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Thyroid hormones, serotonin and mood: of synergy and significance in the adult brain

Abstract

The use of thyroid hormones as an effective adjunct treatment for affective disorders has been studied over the past three decades and has been confirmed repeatedly. Interaction of the thyroid and monoamine neurotransmitter systems has been suggested as a potential underlying mechanism of action. While catecholamine and thyroid interrelationships have been reviewed in detail, the serotonin system has been relatively neglected. Thus, the goal of this article is to review the literature on the relationships between thyroid hormones and the brain serotonin (5-HT) system, limited to studies in adult humans and adult animals. In humans, neuroendocrine challenge studies in hypothyroid patients have shown a reduced 5-HT responsiveness that is reversible with thyroid replacement therapy. In adult animals with experimentally-induced hypothyroid states, increased 5-HT turnover in the brainstem is consistently reported while decreased cortical 5-HT concentrations and 5-HT2A receptor density are less frequently observed. In the majority of studies, the effects of thyroid hormone administration in animals with experimentally-induced hypothyroid states include an increase in cortical 5-HT concentrations and a desensitization of autoinhibitory 5-HT1A receptors in the raphe area, resulting in disinhibition of cortical and hippocampal 5-HT release. Furthermore, there is some indication that thyroid hormones may increase cortical 5-HT2 receptor sensitivity. In conclusion, there is robust evidence, particularly from animal studies, that the thyroid economy has a modulating impact on the brain serotonin system. Thus it is postulated that one mechanism, among others, through which exogenous thyroid hormones may exert their modulatory effects in affective illness is via an increase in serotonergic neurotransmission, specifically by reducing the sensitivity of 5-HT1A autoreceptors in the raphe area, and by increasing 5-HT2 receptor sensitivity.

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References

  1. Whybrow PC, Bauer M . Behavioral and psychiatric aspects of thyrotoxicosis. In: Braverman LE, Utiger RD (eds). Werner and Ingbar's The Thyroid (8th edn) Lippincott-Raven: Philadelphia 2000 pp 673–678

  2. Whybrow PC, Bauer M . Behavioral and psychiatric aspects of hypothyroidism. In: Braverman LE, Utiger RD (eds). Werner and Ingbar's The Thyroid (8th edn) Lippincott-Raven: Philadelphia 2000 pp 837–842

  3. Bauer M, Whybrow PC . Thyroid hormone, neural tissue and mood modulation World J Biol Psych 2001 2: 57–67

    Google Scholar 

  4. Bauer MS, Whybrow PC . Rapid cycling bipolar affective disorders. II. Treatment of refractory rapid cycling with high-dose levothyroxine: a preliminary study Arch Gen Psychiatry 1990 47: 435–440

    CAS  PubMed  Article  Google Scholar 

  5. Baumgartner A, Bauer M, Hellweg R . Treatment of intractable non-rapid cycling bipolar affective disorder with high-dose thyroxine: an open clinical trial Neuropsychopharmacology 1994 10: 183–189

    CAS  PubMed  Article  Google Scholar 

  6. Bauer M, Priebe S, Berghöfer A, Bschor T, Kiesslinger K, Whybrow PC . Subjective response to and tolerability of long-term supraphysiological doses of levothyroxine in refractory mood disorders J Affect Disord 2001 64: 35–42

    CAS  PubMed  Article  Google Scholar 

  7. Altshuler L, Bauer M, Frye M, Gitlin M, Mintz J, Szuba M et al. Does thyroid supplementation accelerate antidepressant response? A review and meta-analysis of the literature Am J Psychiatry (in press)

  8. Aronson R, Offman HJ, Joffe RT, Naylor D . Triiodothyronine augmentation in the treatment of refractory depression. A meta-analysis Arch Gen Psychiatry 1996 53: 842–848

    CAS  PubMed  Article  Google Scholar 

  9. Bauer M, Hellweg R, Gräf KJ, Baumgartner A . Treatment of refractory depression with high-dose thyroxine Neuropsychopharmacology 1998 18: 444–455

