Skip to main content
SpringerLink
Log in
Book cover

Neuropsychiatric Disorders pp 17–32Cite as

Thyroid–Brain Interactions in Neuropsychiatric Disorders

  • Chapter

  • 1478 Accesses

Abstract

Thyroid hormones are important for the development and maturation of the brain as well as for the functioning of the mature brain. Most thyroid hormone-responsive genes are sensitive to thyroid hormones only during distinct periods of brain development, but some are also sensitive in the mature brain. A variety of factors influence the effects of thyroid hormones in the brain: availability of iodine; thyroid diseases and dysfunction; genetic variations that affect thyroid axis-related proteins, such as deiodinases, thyroid hormone transporters, and receptors; and timing of events. Interaction of these factors contributes to the development of the brain as well as to presentation of psychiatric symptoms and disorders in the mature brain. Clinical and subclinical thyroid dysfunction, thyroid autoimmunity, as well as individual genetic variations and mutations of thyroid axis-related proteins, may contribute not only to the presentation of psychiatric symptoms and disorders but also to response to psychiatric treatments. Better understanding of genomic and nongenomic mechanisms related to thyroid hormone metabolism in the brain opens new venues for finding new markers, new targets, and new agents for the treatment of mental disorders.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  1. Bunevicius R (2009) Thyroid disorders in mental patients. Curr Opin Psychiatry 22:391–395

    Article  PubMed  Google Scholar 

  2. Weetman AP (2004) Autoimmune thyroid disease. Autoimmunity 37:337–340

    Article  PubMed  CAS  Google Scholar 

  3. Pedersen IB, Knudsen N, Jorgensen T et al (2003) Thyroid peroxidase and thyroglobulin autoantibodies in a large survey of populations with mild and moderate iodine deficiency. Clin Endocrinol (Oxf) 58:36–42

    Article  Google Scholar 

  4. Peeters RP, van der Deure WM et al (2006) Genetic variation in thyroid hormone pathway genes; polymorphisms in the TSH receptor and the iodothyronine deiodinases. Eur J Endocrinol 155:655–662

    Article  PubMed  CAS  Google Scholar 

  5. Williams GR (2008) Neurodevelopmental and neurophysiological actions of thyroid hormone. J Neuroendocrinol 20:784–794

    Article  PubMed  CAS  Google Scholar 

  6. Suzuki T, Abe T (2008) Thyroid hormone transporters in the brain. Cerebellum 7:75–83

    Article  PubMed  CAS  Google Scholar 

  7. Yen PM (2005) Genomic and nongenomic actions of thyroid hormones. In: Braverman LE, Utiger RD (eds) Warner and Ingbar’s the thyroid: a fundamental and clinical text, 9th edn. Lippincott Williams & Wilkins, Philadelphia

    Google Scholar 

  8. Lifschytz T, Segman R, Shalom G et al (2006) Basic mechanisms of augmentation of antidepressant effects with thyroid hormone. Curr Drug Targets 7:203–210

    Article  PubMed  CAS  Google Scholar 

  9. Refetoff S, Dumitrescu AM (2007) Syndromes of reduced sensitivity to thyroid hormone: genetic defects in hormone receptors, cell transporters and deiodination. Best Pract Res Clin Endocrinol Metab 21:277–305

    Article  PubMed  CAS  Google Scholar 

  10. Hauser P, Zametkin AJ, Martinez P et al (1993) Attention deficit-hyperactivity disorder in people with generalized resistance to thyroid hormone. N Engl J Med 328:997–1001

    Article  PubMed  CAS  Google Scholar 

  11. de Escobar GM, Obregon MJ (2004) del Rey FE (2004) Maternal thyroid hormones early in pregnancy and fetal brain development. Best Pract Res Clin Endocrinol Metab 18:225–248

    Article  PubMed  Google Scholar 

  12. Bernal J, Guadano-Ferraz A, Morte B (2003) Perspectives in the study of thyroid hormone action on brain development and function. Thyroid 13:1005–1012

    Article  PubMed  CAS  Google Scholar 

  13. Zoeller RT, Rovet J (2004) Timing of thyroid hormone action in the developing brain: clinical observations and experimental findings. J Neuroendocrinol 16:809–818

    Article  PubMed  CAS  Google Scholar 

  14. Guo TW, Zhang FC, Yang MS et al (2004) Positive association of the DIO2 (deiodinase type 2) gene with mental retardation in the iodine-deficient areas of China. J Med Genet 2004(41):585–590

