Skip to main content
SpringerLink
Log in

Thyroid Hormones, Brain, and Heart

  • Chapter
  • First Online:
Thyroid and Heart

Abstract

Cerebrovascular disorders (CVDs) remain the leading cause of morbidity and mortality worldwide. Neuropsychiatric symptoms (such as depression and fatigue) and cognitive impairment are common complications in CVD patients which are associated with worse patient-centered health status, adverse clinical outcomes, and worse CVD prognosis. Impairment of normal functioning of the hypothalamic–pituitary–thyroid (HPT) axis (as in the low triiodothyronine syndrome) is also commonly observed in patients with CVDs and is linked to greater neuropsychiatric symptom severity, cognitive impairment, worse quality of life, and shorter survival. However, there are no studies examining whether treatment of subclinical HPT axis dysfunction can improve patient-centered health status of CVD patients. Further studies should attempt to elucidate if treatment of subclinical thyroid dysfunction could improve neuropsychiatric and cognitive symptom severity of CVD survivors and possibly translate into better patient-centered outcomes and longer survival. Evaluation of possible association between genetic polymorphisms of enzymes involved in thyroid hormone transport and metabolism with patient-centered health status could help to more accurately identify high-risk CVD patients and provide with personalized treatment approaches.

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

Access this chapter

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 69.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 89.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
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

Institutional subscriptions

References

  1. Faustino LC, Ortiga-Carvalho TM. Thyroid hormone role on cerebellar development and maintenance: a perspective based on transgenic mouse models. Front Endocrinol. 2014;5:75. https://doi.org/10.3389/fendo.2014.00075.

    Article  Google Scholar 

  2. Gothie JD, Demeneix B, Remaud S. Comparative approaches to understanding thyroid hormone regulation of neurogenesis. Mol Cell Endocrinol. 2017;459:104–15. https://doi.org/10.1016/j.mce.2017.05.020.

    Article  CAS  PubMed  Google Scholar 

  3. Ahmed OM, El-Gareib AW, El-Bakry AM, Abd El-Tawab SM, Ahmed RG. Thyroid hormones states and brain development interactions. Int J Dev Neurosci. 2008;26(2):147–209. https://doi.org/10.1016/j.ijdevneu.2007.09.011.

    Article  CAS  PubMed  Google Scholar 

  4. Kapoor R, Fanibunda SE, Desouza LA, Guha SK, Vaidya VA. Perspectives on thyroid hormone action in adult neurogenesis. J Neurochem. 2015;133(5):599–616. https://doi.org/10.1111/jnc.13093.

    Article  CAS  PubMed  Google Scholar 

  5. Bianco AC, Kim BW. Deiodinases: implications of the local control of thyroid hormone action. J Clin Invest. 2006;116(10):2571–9. https://doi.org/10.1172/jci29812.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Williams AJ, Robson H, Kester MHA, van Leeuwen J, Shalet SM, Visser TJ, et al. Iodothyronine deiodinase enzyme activities in bone. Bone. 2008;43(1):126–34. https://doi.org/10.1016/j.bone.2008.03.019.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Bianco AC, Salvatore D, Gereben B, Berry MJ, Larsen PR. Biochemistry, cellular and molecular biology, and physiological roles of the iodothyronine selenodeiodinases. Endocr Rev. 2002;23(1):38–89. https://doi.org/10.1210/edrv.23.1.0455.

    Article  CAS  PubMed  Google Scholar 

  8. Cheng SY, Leonard JL, Davis PJ. Molecular aspects of thyroid hormone actions. Endocr Rev. 2010;31(2):139–70. https://doi.org/10.1210/er.2009-0007.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Davis PJ, Goglia F, Leonard JL. Nongenomic actions of thyroid hormone. Nat Rev Endocrinol. 2016;12(2):111–21. https://doi.org/10.1038/nrendo.2015.205.

    Article  CAS  PubMed  Google Scholar 

  10. Brent GA. The molecular basis of thyroid hormone action. N Engl J Med. 1994;331(13):847–53. https://doi.org/10.1056/nejm199409293311306.

    Article  CAS  PubMed  Google Scholar 

  11. Bernal J, Guadano-Ferraz A, Morte B. Thyroid hormone transporters—functions and clinical implications. Nat Rev Endocrinol. 2015;11(7):406–17. https://doi.org/10.1038/nrendo.2015.66.

    Article  CAS  PubMed  Google Scholar 

  12. Novara F, Groeneweg S, Freri E, Estienne M, Reho P, Matricardi S, et al. Clinical and molecular characteristics of SLC16A2 (MCT8) mutations in three families with the Allan-Herndon-Dudley syndrome. Hum Mutat. 2017;38(3):260–4. https://doi.org/10.1002/humu.23140.

    Article  CAS  PubMed  Google Scholar 

  13. Panicker V, Cluett C, Shields B, Murray A, Parnell KS, Perry JR, et al. A common variation in deiodinase 1 gene DIO1 is associated with the relative levels of free thyroxine and triiodothyronine. J Clin Endocrinol Metab. 2008;93(8):3075–81. https://doi.org/10.1210/jc.2008-0397.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Dayan CM, Panicker V. Novel insights into thyroid hormones from the study of common genetic variation. Nat Rev Endocrinol. 2009;5(4):211–8. https://doi.org/10.1038/nrendo.2009.19.

    Article  CAS  PubMed  Google Scholar 

  15. Brozaitiene J, Skiriute D, Burkauskas J, Podlipskyte A, Jankauskiene E, Serretti A, et al. Deiodinases, organic anion transporter polypeptide polymorphisms, and thyroid hormones in patients with myocardial infarction. Genet Test Mol Biomarkers. 2018;22(4):270–8. https://doi.org/10.1089/gtmb.2017.0283.

    Article  CAS  PubMed  Google Scholar 

  16. Alkemade A. Thyroid hormone and the developing hypothalamus. Front Neuroanat. 2015;9:15. https://doi.org/10.3389/fnana.2015.00015.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Horn S, Heuer H. Thyroid hormone action during brain development: more questions than answers. Mol Cell Endocrinol. 2010;315(1–2):19–26. https://doi.org/10.1016/j.mce.2009.09.008.

    Article  CAS  PubMed  Google Scholar 

  18. Moog NK, Entringer S, Heim C, Wadhwa PD, Kathmann N, Buss C. Influence of maternal thyroid hormones during gestation on fetal brain development. Neuroscience. 2017;342:68–100. https://doi.org/10.1016/j.neuroscience.2015.09.070.

    Article  CAS  PubMed  Google Scholar 

  19. Endendijk JJ, Wijnen HAA, Pop VJM, van Baar AL. Maternal thyroid hormone trajectories during pregnancy and child behavioral problems. Horm Behav. 2017;94:84–92. https://doi.org/10.1016/j.yhbeh.2017.06.007.

    Article  CAS  PubMed  Google Scholar 

  20. Gilbert ME, Lasley SM. Developmental thyroid hormone insufficiency and brain development: a role for brain-derived neurotrophic factor (BDNF)? Neuroscience. 2013;239:253–70. https://doi.org/10.1016/j.neuroscience.2012.11.022.

    Article  CAS  PubMed  Google Scholar 

  21. Preau L, Fini JB, Morvan-Dubois G, Demeneix B. Thyroid hormone signaling during early neurogenesis and its significance as a vulnerable window for endocrine disruption. Biochim Biophys Acta. 2015;1849(2):112–21. https://doi.org/10.1016/j.bbagrm.2014.06.015.

    Article  CAS  PubMed  Google Scholar 

  22. Kapoor R, van Hogerlinden M, Wallis K, Ghosh H, Nordstrom K, Vennstrom B, et al. Unliganded thyroid hormone receptor alpha1 impairs adult hippocampal neurogenesis. FASEB J. 2010;24(12):4793–805. https://doi.org/10.1096/fj.10-161802.

    Article  CAS  PubMed  Google Scholar 

  23. Sanchez-Huerta K, Garcia-Martinez Y, Vergara P, Segovia J, Pacheco-Rosado J. Thyroid hormones are essential to preserve non-proliferative cells of adult neurogenesis of the dentate gyrus. Mol Cell Neurosci. 2016;76:1–10. https://doi.org/10.1016/j.mcn.2016.08.001.

    Article  CAS  PubMed  Google Scholar 

  24. Pilhatsch M, Marxen M, Winter C, Smolka MN, Bauer M. Hypothyroidism and mood disorders: integrating novel insights from brain imaging techniques. Thyroid Res. 2011;4(Suppl 1):S3. https://doi.org/10.1186/1756-6614-4-s1-s3.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Pasqualetti G, Caraccio N, Dell Agnello U, Monzani F. Cognitive function and the ageing process: the peculiar role of mild thyroid failure. Recent Pat Endocr Metab Immune Drug Discov. 2016;10(1):4–10.

    Article  CAS  PubMed  Google Scholar 

  26. Aubert CE, Bauer DC, da Costa BR, Feller M, Rieben C, Simonsick EM, et al. The association between subclinical thyroid dysfunction and dementia: the Health, Aging and Body Composition (Health ABC) study. Clin Endocrinol. 2017;87(5):617–26. https://doi.org/10.1111/cen.13458.

