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The link between schizophrenia and hypothyroidism: a population-based study


Schizophrenia is considered to be of the severe psychiatric disorders characterized by chronic debilitating course marked with frequent relapses and high clinical and financial burden. Aberrations of thyroid hormone levels have been documented in several psychiatric conditions including bipolar disease. The aim of this study is to provide insight into whether an association exists between hypothyroidism and schizophrenia. A population-based cross-sectional study was conducted using data retrieved from the largest medical records database in Israel, the Clalit Health Services (CHS). Patients were defined as having hypothyroidism or schizophrenia when there was at least one such documented diagnosis in their medical records. The proportion of schizophrenia was compared between hypothyroid and age- and sex frequency-matched healthy controls. A logistic regression model was used to estimate the association between psychiatric manifestations and hypothyroidism in a multivariate analysis adjusted for age, gender, and smoking status. The study included 40,843 patients with hypothyroidism and 40,918 age- and sex frequency-matched controls. The proportion of schizophrenia in hypothyroid patients was higher than that in controls (2.01% vs. 1.25%, respectively, p < 0.0001). Multivariate logistic regression demonstrated a robust independent association between hypothyroidism and schizophrenia (OR 1.62, p ≤ 0.001). Our study confirms a higher proportion of hypothyroidism among patients with schizophrenia. The awareness of such interrelation should drive physicians treating patients with schizophrenia to consider screening for hypothyroidism. Further studies are required to elucidate the underlying mechanism or the common denominator favoring the co-occurrence of schizophrenia and hypothyroidism.

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  1. Mullur R, Liu Y-Y, Brent GA. Thyroid hormone regulation of metabolism. Physiol Rev. 2014;94(2):355–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Chung HR. Iodine and thyroid function. Ann Pediatr Endocrinol Metab. 2014;19(1):8–12.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Zaletel K, Gaberšček S. Hashimoto’s thyroiditis: from genes to the disease. Curr Genomics. 2011;12(8):576–88.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Liontiris MI, Mazokopakis EE. A concise review of Hashimoto thyroiditis (HT) and the importance of iodine, selenium, vitamin D and gluten on the autoimmunity and dietary management of HT patients. Points that need more investigation. Hell J Nucl Med. 2017;20(1):51–6.

    PubMed  Google Scholar 

  5. Doyle L. Myxoedema: some early reports and contributions by British authors, 1873-1898. J R Soc Med. 1991;84(2):103–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. van Os J, Kapur S. Schizophrenia. Lancet. 2009;374(9690):635–45.

    Article  CAS  PubMed  Google Scholar 

  7. Santos NC, Costa P, Ruano D, Macedo A, Soares MJ, Valente J, et al. Revisiting thyroid hormones in schizophrenia. J Thyroid Res. 2012;2012:569147.

  8. MacDonald AW, Schulz SC. What we know: findings that every theory of schizophrenia should explain. Schizophr Bull. 2009;35(3):493–508.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Watad A, Abu Much A, Bracco D, Mahroum N, Comaneshter D, Cohen AD, et al. Association between ischemic heart disease and systemic lupus erythematosus-a large case-control study. Immunol Res. 2017;65:459–63.

  10. Yavne Y, Tiosano S, Watad A, Comaneshter D, Cohen AD, Amital H. Investigating the link between ischemic heart disease and Behcet’s disease: a cross-sectional analysis. Int J Cardiol. 2017;241:41–5.

    Article  PubMed  Google Scholar 

  11. Watad A, Mahroum N, Whitby A, Gertel S, Comaneshter D, Cohen AD, et al. Hypothyroidism among SLE patients: case-control study. Autoimmun Rev. 2016;15(5):484–6.

  12. Watad A, Tiosano S, Yahav D, Comaneshter D, Shoenfeld Y, Cohen AD, et al. Behcet’s disease and familial Mediterranean fever: two sides of the same coin or just an association? A cross-sectional study. Eur J Intern Med. 2017;39:75–8.

  13. Sharif K, Watad A, Tiosano S, Yavne Y, Blokh Kerpel A, Comaneshter D, et al. The link between COPD and ankylosing spondylitis: A population based study. Eur J Intern Med. 2018;53:62–5.

  14. Telo S, Bilgic S, Karabulut N. Thyroid hormone levels in chronic schizophrenic patients: association with psychopathology. West Indian Med J 2016 Mar 15;65(2):312–315.

  15. Bou Khalil R, Richa S. Thyroid adverse effects of psychotropic drugs: a review. Clin Neuropharmacol. 2011;34(6):248–55.

    Article  CAS  PubMed  Google Scholar 

  16. Radhakrishnan R, Calvin S, Singh JK, Thomas B, Srinivasan K. Thyroid dysfunction in major psychiatric disorders in a hospital based sample. Indian J Med Res. 2013;138(6):888–93.

    PubMed  PubMed Central  Google Scholar 

  17. Poyraz BC, Aksoy C, Balcioglu I. Increased incidence of autoimmune thyroiditis in patients with antipsychotic-induced hyperprolactinemia. Eur Neuropsychopharmacol. 2008;18(9):667–72.

