Depressive Symptoms Predict Longitudinal Changes of Chronic Inflammation at the Transition to Adulthood: Based on Restricted Cubic Spline Model (Preprint)

BACKGROUND Inflammation closely relate to poor mental and physical health, including depressive symptoms. However, few studies have explored the linear and nonlinear relationship between depressive symptoms and chronic inflammation levels among college students by using a prospective design. OBJECTIVE We aimed to reveal the relationships and the direction of the relationships between depressive symptom severity at baseline and inflammatory cytokine levels at baseline and after 2 years of follow-up among college students. METHODS In this longitudinal study, we examined 248 college students recruited from two universities in south-central China, who were examined at baseline and after 2 years of follow-up based on a questionnaire survey of online follow-up monitoring. Depressive symptoms were measured by applying the Patient Health Questionnaire 9 (PHQ-9) at baseline. Plasma levels of three inflammatory cytokines, including interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) were assayed at baseline and 2-year follow-up. In addition to the conventional generalized linear models, as well as restricted cubic splines were innovatively used to analyze cross-sectional and longitudinal nonlinear relationship between depressive symptoms and inflammatory cytokines. RESULTS The 248 college students consisted of 42.3% males and had a mean (SD) age of 18.69 (0.97) years at baseline. Generalized linear model analysis revealed that there were no statistical associations between depressive symptoms at baseline and any inflammatory cytokine levels at baseline or at 2-year follow-up. The results of restricted cubic spline demonstrated an inverted U-shaped nonlinear cross-sectional statistical link between depressive symptoms and TNF-α at baseline. Furthermore, longitudinal analyses showed that U-shaped nonlinear association between depressive symptoms and ΔIL-1β or ΔTNF-α (changes in baseline and 2-year follow-up). CONCLUSIONS Our findings suggested that nonlinear dose-response relationship between depressive symptoms and TNF-α at baseline, changes in IL-1β and TNF-α levels during a 2-year follow-up among college students. Simultaneously, more research is warranted to seek the directionality of depressive symptoms and chronic inflammation.