    Article  CAS  Google Scholar 

  27. Beydoun MA, Beydoun HA, Rostant OS, Dore GA, Fanelli-Kuczmarski MT, Evans MK, et al. Thyroid hormones are associated with longitudinal cognitive change in an urban adult population. Neurobiol Aging. 2015;36(11):3056–66. https://doi.org/10.1016/j.neurobiolaging.2015.08.002.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Bunevicius R, Varoneckas G, Prange AJ Jr, Hinderliter AL, Gintauskiene V, Girdler SS. Depression and thyroid axis function in coronary artery disease: impact of cardiac impairment and gender. Clin Cardiol. 2006;29(4):170–4.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Chatonnet F, Flamant F, Morte B. A temporary compendium of thyroid hormone target genes in brain. Biochim Biophys Acta. 2015;1849(2):122–9. https://doi.org/10.1016/j.bbagrm.2014.05.023.

    Article  CAS  PubMed  Google Scholar 

  30. Krausz Y, Freedman N, Lester H, Newman JP, Barkai G, Bocher M, et al. Regional cerebral blood flow in patients with mild hypothyroidism. J Nucl Med. 2004;45(10):1712–5.

    PubMed  Google Scholar 

  31. Li L, Zhi M, Hou Z, Zhang Y, Yue Y, Yuan Y. Abnormal brain functional connectivity leads to impaired mood and cognition in hyperthyroidism: a resting-state functional MRI study. Oncotarget. 2017;8(4):6283–94. https://doi.org/10.18632/oncotarget.14060.

    Article  PubMed  Google Scholar 

  32. Constant EL, de Volder AG, Ivanoiu A, Bol A, Labar D, Seghers A, et al. Cerebral blood flow and glucose metabolism in hypothyroidism: a positron emission tomography study. J Clin Endocrinol Metab. 2001;86(8):3864–70. https://doi.org/10.1210/jcem.86.8.7749.

    Article  CAS  PubMed  Google Scholar 

  33. Begin ME, Langlois MF, Lorrain D, Cunnane SC. Thyroid function and cognition during aging. Curr Gerontol Geriatr Res. 2008;2008:474868. https://doi.org/10.1155/2008/474868.

    Article  CAS  PubMed Central  Google Scholar 

  34. Szlejf C, Suemoto CK, Santos IS, Lotufo PA, Haueisen Sander Diniz MF, Barreto SM, et al. Thyrotropin level and cognitive performance: baseline results from the ELSA-Brasil study. Psychoneuroendocrinology. 2018;87:152–8. https://doi.org/10.1016/j.psyneuen.2017.10.017.

    Article  CAS  PubMed  Google Scholar 

  35. Brandt F, Thvilum M, Almind D, Christensen K, Green A, Hegedus L, et al. Hyperthyroidism and psychiatric morbidity: evidence from a Danish nationwide register study. Eur J Endocrinol. 2014;170(2):341–8. https://doi.org/10.1530/eje-13-0708.

    Article  CAS  PubMed  Google Scholar 

  36. Baek JH, Kang ES, Fava M, Mischoulon D, Nierenberg AA, Lee D, et al. Thyroid stimulating hormone and serum, plasma, and platelet brain-derived neurotrophic factor during a 3-month follow-up in patients with major depressive disorder. J Affect Disord. 2014;169:112–7. https://doi.org/10.1016/j.jad.2014.08.009.

    Article  CAS  PubMed  Google Scholar 

  37. Jia Y, Zhong S, Wang Y, Liu T, Liao X, Huang L. The correlation between biochemical abnormalities in frontal white matter, hippocampus and serum thyroid hormone levels in first-episode patients with major depressive disorder. J Affect Disord. 2015;180:162–9. https://doi.org/10.1016/j.jad.2015.04.005.

    Article  CAS  PubMed  Google Scholar 

  38. McAloon CJ, Boylan LM, Hamborg T, Stallard N, Osman F, Lim PB, et al. The changing face of cardiovascular disease 2000–2012: an analysis of the world health organisation global health estimates data. Int J Cardiol. 2016;224:256–64.

    Article  PubMed  Google Scholar 

  39. Roth GA, Johnson CO, Abate KH, Abd-Allah F, Ahmed M, Alam K, et al. The burden of cardiovascular diseases among US states, 1990-2016. JAMA Cardiol. 2018;3(5):375–89.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Nichols M, Townsend N, Luengo-Fernandez R, Leal J, Gray A, Scarborough P, Rayner M. European cardiovascular disease statistics 2012. Brussels/Sophia Antipolis: European Heart Network/European Society of Cardiology; 2012.

    Google Scholar 

  41. Wilkins E, Wilson L, Wickramasinghe K, Bhatnagar P, Leal J, Luengo-Fernandez R, Burns R, Rayner M, Townsend N. European cardiovascular disease statistics 2017. Brussels: European Heart Network; 2017.

    Google Scholar 

  42. Members ATF, Piepoli MF, Hoes AW, Agewall S, Albus C, Brotons C, et al. 2016 European guidelines on cardiovascular disease prevention in clinical practice: developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). Eur J Prev Cardiol. 2016;23(11):NP1–NP96.

    Article  Google Scholar 

  43. Montalescot G, Sechtem U, Achenbach S, Andreotti F, Arden C, Budaj A, et al. 2013 ESC guidelines on the management of stable coronary artery disease: the task force on the management of stable coronary artery disease of the European Society of Cardiology. Eur Heart J. 2013;34(38):2949–3003. https://doi.org/10.1093/eurheartj/eht296.

    Article  PubMed  Google Scholar 

  44. Suls J. Toxic affect: are anger, anxiety, and depression independent risk factors for cardiovascular disease? Emot Rev. 2018;10(1):6–17.

    Article  Google Scholar 

  45. Celano CM, Villegas AC, Albanese AM, Gaggin HK, Huffman JC. Depression and anxiety in heart failure: a review. Harv Rev Psychiatry. 2018;26(4):175–84. https://doi.org/10.1097/hrp.0000000000000162.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Huffman JC, Celano CM, Beach SR, Motiwala SR, Januzzi JL. Depression and cardiac disease: epidemiology, mechanisms, and diagnosis. Cardiovasc Psychiatry Neurol. 2013;2013:695925.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Rutledge T, Reis VA, Linke SE, Greenberg BH, Mills PJ. Depression in heart failure a meta-analytic review of prevalence, intervention effects, and associations with clinical outcomes. J Am Coll Cardiol. 2006;48(8):1527–37. https://doi.org/10.1016/j.jacc.2006.06.055.

    Article  PubMed  Google Scholar 

  48. Moser DK, Dracup K, Evangelista LS, Zambroski CH, Lennie TA, Chung ML, et al. Comparison of prevalence of symptoms of depression, anxiety, and hostility in elderly patients with heart failure, myocardial infarction, and a coronary artery bypass graft. Heart Lung. 2010;39(5):378–85. https://doi.org/10.1016/j.hrtlng.2009.10.017.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Bunevicius A, Staniute M, Brozaitiene J, Pop VJ, Neverauskas J, Bunevicius R. Screening for anxiety disorders in patients with coronary artery disease. Health Qual Life Outcomes. 2013;11:37. https://doi.org/10.1186/1477-7525-11-37.

    Article  PubMed  PubMed Central  Google Scholar 

  50. van Montfort E, Denollet J, Vermunt JK, Widdershoven J, Kupper N. The tense, the hostile and the distressed: multidimensional psychosocial risk profiles based on the ESC interview in coronary artery disease patients—the THORESCI study. Gen Hosp Psychiatry. 2017;47:103–11. https://doi.org/10.1016/j.genhosppsych.2017.05.006.

    Article  PubMed  Google Scholar 

  51. Riegel B, Moser DK, Buck HG, Dickson VV, Dunbar SB, Lee CS, et al. Self-care for the prevention and management of cardiovascular disease and stroke: a scientific statement for healthcare professionals from the American Heart Association. J Am Heart Assoc. 2017;6(9):e006997.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Lichtman JH, Bigger JT Jr, Blumenthal JA, Frasure-Smith N, Kaufmann PG, Lespérance F, et al. Depression and coronary heart disease: recommendations for screening, referral, and treatment: a science advisory from the American Heart Association Prevention Committee of the Council on Cardiovascular Nursing, Council on Clinical Cardiology, Council on Epidemiology and Prevention, and Interdisciplinary Council on Quality of Care and Outcomes Research: endorsed by the American Psychiatric Association. Circulation. 2008;118(17):1768–75.

    Article  PubMed  Google Scholar 

  53. Thombs BD, Ziegelstein RC, Whooley MA. Optimizing detection of major depression among patients with coronary artery disease using the patient health questionnaire: data from the heart and soul study. J Gen Intern Med. 2008;23(12):2014–7.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Bunevicius A, Deltuva V, Tamasauskas S, Tamasauskas A, Bunevicius R. Screening for psychological distress in neurosurgical brain tumor patients using the patient health questionnaire-2. Psychooncology. 2013;22(8):1895–900. https://doi.org/10.1002/pon.3237.

