Increased atherogenicity in mood disorders: a systematic review, meta-analysis and meta-regression

Background: Major depressive disorder (MDD) and bipolar disorder (BD) often coexist with metabolic syndrome. Both are linked to increased atherogenicity and a higher risk of cardiovascular diseases. Nevertheless, a comprehensive analysis of key atherogenic biomarkers in MDD/BD is still lacking. Objectives: This meta-analysis evaluates the relationship between atherogenic indices and MDD/BD, while identifying the most effective atherogenic biomarker. Methods: This study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched electronic databases, including PubMed, Google Scholar, and Web of Science, for articles published up to August 1, 2024. Results: We included 85 eligible studies (14 on BD and 71 on MDD), covering 70,856 participants: 18,738 patients and 52,118 healthy controls. MDD/BD patients showed significant increases (p < 0.001) in the Castelli Risk Index 2 (CRI2), Atherogenic Index of Plasma (AIP), and (triglyceride or TG + low-density lipoprotein + very low-density lipoprotein)/(high-density lipoprotein cholesterol or HDL + Apolipoprotein A or ApoA) ratio, but not CRI1 and ApoB/ApoA ratio. Significant lower HDL and lecithin: cholesterol acyltransferase activity, and higher TG levels were observed in MDD/BD patients compared with controls. There were no significant differences between MDD and BD patients. Most included studies lacked the most essential information on the inclusion and exclusion of important confounders. Conclusions: AIP is the most effective atherogenicity index for mood disorders. Regular lipid profiling and metabolic syndrome screening are crucial in MDD/BD. Early intervention with lipid-lowering therapies is recommended to prevent the worsening of atherogenicity and disease progression.