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Órgano Oficial del Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz

2018, Number 5

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Salud Mental 2018; 41 (5)

Association of the SLC6A4 gene 5HTTLPR polymorphism and ADHD with epilepsy, gestational diabetes, and parental substance abuse in Mexican mestizo children

Durán-González J, Leal-Ugarte E, Cruz-Alcalá LE, Gutiérrez-Angulo M, Gallegos-Arreola MP, Meza-Espinoza JP, Reyes-Zurita I, Padilla-Macías PL, Cruz-Martín del Campo E, Peralta-Leal V

Language: English
References: 42
Page: 223-227
PDF size: 329.24 Kb.


ABSTRACT

Introduction. Attention deficit hyperactivity disorder (ADHD) is one of the most common neuropsychiatric conditions in childhood and a multifactorial condition attributable to genetic and/or environmental influence. Allelic variants in the serotonin transporter gene (SLC6A4) have been associated to lower transcriptional efficiency, changes in serotonin concentration in several brain regions, and ADHD development. Objective. To identify the association between the SLC6A4 alleles and ADHD diagnosis and risk factor phenotypes in children from a Mexican mestizo population. Method. In this study, 134 unrelated children were included and evaluated for ADHD, genotypification for the 5HTTLPR polymorphism, and identification of multiple phenotypes from their clinical records and family background for association analysis. Results. The following distribution of genotypes was observed: 23% SS, 49% SL, and 28% LL. From the phenotypes evaluated in the present study, gestational diabetes mellitus (p = .045), history of epilepsy (p = .047), and parental substance abuse (p = .033) showed an association with ADHD development in regression analysis along with the S variant. Discussion and conclusion. Results suggest that interaction of the S allele and some of the phenotypes analyzed may play a relevant role in the development of ADHD in the studied population.


REFERENCES

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  2. Chronis, A. M., Lahey, B. B., Pelham, W. E., Kipp, H. L., Baumann, B. L., & Lee, S. S. (2003). Psychopathology and substance abuse in parents of young children with attention-deficit/hyperactivity disorder. Journal of the American Academy of Child & Adolescent Psychiatry, 42(12), 1424-1432. doi: 10.1097/00004583- 200312000-00009

  3. Cohen, R., Senecky, Y., Shuper, A., Inbar, D., Chodick, G., Shalev, V., & Raz, R. (2013). Prevalence of epilepsy and attention-deficit hyperactivity (ADHD) disorder: A population-based study. Journal of Child Neurology, 28(1), 120-123. doi: 10.1177/0883073812440327

  4. Cornejo-Escatell, E., Fajardo-Fregoso, B. F., López-Velázquez, V. M., Soto-Vargas, J., & Ceja-Moreno, H. (2015). Prevalence of attention deficit hyperactivity disorder in children from northeast Jalisco. RevistaMédica MD, 6(3), 190-195.

  5. Cook, E. C., Courchesne, R., Lord, C., Cox, N. J., Yan, S., Lincoln, A., … Leventhal, B. L. (1997). Evidence of linkage between the serotonin transporter and autistic disorder. Molecular Psychiatry, 2(3), 247-250. doi: 10.1038/sj.mp.4000266

  6. Groenman, A. P., Janssen, T. W., & Oosterlaan, J. (2017). Childhood psychiatric disorders as risk factor for subsequent substance abuse: A meta-analysis. Journal of the American Academy of Child & Adolescent Psychiatry, 56(7), 556-569. doi: 10.1016/j.jaac.2017.05.004

  7. Heils, A., Teufel, A., Petri, S., Stöber, G., Riederer, P., Bengel, D., & Lesch, K. P. (1996). Allelic variation of human serotonin transporter gene expression. Journal of Neurochemistry, 66(6), 2621-2624. doi: 10.1046/j.1471- 4159.1996.66062621.x

  8. Leitner, M., Fragner, L., Danner, S., Holeschofsky, N., Leitner, K., Tischler, S., … Kautzky-Willer, W. (2017). Combined metabolomic analysis of plasma and urine reveals AHBA, Tryptophan and Serotonin metabolism as potential risk factors in Gestational Diabetes Mellitus (GDM). Frontiers in Molecular Biosciences, 4, 84. doi: 10.3389/fmolb.2017.00084

  9. Lesch, K. P., Balling, U., Gross, J., Strauss, K., Wolozin, B. L., Murphy, D. L., & Riederer, P. J. (1994). Organization of the human serotonin transporter gene. Journal of Neural Transmission, 95(2), 157-162.

