Behavior Genetics

, Volume 46, Issue 1, pp 72–88 | Cite as

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

  • Thalida E. Arpawong
  • Jinkook Lee
  • Drystan F. Phillips
  • Eileen M. Crimmins
  • Morgan E. Levine
  • Carol A. Prescott
Original Research

Abstract

Depending on genetic sensitivity to it, stress may affect depressive symptomatology differentially. Applying the stress-diathesis hypothesis to older adults, we postulate: (1) recent stress will associate with increased depressive symptom levels and (2) this effect will be greater for individuals with at least one short allele of the serotonin transporter gene promoter region (5-HTTLPR). Further, we employ a design that addresses specific limitations of many prior studies that have examined the 5-HTTLPR × SLE relation, by: (a) using a within-person repeated-measures design to address fluctuations that occur within individuals over time, increase power for detecting G × E, and address GE correlation; (b) studying reports of exogenous stressful events (those unlikely to be caused by depression) to help rule out reverse causation and negativity bias, and in order to assess stressors that are more etiologically relevant to depressive symptomatology in older adults. The sample is drawn from the Health and Retirement Study, a U.S. population-based study of older individuals (N = 28,248; mean age = 67.5; 57.3 % female; 80.7 % Non-Hispanic White, 14.9 % Hispanic/Latino, 4.5 % African American; genetic subsample = 12,332), from whom measures of depressive symptoms and exogenous stressors were collected biannually (1994–2010). Variation in the 5-HTTLPR was characterized via haplotype, using two single nucleotide polymorphisms (SNPs). Ordered logit models were constructed to predict levels of depressive symptoms from 5-HTTLPR and stressors, comparing results of the most commonly applied statistical approaches (i.e., comparing allelic and genotypic models, and continuous and categorical predictors) used in the literature. All models were stratified by race/ethnicity. Overall, results show a main effect of recent stress for all ethnic groups, and mixed results for the variation in 5-HTTLPR × stress interaction, contingent upon statistical model used. Findings suggest there may be a differential effect of stressors and 5-HTTLPR on depressive symptoms by ethnicity, but further research is needed, particularly when using a haplotype to characterize variation in 5-HTTLPR in population-based sample with a diverse ethnic composition.

Keywords

5-HTTLPR Depressive symptoms Stressful life events Race differences Older adults G × E 

Supplementary material

10519_2015_9740_MOESM1_ESM.docx (82 kb)
Supplementary material 1 (DOCX 82 kb)

