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Assessing the Evidence for Causal Associations Between Body Mass Index, C-Reactive Protein, Depression, and Reported

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Summary
This summary is machine-generated.

Childhood trauma and higher body mass index (BMI) are linked to major depressive disorder (MDD) and inflammation, but not directly to C-reactive protein (CRP). Trauma and MDD show a bidirectional causal relationship.

Keywords:
Body mass indexCausationDepressionGeneticsInflammationMendelian randomizationTrauma

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Area of Science:

  • Psychiatry
  • Genetics
  • Epidemiology

Background:

  • Traumatic experiences are strong predictors of major depressive disorder (MDD).
  • Inflammation may mediate the link between trauma and MDD onset.
  • Body mass index (BMI) significantly confounds associations with inflammation and MDD.

Purpose of the Study:

  • To replicate associations between BMI, childhood trauma, inflammation (C-reactive protein - CRP), and MDD in a large UK Biobank cohort.
  • To investigate potential causal relationships using bidirectional Mendelian randomization.

Main Methods:

  • Phenotypic analyses using regression models in 113,481 individuals for CRP and 30,137 for MDD.
  • Bidirectional Mendelian randomization analyses to assess causality between BMI, MDD, childhood trauma, and CRP.

Main Results:

  • No association was found between CRP and MDD.
  • BMI and childhood trauma significantly affected both CRP and MDD.
  • Mendelian randomization confirmed no causal link between CRP and MDD, but supported BMI's causal effect on CRP and a bidirectional relationship between trauma and MDD.

Conclusions:

  • Controlling for BMI and trauma is crucial when examining MDD in relation to inflammation.
  • Traumatic experiences increase MDD risk, and MDD can, in turn, increase the likelihood of experiencing trauma.