    Article  PubMed  Google Scholar 

  55. Albus C, Jordan J, Herrmann-Lingen C. Screening for psychosocial risk factors in patients with coronary heart disease-recommendations for clinical practice. Eur J Cardiovasc Prev Rehabil. 2004;11(1):75–9.

    Article  PubMed  Google Scholar 

  56. Pedersen SS, von Känel R, Tully PJ, Denollet J. Psychosocial perspectives in cardiovascular disease. Eur J Prev Cardiol. 2017;24(3_suppl):108–15.

    Article  PubMed  Google Scholar 

  57. Jackson AC, Le Grande MR, Higgins RO, Rogerson M, Murphy BM. Psychosocial screening and assessment practice within cardiac rehabilitation: a survey of cardiac rehabilitation coordinators in Australia. Heart Lung Circ. 2017;26(1):64–72. https://doi.org/10.1016/j.hlc.2016.04.018.

    Article  PubMed  Google Scholar 

  58. Kroenke K, Spitzer RL, Williams JB. The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med. 2001;16(9):606–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Beck AT, Steer RA, Brown GK. BDI-II, Beck depression inventory: manual. San Antonio: Psychological Corp; 1996.

    Google Scholar 

  60. Zung WK. A self-rating depression scale. Arch Gen Psychiatry. 1965;12(1):63–70. https://doi.org/10.1001/archpsyc.1965.01720310065008.

    Article  CAS  PubMed  Google Scholar 

  61. Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand. 1983;67(6):361–70.

    Article  CAS  PubMed  Google Scholar 

  62. Spitzer RL, Kroenke K, Williams JB, Lowe B. A brief measure for assessing generalized anxiety disorder: the GAD-7. Arch Intern Med. 2006;166(10):1092–7. https://doi.org/10.1001/archinte.166.10.1092.

    Article  PubMed  Google Scholar 

  63. Spielberger CD, Gorsuch RL, Lushene R, Vagg PR, Jacobs GA. Manual for the state-trait anxiety inventory. Palo Alto: Consulting Psychologist Press; 1983.

    Google Scholar 

  64. Liguori I, Russo G, Curcio F, Sasso G, Della-Morte D, Gargiulo G, et al. Depression and chronic heart failure in the elderly: an intriguing relationship. J Geriatr Cardiol. 2018;15(6):451.

    PubMed  PubMed Central  Google Scholar 

  65. Haring B, Leng X, Robinson J, Johnson KC, Jackson RD, Beyth R, et al. Cardiovascular disease and cognitive decline in postmenopausal women: results from the Women’s Health Initiative memory study. J Am Heart Assoc. 2013;2(6):e000369. https://doi.org/10.1161/jaha.113.000369.

    Article  PubMed  PubMed Central  Google Scholar 

  66. Folstein MF, Folstein SE, McHugh PR. “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975;12(3):189–98.

    Article  CAS  PubMed  Google Scholar 

  67. Spreen O, Benton AL. Neurosensory center comprehensive examination for aphasia (NCCEA), 1977 revision: manual of instructions. Victoria: Neuropsychology Laboratory, University of Victoria; 1977.

    Google Scholar 

  68. Strauss E, Sherman E, Spreen O. A compendium of neuropsychological tests: administration, norms, and commentary. New York: Oxford University Press; 2006.

    Google Scholar 

  69. Benton AL, Hamsher KD, Sivan AB. Multilingual aphasia examination: manual of instructions. AJA Association: Iowa City; 1994.

    Google Scholar 

  70. Brandt J. The Hopkins verbal learning test: development of a new memory test with six equivalent forms. Clin Neuropsychol. 1991;5(2):125–42.

    Article  Google Scholar 

  71. WAIS-III. Wechsler Adult Intelligence Scale; WMS-III: Weschler memory scale: technical manual. 3rd ed. San Antonio: The Psychological Corporation; 1997.

    Google Scholar 

  72. Cummings JL, Mega M, Gray K, Rosenberg-Thompson S, Carusi DA, Gornbein J. The neuropsychiatric inventory: comprehensive assessment of psychopathology in dementia. Neurology. 1994;44(12):2308.

    Article  CAS  PubMed  Google Scholar 

  73. Baker DW, Brown J, Chan KS, Dracup KA, Keeler EB. A telephone survey to measure communication, education, self-management, and health status for patients with heart failure: the improving chronic illness care evaluation (ICICE). J Card Fail. 2005;11(1):36–42.

    Article  PubMed  Google Scholar 

  74. Friedman MM, King KB. Correlates of fatigue in older women with heart failure. Heart Lung. 1995;24(6):512–8.

    Article  CAS  PubMed  Google Scholar 

  75. Oka RK, Stotts NA, Dae MW, Haskell WL, Gortner SR. Daily physical activity levels in congestive heart failure. Am J Cardiol. 1993;71(11):921–5.

    Article  CAS  PubMed  Google Scholar 

  76. Schaefer KM, Shober Potylycki MJ. Fatigue associated with congestive heart failure: use of Levine’s conservation model. J Adv Nurs. 1993;18(2):260–8.

    Article  CAS  PubMed  Google Scholar 

  77. McNair DM, Heuchert JP. Profile of mood states, POMS2. North Tonawanda: Educational and Industrial Testing System, Multi-Health Systems; 2012.

    Google Scholar 

  78. Smets EM, Garssen B, Bonke B, De Haes JC. The multidimensional fatigue inventory (MFI) psychometric qualities of an instrument to assess fatigue. J Psychosom Res. 1995;39(3):315–25.

    Article  CAS  PubMed  Google Scholar 

  79. Wang Y, Liu G, Gao X, Zhao Z, Li L, Chen W, et al. Prognostic value of type D personality for in-stent restenosis in coronary artery disease patients treated with drug-eluting stent. Psychosom Med. 2018;80(1):95–102. https://doi.org/10.1097/psy.0000000000000532.

    Article  PubMed  Google Scholar 

  80. Condén E, Rosenblad A, Wagner P, Leppert J, Ekselius L, Åslund C. Is type D personality an independent risk factor for recurrent myocardial infarction or all-cause mortality in post-acute myocardial infarction patients? Eur J Prev Cardiol. 2017;24(5):522–33.

    Article  PubMed  Google Scholar 

  81. Denollet J. DS14: standard assessment of negative affectivity, social inhibition, and type D personality. Psychosom Med. 2005;67(1):89–97.

    Article  PubMed  Google Scholar 

  82. Staniute M, Brozaitiene J, Burkauskas J, Kazukauskiene N, Mickuviene N, Bunevicius R. Type D personality, mental distress, social support and health-related quality of life in coronary artery disease patients with heart failure: a longitudinal observational study. Health Qual Life Outcomes. 2015;13(1):1. https://doi.org/10.1186/s12955-014-0204-2.

    Article  PubMed  PubMed Central  Google Scholar 

  83. Gremigni P, Sommaruga M. Type D personality, a relevant construct in cardiology. Preliminary validation study of the Italian questionnaire. Psicot Cogn Comport. 2005;11:7–18.

    Google Scholar 

  84. Williams L, O’Connor RC, Howard S, Hughes BM, Johnston DW, Hay JL, et al. Type-D personality mechanisms of effect: the role of health-related behavior and social support. J Psychosom Res. 2008;64(1):63–9.

    Article  PubMed  Google Scholar 

  85. Bunevicius A, Staniute M, Brozaitiene J, Stropute D, Bunevicius R, Denollet J. Type D (distressed) personality and its assessment with the DS14 in Lithuanian patients with coronary artery disease. J Health Psychol. 2013;18(9):1242–51. https://doi.org/10.1177/1359105312459098.

    Article  PubMed  Google Scholar 

  86. Spielberger CD, Jacobs GA, Russell S, Crane RS. Assessment of anger: the state-trait anger scale. Advances in personality assessment. Hillsdale: Lawrence Erlbaum Associates; 1983.

    Google Scholar 

  87. Cook WW, Medley DM. Proposed hostility and pharisaic-virtue scales for the MMPI. J Appl Psychol. 1954;38(6):414–8. https://doi.org/10.1037/h0060667.

    Article  Google Scholar 

  88. Enhancing recovery in coronary heart disease patients (ENRICHD): study design and methods. The ENRICHD investigators. Am Heart J. 2000;139(1 Pt 1):1–9.

    Google Scholar 

  89. Zimet GD, Dahlem NW, Zimet SG, Farley GK. The multidimensional scale of perceived social support. J Pers Assess. 1988;52(1):30–41. https://doi.org/10.1207/s15327752jpa5201_2.

    Article  Google Scholar 

  90. Hagström E, Norlund F, Stebbins A, Armstrong P, Chiswell K, Granger C, et al. Psychosocial stress and major cardiovascular events in patients with stable coronary heart disease. J Intern Med. 2018;283(1):83–92.