References

  1. Alexopoulos GS (2005) Depression in the elderly. Lancet 365(9475):1961–1970PubMedCrossRefGoogle Scholar
  2. Araya R, Hu X, Heron J, Enoch MA, Evans J, Lewis G, Nutt D, Goldman D (2009) Effects of stressful life events, maternal depression and 5-HTTLPR genotype on emotional symptoms in pre-adolescent children. Am J Med Genet Part B 150(5):670–682CrossRefGoogle Scholar
  3. Bakermans-Kranenburg MJ, Van IJzendoorn MH (2007) Research review: genetic vulnerability or differential susceptibility in child development: the case of attachment. J Child Psychol Psychiatry 48(12):1160–1173PubMedCrossRefGoogle Scholar
  4. Beck JS (1995) Cognitive therapy. Wiley Online Library, ChichesterGoogle Scholar
  5. Belsky J, Pluess M (2009) Beyond diathesis stress: differential susceptibility to environmental influences. Psychol Bull 135(6):885PubMedCrossRefGoogle Scholar
  6. Belsky J, Jonassaint C, Pluess M, Stanton M, Brummett B, Williams R (2009) Vulnerability genes or plasticity genes quest. Mol Psychiatry 14(8):746–754PubMedPubMedCentralCrossRefGoogle Scholar
  7. Brummett BH, Boyle SH, Siegler IC, Kuhn CM, Ashley-Koch A, Jonassaint CR, Züchner S, Collins A, Williams RB (2008) Effects of environmental stress and gender on associations among symptoms of depression and the serotonin transporter gene linked polymorphic region (5-HTTLPR). Behav Genet 38(1):34–43PubMedPubMedCentralCrossRefGoogle Scholar
  8. Carli V, Mandelli L, Zaninotto L, Roy A, Recchia L, Stoppia L, Gatta V, Sarchiapone M, Serretti A (2011) A protective genetic variant for adverse environments? The role of childhood traumas and serotonin transporter gene on resilience and depressive severity in a high-risk population. Eur Psychiatry 26(8):471–478PubMedCrossRefGoogle Scholar
  9. 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(5631):386–389PubMedCrossRefGoogle Scholar
  10. Cervilla J, Molina E, Rivera M, Torres-Gonzalez F, Bellon J, Moreno B, Luna J, Lorente J, Mayoral F, King M (2007) The risk for depression conferred by stressful life events is modified by variation at the serotonin transporter 5HTTLPR genotype: evidence from the Spanish PREDICT-Gene cohort. Mol Psychiatry 12(8):748–755PubMedCrossRefGoogle Scholar
  11. Chang CC, Chow CC, Tellier LC, Vattikuti S, Purcell SM, Lee JJ (2014) Second-generation PLINK: rising to the challenge of larger and richer datasets. arXiv preprint arXiv:14104803Google Scholar
  12. Chipman P, Jorm A, Prior M, Sanson A, Smart D, Tan X, Easteal S (2007) No interaction between the serotonin transporter polymorphism (5-HTTLPR) and childhood adversity or recent stressful life events on symptoms of depression: results from two community surveys. Am J Med Genet Part B 144(4):561–565CrossRefGoogle Scholar
  13. Chorbov VM, Lobos EA, Todorov AA, Heath AC, Botteron KN, Todd RD (2007) Relationship of 5-HTTLPR genotypes and depression risk in the presence of trauma in a female twin sample. Am J Med Genet Part B 144(6):830–833CrossRefGoogle Scholar
  14. Cicchetti D, Rogosch FA (2014) Genetic moderation of child maltreatment effects on depression and internalizing symptoms by serotonin transporter linked polymorphic region (5-HTTLPR), brain-derived neurotrophic factor (BDNF), norepinephrine transporter (NET), and corticotropin releasing hormone receptor 1 (CRHR1) genes in African American children. Dev Psychopathol 26(4 Pt 2):1219–1239PubMedPubMedCentralCrossRefGoogle Scholar
  15. CIDR (2012) CIDR health and retirement study: imputation report—1000 genomes project reference panel, University of Washington, Seattle, pp 1–25Google Scholar
  16. Consortium GP (2012) An integrated map of genetic variation from 1092 human genomes. Nature 491(7422):56–65CrossRefGoogle Scholar
  17. Cuijpers P, de Graaf R, van Dorsselaer S (2004) Minor depression: risk profiles, functional disability, health care use and risk of developing major depression. J Affect Disord 79(1):71–79PubMedCrossRefGoogle Scholar
  18. Delaneau O, Zagury J-F, Marchini J (2013) Improved whole-chromosome phasing for disease and population genetic studies. Nat Methods 10(1):5–6PubMedCrossRefGoogle Scholar
  19. Delbruck SJ, Wendel B, Grunewald I, Sander T, Morris-Rosendahl D, Crocq MA, Berrettini WH, Hoehe MR (1997) A novel allelic variant of the human serotonin transporter gene regulatory polymorphism. Cytogenet Cell Genet 79(3–4):214–220PubMedGoogle Scholar
  20. Ellis BJ, Boyce WT, Belsky J, Bakermans-Kranenburg MJ, Van IJzendoorn MH (2011) Differential susceptibility to the environment: an evolutionary? Neurodevelopmental theory. Dev Psychopathol 23(1):7PubMedCrossRefGoogle Scholar
  21. Fiske A, Wetherell JL, Gatz M (2009) Depression in older adults. Annu Rev Clin Psychol 5:363–389PubMedPubMedCentralCrossRefGoogle Scholar
  22. Frisch A, Finkel B, Michaelovsky E, Sigal M, Laor N, Weizman R (2000) A rare short allele of the serotonin transporter promoter region (5-HTTLPR) found in an aggressive schizophrenic patient of Jewish Libyan origin. Psychiatry Genet 10(4):179–183CrossRefGoogle Scholar
