Thyroid hormones and the treatment of depression: An examination of basic hormonal actions in the mature mammalian brain

Abstract

Numerous clinical reports indicate that thyroid hormones can influence mood, and a change in thyroid status is an important correlate of depression. Moreover, thyroid hormones have been shown to be effective as adjuncts for traditional antidepressant medications in treatment-resistant patients. In spite of a large clinical literature, little is known about the mechanism by which thyroid hormones elevate mood. The lack of mechanistic insight reflects, in large part, a longstanding bias that the mature mammalian central nervous system is not an important target site for thyroid hormones. Biochemical, physiological, and behavioral evidence is reviewed that provides a clear picture of their importance for neuronal function. This paper offers the hypothesis that the thyroid hormones influence affective state via postreceptor mechanisms that facilitate signal transduction pathways in the adult mammalian brain. This influence is generalizable to widely recognized targets of antidepressant therapies such as noradrenergic and serotonergic neurotransmission.

Paradoxical Hormonal and Behavioral Responses to Hypothyroid and Hyperthyroid States in the Wistar–Kyoto Rat

“…The clinical findings that T 3 can augment the antidepressant response in antidepressant refractory depression (Joffe et al 1995;Henley and Koehnle 1997) supports the hypothesis that subclinical hypothyroidism lowers the threshold of depression or enhances depressive symptoms, but is not sufficient, per se, to cause depression (Kirkegaard and Faber 1991;Haggerty et al 1993).…”

Supraphysiological doses of levothyroxine alter regional cerebral metabolism and improve mood in bipolar depression

“…[16][17][18] Recent studies of the mature mammalian brain have begun to change this situation, 13,[19][20][21][22][23] with new evidence suggesting that thyroid hormones are critically important in maintaining the optimal level of metabolic activity in the mature brain. 20,[24][25][26] For example, hypothyroid adult rats exhibit deficits in 2-deoxy-D [1][2][3][4][5][6][7][8][9][10][11][12][13][14] C]glucose uptake by most brain regions, indicating a general cerebral metabolic deficiency. 27 In addition, serum TSH (inversely related to thyroid hormone levels) is inversely related to cerebral metabolism and blood flow in the dorsolateral and mesial prefrontal cortices of human euthyroid patients with major depression.…”

Supraphysiological Doses of L-Thyroxine in the Maintenance Treatment of Prophylaxis-Resistant Affective Disorders

“…The influence of the thyroid system on neurotransmitters that putatively play a major role in the regulation of mood and behavior, serotonin and norepinephrine, may contribute to the mechanisms of thyroid hormone action (Henley and Koehnle 1997;Bauer et al 2002b). Clinical studies may provide a better understanding of the mood stabilizing effects of T 4 given at supraphysiological doses.…”