 The goals of this proposal are to examine the relationship between Major Depressive Disorder MDD and abnormalities of the hypothalamic pituitary thyroid HPT axis. This protocol will systematically examine the value of supplemental triiodothyronine T3, Cytomel with sertraline Zoloft, a selective serotonin reuptake inhibitor SSRI in the treatment of MDD. The focus will be on two overlapping populations: 1 those with evidence of HPT abnormalities, and 2 those who did not respond to a previous adequate SSRI trial 