Prediction of the Development of Depression in Patients with Autoimmune Thyroiditis and Hypothyroidism

Authors

  • Iryna Kamyshna Department of Medical Rehabilitation, I. Horbachevsky Ternopil National Medical University, Ternopil, Ukraine https://orcid.org/0000-0002-4483-1856
  • Larysa Pavlovych Department of Clinical Immunology, Allergology and Endocrinology, HSEEU “Bukovinian State Medical University”, Chernivtsi, Ukraine
  • Alexandr M. Kamyshnyi Department of Microbiology, Virology, and Immunology, I. Horbachevsky Ternopil National Medical University, Ternopil, Ukraine

DOI:

https://doi.org/10.3889/oamjms.2022.7896

Keywords:

Vitamin D receptor, Brain-derived neurotrophic factor, N-methyl-D-aspartate, Depression, Autoimmune thyroiditis, Hypothyroidism

Abstract

BACKGROUND: Hypothyroidism is frequently accompanied by depression symptoms, whereas depression is considered the most common mental disorder.

AIM: It is crucial to analyze the associations of the brain neurotrophic factor (BDNF) gene polymorphism (rs6265), the VDR gene polymorphism (rs2228570), and the NMDA gene polymorphism (rs4880213) with the depression in patients with autoimmune thyroiditis and hypothyroidism in the Western Ukrainian population and predict the development of depressive disorders in these patients.

METHODS: The study involved a total of 153 patients with various forms of thyroid pathology. BDNF levels in the sera of the patients and healthy individuals were quantified using enzyme-linked immunosorbent assay with highly sensitive Human BDNF ELISA Kit (Elabscience®, United States, Catalog No: E-EL-H0010) on E.I.A. Reader Sirio S (Seac, Italy). Genotyping of the VDR (rs2228570), BDNF (rs6265), and NMDA (rs4880213) gene polymorphism using TaqMan probes and TaqMan Genotyping Master Mix (4371355) on CFX96™Real-Time Polymerase chain reaction (PCR) Detection System (Bio-Rad Laboratories, Inc., USA). PCR for TaqMan genotyping was carried out according to the kit instructions (Applied Biosystems, USA). We used the Student’s t-test, ANOVA, Pearson’s Chi-square test, ROC-analysis, odds ratio test, relative odds ratio test. The odds ratio and 95% confidence interval were computed by binary logistic regression.

RESULTS: When comparing the presence of depression on the Hamilton scale, statistically significant differences were found depending on BDNF gene polymorphism (rs6265) (p < 0.001), and non-statistically noticeable differences were detected depending on the VDR gene polymorphism (rs2228570) and NMDA gene polymorphism (rs4880213). Our study revealed a marked inverse connection between depression and BDNF levels (p < 0.001) and a reverse moderate correlation between depression and fT4 (p < 0.001) and 25-OH Vitamin D levels (p < 0.001). In addition, we identified a direct moderate correlation between pronounced levels of depression and thyroid-stimulating hormone (TSH) in the blood (p < 0.001).

CONCLUSIONS: Indicators such as BDNF, TSH, fT4, anti-TPO, and 25-OH Vitamin D levels were found to be prognostically significant criteria for the risk of developing depression.

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References

Gorkhali B, Sharma S, Amatya M, Acharya D, Sharma M. Anxiety and depression among patients with thyroid function disorders. J Nepal Health Res Counc. 2020;18(3):373-8. https://doi.org/10.33314/jnhrc.v18i3.2499 PMid:33210626 DOI: https://doi.org/10.33314/jnhrc.v18i3.2499

Cohen BM, Sommer BR, Vuckovic A. Antidepressant-resistant depression in patients with comorbid subclinical hypothyroidism or high-normal TSH levels. Am J Psychiatry. 2018;175(7):598-604. https://doi.org/10.1176/appi.ajp.2017.17080949 PMid:29961367 DOI: https://doi.org/10.1176/appi.ajp.2017.17080949