    Article  CAS  PubMed  Google Scholar 

  18. Benros ME, Nielsen PR, Nordentoft M, Eaton WW, Dalton SO, Mortensen PB. Autoimmune diseases and severe infections as risk factors for schizophrenia: a 30-year population-based register study. Am J Psychiatry. 2011;168(12):1303–10.

    Article  PubMed  Google Scholar 

  19. Jones AL, Mowry BJ, Pender MP, Greer JM. Immune dysregulation and self-reactivity in schizophrenia: do some cases of schizophrenia have an autoimmune basis? Immunol Cell Biol. 2005;83(1):9–17.

    Article  CAS  PubMed  Google Scholar 

  20. Müller N, Schwarz MJ. Immune system and schizophrenia. Curr Immunol Rev. 2010;6(3):213–20.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Burch PR. Schizophrenia: some new aetiological considerations. Br J Psychiatry J Ment Sci. 1964;110:818–24.

    Article  CAS  Google Scholar 

  22. Tiosano S, Farhi A, Watad A, Grysman N, Stryjer R, Amital H, et al. Schizophrenia among patients with systemic lupus erythematosus: population-based cross-sectional study. Epidemiol Psychiatr Sci. 2017;26(4):424–9.

  23. Wright P, Sham PC, Gilvarry CM, Jones PB, Cannon M, Sharma T, et al. Autoimmune diseases in the pedigrees of schizophrenic and control subjects. Schizophr Res. 1996;20(3):261–7.

    Article  CAS  PubMed  Google Scholar 

  24. Sasaki T, Matsushita M, Nanko S, Fukuda R, Kennedy JL, Tokunaga K. Schizophrenia and the HLA-DRB1 gene in the Japanese population. Am J Psychiatry. 1999;156(5):771–3.

    CAS  PubMed  Google Scholar 

  25. Grosskopf A, Muller N, Malo A, Wank R. Potential role for the narcolepsy- and multiple sclerosis-associated HLA allele DQB1*0602 in schizophrenia subtypes. Schizophr Res. 1998;30(2):187–9.

    Article  CAS  PubMed  Google Scholar 

  26. Borda T, Perez Rivera R, Joensen L, Gomez RM, Sterin-Borda L. Antibodies against cerebral M1 cholinergic muscarinic receptor from schizophrenic patients: molecular interaction. J Immunol. 2002;168(7):3667–74.

    Article  CAS  PubMed  Google Scholar 

  27. Mukherjee S, Mahadik SP, Korenovsky A, Laev H, Schnur DB, Reddy R. Serum antibodies to nicotinic acetylcholine receptors in schizophrenic patients. Schizophr Res. 1994;12(2):131–6.

    Article  CAS  PubMed  Google Scholar 

  28. Tanaka S, Matsunaga H, Kimura M, Tatsumi K, Hidaka Y, Takano T, et al. Autoantibodies against four kinds of neurotransmitter receptors in psychiatric disorders. J Neuroimmunol. 2003;141(1–2):155–64.

  29. Bergen JR, Grinspoon L, Pyle HM, Martinez JL Jr, Pennell RB. Immunologic studies in schizophrenic and control subjects. Biol Psychiatry. 1980;15(3):369–79.

    CAS  PubMed  Google Scholar 

  30. Heath RG, Krupp IM, Byers LW, Liljekvist JI. Schizophrenia as an immunologic disorder. II. Effects of serum protein fractions on brain function. Arch Gen Psychiatry. 1967;16(1):10–23.

    Article  CAS  PubMed  Google Scholar 

  31. Diamond B, Huerta PT, Mina-Osorio P, Kowal C, Volpe BT. Losing your nerves? Maybe it’s the antibodies. Nat Rev Immunol. 2009;9:449–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Zandi MS, Irani SR, Lang B, Waters P, Jones PB, McKenna P, et al. Disease-relevant autoantibodies in first episode schizophrenia. J Neurol. 2011;258(4):686–8.

  33. de Leon J, Diaz FJ. A meta-analysis of worldwide studies demonstrates an association between schizophrenia and tobacco smoking behaviors. Schizophr Res. 2005;76(2–3):135–57.

    Article  PubMed  Google Scholar 

  34. Cooper B. Social class and prognosis in schizophrenia. Part I. Br J Prev Soc Med. 1961;15(1):17–30.

    PubMed Central  Google Scholar 

  35. Werner S, Malaspina D, Rabinowitz J. Socioeconomic status at birth is associated with risk of schizophrenia: population-based multilevel study. Schizophr Bull. 2007;33(6):1373–8.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Tsui FWL, Tsui HW, Akram A, Haroon N, Inman RD. The genetic basis of ankylosing spondylitis: new insights into disease pathogenesis. Appl Clin Genet. 2014;7:105–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Correspondence to Howard Amital.

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The study was approved by the Ethical Committee of CHS, located at the Soroka Medical Center, Beer Sheva, Israel.

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The authors declare that they have no conflict of interest.

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Sharif, K., Tiosano, S., Watad, A. et al. The link between schizophrenia and hypothyroidism: a population-based study. Immunol Res 66, 663–667 (2018).

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  • Hypothyroidism
  • Schizophrenia
  • Autoimmunity
  • Thyroid dysfunction
  • Psychosis