Aspects of Thyroid Axis Function in Depression

A Review
  • Arthur J. PrangeJr.
  • Peter T. Loosen


Venerable interest in the possible participation of the hypothalamic-pituitary-thyroid (HPT) axis in affective disorders has been rekindled by advances in physiological understanding of the axis, by technological progress, and by specific findings. It is now known that thyrotropin-releasing hormone (TRH), a tripeptide, is the hypothalamic substance that prompts the secretion of the anterior pituitary substance, thyroid-stimulating hormone (TSH, thyrotropin); it is now possible, by radioimmunoassay, to measure all the hormones of the HPT axis. It is now recognized that there is indeed a fault in HPT function in at least some patients with depression. A certain fraction of such patients, a quarter or more depending on criteria, show a blunted TSH response to TRH injection, in the absence of a usual endocrine explanation. In this brief review we will concern ourselves not only with this finding, which may be regarded as an aspect of the diagnostic use of HPT axis physiology, but also with the therapeutic use of hormones of the axis.


Thyroid Hormone Thyrotropin Release Hormone Depressed Woman Trait Marker Endogenous Depression 
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  1. Amsterdam, J. D., Winokur, A., Mendels, J., and Snyder, P., 1979, Distinguishing depression subtypes by thyrotropin response to TRH testing, Lancet II:904.CrossRefGoogle Scholar
  2. Asnis, G. M., Nathan, R. S., Halbreich, U., Halpern, F. S., and Sachar, E. J., 1980, TRH tests in depression, Lancet I:424.CrossRefGoogle Scholar
  3. Bánki, C. M., 1975, Triiodothyronin alkalmazasa a depressio kezeleseben [Triiodothyronine in the treatment of depression], Orv. Hetil. 116:2543.PubMedGoogle Scholar
  4. Bánki, C. M., 1977, Cerebrospinal fluid amine metabolites after combined amitriptyline-triio-dothyronine treatment of depressed women, Eur. J. Clin. Pharmacol. 11:311.PubMedCrossRefGoogle Scholar
  5. Benkert, O., Gordon, A., and Martschke, D., 1974, The comparison of thyrotropin-releasing hormone, luteinizing hormone-releasing hormone and placebo in depressive patients using a double-blind cross-over technique, Psychopharmacologia 40:191.PubMedCrossRefGoogle Scholar
  6. Bjørum, N., and Kirkegaard, C., 1979, Thyrotropin-releasing hormone test in unipolar and bipolar depression, Lancet II:694.CrossRefGoogle Scholar
  7. Brambilla, F., Smeraldi, E., Bellodi, L., Sachetti, E., and Mueller, E., 1980, Neuroendocrine correlates and monoaminergic hypothesis in primary affective disorder, in: Progress in Psy-choneuroendocrinology (F. Brambilla, G. Racagni, and D. de Wied, eds.), pp. 235–245, Else vier/North-Holland, Amsterdam.Google Scholar
  8. Burger, H. G., and Patel, Y. C., 1977, TSH and TRH: Their physiological regulation and the clinical application of TRH, in: Clinical Neuroendocrinology (L. Martini and G. M. Besser, eds.), Academic Press, New York.Google Scholar
  9. Carroll, B. J., and Mendels, J., 1976, Neuroendocrine regulation in affective disorders, in: Hormones, Behavior and Psychopathology (E. J. Sachar, ed.), pp. 193–224, Raven Press, New York.Google Scholar
  10. Chazot, G., Chalumeau, A., Aimard, G., Mornex, R., Garde, A., Schott, B., and Girard, P. F., 1974, Thyrotropin releasing hormone and depressive states: From agroagonines to TRH, Lyon Med. 231:831.Google Scholar