  10. Lesch, K.P., Bengel, D., Heils, A., Sabol, S.Z., Greenberg, B.D., Petri, S., … Murphy, D.L. (1996). Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science, 274(5292), 1527-1531.

  11. Moreau, D. & Waldie, K. E. (2016). Developmental Learning Disorders: From generic interventions to individualized remediation. Frontiers in Psychology, 6, 2053. doi: 10.3389/fpsyg.2015.02053

  12. Nomura, Y., Marks, D. J., Grossman, B., Yoon, M., Loudon, H., Stone, J., & Halperin, J. M. (2012). Exposure to gestational diabetes mellitus and low socioeconomic status: Effects on neurocognitive development and risk of attention-deficit/hyperactivity disorder in offspring. Archives of Pediatrics & Adolescent Medicine, 166(4), 337-343. doi: 10.1001/archpediatrics.2011.784

  13. Pastor, P. N., Duran, C., & Reuben, C. (2015). Quickstats: Percentage of children and adolescents aged 5-17 years with diagnosed attention‐deficit/hyperactivity disorder (ADHD), by race and Hispanic ethnicity-National Health Interview Survey, United States, 1997-2014. Morbidity and Mortality Weekly Report, 64(33), 925.

  14. Parisi, P., Moavero, R., Verrotti, A., & Curatolo, P. (2010). Attention deficit hyperactivity disorder in children with epilepsy. Brain and Development, 32(1), 10-16. doi: 10.1016/j.braindev.2009.03.005

  15. Peralta-Leal, V., Leal-Ugarte, E., Gutiérrez-Angulo, M., Dávalos-Rodríguez, I. P., Gallegos-Arreola, M. P., Meza-Espinoza, J. P., … Durán-González, J. (2015). Promoter polymorphism of the serotonin transporter gene influences the number of sexual partners and smoking habits in a Mexican Mestizo population. Psychiatric Genetics, 25(4), 178-179. doi: 10.1097/ypg.0000000000000089

  16. Peralta-Leal, V., Leal-Ugarte, E., Meza-Espinoza, J. P., Dávalos-Rodríguez, I. P., Bocanegra-Alonso, A., Acosta-González, R. I., … Durán-González, J. (2012). Association of a serotonin transporter gene (SLC6A4) 5-HTTLPR polymorphism with body mass index categories but not type 2 diabetes mellitus in Mexicans. Genetics and Molecular Biology, 35(3), 589-593. doi: 10.1590/s1415- 47572012005000048

  17. Polanczyk, G., de Lima, M. S., Horta, B. L., Biederman, J., & Rohde, L. A. (2007). The worldwide prevalence of ADHD: a systematic review and metaregression analysis. American Journal of Psychiatry, 164(6), 942-948. doi: 10.1176/ ajp.2007.164.6.942

  18. Purcell, S., Neale, B., Todd-Brown, K., Thomas, L., Ferreira, M. A., Bender, D., … Sham, P. C. (2007). PLINK: a tool set for whole-genome association and population- based linkage analyses. The American Journal of Human Genetics, 81(3), 559-575. doi: 10.1086/519795

  19. Schenkel, L. C., Bragatti, J. A., Torres, C. M., Martin, K. C., Manfro, G. G., Leistner- Segal, S., & Bianchin, M. M. (2011). Serotonin transporter gene (5HTT) polymorphisms and temporal lobe epilepsy. Epilepsy Research, 95(1-2), 152- 157. doi: 10.1016/j.eplepsyres.2011.03.013

