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Microglial function interacts with the environment to affect sex-specific depression risk.

Eamon Fitzgerald1, Irina Pokhvisneva2, Sachin Patel2

  • 1Ludmer Centre for Neuroinformatics and Mental Health, McGill University, Canada; Douglas Mental Health University Institute, Department of Psychiatry, McGill University, Canada.

Brain, Behavior, and Immunity
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Summary

Microglial function influences sex-specific depression risk, particularly in females. This study found microglial polygenic scores moderated the link between depression risk factors and depressive symptoms in women.

Keywords:
DepressionGeneticsMicrogliaPsychiatric disordersRisk factorsSex differences

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Area of Science:

  • Neuroscience
  • Genetics
  • Psychiatry

Background:

  • Depression affects females at twice the rate of males.
  • Microglia, immune cells in the brain, are implicated in sex-dependent depression risk.

Purpose of the Study:

  • To investigate the relationship between microglial function and sex-specific depression risk.
  • To determine if microglial genetic predisposition influences depression risk in conjunction with other factors.

Main Methods:

  • Genome-wide association studies (GWAS) enrichment, gene-set enrichment analysis, and Mendelian randomization were used.
  • Polygenic scores (PGS) for microglial function were generated from adult (UK Biobank) and fetal (ALSPAC) data.
  • Interactions between microglial PGS and depression risk factors (BMI, financial insecurity, prenatal depression) were analyzed for sex differences.

Main Results:

  • Minimal evidence for a direct genetic link between microglia and sex-dependent depression risk.
  • Adult microglial PGS moderated the association between BMI and financial insecurity with depressive symptoms in females.
  • Fetal microglial PGS moderated the association between maternal prenatal depression and offspring depression in females.
  • No significant interactions were found in males.

Conclusions:

  • Microglial function plays a role in conferring sex-dependent depression risk.
  • This effect is observed following exposure to depression risk factors in females.
  • The findings highlight potential sex-specific pathways in depression etiology involving microglia.