Childhood maltreatment, circadian preference, and hs-CRP in first-episode, drug-naïve major depressive disorder: total- and symptom-level associations.

BACKGROUND: Major depressive disorder (MDD) is clinically heterogeneous, and psychosocial, circadian, and inflammatory-metabolic factors may relate differently to depressive symptom profiles. We examined childhood maltreatment, circadian preference, and high-sensitivity C-reactive protein (hs-CRP) in relation to overall and symptom-level depressive severity in first episode drug-naïve patients with MDD. METHODS: This cross-sectional study included 133 first episode drug-naïve patients with MDD after excluding participants with hs-CRP ≥10 mg/L. Depression severity was assessed using the Patient Health Questionnaire-9 (PHQ-9) and Montgomery-Åsberg Depression Rating Scale. Childhood maltreatment and circadian preference were assessed using the Childhood Trauma Questionnaire and Morningness-Eveningness Questionnaire. Multivariable linear and ordinal logistic regression models examined total and symptom-level associations. RESULTS: Childhood maltreatment was associated with both PHQ-9 (β=0.362, p<0.001) and MADRS severity (β=0.288, p=0.001). Greater eveningness was associated with PHQ-9 severity (β=-0.264, p=0.002), whereas its association with MADRS did not reach significance in the primary sample (β=-0.168, p=0.067). hs-CRP was not independently associated with either measure. After adjustment for overall depressive burden, no childhood maltreatment-item association survived FDR correction; eveningness remained associated with sleep problems (OR=0.49, FDR-p=0.031). BMI was the strongest correlate of hs-CRP. CONCLUSIONS: Childhood maltreatment showed consistent associations across self-reported and clinician-rated severity, whereas evidence for eveningness was less consistent across measures. In this sample, with moderate-to-severe depression and a relatively narrow BMI distribution, no independent association between hs-CRP and depressive severity was observed. The eveningness-sleep association should be interpreted cautiously because of partial content overlap.