Ittermann T, Völzke H, Baumeister SE, Appel K, Grabe HJ. Diagnosed thyroid disorders are associated with depression and anxiety. Soc Psychiatry Psychiatr Epidemiol. 2015;50(9):1417-25. https://doi.org/10.1007/s00127-015-1043-0 PMid:25777685 DOI: https://doi.org/10.1007/s00127-015-1043-0

Sharma AN, da Costa e Silva BF, Soares JC, Carvalho AF, Quevedo J. Role of trophic factors GDNF, IGF-1 and VEGF in major depressive disorder: A comprehensive review of human studies. J Affect Disord. 2016;197:9-20. https://doi.org/10.1016/j.jad.2016.02.067 PMid:26956384 DOI: https://doi.org/10.1016/j.jad.2016.02.067

Lindholm JS, Castrén E. Mice with altered BDNF signaling as models for mood disorders and antidepressant effects. Front Behav Neurosci. 2014;8:143. https://doi.org/10.3389/fnbeh.2014.00143 PMid:24817844 DOI: https://doi.org/10.3389/fnbeh.2014.00143

Krysiak R, Kowalcze K, Okopień B. The impact of exogenous Vitamin D on thyroid autoimmunity in euthyroid men with autoimmune thyroiditis and early-onset androgenic alopecia. Pharmacol Rep. 2021;73(5):1439-47. https://doi.org/10.1007/s43440-021-00295-3 PMid:34106452 DOI: https://doi.org/10.1007/s43440-021-00295-3

Erensoy H. The association between anxiety and depression with 25(OH)D and thyroid stimulating hormone levels. Neurosciences (Riyadh). 2019;24(4):290-5. https://doi.org/10.17712/nsj.2019.4.20190028 PMid:31872808 DOI: https://doi.org/10.17712/nsj.2019.4.20190028

Mundo E, Tharmalingham S, Neves-Pereira M, Dalton EJ, Macciardi F, Parikh SV, et al. Evidence that the N-methyl-D-aspartate subunit 1 receptor gene (GRIN1) confers susceptibility to bipolar disorder. Mol Psychiatry. 2003;8(2):241-5. https://doi.org/10.1038/sj.mp.4001218 PMid:12610658 DOI: https://doi.org/10.1038/sj.mp.4001218

Saito T, Chiba Y, Abe K, Hattori S, Katsuse O, Takahashi Y, et al. An investigative study of antibodies to NMDA-type glutamate receptor subunits in serum and cerebrospinal fluid in psychiatric patients with anti-thyroid antibodies. Helion. 2020;6(12):e05677. https://doi.org/10.1016/j.heliyon.2020.e05677 PMid:33319115 DOI: https://doi.org/10.1016/j.heliyon.2020.e05677

Degen AS, Krynytska IY, Kamyshnyi AM. Changes in the transcriptional activity of the entero-insular axis genes in streptozotocin-induced diabetes and after the administration of TNF-α non-selective blockers. Endocr Regul. 2020;54(3):160-71. https://doi.org/10.2478/enr-2020-0019 PMid:32857721 DOI: https://doi.org/10.2478/enr-2020-0019

Nosulenko IS, Voskoboynik OY, Berest GG, Safronyuk SL, Kovalenko SI, Kamyshnyi OM, et al. Synthesis and antimicrobial activity of 6-thioxo-6, 7-dihydro-2H-[1, 2, 4] triazino [2, 3-c]-quinazolin-2-one derivatives. Sci Pharm. 2014;82(3):483-500. https://doi.org/10.3797/scipharm.1402-10 PMid:25853063 DOI: https://doi.org/10.3797/scipharm.1402-10

Putilin DA, Evchenko SY, Fedoniuk LY, Tokarskyy OS, Kamyshny OM, Migenko LM, et al. The influence of metformin to the transcriptional activity of the mTOR and FOX3 genes in parapancreatic adipose tissue of streptozotocin-induced diabetic rats. J Med Life. 2020;13(1):50-5. https://doi.org/10.25122/jml-2020-0029 PMid:32341701

Dzhuryak V, Sydorchuk L, Sydorchuk A, Kamyshnyi O, Kshanovska A, Levytska S, et al. The cytochrome 11B2 aldosterone synthase gene CYP11B2 (RS1799998) polymorphism associates with chronic kidney disease in hypertensive patients. Biointerface Res Appl Chem. 2020;10(3):5406-11. DOI: https://doi.org/10.33263/BRIAC103.406411