  11. Coppen, A., Whybrow, P. C., Noguera, R., Maggs, R., and Prange, A. J., Jr., 1972, The comparative antidepressant value of L-tryptophan and imipramine with and without attempted potentiation bv liothyronine, Arch. Gen. Psychiatry 26:234.PubMedCrossRefGoogle Scholar
  12. Coppen, A., Montgomery, S., Peet, M., and Bailey, J., 1974, Thyrotropin-releasing hormone in the treatment of depression, Lancet II:433.CrossRefGoogle Scholar
  13. Deniker, P., Ginestet, D., Loo, H., Zarifian, E., and Cottereau, M. J., 1974, Preliminary study of the action of hypothalamic thyrostimulin (TRH) in depressive states, Ann. Med. Psychol. 1:249.Google Scholar
  14. Dimitrikoudi, M., Hanson-Norty, E., and Jenner, F. A., 1974, T.R.H. in psychoses, Lancet I:456.CrossRefGoogle Scholar
  15. Earle, B. V., 1970, Thyroid hormone and tricyclic antidepressants in resistant depressions, Am. J. Psychiatry 126:1667.PubMedGoogle Scholar
  16. Ehrensing, R. H., and Kastin, A. J., 1974, Melanocyte-stimulating hormone release inhibiting hormone as an antidepressant: A pilot study, Arch. Gen. Psychiatry 30:63.PubMedCrossRefGoogle Scholar
  17. Ehrensing, R. H., and Kastin, A. J., 1978, Dose-related biphasic effect of prolyl-leucyl-glycinamide (MIF-I) in depression, Am. J. Psychiatry 135:562.PubMedGoogle Scholar
  18. Ehrensing, R. H., Kastin, A. J., Schalch, D. S., Friesen, H. G., Vargas, J. R., and Schally, A. V., 1974, Affective state and thyrotropin and prolactin responses after repeated injections of thyrotropin-releasing hormone in depressed patients, Am. J. Psychiatry 131:714.PubMedGoogle Scholar
  19. Ettigi, P. G., Brown, G. M., and Seggie, J. A., 1979, TSH and LH responses in subtypes of depression, Psychosom. Med. 41:203.PubMedGoogle Scholar
  20. Evans, L. E. J., Hunter, P., Hall, R., Johnston, M., and Roy, V. M., 1975, A double-blind trial of intravenous thyrotropin-releasing hormone in the treatment of reactive depression, Br. J. Psychiatry 127:227.PubMedCrossRefGoogle Scholar
  21. Feighner, J. P., King, L. J., Schuckit, M. A., Croughan, J., and Briscoe, W., 1972, Hormonal potentiation of impipramine and ECT in primary depression, Am. J. Psychiatry 128:1230.PubMedGoogle Scholar
  22. Garbutt, J., Malekpour, B., Brunswick, D., Jonnalagadda, M. R., Jolliff, L., Podolak, R., Wilson, I., and Prange, A. J., Jr., 1979, Effects of triiodothyronine on drug levels and cardiac function in depressed patients treated with imipramine, Am. J. Psychiatry 136:980.PubMedGoogle Scholar
  23. Gold, M. S., Pottash, A. L. C., Ryan, N., Sweeney, D. R., Davies, R. K., and Martin, D. M., 1980, TRH induced TSH response in unipolar, bipolar, and secondary depressions: Possible utility in clinical assessment and differential diagnosis, Psychoneuroendocrinology 5:147.PubMedCrossRefGoogle Scholar
  24. Goodwin, F. K., Prange, A. J., Jr., Post, R. M., Muscettola, G., and Lipton, M. A., 1981, l-Triiodothyronine converts tricycle antidepressant non-responders to responders. Am. J. Psychiatry 139:334–338.Google Scholar
  25. Gregoire, F., Brauman, H., De Buck, R., and Corvilain, J., 1977, Hormone release in depressed patients before and after recovery, Psychoneuroendocrinology 2:303.PubMedCrossRefGoogle Scholar
  26. Hall, R., Hunter, P. R., Price, J. S., and Mountjoy, C. Q., 1975, Thyrotropin-releasing hormone in depression, Lancet I:162.CrossRefGoogle Scholar
