Family-based Association Study of 5-HTTLPR/SLC6A4 and uVNTR/MAOA Polymorphisms in Patients with a History of Suicide Attempts
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Abstract
Introduction: Biological factors, especially genetic ones, are associated with the development of suicidal behavior. A 1.7- to 10.6-fold risk of developing suicidal behavior has been observed in individuals with first- or second-degree relatives with suicidal behavior. It has been suggested that the serotonergic and dopaminergic systems are involved in suicide attempts, particularly the SLC6A4 and MAOA genes.
Objective: To analyze the allele transmission of 5-HTTLPR/SLC6A4 and uVNTR/MAOA polymorphisms in families with suicide attempts.
Method: Fifty families with proband with a history of suicide attempts were included. All participants were recruited at the Ramón de la Fuente Muniz National Institute of Psychiatry and evaluated using the International Neuropsychiatric Interview (M.I.N.I.). Allele transmission analysis of the 5-HTTLPR and uVNTR polymorphisms was performed using the Haploview program.
Results: Analysis of allele transmission of the 5-HTTLPR/SLC6A4 polymorphism showed greater transmission of the S allele in probands (χ2 = 6.6, p = .0098) with a previous suicide attempt and in those with two or more suicide attempts (χ2 = 5.4, p = .019). There was no observed preference in uVNTR/MAOA allele transmission.
Discussion and conclusion: Our data support the hypothesis that the serotonin transporter is implicated in the development of suicide attempts in Mexican patients with mood disorders.
References
Aguilar-Velázquez, D. G., González-Castro, T. B., Tovilla-Zárate, C. A., Juárez-Rojop, I. E., López-Narváez, M. L., Fresán, A., Hernández-Díaz, Y., & Guzmán-Priego, C. G. (2017). Gender differences of suicides in children and adolescents: Analysis of 167 suicides in a Mexican population from 2003 to 2013. Psychiatry Research, 258, 83-87. https://doi.org/10.1016/j.psychres.2017.09.083
Bachmann, S. (2018). Epidemiology of Suicide and the Psychiatric Perspective. International Journal of Environmental Research and Public Health, 15(7), 1425. https://doi.org/10.3390/ijerph15071425
Barrett, J. C., Fry, B., Maller, J., & Daly, M. J. (2005). Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics, 21(2), 263-265. https://doi.org/10.1093/bioinformatics/bth457
Bertolote, J. M., & Fleischmann, A. (2002). Suicide and psychiatric diagnosis: a worldwide perspective. World Psychiatry, 1(3), 181-185. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1489848/
Borges, G., Orozco, R., Benjet, C., & Medina-Mora, M. E. (2010). Suicide and suicidal behaviors in Mexico: Retrospective and current status. Salud Publica de México, 52(4), 292-304. https://pubmed.ncbi.nlm.nih.gov/20657958/
Brådvik, L. (2018). Suicide Risk and Mental Disorders. International Journal of Environmental Research and Public Health, 15(9), 2028. https://doi.org/10.3390/ijerph15092028
Brent, D. A., & Melhem, N. (2008). Familial Transmission of Suicidal Behavior. Psychiatric Clinics of North America, 31(2), 157-177. https://doi.org/10.1016/j.psc.2008.02.001
Cabrera-Mendoza, B., Martínez-Magaña, J. J., Genis-Mendoza, A. D., Sarmiento, E., Ruíz-Ramos, D., Tovilla-Zárate, C. A., González-Castro, T. B., Juárez-Rojop, I. E., García-de la Cruz, D. D., López-Armenta, M., Real, F., García-Dolores, F., Flores, G., Vázquez-Roque, R. A., Lanzagorta, N., Escamilla, M., Saucedo‐Uribe, E., Rodríguez-Mayoral, O., Jiménez-Genchi, J., Castañeda-González, C., Roche-Bergua, A., & Nicolini, H. (2020). High polygenic burden is associated with blood DNA methylation changes in individuals with suicidal behavior. Journal of Psychiatric Research, 123, 62-71. https://doi.org/10.1016/j.jpsychires.2020.01.008