    CAS  PubMed  Article  Google Scholar 

  10. Porterfield SP, Hendrich CE . The role of thyroid hormones in prenatal and neonatal neurological development—current perspectives Endocr Rev 1993 14: 94–106

    CAS  PubMed  Google Scholar 

  11. Bernal J, Nunez J . Thyroid hormones and brain development Eur J Endocrinol 1995 133: 390–398

    CAS  PubMed  Article  Google Scholar 

  12. Sokoloff L, Wechsler RL, Mangold R, Balls K, Kety SS . Cerebral blood flow and oxygen consumption in hyperthyroidism before and after treatment J Clin Invest 1953 32: 202–208

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  13. Sensenbach W, Madison L, Eisenberg S, Ochs L . The cerebral circulation and metabolism in hyperthyroidism and myxedema J Clin Invest 1954 33: 1434–1440

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  14. O'Brien MD, Harris PH . Cerebral-cortex perfusion-rates in myxoedema Lancet 1968 1: 1170–1172

    CAS  PubMed  Article  Google Scholar 

  15. Anderson GW, Mariash CN, Oppenheimer JH . Molecular actions of thyroid hormone. In: Braverman LE, Utiger RD (eds). Werner and Ingbar's The Thyroid (8th edn) Lippincott-Raven: Philadelphia 2000 pp 174–195

  16. Henley WN, Koehnle TJ . Thyroid hormones and the treatment of depression: an examination of basic hormonal actions in the mature mammalian brain Synapse 1997 27: 36–44

    CAS  PubMed  Article  Google Scholar 

  17. Schwartz HL, Oppenheimer JH . Nuclear triiodothyronine receptor sites in brain: probable identity with hepatic receptors and regional distribution Endocrinology 1978 103: 267–273

    CAS  PubMed  Article  Google Scholar 

  18. Ruel J, Faure R, Dussault JH . Regional distribution of nuclear T3 receptors in rat brain and evidence for preferential localization in neurons J Endocrinol Invest 1985 8: 343–348

    CAS  PubMed  Article  Google Scholar 

  19. St Germain DL, Galton VA . The deiodinase family of selenoproteins Thyroid 1997 7: 655–668

    CAS  PubMed  Article  Google Scholar 

  20. Van Doorn J, Roelfsma F, van der Heide D . Concentrations of thyroxine and 3,5,3′-triiodothyronine at 34 different sites in euthyroid rats as determined by an isotopic equilibrium technique Endocrinology 1985 117: 1201–1208

    CAS  PubMed  Article  Google Scholar 

  21. Leonard JL . Dibutyryl cAMP induction of type II 5’deiodinase activity in rat brain astrocytes in culture Biochem Biophys Res Commun 1988 151: 1164–1172

    CAS  PubMed  Article  Google Scholar 

  22. Campos-Barros A, Hoell T, Musa A, Sampaolo S, Stoltenburg G et al. Phenolic and tyrosyl ring iodothyronine deiodination and thyroid hormone concentrations in the human central nervous system J Clin Endocrinol Metab 1996 81: 2179–2185

    CAS  PubMed  Google Scholar 

  23. Blier P, Montigny de C . Current advances and trends in the treatment of depression TIPS 1994 15: 220–226

    CAS  PubMed  Google Scholar 

  24. Schatzberg AF, Schildkraut JJ . Recent studies on norepinephrine systems in mood disorders. In: Bloom FE, Kupfer DJ (eds) Psychopharmacology: The Fourth Generation of Progess Raven Press: New York, NY 1995 pp 911–920

    Google Scholar 

  25. Maes M, Meltzer HY . The serotonin hypotheses of major depression. In: Bloom FE, Kupfer DJ (eds) Psychopharmacology: The Fourth Generation of Progess Raven Press: New York NY 1995 pp 933–944

