Skip to main content
SpringerLink
Log in

The combined effect of norepinephrine transporter gene and negative life events in major depression of Chinese Han population

  • Basic Neurosciences, Genetics and Immunology - Original Article
  • Published:
Journal of Neural Transmission Aims and scope Submit manuscript

Abstract

The aim of the present study was to detect the combined effect of negative life events and the norepinephrine transporter (NET) gene on the development of major depression (MD) in a Chinese population. We recruited 388 unrelated patients affected with MD and 388 healthy controls in this study. The score of 32 was used as a cut-off value for grouping the negative life events into the severe and moderate forms using the Life Events Scale (LES). SNPs including rs2242446 and rs5569 of the NET gene were genotyped. The chi-square (χ 2) test showed allelic association for the T-182C polymorphism (χ 2 = 6.46, corrected P = 0.011) and also showed genotypic association (χ 2 = 6.87, corrected P = 0.034). Multifactor dimensionality reduction (MDR) showed that the interaction between the rs2242446–rs5569 combination and negative life events had a CV consistency of 10 and PE of 0.3487. Compared with those having both T-G-MN combination used as reference group, we found that the OR scaled up from 1 to 7.39 (95%CI 3.40–16.06) in the C-A-SN group. The present study suggests that the combined effect of rs2242446 and rs5569 in the NET gene could modify the response to the negative life events in triggering MD.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • American Psychiatric Association (2000) Diagnostic and statistical manual of mental disorders, 4th edn. Text Revision. American Psychiatric Association, Washington

  • Ayuso-Mateos JL, Vázquez-Barquero JL, Dowrick C, Lehtinen V, Dalgard OS, Casey P, Wilkinson C, Lasa L, Page H, Dunn G, Wilkinson G, ODIN Group (2001) Depressive disorders in Europe: prevalence figures from the ODIN study. Br J Psychiatry 179:308–316

    Article  PubMed  CAS  Google Scholar 

  • Bennett AJ, Lesch KP, Heils A, Long JC, Lorenz JG, Shoaf SE, Champoux M, Suomi SJ, Linnoila MV, Higley JD (2002) Early experience and serotonin transporter gene variation interact to influence primate CNS function. Mol Psychiatry 7:118–122

    Article  PubMed  CAS  Google Scholar 

  • Barr CS, Newman TK, Shannon C, Parker C, Dvoskin RL, Becker ML, Schwandt M, Champoux M, Lesch KP, Goldman D, Suomi SJ, Higley JD (2004) Rearing condition and rh5-HTTLPR interact to influence limbic-hypothalamic-pituitaryadrenal axis response to stress in infant macaques. Biol Psychiatry 55:733–738

    Article  PubMed  CAS  Google Scholar 

  • Charney DS (1998) Monoamine dysfunction and the pathophysiology and treatment of depression. J Clin Psychiatry 59:11–14

    PubMed  CAS  Google Scholar 

  • Caspi A, McClay J, Moffitt TE, Mill J, Martin J, Craig IW, Taylor A, Poulton R (2002) Role of genotype in the cycle of violence in maltreated children. Science 297:851–854

    Article  PubMed  CAS  Google Scholar 

  • Caspi A, Sugden K, Moffitt TE, Taylor A, Craig IW, Harrington H (2003) Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science 301:386–389

    Article  PubMed  CAS  Google Scholar 

  • Chang C-C, Lu R-B, Chen C-L, Chu C-M, Chang H-A, Huang C-C, Huang Y-L, Huang S-Y (2007) Lack of association between the norepinephrine transporter gene and major depression in a Han Chinese population. J Psychiatry Neurosci 32:121–128

    PubMed  Google Scholar 

  • Dupont WD, Plummer WD (1998) Power and sample size calculations for studies involving linear regression. Control Clin Trials 19:589–601

    Article  PubMed  CAS  Google Scholar 

  • Dudbridge F (2003) Pedigree disequilibrium tests for multilocus haplotypes. Genet Epidemiol 25:115–121

    Article  PubMed  Google Scholar 

  • Dindo L, Coryell W (2004) Comorbid major depression and panic disorder: significance of temporal sequencing to familial transmission. J Affect Disord 82:119–123

