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Related Experiment Video

Updated: Jul 31, 2025

An Unpredictable Chronic Mild Stress Protocol for Instigating Depressive Symptoms, Behavioral Changes and Negative Health Outcomes in Rodents
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Circulating metabolites and depression: a bidirectional Mendelian randomization.

Yankai Dong1,2, Zengxiao Zou1,2, Pin Deng3

  • 1Department of Cardiovascular Surgery, Guangdong Provincial Hospital of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China.

Frontiers in Neuroscience
|May 8, 2023
PubMed
Summary

This study used Mendelian randomization to investigate the causal links between circulating metabolites and depression. Apolipoprotein A-I and glutamine show protective effects, while other metabolites may increase depression risk.

Keywords:
Mendelian randomizationbidirectionalcirculating metabolitesdepressioninstrumental variable

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Area of Science:

  • Metabolomics
  • Psychiatric Genetics
  • Biomarkers

Background:

  • Depression is linked to circulating metabolites, but causal relationships remain unclear.
  • Understanding these links is crucial for identifying depression risk factors and therapeutic targets.

Purpose of the Study:

  • To elucidate the causal relationship between circulating metabolites and depression.
  • To explore the role of specific metabolites in the development of depression.

Main Methods:

  • Utilized two-sample Mendelian randomization (MR) with genome-wide association study data.
  • Analyzed top single-nucleotide polymorphisms (SNPs) for metabolites (n=24,925) and depression (n=322,580).
  • Employed various MR methods including inverse variance weighted and MR Egger.

Main Results:

  • Apolipoprotein A-I and glutamine demonstrated protective causal effects against depression.
  • Acetoacetate, glycoproteins, isoleucine, and urea were identified as potential risk factors for depression.
  • Reverse MR analysis indicated no causal effect of depression on these metabolites.

Conclusions:

  • Apolipoprotein A-I and glutamine may offer protection against depression.
  • Acetoacetate, glycoproteins, isoleucine, glucose, and urea could be associated with increased depression risk.
  • Further research is needed to translate these findings into clinical practice.