to global disability burdens. Emerging evidence implicates circadian rhythm variations in mental health outcomes, with evening chronotypes potentially exacerbating depression risk through multifactorial pathways, including circadian misalignment, increased social isolation, and dysregulated stress responses.
METHODS: We conducted a systematic meta-analysis of observational studies (cross-sectional/cohort designs) from PubMed//Cochrane/Web of Science through September 5, 2025. Eligible studies assessed depression outcomes by chronotype. Pooled risk ratios (RRs, 95% CIs) were derived using random-effects models. Heterogeneity was evaluated via Q-statistics and I², with stratification by study design/assessment tools. Publication bias was assessed using funnel plots (Begg's and Egger's tests), and result stability was verified via sensitivity analyses with iterative imputation.
RESULTS: Our analysis synthesized data from 22 rigorously selected studies (20 cross-sectional, 2 cohort). Evening chronotype demonstrated a significant association with elevated depression risk across study designs: cross-sectional RR=1.83 (1.40∼2.38); cohort RR=1.79 (0.59∼5.46). Morning preference exhibited protective effects, particularly in longitudinal analyses: cohort RR=0.88 (0.81∼0.96) versus cross-sectional RR=0.80 (0.59∼1.09). High heterogeneity was observed (I²=91.1∼97.3%), resolved through stratification by study design and assessment tools. Sensitivity analyses confirmed result stability, with no evidence of publication bias.
CONCLUSION: This meta-analysis substantiates the chronotype-depression relationship through robust epidemiological evidence. Evening-type individuals face substantially heightened depression risk (83% increase in cross-sectional data), while morning orientation demonstrates consistent protective associations, particularly in longitudinal studies. These findings emphasize chronotype assessment as a potential biomarker for depression risk stratification. Mechanistic investigations into circadian disruption pathways and targeted chronotherapeutic interventions are urgently warranted.
Circadian Biology