  27. Hatotani, N., Tsujimura, R., Nishikubo, M., Yamaguchi, T., Endo, M., and Endo, J., 1974, Endocrinological studies of depressive states, with special reference to hypothalamo-pituitary function, First World Congress of Biological Psychiatry, Buenos Aires, Abstract 101.Google Scholar
  28. Hatotani, N., Nomura, J., Yamaguchi, T., and Kitayama, I., 1977, Clinical and experimental studies on the pathogenesis of depression, Psychoneuroendocrinology 2:115.PubMedCrossRefGoogle Scholar
  29. Hollister, L. E., Berger, P., Ogle, F. L., Arnold, R. C., and Johnson, A., 1974, Protirelin (TRH) in depression, Arch. Gen. Psychiatry 31:468.PubMedCrossRefGoogle Scholar
  30. Hollister, L. E., Davis, K. L., and Berger, P. A., 1976, Pituitary response to thyrotropin-releasing hormone in depression, Arch. Gen. Psychiatry 33:1393.PubMedCrossRefGoogle Scholar
  31. Huey, L. Y., Janowsky, D. S., Mandell, A. J., Judd, L. L., and Pendery, M., 1975, Preliminary studies on the use of thyrotropin-releasing hormone in manic states, depression, and the dysphoria of alcohol withdrawal, Psychopharmacol. Bull. 11:24.PubMedGoogle Scholar
  32. Ingbar, S. H., and Woeber, K. A., 1974, The thyroid gland, in: Textbook of Endocrinology (R. H. Williams, ed.), pp. 95–232, Saunders, Philadelphia.Google Scholar
  33. Itil, T. M., Patterson, C. D., Polvan, N., Bigelow, A., and Bergey, B., 1975, Clinical and CNS effects of oral and I.V. thyrotropin-releasing hormone in depressed patients, Dis. Nerv. Syst. 36:529.PubMedGoogle Scholar
  34. Karlberg, B. E., Kjellman, B. F., and Kägedal, B., 1978, Treatment of endogenous depression with oral thyrotropin-releasing hormone and amitriptyline, Acta Psychiatr. Scand. 58:389.PubMedCrossRefGoogle Scholar
  35. Kastin, A. J., Ehrensing, R. H., Schalch, D. S., and Anderson, M. S., 1972, Improvement in mental depression with decreased thyrotropin response after administration of thyrotropin-releasing hormone, Lancet II:740.CrossRefGoogle Scholar
  36. Kieley, W. F., Adrian, A. D., Lee, J. H., and Nicoloff, J. T., 1976, Therapeutic failure of oral thyrotropin-releasing hormone in depression, Psychosom. Med. 38:233.Google Scholar
  37. Kirkegaard, C., and Bjørum, N., 1980, TSH responses to TRH in endogenous depression, Lancet I:152.CrossRefGoogle Scholar
  38. Kirkegaard, C., and Carroll, B. J., 1980, Dissociation of TSH and adrenocortical disturbances in endogenous depression, Psychiatry Res. 3:253.PubMedCrossRefGoogle Scholar
  39. Kirkegaard, C., Norlem, N., Lauridsen, U. B., Bjørum, N., and Christiansen, C., 1975, Protirelin stimulation test and thyroid function during treatment of depression, Arch. Gen. Psychiatry 32:1115.PubMedCrossRefGoogle Scholar
  40. Kirkegaard, C., Bjørum, N., Cohn, D., and Lauridsen, U. B., 1978, Thyrotropin-releasing hormone (TRH) stimulation test in manic depressive illness, Arch. Gen. Psychiatry 35:1017.PubMedCrossRefGoogle Scholar
  41. Klaiber, E. L., Broverman, D. M., Vogel, W., and Kobayashi, Y., 1979, Estrogen therapy for severe persistent depressions in women, Arch. Gen. Psychiatry 36:550.PubMedCrossRefGoogle Scholar
  42. Koenig, G., Langer, G., Schoenbeck, G., Schuessler, M., and Reiter, H., 1980, Neuroendocrine status of depressed patients at admission and during clomipramine treatment, Proc. XI Int. Congr. Soc. Psychoendocrinol., Florence, Italy, p. 74.Google Scholar