    Article  PubMed  Google Scholar 

  91. Karasek R, Brisson C, Kawakami N, Houtman I, Bongers P, Amick B. The job content questionnaire (JCQ): an instrument for internationally comparative assessments of psychosocial job characteristics. J Occup Health Psychol. 1998;3(4):322–55. https://doi.org/10.1037/1076-8998.3.4.322.

    Article  CAS  PubMed  Google Scholar 

  92. Siegrist J, Starke D, Chandola T, Godin I, Marmot M, Niedhammer I, et al. The measurement of effort–reward imbalance at work: European comparisons. Soc Sci Med. 2004;58(8):1483–99. https://doi.org/10.1016/S0277-9536(03)00351-4.

    Article  PubMed  Google Scholar 

  93. Denollet J, van Felius RA, Lodder P, Mommersteeg PM, Goovaerts I, Possemiers N, et al. Predictive value of type D personality for impaired endothelial function in patients with coronary artery disease. Int J Cardiol. 2018;259:205–10.

    Article  PubMed  Google Scholar 

  94. Wang Y, Zhao Z, Gao X, Li L, Liu G, Chen W, et al. Type D personality and coronary plaque vulnerability in patients with coronary artery Disease: an optical coherence tomography study. Psychosom Med. 2016;78(5):583–92. https://doi.org/10.1097/psy.0000000000000307.

    Article  PubMed  Google Scholar 

  95. Jackson AC, Ski CF, Murphy BM, Fernandez E, Alvarenga ME, Le Grande MR, et al. What role does personality play in cardiovascular disease? Br J Card Nurs. 2018;13(7):330–7.

    Article  Google Scholar 

  96. Busch LY, Pössel P, Valentine JC. Meta-analyses of cardiovascular reactivity to rumination: a possible mechanism linking depression and hostility to cardiovascular disease. Psychol Bull. 2017;143(12):1378.

    Article  PubMed  Google Scholar 

  97. Kupper N, Denollet J. Type D personality as a risk factor in coronary heart Disease: a review of current evidence. Curr Cardiol Rep. 2018;20(11):104.

    Article  PubMed  PubMed Central  Google Scholar 

  98. Pedersen SS, Denollet J. Is type D personality here to stay? Emerging evidence across cardiovascular disease patient groups. Curr Cardiol Rev. 2006;2(3):205–13.

    Article  Google Scholar 

  99. Eckhardt AL, Devon HA, Piano MR, Ryan CJ, Zerwic JJ. Fatigue in the presence of coronary heart disease. Nurs Res. 2014;63(2):83–93. https://doi.org/10.1097/NNR.0000000000000019.

  100. Ter Hoeve N, Sunamura M, Stam HJ, van Domburg RT, van den Berg-Emons RJ. Extended cardiac rehabilitation improves aerobic capacity and fatigue: a randomized controlled trial. Optim Card Rehabil. 2018:189.

    Google Scholar 

  101. Staniute M, Bunevicius A, Brozaitiene J, Bunevicius R. Relationship of health-related quality of life with fatigue and exercise capacity in patients with coronary artery disease. Eur J Cardiovasc Nurs. 2014;13(4):338–44. https://doi.org/10.1177/1474515113496942.

    Article  PubMed  Google Scholar 

  102. Irvine J, Basinski A, Baker B, Jandciu S, Paquette M, Cairns J, et al. Depression and risk of sudden cardiac death after acute myocardial infarction: testing for the confounding effects of fatigue. Psychosom Med. 1999;61(6):729–37.

    Article  CAS  PubMed  Google Scholar 

  103. Bunevicius A, Brozaitiene J, Stankus A, Bunevicius R. Specific fatigue-related items in self-rating depression scales do not bias an association between depression and fatigue in patients with coronary artery disease. Gen Hosp Psychiatry. 2011;33(5):527–9. https://doi.org/10.1016/j.genhosppsych.2011.06.009.

    Article  PubMed  Google Scholar 

  104. Shavelle RM, Paculdo DR, Strauss DJ, Kush SJ. Cognitive impairment and mortality in the Cardiovascular Health Study. J Insur Med. 2009;41(2):110–6.

    PubMed  Google Scholar 

  105. Fried LP, Kronmal RA, Newman AB, Bild DE, Mittelmark MB, Polak JF, et al. Risk factors for 5-year mortality in older adults: the cardiovascular health study. JAMA. 1998;279(8):585–92.

    Article  CAS  PubMed  Google Scholar 

  106. Freiheit EA, Hogan DB, Eliasziw M, Patten SB, Demchuk AM, Faris P, et al. A dynamic view of depressive symptoms and neurocognitive change among patients with coronary artery disease. Arch Gen Psychiatry. 2012;69(3):244–55. https://doi.org/10.1001/archgenpsychiatry.2011.1361.

    Article  PubMed  Google Scholar 

  107. Satizabal C, Beiser AS, Seshadri S. Incidence of dementia over three decades in the Framingham heart study. N Engl J Med. 2016;375(1):93–4. https://doi.org/10.1056/NEJMc1604823.

    Article  PubMed  PubMed Central  Google Scholar 

  108. Duijndam S, Denollet J, Nyklicek I, Kupper N. Perceived cognition after percutaneous coronary intervention: association with quality of life, mood and fatigue in the THORESCI study. Int J Behav Med. 2017;24(4):552–62. https://doi.org/10.1007/s12529-016-9624-1.

    Article  PubMed  Google Scholar 

  109. Burkauskas J, Brozaitiene J, Kazukauskiene N, Fineberg NA, Mickuviene NP. Cognitive functioning and health-related quality of life in coronary artery disease patients with heart failure: a longitudinal observational study. Eur Neuropsychopharmacol. 2016;26:S339. https://doi.org/10.1016/S0924-977X(16)31262-7.

    Article  Google Scholar 

  110. Hachinski V, Iadecola C, Petersen RC, Breteler MM, Nyenhuis DL, Black SE, et al. National Institute of Neurological Disorders and Stroke–Canadian stroke network vascular cognitive impairment harmonization standards. Stroke. 2006;37(9):2220–41.

    Article  PubMed  Google Scholar 

  111. Burkauskas J, Noreikaite A, Bunevicius A, Brozaitiene J, Neverauskas J, Mickuviene N, et al. Beta-1-selective beta-blockers and cognitive functions in patients with coronary artery disease: a cross-sectional study. J Neuropsychiatry Clin Neurosci. 2015;28(2):143–6. https://doi.org/10.1176/appi.neuropsych.15040088.

    Article  PubMed  Google Scholar 

  112. Lanctot KL, O’Regan J, Schwartz Y, Swardfager W, Saleem M, Oh PI, et al. Assessing cognitive effects of anticholinergic medications in patients with coronary artery disease. Psychosomatics. 2014;55(1):61–8. https://doi.org/10.1016/j.psym.2013.04.004.

    Article  PubMed  Google Scholar 

  113. Burkauskas J, Lang P, Bunevicius A, Neverauskas J, Buciute-Jankauskiene M, Mickuviene N. Cognitive function in patients with coronary artery disease: a literature review. J Int Med Res. 2018;46(10):4019–31. https://doi.org/10.1177/0300060517751452.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Valenza G, Toschi N, Barbieri R. Uncovering brain-heart information through advanced signal and image processing. Philos Transact A Math Phys Eng Sci. 2016;374(2067). https://doi.org/10.1098/rsta.2016.0020.

  115. Kim MS, Kim JJ. Heart and brain interconnection—clinical implications of changes in brain function during heart failure. Circ J. 2015;79(5):942–7. https://doi.org/10.1253/circj.CJ-15-0360.

    Article  PubMed  Google Scholar 

  116. Woo MA, Kumar R, Macey PM, Fonarow GC, Harper RM. Brain injury in autonomic, emotional, and cognitive regulatory areas in patients with heart failure. J Card Fail. 2009;15(3):214–23. https://doi.org/10.1016/j.cardfail.2008.10.020.

    Article  PubMed  Google Scholar 

  117. Dublin S, Anderson ML, Heckbert SR, Hubbard RA, Sonnen JA, Crane PK, et al. Neuropathologic changes associated with atrial fibrillation in a population-based autopsy cohort. J Gerontol Ser A Biol Sci Med Sci. 2014;69(5):609–15. https://doi.org/10.1093/gerona/glt141.

    Article  Google Scholar 

  118. Meissner A. Hypertension and the brain: a risk factor for more than heart disease. Cerebrovasc Dis. 2016;42(3–4):255–62. https://doi.org/10.1159/000446082.

    Article  PubMed  Google Scholar 

  119. Roy B, Woo MA, Wang DJJ, Fonarow GC, Harper RM, Kumar R. Reduced regional cerebral blood flow in patients with heart failure. Eur J Heart Fail. 2017;19(10):1294–302. https://doi.org/10.1002/ejhf.874.

    Article  PubMed  Google Scholar 

  120. von Rhein M, Buchmann A, Hagmann C, Huber R, Klaver P, Knirsch W, et al. Brain volumes predict neurodevelopment in adolescents after surgery for congenital heart disease. Brain J Neurol. 2014;137(Pt 1):268–76. https://doi.org/10.1093/brain/awt322.

