Thyroid Axis and Depressive Disorders

  • Andrew Winokur
Part of the The Depressive Illness Series book series (DISS, volume 3)


Interest has been directed to the relationship between depressive disorders and thyroid axis function for many years. In the past 20 years, numerous studies have examined various indices of thyroid axis function in patients with depressive disorders and effects of thyroid axis hormones on mood and behavior. A third line of interest has involved effects of various psychotropic drugs used in the treatment of affective disorders on thyroid axis function. The major focus of this chapter will be on studies examining the interaction between the thyroid axis and depression. However, we start with a brief overview of reasons for interest in a role of the thyroid axis in depression.


Thyroid Hormone Depressed Patient Sleep Deprivation Ground Squirrel Thyrotropin Release Hormone 
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  1. Bartalena L, Pellegrini L, Meschi M, Antonangeli L, Bogazzi F, Dell ‘Osso L, Pinchera A, Placidi GF: Evaluation of thyroid function in patients with rapid-cycling and non-rapid-cycling bipolar disorder. Psychiat Res 1990; 34: 13–37.CrossRefGoogle Scholar
  2. Bauer MS, Whybrow PC: Thyroid hormones and the central nervous system in affective illness: Interactions that may have clinical significance. Integr Psychiat 1988; 6: 75–100.Google Scholar
  3. Bauer MS, Whybrow PC: Rapid cycling bipolar effective disorder. II. Treatment of refractory rapid cycling with high-dose levothyroxine: A preliminary study. Arch Gen Psychiat 1990; 47: 435–440.PubMedCrossRefGoogle Scholar
  4. Bauer MS, Whybrow PC, Winokur A: Rapid cycling bipolar affective disorder I. Association with grade I hypothyroidism. Arch Gen Psychiat 1990; 47: 427–432.PubMedCrossRefGoogle Scholar
  5. Baumgartner A, Gräf KJ, Kürten I, Meinhold H: The hypothalamic-pituitarythyroid axis in psychiatric patients and healthy subjects. Part II. Repeated measurements of thyroxine, free thyroxine, triiodothyronine in patients with major depressive disorder and schizophrenia and healthy subjects. Psychiat Res. 1988; 24: 283–305.CrossRefGoogle Scholar
  6. Baumgartner A, Gräf KJ, Kürten I, Meinhold H, Scholz P: Neuroendocrinological investigations during sleep deprivation in depression. I. Early morning levels of thyroxine, TH cortisol, prolactin, LH. FSH, cortisol, prolactin, LH, FSH, estradiol and testosterone. Biol Psychiat 1990; 28: 556–558.PubMedCrossRefGoogle Scholar
  7. Bhargava HN, Ramarao P, Gulati A: Changes in multiple opioid receptors in regions of the brain in rats treated chronically with thyroxine. Neuropharmacology 1989; 28: 955–960.PubMedCrossRefGoogle Scholar
  8. Borst GC, Eil C, Burman KD: Euthyroid hyperthyroxinemia. Ann Internal Med 1983; 98: 366–378.CrossRefGoogle Scholar
  9. Brabant G, Prank K, Rauft U, Schuermeyer Th, Wagner TOF, Hauser H, Hesch RD, Von Zur Muhlen A: Physiological regulating of circadian and pulsatile thyrotropin secretion in normal thyrotropin secretion in normal man and woman. J Clin Endocrinol Metab 1990; 70: 403–409.PubMedCrossRefGoogle Scholar
  10. Brady KJ, Anton RF: The thyroid axis and desipramine treatment in depression. Biol Psychiat 1989; 25: 703–709.PubMedCrossRefGoogle Scholar
  11. Breese GR, Cooper BR, Prange AJ, Cott JM, Lipton MA: Interactions of thyrotropin-releasing hormone with centrally action drugs. In: Prange AJ (Ed.), The Thyroid Axis, Drugs and Behavior, New York: Raven Press, 1974, 115–128.Google Scholar
