Korean Journal of Biological Psychiatry (생물정신의학)

The Korean Society of Biological Psychiatry (대한생물정신의학회)
권호 표지

Investigation into the Possible Genetic Role of Serotonin and Dopamine Transporters in Psychological Resilience

  • Cho, Sang Hyun (Department of Psychiatry, Eulji University, Nowon Eulji Medical Center) ;
  • Chung, Jae Kyung (Department of Psychiatry, Eumsung-somang Hospital) ;
  • Bang, Yang Weon (Department of Psychiatry, Keyo Hospital) ;
  • Joo, Eun-Jeong (Department of Psychiatry, Eulji University, Nowon Eulji Medical Center)
  • Received : 2017.10.23
  • Accepted : 2018.01.12
  • Published : 2018.02.28
Download PDF
⟨ Previous Next ⟩

Abstract

Objectives Psychological resilience is the ability to cope with stress. The genetic background behind psychological resilience is not much known. The serotonin transporter and dopamine transporter are implicated in stress related psychology and emotional processing. The aim of this study is to investigate a possible genetic role of functional polymorphisms of serotonin and dopamine transporters for psychological resilience. Methods A total of 951 healthy adult subjects were included. Psychological resilience was measured using Connor-Davidson Resilience Scale (CD-RISC). Genotyping was performed for serotonin transporter gene(SERT) promoter variable number tandem repeat (VNTR) and dopamine transporter gene(DAT1) 3'-untranslated region (UTR) VNTR. Genetic association analysis was conducted between genotypes and the CD-RISC score. Results No genetic association was observed for SERT promoter VNTR or DAT1 3'-UTR VNTR with CD-RISC score. No genetic interaction between SERT promoter VNTR and DAT1 3'-UTR VNTR with CD-RISC score was detected. Conclusions Either serotonin or dopamine transporter did not seem to play a significant role for psychological resilience in this sample.

