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Letter to the Editor   |    
Thyroid Hormones and Seasonal Mood Change
LEO SHER, M.D.
Am J Psychiatry 2001;158:323-323. doi:10.1176/appi.ajp.158.2.323

To the Editor: Several studies of peripheral thyroid economy in seasonal affective disorder have shown inconsistent results (1). However, measurements of the peripheral thyroid state may not provide a reliable index of the central thyroid state (2).

In contrast to the peripheral tissues, where most of the nuclear-bound triiodothyronine (T3) is imported from the plasma pool, in the brain the supply of T3 depends mostly on the cellular uptake and intracellular deiodination of thyroxin by type II 5′-iodothyronine deiodinase (3). The existence of a separate pathway in the brain for thyroxin deiodination suggests that the adult central nervous system has the ability to autoregulate thyroid status (4).

A short photoperiod and low ambient temperature are direct stimuli that could affect type II 5′-iodothyronine deiodinase activity (5). Other effects of temperature and photoperiod (e.g., decreased pituitary and gonadal hormones) could be indirect factors that stimulate type II 5′-iodothyronine deiodinase activity. Thus, seasonal changes in light andtemperature may affect the metabolism of brain thyroid hormones.

T3 may itself be a neurotransmitter, and it may have an antidepressant effect (6). It enhances the effects of norepinephrine (7), serotonin (8), and γ-aminobutyric acid (9). Small alterations of brain thyroid economy, independent of peripheral changes in thyroid status, may produce significant behavioral effects. Therefore, it is reasonable to suggest that brain thyroid hormones might be involved in the mechanisms of seasonal changes in mood and behavior.

Sher L, Rosenthal NE, Wehr TA: Free thyroxine and thyroid-stimulating hormone levels in patients with seasonal affective disorder and matched controls. J Affect Disord  1999; 56:195–199
[PubMed]
[CrossRef]
 
Esposito S, Prange AJ Jr, Golden RN: The thyroid axis and mood disorders: overview and future prospects. Psychopharmacol Bull  1997; 33:205–217
[PubMed]
 
Crantz FR, Silva JE, Larsen PR: An analysis of the sources and quantity of 3,5,5′-triiodothyronine specifically bound to nuclear receptors in rat cerebral cortex and cerebellum. Endocrinology  1982; 110:367–375
[PubMed]
[CrossRef]
 
Dratman M, Crutchfield F, Gordon J, Jennings A: Iodothyronine homeostasis in rat brain during hypo-hyperthyroidism. Am J Physiol  1983; 245:185–193
 
Puig-Domingo M, Guerrero JM, Vaughan MK, Little JC, Reiter RJ: Activation of cerebrocortical type II 5′-deiodinase activity in Syrian hamsters kept under short photoperiod and reduced ambient temperature. Brain Res Bull  1989; 22:975–979
[PubMed]
[CrossRef]
 
Mason GA, Walker CH, Prange AJ Jr: L-Triiodothyronine: is this peripheral hormone a central neurotransmitter? Neuropsychopharmacology  1993; 3:253–258
 
Gordon JT, Martens DA, Tomlinson EE, Greenberg J, Dratman MB: Desmethylimipramine, a potent inhibitor of synaptosomal norepinephrine intake, has diverse effects on thyroid hormone processing in rat brain, II: effect on in vivo 5′-deiodination of [125I]thyroxine. Brain Res  1994; 634:96–104
[PubMed]
[CrossRef]
 
Mason GA, Bondy SC, Nemeroff CB, Walker CH, Prange AJ Jr: The effects of thyroid state on beta-adrenergic and serotonergic receptors in rat brain. Psychoneuroendocrinology  1987; 12:261–270
[PubMed]
[CrossRef]
 
Mason GA, Walker CH, Prange AJ Jr: Modulation of gamma-aminobutyric acid uptake of rat brain synaptosomes by thyroid hormones. Neuropsychopharmacology  1987; 1:63–70
[PubMed]
[CrossRef]
 
+

References

Sher L, Rosenthal NE, Wehr TA: Free thyroxine and thyroid-stimulating hormone levels in patients with seasonal affective disorder and matched controls. J Affect Disord  1999; 56:195–199
[PubMed]
[CrossRef]
 
Esposito S, Prange AJ Jr, Golden RN: The thyroid axis and mood disorders: overview and future prospects. Psychopharmacol Bull  1997; 33:205–217
[PubMed]
 
Crantz FR, Silva JE, Larsen PR: An analysis of the sources and quantity of 3,5,5′-triiodothyronine specifically bound to nuclear receptors in rat cerebral cortex and cerebellum. Endocrinology  1982; 110:367–375
[PubMed]
[CrossRef]
 
Dratman M, Crutchfield F, Gordon J, Jennings A: Iodothyronine homeostasis in rat brain during hypo-hyperthyroidism. Am J Physiol  1983; 245:185–193
 
Puig-Domingo M, Guerrero JM, Vaughan MK, Little JC, Reiter RJ: Activation of cerebrocortical type II 5′-deiodinase activity in Syrian hamsters kept under short photoperiod and reduced ambient temperature. Brain Res Bull  1989; 22:975–979
[PubMed]
[CrossRef]
 
Mason GA, Walker CH, Prange AJ Jr: L-Triiodothyronine: is this peripheral hormone a central neurotransmitter? Neuropsychopharmacology  1993; 3:253–258
 
Gordon JT, Martens DA, Tomlinson EE, Greenberg J, Dratman MB: Desmethylimipramine, a potent inhibitor of synaptosomal norepinephrine intake, has diverse effects on thyroid hormone processing in rat brain, II: effect on in vivo 5′-deiodination of [125I]thyroxine. Brain Res  1994; 634:96–104
[PubMed]
[CrossRef]
 
Mason GA, Bondy SC, Nemeroff CB, Walker CH, Prange AJ Jr: The effects of thyroid state on beta-adrenergic and serotonergic receptors in rat brain. Psychoneuroendocrinology  1987; 12:261–270
[PubMed]
[CrossRef]
 
Mason GA, Walker CH, Prange AJ Jr: Modulation of gamma-aminobutyric acid uptake of rat brain synaptosomes by thyroid hormones. Neuropsychopharmacology  1987; 1:63–70
[PubMed]
[CrossRef]
 
+
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