Epigenetics and suicidal behaviour

  • Katarina Uršič Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
  • Alja Videtič Paska Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
Keywords: epigenetic modifications, suicide, DNA methylation, miRNA, histone modification


Suicide is a well-defined public health problem. Slovenia is ranked as one of the European leading countries regarding suicide rate. So far, many neurotransmitter systems have been studied on genetic and biochemical levels. In recent years, focus shifted towards research in the field of epigenetics, which includes noncoding RNA (miRNA), DNA methylation, and post-translational histone modification. miRNAs are short, 19 to 25 nucleotides long single-stranded RNA molecules that bind specifically to mRNA and decrease the expression of targeted genes. Suicide victims showed changes in the expression of miRNA associated with brain neurotrophic factor (BDNF) and its receptor (TrkB), transcription and growth factors, and the polyamine system. DNA methylation is the process of adding methyl group to the 5C site of the cytosine and it results in a decrease of gene transcription. Studies of global methylation identified changes in the patterns of promoter methylation in suicide victims. Many promoters belonged to genes involved in cognitive functions. Looking at candidate genes, changes in methylation pattern were observed at genes for BDNF, TrkB, ribosomal RNA, and the type 2A serotonin receptor promoter region. Histones are the core building blocks of chromatin, representing the protein base around which the DNA is coiled and forming nucleosomes. Histones consist of a globular core part and an N-terminal tail of different lengths, which can be post-translationally modified. Most common modifications are lysine and arginine acetylation and methylation, serine and threonine phosphorylation, lysine ubiquitination and sumoylation, and ADP-ribosylation. Histone modifications of TrkB and polyamine system were observed in suicide victims. Numerous studies thus link epigenetic mechanisms to suicidal behaviour.


Download data is not yet available.


World Health Organization. Mental health action plan 2013–2020 2013 [cited 2017 Jul 4]. Available from: http://www.who.int/mental_health/publications/action_plan/en/

Chesney E, Goodwin GM, Fazel S. Risks of all-cause and suicide mortality in mental disorders: a meta-review. World Psychiatry. 2014 Jun;13(2):153–60. https://doi.org/10.1002/wps.20128 PMID:24890068

Bondy B, Buettner A, Zill P. Genetics of suicide. Mol Psychiatry. 2006 Apr;11(4):336–51. https://doi.org/10.1038/sj.mp.4001803 PMID:16462816

Sadkowski M, Dennis B, Clayden RC, Elsheikh W, Rangarajan S, Dejesus J, et al. The role of the serotonergic system in suicidal behavior. Neuropsychiatr Dis Treat. 2013;9:1699–716. PMID:24235834

Varga G, Szekely A, Sasvari-Szekely M. Candidate gene studies of dopaminergic and serotonergic polymorphisms. Neuropsychopharmacologia Hungarica : a Magyar Pszichofarmakologiai Egyesulet lapja = official journal of the Hungarian Association of Psychopharmacology. 2011;13(2):93–101.

Kim YK, Hwang JA, Lee HJ, Yoon HK, Ko YH, Lee BH, et al. Association between norepinephrine transporter gene (SLC6A2) polymorphisms and suicide in patients with major depressive disorder. J Affect Disord. 2014 Apr;158:127–32. https://doi.org/10.1016/j.jad.2014.01.018 PMID:24655776

Nagy C, Suderman M, Yang J, Szyf M, Mechawar N, Ernst C, et al. Astrocytic abnormalities and global DNA methylation patterns in depression and suicide. Mol Psychiatry. 2015 Mar;20(3):320–8. https://doi.org/10.1038/mp.2014.21 PMID:24662927

Pregelj P, Nedic G, Paska AV, Zupanc T, Nikolac M, Balažic J, et al. The association between brain-derived neurotrophic factor polymorphism (BDNF Val66Met) and suicide. J Affect Disord. 2011 Feb;128(3):287–90. https://doi.org/10.1016/j.jad.2010.07.001 PMID:20667416

Pungercic G, Videtic A, Pestotnik A, Pajnic IZ, Zupanc T, Balazic J, et al. Serotonin transporter gene promoter (5-HTTLPR) and intron 2 (VNTR) polymorphisms: a study on Slovenian population of suicide victims. Psychiatr Genet. 2006 Oct;16(5):187–91. https://doi.org/10.1097/01.ypg.0000218617.65633.9e PMID:16969272