  43. Langer, G., Schoenbeck, G., Koenig, G., Reiter, H., Schuessler, M., Aschauer, H., and Lesch, O., 1980, Evidence for neuroendocrine involvement in the therapeutic effects of antidepressant drugs, in: Progress in Psychoneuroendocrinology (F. Brambilla, G. Racagni, and D. de Wied, eds.), pp. 197–208, Elsevier/North-Holland, Amsterdam.Google Scholar
  44. Lipton, M. A., and Goodwin, F. K., 1975, A controlled study of thyrotropin releasing hormone in hospitalized depressed patients, Psychopharmacol. Bull. 11:28.PubMedGoogle Scholar
  45. Loosen, P. T., and Prange, A. J., Jr., 1982, Serum thyrotropin response to thyrotropin-releasing hormone in psychiatric patients: A review, Am. J. Psychiatry 139:405.PubMedGoogle Scholar
  46. Loosen, P. T., Prange, A. J., Jr., Wilson, I. C., Lara, P. P., and Pettus, C., 1977, Thyroid stimulating hormone response after thyrotropin releasing hormone in depressed, schizophrenic and normal women, Psychoneuroendocrinology 2:137PubMedCrossRefGoogle Scholar
  47. Loosen, P. T., Prange, A. J., Jr., and Wilson, I. C., 1978a, Influence of Cortisol on TRH-induced TSH response in depression, Am. J. Psychiatry 135:244.PubMedGoogle Scholar
  48. Loosen, P. T., Prange, A. J., Jr., and Wilson, I. C., 1978b, The thyrotropin response to thyrotropin-releasing hormone in psychiatric patients: Relation to serum Cortisol, Prog. Neuro-Psycho-pharmacol. 2:479.CrossRefGoogle Scholar
  49. Loosen, P. T., Wilson, I. C., and Prange, A. J., Jr., 1980, Endocrine and behavioral changes in depression after thyrotropin-releasing hormone (TRH): Alteration by pretreatment with thyroid hormones, J. Affect. Disorders 2:267.PubMedCrossRefGoogle Scholar
  50. McClure, D. J., and Cleghorn, R. A., 1968, Suppression studies in affective disorders, Can. Psychiatry. Assoc. J. 13:477.Google Scholar
  51. Maeda, K., Kato, Y., Ohgo, S., Chihara, K., Yoshimoto, Y., Yamaguchi, N., Kuromaru, S., and Imura, H., 1975, Growth hormone and prolactin release after injection of thyrotropin-releasing hormone in patients with depression. J. Clin. Endocrinol. Metab. 40:501.PubMedCrossRefGoogle Scholar
  52. Maggini, C., Guazzelli, M., Mauri, M., Carrara, S., Formaro, P., Martino, E., Macchina, E., and Baschieri, L., 1974, Sleep, clinical and endocrine studies in depressive patients treated with thyrotropin releasing hormone, in: Second European Congress of Sleep (W. P. Koella, P. Levin, and M. Bertini, eds.), Karger, Basel.Google Scholar
  53. Mendlewicz, J., Linkowski, P., and Brauman, H., 1979, TSH responses to TRH in women with unipolar and bipolar depression, Lancet II:1079.CrossRefGoogle Scholar
  54. Mountjoy, C. Q., Weiler, M., Hall, R., Price, J. S., Hunter, P., and Dewar, J. H., 1974, A double-blind crossover sequential trial of oral thyrotropin-releasing hormone in depression, Lancet I:958.CrossRefGoogle Scholar
  55. Obiols, J., Pujol, J., and Obiols-Llandrich, J., 1974, Hormonas hipotalamicasy function tiroidea en los sindromes de presivos, 1st World Congress of Biological Psychiatry, Buenos Aires.Google Scholar
  56. Ogura, C., Okuma, T., Uchida, Y., Imai, S., Yogi, H., and Sunami, Y., 1974, Combined thyroid (triiodothyronine)-tricyclic antidepressant treatment in depressive states, Folia Psychiatr. Neurol. Jpn. 28:179.PubMedGoogle Scholar
  57. Otsuki, M., Dakoda, M., and Baba, S., 1973, Influence of glucocorticoids on TRF induced TSH response in man, J. Clin. Endocrinol. Metab. 36:95.PubMedCrossRefGoogle Scholar
