Systemic inflammation and mental health: A J-shaped dose-response pattern in depression based on NHANES 2005 to 2018

Inflammation is increasingly being recognized as a central factor in the development of depression, a common and debilitating condition. However, the relationship between depression and systemic inflammation indices - systemic immune-inflammation index (SII), pan-immune-inflammatory value (PIV), and systemic inflammatory response index (SIRI) - is not fully understood. In this cross-sectional study, data from the National Health and Nutrition Examination Survey 2005 to 2018, including 22,936 adults in the United States, were analyzed using multivariate logistic regression, smoothed curve fitting, and threshold and subgroup analyses to examine the associations between SII, PIV, SIRI, and depression, as well as their potential nonlinear characteristics. The analysis revealed that a 1-unit increase in Ln(SII), Ln(PIV), and Ln(SIRI) was associated with 18.2%, 14%, and 9.5% higher odds of prevalent depression, respectively. Nonlinear "J-shaped" relationships were observed for all the 3 indices. The threshold effect analysis identified significantly higher odds for Ln(SII) > 6.187, Ln(PIV) > 5.581, and Ln(SIRI) > 0.95. The subgroup analysis showed that smoking, diabetes, and liver disease significantly modified these associations. SII, PIV, and SIRI are closely linked to depressive symptoms, suggesting that they could serve as accessible inflammatory correlates of depression. Longitudinal research is required to test their prognostic utility and unravel their underlying biology.