  12. Breese GR, Prange AJ, Lipton MA: Pharmacological studies and thyroidimipramine interactions in animals. In: Prange AJ (Ed.), The Thyroid Axis, Drugs and Behavior, New York: Raven Press, 1974, 29–48.Google Scholar
  13. Cho JT, Bone S, Dunner DL, Colt E: The effect of lithium treatment on thyroid function in patients with primary affective disorder. Am J Psychiat 1979; 136: 115–116.PubMedGoogle Scholar
  14. Cohen KL, Swigar ME: Thyroid function screening in psychiatric patients. J Am Med Assoc 1979; 242: 254–257.CrossRefGoogle Scholar
  15. Cowdry RW, Wehr TA, Zis AO, Goodwin FK: Thyroid abnormalities associated with rapid-cycling bipolar illness. Arch Gen Psychiat 1983; 40: 414–420.PubMedCrossRefGoogle Scholar
  16. Dratman MB, Crutchfield FL, Axelrod J, Collburn RW, Thoa N: Localization of triiodothyronine in nerve endings fractions of rat brain. Proc Nat Acad Sci 1976; 3: 941–944.CrossRefGoogle Scholar
  17. Dratman MB, Crutchfield FL, Gordon JT: Thyroid hormones and adrenergic neurotransmitter. In: Catecholamines, Neuropharmacology and Central Nervous System: Theoretical Aspects, New York: Alan R. Liss, 1984, 425–436.Google Scholar
  18. Dunner DL, Fieve RR: Clinical factors in lithium prophylaxis failure. Arch Gen Psychiat 1974; 30: 229–233.PubMedCrossRefGoogle Scholar
  19. Duval F, Macher JP, Mokrani MC: Difference between evening and morning thyrotropin responses to protirelin in major depressive episode. Arch Gen Psychiat 1990; 47: 443–448.PubMedCrossRefGoogle Scholar
  20. Everett GM: The DOPA response potentiation test and its use in screening for antidepressant drugs. Excerpta Med Int Congr Sery No. 122, 1966.Google Scholar
  21. Ford DH, Cramer EB: Developing nervous system in relation to thyroid hormones. In: Grave GD (Ed.), Thyroid Hormones and Brain Development, New York: Raven Press, 1977, 1–17.Google Scholar
  22. Frazer A, Pandey G, Mendels J, Neeley S, Kane M, Hess ME: The effect of tri-iodothyrone in combination with imipramine on (3H)-cyclic AMP production in slices of rat cerebral cortex. Neuropharmacology 1974; 13: 1131–1140.CrossRefGoogle Scholar
  23. Gavish M, Weisman A, Akun F, Youdim MBH: Modulatory effects of thyroxine treatment on central and peripheral benzodiazepine receptors in the rat. J Neurochem 1986; 47: 1106–1110.PubMedCrossRefGoogle Scholar
  24. Gitlin MJ, Weiner H, Fairbanks L, Hershman JM, Friedfeld N: Failure of T3 to potentiate tricyclic antidepressant response. J Affect Disord 1987; 13: 267–272.PubMedCrossRefGoogle Scholar
  25. Gjessing L: A review of periodic catatonia. Biol Psychiat 1974; 8: 23–45.PubMedGoogle Scholar
  26. Gold MS, Pottash AL, Extein IRL: Hypothyroidism and depression. Evidence from complete thyroid function evaluation. J Am Med Assoc 1981; 245: 1919–1922.CrossRefGoogle Scholar
  27. Goldman M, Dratman MB, Cruthchfield FL, Jennings AS, Maruniak JA, Gibbons R: Intrathecal triiodothyronine administration causes greater heart rate stimulation in hypothyroid rats than intravenously delivered hormone. J Clin Invest 1985; 76: 1622–1625.PubMedCrossRefGoogle Scholar
  28. Goodwin FK, Prange AJ, Jr, Post RM, Muscettola G, Lipton MA: Potentiation of antidepressant effects by L-triiodothyronine in tricyclic nonresponders. Am J Psychiat 1982; 139: 34–38.PubMedGoogle Scholar
  29. Herman R, Obarzanek E, Mikalayskas KM, Post RM, Jimerson DC: The effects of carbamazepine on resting metabolic rate and thyroid function in depressed patients. Biol Psychiat 1991; 29: 779–788.PubMedCrossRefGoogle Scholar
  30. Kardon FC, Winokur A, Utiger RD: Thyrotropin releasing hormone (TRH) in rat spinal cord. Brain Res 1977; 122: 578–581.PubMedCrossRefGoogle Scholar
  31. Kasper S, Sack DA, Wehr TA, Kick H, Voll G, Vieira H: Nocturnal TSH and prolactin, secretion during sleep deprivation and prediction of antidepressant response in patients with major depression. Biol Psychiat 1988; 24: 631–691.PubMedCrossRefGoogle Scholar
  32. Kastin AJ, Ehrensing RH, Schalch DS, Anderson MS: Improvement in mental depression with decreased thyrotropin response after administration of thyrotropin-releasing hormone. Lancet 1972; 11: 740–742.CrossRefGoogle Scholar
  33. Kijore B, Aggernaes H, Fog-Miller F, Anderson HH, Nissen J, Kirkegaard C, Bjdrum N: Circadian variation of serum thyrotropin in endogenous depression. Psychiat Res 1982; 6: 277–282.CrossRefGoogle Scholar
  34. Kirkegaard C: The thyrotropin response to thyrotropin-releasing hormone in endogenous depression. Psychoneuroendocrinology 1981; 6: 189–212.PubMedCrossRefGoogle Scholar
  35. Kramlinger KG, Gharib H, Swanson DW, Maruth T: Normal serum thyroxine values in patients with acute psychiatric illness. Am J Med 1984; 76: 799–801.PubMedCrossRefGoogle Scholar
  36. Langer G, Koinig G, Hatzinger R, Schonbeck G, Resch F, Aschauer H, Keshavan MS, Sieghart W: Response of thyrotropin to thyrotropin-releasing hormone as predictor of treatment outcome. Arch Gen Psychiat 1969; 43: 861–868.CrossRefGoogle Scholar
  37. Levy RP, Jensen JB, Laus VG, Ogle DP, Engle IM: Serum thyroid hormone abnormalities in psychiatric disease. Metabolism 1981; 30: 1060–1064.PubMedCrossRefGoogle Scholar
  38. Loosen PT: The TRH-induced TSH response in psychiatric patients: A possible neuro-endocrine marker. Psychoneuroendocrinology 1985; 10: 237–260.PubMedCrossRefGoogle Scholar
  39. Loosen PT, Prange AJ: The serum thyrotropin (TSH) response to thyrotropinreleasing hormone (TRH) in depression: A review. Am J Psychiat 1982; 139: 405–416.PubMedGoogle Scholar
  40. Manaker S, Winokur A, Rostene WH, Rainbow TC: Autoradiographic localization of thyrotropin releasing hormone (TRH) receptors in the rat CNS. J Nueurosci 1985; 35: 167–174.Google Scholar
  41. Mason GA, Bondy SC, Nemeroff CB, Walker CH, Prange AJ: The effects of thyroid state on beta-adrenergic and serotonergic receptors in rat brain. Psychoneuroendocrinology 1987; 12: 261–270.PubMedCrossRefGoogle Scholar
  42. Mason GA, Walker CH, Prange AJ: Modulation of gamma-aminobutryric acid uptake of brain synaptosomes by thyroid hormones. Neuropsychopharmacology 1987; 1: 63–70.PubMedCrossRefGoogle Scholar
  43. Morley JE: Neuroendocrine control of thyrotropin secretion. Endocrine Rev 1981; 2: 396–435.CrossRefGoogle Scholar
  44. Perrild H, Hegedus L, Baastrup PC, Kayser L, Kastberg S: Thyroid function and ultrasonically determined thyroid size in patients receiving long-term lithium treatment. Am J Psychiat 1990; 147: 1518–1521.PubMedGoogle Scholar
  45. Plotnitcoff NP, Prange AJ, Breese GR, Anderson MS, Wilson IC: Thyrotropin releasing hormone: Enhancement of DOPA activity by a hypothalamic hormone. Science 1972; 178: 417–418.CrossRefGoogle Scholar
  46. Prange AJ, Wilson IC, Lara PP, Alltop LB, Breese GR: Effects of thyrotropinreleasing hormone (TRH) in depression. Lancet 1972; 11: 999–1002.CrossRefGoogle Scholar
