The study robustly highlights associations between immune markers and MDD but relies on case-control data, limiting its ability to establish causality. For example, the elevated CD4+/CD8+ ratios could be a consequence of MDD-related systemic inflammation or a predisposing factor. Could the authors explore whether longitudinal studies or Mendelian randomization approaches might better disentangle causality?
Furthermore, the discussion mentions potential antidepressant-induced immunomodulatory effects, yet does not differentiate the influence of various classes of antidepressants. Could the findings benefit from subgroup analyses stratified by antidepressant type to identify differential impacts on immune markers?