Kamyshna I. Molecular mechanisms in the development of psychoneurological complications in patients with thyroid diseases: predicting onset and search for pathogenetic therapy

Українська версія

Thesis for the degree of Doctor of Science (DSc)

State registration number

0523U100201

Applicant for

Specialization

  • 14.03.04 - Патологічна фізіологія

08-11-2023

Specialized Academic Board

Д 58.601.01

Ternopil National Medical University named after I. Gorbachevsky of the Ministry of Health of Ukraine

Essay

The dissertation is devoted to the clinical and pathogenetic features of neuropsychiatric disorders in thyroid gland (TG) pathology, vital molecular mechanisms in their development in terms of genetic, neurotrophic, and immunologically mediated factors, as well as the prediction of complications and pathogenetic ways of correcting the detected changes. The allelic state of the BDNF (rs6265), VDR (rs2228570) and NMDA (rs4880213) genes in the structure of risk factors for thyroid pathology has been studied. The relationship between certain humoral markers of neurotransmission and thyroid hormonal activity has been evaluated, considering the polymorphism of the BDNF (rs6265), VDR (rs2228570) and NMDA (rs4880213) genes. The expression of neurotrophin genes and their receptors, neuropeptides, transcription factors, cytokines, and apoptosis regulatory genes in the blood of patients with thyroid pathology has been analyzed. The role of the genes BDNF (rs6265), VDR (rs2228570) and NMDA (rs4880213) in the development of neuropsychiatric disorders in thyroid pathology has been investigated. The prognostic models of the probable development of cognitive impairment, depression, and anxiety disorders have been built depending on the individual genotype of the BDNF (rs6265), VDR (rs2228570), and NMDA (rs4880213) genes, as well as clinical and laboratory parameters. The effect of complex treatment of patients with hypothyroidism and AIT on thyroid hormone activity, neuropsychological status, transcriptional activity of genes regulating neurotransmission, neurogenesis and apoptosis, and specific clinical and laboratory parameters have been analyzed. The mechanisms of development of neuropsychiatric disorders in thyroid pathology are schematically summarized, considering the polymorphism of the genes BDNF (rs6265), VDR (rs2228570), NMDA (rs4880213) and based on the obtained indicators of changes in the transcriptome of the studied genetic markers, metabolic and hormonal changes.

Research papers

1. Bilous II, Pavlovych LB, Chornenka ZhA. Current situation with thyroid gland disease incidence in Chernivtsi region. The scientific heritage. 2017;11(11):53-56.

2. Bilous II. Features of the peripheral nervous system affection in patients with primary hypothyroidism. Клінічна та експериментальна патологія. 2018;1(63):13-16. DOI: 10.24061/1727-4338.XVII.1.63.2018.3

3. Bilous II, Pavlovych LB. Symptoms of organic brain damage in primary hyроthyroidism. Sciences of Europe. 2018;1(25):24-26.

4. Bilous II, Korda MM, Krynytska IY, Kamyshnyi AM. Nerve impulse transmission pathway-focused genes expression analysis in patients with primary hypothyroidism and autoimmune thyroiditis. Endocrine Regulations. 2020 Apr 1;54(2):109-118. DOI: 10.2478/enr-2020-0013. (SCOPUS, Q3)

5. 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 Macedonian Journal of Medical Sciences. 2020 May 20;8(B):784-792. DOI: 10.3889/oamjms.2020.4760 (SCOPUS, Q3)

6. Bilous II, Pavlovych LL, Kamyshnyi AM. Primary hypothyroidism and autoimmune thyroiditis alter the transcriptional activity of genes regulating neurogenesis in the blood of patients. Endocrine Regulations. 2021 Jan 29;55(1):5-15. DOI: 10.2478/enr-2021-0002. (SCOPUS, Q3)

7. 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 Macedonian Journal of Medical Sciences. 2021 May 2;9(A):208-216. DOI: 10.3889/oamjms.2021.6037 (SCOPUS, Q3)

8. 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 Macedonian Journal of Medical Sciences. 2021 Aug 31;9(A):659-664. DOI: 10.3889/oamjms.2021.6631 (SCOPUS, Q3)

9. Kamyshna II, Pavlovych LB, Malyk IV, Kamyshnyi AM. 25-OH Vitamin D blood serum linkage with VDR gene polymorphism (rs2228570) in thyroid pathology patients in the West-Ukrainian population. Journal of Medicine and Life. 2021 Jul-Aug;14(4):549-556. DOI: 10.25122/jml-2021-0101. (SCOPUS, Q3)

10. Kamyshna II, Pavlovych LB, Maslyanko VA, Kamyshnyi AM. Analysis of the transcriptional activity of genes of neuropeptides and their receptors in the blood of patients with thyroid pathology. Journal of Medicine and Life. 2021 Mar-Apr;14(2):243-249. DOI: 10.25122/jml-2020-0183. (SCOPUS, Q3)

11. Kamyshna II, Pavlovych LB, Sydorchuk LP, Malyk IV, Kamyshnyi AM. BDNF blood serum linkage with BDNF gene polymorphism (rs6265) in thyroid pathology patients in the West-Ukrainian population. Endocrine Regulations. 2021 Dec 7;55(4):193-203. DOI: 10.2478/enr-2021-0021. (SCOPUS, Q3)

