Arathimos R, Ronaldson A, Howe LJ, et al. - The associations between vitamin D and two subtypes of major depressive disorder (MDD)—treatment-resistant depression (TRD) and atypical depression (AD)—are examined.

• A dual approach was employed, integrating observational data with genetic evidence from polygenic risk scores (PRS) and two-sample Mendelian randomization (MR), in the UK Biobank.

• Observational analyses indicated a weak association between vitamin D and both incident TRD (Ncases = 830) and AD (Ncases = 2,366); after adjusting for confounders, the association attenuated largely.

• A causal link did not appear between vitamin D and either TRD or AD as per genetic evidence generated from PRS and two-sample MR.

• Further clinical trials of vitamin D are not supported in these MDD subtypes but existence of small effects could not be ruled out.