Association between serum bilirubin levels and depressive symptoms among university students in Aden, Yemen: a cross-sectional study

Abstract Background Depressive symptoms are common among university students and have been linked to increased oxidative stress and impaired antioxidant defense. Bilirubin, an endogenous antioxidant, has recently emerged as a potential biomarker in psychiatric research; however, evidence regarding its association with depressive symptoms in university student populations remains limited and inconsistent. This study investigated the association between serum total and direct bilirubin levels and depressive symptoms among university students. Methods A cross-sectional study was conducted among 422 university students aged 18–42 years who were recruited from public and private universities in Aden, Yemen. Sociodemographic and lifestyle characteristics were collected using a structured questionnaire. Depressive symptoms were assessed using the Patient Health Questionnaire-9 (PHQ-9). Fasting venous blood samples were collected to measure serum total and direct bilirubin concentrations using the cobas c 311 clinical chemistry analyzer (Roche Diagnostics, Mannheim, Germany). Data were analyzed using descriptive statistics, correlation analyses, one-way analysis of variance (ANOVA), and multiple linear regression analyses. Results Depressive symptoms (PHQ-9 ≥ 5) were identified in 88.2% of participants, with mild symptoms being the most frequent category (32.0%), followed by severe (23.9%), moderate (22.0%), and moderately severe symptoms (10.2%). In addition, 56.2% of participants had clinically significant depressive symptoms (PHQ-9 ≥ 10). The mean serum total and direct bilirubin concentrations were 0.510 ± 0.247 mg/dL and 0.115 ± 0.056 mg/dL, respectively. PHQ-9 scores showed significant inverse correlations with total bilirubin ( r = − 0.595, p < 0.001) and direct bilirubin ( r = − 0.452, p < 0.001). After adjustment for age, sex, marital status, field of study, monthly income, and academic stress, both total bilirubin (β = −0.568, p < 0.001) and direct bilirubin (β = −0.431, p < 0.001) remained significantly associated with PHQ-9 scores. The model including total bilirubin explained a greater proportion of the variability in depressive symptom scores than the model including direct bilirubin (adjusted R² = 0.417 vs. 0.287). Conclusions Lower serum bilirubin levels were significantly associated with greater depressive symptom severity among university students, with total bilirubin showing a stronger association than direct bilirubin. These findings support an association between serum bilirubin levels and depressive symptoms rather than a causal relationship. Prospective longitudinal studies are warranted to determine the temporal direction and clinical significance of this association.