    Article  Google Scholar 

  15. Haddow JE, Palomaki GE, Allan WC et al (1999) Maternal thyroid deficiency during pregnancy and subsequent neuropsychological development of the child. N Engl J Med 341:549–555

    Article  PubMed  CAS  Google Scholar 

  16. Pop VJ, Brouwers EP, Vader HL et al (2003) Maternal hypothyroxinaemia during early pregnancy and subsequent child development: a 3-year follow-up study. Clin Endocrinol (Oxf) 59:280–281

    Article  Google Scholar 

  17. de Escobar GM, Obregón MJ, del Rey FE (2007) Iodine deficiency and brain development in the first half of pregnancy. Public Health Nutr 10:1554–1570

    Article  PubMed  Google Scholar 

  18. Bunevicius R, Kusminskas L, Mickuviene N et al (2009) Depressive disorder and thyroid axis functioning during pregnancy. World J Biol Psychiatry 10(4):324–329

    Article  PubMed  Google Scholar 

  19. Zhang L, Hernandez VS, Medina-Pizarro M et al (2008) Maternal hyperthyroidism in rats impairs stress coping of adult offspring. Neurosci Res 86:1306–1315

    Article  CAS  Google Scholar 

  20. Visser WE, Friesema EC, Jansen J et al (2008) Thyroid hormone transport in and out of cells. Trends Endocrinol Metab 19:50–56

    Article  PubMed  CAS  Google Scholar 

  21. Haggerty JJ Jr, Prange AJ Jr (1995) Borderline hypothyroidism and depression. Annu Rev Med 46:37–46

    Article  PubMed  CAS  Google Scholar 

  22. Bauer M, Goetz T, Glenn T et al (2008) The thyroid–brain interaction in thyroid disorders and mood disorders. J Neuroendocrinol 20:1101–1114

    Article  PubMed  CAS  Google Scholar 

  23. Tan ZS, Beiser A, Vasan RS et al (2008) Thyroid function and the risk of Alzheimer disease: the Framingham study. Arch Intern Med 168:1514–1520

    Article  PubMed  CAS  Google Scholar 

  24. Saravanan P, Chau WF, Roberts N et al (2002) Psychological well-being in patients on ‘adequate’ doses of l-thyroxine: results of a large, controlled community-based questionnaire study. Clin Endocrinol (Oxf) 57:577–585

    Article  CAS  Google Scholar 

  25. Panicker V, Saravanan P, Vaidya B et al (2009) Common variation in the DIO2 gene predicts baseline psychological well-being and response to combination thyroxine plus triiodothyronine therapy in hypothyroid patients. J Clin Endocrinol Metab 94:1623–1629

    Article  PubMed  CAS  Google Scholar 

  26. van der Deure WM, Appelhof BC, Peeters RP et al (2008) Polymorphisms in the brain-specific thyroid hormone transporter OATP1C1 are associated with fatigue and depression in hypothyroid patients. Clin Endocrinol (Oxf) 69:804–811

    Article  Google Scholar 

  27. Bunevicius R, Kazanavicius G, Zalinkevicius R et al (1999) Effects of thyroxine as compared with thyroxine plus triiodothyronine in patients with hypothyroidism. N Engl J Med 340:424–429

    Article  PubMed  CAS  Google Scholar 

  28. Escobar-Morreale HF, Botella-Carretero JI, Escobar del Rey F et al (2005) Review: Treatment of hypothyroidism with combinations of levothyroxine plus liothyronine. J Clin Endocrinol Metab 90:4946–4954

    Article  PubMed  CAS  Google Scholar 

  29. Appelhof BC, Peeters RP, Wiersinga WM et al (2005) Polymorphisms in type 2 deiodinase are not associated with wellbeing, neurocognitive functioning and preference for combined T4/T3 therapy. J Clin Endocrinol Metab 90:6296–6299

    Article  PubMed  CAS  Google Scholar 

  30. Mason GA, Bondy SC, Nemeroff CB et al (1987) The effects of thyroid state on beta-adrenergic and serotonergic receptors in rat brain. Psychoneuroendocrinology 12:261–270

    Article  PubMed  CAS  Google Scholar 

  31. Grabe HJ, Volzke H, Ludemann J et al (2005) Mental and physical complaints in thyroid disorders in the general population. Acta Psychiatr Scand 112:286–293

    Article  PubMed  CAS  Google Scholar 

  32. Samuels MH, Schuff KG, Carlson NE et al (2008) Health status, mood, and cognition in experimentally induced subclinical thyrotoxicosis. J Clin Endocrinol Metab 93:1730–1736