  58. Papakostas, Y., Fink, M., Lee, J., Irwin, P., and Johnson, L., 1981, Neuroendocrine measures in psychiatric patients: Course and outcome with ECT, Psychiatry Res. 4:55.PubMedCrossRefGoogle Scholar
  59. Pecknold, J. C., and Ban, T. A., 1977, TRH in depressive illness, Int. Pharmacopsychiatry 12:166.PubMedGoogle Scholar
  60. Prange, A. J., Jr., 1971, Therapeutic and theoretical implications of imipramine-hormone interactions in depressive disorders, in: Proceedings of the V World Congress of Psychiatry, Ex-cerpta Medica, Amsterdam.Google Scholar
  61. Prange, A. J., Jr., and Loosen, P. T., 1981, Findings in affective disorders relevant to the thyroid axis, melanotropin, oxytocin, and vasopressin, Psychoneuroendocrinology Symposium, Hamilton, Ontario.Google Scholar
  62. Prange, A. J., Jr., and Wilson, I. C., 1972, Thyrotropin releasing hormone (TRH) for the immediate relief of depression: A preliminary report, Psychopharmacologia 26:82.Google Scholar
  63. Prange, A. J., Jr., Wilson, I. C., Rabon, A. M., and Lipton, M. A., 1969, Enhancement of imi-pramine antidepressant activity by thyroid hormone, Am. J. Psychiatry 126:457.PubMedGoogle Scholar
  64. Prange, A. J., Jr., Wilson, I. C., Knox, A., McClane, T. K., and Lipton, M. A., 1970, Enhancement of imipramine by thyroid stimulating hormone: Clinical and theoretical implications, Am. J. Psychiatry 127:191.PubMedGoogle Scholar
  65. Prange, A. J., Jr., Wilson, I. C., Lara, P. P., Alltop, L. B., and Breese, G. R., 1972, Effects of thyrotropin releasing hormone in depression, Lancet II:999.CrossRefGoogle Scholar
  66. Prange, A. J., Jr., Wilson, I. C., Breese, G. R., and Lipton, M. A., 1976, Hormonal alteration of imipramine response: A review, in: Hormones, Behavior, and Psychopathology (E. J. Sachar, ed.), pp. 41–67, Raven Press, New York.Google Scholar
  67. Prange, A. J., Jr., Loosen, P. T., and Nemeroff, C. B., 1979, Peptides: Application to research in nervous and mental disorders, in: New Frontiers of Psychotropic Drug Research (S. Fielding, ed.), pp. 117–189, Futura Publishing Co., Mt. Kisko, N.Y.Google Scholar
  68. Re, R. N., Kourides, I. A., Ridgway, E. C., Weintraub, B. D., and Maloof, F., 1976, The effect of glucocorticoid administration on human pituitary secretion of thyrotropin and prolactin, J. Clin. Endocrinol. Metab. 43:338.CrossRefGoogle Scholar
  69. Ruiz Ruiz, M., Zardon Perez, J. M., and Brotat Ester, M., 1980, Investigacion controlada con T.R.H. en las afecciones depresivas [Controlled investigation with TRH in depression], in: Progresos en Psicofarmacologia, Vol. 2 (M. Ruiz Ruiz, ed.), pp. 25–34, Bepya, Barcelona.Google Scholar
  70. Sacher, E. J., Halbreich, U., Asnis, G., Nathan, S., and Halpern, F. S., 1980, Neuroendocrine disturbance in depression, in: Progress in Psychoneuroendocrinology (F. Brambilla, G. Racagni, and D. de Wied, eds.), pp. 265–272, Elsevier/North-Holland, New York.Google Scholar
  71. Sorensen, R., Svendsen, K., and Schou, M., 1974, T.R.H. in depression, Lancet II:865.CrossRefGoogle Scholar
  72. Sugarman, A. A., Mueller, P. S., Swartzburg, M., and Rochford, J., 1975, Abbott-38579 (synthetic TRH) in the treatment of depression: A controlled study of oral administration, Psychophar-macol. Bull. 11:30.Google Scholar
  73. Takahashi, S., Kondo, H., Yoshimura, M., and Ochi, Y., 1973, Antidepressant effect ofthyro-tropin-releasing hormone (TRH) and the plasma thyrotropin levels in depression, Folia Psy-chiatr. Neurol. Jpn. 27:305.Google Scholar