Lyubomirskaya ES, Kamyshnyi AM, Krut YY, Smiianov VA, Fedoniuk LY, Romanyuk LB, et al. SNPs and transcriptional activity of genes of innate and adaptive immunity at the maternal-fetal interface in woman with preterm labour, associated with preterm premature rupture of membranes. Wiad Lek. 2020;73(1):25-30. PMid:32124801

Bilous II, Pavlovych LL, Kamyshnyi AM. Primary hypothyroidism and autoimmune thyroiditis alter the transcriptional activity of genes regulating neurogenesis in the blood of patients. Endocr Regul. 2021;55(1):5-15. https://doi.org/10.2478/enr-2021-0002 PMid:33600668 DOI: https://doi.org/10.2478/enr-2021-0002

Kamyshna I, Kamyshnyi A. Transcriptional activity of neurotrophins genes and their receptors in the peripheral blood in patients with thyroid diseases in Bukovinian population of Ukraine. Open Access Maced J Med Sci. 2021;9(A):208-16. https://doi.org/10.3889/oamjms.2021.6037 DOI: https://doi.org/10.3889/oamjms.2021.6037

Bilous II, Korda MM, Krynytska IY, Kamyshnyi AM. Nerve impulse transmission pathway-focused genes expression analysis in patients with primary hypothyroidism and autoimmune thyroiditis. Endocr Regul. 2020;54(2):109-18. https://doi.org/10.2478/enr-2020-0013 PMid:32597152 DOI: https://doi.org/10.2478/enr-2020-0013

Bilous I, Pavlovych L, Krynytska I, Marushchak M, Kamyshnyi A. Apoptosis and cell cycle pathway-focused genes expression analysis in patients with different forms of thyroid pathology. Open Access Maced J Med Sci. 2020;8(B):784-92. https://doi.org/10.3889/oamjms.2020.4760 DOI: https://doi.org/10.3889/oamjms.2020.4760

Kamyshna I, Pavlovych L, Kamyshnyi A. Association between serum brain-derived neurotrophic factor and 25-OH Vitamin D levels with Vitamin D receptors gene polymorphism (rs2228570) in patients with autoimmune thyroiditis and hypothyroidism. Open Access Maced J Med Sci. 2021;9(A):659-64. Available from: https://www.oamjms.eu/index.php/mjms/article/view/6631 [Last accessed on 2021 Oct 07]. DOI: https://doi.org/10.3889/oamjms.2021.6631

Kamyshna I, Pavlovych L, Malyk I, Kamyshnyi A. 25-OH Vitamin D blood serum linkage with VDR gene polymorphism (rs2228570) in thyroid pathology patients in the West-Ukrainian population. J Med Life. 2021;14(4):549-56. DOI: https://doi.org/10.25122/jml-2021-0101

Kamyshna I, Pavlovych L, Maslyanko V, Kamyshnyi A. Analysis of the transcriptional activity of genes of neuropeptides and their receptors and their receptors in the blood of patients with thyroid pathology. J Med Life. 2021;14(2):243-9. https://doi.org/10.25122/jml-2020-0183 PMid:34104248 DOI: https://doi.org/10.25122/jml-2020-0183

Kamyshna I, Pavlovych L, Sydorchuk L, Malyk I, Kamyshnyi A. BDNF blood serum linkage with BDNF gene polymorphism (rs6265) in thyroid pathology patients in the West-Ukrainian population. Endocr Regul. 2021;55(4):101-11. https://doi.org/10.2478/enr-2021-0021 PMid:34879183 DOI: https://doi.org/10.2478/enr-2021-0021

Garber JR, Cobin RH, Gharib H, Hennessey JV, Klein I, Mechanick JI, et al. Clinical practice guidelines for hypothyroidism in adults: Cosponsored by the American association of clinical endocrinologists and the American thyroid association. Endocr Pract. 2012;18(6):988-1028. https://doi.org/10.4158/EP12280.GL PMid:23246686 DOI: https://doi.org/10.4158/EP12280.GL

Blacker D. Rating scales in psychiatry. In: Sadock BJ, Sadock VA, editors. Comprehensive Textbook of Psychiatry. 8th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2007. p. 929-43.