    Article  PubMed  CAS  Google Scholar 

  33. Bunevicius R, Velickiene D, Prange AJ Jr (2005) Mood and anxiety disorders in women with treated hyperthyroidism and ophthalmopathy caused by Graves’ disease. Gen Hosp Psychiatry 27:133–139

    Article  PubMed  Google Scholar 

  34. Trzepacz PT, McCue M, Klein I et al (1988) Psychiatric and neuropsychological response to propranolol in Graves’ disease. Biol Psychiatry 23:678–688

    Article  PubMed  CAS  Google Scholar 

  35. Bunevicius R, Prange AJ Jr (2006) Psychiatric manifestations of Graves’ hyperthyroidism: pathophysiology and treatment options. CNS Drugs 20:897–909

    Article  PubMed  Google Scholar 

  36. Bunevicius R (2009) Low triiodothyronine syndrome and depression in patients with chronic heart failure. In: Iervasi G, Pingitore A (eds) Thyroid and heart failure: from pathophysiology to clinics. Springer, Milan

    Google Scholar 

  37. Mafrica F, Fodale V (2008) Thyroid function, Alzheimer’s disease and postoperative cognitive dysfunction: a tale of dangerous liaisons? J Alzheimers Dis 14:95–105

    PubMed  CAS  Google Scholar 

  38. Premachandra BN, Kabir MA, Williams IK (2006) Low T3 syndrome in psychiatric depression. J Endocrinol Invest 29:568–572

    PubMed  CAS  Google Scholar 

  39. Yazici K, Yazici AE, Taneli B (2002) Different neuroendocrine profiles of remitted and nonremitted schizophrenic patients. Prog Neuropsychopharmacol Biol Psychiatry 26:579–584

    Article  PubMed  CAS  Google Scholar 

  40. Engum A, Bjoro T, Mykletun A et al (2002) An association between depression, anxiety and thyroid function: a clinical fact or an artefact? Acta Psychiatr Scand 106:27–34

    Article  PubMed  CAS  Google Scholar 

  41. Bunevicius R, Peceliuniene J, Mickuviene N et al (2007) Mood and thyroid immunity assessed by ultrasonographic imaging in a primary health care. J Affect Disord 97:85–90

    Article  PubMed  Google Scholar 

  42. Pop VJ, Wijnen HA, Lapkiene L et al (2006) The relation between gestational thyroid parameters and depression: a reflection of the downregulation of the immune system during pregnancy? Thyroid 16:485–492

    Article  PubMed  Google Scholar 

  43. Bunevicius R, Lasas L, Kazanavicius G et al (1996) Pituitary responses to thyrotropin releasing hormone stimulation in depressed women with thyroid gland disorders. Psychoneuroendo­crinology 21:631–639

    Article  PubMed  CAS  Google Scholar 

  44. Zettinig G, Asenbaum S, Fueger BJ et al (2003) Increased prevalence of subclinical brain perfusion abnormalities in patients with autoimmune thyroiditis: evidence of Hashimoto’s encephalitis? Clin Endocrinol (Oxf) 59:637–643

    Article  Google Scholar 

  45. Chong JY, Rowland LP, Utiger RD (2003) Hashimoto encephalopathy: syndrome or myth? Arch Neurol 60:164–171

    Article  PubMed  Google Scholar 

  46. Kirkegaard C, Faber J (1991) Free thyroxine and 3, 3’, 5’-triiodothyronine levels in cerebrospinal fluid in patients with endogenous depression. Acta Endocrinol (Copenh) 124:166–172

    CAS  Google Scholar 

  47. Baumgartner A (2000) Thyroxine and the treatment of affective disorders: an overview of the results of basic and clinical research. Int J Neuropsychopharmacol 3:149–165

    Article  PubMed  CAS  Google Scholar 

  48. DeLisi LE, Boccio AM, Riordan H et al (1991) Familial thyroid disease and delayed language development in first admission patients with schizophrenia. Psychiatry Res 38:39–50

    Article  PubMed  CAS  Google Scholar 

  49. Philibert RA, Sandhu HK, Hutton AM et al (2001) Population-based association analyses of the HOPA12bp polymorphism for schizophrenia and hypothyroidism. Am J Med Genet 105:130–134

    Article  PubMed  CAS  Google Scholar 

  50. Baumgartner A, Pietzcker A, Gaebel W (2000) The hypothalamic-pituitary-thyroid axis in patients with schizophrenia. Schizophr Res 44:233–243