12. Kamyshna I, Pavlovych L, Maslyanko V, Сhornenka Z Epidemiological assessment of dymamics of the prevalence and incidence of the thyroid gland diseases in Ukraine and Chernivtsi region. Клінічна та експериментальна патологія. 2021;20(3):75-81. DOI: 10.24061/1727-4338.XX.3.77.2021.11

13. Kamyshna I, Kamyshnyi A. Transcription Factors and Regulators Pathway-focused Genes Expression Analysis in Patients with Different Forms of Thyroid Pathology. Current Pharmaceutical Biotechnology. 2022;23(11):1396-1404. DOI: 10.2174/1389201023666220217123454. (SCOPUS, Q2)

14. Kamyshna II, Pavlovych LB, Kamyshnyi AM. Association between NMDA gene polymorphism (rs4880213) and GRIN2B blood serum levels in thyroid pathology patients. Journal of Medicine and Life. 2022 Jan;15(1):109-116. DOI: 10.25122/jml-2021-0372. (SCOPUS, Q3)

15. Kamyshna II, Pavlovych LB, Kamyshnyi AM. Prediction of the cognitive impairment development in patients with autoimmune thyroiditis and hypothyroidism. Endocrine Regulations. 2022 Jul 13;56(3):178-189. DOI: 10.2478/enr-2022-0019. (SCOPUS, Q3)

16. Kamyshna I, Kamyshnyi A. Expression of cytokines and cytokine receptors-genes in patients with different forms of thyroid pathology in ukrainian population. Serbian Journal of Experimental and Clinical Research. 2022;23(4)6:299-308. DOI: 10.2478/sjecr-2021-0038 (SCOPUS, Q4)

17. Kamyshna I, Pavlovych L, Kamyshnyi AM. Prediction of the Development of Depression in Patients with Autoimmune Thyroiditis and Hypothyroidism. Open Access Macedonian Journal of Medical Sciences. 2022 Jan. 31;10(B):137-145. DOI: 10.3889/oamjms.2022.7896 (SCOPUS, Q3)

18. Kamyshna I, Pavlovych L, Kamyshnyi A. Vitamin D alters the transcriptional profile of blood cells in patients with primary hypothyroidism. Фізіологічний журнал. 2022;68(5):16-24. DOI: 10.15407/fz68.05.016 (SCOPUS, Q4)

19. Kamyshna I. Effect of vitamin D on serum BDNF level in patients with hypothyroidism caused by autoimmune thyroiditis. Міжнародний ендокринологічний журнал. 2022;18(5):297-301. DOI: 10.22141/2224-0721.18.5.2022.1189. (SCOPUS, Q4)

20. Kamyshna I. The role of vitamin D for the management of depression in the Western Ukrainian population with autoimmune thyroiditis and hypothyroidism. Міжнародний ендокринологічний журнал. 2022;18(7):208-212. DOI: 10.22141/2224-0721.18.4.2022.1173 (SCOPUS, Q4)

21. Kamyshna I. Vitamin D in the treatment of anxiety in patients with autoimmune thyroiditis and hypothyroidism in the West-Ukrainian population. Клінічна ендокринологія та ендокринна хірургія. 2022;3(79):20-24. DOI: 10.30978/CEES-2022-3-20

22. Kamyshna I, Pavlovych L, Pankiv V, Pankiv I, Kamyshnyi A. Anxiety disorders and prediction of their development in patients with hypothyroidism and autoimmune thyroiditis. Open Access Macedonian Journal of Medical Sciences. 2022 Feb 05;10(B):1-10. DOI: 10.3889/oamjms.2022.9746 (SCOPUS, Q3)

23. Kamyshna I, Pavlovych L, Pankiv I, Pankiv V, Maslyanko V, Bytsko N, Kamyshnyi A The complex influence of the combination of BDNF (rs6265), VDR (rs2228570) and NMDA (rs4880213) genotypes on the development of cognitive disorders in patients with thyroid pathology. Міжнародний ендокринологічний журнал. 2023;19(1):9-15. DOI:  10.22141/2224-0721.19.1.2023.1235 (SCOPUS, Q4)

24. Kamyshna I, Pavlovych L, Pankiv I, Pankiv V, Maslyanko V, Kamyshnyi A. Evaluation of the influence of single-nucleotide polymorphisms of BDNF (rs6265), VDR (rs2228570) and NMDA (rs4880213) genes on gene expression in different tissues. Міжнародний ендокринологічний журнал. 2023;19(2):83-88. DOI: 10.22141/2224-0721.19.2.2023.1250 (SCOPUS, Q4)

25. Kamyshna I. The impact of cholecalciferol on cognitive performance in individuals diagnosed with hypothyroidism and autoimmune thyroiditis. Клінічна ендокринологія та ендокринна хірургія. 2023;1(81):32-38. DOI: 10.30978/CEES-2023-1-32

26. Білоус ІІ, Павлович ЛБ. Особливості ураження нервової системи при первинному гіпотиреозі. Міжнародний ендокринологічний журнал. 2018;14(2):168-172. DOI: 10.22141/2224-0721.14.2.2018.130563

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