    Article  Google Scholar 

  121. Ogren JA, Fonarow GC, Woo MA. Cerebral impairment in heart failure. Curr Heart Fail Rep. 2014;11(3):321–9. https://doi.org/10.1007/s11897-014-0211-y.

    Article  PubMed  Google Scholar 

  122. Pan A, Kumar R, Macey PM, Fonarow GC, Harper RM, Woo MA. Visual assessment of brain magnetic resonance imaging detects injury to cognitive regulatory sites in patients with heart failure. J Card Fail. 2013;19(2):94–100. https://doi.org/10.1016/j.cardfail.2012.12.001.

    Article  PubMed  PubMed Central  Google Scholar 

  123. Kumar R, Nguyen HD, Ogren JA, Macey PM, Thompson PM, Fonarow GC, et al. Global and regional putamen volume loss in patients with heart failure. Eur J Heart Fail. 2011;13(6):651–5. https://doi.org/10.1093/eurjhf/hfr012.

    Article  PubMed  PubMed Central  Google Scholar 

  124. Alosco ML, Brickman AM, Spitznagel MB, Garcia SL, Narkhede A, Griffith EY, et al. Cerebral perfusion is associated with white matter hyperintensities in older adults with heart failure. Congest Heart Fail. 2013;19(4):E29–34. https://doi.org/10.1111/chf.12025.

    Article  PubMed  PubMed Central  Google Scholar 

  125. Alosco ML, Brickman AM, Spitznagel MB, Griffith EY, Narkhede A, Raz N, et al. Independent and interactive effects of blood pressure and cardiac function on brain volume and white matter hyperintensities in heart failure. J Am Soc Hypertens. 2013;7(5):336–43. https://doi.org/10.1016/j.jash.2013.04.011.

    Article  PubMed  PubMed Central  Google Scholar 

  126. Woo MA, Ogren JA, Abouzeid CM, Macey PM, Sairafian KG, Saharan PS, et al. Regional hippocampal damage in heart failure. Eur J Heart Fail. 2015;17(5):494–500. https://doi.org/10.1002/ejhf.241.

    Article  PubMed  Google Scholar 

  127. Menteer J, Macey PM, Woo MA, Panigrahy A, Harper RM. Central nervous system changes in pediatric heart failure: a volumetric study. Pediatr Cardiol. 2010;31(7):969–76. https://doi.org/10.1007/s00246-010-9730-9.

    Article  PubMed  PubMed Central  Google Scholar 

  128. Park B, Roy B, Woo MA, Palomares JA, Fonarow GC, Harper RM, et al. Lateralized resting-state functional brain network organization changes in heart failure. PLoS One. 2016;11(5):e0155894. https://doi.org/10.1371/journal.pone.0155894.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Bernard C, Catheline G, Dilharreguy B, Couffinhal T, Ledure S, Lassalle-Lagadec S, et al. Cerebral changes and cognitive impairment after an ischemic heart disease: a multimodal MRI study. Brain Imaging Behav. 2016;10(3):893–900. https://doi.org/10.1007/s11682-015-9483-4.

    Article  PubMed  Google Scholar 

  130. Harper RM, Kumar R, Macey PM, Woo MA, Ogren JA. Affective brain areas and sleep-disordered breathing. Prog Brain Res. 2014;209:275–93. https://doi.org/10.1016/b978-0-444-63274-6.00014-x.

    Article  PubMed  PubMed Central  Google Scholar 

  131. Tummala S, Palomares J, Kang DW, Park B, Woo MA, Harper RM, et al. Global and regional brain non-Gaussian diffusion changes in newly diagnosed patients with obstructive sleep apnea. Sleep. 2016;39(1):51–7. https://doi.org/10.5665/sleep.5316.

    Article  PubMed  PubMed Central  Google Scholar 

  132. Bernal J. Thyroid hormones in brain development and function. In: De Groot LJ, Chrousos G, Dungan K, Feingold KR, Grossman A, Hershman JM, et al., editors. Endotext. South Dartmouth: MDText.com; 2000.

    Google Scholar 

  133. Ritchie M, Yeap BB. Thyroid hormone: influences on mood and cognition in adults. Maturitas. 2015;81(2):266–75. https://doi.org/10.1016/j.maturitas.2015.03.016.

    Article  CAS  PubMed  Google Scholar 

  134. Villar HCCE, Saconato H, Valente O, Atallah ÁN. Thyroid hormone replacement for subclinical hypothyroidism. Cochrane Database Syst Rev. 2007;(3):CD003419.

    Google Scholar 

  135. Samuels MH. Psychiatric and cognitive manifestations of hypothyroidism. Curr Opin Endocrinol Diabetes Obes. 2014;21(5):377–83. https://doi.org/10.1097/med.0000000000000089.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Pasqualetti G, Pagano G, Rengo G, Ferrara N, Monzani F. Subclinical Hypothyroidism and cognitive impairment: systematic review and meta-analysis. J Clin Endocrinol Metabol. 2015;100(11):4240–8. https://doi.org/10.1210/jc.2015-2046.

    Article  CAS  Google Scholar 

  137. Akintola A, Jansen S, van Bodegom D, van der Grond J, Westendorp R, de Craen A, et al. Subclinical hypothyroidism and cognitive function in people over 60 years: a systematic review and meta-analysis. Front Aging Neurosci. 2015;7:150. https://doi.org/10.3389/fnagi.2015.00150.

    Article  PubMed  PubMed Central  Google Scholar 

  138. Cooper DS, Biondi B. Subclinical thyroid disease. Lancet. 2012;379(9821):1142–54. https://doi.org/10.1016/S0140-6736(11)60276-6.

    Article  PubMed  Google Scholar 

  139. Chaker L, Baumgartner C, Den Elzen WP, Ikram MA, Blum MR, Collet T-H, et al. Subclinical hypothyroidism and the risk of stroke events and fatal stroke: an individual participant data analysis. J Clin Endocrinol Metabol. 2015;100(6):2181–91.

    Article  CAS  Google Scholar 

  140. Pasqualetti G, Tognini S, Polini A, Caraccio N, Monzani F. Is subclinical hypothyroidism a cardiovascular risk factor in the elderly? J Clin Endocrinol Metab. 2013;98(6):2256–66. https://doi.org/10.1210/jc.2012-3818.

    Article  CAS  PubMed  Google Scholar 

  141. Surks MI, Hollowell JG. Age-specific distribution of serum thyrotropin and antithyroid antibodies in the U.S. population: implications for the prevalence of subclinical hypothyroidism. J Clin Endocrinol Metabol. 2007;92(12):4575–82. https://doi.org/10.1210/jc.2007-1499.

    Article  CAS  Google Scholar 

  142. Ross DS. Serum thyroid-stimulating hormone measurement for assessment of thyroid function and disease. Endocrinol Metab Clin North Am. 2001;30(2):245–64, vii.

    Article  CAS  PubMed  Google Scholar 

  143. Pearce EN. Subclinical hyperthyroidism with serum TSH< 0.1 mIU/L is associated with increased dementia risk in older adults. Clin Thyroidol. 2017;29(10):382–4.

    Article  Google Scholar 

  144. Collet TH, Gussekloo J, Bauer DC, den Elzen WP, Cappola AR, Balmer P, et al. Subclinical hyperthyroidism and the risk of coronary heart disease and mortality. Arch Intern Med. 2012;172(10):799–809. https://doi.org/10.1001/archinternmed.2012.402.

    Article  CAS  PubMed  Google Scholar 

  145. Selmer C, Olesen JB, Hansen ML, Lindhardsen J, Olsen AM, Madsen JC, et al. The spectrum of thyroid disease and risk of new onset atrial fibrillation: a large population cohort study. BMJ. 2012;345:e7895. https://doi.org/10.1136/bmj.e7895.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  146. Gencer B, Collet TH, Virgini V, Bauer DC, Gussekloo J, Cappola AR, et al. Subclinical thyroid dysfunction and the risk of heart failure events: an individual participant data analysis from 6 prospective cohorts. Circulation. 2012;126(9):1040–9. https://doi.org/10.1161/circulationaha.112.096024.

    Article  CAS  PubMed  Google Scholar 

  147. Nishtala A, Piers RJ, Himali JJ, Beiser AS, Davis-Plourde KL, Saczynski JS, et al. Atrial fibrillation and cognitive decline in the Framingham heart study. Heart Rhythm. 2018;15(2):166–72.

    Article  PubMed  Google Scholar 

  148. Lutski M, Weinstein G, Goldbourt U, Tanne D. Cardiovascular health and cognitive decline 2 decades later in men with preexisting coronary artery disease. Am J Cardiol. 2018;121(4):410–5.

    Article  PubMed  Google Scholar 

  149. Ottens TH, Hendrikse J, Nathoe HM, Biessels GJ, van Dijk D. Brain volume and cognitive function in patients with revascularized coronary artery disease. Int J Cardiol. 2017;230:80–4. https://doi.org/10.1016/j.ijcard.2016.12.079.