  74. Takahashi, S., Kondo, H., Yoshimura, M., and Ochi, Y., 1974, Thyrotropin responses to TRH in depressive illness: Relation to clinical subtypes and prolonged duration of depressive episode, Folia Psychiatr. Neurol. Jpn. 28:355.PubMedGoogle Scholar
  75. Tsutsui, S., Yamazaki, Y., Namba, T., and Tsushima, M., 1979, Combined therapy of T3 and antidepressants in depression, J. Int. Med. Res. 7:138.PubMedGoogle Scholar
  76. Turek, I. S., and Rocha, J., 1974, Oral thyrotropin-releasing hormone (TRH) in depressive illness, J. Clin. Pharmacol. 14:612.PubMedGoogle Scholar
  77. Van den Burg, W., van Praag, H. M., Bos, E. R. H., Piers, D. A., van Zanten, A. K., and Doorenbos, H., 1975, Thyrotropin-releasing hormone (TRH) as a possible quick-acting but short-lasting antidepressant, Psychol. Med. 5:404.PubMedCrossRefGoogle Scholar
  78. Van den Burg, W., van Praag, H. M., Bos, E. R. H., Piers, D. A., van Zanten, A. K., and Doorenbos, H., 1976, TRH by slow, continuous infusion: An antidepressant?, Psychol. Med. 6:393.PubMedCrossRefGoogle Scholar
  79. Van der Vis-Melsen, M. J. E., and Wiener, J. D., 1972, Improvement in mental depression with decreased thyrotropin response after administration of thyrotropin-releasing hormone, Lancet II:1415.CrossRefGoogle Scholar
  80. Verebey, K., Volavka, J., and Clouet, D., 1978, Endorphins in psychiatry: An overview and a hypothesis, Arch. Gen. Psychiatry 35:877.PubMedCrossRefGoogle Scholar
  81. Vogel, H. P., Benkert, O., Illig, R., Mueller-Oerlinghausen, B., and Poppenberg, A., 1977, Psy-choendocrinological and therapeutic effects of TRH in depression, Acta Psychiatr. Scand. 56:223.PubMedCrossRefGoogle Scholar
  82. Wheatley, D., 1972, Potentiation of amitriplyline by thyroid hormone, Arch. Gen. Psychiatry 26:229.PubMedCrossRefGoogle Scholar
  83. Whybrow, P. C., Coppen, A., Prange, A. J., Jr., Noguera, R., and Bailey, J. E., 1972, Thyroid function and the response to liothyronine in depression, Arch. Gen. Psychiatry 26:242.PubMedCrossRefGoogle Scholar
  84. Widerlov, E., and Sjostrom, R., 1975, Effects of thyrotropin releasing hormone on endogenous depression, Nord Psykiatr. Tidsskr. 29:503.CrossRefGoogle Scholar
  85. Wilbur, J. G., 1979, Human pituitary thyrotropin, in: Endocrinology, Vol. 1 (L. J. DeGroot and G. H. Cahill, Jr., eds.), Grune & Stratton, New York.Google Scholar
  86. Wilson, I. C., Prange, A. J., Jr., McClane, T. K., Rabon, A. M., and Lipton, M. A., 1970, Thyroid-hormone enhancement of imipramine in nonretarded depressions, N. Engl. J. Med. 282:1063.PubMedCrossRefGoogle Scholar
  87. Wilson, I. C., Prange, A. J., Jr., and Lara, P. P., 1974, Methyltestosterone with imipramine in men: Conversion of depression to paranoid reaction, Am. J. Psychiatry 131:21.PubMedGoogle Scholar
  88. Ziegler, L. H., and Le vine, B. S., 1925. The influence of emotional reactions on basal metabolism, Am. J. Med. Sci. 169:68.CrossRefGoogle Scholar

Copyright information

© Plenum Publishing Corporation 1984

Authors and Affiliations

  • Arthur J. PrangeJr.
    • 1
  • Peter T. Loosen
    • 2
  1. 1.Department of Psychiatry, Biological Sciences Research CenterUniversity of North Carolina at Chapel Hill, School of MedicineChapel HillUSA
  2. 2.Clinical Research UnitDorothea Dix HospitalRaleighUSA

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