    Google Scholar 

  26. Harrison TS . Adrenal, medullary, and thyroid relationships Physiol Rev 1964 44: 161–185

    CAS  PubMed  Article  Google Scholar 

  27. Whybrow PC, Prange AJ Jr . A hypotheses of thyroid-catecholamine-receptor interaction Arch Gen Psychiatry 1981 38: 106–113

    CAS  PubMed  Article  Google Scholar 

  28. Rozanov CB, Dratman MB . Immunohistochemical mapping of brain triiodothyronine reveals prominent localization in central noradrenergic systems Neuroscience 1996 74: 897–915

    CAS  PubMed  Article  Google Scholar 

  29. Gordon JT, Kaminski DM, Rozanov CB, Dratman MB . Evidence that 3,3’,5-triiodothyronine is concentrated in and delivered from the locus coeruleus to its noradrenergic targets via anterograde axonal transport Neuroscience 1999 93: 943–954

    CAS  PubMed  Article  Google Scholar 

  30. Jacobs BL, Azmitia EC . Structure and function of the brain serotonin system Physiol Rev 1992 72: 165–229

    CAS  PubMed  Article  Google Scholar 

  31. Coppen A . The biochemistry of affective disorders Br J Psychiatry 1967 113: 1237–1264

    CAS  PubMed  Article  Google Scholar 

  32. Asberg M, Thoren P, Traskman L, Bertilsson L, Ringberger V . ’Serotonin depression‘_a biochemical subgroup within the affective disorders? Science 1976 191: 478–480

    CAS  PubMed  Article  Google Scholar 

  33. Delgado PL, Lawrence HP, Miller HL, Salomon RM, Aghajanian GK, Heninger GR et al. Serotonin and the neurobiology of depression. Effects of tryptophan depletion in drug-free depressed patients Arch Gen Psychiatry 1994 51: 865–874

    CAS  PubMed  Article  Google Scholar 

  34. Blier P, De Montigny C, Chaput Y . Modifications of the serotonin system by antidepressant treatments: implications for the therapeutic response in major depression J Clin Psychopharmacol 1987 7 (Suppl): 24S–35S

    Google Scholar 

  35. Delgado PL, Charney DS, Price LH, Aghajanian GK, Ladis H, Henninger GR . Serotonin function and the mechanisms of antidepressant action. Reversal of antidepressant induced remission by rapid depletion of plasma tryptophan Arch Gen Psychiatry 1990 47: 411–418

    CAS  PubMed  Article  Google Scholar 

  36. Heinz A, Ragan P, Jones DW, Hommer D, Williams W, Knable MB, Gorey J et al. Reduced serotonin transporters in alcoholism Am J Psychiatry 1998 155: 1544–1549

    CAS  PubMed  Article  Google Scholar 

  37. Malison RT, Price LH, Berman R, van Dyck CH, Pelton GH, Carpenter L et al. Reduced brain serotonin transporter availability in major depression as measured by [123I]-2-β-carbomethoxy-3β-(4-iodophenyl)tropane and single photon emission computed tomography Biol Psychiatry 1998 44: 1090–1098

    CAS  Article  PubMed  Google Scholar 

  38. Savard P, Merand Y, Di Paolo T, Dupont A . Effect of neonatal hypothyroidism on the serotonin system of the rat brain Brain Res 1984 292: 99–108

    CAS  PubMed  Article  Google Scholar 

  39. Singhal RL, Rastogi RB, Hrdina PD . Brain biogenic amines and altered thyroid function Life Sci 1975 17: 1617–1626

    CAS  PubMed  Article  Google Scholar 

  40. Schwark WS, Keesey RR . Thyroid hormone control of serotonin in developing rat brain Res Commun Chem Pathol Pharmacol 1975 10: 37–50

    CAS  PubMed  Google Scholar 

  41. Savard P, Merand Y, Di Paolo T, Dupont A . Effects of thyroid state on serotonin, 5-hydroxyindoleacetic acid and substance P contents in discrete brain nuclei of adult rats Neuroscience 1983 10: 1399–1404