    Article  PubMed  Google Scholar 

  150. Myserlis PG, Malli A, Kalaitzoglou DK, Kalaitzidis G, Miligkos M, Kokkinidis DG, et al. Atrial fibrillation and cognitive function in patients with heart failure: a systematic review and meta-analysis. Heart Fail Rev. 2017;22(1):1–11.

    Article  PubMed  Google Scholar 

  151. Yudiarto FL, Muliadi L, Moeljanto D, Hartono B. Neuropsychological findings in hyperthyroid patients. Acta Med Indones. 2006;38(1):6–10.

    PubMed  Google Scholar 

  152. Yuan L, Tian Y, Zhang F, Ma H, Chen X, Dai F, et al. Decision-making in patients with hyperthyroidism: a neuropsychological study. PLoS One. 2015;10(6):e0129773. https://doi.org/10.1371/journal.pone.0129773.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Samuels MH. Cognitive function in untreated hypothyroidism and hyperthyroidism. Curr Opin Endocrinol Diabetes Obes. 2008;15(5):429–33. https://doi.org/10.1097/MED.0b013e32830eb84c.

    Article  PubMed  Google Scholar 

  154. Vogel A, Elberling TV, Hording M, Dock J, Rasmussen AK, Feldt-Rasmussen U, et al. Affective symptoms and cognitive functions in the acute phase of Graves’ thyrotoxicosis. Psychoneuroendocrinology. 2007;32(1):36–43. https://doi.org/10.1016/j.psyneuen.2006.09.012.

    Article  PubMed  Google Scholar 

  155. Lillevang-Johansen M, Petersen I, Christensen K, Hegedüs L, Brix TH. Is previous hyperthyroidism associated with long-term cognitive dysfunction? A twin study. Clin Endocrinol. 2014;80(2):290–5.

    Article  Google Scholar 

  156. Constant EL, Adam S, Seron X, Bruyer R, Seghers A, Daumerie C. Anxiety and depression, attention, and executive functions in hypothyroidism. J Int Neuropsychol Soc. 2005;11(5):535–44. https://doi.org/10.1017/s1355617705050642.

    Article  CAS  PubMed  Google Scholar 

  157. Davis JD, Tremont G. Neuropsychiatric aspects of hypothyroidism and treatment reversibility. Minerva Endocrinol. 2007;32(1):49–65.

    CAS  PubMed  Google Scholar 

  158. Osterweil D, Syndulko K, Cohen SN, Pettler-Jennings PD, Hershman JM, Cummings JL, et al. Cognitive function in non-demented older adults with hypothyroidism. J Am Geriatr Soc. 1992;40(4):325–35.

    Article  CAS  PubMed  Google Scholar 

  159. Smith CD, Grondin R, LeMaster W, Martin B, Gold BT, Ain KB. Reversible cognitive, motor, and driving impairments in severe hypothyroidism. Thyroid. 2015;25(1):28–36.

    Article  CAS  PubMed  Google Scholar 

  160. Correia N, Mullally S, Cooke G, Tun TK, Phelan N, Feeney J, et al. Evidence for a specific defect in hippocampal memory in overt and subclinical hypothyroidism. J Clin Endocrinol Metab. 2009;94(10):3789–97. https://doi.org/10.1210/jc.2008-2702.

    Article  CAS  PubMed  Google Scholar 

  161. Miller KJ, Parsons TD, Whybrow PC, Van Herle K, Rasgon N, Van Herle A, et al. Verbal memory retrieval deficits associated with untreated hypothyroidism. J Neuropsychiatry Clin Neurosci. 2007;19(2):132–6. https://doi.org/10.1176/jnp.2007.19.2.132.

    Article  PubMed  Google Scholar 

  162. Burmeister LA, Ganguli M, Dodge HH, Toczek T, Dekosky ST, Nebes RD. Hypothyroidism and cognition: preliminary evidence for a specific defect in memory. Thyroid. 2001;11(12):1177–85.

    Article  CAS  PubMed  Google Scholar 

  163. Cooke GE, Mullally S, Correia N, O'Mara SM, Gibney J. Hippocampal volume is decreased in adults with hypothyroidism. Thyroid. 2014;24(3):433–40. https://doi.org/10.1089/thy.2013.0058.

    Article  CAS  PubMed  Google Scholar 

  164. He XS, Ma N, Pan ZL, Wang ZX, Li N, Zhang XC, et al. Functional magnetic resource imaging assessment of altered brain function in hypothyroidism during working memory processing. Eur J Endocrinol. 2011;164(6):951–9. https://doi.org/10.1530/eje-11-0046.

    Article  CAS  PubMed  Google Scholar 

  165. Miller KJ, Parsons TD, Whybrow PC, van Herle K, Rasgon N, van Herle A, et al. Memory improvement with treatment of hypothyroidism. Int J Neurosci. 2006;116(8):895–906. https://doi.org/10.1080/00207450600550154.

    Article  CAS  PubMed  Google Scholar 

  166. Goyal S, Dixit A, Vaney N, Madhu S. Cognitive status in hypothyroid patients before & after attainment of euthyroid state. Indian J Physiol Pharmacol. 2018;62(1):113–9.

    CAS  Google Scholar 

  167. Capet C, Jego A, Denis P, Noel D, Clerc I, Cornier AC, et al. [Is cognitive change related to hypothyroidism reversible with replacement therapy?]. La Revue de medecine interne. 2000;21(8):672–8.

    Google Scholar 

  168. Prinz PN, Scanlan JM, Vitaliano PP, Moe KE, Borson S, Toivola B, et al. Thyroid hormones: positive relationships with cognition in healthy, euthyroid older men. J Gerontol A Biol Sci Med Sci. 1999;54(3):M111–6.

    Article  CAS  PubMed  Google Scholar 

  169. Beydoun MA, Beydoun HA, Kitner-Triolo MH, Kaufman JS, Evans MK, Zonderman AB. Thyroid hormones are associated with cognitive function: moderation by sex, race, and depressive symptoms. J Clin Endocrinol Metab. 2013;98(8):3470–81. https://doi.org/10.1210/jc.2013-1813.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  170. Hogervorst E, Huppert F, Matthews FE, Brayne C. Thyroid function and cognitive decline in the MRC cognitive function and ageing study. Psychoneuroendocrinology. 2008;33(7):1013–22. https://doi.org/10.1016/j.psyneuen.2008.05.008.

    Article  CAS  PubMed  Google Scholar 

  171. Grigorova M, Sherwin BB. Thyroid hormones and cognitive functioning in healthy, euthyroid women: a correlational study. Horm Behav. 2012;61(4):617–22. https://doi.org/10.1016/j.yhbeh.2012.02.014.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  172. Bojar I, Bejga P, Witczak M, Łyszcz R, Makara-Studzinska M. Standards for thyroid laboratory testing, and cognitive functions after menopause. Prz Menopauzalny. 2014;13(4):233–41. https://doi.org/10.5114/pm.2014.44999.

    Article  PubMed  PubMed Central  Google Scholar 

  173. Burkauskas J, Bunevicius A, Brozaitiene J, Neverauskas J, Lang P, Duwors R, et al. Cognitive functioning in coronary artery disease patients: associations with thyroid hormones, N-terminal pro-B-type natriuretic peptide and high-sensitivity C-reactive protein. Arch Clin Neuropsychol. 2017;32(2):245–51. https://doi.org/10.1093/arclin/acx004.

    Article  PubMed  Google Scholar 

  174. Shabani S, Sarkaki A, Ali Mard S, Ahangarpour A, Khorsandi L, Farbood Y. Central and peripheral administrations of levothyroxine improved memory performance and amplified brain electrical activity in the rat model of Alzheimer’s disease. Neuropeptides. 2016;59:111–6. https://doi.org/10.1016/j.npep.2016.09.003.

    Article  CAS  PubMed  Google Scholar 

  175. Ma J, Yang X, Yin H, Wang Y, Chen H, Liu C, et al. Effect of thyroid hormone replacement therapy on cognition in long-term survivors of aneurysmal subarachnoid hemorrhage. Exp Ther Med. 2015;10(1):369–73. https://doi.org/10.3892/etm.2015.2475.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  176. Bauer M, Silverman DH, Schlagenhauf F, London ED, Geist CL, van Herle K, et al. Brain glucose metabolism in hypothyroidism: a positron emission tomography study before and after thyroid hormone replacement therapy. J Clin Endocrinol Metab. 2009;94(8):2922–9. https://doi.org/10.1210/jc.2008-2235.

    Article  CAS  PubMed  Google Scholar 

  177. Sangun O, Demirci S, Dundar N, Pirgon O, Koca T, Dogan M, et al. The effects of six-month L-thyroxine treatment on cognitive functions and event-related brain potentials in children with subclinical hypothyroidism. J Clin Res Pediatr Endocrinol. 2015;7(2):102–8. https://doi.org/10.4274/jcrpe.1684.

