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Serotonin transporter polymorphism, depressive symptoms, and emotional impulsivity among advanced breast cancer patients

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Abstract

Purpose

This study tested a theory linking a marker of low serotonergic function to both depression and impulsivity in a sample of advanced breast cancer patients, among whom elevated depressive symptoms and difficulty regulating emotions are commonly reported.

Methods

A total of 95 patients provided blood samples for serotonin transporter polymorphic region of the gene (5-HTTLPR) and completed questionnaires that measured depressive symptoms and emotional impulsivity.

Results

Structural equation modeling revealed that the s allele of 5-HTTLPR was related to greater depressive symptoms (β = .20, p < .042) but only marginally to greater emotional impulsivity (β = .19, p < .068). Depressive symptoms and emotional impulsivity were positively related (β = .33, p < .003). Further tests explored possible mediation from genotype to one psychological variable via the other. Results suggest that depressive symptoms, particularly perceived interpersonal rejection, may be a pathway linking genotype to emotional impulsivity.

Conclusions

Findings provide the first evidence that low serotonergic function contributes to both depression and impulsivity within a clinically meaningful sample. Furthermore, the link of s allele of 5-HTTLPR to emotional impulsivity was mediated by depressive symptoms, particularly perceptions of social rejection. Findings have implications for advanced breast cancer patients’ treatment decision.

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References

  1. Beitchman, J. H., Davidge, K. M., Kennedy, J. L., Atkinson, L., Lee, V., Shapiro, S., & Douglas L. (2003). The serotonin transporter gene in aggressive children with and without ADHD and nonaggressive matched controls. Annals of New York Academy of Science, 1008, 248–251

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

    Article  CAS  PubMed  Google Scholar 

  3. Collier DA, Stöber G, Li T, Heils A, Catalano M, di Bella D, Arranz MJ, Murray RM, Vallada HP, Bengel D, Müller CR, Roberts GW, Smeraldi E, Kirov G, Sham P, Lesch KP (1996) A novel functional polymorphism within the promoter of the serotonin transporter gene: possible role in susceptibility to affective disorders. Mol Psychiatry 1:453–460

    CAS  PubMed  Google Scholar 

  4. Hoefgen B, Schulze TG, Ohlraun S, von Widdern O, Höfels S, Gross M, Heidmann V, Kovalenko S, Eckermann A, Kölsch H, Metten M, Zobel A, Becker T, Nöthen MM, Propping P, Heun R, Maier W, Rietschel M (2005) The power of sample size and homogenous sampling: association between the 5-HTTLPR serotonin transporter polymorphism and major depressive disorder. Biol Psychiatry 57:247–251

    Article  CAS  PubMed  Google Scholar 

  5. Cools R, Blackwell A, Clark L, Menzies L, Cox S, Robbins TW (2005) Tryptophan depletion disrupts the motivational guidance of goal-directed behavior as a function of trait impulsivity. Neuropsychopharmacology 30:1362–1373

    Article  CAS  PubMed  Google Scholar 

  6. Lyons-Ruth K, Holmes BM, Sasvari-Szekely M, Ronai Z, Nemoda Z, Pauls D (2007) Serotonin transporter polymorphism and borderline or antisocial traits among low-income young adults. Psychiatr Genet 17:339–343

    Article  PubMed  PubMed Central  Google Scholar 

  7. Carver CS, Miller CJ (2006) Relations of serotonin function to personality: current views and a key methodological issue. Psychiatry Res 144:1–15

    Article  CAS  PubMed  Google Scholar 

  8. Carver CS, Johnson SL, Joormann J (2008) Serotonergic function, two-mode models of self-regulation, and vulnerability to depression: what depression has in common with impulsive aggression. Psychol Bull 134:912–943

    Article  PubMed  PubMed Central  Google Scholar 

  9. Depue RA, Spoont MR (1986) Conceptualizing a serotonin trait: a behavioral dimension of constraint. Ann N Y Acad Sci 487:47–62

    Article  CAS  PubMed  Google Scholar 

  10. Spoont MR (1992) Modulatory role of serotonin in neural information processing: implications for human psychopathology. Psychological Bulletin 112:330–350

    Article  CAS  PubMed  Google Scholar 

  11. Carver CS, Johnson SL, Joormann J (2013) Major depressive disorder and impulsive reactivity to emotion: toward a dual process view of depression. Br J Clin Psychol 52:285–299

    Article  PubMed  PubMed Central  Google Scholar 

  12. Carver CS, Johnson SL, Joormann J, Kim Y, Nam JY (2011) Serotonin transporter polymorphism interacts with childhood adversity to predict aspects of impulsivity. Psychol Sci 22:589–595

    Article  PubMed  Google Scholar 

  13. Stoltenberg SF, Christ CC, Highland KB (2012) Serotonin system gene polymorphisms are associated with impulsivity in a context dependent manner. Prog Neuro-Psychopharmacol Biol Psychiatry 39:182–191

    Article  CAS  Google Scholar 

  14. 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. American Journal of Psychiatry 167:502–527

    Article  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  16. Golden-Kreutz DM, Andersen BL (2004) Depressive symptoms after breast cancer surgery: relationships with global, cancer-related, and life event stress. Psycho-Oncology 13:211–220

    Article  PubMed  PubMed Central  Google Scholar 

  17. Mehnert A, Koch U (2007) Prevalence of acute and post-traumatic stress disorder and comorbid mental disorders in breast cancer patients during primary cancer care: a prospective study. Psycho-Oncology 16:181–188

    Article  PubMed  Google Scholar 

  18. Andersen BL, DeRubeis RJ, Berman BS, Gruman J, Champion VL, Massie MJ, Holland JC, Patridge AH, Bak K, Somerfield MR, Rowland JH (2014) Screening, assessment, and care of anxiety and depressive symptoms in adults with cancer: an American Society of Clinical Oncology guideline adaptation. J Clin Oncol 32:1605–1619

    Article  PubMed  PubMed Central  Google Scholar 

  19. Walker J, Holm-Hansen C, Martin P, Sawhney A, Thekkumpurath P, Beals C, Symeonides S, Wall L, Murray G, Sharpe M (2013) Prevalence of depression in adults with cancer: a systematic review. Ann Oncol 24:895–900

    Article  CAS  PubMed  Google Scholar 

  20. Holland JC, Alici Y (2010) Management of distress in cancer patients. J Support Oncol 8:4–12

    PubMed  Google Scholar 

  21. Warren M (2010) Uncertainty, lack of control and emotional functioning in women with metastatic breast cancer: a review and secondary analysis of the literature using the critical appraisal technique. Eur J Cancer Care 19:564–574

    Article  CAS  Google Scholar 

  22. Giege-Davis J, Collie K, Rancourt KM, Neri E, Kraemer HC, Spiegel D (2011) Decreased in depression symptoms is associated with longer survival in patients with metastatic breast cancer: a secondary analysis. J Clin Oncol 29:413–420

    Article  Google Scholar 

  23. Mitchell AJ, Chan M, Bhatti H, Halton M, Grassi L, Johnsen C, Meader N (2011) Prevalence of depression, anxiety, and adjustment disorder in oncological, haematological, and palliative-care settings: a meta-analysis of 94 interview-based studies. Lancet Oncol 12:160–174

    Article  PubMed  Google Scholar 

  24. Aldridge-Gerry A, Zeitzer JM, Palesh OG, Jo B, Nouriani B, Neri E, Spiegel D (2013) Psychosocial correlates of sleep quality and architecture in women with metastatic breast cancer. Sleep Med 14:1178–1186

    Article  PubMed  Google Scholar 

  25. Heils A, Teufel A, Petri S, Stöber G, Riederer P, Bengel D, Lesch KP (1996) Allelic variation of human serotonin transporter gene expression. J Neurochem 66:2621–2624

    Article  CAS  PubMed  Google Scholar 

  26. Radloff LS (1977) The CES-D scale: a self-report depression scale for research in the general population. Appl Psychol Meas 1:385–401

    Article  Google Scholar 

  27. Gratz KL, Roemer L (2004) Multidimensional assessment of emotion regulation and dysregulation: development, factor structure, and initial validation of the difficulties in emotion regulation scale. J Psychopathol Behav Assess 26:41–54

    Article  Google Scholar 

  28. AMOS 21.0. (2012). SPSS Amos users’ guide, Version 21.0. IBM

  29. Bollen KA (1989) Structural equations with latent variables. Wiley, New York

    Book  Google Scholar 

  30. Hu L, Bentler PM (1999) Cutoff criteria for fit indices in covariance structure analysis: conventional criteria versus new alternatives. Struct Equ Model 6:1–55

    Article  Google Scholar 

  31. Shafer A (2006) Meta-analysis of the factor structures of four depression questionnaires: Beck, CES-D, Hamilton, and Zung. J Clin Psychol 62:123–146

    Article  PubMed  Google Scholar 

  32. Kissane D (2009) Beyond the psychotherapy and survival debate: the challenge of social disparity, depression and treatment adherence in psychosocial cancer care. Psycho-Oncology 18:1–5