Leyhe T, Müssig K. Cognitive and affective dysfunctions in autoimmune thyroiditis. Brain Behav Immun. 2014;41:261-6. https://doi.org/10.1016/j.bbi.2014.03.008 PMid:24685840 DOI: https://doi.org/10.1016/j.bbi.2014.03.008

Siegmann EM, Müller HH, Luecke C, Philipsen A, Kornhuber J, Grömer TW. Association of depression and anxiety disorders with autoimmune thyroiditis: A systematic review and meta-analysis. JAMA Psychiatry. 2018;75(6):577-84. https://doi.org/10.1001/jamapsychiatry.2018.0190 PMid:29800939 DOI: https://doi.org/10.1001/jamapsychiatry.2018.0190

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 PMid:25973566 DOI: https://doi.org/10.1016/j.psyneuen.2015.04.016

Panicker V, Evans J, Bjøro T, Åsvold BO, Dayan CM, Bjerkeset O. A paradoxical difference in relationship between anxiety, de-pression and thyroid function in subjects on and not on T4: Findings from the HUNT study. Clin Endocrinol (Oxf). 2009;71(4):574-80. https://doi.org/10.1111/j.1365-2265.2008.03521 PMid:19751298 DOI: https://doi.org/10.1111/j.1365-2265.2008.03521.x

Fukao A, Takamatsu J, Kubota S, Miyauchi A, Hanafusa T. The thyroid function of Graves’ disease patients is aggravated by depressive personality during antithyroid drug treatment. Biopsychosoc Med. 2011;5:9. https://doi.org/10.1186/1751-0759-5-9 PMid:21827669 DOI: https://doi.org/10.1186/1751-0759-5-9

Bárez-López S, Montero-Pedrazuela A, Bosch-García D, Venero C, Guadaño-Ferraz A. Increased anxiety and fear memory in adult mice lacking Type 2 deiodinase. Psychoneuroendocrinology. 2017;84:51-60. https://doi.org/10.1016/j.psyneuen.2017.06.013 PMid:28654773 DOI: https://doi.org/10.1016/j.psyneuen.2017.06.013

Duman RS, Monteggia LM. A neurotrophic model for stress-related mood disorders. Biol Psychiatry. 2006;59(12):1116-27. https://doi.org/10.1016/j.biopsych.2006.02.013 PMid:16631126 DOI: https://doi.org/10.1016/j.biopsych.2006.02.013

Allen AP, Naughton M, Dowling J, Walsh A, Ismail F, Shorten G, et al. Serum BDNF as a peripheral biomarker of treatment-resistant depression and the rapid antidepressant response: A comparison of ketamine and ECT. J Affect Disord. 2015;186:306-11. https://doi.org/10.1016/j.jad.2015.06.033 PMid:26275358 DOI: https://doi.org/10.1016/j.jad.2015.06.033

Neto FL, Borges G, Torres-Sanchez S, Mico JA, Berrocoso E. Neurotrophins role in depression neurobiology: A review of basic and clinical evidence. Curr Neuropharmacol. 2011;9(4):530-52. https://doi.org/10.2174/157015911798376262 PMid:22654714 DOI: https://doi.org/10.2174/157015911798376262

Masi G, Brovedani P. The hippocampus, neurotrophic factors and depression possible implications for the pharmacotherapy of depression. Cns Drugs. 2011;25(11):913-31. https://doi.org/10.2165/11595900-000000000-00000 PMid:22054117 DOI: https://doi.org/10.2165/11595900-000000000-00000

Fu X, Wang J, Du J, Sun J, Baranova A, Zhang F. BDNF Gene’s role in schizophrenia: From risk allele to methylation implications. Front Psychiatry. 2020;11:564277. https://doi.org/10.3389/fpsyt.2020.564277 PMid:33384622 DOI: https://doi.org/10.3389/fpsyt.2020.564277

