Several observational studies have highlighted the associations between C-reactive protein and interleukin, a cytokine-stimulating substance that induces depressive symptoms. However, whether inflammatory activity caused by C-reactive protein is related to depressive symptoms or not is not clear. This study aims to derive the association between inflammatory activity, metabolic dysregulation, and individual depressive symptoms.

This Mendelian randomization study included genome-wide association study (GWAS) summary data that included participants from three different trials: one including 204,402 individuals studies for 9 depressive symptoms; a Patient Health Questionnaire 9 including 117,907 individuals; Biobank study including  230 214 individuals. The primary outcome was a coheritability between CRP levels and individual depressive symptoms.

Genetic correlation analysis conducted by the researchers resulted in a false discovery rate-controlled associations between CRP levels and depressive symptoms. Furthermore, two-sample MR analyses indicated that the genetic upregulation of IL-6 was associated with a higher risk of suicidality. Mendelian randomization analyses did not demonstrate a clear correlation between higher CRP levels or IL-6 and individual depressive symptoms. However, higher BMI was associated with tiredness and anhedonia.

The research concluded that there was a substantial coheritability between CRP levels and individual depression, with potential causes being metabolic dysregulation, anhedonia, and tiredness.