Keywords

References

  1. Campbell-Sills L, Cohan SL, Stein MB. Relationship of resilience to personality, coping, and psychiatric symptoms in young adults. Behav Res Ther 2006;44:585-599. https://doi.org/10.1016/j.brat.2005.05.001
  2. Caspi A, Sugden K, Moffitt TE, Taylor A, Craig IW, Harrington H, et al. Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science 2003;301:386-389. https://doi.org/10.1126/science.1083968
  3. Charney DS. Psychobiological mechanisms of resilience and vulnerability: implications for successful adaptation to extreme stress. Am J Psychiatry 2004;161:195-216. https://doi.org/10.1176/appi.ajp.161.2.195
  4. Haskett ME, Nears K, Ward CS, McPherson AV. Diversity in adjustment of maltreated children: factors associated with resilient functioning. Clin Psychol Rev 2006;26:796-812. https://doi.org/10.1016/j.cpr.2006.03.005
  5. Benetti C, Kambouropoulos N. Affect-regulated indirect effects of trait anxiety and trait resilience on self-esteem. Pers Individ Dif 2006;41:341-352. https://doi.org/10.1016/j.paid.2006.01.015
  6. Sexton MB, Hamilton L, McGinnis EW, Rosenblum KL, Muzik M. The roles of resilience and childhood trauma history: main and moderating effects on postpartum maternal mental health and functioning. J Affect Disord 2015;174:562-568. https://doi.org/10.1016/j.jad.2014.12.036
  7. Sharpley CF, Christie DRH, Bitsika V, Andronicos NM, Agnew LL, McMillan ME. Does psychological resilience buffer against the link between the 5-HTTLPR polymorphism and depression following stress. Physiol Behav 2017;180:53-59. https://doi.org/10.1016/j.physbeh.2017.07.029
  8. Bruenig D, Morris CP, Mehta D, Harvey W, Lawford B, Young RM, et al. Nitric oxide pathway genes (NOS1AP and NOS1) are involved in PTSD severity, depression, anxiety, stress and resilience. Gene 2017;625:42-48. https://doi.org/10.1016/j.gene.2017.04.048
  9. Bruenig D, Mehta D, Morris CP, Harvey W, Lawford B, Young RM, et al. Genetic and serum biomarker evidence for a relationship between $TNF{\alpha}$ and PTSD in Vietnam war combat veterans. Compr Psychiatry 2017;74:125-133. https://doi.org/10.1016/j.comppsych.2017.01.015
  10. Clarke H, Flint J, Attwood AS, Munafo MR. Association of the 5-HTTLPR genotype and unipolar depression: a meta-analysis. Psychol Med 2010;40:1767-1778. https://doi.org/10.1017/S0033291710000516
  11. Grabe HJ, Lange M, Wolff B, Volzke H, Lucht M, Freyberger HJ, et al. Mental and physical distress is modulated by a polymorphism in the 5-HT transporter gene interacting with social stressors and chronic disease burden. Mol Psychiatry 2005;10:220-224. https://doi.org/10.1038/sj.mp.4001555
  12. Karg K, Burmeister M, Shedden K, Sen S. The serotonin transporter promoter variant (5-HTTLPR), stress, and depression meta-analysis revisited evidence of genetic moderation. Arch Gen Psychiatry 2011;68:444-454. https://doi.org/10.1001/archgenpsychiatry.2010.189
  13. Garcia-Garcia M, Clemente I, Dominguez-Borras J, Escera C. Dopamine transporter regulates the enhancement of novelty processing by a negative emotional context. Neuropsychologia 2010;48:1483-1488. https://doi.org/10.1016/j.neuropsychologia.2010.01.018
  14. Greenwood TA, Alexander M, Keck PE, McElroy S, Sadovnick AD, Remick RA, et al. Segmental linkage disequilibrium within the dopamine transporter gene. Mol Psychiatry 2002;7:165-173. https://doi.org/10.1038/sj.mp.4000958
  15. Mehler-Wex C, Riederer P, Gerlach M. Dopaminergic dysbalance in distinct basal ganglia neurocircuits: implications for the pathophysiology of Parkinson's disease, schizophrenia and attention deficit hyperactivity disorder. Neurotox Res 2006;10:167-179. https://doi.org/10.1007/BF03033354
  16. Heinz A, Goldman D, Jones DW, Palmour R, Hommer D, Gorey JG, et al. Genotype influences in vivo dopamine transporter availability in human striatum. Neuropsychopharmacology 2000;22:133-139. https://doi.org/10.1016/S0893-133X(99)00099-8
  17. Baek HS, Lee KU, Joo EJ, Lee MY, Choi KS. Reliability and validity of the Korean version of the connor-davidson resilience scale. Psychiatry Investig 2010;7:109-115. https://doi.org/10.4306/pi.2010.7.2.109
  18. Eun TK, Jeong SH, Lee KY, Kim SH, Ahn YM, Bang YW, et al. Association between the 5-HTTLPR genotype and childhood characteristics in mood disorders. Clin Psychopharmacol Neurosci 2016;14:88-95. https://doi.org/10.9758/cpn.2016.14.1.88