    CAS  PubMed  Article  Google Scholar 

  42. Henley WN, Chen X, Klettner C, Bellush LL, Notestine MA . Hypothyroidism increases serotonin turnover and sympathetic activity in the adult rat Can J Physiol Pharmacol 1991 69: 205–210

    CAS  PubMed  Article  Google Scholar 

  43. Henley WN, Bellush LL . Streptozotocin-induced decreases in serotonin turnover are prevented by thyroidectomy Neuroendocrinology 1992 56: 354–363

    CAS  PubMed  Article  Google Scholar 

  44. Henley WN, Vladic F . Hypothyroid-induced changes in autonomic control have a central serotonergic component Am J Physiol 1997 272: H894–903

    CAS  PubMed  Article  Google Scholar 

  45. Henley WN, Bellush LL, Tressler M . Bulbospinal serotonergic activity during changes in thyroid status Can J Physiol Pharmacol 1998 76: 1120–1131

    CAS  PubMed  Article  Google Scholar 

  46. Ito JM, Valcana T, Timiras PS . Effect of hypo- and hyperthyroidism on regional monoamine metabolism in the adult rat brain Neuroendocrinology 1977 24: 55–64

    CAS  PubMed  Article  Google Scholar 

  47. Upadhyaya L, Agrawal JK . Effect of L-thyroxine and carbimazole on brain biogenic amines and amino acids in rats Endocr Res 1993 19: 87–99

    CAS  PubMed  Article  Google Scholar 

  48. Jacoby JH, Mueller G, Wurtman RJ . Thyroid state and brain monoamine metabolism Endocrinology 1975 97: 1332–1335

    CAS  PubMed  Article  Google Scholar 

  49. Hong TP, Huang TY, Qiu XC . Effects of different thyroid states on 5-HT1A receptor in adult rat brain [Article in Chinese] Sheng Li Hsueh Pao 1992 44: 75–80

    CAS  PubMed  Google Scholar 

  50. Tejani-Butt SM, Yang J, Kaviani A . Time course of altered thyroid states on 5-HT1A receptors and 5-HT uptake sites in rat brain: an autoradiographic analysis Neuroendocrinology 1993 57: 1011–1018

    CAS  PubMed  Article  Google Scholar 

  51. Kulikov A, Moreau X, Jeanningros R . Effects of experimental hypothyroidism on 5-HT1A, 5-HT2A receptors, 5-HT uptake sites and tryptophan hydroxylase activity in mature rat brain Neuroendocrinology 1999 69: 453–459

    CAS  PubMed  Article  Google Scholar 

  52. 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

    CAS  PubMed  Article  Google Scholar 

  53. Rastogi RB, Singhal RL . Influence of neonatal and adult hyperthyroidism on behavior and biosynthetic capacity for norepinephrine, dopamine and 5-hydroxytryptamine in rat brain J Pharmacol Exp Ther 1976 198: 609–618

    CAS  PubMed  Google Scholar 

  54. Heal DJ, Smith SL . The effects of acute and repeated administration of T3 to mice on 5-HT1 and 5-HT2 function in the brain and its influence on the actions of repeated electroconvulsive shock Neuropharmacology 1988 27: 1239–1248

    CAS  PubMed  Article  Google Scholar 

  55. Engström G, Strombom U, Svensson TH, Waldeck B . Brain monoamine synthesis and receptor sensitivity after single or repeated administration of thyroxine J Neural Transm 1975 37: 1–10

    PubMed  Article  Google Scholar 

  56. Strömbom U, Svensson TH, Jackson DM, Engstrom G . Hyperthyroidism: specifically increased response to central NA-(alpha-)receptor stimulation and generally increased monoamine turnover in brain J Neural Transm 1977 41: 73–92

