Molecular markers of a person's predisposition to commit suicidal acts
Suggested citation:
Pechenkina AA, Tyuneva AI, Cygankov BD. [Molecular markers of a person's predisposition to commit suicidal acts]. Rossiiskii psikhiatricheskii zhurnal [Russian Journal of Psychiatry]. 2021;(4):68-79. Russian
In the scientific review, in order to structure the achievements of molecular medicine in the field of suicidology and to determine the specific, prognostically most valuable molecular markers (genetic, epigenetic and biochemical determinants) of a person's predisposition to commit suicidal acts, an analysis of the literature data was carried out. As a result of our research, it was determined that there are currently 4 main scientific directions on the topic: serotonergic model, model of epigenetic changes, model of lipid metabolism and other models; this work brings together the achievements of molecular suicidology. In addition, this review separately discusses the topic of the so-called molecular comorbidity of suicide and other pathologies that have deep intersections with it at the level of biochemistry and epigenetics, which should undoubtedly be taken into account when drawing up a therapy program and consulting patients.
Keywords suicidal ideation; suicidal behavior; suicide genetics; molecular suicidology; serotonin genetics; DNA methylation
1. Fazel S, Runeson B. Suicide. N Engl J Med. 2020;382(3):266–74. DOI: https://doi.org/10.1056/NEJMra1902944; PMID: 31940700 2. Stone DM, Simon TR, Fowler KA, et al. Vital Signs: Trends in State Suicide Rates – United States, 1999–2016 and Circumstances Contributing to Suicide – 27 States, 2015. MMWR Morb Mortal Wkly Rep. 2018;67(22):617–24. DOI: https://doi.org/10.15585/mmwr.mm6722a1; PMID: 29879094 3. World Health Organization. Russian Federation: Suicide rates, age-standardized, per 100 000 population, by sex and year. WHO Mortality Database. 2017. URL: http://apps.who.int/healthinfo/statistics/mortality/whodpms/ (accessed on: 27.06.2021). 4. World Health Organisation. Suicide rate estimates, age-standardized Estimates by country. Global Health Observatory data repository. 2018. URL: https://apps.who.int/gho/data/view.main.MHSUICIDEASDRv?lang=en (accessed on: 27.06.2021). 5. Large MM, Ryan CJ, Carter G, et al. Can we usefully stratify patients according to suicide risk? BMJ (Online). BMJ Publishing Group. 2017;(359):j4627. DOI: https://doi.org/10.1136/bmj.j4627; PMID: 29042363 6. Tsygankov BD, Vaulin SV. Suitsidy i suitsidal'nye popytki (klinika, diagnostika, lechenie). Smolensk; 2012. 232 p. (In Russ.) 7. Lesch KP, Bengel D, Heils A, et al. Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science. 1996;274:1527–31. DOI: https://doi.org/10.1126/science.274.5292.1527; PMID: 8929413 8. Roy A. Biological Psychiatry Original Paper Suicidal Behavior in Depression: Relationship to Platelet Serotonin Transporter. Neuropsychobiology. 1999;39:71–5. DOI: https://doi.org/10.1159/000026563 9. Turecki G, Brière R, Dewar K, et al. Prediction of level of serotonin 2A receptor binding by serotonin receptor 2A genetic variation in postmortem brain samples from subjects who did or did not commit suicide. Am J Psychiatry. 1999;156(9):1456–8. DOI: https://doi.org/10.1176/ajp.156.9.1456; PMID: 10484964 10. Hong C-J, Pan G-M, Tsai S-J. Association Study of Onset Age, Attempted Suicide, Aggressive Behavior, and Schizophrenia with a Serotonin 1B Receptor (A-161T) Genetic Polymorphism. Neuropsychobiology. 2004;49(1):1–4. DOI: https://doi.org/10.1159/000075330; PMID: 14730192 11. Zouk H, McGirr A, Lebel V, et al. The effect of genetic variation of the serotonin 1B receptor gene on impulsive aggressive behavior and suicide. Am J Med Genet B Neuropsychiatr Genet. 