Brain, behavior, and immunity · 2026
The acute phase inflammatory response as a key determinant of reduced lipid-associated antioxidant defenses in Chinese patients with major depressive disorder.
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Chen Tangcong, Niu Mengqi, Luo Yueyang, Li Jing, Almulla Abbas F, Zhang Yingqian, Maes Michael
Аннотация
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.
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.