    PubMed  Article  Google Scholar 

  57. Suzuki S, Yoshida T, Sugita S, Kobayashi A, Nakazawa K . Triiodothyronine increases desipramine by changing the concentrations of monoamines, in the brain of rats given imipramine Eur J Pharmacol 1993 231: 297–300

    CAS  PubMed  Article  Google Scholar 

  58. Sandrini M, Vitale G, Vergoni AV, Ottani A, Bertolini A . Effect of acute and chronic treatment with triiodothyronine on serotonin levels and serotonergic receptor subtypes in the rat brain Life Sci 1996 58: 1551–1559

    CAS  PubMed  Article  Google Scholar 

  59. Gur E, Lerer B, Newman ME . Chronic clomipramine and triiodothyronine increase serotonin levels in rat frontal cortex in vivo: relationship to serotonin autoreceptor activity J Pharmacol Exp Ther 1999 288: 81–87

    CAS  PubMed  Google Scholar 

  60. Atterwill CK . Effect of acute and chronic tri-iodothyronine (T3) administration to rats on central 5-HT and dopamine-mediated behavioural responses and related brain biochemistry Neuropharmacology 1981 20: 131–144

    CAS  PubMed  Article  Google Scholar 

  61. Watanabe A . The influence of L-triiodothyronine on the action of desipramine on beta and serotonin 2A receptor, monoamines in rat brain [Article in Japanese] Nihon Shinkei Seishin Yakurigaku Zasshi 1999 19: 139–146

    CAS  PubMed  Google Scholar 

  62. Ramalho MJ, Reis JC, Antunes-Rodrigues J, Nonaka KO, De Castro e Silva E . Reduced prolactin release during immobolization stress in thyrotoxic rats: role of the central serotonergic system Horm Metab Res 1995 27: 121–125

    CAS  PubMed  Article  Google Scholar 

  63. Artigas F, Perez V, Alvarez E . Pindolol induces a rapid improvement of depressed patients treated with serotonin reuptake inhibitors Arch Gen Psychiatry 1994 51: 248–251

    CAS  PubMed  Article  Google Scholar 

  64. Sjöberg S, Eriksson M, Nordin C . L-thyroxine treatment and neurotransmitter levels in the cerebrospinal fluid of hypothyroid patients: a pilot study Eur J Endocrinol 1998 139: 493–497

    PubMed  Article  Google Scholar 

  65. Cleare AJ, McGregor A, O'Keane V . Neuroendocrine evidence for an association between hypothyroidism, reduced central 5-HT activity and depression Clin Endocrinol (Oxf) 1995 43: 713–719

    CAS  Article  Google Scholar 

  66. Meltzer HY, Maes M . Pindolol treatment blocks stimulation by meta-chlorophenylpiperazine of prolactin but not cortisol secretion in normal men Psychiat Res 1995 58: 89–98

    CAS  Article  Google Scholar 

  67. Cleare AJ, McGregor A, Chambers SM, Dawling S, O‘Keane V . Thyroxine replacement increases central 5-hydroxytryptamine activity and reduces depressive symptoms in hypothyroidism Neuroendocrinology 1996 64: 65–69

    CAS  PubMed  Article  Google Scholar 

  68. Upadhyaya L, Agrawal JK, Dubey GP, Udupa KN . Biogenic amines and thyrotoxicosis Acta Endocrinol 1992 126: 315–318

    CAS  Article  Google Scholar 

  69. Duval F, Mokrani MC, Bailey P, Correa H, Diep TS, Crocq MA et al. Thyroid axis activity and serotonin function in major depressive episode Psychoneuroendocrinology 1999 24: 695–712

    CAS  PubMed  Article  Google Scholar 

  70. Murphy DL . Peripheral indices of central serotonin function in humans Ann NY Acad Sci 1990 600: 282–295

    CAS  PubMed  Article  Google Scholar 

  71. Praag van HM, Lemus C, Kahn R . Hormonal probes of central serotonergic activity? Do they really exist? Biol Psychiatry 1987 22: 86–98