    Article  PubMed  Google Scholar 

  • First MB, Spitzer RL, Gibbon M (1995) Structured clinical interview for DSM-IV axis 1 disorder. Biometrics Research Department, New York State Psychiatric Institute, New York

  • Grabe HJ, Lange M, Wolff B, Völzke H, Lucht M, Freyberger HJ, John U, Cascorbi I (2005) 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 10:220–224

    Article  PubMed  CAS  Google Scholar 

  • Hammen C, Shih JH, Brennan PA (2004) Intergenerational transmission of depression: test of an interpersonal stress model in a community sample. J Consult Clin Psychol 72:511–522

    Article  PubMed  Google Scholar 

  • Inoue K, Itoh K, Yoshida K, Shimizu T, Suzuki T (2004) Positive association between T-182C polymorphism in the norepinephrine transporter gene and susceptibility to major depressive disorder in a Japanese population. Neuropsychobiology 50:301–304

    Article  PubMed  CAS  Google Scholar 

  • Kendler KS, Karkowski L, Prescott CA (1998) Stressful life events and major depression: risk period, long-term contextual threat and diagnostic specificity. J Nerv Ment Dis 186:661–669

    Article  PubMed  CAS  Google Scholar 

  • Kendler KS, Karkowski LM, Prescott CA (1999) Causal relationship between stressful life events and the onset of major depression. Am J Psychiatry 156:837–841

    PubMed  CAS  Google Scholar 

  • Kraaij V, Arensman E, Spinhoven P (2002) Negative life events and depression in elderly persons: a meta-analysis. J Gerontol B Psychol Sci Soc Sci 57:87–94

    Google Scholar 

  • Kendler KS, Kuhn JW, Vittum J, Prescott CA, Riley B (2005) The interaction of stressful life events and a serotonin transporter polymorphism in the prediction of episodes of major depression: a replication. Arch Gen Psychiatry 62:529–535

    Article  PubMed  CAS  Google Scholar 

  • Kessler RC, Merikangas KR, Wang PS (2007) Prevalence, comorbidity, and service utilization for mood disorders in the United States at the beginning of the twenty-first century. Annu Rev Clin Psychol 3:137–158

    Article  PubMed  Google Scholar 

  • Levinson DF (2006) The genetics of depression: a review. Biol Psychiatry 60:84–92

    Article  PubMed  CAS  Google Scholar 

  • Murphy DL, Li Q, Engel S, Wichems C, Andrews A, Lesch KP, Uhl G (2001) Genetic perspectives on the serotonin transporter. Brain Res Bull 56:487–494

    Article  PubMed  CAS  Google Scholar 

  • Mazure CM, Maciejewski PK (2003) A model of risk for major depression: effects of life stress and cognitive style vary by age. Depress Anxiety 17:26–33

    Article  PubMed  Google Scholar 

  • Mandelli L, Serretti A, Marino E, Pirovano A, Calati R, Colombo C (2007) Interaction between serotonin transporter gene, catechol-O-methyltransferase gene and stressful like events in mood disorders. Int J Neuropsychopharmacol 10:437–447

    Article  PubMed  CAS  Google Scholar 

  • Nelson JC, Charney DS (1981) The symptoms of major depressive illness. Am J Psychiatry 138:1–13

    PubMed  CAS  Google Scholar 

  • Nobile M, Cataldo MG, Giorda R, Battaglia M, Baschirotto C, Bellina M, Marino C, Molteni M (2004) A case-control and family-based association study of the 5-HTTLPR in pediatric-onset depressive disorders. Biol Psychiatry 56:292–295

    Article  PubMed  CAS  Google Scholar 

  • Owens MJ (1997) Molecular and cellular mechanisms of antidepressant drugs. Depress Anxiety 4:153–159

    Article  CAS  Google Scholar 

  • Owen D, Du L, Bakish D, Lapierre YD, Hrdina PD (1999) Norepinephrine transporter gene polymorphism is not associated with susceptibility to major depression. Psychiatry Res 87:1–5