Camarena, B., Rinetti, G., Cruz, C., Hernández, S., de la Fuente, J. R., & Nicolini, H. (2001). Association study of the serotonin transporter gene polymorphism in obsessive-compulsive disorder. International Journal of Neuropsychopharmacology, 4(3), 269-272. https://pubmed.ncbi.nlm.nih.gov/11602033/
Campillo Serrano, C., & Fajardo-Dolci, G. (2021). Suicide prevention and suicidal behavior. Gaceta Médica de México, 157(5). https://doi.org/10.24875/gmm.m21000611
De Luca, V., Tharmalingam, S., Sicard, T., & Kennedy, J. L. (2005). Gene-gene interaction between MAOA and COMT in suicidal behavior. Neuroscience Letters, 383(1-2), 151-154. https://doi.org/10.1016/j.neulet.2005.04.001
Fanelli, G., & Serretti, A. (2019). The influence of the serotonin transporter gene 5-HTTLPR polymorphism on suicidal behaviors: a meta-analysis. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 88, 375-387. https://doi.org/10.1016/j.pnpbp.2018.08.007
Genis-Mendoza, A., López-Narvaez, M., Tovilla-Zárate, C., Sarmiento, E., Chavez, A., Martinez-Magaña, J., González-Castro, T., Hernández-Díaz, Y., Juárez-Rojop, I., Ávila-Fernández, Á., & Nicolini, H. (2017). Association between Polymorphisms of the DRD2 and ANKK1 Genes and Suicide Attempt: A Preliminary Case-Control Study in a Mexican Population. Neuropsychobiology, 76(4), 193-198. https://doi.org/10.1159/000490071
Gonda, X., Fountoulakis, K. N., Harro, J., Pompili, M., Akiskal, H. S., Bagdy, G., & Rihmer, Z. (2011). The possible contributory role of the S allele of 5-HTTLPR in the emergence of suicidality. Journal of Psychopharmacology, 25(7), 857-866. https://doi.org/10.1177/0269881110376693
González‐Castro, T. B., Martínez‐Magaña, J. J., Tovilla‐Zárate, C. A., Juárez‐Rojop, I. E., Sarmiento, E., Genis‐Mendoza, A. D., & Nicolini, H. (2019). Gene‐level genome‐wide association analysis of suicide attempt, a preliminary study in a psychiatric Mexican population. Molecular Genetics & Genomic Medicine, 7(12). https://doi.org/10.1002/mgg3.983
Isometsä, E. (2014). Suicidal Behaviour in Mood Disorders—Who, When, and Why? The Canadian Journal of Psychiatry, 59(3), 120-130. https://doi.org/10.1177/070674371405900303
Jamison, K. R. (2000). Suicide and bipolar disorder. The Journal of Clinical Psychiatry, 61(Suppl 9), 47-51. https://pubmed.ncbi.nlm.nih.gov/10826661/
Joiner, T. E., Johnson, F., & Soderstrom, K. (2002). Association Between Serotonin Transporter Gene Polymorphism and Family History of Attempted and Completed Suicide. Suicide and Life-Threatening Behavior, 32(3), 329-332. https://doi.org/10.1521/suli.32.3.329.22167
Kposowa, A. J., & McElvain, J. P. (2006). Gender, place, and method of suicide. Social Psychiatry and Psychiatric Epidemiology, 41(6), 435-443. https://doi.org/10.1007/s00127-006-0054-2
Lee, J., Min, S., Ahn, J., Kim, H., Cha, Y., Oh, E., Moon, J. S., & Kim, M. (2019). Identifying alcohol problems among suicide attempters visiting the emergency department. BMC Psychiatry, 19(1). https://doi.org/10.1186/s12888-019-2347-5
Lesch, K., Bengel, D., Heils, A., Sabol, S. Z., Greenberg, B. D., Petri, S., Benjamin, J., Müller, C. R., Hamer, D. H., & Murphy, D. L. (1996). Association of Anxiety-Related Traits with a Polymorphism in the Serotonin Transporter Gene Regulatory Region. Science, 274(5292), 1527-1531. https://doi.org/10.1126/science.274.5292.1527
Li, D., & He, L. (2007). Meta-analysis supports association between serotonin transporter (5-HTT) and suicidal behavior. Molecular Psychiatry, 12(1), 47-54. https://doi.org/10.1038/sj.mp.4001890
Lutz, P., Mechawar, N., & Turecki, G. (2017). Neuropathology of suicide: recent findings and future directions. Molecular Psychiatry, 22(10), 1395-1412. https://doi.org/10.1038/mp.2017.141
Lynch, F. L., Peterson, E. L., Lu, C. Y., Hu, Y., Rossom, R. C., Waitzfelder, B. E., Owen-Smith, A. A., Hubley, S., Prabhakar, D., Keoki Williams, L., Beck, A., Simon, G. E., & Ahmedani, B. K. (2020). Substance use disorders and risk of suicide in a general US population: a case control study. Addiction Science & Clinical Practice, 15(1). https://doi.org/10.1186/s13722-020-0181-1