Uršič K, Zupanc T, Paska AV. Analysis of promoter polymorphism in monoamine oxidase A (MAOA) gene in completed suicide on Slovenian population. Neurosci Lett. 2018 Apr;673:111–5. https://doi.org/10.1016/j.neulet.2018.02.063 PMID:29505805

Videtic A, Peternelj TT, Zupanc T, Balazic J, Komel R. Promoter and functional polymorphisms of HTR2C and suicide victims. Genes Brain Behav. 2009 Jul;8(5):541–5. https://doi.org/10.1111/j.1601-183X.2009.00505.x PMID:19496825

Videtic A, Zupanc T, Pregelj P, Balazic J, Tomori M, Komel R. Suicide, stress and serotonin receptor 1A promoter polymorphism -1019C>G in Slovenian suicide victims. Eur Arch Psychiatry Clin Neurosci. 2009 Jun;259(4):234–8. https://doi.org/10.1007/s00406-008-0861-4 PMID:19224112

Zupanc T, Pregelj P, Paska AV. Tryptophan hydroxylase 2 (TPH 2) single nucleotide polymorphisms, suicide, and alcohol-related suicide. Psychiatr Danub. 2013 Sep;25 Suppl 2:S332–6. PMID:23995203

Zupanc T, Pregelj P, Tomori M, Komel R, Paska AV. TPH2 polymorphisms and alcohol-related suicide. Neurosci Lett. 2011 Feb;490(1):78–81. https://doi.org/10.1016/j.neulet.2010.12.030 PMID:21182896

van Vliet J, Oates NA, Whitelaw E. Epigenetic mechanisms in the context of complex diseases. Cell Mol Life Sci. 2007 Jun;64(12):1531–8. https://doi.org/10.1007/s00018-007-6526-z PMID:17458502

Jaenisch R, Bird A. Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals. Nat Genet. 2003 Mar;33(3s Suppl):245–54. https://doi.org/10.1038/ng1089 PMID:12610534

Ambros V. microRNAs: tiny regulators with great potential. Cell. 2001 Dec;107(7):823–6. https://doi.org/10.1016/S0092-8674(01)00616-X PMID:11779458

Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell. 1993 Dec;75(5):843–54. https://doi.org/10.1016/0092-8674(93)90529-Y PMID:8252621

Reinhart BJ, Slack FJ, Basson M, Pasquinelli AE, Bettinger JC, Rougvie AE, et al. The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans. Nature. 2000 Feb;403(6772):901–6. https://doi.org/10.1038/35002607 PMID:10706289

miRBase database: University of Manchester; [cited 2017 4 Jul]. Available from: http://www.mirbase.org

Millar AA, Waterhouse PM. Plant and animal microRNAs: similarities and differences. Funct Integr Genomics. 2005 Jul;5(3):129–35. https://doi.org/10.1007/s10142-005-0145-2 PMID:15875226

Lee Y, Jeon K, Lee JT, Kim S, Kim VN. MicroRNA maturation: stepwise processing and subcellular localization. EMBO J. 2002 Sep;21(17):4663–70. https://doi.org/10.1093/emboj/cdf476 PMID:12198168

Friedman RC, Farh KK, Burge CB, Bartel DP. Most mammalian mRNAs are conserved targets of microRNAs. Genome Res. 2009 Jan;19(1):92–105. https://doi.org/10.1101/gr.082701.108 PMID:18955434

Kawamata T, Seitz H, Tomari Y. Structural determinants of miRNAs for RISC loading and slicer-independent unwinding. Nat Struct Mol Biol. 2009 Sep;16(9):953–60. https://doi.org/10.1038/nsmb.1630 PMID:19684602

Okamura K, Phillips MD, Tyler DM, Duan H, Chou YT, Lai EC. The regulatory activity of microRNA* species has substantial influence on microRNA and 3′ UTR evolution. Nat Struct Mol Biol. 2008 Apr;15(4):354–63. https://doi.org/10.1038/nsmb.1409 PMID:18376413