2007;144B(8):996–1002. DOI: https://doi.org/10.1002/ajmg.b.30521; PMID: 17510950 12. Pedersen NL, Fiske A. Genetic influences on suicide and nonfatal suicidal behavior: Twin study findings. Eur Psychiatry. 2010;25(5):264–7. DOI: https://doi.org/10.1016/j.eurpsy.2009.12.008; PMID: 20444580 13. Samadi RB, Ghasemi A, Seifi M, et al. Serotonin 1A receptor genetic variations, suicide, and life events in the Iranian population. Psychiatry Clin Neurosci. 2012;66(4):337–43. DOI: https://doi.org/10.1111/j.1440-1819.2012.02333.x; PMID: 22624739 14. Dell’Osso L, Mandelli L, Carlini M, et al. Temperamental and Genetic Predictors of Suicide Attempt and Self-Mutilation. Neuropsychobiology. 2013;68(4):250–7. DOI: https://doi.org/10.1159/000356228; PMID: 24280759 15. de Medeiros Alves V, Bezerra D, de Andrade T, et al. Genetic Polymorphisms Might Predict Suicide Attempts in Mental Disorder Patients: A Systematic Review And Meta-Analysis. CNS Neurol Disord Drug Targets. 2015;14(7):820–7. DOI: https://doi.org/10.2174/1871527314666150713104619; PMID: 26166439 16. Pompili M, Gentile G, Scassellati C, et al. Genetic association analysis of serotonin and signal transduction pathways in suicide attempters from an Italian sample of psychiatric patients. Neurosci Lett. 2017;656:94–102. DOI: https://doi.org/10.1016/j.neulet.2017.07.020; PMID: 28716530 17. Li J, Yoshikawa A, Meltzer HY. Replication of rs300774, a genetic biomarker near ACP1, associated with suicide attempts in patients with schizophrenia: Relation to brain cholesterol biosynthesis. J Psychiatr Res. 2017;94:54–61. DOI: https://doi.org/10.1016/j.jpsychires.2017.06.005; PMID: 28668716 18. Ghasemi A, Seifi M, Baybordi F, et al. Association between serotonin 2A receptor genetic variations, stressful life events and suicide. Gene. 2018;658:191–7. DOI: https://doi.org/10.1016/j.gene.2018.03.023; PMID: 29526601 19. Daray FM, Arena AR, Armesto AR, et al. Serotonin transporter gene polymorphism as a predictor of short-term risk of suicide reattempts. Eur Psychiatry. 2018;54:19–26. DOI: https://doi.org/10.1016/j.gene.2018.03.023; PMID: 29526601 20. Knowles EEM, Curran JE, Meikle PJ, et al. Disentangling the genetic overlap between cholesterol and suicide risk. Neuropsychopharmacology. 2018;43(13):2556–63. DOI: https://doi.org/10.1038/s41386-018-0162-1; PMID: 30082891 21. Ono H, Shirakawa O, Kitamura N, et al. Tryptophan hydroxylase immunoreactivity is altered by the genetic variation in postmortem brain samples of both suicide victims and controls. Mol Psychiatry. 2002;7(10):1127–32. DOI: https://doi.org/10.1038/sj.mp.4001150; PMID: 12476329 22. Schneider E, El Hajj N, Müller F, et al. Epigenetic Dysregulation in the Prefrontal Cortex of Suicide Completers. Cytogenet Genome Res. 2015;146:19–27. DOI: https://doi.org/10.1159/000435778; PMID: 26160260 23. Haghighi F, Galfalvy H, Chen S, et al. DNA Methylation Perturbations in Genes Involved in Polyunsaturated Fatty Acid Biosynthesis Associated with Depression and Suicide Risk. Front Neurol. 2015;6:92. DOI: https://doi.org/10.3389/fneur.2015.00092; PMID: 25972837 24. Bani-Fatemi A, Raymond R, Adanty C, et al. Global DNA methylation in suicidal ideation and suicide attempt in schizophrenia. Psychiatr Genet. 2021;31(2):65–71. DOI: https://doi.org/10.1097/YPG.0000000000000273; PMID: 33399315 25. Czamara D, Tissink E, Tuhkanen J, et al. Combined effects of genotype and childhood adversity shape variability of DNA methylation across age. Transl Psychiatry. 2021;11(1):88. DOI: https://doi.org/10.1038/s41398-020-01147-z; PMID: 33526782 26. Lutz P-E, Chay M-A, Pacis A, et al. Non-CG methylation and multiple histone profiles associate child abuse with immune and small GTPase dysregulation. Nat Commun. 