  20. van der Meer, D., Hoekstra, P. J., Zwiers, M., Mennes, M., Schweren, L. J., Franke, B., … Hartman, C. A. (2015). Brain Correlates of the Interaction Between 5-HTTLPR and Psychosocial Stress Mediating Attention Deficit Hyperactivity Disorder Severity. American Journal of Psychiatry, 172(8), 768-775. doi: 10.1176/appi.ajp.2015.14081035

  21. Watkins, K. E., Cuellar, A. E., Hepner, K. A., Hunter, S. B., Paddock, S. M., Ewing, B. A., & de la Cruz, E. (2014). The cost-effectiveness of depression treatment for co-occurring disorders: A clinical trial. Journal of Substance Abuse Treatment, 46(2), 128-133. doi: 10.1016/j.jsat.2013.08.006

  22. Blazevic, S., Horvaticek, M., Kesic, M., Zill, P., Hranilovic, D., Ivanisevic, M., … Stefulj, J. (2017). Epigenetic adaptation of the placental serotonin transporter gene (SLC6A4) to gestational diabetes mellitus. PLOS ONE, 12(6), e0179934. doi: 10.1371/journal.pone.0179934

  23. Chronis, A. M., Lahey, B. B., Pelham, W. E., Kipp, H. L., Baumann, B. L., & Lee, S. S. (2003). Psychopathology and substance abuse in parents of young children with attention-deficit/hyperactivity disorder. Journal of the American Academy of Child & Adolescent Psychiatry, 42(12), 1424-1432. doi: 10.1097/00004583- 200312000-00009

  24. Cohen, R., Senecky, Y., Shuper, A., Inbar, D., Chodick, G., Shalev, V., & Raz, R. (2013). Prevalence of epilepsy and attention-deficit hyperactivity (ADHD) disorder: A population-based study. Journal of Child Neurology, 28(1), 120-123. doi: 10.1177/0883073812440327

  25. Cornejo-Escatell, E., Fajardo-Fregoso, B. F., López-Velázquez, V. M., Soto-Vargas, J., & Ceja-Moreno, H. (2015). Prevalence of attention deficit hyperactivity disorder in children from northeast Jalisco. RevistaMédica MD, 6(3), 190-195.

  26. Cook, E. C., Courchesne, R., Lord, C., Cox, N. J., Yan, S., Lincoln, A., … Leventhal, B. L. (1997). Evidence of linkage between the serotonin transporter and autistic disorder. Molecular Psychiatry, 2(3), 247-250. doi: 10.1038/sj.mp.4000266

  27. Groenman, A. P., Janssen, T. W., & Oosterlaan, J. (2017). Childhood psychiatric disorders as risk factor for subsequent substance abuse: A meta-analysis. Journal of the American Academy of Child & Adolescent Psychiatry, 56(7), 556-569. doi: 10.1016/j.jaac.2017.05.004

  28. Heils, A., Teufel, A., Petri, S., Stöber, G., Riederer, P., Bengel, D., & Lesch, K. P. (1996). Allelic variation of human serotonin transporter gene expression. Journal of Neurochemistry, 66(6), 2621-2624. doi: 10.1046/j.1471- 4159.1996.66062621.x

  29. Leitner, M., Fragner, L., Danner, S., Holeschofsky, N., Leitner, K., Tischler, S., … Kautzky-Willer, W. (2017). Combined metabolomic analysis of plasma and urine reveals AHBA, Tryptophan and Serotonin metabolism as potential risk factors in Gestational Diabetes Mellitus (GDM). Frontiers in Molecular Biosciences, 4, 84. doi: 10.3389/fmolb.2017.00084

  30. Lesch, K. P., Balling, U., Gross, J., Strauss, K., Wolozin, B. L., Murphy, D. L., & Riederer, P. J. (1994). Organization of the human serotonin transporter gene. Journal of Neural Transmission, 95(2), 157-162.

  31. Lesch, K.P., Bengel, D., Heils, A., Sabol, S.Z., Greenberg, B.D., Petri, S., … Murphy, D.L. (1996). Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science, 274(5292), 1527-1531.