Hu HY, Yan Z, Xu Y, Hu H, Menzel C, Zhou YH, et al. Sequence features associated with microRNA strand selection in humans and flies. BMC Genomics. 2009 Sep;10(1):413. https://doi.org/10.1186/1471-2164-10-413 PMID:19732433

Sun G, Yan J, Noltner K, Feng J, Li H, Sarkis DA, et al. SNPs in human miRNA genes affect biogenesis and function. RNA. 2009 Sep;15(9):1640–51. https://doi.org/10.1261/rna.1560209 PMID:19617315

Xhemalce B, Robson SC, Kouzarides T. Human RNA methyltransferase BCDIN3D regulates microRNA processing. Cell. 2012 Oct;151(2):278–88. https://doi.org/10.1016/j.cell.2012.08.041 PMID:23063121

Li Y, Kowdley KV. MicroRNAs in common human diseases. Genomics Proteomics Bioinformatics. 2012 Oct;10(5):246–53. https://doi.org/10.1016/j.gpb.2012.07.005 PMID:23200134

Bestor TH. The DNA methyltransferases of mammals. Hum Mol Genet. 2000 Oct;9(16):2395–402. https://doi.org/10.1093/hmg/9.16.2395 PMID:11005794

Prokhortchouk E, Defossez PA. The cell biology of DNA methylation in mammals. Biochim Biophys Acta. 2008 Nov;1783(11):2167–73. https://doi.org/10.1016/j.bbamcr.2008.07.015 PMID:18706939

Illingworth RS, Bird AP. CpG islands—‘a rough guide’. FEBS Lett. 2009 Jun;583(11):1713–20. https://doi.org/10.1016/j.febslet.2009.04.012 PMID:19376112

Bird A. DNA methylation patterns and epigenetic memory. Genes Dev. 2002 Jan;16(1):6–21. https://doi.org/10.1101/gad.947102 PMID:11782440

Kohli RM, Zhang Y. TET enzymes, TDG and the dynamics of DNA demethylation. Nature. 2013 Oct;502(7472):472–9. https://doi.org/10.1038/nature12750 PMID:24153300

Gräff J, Mansuy IM. Epigenetic codes in cognition and behaviour. Behav Brain Res. 2008 Sep;192(1):70–87. https://doi.org/10.1016/j.bbr.2008.01.021 PMID:18353453

Pidsley R, Mill J. Epigenetic studies of psychosis: current findings, methodological approaches, and implications for postmortem research. Biol Psychiatry. 2011 Jan;69(2):146–56. https://doi.org/10.1016/j.biopsych.2010.03.029 PMID:20510393

Mill J, Tang T, Kaminsky Z, Khare T, Yazdanpanah S, Bouchard L, et al. Epigenomic profiling reveals DNA-methylation changes associated with major psychosis. Am J Hum Genet. 2008 Mar;82(3):696–711. https://doi.org/10.1016/j.ajhg.2008.01.008 PMID:18319075

Melka MG, Castellani CA, Rajakumar N, O’Reilly R, Singh SM. Olanzapine-induced methylation alters cadherin gene families and associated pathways implicated in psychosis. BMC Neurosci. 2014 Sep;15(1):112. https://doi.org/10.1186/1471-2202-15-112 PMID:25266742

Asai T, Bundo M, Sugawara H, Sunaga F, Ueda J, Tanaka G, et al. Effect of mood stabilizers on DNA methylation in human neuroblastoma cells. Int J Neuropsychopharmacol. 2013 Nov;16(10):2285–94. https://doi.org/10.1017/S1461145713000710 PMID:23931339

Perisic T, Zimmermann N, Kirmeier T, Asmus M, Tuorto F, Uhr M, et al. Valproate and amitriptyline exert common and divergent influences on global and gene promoter-specific chromatin modifications in rat primary astrocytes. Neuropsychopharmacology. 2010 Feb;35(3):792–805. https://doi.org/10.1038/npp.2009.188 PMID:19924110

Zimmermann N, Zschocke J, Perisic T, Yu S, Holsboer F, Rein T. Antidepressants inhibit DNA methyltransferase 1 through reducing G9a levels. Biochem J. 2012 Nov;448(1):93–102. https://doi.org/10.1042/BJ20120674 PMID:22880885

Le François B, Soo J, Millar AM, Daigle M, Le Guisquet AM, Leman S, et al. Chronic mild stress and antidepressant treatment alter 5-HT1A receptor expression by modifying DNA methylation of a conserved Sp4 site. Neurobiol Dis. 2015 Oct;82:332–41. https://doi.org/10.1016/j.nbd.2015.07.002 PMID:26188176

Melas PA, Rogdaki M, Lennartsson A, Björk K, Qi H, Witasp A, et al. Antidepressant treatment is associated with epigenetic alterations in the promoter of P11 in a genetic model of depression. Int J Neuropsychopharmacol. 2012 Jun;15(5):669–79. https://doi.org/10.1017/S1461145711000940 PMID:21682946

Wei Y, Melas PA, Wegener G, Mathé AA, Lavebratt C. Antidepressant-like effect of sodium butyrate is associated with an increase in TET1 and in 5-hydroxymethylation levels in the Bdnf gene. Int J Neuropsychopharmacol. 2014 Oct;18(2):pyu032. https://doi.org/10.1093/ijnp/pyu032 PMID:25618518

Sun H, Kennedy PJ, Nestler EJ. Epigenetics of the depressed brain: role of histone acetylation and methylation. Neuropsychopharmacology. 2013 Jan;38(1):124–37. https://doi.org/10.1038/npp.2012.73 PMID:22692567

Kornberg RD, Thomas JO. Chromatin structure; oligomers of the histones. Science. 1974 May;184(4139):865–8. https://doi.org/10.1126/science.184.4139.865 PMID:4825888

Arents G, Moudrianakis EN. The histone fold: a ubiquitous architectural motif utilized in DNA compaction and protein dimerization. Proc Natl Acad Sci USA. 1995 Nov;92(24):11170–4. https://doi.org/10.1073/pnas.92.24.11170 PMID:7479959

Davey CA, Sargent DF, Luger K, Maeder AW, Richmond TJ. Solvent mediated interactions in the structure of the nucleosome core particle at 1.9 a resolution. J Mol Biol. 2002 Jun;319(5):1097–113. https://doi.org/10.1016/S0022-2836(02)00386-8 PMID:12079350

Mariño-Ramírez L, Kann MG, Shoemaker BA, Landsman D. Histone structure and nucleosome stability. Expert Rev Proteomics. 2005 Oct;2(5):719–29. https://doi.org/10.1586/14789450.2.5.719 PMID:16209651

Rothbart SB, Strahl BD. Interpreting the language of histone and DNA modifications. Biochim Biophys Acta. 2014 Aug;1839(8):627–43. https://doi.org/10.1016/j.bbagrm.2014.03.001 PMID:24631868

Peterson CL, Laniel MA. Histones and histone modifications. Curr Biol. 2004 Jul;14(14):R546–51. https://doi.org/10.1016/j.cub.2004.07.007 PMID:15268870

Kazantsev AG, Thompson LM. Therapeutic application of histone deacetylase inhibitors for central nervous system disorders. Nat Rev Drug Discov. 2008 Oct;7(10):854–68. https://doi.org/10.1038/nrd2681 PMID:18827828

Wang Y, Xia J, Helfer B, Li C, Leucht S. Valproate for schizophrenia. Cochrane Database Syst Rev. 2016 Nov;11:CD004028. PMID:27884042

Misztak P, Pańczyszyn-Trzewik P, Sowa-Kućma M. Histone deacetylases (HDACs) as therapeutic target for depressive disorders. Pharmacol Rep. 2018 Apr;70(2):398–408. https://doi.org/10.1016/j.pharep.2017.08.001 PMID:29456074

Machado-Vieira R, Ibrahim L, Zarate CA Jr. Histone deacetylases and mood disorders: epigenetic programming in gene-environment interactions. CNS Neurosci Ther. 2011 Dec;17(6):699–704. https://doi.org/10.1111/j.1755-5949.2010.00203.x PMID:20961400

Fuchikami M, Yamamoto S, Morinobu S, Okada S, Yamawaki Y, Yamawaki S. The potential use of histone deacetylase inhibitors in the treatment of depression. Prog Neuropsychopharmacol Biol Psychiatry. 2016 Jan;64:320–4. https://doi.org/10.1016/j.pnpbp.2015.03.010 PMID:25818247

Strahl BD, Allis CD. The language of covalent histone modifications. Nature. 2000 Jan;403(6765):41–5. https://doi.org/10.1038/47412 PMID:10638745

Li B, Carey M, Workman JL. The role of chromatin during transcription. Cell. 2007 Feb;128(4):707–19. https://doi.org/10.1016/j.cell.2007.01.015 PMID:17320508

Portela A, Esteller M. Epigenetic modifications and human disease. Nat Biotechnol. 2010 Oct;28(10):1057–68. https://doi.org/10.1038/nbt.1685 PMID:20944598

Nestler EJ, Peña CJ, Kundakovic M, Mitchell A, Akbarian S. Epigenetic Basis of Mental Illness. Neuroscientist. 2016 Oct;22(5):447–63. https://doi.org/10.1177/1073858415608147 PMID:26450593

Maussion G, Yang J, Yerko V, Barker P, Mechawar N, Ernst C, et al. Regulation of a truncated form of tropomyosin-related kinase B (TrkB) by Hsa-miR-185* in frontal cortex of suicide completers. PLoS One. 2012;7(6):e39301. https://doi.org/10.1371/journal.pone.0039301 PMID:22802923

Kozaki K, Imoto I, Mogi S, Omura K, Inazawa J. Exploration of tumor-suppressive microRNAs silenced by DNA hypermethylation in oral cancer. Cancer Res. 2008 Apr;68(7):2094–105. https://doi.org/10.1158/0008-5472.CAN-07-5194 PMID:18381414

Duursma AM, Kedde M, Schrier M, le Sage C, Agami R. miR-148 targets human DNMT3b protein coding region. RNA. 2008 May;14(5):872–7. https://doi.org/10.1261/rna.972008 PMID:18367714

Smalheiser NR, Lugli G, Rizavi HS, Torvik VI, Turecki G, Dwivedi Y. MicroRNA expression is down-regulated and reorganized in prefrontal cortex of depressed suicide subjects. PLoS One. 2012;7(3):e33201. https://doi.org/10.1371/journal.pone.0033201 PMID:22427989

Xiao F, Zuo Z, Cai G, Kang S, Gao X, Li T. miRecords: an integrated resource for microRNA-target interactions. Nucleic Acids Res. 2009 Jan;37(Database issue):D105–10. https://doi.org/10.1093/nar/gkn851 PMID:18996891

Fiori LM, Turecki G. Implication of the polyamine system in mental disorders. J Psychiatry Neurosci. 2008 Mar;33(2):102–10. PMID:18330456

Lopez JP, Fiori LM, Gross JA, Labonte B, Yerko V, Mechawar N, et al. Regulatory role of miRNAs in polyamine gene expression in the prefrontal cortex of depressed suicide completers. Int J Neuropsychopharmacol. 2014 Jan;17(1):23–32. https://doi.org/10.1017/S1461145713000941 PMID:24025154

Pantazatos SP, Andrews SJ, Dunning-Broadbent J, Pang J, Huang YY, Arango V, et al. Isoform-level brain expression profiling of the spermidine/spermine N1-Acetyltransferase1 (SAT1) gene in major depression and suicide. Neurobiol Dis. 2015 Jul;79:123–34. https://doi.org/10.1016/j.nbd.2015.04.014 PMID:25959060

Pantazatos SP, Huang YY, Rosoklija GB, Dwork AJ, Arango V, Mann JJ. Whole-transcriptome brain expression and exon-usage profiling in major depression and suicide: evidence for altered glial, endothelial and ATPase activity. Mol Psychiatry. 2017 May;22(5):760–73. https://doi.org/10.1038/mp.2016.130 PMID:27528462

Roy B, Wang Q, Palkovits M, Faludi G, Dwivedi Y. Altered miRNA expression network in locus coeruleus of depressed suicide subjects. Sci Rep. 2017 Jun;7(1):4387. https://doi.org/10.1038/s41598-017-04300-9 PMID:28663595

Shendure J, Ji H. Next-generation DNA sequencing. Nat Biotechnol. 2008 Oct;26(10):1135–45. https://doi.org/10.1038/nbt1486 PMID:18846087

Labonté B, Suderman M, Maussion G, Lopez JP, Navarro-Sánchez L, Yerko V, et al. Genome-wide methylation changes in the brains of suicide completers. Am J Psychiatry. 2013 May;170(5):511–20. https://doi.org/10.1176/appi.ajp.2012.12050627 PMID:23511308

Haghighi F, Xin Y, Chanrion B, O’Donnell AH, Ge Y, Dwork AJ, et al. Increased DNA methylation in the suicide brain. Dialogues Clin Neurosci. 2014 Sep;16(3):430–8. PMID:25364291

Schneider E, El Hajj N, Müller F, Navarro B, Haaf T. Epigenetic Dysregulation in the Prefrontal Cortex of Suicide Completers. Cytogenet Genome Res. 2015;146(1):19–27. https://doi.org/10.1159/000435778 PMID:26160260

Keller S, Sarchiapone M, Zarrilli F, Videtic A, Ferraro A, Carli V, et al. Increased BDNF promoter methylation in the Wernicke area of suicide subjects. Arch Gen Psychiatry. 2010 Mar;67(3):258–67. https://doi.org/10.1001/archgenpsychiatry.2010.9 PMID:20194826

McGowan PO, Sasaki A, Huang TC, Unterberger A, Suderman M, Ernst C, et al. Promoter-wide hypermethylation of the ribosomal RNA gene promoter in the suicide brain. PLoS One. 2008 May;3(5):e2085. https://doi.org/10.1371/journal.pone.0002085 PMID:18461137

Abdolmaleky HM, Yaqubi S, Papageorgis P, Lambert AW, Ozturk S, Sivaraman V, et al. Epigenetic dysregulation of HTR2A in the brain of patients with schizophrenia and bipolar disorder. Schizophr Res. 2011 Jul;129(2-3):183–90. https://doi.org/10.1016/j.schres.2011.04.007 PMID:21550210

Ernst C, Deleva V, Deng X, Sequeira A, Pomarenski A, Klempan T, et al. Alternative splicing, methylation state, and expression profile of tropomyosin-related kinase B in the frontal cortex of suicide completers. Arch Gen Psychiatry. 2009 Jan;66(1):22–32. https://doi.org/10.1001/archpsyc.66.1.22 PMID:19124685

Davies MN, Volta M, Pidsley R, Lunnon K, Dixit A, Lovestone S, et al. Functional annotation of the human brain methylome identifies tissue-specific epigenetic variation across brain and blood. Genome Biol. 2012 Jun;13(6):R43. https://doi.org/10.1186/gb-2012-13-6-r43 PMID:22703893

Aberg KA, Xie LY, McClay JL, Nerella S, Vunck S, Snider S, et al. Testing two models describing how methylome-wide studies in blood are informative for psychiatric conditions. Epigenomics. 2013 Aug;5(4):367–77. https://doi.org/10.2217/epi.13.36 PMID:23895651

Ernst C, Chen ES, Turecki G. Histone methylation and decreased expression of TrkB.T1 in orbital frontal cortex of suicide completers. Mol Psychiatry. 2009 Sep;14(9):830–2. https://doi.org/10.1038/mp.2009.35 PMID:19696771

Fiori LM, Turecki G. Genetic and epigenetic influences on expression of spermine synthase and spermine oxidase in suicide completers. Int J Neuropsychopharmacol. 2010 Jul;13(6):725–36. https://doi.org/10.1017/S1461145709991167 PMID:20059804

Fiori LM, Turecki G. Epigenetic regulation of spermidine/spermine N1-acetyltransferase (SAT1) in suicide. J Psychiatr Res. 2011 Sep;45(9):1229–35. https://doi.org/10.1016/j.jpsychires.2011.03.015 PMID:21501848

Fiori LM, Gross JA, Turecki G. Effects of histone modifications on increased expression of polyamine biosynthetic genes in suicide. Int J Neuropsychopharmacol. 2012 Sep;15(8):1161–6. https://doi.org/10.1017/S1461145711001520 PMID:22008221

How to Cite
Uršič K, Videtič Paska A. Epigenetics and suicidal behaviour. ZdravVestn [Internet]. 28Oct.2018 [cited 21Jul.2019];87(9-10):417-28. Available from: https://vestnik.szd.si/index.php/ZdravVest/article/view/2660