Background This study aimed to provide a comprehensive synthesis of the evidence examining lipid profiles in drug-naïve MDD patients. Materials and methods We searched PubMed, Scopus, and ISI Web of Science up to August 2023 for total cholesterol, HDL-C, LDL-C, and triglyceride levels in drug-naïve MDD patients. Results A total of 17 articles comprising 2174 individuals including drug-naïve MDD subjects and controls were included. Our results showed that concentrations of total cholesterol were lower in drug-naïve MDD patients compared with healthy controls (SMD −0.49, 95% CI −0.881 to −0.105; p = 0.015; I2 = 90.6%). However, comparison of other lipid levels between MDD patients and healthy controls demonstrated no significant difference. The results revealed that the association of total cholesterol levels with MDD is more prominent in male-dominant studies (SMD −1.20, 95% CI −2.23 to −0.18, I2 = 87.9%) than in female-dominant studies (SMD −0.25, 95% CI −0.63–0.13, I2 = 89.0%). In meta-regression, none of the factors including year of publication, Newcastle-Ottawa Scale score, sample size, BMI, and mean age of participants had a significant influence on the association between cholesterol levels and MDD. Conclusions Lower levels of total cholesterol, especially in males, are associated with MDD, so early lipid monitoring and targeted interventions are necessary.
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