    Article  PubMed  CAS  Google Scholar 

  51. Jick H, Kaye JA, Jick SS (2004) Antidepressants and the risk of suicidal behaviors. JAMA 292:338–343

    Article  PubMed  CAS  Google Scholar 

  52. Altshuler LL, Bauer M, Frye MA et al (2001) Does thyroid supplementation accelerate tricyclic antidepressant response? A review and meta-analysis of the literature. Am J Psychiatry 158:1617–1622

    Article  PubMed  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  54. Papakostas GI, Cooper-Kazaz R, Appelhof BC et al (2009) Simultaneous initiation (coinitiation) of pharmacotherapy with triiodothyronine and a selective serotonin reuptake inhibitor for major depressive disorder: a quantitative synthesis of double-blind studies. Int Clin Psychopharmacol 24:19–25

    Article  PubMed  Google Scholar 

  55. Cooper-Kazaz R, van der Deure WM, Medici M et al (2009) Preliminary evidence that a functional polymorphism in type 1 deiodinase is associated with enhanced potentiation of the antidepressant effect of sertraline by triiodothyronine. J Affect Disord 116:113–116

    Article  PubMed  CAS  Google Scholar 

  56. Iosifescu DV, Bolo NR, Nierenberg AA et al (2008) Brain bioenergetics and response to triiodothyronine augmentation in major depressive disorder. Biol Psychiatry 63:1127–1134

    Article  PubMed  CAS  Google Scholar 

  57. Joffe RT, Singer W (1990) A comparison of triiodothyronine and thyroxine in the potentiation of tricyclic antidepressants. Psychiatry Res 32:241–251

    Article  PubMed  CAS  Google Scholar 

  58. Gary KA, Sevarino KA, Yarbrough GG et al (2003) The thyrotropin-releasing hormone (TRH) hypothesis of homeostatic regulation: Implications for TRH-based therapeutics. J Pharmacol Exp Ther 305:410–416

    Article  PubMed  CAS  Google Scholar 

  59. Kamath J, Yarbrough GG, Prange AJ Jr et al (2009) The thyrotropin-releasing hormone (TRH)-immune system homeostatic hypothesis. Pharmacol Ther 121:20–28

    Article  PubMed  CAS  Google Scholar 

  60. Yarbrough GG, Kamath J, Winokur A et al (2007) Thyrotropin-releasing hormone (TRH) in the neuroaxis: therapeutic effects reflect physiological functions and molecular actions. Med Hypotheses 69:1249–1256

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors thank the Hope for Depression Research Foundation (HDRF) and the Institute of the Study of Affective Neuroscience (ISAN) for research support.

Author information

Authors and Affiliations

  1. Institute of Psychophysiology and Rehabilitation, Kaunas University of Medicine, Vyduno 4, 00135, Palanga, Lithuaniae

    Robertas Bunevičius

  2. Department of Psychiatry, University of North Carolina at Chapel Hill, Campus Box #7160, Chapel Hill, NC, 27599-7160, USA

    Arthur J. Prange Jr

Authors
  1. Robertas Bunevičius
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Arthur J. Prange Jr
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Robertas Bunevičius .

Editor information

Editors and Affiliations

  1. Jinmeikai Research Institute for Mental Health, 53-20 Kabutoyama-cho, Nishinomiya, Hyogo, 662-0001, Japan

    Koho Miyoshi M.D., Ph.D. (Director, The former Professor) & Yasushi Morimura M.D., Ph.D. (Chief Executive Officer) (Director, The former Professor) &  (Chief Executive Officer)

  2. Ohmura Hospital, 200 Kitayama-Ohmura, Miki, Hyogo, 673-0404, Japan

    Koho Miyoshi M.D., Ph.D. (Director, The former Professor) (Director, The former Professor)

  3. Department of Occupational Therapy, Kobe Gakuin University School of Rehabilitation, 518 Ikawadani-cho, Nishi-ku, Kobe, 651-2180, Japan

    Kiyoshi Maeda M.D., Ph.D. (Professor) (Professor)

Rights and permissions

Reprints and permissions

Copyright information

© 2010 Springer

About this chapter

Cite this chapter

Bunevičius, R., Prange, A.J. (2010). Thyroid–Brain Interactions in Neuropsychiatric Disorders. In: Miyoshi, K., Morimura, Y., Maeda, K. (eds) Neuropsychiatric Disorders. Springer, Tokyo. https://doi.org/10.1007/978-4-431-53871-4_2

Download citation

  • DOI: https://doi.org/10.1007/978-4-431-53871-4_2

  • Publisher Name: Springer, Tokyo

  • Print ISBN: 978-4-431-53870-7

  • Online ISBN: 978-4-431-53871-4

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation