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Serotonin transporter gene (5-HTT) rs6354 polymorphism, job-related stress, and their interaction in burnout in healthcare workers in a Chinese hospital

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Abstract

Objective

Many studies have reported that long-term exposure to job-related stress can lead to burnout, which may be influenced by genetic and environmental factors. Burnout correlates with depression. This study investigated whether one tag polymorphism rs6354 in 5-HTT gene modulated the influence of job-related stress on burnout in the medical professionals in a Chinese Han population, which to our best knowledge has not been explored.

Methods

Seven hundred twelve subjects were recruited from a general hospital and measured for burnout symptoms using the Maslach Burnout Inventory (MBI), the stress using the House and Rizzo’s Work Stress Scale, and the stressors using the Evers, Frese, and Cooper’s Sources of Pressure Scale. The 5-HTT rs6354 polymorphism was genotyped in 376 subjects.

Results

The majority of correlations between the work stress score or the six stressor scores and three burnout subscores were significant (all p < 0.05). There was no significant main effect of the 5-HTT rs6354 genotype on burnout symptoms; however, there was a statistically significant interaction between 5-HTT rs6354 and work stress on burnout (F = 5.08, df = 2, 369, p = 0.007). In the low stress group, G allele carriers had significantly higher burnout level than TT homozygote (F = 11.60, df = 1, 48, p < 0.001). On the contrary, in the high stress group, G allele carriers exhibited significantly lower burnout level compared to TT homozygote (F = 3.86, df = 1, 103, p = 0.025).

Conclusions

Our findings suggest that the 5-HTT rs6354 polymorphism may modulate the influence of job-related stress on burnout by adjusting serotonin transporter function and neurotransmission, showing that individuals with TT genotype displayed a greater susceptibility to both the detrimental effects of higher stress and the beneficial effects of lower stress compared to those with G allele, which supports the differential-susceptibility hypothesis.

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References

  • Ahola K, Honkonen T, Isometsä E, Kalimo R, Nykyri E, Aromaa A, Lonnqvist J (2005) The relationship between job-related burnout and depressive disorders—results from the Finnish Health 2000 Study. J Affect Disord 88:55–62

    Article  Google Scholar 

  • Aiken LH, Clarke SP, Sloane DM, Sochalski J, Silber JH (2002) Hospital nurse staffing and patient mortality, nurse burnout, and job dissatisfaction. JAMA 288:1987–1993

    Article  Google Scholar 

  • Arpawong TE, Lee J, Phillips DF, Crimmins EM, Levine ME, Prescott CA (2015) Effects of recent stress and variation in the serotonin transporter polymorphism (5-HTTLPR) on depressive symptoms: a repeated-measures study of adults age 50 and older. Behav Genet 46:72–88

    Article  Google Scholar 

  • Bakusic J, Schaufeli W, Claes S, Godderis L (2017) Stress, burnout and depression: a systematic review on DNA methylation mechanisms. J Psychosom Res 92:34–44

    Article  Google Scholar 

  • Bauer IE, Graham DP, Soares JC, Nielsen DA (2015) Serotonergic gene variation in substance use pharmacotherapy: a systematic review. Pharmacogenomics 16:1307–1314

    Article  Google Scholar 

  • Beck J, Gerber M, Brand S, Pühse U, Holsboer-Trachsler E (2013) Executive function performance is reduced during occupational burnout but can recover to the level of healthy controls. J Psychiatr Res 47:1824–1830

    Article  Google Scholar 

  • Belsky J, Pluess M (2009) Beyond diathesis stress: differential susceptibility to environmental influences. Psychol Bull 135(6):885–908

    Article  Google Scholar 

  • Bianchi R, Schonfeld IS, Laurent E (2015) Burnout-depression overlap: a review. Clin Psychol Rev 36:28–41

    Article  Google Scholar 

  • Blom V, Bergström G, Hallsten L, Bodin L, Svedberg P (2012) Genetic susceptibility to burnout in a Swedish twin cohort. Eur J Epidemiol 27:225–231

    Article  Google Scholar 

  • Bogdan R, Agrawal A, Gaffrey MS, Tillman R, Luby JL (2014) Serotonin transporter-linked polymorphic region (5-HTTLPR) genotype and stressful life events interact to predict preschool-onset depression: a replication and developmental extension. J Child Psychol Psychiatry 55:448–457

    Article  Google Scholar 

  • Caspi A, Sugden K, Moffitt TE, Taylor A, Craig LW, Harrington H, Mcclay J, Mill J, Martin J, Braithwaite AW, Poulton R (2003) Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science 301:386–389

    Article  CAS  Google Scholar 

  • Caspi A, Hariri AR, Holmes A, Uher R, Moffitt TE (2010) Genetic sensitivity to the environment: the case of the serotonin transporter gene and its implications for studying complex diseases and traits. Focus 8:398–416

    Article  Google Scholar 

  • Choi S, Cheong KJ, Feinberg RA (2012) Moderating effects of supervisor support, monetary rewards, and career paths on the relationship between job burnout and turnover intentions in the context of call centers. Manag Serv Qual 22:492–516

    Article  Google Scholar 

  • Chou LP, Li CY, Hu SC (2014) Job stress and burnout in hospital employees: comparisons of different medical professions in a regional hospital in Taiwan. BMJ Open 4:1–7

    Google Scholar 

  • Chuang CH, Tseng PC, Lin CY, Lin KH, Chen YY (2016) Burnout in the intensive care unit professionals: a systematic review. Medicine 18:139–143

    Google Scholar 

  • Deligkaris P, Panagopoulou E, Montgomery AJ, Masoura E (2014) Job burnout and cognitive functioning: a systematic review. Work Stress 28:107–123

    Google Scholar 

  • Duman EA, Canli T (2015) Influence of life stress, 5-HTTLPR genotype, and SLC6A4 methylation on gene expression and stress response in healthy Caucasian males. Biol Mood Anxiety Disord 5:1–14

    Article  CAS  Google Scholar 

  • Eckleberry-Hunt J, Kirkpatrick H, Barbera T (2018) The problems with burnout research. Acad Med 93(3):367–370

    Article  Google Scholar 

  • Evers A, Frese M, Cooper CL (2000) Revisions and further developments of the Occupational Stress Indicator: LISREL results from four Dutch studies. J Occup Organ Psychol 73:221–240

    Article  Google Scholar 

  • Fisher HL, Cohen-Woods S, Hosang GM, Uher R, Powell-Smith G, Keers R, Tropeano M, Korszun A, Jones L, Jones I, Owen MJ, Craddock N, Craig IW, Farmer A, Mcguffin P (2012) Stressful life events and the serotonin transporter gene (5-HTT) in recurrent clinical depression. J Affect Disord 136:189–193

    Article  CAS  Google Scholar 

  • Hayes AF (2013) Introduction to mediation, moderation, and conditional process analysis: a regression-based approach. New York, NY: The Guilford Press. J Educ Meas 51:335–337

    Google Scholar 

  • Honkonen T, Ahola K, Pertovaara M, Isometsä E, Kalimo R, Nykyri E, Aromaa A, Lönnqvist J (2006) The association between burnout and physical illness in the general population—results from the Finnish Health 2000 Study. J Psychosom Res 61(1):59–66

    Article  Google Scholar 

  • House RJ, Rizzo JR (1972) Role conflict and ambiguity as critical variables in a model of organizational behavior. Organ Behav Hum Perform 7:467–505

    Article  Google Scholar 

  • Karg K, Burmeister M, Shedden K, Sen S (2011) The serotonin transporter promoter variant (5-HTTLPR), stress, and depression meta-analysis revisited: evidence of genetic moderation. Arch Gen Psychiatry 68(5):444–454

    Article  Google Scholar 

  • Kumar S (2016) Burnout and doctors: prevalence, prevention and intervention. Healthcare 4:37

    Article  CAS  Google Scholar 

  • Lazarus RS, Folkman S (1984) Stress, appraisal, and coping. Springer, New York

    Google Scholar 

  • Lesch KP, Bengel D, Heils A, Sabol SZ, Greenberg BD, Petri S, Benjamin J, Muller CR, Hamer DH, Murphy DL (1996) Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science 274:1527–1531

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Li L, Yang X, Wang F, XIaohui Q, Zhangxue Q, Lin W, Yan X, Yang Y (2013) Study on job burnout and personality characteristics of teachers. Chin. Prim.Health Care 27(1):27–28.

    CAS  Google Scholar 

  • Lu AC, Gursoy D (2016) Impact of job burnout on satisfaction and turnover intention do generational differences matter? J Hosp Tour Res 40:210–235

    Article  Google Scholar 

  • Mandelli L, Antypa N, Nearchou FA, Vaiopoulos C, Stefanis CN, Serretti A, Stefanis NC (2012) The role of serotonergic genes and environmental stress on the development of depressive symptoms and neuroticism. J Affect Disord 142(1):82–89

    Article  CAS  Google Scholar 

  • Maslach C, Jackson SE (1981) The measure of experienced burnout. J Organ Behav 2:99–113

    Article  Google Scholar 

  • Maslach C, Schaufeli WB, Leiter MP (2001) Job burnout. Annu Rev Psychol 52:397–422

    Article  CAS  Google Scholar 

  • Meng X, Yu Y, Kou C, D'Arcy C, Shi J (2013) No genetic association between single-nucleotide polymorphisms in the coding region of the SLC6A4 gene and internalizing disorders in mainland Chinese university students. Psychiatr Genet 23:36–37

    Article  Google Scholar 

  • Murthy NV, Selvaraj S, Cowen PJ, Bhagwagar Z, Riedel WJ, Peers PV, Kennedy J, Sahakian BJ, Laruelle M, Rabiner EA, Grasby PM (2010) Serotonin transporter polymorphisms (SLC6A4 insertion/deletion and rs25531) do not affect the availability of 5-HTT to [11 C] DASB binding in the living human brain. NeuroImage 52:50–54

    Article  CAS  Google Scholar 

  • Myhren H, Ekeberg Ø, Stokland O (2013) Job satisfaction and burnout among intensive care unit nurses and physicians. Crit Care Res Pract 2013:1–6

    Article  Google Scholar 

  • Naugle KE, Behar-Horenstein LS, Dodd VJ, Tillman MD, Borsa PA (2013) Perceptions of wellness and burnout among certified athletic trainers: sex differences. J Athl Train 48(3):424–430

    Article  Google Scholar 

  • Nugent NR, Tyrka AR, Carpenter LL, Price LH (2011) Gene–environment interactions: early life stress and risk for depressive and anxiety disorders. Psychopharmacology 214:175–196

    Article  CAS  Google Scholar 

  • Purvanova RK, Muros JP (2010) Gender differences in burnout: a meta-analysis. J Vocat Behav 77:168–185

    Article  Google Scholar 

  • Rezaei O, Habibi K, Arab DG, Ghahestany DA, Sayadnasiri M, Armoon B, Khan V, Moghadam LF (2018) Factors related to job burnout among nurses in the Razi Psychiatric Hospital, Iran. Int J Adolesc Med Health

  • Su S, Zhao J, Bremner JD, Miller AH, Tang W, Bouzyk M, Sneider H, Novik O, Afzal N, Goldberg J, Vaccarino V (2009) Serotonin transporter gene, depressive symptoms, and interleukin-6. Circ Cardiovasc Genet 2:614–620

    Article  CAS  Google Scholar 

  • Sulkava S, Ollila HM, Ahola K, Partonen T, Viitasalo K, Kettunen J, Lappalainen M, Kivimäki M, Vahtera J, Lindström J, Härmä M, Puttonen S, Salomaa V, Paunio T (2013) Genome-wide scan of job-related exhaustion with three replication studies implicate a susceptibility variant at the UST gene locus. Hum Mol Genet 22:3363–3372

    Article  CAS  Google Scholar 

  • Uher R, McGuffin P (2010) The moderation by the serotonin transporter gene of environmental adversity in the etiology of depression: 2009 update. Mol Psychiatry 15:18–22

    Article  CAS  Google Scholar 

  • Wang TY, Lee SY, Chen SL, Huang SY, Chang YH, Tzeng NS, Wang C, Lee IH, Yeh TZ, Yang YK, Lu R (2013) Association between DRD2, 5-HTTLPR, and ALDH2 genes and specific personality traits in alcohol- and opiate-dependent patients. Behav Brain Res 250:285–292

    Article  CAS  Google Scholar 

  • Wei H, Liu L, Sun W, Zhao X, Wang JN, Wang L (2014) Factors related to burnout among Chinese female hospital nurses: cross-sectional survey in Liaoning Province of China. J Knurs Manage 22:621–629

    CAS  Google Scholar 

  • Wendland JR, Martin BJ, Kruse MR, Lesch KP, Murphy DL (2006) Simultaneous genotyping of four functional loci of human SLC6A4, with a reappraisal of 5-HTTLPR and rs25531. Mol Psychiatry 11:224–226

    Article  CAS  Google Scholar 

  • Wray NR, James MR, Gordon SD, Dumenil T, Ryan L, Coventry WL, Statham DJ, Pergadia ML, Madden PAF, Heath AC, Montgomery GW, Martin NG (2009) Accurate, large-scale genotyping of 5HTTLPR and flanking single nucleotide polymorphisms in an association study of depression, anxiety, and personality measures. Biol Psychiatry 66:468–476

    Article  CAS  Google Scholar 

  • Zalsman G, Huang Y, Oquendo MA, Burke AK, Hu Z, Brent DA, Ellis SP, Goldman D, Mann JJ (2006) Association of a triallelic serotonin transporter gene promoter region (5-HTTLPR) polymorphism with stressful life events and severity of depression. Am J Psychiatr 163:1588–1593

    Article  Google Scholar 

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Funding

This study was funded by the National Natural Science Foundation of China (81271491, 81571322, and 81371477). These sources had no further role in this study design, in the data collection and analysis, in the writing of the report, and in the decision to submit the paper for publication.

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Correspondence to Shu-Chang He or Xiang Yang Zhang.

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Cao, Z., Wu, S., Wang, C. et al. Serotonin transporter gene (5-HTT) rs6354 polymorphism, job-related stress, and their interaction in burnout in healthcare workers in a Chinese hospital. Psychopharmacology 235, 3125–3135 (2018). https://doi.org/10.1007/s00213-018-5009-2

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