Although anti-TNF is thought to potentially reduce depression,18 TNF levels in depression are unpredictable and it is possible that paradoxical effects may be seen modulating TNF,19 as unexpectedly as was seen in heart failure studies.20 We conducted a systematic review and meta-analysis to assess the APE of the currently available biologic therapies used for IBD, including infliximab, adalimumab, golimumab, certolizumab, vedolizumab, and ustekinumab. The gene discussed is TNF; the disease is depressive disorder.