    Article  Google Scholar 

  72. Adell A, Artigas F . Differential effects of clomipramine given locally or systematically on extracellular 5-hydroxytryptamine in raphe nuclei and frontal cortex: an in vivo microdialysis study Naunyn-Schmiedeberg's Arch Pharmacol 1991 343: 237–244

    CAS  Article  Google Scholar 

  73. Bel N, Artigas F . Fluvoxamine preferentially increases extracellular 5-hydroxytryptamine in the raphe nuclei: an in vivo microdialysis study Eur J Pharmacol 1992 229: 101–103

    CAS  PubMed  Article  Google Scholar 

  74. Bel N, Artigas F . Chronic treatment with fluvoxamine increases extracellular serotonin in frontal cortex but not in raphe nuclei Synapse 1993 15: 243–245

    CAS  PubMed  Article  Google Scholar 

  75. Hjorth S . Serotonin 5-HT1A autoreceptor blockade potentiates the ability of the 5-HT reuptake inhibitor citalopram to increase nerve terminal output of 5-HT in vivo: a microdialysis study J Neurochem 1992 60: 776–779

    Article  Google Scholar 

  76. Artigas F . Pindolol, 5-hydroxytryptamine, and antidepressant augmentation Arch Gen Psychiatry 1995 52: 969–971

    CAS  PubMed  Article  Google Scholar 

  77. Cleare AJ, Murray RM, O'Keane V . Reduced prolactin and cortisol responses to d-fenfluramine in depressed compared to healthy matched control subjects Neuropsychopharmacology 1996 14: 349–354

    CAS  PubMed  Article  Google Scholar 

  78. Anand A, Charney DS, Delgado PL, McDougle CJ, Heninger GR, Price LH . Neuroendocrine and behavioral responses to intravenous m-chlorophenylpiperazine (mCPP) in depressed patients and healthy comparison subjects Am J Psychiatry 1994 151: 1626–1630

    CAS  PubMed  Article  Google Scholar 

  79. O'Keane V, Dinan TG . Prolactin and cortisol responses to d-fenfluramine in major depression: evidence for diminished responsivity of central serotonergic function Am J Psychiatry 1991 148: 1009–1015

    CAS  PubMed  Article  Google Scholar 

  80. Weizman A, Mark M, Gil-Ad I, Tyano S, Laron Z . Plasma cortisol, prolactin, growth hormone, and immunoreactive beta-endorphin response to fenfluramine challenge in depressed patients Clin Neuropharmacol 1988 11: 250–256

    CAS  PubMed  Article  Google Scholar 

  81. Park SB, Williamson DJ, Cowen PJ . 5-HT neuroendocrine function in major depression: prolactin and cortisol responses to d-fenfluramine Psychol Med 1996 26: 1191–1196

    CAS  PubMed  Article  Google Scholar 

  82. Meltzer H, Bastani B, Jayathilake K, Maes M . Fluoxetine, but not tricyclic antidepressants, potentiates the 5-hydroxytryptophan-mediated increase in plasma cortisol and prolactin secretion in subjects with major depression or with obsessive compulsive disorder Neuropsychopharmacology 1997 17: 1–11

    CAS  PubMed  Article  Google Scholar 

  83. Sargent PA, Quested DJ, Cowen PJ . Clomipramine enhances the cortisol response to 5-HTP: implications for the therapeutic role of 5-HT2 receptors Psychopharmacol (Berl) 1998 140: 120–122

    CAS  Article  Google Scholar 

  84. O'Keane V, McLoughlin D, Dinan TG . D-fenfluramine-induced prolactin and cortisol release in major depression: response to treatment J Affect Disord 1992 26: 143–150

    CAS  PubMed  Article  Google Scholar 

  85. Schwartz PJ, Murphy DL, Wehr TA, Garcia-Borreguero D, Oren DA, Moul DE et al. Effects of meta-chlorophenylpiperazine infusions in patients with seasonal affective disorder and healthy control subjects. Diurnal responses and nocturnal regulatory mechanisms Arch Gen Psychiatry 1997 54: 375–385