  19. Connor KM, Davidson JR. Development of a new resilience scale: the Connor-Davidson Resilience Scale (CD-RISC). Depress Anxiety 2003;18:76-82. https://doi.org/10.1002/da.10113
  20. Jung YE, Min JA, Shin AY, Han SY, Lee KU, Kim TS, et al. The Korean version of the Connor-Davidson Resilience Scale: an extended validation. Stress Health 2012;28:319-326. https://doi.org/10.1002/smi.1436
  21. Jeong SH, Choi KS, Lee KY, Kim EJ, Kim YS, Joo EJ. Association between the dopamine transporter gene (DAT1) and attention deficit hyperactivity disorder-related traits in healthy adults. Psychiatr Genet 2015;25:119-126. https://doi.org/10.1097/YPG.0000000000000086
  22. Heils A, Teufel A, Petri S, Seemann M, Bengel D, Balling U, et al. Functional promoter and polyadenylation site mapping of the human serotonin (5-HT) transporter gene. J Neural Transm Gen Sect 1995;102:247-254. https://doi.org/10.1007/BF01281159
  23. Heils A, Teufel A, Petri S, Stober G, Riederer P, Bengel D, et al. Allelic variation of human serotonin transporter gene expression. J Neurochem 1996;66:2621-2624.
  24. Greenwood TA, Schork NJ, Eskin E, Kelsoe JR. Identification of additional variants within the human dopamine transporter gene provides further evidence for an association with bipolar disorder in two independent samples. Mol Psychiatry 2006;11:125-133, 115. https://doi.org/10.1038/sj.mp.4001764
  25. Brunswick DJ, Amsterdam JD, Mozley PD, Newberg A. Greater availability of brain dopamine transporters in major depression shown by [$^{99m}Tc$]TRODAT-1 SPECT imaging. Am J Psychiatry 2003;160:1836-1841. https://doi.org/10.1176/appi.ajp.160.10.1836
  26. Haeffel GJ, Getchell M, Koposov RA, Yrigollen CM, Deyoung CG, Klinteberg BA, et al. Association between polymorphisms in the dopamine transporter gene and depression: evidence for a gene-environment interaction in a sample of juvenile detainees. Psychol Sci 2008;19:62-69. https://doi.org/10.1111/j.1467-9280.2008.02047.x
  27. Gizer IR, Ficks C, Waldman ID. Candidate gene studies of ADHD: a meta-analytic review. Hum Genet 2009;126:51-90. https://doi.org/10.1007/s00439-009-0694-x
  28. Keikhaee MR, Fadai F, Sargolzaee MR, Javanbakht A, Najmabadi H, Ohadi M. Association analysis of the dopamine transporter (DAT1)-67A/T polymorphism in bipolar disorder. Am J Med Genet B Neuropsychiatr Genet 2005;135B:47-49. https://doi.org/10.1002/ajmg.b.30174
  29. van der Zwaluw CS, Engels RC, Buitelaar J, Verkes RJ, Franke B, Scholte RH. Polymorphisms in the dopamine transporter gene (SLC6A3/DAT1) and alcohol dependence in humans: a systematic review. Pharmacogenomics 2009;10:853-866. https://doi.org/10.2217/pgs.09.24
  30. Fuke S, Suo S, Takahashi N, Koike H, Sasagawa N, Ishiura S. The VNTR polymorphism of the human dopamine transporter (DAT1) gene affects gene expression. Pharmacogenomics J 2001;1:152-156. https://doi.org/10.1038/sj.tpj.6500026
  31. Mill J, Asherson P, Browes C, D'Souza U, Craig I. Expression of the dopamine transporter gene is regulated by the 3' UTR VNTR: evidence from brain and lymphocytes using quantitative RT-PCR. Am J Med Genet 2002;114:975-979. https://doi.org/10.1002/ajmg.b.10948
  32. Lim MH, Kim HW, Paik KC, Cho SC, Yoon DY, Lee HJ. Association of the DAT1 polymorphism with attention deficit hyperactivity disorder (ADHD): a family-based approach. Am J Med Genet B Neuropsychiatr Genet 2006;141B:309-311. https://doi.org/10.1002/ajmg.b.30282
  33. Huang CC, Lu RB, Shih MC, Yen CH, Huang SY. Association study of the dopamine transporter gene with personality traits and major depressive disorder in the Han Chinese population. Pharmacogenet Genomics 2011;21:94-97. https://doi.org/10.1097/FPC.0b013e3283424d94
  34. Opmeer EM, Kortekaas R, Aleman A. Depression and the role of genes involved in dopamine metabolism and signalling. Prog Neurobiol 2010;92:112-133. https://doi.org/10.1016/j.pneurobio.2010.06.003
  35. Jeon HJ, Bang YR, Park HY, Kim SA, Yoon IY. Differential effects of circadian typology on sleep-related symptoms, physical fatigue and psychological well-being in relation to resilience. Chronobiol Int 2017;34:677-686. https://doi.org/10.1080/07420528.2017.1309425