    Article  PubMed  Google Scholar 

  33. Lash TL, Fox MP, Westrup JL, Fink AK, Silliman RA (2006) Adherence to tamoxifen over the five-year course. Breast Cancer Research & Treatment 99:215–220

    Article  Google Scholar 

  34. Ziller V, Kalder M, Albert US, Holzhauer W, Ziller M, Wagner U, Hadji P (2009) Adherence to adjuvant endocrine therapy in postmenopausal women with breast cancer. Ann Oncol 20:431–436

    Article  CAS  PubMed  Google Scholar 

  35. DiMatteo MR, Lepper HS, Croghan TW (2000) Depression is a risk factor for noncompliance with medical treatment: meta-analysis of the effects of anxiety and depression on patient adherence. Arch Intern Med 160:2101–2107

    Article  CAS  PubMed  Google Scholar 

  36. Kurian AW, Lichtensztajn DY, Keegan TH, Nelson DO, Clarke CA, Gomez SL (2014) Use of and mortality after bilateral mastectomy compared with other surgical treatments for breast cancer in California, 1998-2011. JAMA 312:902–914

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Connolly T, Reb J (2005) Regret in cancer-related decisions. Health Psychol 24:S29–S34

    Article  PubMed  Google Scholar 

  38. Hack TF, Degner LF, Watson P, Sinha L (2006) Do patients benefit from participation in medical decision making? Longitudinal follow-up of women with breast cancer. Psycho-Oncology 15:9–19

    Article  PubMed  Google Scholar 

  39. Lantz PM, Janz NK, Fagerlin A, Schwartz K, Liu L, Lakhani I, Salem B, Katz SJ (2005) Satisfaction with surgery outcomes and the decision process in a population-based sample of women with breast cancer. Health Serv Res 40:745–768

    Article  PubMed  PubMed Central  Google Scholar 

  40. Sheehan J, Sherman KA, Lam T, Boyages J (2007) Association of information satisfaction, psychological distress and monitoring coping style with post-decision regret following breast reconstruction. Psycho-Oncology 16:342–351

    Article  PubMed  Google Scholar 

  41. Hilner BE, Smith TJ (1991) Efficacy and cost effectiveness of adjuvant chemotherapy in women with node-negative breast cancer—a decision-analysis model. N Engl J Med 324:160–168

    Article  Google Scholar 

  42. Lo SS, Mumby PB, Norton J, Rychlik K, Smerage J, Kash J, Chew HK, Gaynor ER, Hayes DF, Epstein A, Albain KS (2010) Prospective multicenter study of the impact of the 21-gene recurrence score assay on medical oncologist and patient adjuvant breast cancer treatment selection. J Clin Oncol 28:1671–1676

    Article  PubMed  Google Scholar 

  43. Meropol NJ, Schrag D, Smith TJ, Mulvey TM, Landon RM, Blum D, Ubel PA, Schnipper LE (2009) American Society of Clinical Oncology guidance statement: the cost of cancer care. J Clin Oncol 27:3868–3874

    Article  PubMed  Google Scholar 

  44. Smith TJ, Hillner BE (2011) Bending the cost curve in cancer care. N Engl J Med 364:2060–2065

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Spiegel D, Riba MB (2015) Managing anxiety and depression during treatment. Breast J 21:97–103

    Article  PubMed  Google Scholar 

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Acknowledgements

The authors extend their appreciation to all the study participants and the Dr. Susan Love Research Foundation’s Love/Avon Army of Women Program for their assistance in recruitment. The first author dedicates this research to the memory of Heekyoung Kim and Keun Meeso.

Funding

This study was funded by the National Cancer Institute (R01CA118567) and the National Center for Research Resources (UL1 RR025744) to DS. Writing of this manuscript was supported by American Cancer Society Research Scholar Grants (121909-RSG-12-042-01-CPPB) to YK.

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Correspondence to Youngmee Kim.

Ethics declarations

The study was carried out in accordance with the latest version of the Declaration of Helsinki and the study design was reviewed by the Stanford University Institutional Review Board. Informed consent of the participants was obtained after the nature of the procedures had been fully explained.

Conflict of interest

The authors declare that they have no conflict of interest.

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Kim, Y., Carver, C.S., Hallmayer, J.F. et al. Serotonin transporter polymorphism, depressive symptoms, and emotional impulsivity among advanced breast cancer patients. Support Care Cancer 26, 1181–1188 (2018). https://doi.org/10.1007/s00520-017-3940-0

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  • DOI: https://doi.org/10.1007/s00520-017-3940-0

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