    Article  PubMed  PubMed Central  Google Scholar 

  178. Kim EY, Kim SH, Rhee SJ, Huh I, Ha K, Kim J, et al. Relationship between thyroid-stimulating hormone levels and risk of depression among the general population with normal free T4 levels. Psychoneuroendocrinology. 2015;58:114–9. https://doi.org/10.1016/j.psyneuen.2015.04.016.

    Article  CAS  PubMed  Google Scholar 

  179. Duntas LH, Maillis A. Hypothyroidism and depression: salient aspects of pathogenesis and management. Minerva Endocrinol. 2013;38(4):365–77.

    CAS  PubMed  Google Scholar 

  180. Berent D, Zboralski K, Orzechowska A, Galecki P. Thyroid hormones association with depression severity and clinical outcome in patients with major depressive disorder. Mol Biol Rep. 2014;41(4):2419–25. https://doi.org/10.1007/s11033-014-3097-6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  181. Brouwer JP, Appelhof BC, Hoogendijk WJ, Huyser J, Endert E, Zuketto C, et al. Thyroid and adrenal axis in major depression: a controlled study in outpatients. Eur J Endocrinol. 2005;152(2):185–91. https://doi.org/10.1530/eje.1.01828.

    Article  CAS  PubMed  Google Scholar 

  182. Wei J, Sun G, Zhao L, Liu X, Lin D, Li T, et al. Hair thyroid hormones concentration in patients with depression changes with disease episodes in female Chinese. Psychiatry Res. 2014;220(1–2):251–3. https://doi.org/10.1016/j.psychres.2014.07.029.

    Article  CAS  PubMed  Google Scholar 

  183. Pae CU, Mandelli L, Han C, Ham BJ, Masand PS, Patkar AA, et al. Thyroid hormones affect recovery from depression during antidepressant treatment. Psychiatry Clin Neurosci. 2009;63(3):305–13. https://doi.org/10.1111/j.1440-1819.2009.01938.x.

    Article  CAS  PubMed  Google Scholar 

  184. Pan T, Zhong M, Zhong X, Zhang Y, Zhu D. Levothyroxine replacement therapy with vitamin E supplementation prevents oxidative stress and cognitive deficit in experimental hypothyroidism. Endocrine. 2013;43(2):434–9. https://doi.org/10.1007/s12020-012-9801-1.

    Article  CAS  PubMed  Google Scholar 

  185. Saravanan P, Visser TJ, Dayan CM. Psychological well-being correlates with free thyroxine but not free 3,5,3′-triiodothyronine levels in patients on thyroid hormone replacement. J Clin Endocrinol Metab. 2006;91(9):3389–93. https://doi.org/10.1210/jc.2006-0414.

    Article  CAS  PubMed  Google Scholar 

  186. Kelly T, Denmark L, Lieberman DZ. Elevated levels of circulating thyroid hormone do not cause the medical sequelae of hyperthyroidism. Prog Neuropsychopharmacol Biol Psychiatry. 2016;71:1–6. https://doi.org/10.1016/j.pnpbp.2016.06.001.

    Article  CAS  PubMed  Google Scholar 

  187. Kelly T. An examination of myth: a favorable cardiovascular risk-benefit analysis of high-dose thyroid for affective disorders. J Affect Disord. 2015;177:49–58. https://doi.org/10.1016/j.jad.2015.01.016.

    Article  PubMed  Google Scholar 

  188. Mohagheghi A, Arfaie A, Amiri S, Nouri M, Abdi S, Safikhanlou S. Preventive effect of liothyronine on electroconvulsive therapy-induced memory deficit in patients with major depressive disorder: a double-blind controlled clinical trial. Biomed Res Int. 2015;2015:503918. https://doi.org/10.1155/2015/503918.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  189. Kalra S, Balhara YP. Euthyroid depression: the role of thyroid hormone. Recent Pat Endocr Metab Immune Drug Dis. 2014;8(1):38–41.

    Article  CAS  Google Scholar 

  190. Baumgartner C, Blum MR, Rodondi N. Subclinical hypothyroidism: summary of evidence in 2014. Swiss Med Wkly. 2014;144:w14058. https://doi.org/10.4414/smw.2014.14058.

    Article  PubMed  Google Scholar 

  191. Samuels MH, Kolobova I, Smeraglio A, Niederhausen M, Janowsky JS, Schuff KG. Effect of thyroid function variations within the laboratory reference range on health status, mood, and cognition in levothyroxine-treated subjects. Thyroid. 2016;26(9):1173–84. https://doi.org/10.1089/thy.2016.0141.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  192. Baethge C, Reischies FM, Berghofer A, Baur H, Schlattmann P, Whybrow PC, et al. Effects of supraphysiological doses of L-thyroxine on cognitive function in healthy individuals. Psychiatry Res. 2002;110(2):117–23.

    Article  CAS  PubMed  Google Scholar 

  193. Kraemer S, Danker-Hopfe H, Pilhatsch M, Bes F, Bauer M. Effects of supraphysiological doses of levothyroxine on sleep in healthy subjects: a prospective polysomnography study. J Thyroid Res. 2011;2011:420580. https://doi.org/10.4061/2011/420580.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  194. Panicker V, Saravanan P, Vaidya B, Evans J, Hattersley AT, Frayling TM, et al. 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. 2009;94(5):1623–9. https://doi.org/10.1210/jc.2008-1301.

    Article  CAS  PubMed  Google Scholar 

  195. Xue C, Bian L, Xie YS, Yin ZF, Xu ZJ, Chen QZ, et al. Low fT3 is associated with diminished health-related quality of life in patients with acute coronary syndrome treated with drug-eluting stent: a longitudinal observational study. Oncotarget. 2017;8(55):94580–90. https://doi.org/10.18632/oncotarget.21811.

    Article  PubMed  PubMed Central  Google Scholar 

  196. Bunevicius A, Laws ER, Deltuva V, Tamasauskas A. Association of thyroid hormone concentrations with quality of life of primary brain tumor patients: a pilot study. J Neurooncol. 2017;131(2):385–91. https://doi.org/10.1007/s11060-016-2311-x.

    Article  CAS  PubMed  Google Scholar 

  197. Klaver EI, van Loon HC, Stienstra R, Links TP, Keers JC, Kema IP, et al. Thyroid hormone status and health-related quality of life in the LifeLines Cohort Study. Thyroid. 2013;23(9):1066–73. https://doi.org/10.1089/thy.2013.0017.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  198. Kazukauskiene N, Burkauskas J, Macijauskiene J, Mickuviene N, Brozaitiene J. Exploring potential biomarkers associated with health-related quality of life in patients with coronary artery disease and heart failure. Eur J Cardiovasc Nurs. 2018;17(7):645–51.

    Article  PubMed  Google Scholar 

  199. Wouters HJ, van Loon HC, van der Klauw MM, Elderson MF, Slagter SN, Kobold AM, et al. No effect of the Thr92Ala polymorphism of deiodinase-2 on thyroid hormone parameters, health-related quality of life, and cognitive functioning in a large population-based cohort study. Thyroid. 2017;27(2):147–55. https://doi.org/10.1089/thy.2016.0199.

    Article  CAS  PubMed  Google Scholar 

  200. Wekking EM, Appelhof BC, Fliers E, Schene AH, Huyser J, Tijssen JG, et al. Cognitive functioning and well-being in euthyroid patients on thyroxine replacement therapy for primary hypothyroidism. Eur J Endocrinol. 2005;153(6):747–53. https://doi.org/10.1530/eje.1.02025.

    Article  CAS  PubMed  Google Scholar 

  201. Djurovic M, Pereira AM, Smit JWA, Vasovic O, Damjanovic S, Jemuovic Z, et al. Cognitive functioning and quality of life in patients with Hashimoto thyroiditis on long-term levothyroxine replacement. Endocrine. 2018;62(1):136–43. https://doi.org/10.1007/s12020-018-1649-6.

    Article  CAS  PubMed  Google Scholar 

  202. Nygaard B, Jensen EW, Kvetny J, Jarlov A, Faber J. Effect of combination therapy with thyroxine (T4) and 3,5,3′-triiodothyronine versus T4 monotherapy in patients with hypothyroidism, a double-blind, randomised cross-over study. Eur J Endocrinol. 2009;161(6):895–902. https://doi.org/10.1530/eje-09-0542.

    Article  CAS  PubMed  Google Scholar 

  203. Brozaitiene J, Mickuviene N, Podlipskyte A, Burkauskas J, Bunevicius R. Relationship and prognostic importance of thyroid hormone and N-terminal pro-B-type natriuretic peptide for patients after acute coronary syndromes: a longitudinal observational study. BMC Cardiovasc Disord. 2016;16(1):45. https://doi.org/10.1186/s12872-016-0226-2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  204. Fontana M, Passino C, Poletti R, Zyw L, Prontera C, Scarlattini M, et al. Low triiodothyronine and exercise capacity in heart failure. Int J Cardiol. 2012;154(2):153–7. https://doi.org/10.1016/j.ijcard.2010.09.002.