  47. Prange AJ, Jr, Wilson IC, Rabon AM, Lipton MA: Enhancement of imipramine antidepressant activity by thyroid hormone. Am J Psychiat 1969; 126: 457–469.PubMedGoogle Scholar
  48. Rubin RI, Poland RE, Lesser IM, Martin DJ: Neuroendocrine aspects of primary endogenous depression IV. Pituitary-thyroid axis activity in patients and matched control subjects. Psychoneuroendocrinology 1987; 12: 333–347.PubMedCrossRefGoogle Scholar
  49. Sack DA, James SP, Rosenthal NE, Wehr TA: Deficient nocturnal surge of TSH secretion during sleep and sleep deprivation in rapid-cycling bipolar illness. Psychiat Res 1988; 23: 179–191.CrossRefGoogle Scholar
  50. Savard P, Mérand 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.PubMedCrossRefGoogle Scholar
  51. Schildkraut JJ, Winokur A, Draskozy PR, Hensle JH: Changes in norepinephrine turnover in rat brain during chronic administration of imipramine and protriptyline: A possible explanation for the delay in onset of clinical antidepressant effects. Am J Psychiat 1971; 127: 1032–1039.PubMedGoogle Scholar
  52. Schmidt BH, Schultz JE: Chronic thyroxine treatment of rats down-regulates the noradrenergic cyclic AMP generating system in cerebral cortex. J Pharmacol Exp Therapeut 1985; 233: 466–472.Google Scholar
  53. Schou M, Amidson A, Jesen SE, Olsen T: Occurrence of goiter during lithium treatment. Br Med J 1968; 3: 710–713.PubMedCrossRefGoogle Scholar
  54. Spratt DI, Pont A, Miller MB, McDougall IR, Bayer MF, McLaughlin WT, Am J Med 1982; 73: 41–48.PubMedCrossRefGoogle Scholar
  55. Stanton TL, Winokur A, Beckman AL: Reversal of natural CNS depression by TRH action in the hippocampus. Brain Res 1980; 137: 470–475.CrossRefGoogle Scholar
  56. Stanton TL, Winokur A, Beckman AL: TRH effects in the CNS: dependence on arousal site. Science 1981; 214: 678–681.PubMedCrossRefGoogle Scholar
  57. Sterling K: Thyroid hormone action at the cell level. New Eng J Med 1975; 300: 117–123, 173–177.Google Scholar
  58. Waldstein S: Thyroid-catecholamine interrelations. Ann Rev Med 1966; 17: 123–132.PubMedCrossRefGoogle Scholar
  59. Weeke A, Weeke J: Disturbed circadian variation of serum thyrotropin in patients with endogenous depression. Acta Psychiat Scand 1978; 57: 281–289.PubMedCrossRefGoogle Scholar
  60. Weeke A, Weeke J: The 24-hour pattern of serum TSH in patients with endogenous depression. Acta Psychiat Scand 1980; 62: 69–74.PubMedCrossRefGoogle Scholar
  61. Whybrow PC, Bauer MS: Effects of peripheral thyroid hormones on the central nervous system: Relevance to disorders of mood. Curr Top Neuroendocrinol 1988; 8: 309–326.CrossRefGoogle Scholar
  62. Winokur A: The relevance of thyrotropin-releasing hormone to psychiatric disorders. In: Nemeroff CB (Ed.), Neuropeptides and Psychiatric Disorders, Washington, DC: American Psychiatric Press, 1990, 13–281.Google Scholar
  63. Winokur A, Davies R, Utiger RD: Subcellular distribution of thyrotropin-releasing hormone (TRH) in rat brain and hypothalamus. Brain Res 1977; 120: 423–434.PubMedCrossRefGoogle Scholar
  64. Winokur A, Utiger RD: Thyrotropin-releasing hormone: Regional distribution in rat brain. Science 1974; 185: 265–267.PubMedCrossRefGoogle Scholar
  65. Yarbrough GG: On the neuropharmacology of thyrotropin-releasing hormone (TRH). Prog Neurobiol 1979; 12: 291–312.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1993

Authors and Affiliations

  • Andrew Winokur
    • 1
  1. 1.Department of PsychiatryUniversity of PennsylvaniaPhiladelphiaUSA

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