Thyroid hormones and depressive illness: implications for clinical and basic research.

Abstract

It has been well-known for at least 100 years that both hypo- and hyperthyroidism may cause almost any psychiatric symptom, depending on the severity of the illness. No thyroid disorder, however, induces symptoms that are specific for a psychiatric disorder. Laboratory tests show depressed patients to be euthyroid. Any abnormalities that have been found, such as slightly elevated T4 levels or decreased T3 or TSH concentrations, have frequently failed to be replicated and do not fit any endocrinological diagnosis. They could reflect either "intervening factors" such as stress, methodological problems or a disturbance of central thyroid hormone metabolism. All antidepressant therapies (antidepressant drugs, carbamazepine, lithium, electroconvulsive therapy and sleep deprivation) have a marked influence on peripheral thyroid hormone levels. In particular, decreases in serum T4 and rT3 levels are often correlated to antidepressant response, suggesting that an effect on central thyroid hormone metabolism is involved in the as yet unknown mechanism of action of these therapies. Indeed, animal studies have shown that antidepressants do affect deiodinase activities and T3 and T4 concentrations in rat brain. However, the effects are highly area specific and dependent on the drug administered and the time of day at which the investigation was conducted. Although the mechanism of thyroid hormone action on CSF signal transduction is as yet unknown, effects on "general CNS functions" such as second messengers, G-proteins or calcium homeostasis seem more likely than specific effects on the different receptor systems.