    CAS  PubMed  Article  Google Scholar 

  86. Coccarro EF, Kavoussi RJ, Trestman RL, Gabriel SM, Cooper TB, Siever LJ . Serotonin function in human subjects: intercorrelations among central 5-HT indices and aggressiveness Psychiatry Res 1997 73: 1–14

    Article  Google Scholar 

  87. Meltzer HY, Maes M . Effect of pindolol on hormone secretion and body temperature: partial agonist effects J Neural Transm 1996 103: 77–88

    CAS  PubMed  Article  Google Scholar 

  88. Yates M, Leake A, Candy JM, Fairbairn AF, McKeuth IG, Ferrier IN . 5-HT2 receptor changes in major depression Biol Psychiatry 1990 27: 489–496

    CAS  PubMed  Article  Google Scholar 

  89. Yatham LN, Liddle PF, Dennie J, Shiah IS, Adam MJ, Lane CJ et al. Decrease in brain serotonin 2 receptor binding in patients with major depression following desipramine treatment Arch Gen Psychiatry 1999 56: 705–711

    CAS  PubMed  Article  Google Scholar 

  90. Orford M, Mazurkiewicz D, Milligan G, Saggerson D . Abundance of the alpha-subunits of Gi1, Gi2 and Go in synaptosomal membranes from several regions of the rat brain is increased in hypothyroidism Biochem J 1991 275: 183–186

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  91. Orford MR, Leung FC, Milligan G, Saggerson ED . Treatment with triiodothyronine decreases the abundance of the alpha-subunits of Gi1 and Gi2 in the cerebral cortex J Neurol Sci 1992 112: 34–37

    CAS  PubMed  Article  Google Scholar 

  92. Mazurkiewicz D, Saggerson ED . Inhibition of adenylate cyclase in rat brain synaptosomal membranes by GTP and phenylisopropyladenosine is enhanced in hypothyroidism Biochem J 1989 263: 829–835

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  93. Iriuchijima T, Michimata T, Mizuma H, Murakami M, Yamada M, Mori M . Hypothyroidism inhibits the formation of inositol phosphate in response to carbachol in the striatum of adult rat Res Commun Chem Pathol Pharmacol 1991 73: 173–180

    CAS  PubMed  Google Scholar 

  94. Brent GA . The molecular basis of thyroid hormone action N Engl J Med 1994 29: 847–853

    Google Scholar 

  95. Forrest D, Hanebuth E, Smeyne RJ, Everds N, Stewart CL, Wehner JM et al. Recessive resistance to thyroid hormone in mice lacking thyroid hormone receptor beta: evidence for tissue-specific modulation of receptor function EMBO J 1996 15: 3006–3015

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  96. Fraichard A, Chassande O, Plateroti M, Roux JP, Trouillas J, Dehay C et al. The T3R alpha gene encoding a thyroid hormone receptor is essential for post-natal development and thyroid hormone production EMBO J 1997 16: 4412–4420

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  97. Wikstrom L, Johansson C, Salto C, Barlow C, Campos Barros A, Baas F et al. Abnormal heart rate and body temperature in mice lacking thyroid hormone receptor alpha 1 EMBO J 1998 17: 455–461

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  98. Göthe S, Wang Z, Ng L, Kindblom JM, Barros AC, Ohlsson C et al. Mice devoid of all known thyroid hormone receptors are viable but exhibit disorders of the pituitary-thyroid axis, growth, and bone maturation Genes Dev 1999 13: 1329–1341

    PubMed  PubMed Central  Article  Google Scholar 

  99. Hashimoto K, Curty FH, Borges PP, Lee CE, Abel ED, Elmquist JK et al. An unliganded thyroid hormone receptor causes severe neurological dysfunction Proc Natl Acad Sci USA 2001 98: 3998–4003