Picouto, M. D., Villar, F., & Braquehais, M. D. (2015). The role of serotonin in adolescent suicide: theoretical, methodological, and clinical concerns. International Journal of Adolescent Medicine and Health, 27(2), 129-133. https://doi.org/10.1515/ijamh-2015-5003
R Core Team. (2018). R: A language and environment for statistical computing. R Foundation for Statistical Computing. https://www.R-project.org/
Rihmer, Z., & Rihmer, A. (2019). Depression and suicide - the role of underlying bipolarity. Psychiatria Hungarica, 34(4), 359-368. https://pubmed.ncbi.nlm.nih.gov/31767796/
Sabol, S. Z., Hu, S., & Hamer, D. (1998). A functional polymorphism in the monoamine oxidase A gene promoter. Human Genetics, 103(3), 273-279. https://doi.org/10.1007/s004390050816
Sanabrais-Jiménez, M. A., Aguilar-García, A., Hernández-Muñoz, S., Sarmiento, E., Ulloa, R. E., Jiménez-Anguiano, A., & Camarena, B. (2022). Association study of Catechol-O-Methyltransferase (COMT) rs4680 Val158Met gene polymorphism and suicide attempt in Mexican adolescents with major depressive disorder. Nordic Journal of Psychiatry, 76(3), 202-206. https://doi.org/10.1080/08039488.2021.1945682
Sarmiento-Hernández, E. I., Ulloa-Flores, R. E., Camarena-Medellín, B., Sanabrias-Jiménez, M. A., Aguilar-García, A., & Hernández-Muñoz, S. (2019). Association between 5-HTTLPR polymorphism, suicide attempt, and comorbidity in Mexican adolescents with major depressive disorder. Actas Españolas de Psiquiatría, 47(1), 1-6. https://pubmed.ncbi.nlm.nih.gov/30724325/
Segal, D. L. (2010). Diagnostic Interview Schedule for DSM-IV (DIS-IV). The Corsini Encyclopedia of Psychology. https://doi.org/10.1002/9780470479216.corpsy0273
Sheehan, D. V., Lecrubier, Y., Sheehan, K. H., Amorim, P., Janavs, J., Weiller, E., Hergueta, T., Baker, R., & Dunbar, G. C. (1998). The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. The Journal of Clinical Psychiatry, 59(Suppl 20), 22-33. https://pubmed.ncbi.nlm.nih.gov/9881538/
Sivaramakrishnan, S., Venkatesan, V., Paranthaman, S. K., Sathianathan, R., Raghavan, S., & Pradhan, P. (2023). Impact of Serotonin Pathway Gene Polymorphisms and Serotonin Levels in Suicidal Behaviour. Medical Principles and Practice, 32(4-5), 250-259. https://doi.org/10.1159/000534069
Tondo, L., Vazquez, G. H., & Baldessarini, R. J. (2020). Suicidal Behavior Associated with Mixed Features in Major Mood Disorders. Psychiatric Clinics of North America, 43(1), 83-93. https://doi.org/10.1016/j.psc.2019.10.008
Tsirigotis, K., Gruszczynski, W., & Tsirigotis-Woloszczak, M. (2011). Gender differentiation in methods of suicide attempts. Medical Science Monitor, 17(8), PH65-PH70. https://doi.org/10.12659/msm.881887
Turecki, G. (2014). The molecular bases of the suicidal brain. Nature Reviews Neuroscience, 15(12), 802-816. https://doi.org/10.1038/nrn3839
Turecki, G., & Brent, D. A. (2016). Suicide and suicidal behaviour. The Lancet, 387(10024), 1227-1239. https://doi.org/10.1016/s0140-6736(15)00234-2
Waltes, R., Chiocchetti, A. G., & Freitag, C. M. (2016). The neurobiological basis of human aggression: A review on genetic and epigenetic mechanisms. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 171(5), 650-675.
Wu, Y., Schwebel, D. C., Huang, Y., Ning, P., Cheng, P., & Hu, G. (2020). Sex-specific and age-specific suicide mortality by method in 58 countries between 2000 and 2015. Injury Prevention, 27(1), 61-70. https://doi.org/10.1136/injuryprev-2019-043601
Zalsman, G., Frisch, A., Bromberg, M., Gelernter, J., Michaelovsky, E., Campino, A., Erlich, Z., Tyano, S., Apter, A., & Weizman, A. (2001). Family‐based association study of serotonin transporter promoter in suicidal adolescents: No association with suicidality but possible role in violence traits. American Journal of Medical Genetics, 105(3), 239-245. https://doi.org/10.1002/ajmg.1261