2021;12(1):1132. DOI: https://doi.org/10.1038/s41467-021-21365-3; PMID: 33602921 27. Bani-Fatemi A, Adanty C, Dai N, et al. Genome-wide methylation association with current suicidal ideation in schizophrenia. J Neural Transm (Vienna). 2020;127(9):1315–22. DOI: https://doi.org/10.1007/s00702-020-02225-8; PMID: 32661777 28. Cabrera-Mendoza B, Martínez-Magaña JJ, Genis-Mendoza AD, et al. Brain Gene Expression-DNA Methylation Correlation in Suicide Completers: Preliminary Results. Rev Invest Clin. 2020;72(5):283–92. DOI: https://doi.org/10.24875/RIC.19003250; PMID: 33057323 29. Policicchio S, Washer S, Viana J, et al. Genome-wide DNA methylation meta-analysis in the brains of suicide completers. Transl Psychiatry. 2020;10(1):69. DOI: https://doi.org/10.1038/s41398-020-0752-7; PMID: 32075955 30. Zhang JY, Kothapalli KSD, Brenna JT. Desaturase and elongase-limiting endogenous long-chain polyunsaturated fatty acid biosynthesis. Curr Opin Clin Nutr Metab Care. 2016;19(2):103–10. DOI: https://doi.org/ https://doi.org/10.1097/MCO.0000000000000254; PMID: 26828581 31. Li J, Yoshikawa A, Meltzer HY. Replication of rs300774, a genetic biomarker near ACP1, associated with suicide attempts in patients with schizophrenia: Relation to brain cholesterol biosynthesis. J Psychiatr Res. 2017;94:54–61. DOI: https://doi.org/10.1016/j.jpsychires.2017.06.005; PMID: 28668716 32. Sankaranarayanan A, Pratt R, Anoop A, et al. Serum lipids and suicidal risk among patients with schizophrenia spectrum disorders: Systematic review and meta‐analysis. Acta Psychiatr Scand. 2021;144(2):125–52. DOI: https://doi.org/10.1111/acps.13305; PMID: 33834474 33. Bai S, Fang L, Xie J, et al. Potential Biomarkers for Diagnosing Major Depressive Disorder Patients with Suicidal Ideation. J Inflamm Res. 2021;14:495–503. DOI: https://doi.org/10.2147/JIR.S297930; PMID: 33654420 34. Kułak-Bejda A, Bejda G, Lech M, et al. Are Lipids Possible Markers of Suicide Behaviors? J Clin Med. 2021;10(2):333. DOI: https://doi.org/ https://doi.org/10.3390/jcm10020333; PMID: 33477435 35. Fusar-Poli L, Aguglia A, Amerio A, et al. Peripheral BDNF levels in psychiatric patients with and without a history of suicide attempt: A systematic review and meta-analysis. Prog Neuropsychopharmacol Biol Psychiatry. 2021;111:110342. DOI: https://doi.org/10.1016/j.pnpbp.2021.110342; PMID: 33961965 36. Pasi S, Singh PK, Pandey RK, et al. Evaluation of psychiatric and genetic risk factors among primary relatives of suicide completers in Delhi NCR region, India. Psychiatry Res. 2015;229(3):939–9. DOI: https://doi.org/10.1016/j.psychres.2015.07.015; PMID: 26205629 37. Gao Y, Xiong Y, Liu X, Wang H. The Effects of Childhood Maltreatment on Non-Suicidal Self-Injury in Male Adolescents: The Moderating Roles of the Monoamine Oxidase A (MAOA) Gene and the Catechol-O-Methyltransferase (COMT) Gene. Int J Environ Res Public Health. 2021;18(5):2598. DOI: https://doi.org/10.3390/ijerph18052598; PMID: 33807669 38. Prokop JW, Bupp CP, Frisch A, et al. Emerging Role of ODC1 in Neurodevelopmental Disorders and Brain Development. Genes. 2021;12(4):470. DOI: https://doi.org/10.3390/genes12040470; PMID: 33806076 39. Knowles EEM, Curran JE, Göring HHH, et al. Family-based analyses reveal novel genetic overlap between cytokine interleukin-8 and risk for suicide attempt. Brain Behav Immun. 2019;80:292–9. DOI: https://doi.org/10.1016/j.bbi.2019.04.004; PMID: 30953777 40. Deflesselle E, Colle R, Rigal L, et al. The TRKB rs2289656 genetic polymorphism is associated with acute suicide attempts in depressed patients: A transversal case control study. PLoS One. 2018;13(10):e0205648. DOI: https://doi.org/10.1371/journal.pone.0205648; PMID: 30308049 41. Costanza A, Radomska M, Bondolfi G, et al. Suicidality Associated With Deep Brain Stimulation in Extrapyramidal Diseases: A Critical Review and Hypotheses on Neuroanatomical and Neuroimmune Mechanisms. Front Integr Neurosci. 