    Article  PubMed  CAS  Google Scholar 

  • Porzgen P, Bonisch H, Bruss M (1995) Molecular cloning and organization of the coding region of the human norepinephrine transporter gene. Biochem Biophys Res Commun 215:1145–1150

    Article  PubMed  CAS  Google Scholar 

  • Paykel ES (2003) Life events and affective disorders. Acta Psychiatr Scand Suppl 418:61–66

    Article  PubMed  Google Scholar 

  • Rice F, Harold GT, Thapar A (2003) Negative life events as an account of age-related differences in the genetic aetiology of depression in childhood and adolescence. J Child Psychol Psychiatry 44:977–987

    Article  PubMed  Google Scholar 

  • Ryu SH, Lee SH, Lee HJ, Cha JH, Ham BJ, Han CS, Choi MJ, Lee MS (2004) Association between norepinephrine transporter gene polymorphism and major depression. Neuropsychobiology 49:174–177

    Article  PubMed  CAS  Google Scholar 

  • Spiessl H, Hubner-Liebermann B, Hajak G (2006) Depression, a widespread disease. Epidemiology, care situation, diagnosis, therapy and prevention. Dtsch Med Wochenschr 131:35–40

    Article  PubMed  CAS  Google Scholar 

  • Veith RC, Lewis N, Linares OA, Barnes RF, Raskind MA, Villacres EC, Murburg HM, Ashleigh EA, Castillo S, Peskind ER, Pascualy M, Halter JB (1994) Sympathetic nervous system activity in major depression. Arch Gen Psychiatry 51:411–422

    PubMed  CAS  Google Scholar 

  • Wilhelm K, Mitchell PB, Niven H, Finch A, Wedgwood L, Scimone A, Blair IP, Parker G, Schofield PR (2006) Life events, first depression onset and the serotonin transporter gene. Br J Psychiatry 188:210–215

    Article  PubMed  Google Scholar 

  • Yang DS, Zhang YL (1999) Life Event Scale (LES). In: Wang XD, Wang XL, Ma H (eds) Rating Scales for Mental Health. Chinese Mental Health Journal, Beijing, pp 101–106 (Press in Chinese)

    Google Scholar 

  • Zill P, Engel R, Baghai TC, Juckel G, Frodl T, Müller-Siecheneder F, Zwanzger P, Schüle C, Minov C, Behrens S, Rupprecht R, Hegerl U, Möller HJ, Bondy B (2002) Identification of a naturally occurring polymorphism in the promoter region of the norepinephrine transporter and analysis in major depression. Neuropsychopharmacology 26:489–494

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This project was supported by grants from the National Natural Science Foundation of China (Grant No. 30770770), National Natural Science Foundation of China (Grant No.30721063), Programs for Science and Technology Development of Shanxi (Grant No. 2007031091-3), Science Foundation for Youths of Shanxi (Grant No. 2007021050), National 863 program (Grant No.2006AA 02A 407), National 973 Program (Grant No. 2004CB518601) and International S&T Cooperation Program of China (Grant No. 2006DFA31440).

Author information

Authors and Affiliations

  1. Department of Psychiatry, First Hospital of Shanxi Medical University, 030001, Taiyuan, China

    Ning Sun, Yong Xu, Yanfang Wang, Huijun Duan, Shan Wang, Yan Ren, Juyi Peng, Qiaorong Du & Kerang Zhang

  2. Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), 100005, Beijing, China

    Yan Shen & Qi Xu

  3. Nursing College of Shanxi Medical University, 030001, Taiyuan, China

    Ning Sun

Authors
  1. Ning Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yong Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yanfang Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Huijun Duan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Shan Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yan Ren
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Juyi Peng
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Qiaorong Du
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Yan Shen
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Qi Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Kerang Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Qi Xu or Kerang Zhang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sun, N., Xu, Y., Wang, Y. et al. The combined effect of norepinephrine transporter gene and negative life events in major depression of Chinese Han population. J Neural Transm 115, 1681–1686 (2008). https://doi.org/10.1007/s00702-008-0109-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00702-008-0109-5

Keywords

Search

Navigation