Egan MF, Kojima M, Callicott JH, Goldberg TE, Kolachana BS, Bertolino A, et al. The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function. Cell. 2003;112(2):257-69. https://doi.org/10.1016/s0092-8674(03)00035-7 PMid:12553913 DOI: https://doi.org/10.1016/S0092-8674(03)00035-7

Notaras M, van den Buuse M. Brain-derived neurotrophic factor (BDNF): Novel insights into regulation and genetic variation. Neuroscientist. 2019;25(5):434-54. https://doi.org/10.1177/1073858418810142 PMid:30387693 DOI: https://doi.org/10.1177/1073858418810142

Gallinat J, Schubert F, Brühl R, Hellweg R, Klär AA, Kehrer C, et al. Met carriers of BDNF Val66Met genotype show increased N-acetylaspartate concentration in the anterior cingulate cortex. Neuroimage. 2010;49(1):767-71. https://doi.org/10.1016/j.neuroimage.2009.08.018 PMid:19683059 DOI: https://doi.org/10.1016/j.neuroimage.2009.08.018

Bath KG, Jing DQ, Dincheva I, Neeb CC, Pattwell SS, Chao MV, et al. BDNF Val66Met impairs fluoxetine-induced enhancement of adult hippocampus plasticity. Neuropsychopharmacology. 2012;37:1297-304. https://doi.org/10.1038/npp.2011.318 PMid:22218094 DOI: https://doi.org/10.1038/npp.2011.318

Lang UE, Hellweg R, Sander T, Gallinat J. The met allele of the BDNF Val66Met polymorphism is associated with increased BDNF serum concentrations. Mol Psychiatry. 2009;14(2):120-2. https://doi.org/10.1038/mp.2008.80 PMid:19156154 DOI: https://doi.org/10.1038/mp.2008.80

Hoogendijk WJ, Lips P, Dik MG, Deeg DJ, Beekman AT, Penninx BW. Depression is associated with decreased 25-hydroxyvitamin D and increased parathyroid hormone levels in older adults. Arch Gen Psychiatry. 2008;65(5):508-12. https://doi.org/10.1001/archpsyc.65.5.508 PMid:18458202 DOI: https://doi.org/10.1001/archpsyc.65.5.508

Talaei A, Ghorbani F, Asemi Z. The effects of Vitamin D supplementation on thyroid function in hypothyroid patients: A randomized, double-blind, placebo-controlled trial. Indian J Endocrinol Metab. 2018;22(5):584-8. https://doi.org/10.4103/ijem.ijem_603_17 PMid:30294564 DOI: https://doi.org/10.4103/ijem.IJEM_603_17

Mackawy AM, Al-Ayed BM, Al-Rashidi BM. Vitamin d deficiency and its association with thyroid disease. Int J Health Sci (Qassim). 2013;7(3):267-75. https://doi.org/10.12816/0006054 PMid:24533019 DOI: https://doi.org/10.12816/0006054

Carta MG, Hardoy MC, Carpiniello B, Murru A, Marci AR, Carbone F, et al. A case control study on psychiatric disorders in Hashimoto disease and Euthyroid Goitre: Not only depressive but also anxiety disorders are associated with thyroid autoimmunity. Clin Pract Epidemiol Ment Health. 2005;1:23. https://doi.org/10.1186/1745-0179-1-23 PMid:16285879 DOI: https://doi.org/10.1186/1745-0179-1-23

Kirim S, Keskek SO, Köksal F, Haydardedeoglu FE, Bozkirli` E, Toledano Y. Depression in patients with euthyroid chronic autoimmune thyroiditis. Endocr J. 2012;59(8):705-8. https://doi.org/10.1507/endocrj.ej12-0035 PMid:22673294 DOI: https://doi.org/10.1507/endocrj.EJ12-0035

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2022-01-31

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1.
Kamyshna I, Pavlovych L, Kamyshnyi AM. Prediction of the Development of Depression in Patients with Autoimmune Thyroiditis and Hypothyroidism. Open Access Maced J Med Sci [Internet]. 2022 Jan. 31 [cited 2024 Nov. 21];10(B):137-45. Available from: https://oamjms.eu/index.php/mjms/article/view/7896