The role of thyroid hormones in depression

During the last 30 years a huge number of scientific articles have appeared on the subject of relationships between psychiatric disease and thyroid hormones. These studies have demonstrated the presence of numerous changes in the hypothalamo–pituitary– thyroid (HPT) axis, mainly in patients with depression, but also in patients with other psychiatric diseases. Simultaneously, many studies have been published on the possible therapeutic effects in depression of the hormones involved in the HPT axis. Despite great efforts to standardize the classification of depression, this is still a less well-defined disease, possibly including several subtypes with different pathogenesis and biochemical abnormalities. Furthermore the classification has changed over time, making it difficult to interpret previously published data. The most accepted classifications are the DSM-IV and ICD-10. These cover a spectrum from minor depression (neurotic depression) through major depression to melancholic (endogenous and psychotic) depression. Furthermore major and melancholic depressions are divided into uniand bipolar depressions, the latter also demonstrating episodes of mania. Rapid cycling bipolar psychosis is a subgroup of the bipolar depression, demonstrating four or more episodes in any year of observation. The present review focuses on the concentrations of hormones of the HPT-axis seen in uniand bipolar depression, their relation to relapse after antidepressive treatment, and a survey of therapeutic trials with thyrotropin-releasing hormone (TRH), thyroid-stimulating hormone (TSH) and thyroid hormones, as well as the effect of the various drugs used in depression on the HPT-axis. The hypothesis is put forward that the changes seen in the HPT-axis during depression might be explained by cerebral serotonin deficiency, and that tri-iodothyronine (T3) treatment, to some degree, can revert this deficiency.