  32. Moreau, D. & Waldie, K. E. (2016). Developmental Learning Disorders: From generic interventions to individualized remediation. Frontiers in Psychology, 6, 2053. doi: 10.3389/fpsyg.2015.02053

  33. Nomura, Y., Marks, D. J., Grossman, B., Yoon, M., Loudon, H., Stone, J., & Halperin, J. M. (2012). Exposure to gestational diabetes mellitus and low socioeconomic status: Effects on neurocognitive development and risk of attention-deficit/hyperactivity disorder in offspring. Archives of Pediatrics & Adolescent Medicine, 166(4), 337-343. doi: 10.1001/archpediatrics.2011.784

  34. Pastor, P. N., Duran, C., & Reuben, C. (2015). Quickstats: Percentage of children and adolescents aged 5-17 years with diagnosed attention‐deficit/hyperactivity disorder (ADHD), by race and Hispanic ethnicity-National Health Interview Survey, United States, 1997-2014. Morbidity and Mortality Weekly Report, 64(33), 925.

  35. Parisi, P., Moavero, R., Verrotti, A., & Curatolo, P. (2010). Attention deficit hyperactivity disorder in children with epilepsy. Brain and Development, 32(1), 10-16. doi: 10.1016/j.braindev.2009.03.005

  36. Peralta-Leal, V., Leal-Ugarte, E., Gutiérrez-Angulo, M., Dávalos-Rodríguez, I. P., Gallegos-Arreola, M. P., Meza-Espinoza, J. P., … Durán-González, J. (2015). Promoter polymorphism of the serotonin transporter gene influences the number of sexual partners and smoking habits in a Mexican Mestizo population. Psychiatric Genetics, 25(4), 178-179. doi: 10.1097/ypg.0000000000000089

  37. Peralta-Leal, V., Leal-Ugarte, E., Meza-Espinoza, J. P., Dávalos-Rodríguez, I. P., Bocanegra-Alonso, A., Acosta-González, R. I., … Durán-González, J. (2012). Association of a serotonin transporter gene (SLC6A4) 5-HTTLPR polymorphism with body mass index categories but not type 2 diabetes mellitus in Mexicans. Genetics and Molecular Biology, 35(3), 589-593. doi: 10.1590/s1415- 47572012005000048

  38. Polanczyk, G., de Lima, M. S., Horta, B. L., Biederman, J., & Rohde, L. A. (2007). The worldwide prevalence of ADHD: a systematic review and metaregression analysis. American Journal of Psychiatry, 164(6), 942-948. doi: 10.1176/ ajp.2007.164.6.942

  39. Purcell, S., Neale, B., Todd-Brown, K., Thomas, L., Ferreira, M. A., Bender, D., … Sham, P. C. (2007). PLINK: a tool set for whole-genome association and population- based linkage analyses. The American Journal of Human Genetics, 81(3), 559-575. doi: 10.1086/519795

  40. Schenkel, L. C., Bragatti, J. A., Torres, C. M., Martin, K. C., Manfro, G. G., Leistner- Segal, S., & Bianchin, M. M. (2011). Serotonin transporter gene (5HTT) polymorphisms and temporal lobe epilepsy. Epilepsy Research, 95(1-2), 152- 157. doi: 10.1016/j.eplepsyres.2011.03.013

  41. van der Meer, D., Hoekstra, P. J., Zwiers, M., Mennes, M., Schweren, L. J., Franke, B., … Hartman, C. A. (2015). Brain Correlates of the Interaction Between 5-HTTLPR and Psychosocial Stress Mediating Attention Deficit Hyperactivity Disorder Severity. American Journal of Psychiatry, 172(8), 768-775. doi: 10.1176/appi.ajp.2015.14081035

  42. Watkins, K. E., Cuellar, A. E., Hepner, K. A., Hunter, S. B., Paddock, S. M., Ewing, B. A., & de la Cruz, E. (2014). The cost-effectiveness of depression treatment for co-occurring disorders: A clinical trial. Journal of Substance Abuse Treatment, 46(2), 128-133. doi: 10.1016/j.jsat.2013.08.006




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