2021;15:632249. DOI: https://doi.org/10.3389/fnint.2021.632249; PMID: 33897384 42. Farrer LA. Suicide and attempted suicide in Huntington disease: Implications for preclinical testing of persons at risk. Am J Med Genet. 1986;24(2):305–11. DOI: https://doi.org/10.1002/ajmg.1320240211; PMID: 2940862 43. Strawbridge RJ, Ward J, Ferguson A, et al. Identification of novel genome-wide associations for suicidality in UK Biobank, genetic correlation with psychiatric disorders and polygenic association with completed suicide. EBioMedicine. 2019;41:517–25. DOI: https://doi.org/10.1016/j.ebiom.2019.02.005; PMID: 30745170 44. Bozorgmehr A, Alizadeh F, Ofogh SN, et al. What do the genetic association data say about the high risk of suicide in people with depression? A novel network-based approach to find common molecular basis for depression and suicidal behavior and related therapeutic targets. J Affect Disord. 2018;229:463–8. DOI: https://doi.org/10.1016/j.jad.2017.12.079; PMID: 29331709 45. Mullins N, Perroud N, Uher R, et al. Genetic relationships between suicide attempts, suicidal ideation and major psychiatric disorders: A genome-wide association and polygenic scoring study. Am J Med Genet B Neuropsychiatr Genet. 2014;165(5):428–37. DOI: https://doi.org/10.1002/ajmg.b.32247; PMID: 24964207 46. Biegon A, Israeli M. Regionally selective increases in β-adrenergic receptor density in the brains of suicide victims. Brain Res. 1988;442(1):199–203. DOI: https://doi.org/10.1016/0006-8993(88)91453-9; PMID: 2834015 47. Haberlandt WF. Aportación a la genética del suicidio. (Datos en gemelos y hallazgos familiares) [Contribution to the genetics of suicide. (Data in twins and familial findings)]. Folia Clin Int (Barc). 1967;17(6):319–22. PMID: 5606076 48. Goodwin F, Post R. 5-hydroxytryptamine and depression: a model for the interaction of normal variance with pathology. Br J Clin Pharmacol. 1983;15(S3):393S–405S. DOI: https://doi.org/10.1111/j.1365-2125.1983.tb02130.x; PMID: 6190490 49. Korpi ER, Goodman SI, Kleinman JE, et al. Relationship between tryptophan and serotonin concentrations in postmortem human brain. Med Biol. 1987;65(4):217–20. PMID: 2449590 50. Lo M-T, Wang Y, Kauppi K, et al. Modeling prior information of common genetic variants improves gene discovery for neuroticism. Hum Mol Genet. 2017;26(22):4530–9. DOI: https://doi.org/ https://doi.org/10.1093/hmg/ddx340; PMID: 28973307 51. Cabrera B, Monroy-Jaramillo N, Fries GR, et al. Brain Gene Expression Pattern of Subjects with Completed Suicide and Comorbid Substance Use Disorder. Mol Neuropsychiatry. 2019;5(1):60–73. DOI: https://doi.org/ https://doi.org/10.1159/000493940; PMID: 31019919 52. Schneider B, Wolfersdorf M, Wurst FM. Suizid und Suizidprävention im psychiatrischen Krankenhaus. Fortschr Neurol Psychiatr. 2018;86(12):778–96. DOI: https://doi.org/10.1055/a-0648-0408 53. Lee J, Chang SJ, Kim H, et al. Prolonged risk of suicide reattempts in patients with alcohol use disorder and acute alcohol use: A register-based follow-up study (2010-2015). Psychiatry Investig. 2019;16(2):145–53. DOI: https://doi.org/10.30773/pi.2018.11.22; PMID: 30808121 54. Nabiullina RR, Tsygankov BD, Oslopov VN. Lichnost' bol'nogo gipertonicheskoi bolezn'yu: geneticheskie prediktory effektivnoi psikhoterapii. Kazan'; 2013. 304 p. (In Russ.)
DOI: http://dx.doi.org/10.47877/1560-957Х-2021-10408
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