    Article  PubMed  Google Scholar 

  205. Molinaro S, Iervasi G, Lorenzoni V, Coceani M, Landi P, Srebot V, et al. Persistence of mortality risk in patients with acute cardiac diseases and mild thyroid dysfunction. Am J Med Sci. 2012;343(1):65–70. https://doi.org/10.1097/MAJ.0b013e31822846bd.

    Article  PubMed  Google Scholar 

  206. Rothberger GD, Gadhvi S, Michelakis N, Kumar A, Calixte R, Shapiro LE. Usefulness of serum triiodothyronine (T3) to predict outcomes in patients hospitalized with acute heart failure. Am J Cardiol. 2017;119(4):599–603. https://doi.org/10.1016/j.amjcard.2016.10.045.

    Article  CAS  PubMed  Google Scholar 

  207. Kowalczuk-Wieteska A, Baranska-Kosakowska A, Zakliczynski M, Lindon S, Zembala M. Do thyroid disorders affect the postoperative course of patients in the early post-heart transplant period? Ann Transplant. 2011;16(3):77–81.

    Article  PubMed  Google Scholar 

  208. Sousa PA, Providencia R, Albenque JP, Khoueiry Z, Combes N, Combes S, et al. Impact of free thyroxine on the outcomes of left atrial ablation procedures. Am J Cardiol. 2015;116(12):1863–8. https://doi.org/10.1016/j.amjcard.2015.09.028.

    Article  CAS  PubMed  Google Scholar 

  209. Pingitore A, Iervasi G, Barison A, Prontera C, Pratali L, Emdin M, et al. Early activation of an altered thyroid hormone profile in asymptomatic or mildly symptomatic idiopathic left ventricular dysfunction. J Card Fail. 2006;12(7):520–6. https://doi.org/10.1016/j.cardfail.2006.05.009.

    Article  CAS  PubMed  Google Scholar 

  210. Suh S, Kim DK. Subclinical hypothyroidism and cardiovascular disease. Endocrinol Metab. 2015;30(3):246–51. https://doi.org/10.3803/EnM.2015.30.3.246.

    Article  CAS  Google Scholar 

  211. Beyer C, Plank F, Friedrich G, Wildauer M, Feuchtner G. Effects of hyperthyroidism on coronary artery disease: a computed tomography angiography study. Can J Cardiol. 2017;33(10):1327–34. https://doi.org/10.1016/j.cjca.2017.07.002.

    Article  PubMed  Google Scholar 

  212. Ilic S, Tadic M, Ivanovic B, Caparevic Z, Trbojevic B, Celic V. Left and right ventricular structure and function in subclinical hypothyroidism: the effects of one-year levothyroxine treatment. Med Sci Monit. 2013;19:960–8. https://doi.org/10.12659/msm.889621.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  213. Brenta G, Thierer J, Sutton M, Acosta A, Vainstein N, Brites F, et al. Low plasma triiodothyronine levels in heart failure are associated with a reduced anabolic state and membrane damage. Eur J Endocrinol. 2011;164(6):937–42. https://doi.org/10.1530/eje-11-0094.

    Article  CAS  PubMed  Google Scholar 

  214. Arikan S, Tuzcu A, Gokalp D, Bahceci M, Danis R. Hyperthyroidism may affect serum N-terminal pro-B-type natriuretic peptide levels independently of cardiac dysfunction. Clin Endocrinol. 2007;67(2):202–7. https://doi.org/10.1111/j.1365-2265.2007.02861.x.

    Article  CAS  Google Scholar 

  215. Adamopoulos S, Gouziouta A, Mantzouratou P, Laoutaris ID, Dritsas A, Cokkinos DV, et al. Thyroid hormone signalling is altered in response to physical training in patients with end-stage heart failure and mechanical assist devices: potential physiological consequences? Interact Cardiovasc Thorac Surg. 2013;17(4):664–8. https://doi.org/10.1093/icvts/ivt294.

    Article  PubMed  PubMed Central  Google Scholar 

  216. Pinelli M, Bindi M, Cassetti G, Moroni F, Pandolfo C, Rosada J, et al. Relationship between low T3 syndrome and NT-proBNP levels in non-cardiac patients. Acta Cardiol. 2007;62(1):19–24. https://doi.org/10.2143/ac.62.1.2019366.

    Article  PubMed  Google Scholar 

  217. Utku U, Gokce M, Ozkaya M. Changes in cerebral blood flow velocity in patients with hypothyroidism. Eur J Endocrinol. 2011;165(3):465–8. https://doi.org/10.1530/eje-11-0254.

    Article  CAS  PubMed  Google Scholar 

  218. Pingitore A, Galli E, Barison A, Iervasi A, Scarlattini M, Nucci D, et al. Acute effects of triiodothyronine (T3) replacement therapy in patients with chronic heart failure and low-T3 syndrome: a randomized, placebo-controlled study. J Clin Endocrinol Metab. 2008;93(4):1351–8. https://doi.org/10.1210/jc.2007-2210.

    Article  CAS  PubMed  Google Scholar 

  219. Shatynska-Mytsyk I, Rodrigo L, Cioccocioppo R, Petrovic D, Lakusic N, Compostella L, et al. The impact of thyroid hormone replacement therapy on left ventricular diastolic function in patients with subclinical hypothyroidism. J Endocrinol Invest. 2016;39(6):709–13. https://doi.org/10.1007/s40618-015-0262-2.

    Article  CAS  PubMed  Google Scholar 

  220. Gerdes AM, Iervasi G. Thyroid replacement therapy and heart failure. Circulation. 2010;122(4):385–93. https://doi.org/10.1161/circulationaha.109.917922.

    Article  PubMed  Google Scholar 

  221. Pingitore A, Nicolini G, Kusmic C, Iervasi G, Grigolini P, Forini F. Cardioprotection and thyroid hormones. Heart Fail Rev. 2016;21(4):391–9. https://doi.org/10.1007/s10741-016-9545-8.

    Article  CAS  PubMed  Google Scholar 

  222. Zhang Y, Dedkov EI, Lee B 3rd, Li Y, Pun K, Gerdes AM. Thyroid hormone replacement therapy attenuates atrial remodeling and reduces atrial fibrillation inducibility in a rat myocardial infarction-heart failure model. J Card Fail. 2014;20(12):1012–9. https://doi.org/10.1016/j.cardfail.2014.10.003.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  223. Curotto Grasiosi J, Peressotti B, Machado RA, Filipini EC, Angel A, Delgado J et al. [Improvement in functional capacity after levothyroxine treatment in patients with chronic heart failure and subclinical hypothyroidism]. Endocrinol Nutr. 2013;60(8):427–32. https://doi.org/10.1016/j.endonu.2013.01.013.

  224. Arcopinto M, Salzano A, Isgaard J, Cittadini A. Hormone replacement therapy in heart failure. Curr Opin Cardiol. 2015;30(3):277–84. https://doi.org/10.1097/hco.0000000000000166.

    Article  PubMed  Google Scholar 

  225. Deladoey J, Harrington K. Has triiodothyronine treatment of children after cardiopulmonary bypass surgery any long-term effects? Horm Res Paediatr. 2015;84(2):137–8. https://doi.org/10.1159/000380782.

    Article  CAS  PubMed  Google Scholar 

  226. Carney RM, Freedland KE, Steinmeyer B, Rubin EH, Mann DL, Rich MW. Cardiac risk markers and response to depression treatment in patients with coronary heart disease. Psychosom Med. 2016;78(1):49–59. https://doi.org/10.1097/psy.0000000000000245.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Conflicts of Interest

The authors disclose no conflict of interest, except Julius Burkauskas who has served as a consultant at Cogstate Ltd.

Author information

Authors and Affiliations

  1. Neuroscience Institute, Lithuanian University of Health Sciences, Kaunas, Lithuania

    Julius Burkauskas, Aiste Pranckeviciene & Adomas Bunevicius

Authors
  1. Julius Burkauskas
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Aiste Pranckeviciene
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Adomas Bunevicius
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Adomas Bunevicius .

Editor information

Editors and Affiliations

  1. Institute of Clinical Physiology (IFC) National Research Council (CNR), Pisa, Italy

    Giorgio Iervasi

  2. Institute of Clinical Physiology (IFC) National Research Council (CNR), Pisa, Italy

    Alessandro Pingitore

  3. NYITCOM College of Osteopathic Medicine Biomedical Sciences Department, Old Westbury, NY, USA

    A.Martin Gerdes

  4. Institute of Clinical and Translational Medicine, Newcastle University/Queen Elizabeth Hospital, Newcastle upon Tyne, UK

    Salman Razvi

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Burkauskas, J., Pranckeviciene, A., Bunevicius, A. (2020). Thyroid Hormones, Brain, and Heart. In: Iervasi, G., Pingitore, A., Gerdes, A., Razvi, S. (eds) Thyroid and Heart . Springer, Cham. https://doi.org/10.1007/978-3-030-36871-5_25

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-36871-5_25

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-36870-8

  • Online ISBN: 978-3-030-36871-5

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation