According to World Health Organization more about 800.000 people die yearly from suicide thus representing a serious health problem worldwide. Among countries reporting suicide rates, the highest are found in Eastern Europe, including Slovenia (19.89 victims/100,000 citizens for the year 2017; 31.87 for man and 8.08 for women). Over last decades, the interest for neurobiology of suicide has been growing. Genetic-epidemiological studies clearly indicate that genes play an important and specific role in the aetiology of suicidal behaviour and there is also consistent evidence suggesting that even predisposition for suicidal behaviour has a genetic component. Studies of candidate genes are oriented mostly towards the study of neurotransmitter systems (serotonergic, dopaminergic and noradrenergic systems), genes associated with stress response that influence the hypothalamic-pituitary-adrenal (HPA) function, and neurotrophins.
Suicide represents a complex psychiatric phenotype, and like other psychiatric disorders, it is a consequence of interplay between numerous environmental and genetic factors. However, the contributions of individual factors are small, but together they may lead to a disorder. Thus, we are looking for putative genetic markers that may be helpful for the early detection and prevention of suicidal behaviour and possibly, in the future, also for the design of selective targeting drugs. In our past research we focused on genetic variants or SNPs of the genes (and their regulatory regions) from the serotonergic system and their association with suicide alone as well as with suicidal behaviour associated psychiatric disorders, in particular with alcohol consumption having a significant association with regional suicide rates in the Slovenian population.
Our recent work, however, became oriented towards epigenetics. Namely, epigenetics might help us link the environmental and genetic factors, and therefore importantly contribute towards better and deeper understanding of psychopathologies. Our central research topic is DNA methylation, genome-wide and also targeted to specific candidate genes. Future plans include also studying of other epigenetic mechanisms, like histone marks and miRNA.
⇒ Link to a current core research project: Alzehimer’s disease
Past and Present Research Projects:
- Z3- Zinc finger 714 as a potential biomarker of suicidal behaviour; basic post-doctoral project, K. Kouter, 1/9/2020 – 31.8.2022; http://Z3-2653
- J3-9293 Early detection of Alzheimer’s disease by determining the methylation of candidate genes in free circulating DNA; basic research project, A. Videtič-Paska, 1/7/2018 – 30/6/2021; http://www.sicris.si/search/prj.aspx?lang=slv&id=17319.
- National research program P1-0390 Functional Genomics and Biotechnology for Health; R. Komel, 1/1/2015 – 10/7/2017 / D. Rozman, 10/7/2017 – 31/12/2020 (previously P1-0104; 2009-2014, R. Komel); A/ Molecular and Cellular Understanding of Selected Complex Multifactorial Disorders: WP3 – Molecular-genetic basis of psychiatric disorders (A. Videtič Paska).
- BI-MK/17-18-003 Bilateral project Slovenia-Macedonia: Analysis of forensic and ancestry informative Y chromosome SNPs, A. Videtič Paska, 2017-2018.
- J3-7132 Epigenetic factors and gene expression in suicidal behaviour; basic research project, A. Videtič-Paska, 1/1/2016―31/12/2018; http://www.sicris.si/search/prj.aspx?lang=slv&id=9934.
- J3-7320 Influence of different neuronavigation procedures on treatment efficacy of repetitive transcranial magnetic stimulation in depression; basic research project, P. Pregelj (University Psychiatric Clinic Ljubljana), A. Videtič Paska was leader of the research group at the Faculty of Medicine, 1/1/2016 – 31/12/2018; http://www.sicris.si/search/prj.aspx?lang=slv&id=9940.
- Bilateral project Slovenia-Croatia. A. Videtič Paska was a collaborator in the project of the UKC Psychiatric Clinic project Molecular genetics of suicide – looking for association with BDNF and COMPT genes; 2010-2011.
- Z3-2180 Association of genetic, epigenetic and phenotypic characteristics at suicide victims; post-doctoral research project, A. Videtič-Paska, 1/5/2009 ― 30/4/2011; http://www.sicris.si/search/prj.aspx?lang=slv&id=6647.
Clinical partner:
- University Psychiatric Clinic Ljubljana (Prof. Peter Pregelj, MD, PhD; Assist. Prof. Jurij Bon, MD, PhD)
Collaborating research/faculty institute:
- Faculty of Medicine UL, Institute for Forensic Medicine (Assist. Prof. Tomaž Zupanc, MD, PhD)
Collaborating company:
International collaboration:
- Ruđer Bošković Institute, Zagreb, Croatia: Laboratory of Molecular neuro-psychiatry (Prof. Nela Pivac, DVM, PhD)
- University “Ss. Cyril and Methodius”, Medical Faculty, •Institute of Forensic Medicine and Criminalistics, Skopje, Macedonia (Assist. Prof. Renata Jankova, MD, PhD)
- University of Molisse, Campobasso, Italy (Prof. Marco Sarchiapone, MD, PhD).
Researchers involved:
| Researcher | Position |
| Alja Videtič Paska | Project leader, P.I. |
| Katarina Kouter | PostDoc Researcher |
| Iris Šalamon | PhD student / JR |
| Former Researchers | |
| Sandra Ropret | Former PhD student |
| Radovan Komel | MCMB leader, former contributor |
| Galina Pungerčič† | Former senior researcher |
Education:
| Student | Thesis | Title | Year | Supervisors |
| Marija Atanasova | MSc | DNA methylation of candidate genes and quantification of cfDNA in patients with depression. | 2020 | Alja Videtič Paska |
| Katarina Kouter | PhD | DNA methylation in Slovenian male suicide victims by hanging. | 2019 | Alja Videtič Paska |
| Tjaša Grum | MSc | Determination of DNA methylation and suicidal behaviour. | 2019 | Alja Videtič Paska |
| Marjeta Horvat | MSc | DNA methylation and suicidal behavior. | 2018 | Alja Videtič Paska |
| Anka Hotko | MSc | Expression and methylation of the RELN gene in suicide victims. | 2017 | Alja Videtič Paska |
| Sandra Ropret | PhD | Genetic and epigenetic changes in neurotrophin system genes. Association with suicide. | 2017 |
Alja Videtič Paska Radovan Komel |
| Katarina Uršič | MSc | Investigation of MAO A gene promotor polymorphism in suicide victims and of TPH2 gene polymorphism in subjects suffering from alcohol addiction syndrome. | 2015 | Alja Videtič Paska |
| Marjeta Horvat | Dipl | Analysis of candidate gene expression in suicide victims | 2015 | Alja Videtič paska |
| Karmen Kmet | Dipl | Study of brain neurothropic factor single nucleotide polymorphisms in suicide victims. | 2015 | Alja Videtič Paska |
| Tanja Čugura & Jakob Boh | Prešern award | Complex suicide and polmorphisms in the genes of MAOA and MAOB. | 2014 | Alja Videtič Paska |
| Žan Rojc | Dipl | Analysis of DRD2 gene polymorphisms in suicide victims. | 2014 |
Radovan Komel Alja Videtič Paska |
| Vesna Štorgel | Dipl | Analysis of polymorphisms in the genes HTR2A and CACNA1C in suicide victims. | 2012 |
Radovan Komel Alja Videtič Paska |
| Martina Grgić | Dipl | Analysis of reelin gene polymorphisms in suicide victims. | 2011 |
Radovan Komel Alja Videtič Paska |
| Alja Videtič Paska | PhD | Molecular analysis of serotonin signaling pasthway genes ans suicide in Slovenia. | 2007 |
Radovan Komel Martina Tomori |
| Rok Kopinč | Dipl | Analysis of serotonin 1B and 2C receptor gene polymophisms in suicide victims. | 2007 |
Radovan Komel Alja Videtič Paska |
| Tina T. Peternelj | Dipl | Study of serotonine receptor 2C gene polymorphism G(-995)A at suicide victims with RFLP and DNA melting methods. | 2007 |
Radovan Komel Alja Videtič Paska |
| Anita Pestotnik | Dipl | Analysis of polymorphisms in the promoter and in the intron 2 of the serotonin transporter gene in suicide victims. | 2004 |
Janja Marc Radovan Komel Alja Videtič Paska |
Selected publications:
- Nikolac Perković M., Videtič Paska A., Konjevod M., Kouter K., Svob Strac D., Nedić Erjavec G., PivacN. (2021) : Epigenetics of Alzheimer’s disease (Review). Biomolecules 11(2): 1-38; https://www.mdpi.com/2218-273X/11/2/195, doi: 10.3390/biom11020195.
- Gašperšič J., Kristan A., Kunej T., Preložnik-Zupan I., Debeljak N. (2020): Erythrocytosis : genes and pathways involved in disease development (Review). Blood Transfusion – on line first; http://www.bloodtransfusion.it/articolosing.aspx?id=001129, doi: 10.2450/2020.0197-20.
- Videtič Paska A., Kouter K. (2020): Machine learning as the new approach in understanding biomarkers of suicidal behavior (Review). Bosnian Journal of Basic Medical Sciences xx; https://bjbms.org/ojs/index.php/bjbms/article/view/4623/1309, https://www.bjbms.org/ojs/index.php/bjbms/article/view/5146, doi: 10.17305/bjbms.2020.5146.
- Kouter K., Videtič PaskaA. (2020): Biomarkers for suicidal behavior : miRNAs and their potential for diagnostics through liquid biopsy – a systematic review (Review). Epigenomics xx; https://www.futuremedicine.com/doi/10.2217/epi-2020-0196, doi: 10.2217/epi-2020-0196.
- Gašperšič J., Videtič PaskaA. (2020) : Potential of modern circulating cell-free DNA diagnostic tools for detection of specific tumour cells in clinical practice (Review). Biochemia Medica 30(3): 1-13; doi: 10.11613/BM.2020.030504.
- Jankova-Ajanovska R., Geppert M., Videtič Paska A., Willuweit S., Roewer L. (2019): Y-chromosome diversity of the three major ethno-linguistic groups in the Republic of North Macedonia. Forensic Science International, Genetics 42: 165-170; doi: 10.1016/j.fsigen.2019.07.007.
- Kouter K., Zupanc T., Videtič Paska A. (2019): Genome-wide DNA methylation in suicide victims revealing impact on gene expression. J. Affect. Disord.; doi: 10.1016/j.jad.2019.04.077.
- Kouter K., Zupanc T., Videtič Paska A. (2019): Genome-wide DNA methylation patterns in suicide victims : identification of new candidate genes (Review). Psychiatria Danubina 31(4): 392-396. http://www.psychiatria-danubina.com/UserDocsImages/pdf/dnb_vol31_no4/dnb_vol31_no4_392.pdf.
- Kouter K., Zupanc T., Videtič Paska A. (2018): Analysis of promoter polymorphism in monoamine oxidase A (MAOA) gene in completed suicide on Slovenian population. Neuroscience Letters 673: 111-115; doi: 10.1016/j.neulet.2018.02.063.
- Čugura T., Boh J., Zupanc T., Pregelj P., Videtič Paska A. (2018): Differences in SNP genotype distributions between complex and simple suicides. Int. J. Leg. Med. 132(6): 1595-1601; doi: 10.1007/s00414-018-1820-x .
- Politakis V. A., Pregelj P., Videtič Paska A., Zupanc T. (2017): Association between alcohol abuse, childhood adverse events and suicide. Zdravniški vestnik / Medical Journal 86(9/10): 365-372.
- Bučić M. et al. (2016): Completed suicide, depression, and RELN polymorphisms. Psychiatr. Genet. 26(5): 218-22; doi:10.1097/YPG.0000000000000142.
- Ropret S. et al (2015): Investigating the associations between polymorphisms in the NTRK2 and NGFR genes and completed suicide in the Slovenian sample. Psychiatr. Genet. 6: 241-248; doi: 10.1097/YPG.0000000000000109.
- Ropret S. et al. (2015): Single nucleotide polymorphisms in the BDNF gene and suicide in the Slovenian population. Neurosci. Lett. 602: 12-16; doi: 10.1016/j.neulet.2015.06.027.
- Ropret S. et al. (2015): Data in support of association study of the brain-derived neurotrophic factor gene SNPs and completed suicide in the Slovenian sample. Data in Brief 4: 529-533; doi:10.1016/j.dib.2015.07.015.
- Pivac N. et al. (2011): The association between brain-derived neurotrophic factor polymorphism (BDNF Val66Met) and suicide. J. Affect. Disord. 128(3): 287-90. doi: 10.1016/j.jad.2010.07.001.
- Keller S. et al. (2011): TrkB gene expression and DNA methylation state in Wernicke area does not associate with suicidal behavior. J. Affect. Disord. 135(1-3): 400-4; doi: 10.1016/j.jad.2011.07.003.
- Pregelj P. et al. (2011): The association between brain-derived neurotrophic factor polymorphism (BDNF Val66Met) and suicide. J. Affect. Disord. 128(3): 287-290; doi:10.1016/j.jad.2010.07.001.
- Zupanc T. et al. (2011): TPH2 polymorphisms and alcohol-related suicide. Neuroscience Letters 490(1): 78-81; doi: 10.1016/j.neulet.2010.12.030.
- Keller S. et al. (2010): Increased BDNF promoter methylation in the wernicke area of suicide subjects. Psychiatry 67(3): 258-267; doi: 10.1001/archgenpsychiatry.2010.9.
- Zupanc T. et al. (2010): No association between polymorphisms in four serotonin receptor genes, serotonin transporter gene and alcohol-related suicide. Psychiatria Danubina 22(4): 522-527; http://www.psychiatria-danubina.com/UserDocsImages/pdf/dnb_vol22_no4/dnb_vol22_no4_522.pdf.
- Videtič A. et al. (2009): Suicide, stress and serotonin receptor 1A promoter polymorphism -1019C>G in Slovenian suicide victims. Psych. & Clin. Neurosci. 259(4): 234-238; doi: 10.1007/s00406-008-0861-4.
- Videtič A. et al. (2009): Promoter and functional polymorphisms of HTR2C and suicide victims. Genes, Brain and Behavior 5(8): 541-545; doi: 10.1111/j.1601-183X.2009.00505.x.
- Videtič A. et al. (2008): Case report on the analysis of single nucleotide polymorphisms of serotonergic pathway and array-based comparative genomic hybridisation of a suicide victim. Psychiatria Danubina 20(2): 245-248; https://www.ncbi.nlm.nih.gov/pubmed/18587299.
- Videtič A. et al. (2006): Association study of seven polymorphisms in four serotonin receptor genes on suicide victims. Med. Genet. Part B, Neuropsych. Genet. 141B(6): 669-672; doi:1 0.1002/ajmg.b.30390.
- Pungerčič G. et al. (2006): Serotonin transporter gene promoter (5-HTTLPR) and intron 2 (VNTR) polymorphisms : a study on Slovenian population of suicide victims. Psychiatric Genetics 16(5): 187-191; doi: 10.1097/01.ypg.0000218617.65633.9e.