Brain insulin resistance is associated with depression.29, 30 It is known that thiazolidinediones (pioglitazone and rosiglitazone) and metformin reduce insulin resistance and improve insulin sensitivity.6, 49 In addition, these drugs penetrate the blood‐brain barrier (BBB).50, 51, 52 For this reason, these drugs may improve insulin resistance in brain tissue as well as peripheral tissue.53 However, the use of these drugs did not reduce the risk of depression in the present study. This evidence concerns the gene INS and depressive symptom measurement.