The acute phase inflammatory response as a key determinant of reduced lipid-associated antioxidant defenses in Chinese patients with major depressive disorder

Abstract Background Major depressive disorder (MDD) is characterized by interacting neuro-immune, metabolic, and oxidative stress pathways. Here we examine the interactions between the acute phase (AP) response and serum lipids in Chinese MDD patients. Methods This case-control study assessed serum lipids and the AP response in 125 MDD patients and 40 healthy controls (HC), while controlling for metabolic confounders, including metabolic syndrome. Results We found an impaired lipid profile in MDD, characterized by reduced levels of high-density lipoprotein cholesterol (HDL), apolipoprotein (Apo) A1, chloromethyl phenylacetate (CMPA)ase activity, a reverse cholesterol transport (RCT) index, and increased ApoB/ApoA1 index. MDD was characterized by an AP response as conceptualized by lower serum albumin and transferrin and increased monomeric C-reactive protein (mCRP). The AP response was significantly and inversely associated with total cholesterol, HDL, low-density lipoprotein cholesterol, ApoA1, ApoB, lecithin cholesterol acyltransferase, CMPAase activity, and RCT index. After adjusting for the AP response, MDD diagnosis maintained significant independent associations with lower HDL-C, ApoA1, RCT, and higher ApoB/ApoA1 ratio. Multivariate (logistic) regression analyses confirmed that these lipid-inflammatory alterations strongly predict MDD diagnosis and clinical symptom severity. We found that around 81.5% of the MDD patients showed metabolic-inflammatory aberrations with a specificity of 82.1% and an area under the receiver operating characteristic (ROC) curve of 0.873. Lower ApoA1 emerged as a particularly robust protective biomarker, showing significant inverse relationships with affective and chronic fatigue severity scores. Conclusions These findings illuminate the complex interplay between a smoldering inflammatory response and lipid metabolism in many patients with MDD.