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  100. Köhrle J . Thyroid hormone metabolism and action in the brain and pituitary Acta Med Austriaca 2000 27: 1–7

    PubMed  Article  Google Scholar 

  101. Bernal J, Rodriguez-Pena A, Iniguez MA, Ibarrola N, Munoz A . Influence of thyroid hormone on brain gene expression Acta Med Austriaca 1992 19 (Suppl?1): 32–35

    Google Scholar 

  102. Iniguez MA, Rodriguez-Pena A, Ibarrola N, Morreale de Escobar G, Bernal J . Adult rat brain is sensitive to thyroid hormone. Regulation of RC3/neurogranin mRNA J Clin Invest 1991 90: 554–558

    Article  Google Scholar 

  103. Mooradian AD . Metabolic fuel and amino acid transport into the brain in experimental hypothyroidism Acta Endocrinol (Copenh) 1990 122: 156–162

    CAS  Article  Google Scholar 

  104. Roeder LM, Hopkins IB, Kaiser JR, Hanukoglu L, Tildon JT . Thyroid hormone action on glucose transporter activity in astrocytes Biochem Biophys Res Commun 1988 156: 275–281

    CAS  PubMed  Article  Google Scholar 

  105. Pardridge WM, Boado RJ, Farrell CR . Brain-type glucose transporter (GLUT-1) is selectively localized to the blood–brain barrier. Studies with quantitative western blotting and in situ hybridization J Biol Chem 1990 265: 18035–18040

    CAS  PubMed  Article  Google Scholar 

  106. Segerson TP, Kauer J, Wolfe HC, Mobtaker H, Wu P, Jackson IMD, Lechan RM . Thyroid hormone regulates (TRH) biosynthesis in the paraventricular nucleus of the rat hypothalamus Science 1987 238: 78–80

    CAS  PubMed  Article  Google Scholar 

  107. Ceccatelli S, Giardino L, Calza L . Response of hypothalamic peptide mRNAs to thyroidectomy Neuroendocrinology 1992 56: 694–703

    CAS  PubMed  Article  Google Scholar 

  108. Giordano T, Pan JB, Casuto D, Watanabe S, Arneric SP . Thyroid hormone regulation of NGF, NT-3 and BDNF RNA in the adult rat brain Mol Brain Res 1992 16: 239–245

    CAS  PubMed  Article  Google Scholar 

  109. Alvarez-Dolado M, Iglesias T, Rodriguez-Pena A, Bernal J, Munoz A . Expression of neurotrophins and the trk family of neurotrophin receptors in normal and hypothyroid rat brain Brain Res Mol Brain Res 1994 27: 249–257

    CAS  PubMed  Article  Google Scholar 

  110. Hong-Brown LQ, Deschepper CF . Effects of thyroid hormones on angiotensinogen gene expression in rat liver, brain, and cultured cells Endocrinology 1992 130: 1231–1237

    CAS  PubMed  Google Scholar 

  111. Vaidya VA, Castro ME, Pei Q, Sprakes ME, Grahame-Smith DG . Influence of thyroid hormone on 5-HT1A and 5-HT2A receptor-mediated regulation of hippocampal BDNF mRNA expression Neuropharmacology 2001 40: 48–56

    CAS  PubMed  Article  Google Scholar 

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Acknowledgements

We thank Georg Juckel, MD, and Faustino Lopez-Rodriguez, PhD, MD, for comments on the manuscript. This work has been supported by a grant from the Deutsche Forschungsgemeinschaft to MB (Ba 1504/3–1).

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Bauer, M., Heinz, A. & Whybrow, P. Thyroid hormones, serotonin and mood: of synergy and significance in the adult brain. Mol Psychiatry 7, 140–156 (2002). https://doi.org/10.1038/sj.mp.4000963

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Keywords

  • thyroid system
  • T4
  • T3
  • serotonin system
  • adult brain
  • 5-HT receptor
  • mood modulation
  • affective disorders
  • depression

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