Reverse cholesterol transport and lipid peroxidation biomarkers in major depression and bipolar disorder: A systematic review and meta-analysis

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#humans #bipolar-disorder #lipid-peroxidation #depression #antioxidants

Reverse cholesterol transport and lipid peroxidation biomarkers in major depression and bipolar disorder: A systematic review and meta-analysis

Almulla et al., 2023 | Brain Behav Immun | Meta Analysis

Citation

Almulla Abbas F, Thipakorn Yanin, ... Maes Michael. Reverse cholesterol transport and lipid peroxidation biomarkers in major depression and bipolar disorder: A systematic review and meta-analysis. Brain Behav Immun. 2023-Oct;113:374-388. doi:10.1016/j.bbi.2023.08.007

Abstract

BACKGROUND: Major depression (MDD) and bipolar disorder (BD) are linked to immune activation, increased oxidative stress, and lower antioxidant defenses. OBJECTIVES: To systematically review and meta-analyze all data concerning biomarkers of reverse cholesterol transport (RCT), lipid-associated antioxidants, lipid peroxidation products, and autoimmune responses to oxidatively modified lipid epitopes in MDD and BD. METHODS: Databases including PubMed, Google scholar and SciFinder were searched to identify eligible studies from inception to January 10th, 2023. Guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. RESULTS: The current meta-analysis included 176 studies (60 BD and 116 MDD) and examined 34,051 participants, namely 17,094 with affective disorders and 16,957 healthy controls. Patients with MDD and BD showed a) significantly decreased RCT (mainly lowered high-density lipoprotein cholesterol and paraoxonase 1); b) lowered lipid soluble vitamins (including vitamin A, D, and coenzyme Q10); c) increased lipid peroxidation and aldehyde formation, mainly increased malondialdehyde (MDA), 4-hydroxynonenal, peroxides, and 8-isoprostanes; and d) Immunoglobulin (Ig)G responses to oxidized low-density lipoprotein and IgM responses to MDA. The ratio of all lipid peroxidation biomarkers/all lipid-associated antioxidant defenses was significantly increased in MDD (standardized mean difference or SMD = 0.433; 95% confidence intervals (CI): 0.312; 0.554) and BD (SMD = 0.653; CI: 0.501-0.806). This ratio was significantly greater in BD than MDD (p = 0.027). CONCLUSION: In MDD/BD, lowered RCT, a key antioxidant and anti-inflammatory pathway, may drive increased lipid peroxidation, aldehyde formation, and autoimmune responses to oxidative specific epitopes, which all together cause increased immune-inflammatory responses and neuro-affective toxicity.

Key Findings

The current meta-analysis included 176 studies (60 BD and 116 MDD) and examined 34,051 participants, namely 17,094 with affective disorders and 16,957 healthy controls. Patients with MDD and BD showed a) significantly decreased RCT (mainly lowered high-density lipoprotein cholesterol and paraoxonase 1); b) lowered lipid soluble vitamins (including vitamin A, D, and coenzyme Q10); c) increased lipid peroxidation and aldehyde formation, mainly increased malondialdehyde (MDA), 4-hydroxynonenal, per

Outcomes Measured

  • depression
  • inflammatory markers

Population

Field Value
Population mdd and bd showed
Sample Size 34051
Age Range See abstract
Condition depression

MeSH Terms

  • Humans
  • Bipolar Disorder
  • Lipid Peroxidation
  • Depression
  • Antioxidants
  • Major Depressive Disorder
  • Aldehydes
  • Biomarkers
  • Cholesterol
  • Lipids

Evidence Classification

  • Level: Meta Analysis
  • Publication Types: Meta-Analysis, Systematic Review, Journal Article, Research Support, Non-U.S. Gov't
  • Vertical: vitamin-a

Provenance

Source extracted via PubMed E-utilities API on 2026-04-09