Endocrine Abstracts

A link between thyroid function and psychiatric illness, particularly major depressive disorder (MDD) is well established. Hypothyroidism has been shown to render patients more susceptible to MDD and less responsive to antidepressant drugs. Triiodothyronine (T3) has been shown to enhance antidepressant response in euthyroid patients who have not responded to standard antidepressant treatment. Furthermore, concurrent treatment with T3 may enhance and possibly accelerate treatment response when administered from the onset of treatment concurrently with antidepressant medication. In mouse studies we have shown that antidepressant effects of T3 as a sole treatment are dose dependent and linked to enhanced serotonin release mediated via effects of chronic administration on 5-HT-1A and 1-B autoreceptors. We have further shown that combined treatment with T3 and an antidepressant enhances hippocampal neurogenesis to a greater extent than antidepressant alone. Since long-term administration of T3 to euthyroid patients is not clinically feasible, we have sought avenues to enhance brain T3 levels by alternate routes. One direction we have explored is specific inhibition of deiodinase 3 (DIO3) by means of novel small molecules synthesized by the use of a DIO3 mimic. Preliminary findings in mice suggest that brain T3 levels may be enhanced by these novel compounds and antidepressant effects may be demonstrable on screening tests. Further studies are in progress.