THE THYROID AXIS AND DEPRESSION

Hypothyroidism may give rise to frank depression that usually responds to thyroxine therapy. Depressed subjects with subclinical hypothyroid ism and/or autoimmune thyroiditis should probably also be treated simi larly. Most patients with depression, although generally viewed as che mically euthyroid, have alterations in their thyroid function includin g slight elevation of the serum thyroxine (T-4), blunted thyrotropin ( TSH) response to thyrotropin-releasing hormone (TRH) stimulation, and loss of the nocturnal TSH rise. These changes are generally reversed f ollowing alleviation of the depression. The role of adjuvant triiodoth yronine (T-3) treatment in resistant depression has not been establish ed, but the data suggest that it will be beneficial in about 25% of ca ses. However, controlled trials to establish this approach are needed. The underlying mechanism leading to the beneficial response from T-3 is unknown, but may reflect brain hypothyroidism in the context of sys temic euthyroidism. The hypothalamus in culture, which is analogous to a deafferentated hypothalamus in vivo, shows a paradoxic increase in TRH production after glucocorticoid stimulation. It is known that in h uman depression there is a functional disconnection of the hypothalamu s with impairment of the inhibitory glucocorticoid feedback pathway fr om the hippocampus to the hypothalamus that results in the typical ele vated cortisol levels and impaired dexamethasone suppression. It is po stulated that a similar situation prevails with regards to the thyroid axis and that the increased T-4 in depression, as well as the blunted TSH response to exogenous TRH, reflects glucocorticoid activation of the TRH neuron leading to increased TRH secretion with resultant down regulation of the TRH receptor on the thyrotrope. Normalization of thy roid function after treatment may result in part from an inhibitory re sponse of the TRH neuron to antidepressant medication, although other effects may also be responsible.