Depressed patients, although viewed as chemically euthyroid, have alterations in the function of hypothalamic-pituitary-thyroid axis including slight elevation of the serum thyroxine (T4), loss of the nocturnal TSH rise, blunted thyrotropin (TSH) response to thyrotropin-releasing hormone (TRH) stimulation and predisposition to autoimmune thyroiditis. Both hypothyroid and depressed patients share a number of clinical features in common. This is the reason that some research workers use the "brain hypothyroidism" hypothesis to explain the pathogenesis of depression. They suggest that depression is a state of local hypothyroidism in brain with normal peripheral thyroid hormone concentrations as a result of brain type II deiodinase inhibition and impaired transport T4 across the blood brain barrier. This theory seems to be compatible with the serotonin deficiency hypothesis of depression. Some studies confirm the existence of classical feedback between serotoninergic and hypothalamus-pituitary-thyroid systems. TRH remains under a constant inhibition by serotonin and reduced intracerebral serotonin concentration seen in depression will lead to increased TRH concentration in brain tissue. This mechanism is probably responsible for blunted TSH response to TRH stimulation.