Eur Arch Psychiatry Clin Neurosci. 2026 May 11. doi: 10.1007/s00406-026-02258-2. Online ahead of print.
ABSTRACT
OBJECTIVE: Although depression and biological aging share dyslipidemia as a common pathological feature, the extent to which dyslipidemia is involved in their association remains unclear. This study aimed to explore the association between depressive symptoms and accelerated biological aging, with a particular focus on whether dyslipidemia, as measured by the lipid accumulation product (LAP), statistically mediates this association.
METHODS: A total of 4,150 American adults aged ≥ 20 years from the National Health and Nutrition Examination Survey (NHANES) database were included. Depressive symptoms were assessed using the Patient Health Questionnaire-9 (PHQ-9), and accelerated aging was measured via phenotypic age acceleration (PhenoAgeAccel). Weighted multivariable linear regression, restricted cubic spline (RCS) analyses, subgroup analyses, and interaction tests were conducted to examine the associations between depressive symptoms and PhenoAgeAccel. Mediation analysis was subsequently conducted to assess the statistical mediating role of LAP in this association.
RESULTS: Among the 4,150 participants, 375 (9.0%) had probable depression (PHQ-9 score ≥ 10). In the fully adjusted model, both depression status and continuous PHQ-9 score were positively associated with PhenoAgeAccel (depression: β = 0.76, 95% CI: 0.03-1.49; PHQ-9: β = 0.06, 95% CI: 0.01-0.11) and with LAP (depression: β = 4.01, 95% CI: 0.25-7.76; PHQ-9: β = 0.34, 95% CI: 0.09-0.60). Mediation analysis revealed that LAP accounted for 12.05% (95% CI: 2.52%-24.95%, P = 0.01) of the association between depression and PhenoAgeAccel in the fully adjusted model. Subgroup analyses indicated that the associations were stronger among individuals with higher income (poverty income ratio [PIR] > 3.5), those with diabetes, and those without cardiovascular disease (CVD) or chronic obstructive pulmonary disease (COPD) (all P < 0.05). Interaction analyses further indicate significant interactions of PIR and diabetes status with the association between depression and PhenoAgeAccel (both P for interaction < 0.05).
CONCLUSIONS: Depressive symptoms were significantly associated with accelerated biological aging, and this association was partially statistically mediated by LAP. Further prospective studies with longitudinal designs are warranted to establish temporal precedence and investigate the potential biological pathways linking depression, LAP, and accelerated biological aging.
PMID:42113055 | DOI:10.1007/s00406-026-02258-2