  23. Gelernter J, Kranzler H, Cubells JF (1997) Serotonin transporter protein (SLC6A4) allele and haplotype frequencies and linkage disequilibria in African-and European-American and Japanese populations and in alcohol-dependent subjects. Hum Genet 101(2):243–246PubMedCrossRefGoogle Scholar
  24. Gillespie NA, Whitfield JB, Williams B, Heath AC, Martin NG (2005) The relationship between stressful life events, the serotonin transporter (5-HTTLPR) genotype and major depression. Psychol Med 35(01):101–111PubMedCrossRefGoogle Scholar
  25. Goldman N, Glei DA, Lin YH, Weinstein M (2010) The serotonin transporter polymorphism (5-HTTLPR): allelic variation and links with depressive symptoms. Depress Anxiety 27(3):260–269PubMedPubMedCentralCrossRefGoogle Scholar
  26. Grabe HJ, Lange M, Wolff B, Völzke H, Lucht M, Freyberger H, 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(2):220–224PubMedCrossRefGoogle Scholar
  27. Gyurak A, Haase CM, Sze J, Goodkind MS, Coppola G, Lane J, Miller BL, Levenson RW (2013) The effect of the serotonin transporter polymorphism (5-HTTLPR) on empathic and self-conscious emotional reactivity. Emotion 13(1):25PubMedPubMedCentralCrossRefGoogle Scholar
  28. Haase CM, Saslow LR, Bloch L, Saturn SR, Casey JJ, Seider BH, Lane J, Coppola G, Levenson RW (2013) The 5-HTTLPR polymorphism in the serotonin transporter gene moderates the association between emotional behavior and changes in marital satisfaction over time. Emotion 13(6):1068Google Scholar
  29. 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(6):2621–2624PubMedCrossRefGoogle Scholar
  30. Howie BN, Donnelly P, Marchini J (2009) A flexible and accurate genotype imputation method for the next generation of genome-wide association studies. PLoS Genet 5(6):e1000529PubMedPubMedCentralCrossRefGoogle Scholar
  31. HRS (2011) Sample Sizes and Response Rates, University of Michigan, Ann Arbor, pp 1–13. http://www.hrsonline.isr.umich.edu/sitedocs/sampleresponse.pdf. Accessed 15 Mar 2015
  32. HRS (2012) Quality control report for genotypic data, University of Washington, St. Louis, pp 1–44. http://www.hrsonline.isr.umich.edu/sitedocs/genetics/HRS_QC_REPORT_MAR2012.pdf. Accessed Mar 2015
  33. Hu X, Oroszi G, Chun J, Smith TL, Goldman D, Schuckit MA (2005) An expanded evaluation of the relationship of four alleles to the level of response to alcohol and the alcoholism risk. Alcohol Clin Exp Res 29(1):8–16PubMedCrossRefGoogle Scholar
  34. Hu XZ, Lipsky RH, Zhu G, Akhtar LA, Taubman J, Greenberg BD, Xu K, Arnold PD, Richter MA, Kennedy JL, Murphy DL, Goldman D (2006) Serotonin transporter promoter gain-of-function genotypes are linked to obsessive-compulsive disorder. Am J Hum Genet 78(5):815–826PubMedPubMedCentralCrossRefGoogle Scholar
  35. Jackson JS, Knight KM, Rafferty JA (2010) Race and unhealthy behaviors: chronic stress, the HPA axis, and physical and mental health disparities over the life course. Am J Public Health 100(5):933–939PubMedPubMedCentralCrossRefGoogle Scholar
  36. Jacobs N, Kenis G, Peeters F, Derom C, Vlietinck R, Van Os J (2006) Stress-related negative affectivity and genetically altered serotonin transporter function: evidence of synergism in shaping risk of depression. Arch Gen Psychiatry 63(9):989–996PubMedCrossRefGoogle Scholar
  37. Kapteyn A, Michaud P-C, Smith JP, Van Soest A (2006) Effects of attrition and non-response in the Health and Retirement Study. In. IZA Discussion Papers No. 2246. Institute for the Study of Labor, Bonn, pp 1–43Google Scholar
  38. 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):444–454PubMedPubMedCentralCrossRefGoogle Scholar
  39. Kendler KS, Kessler RC, Walters EE, MacLean C, Neale MC, Heath AC, Eaves LJ (1995) Stressful life events, genetic liability, and onset of an episode of major depression in women. Am J Psychiatry 152(6):833–842PubMedCrossRefGoogle Scholar
  40. Kendler KS, Kuhn JW, Prescott CA (2004) Childhood sexual abuse, stressful life events and risk for major depression in women. Psychol Med 34(08):1475–1482PubMedCrossRefGoogle Scholar
  41. 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(5):529–535PubMedCrossRefGoogle Scholar
  42. Keyes CL (2009) The Black-White paradox in health: flourishing in the face of social inequality and discrimination. J Pers 77(6):1677–1706PubMedCrossRefGoogle Scholar
  43. Kilpatrick DG, Koenen KC, Ruggiero KJ, Acierno R, Galea S, Resnick HS, Roitzsch J, Boyle J, Gelernter J (2007) The serotonin transporter genotype and social support and moderation of posttraumatic stress disorder and depression in hurricane-exposed adults. Am J Psychiatry 164(11):1693–1699PubMedCrossRefGoogle Scholar
  44. Kim Y, Schulz R, Carver CS (2007) Benefit finding in the cancer caregiving experience. Psychosom Med 69(3):283–291PubMedCrossRefGoogle Scholar
  45. Kohout FJ, Berkman LF, Evans DA, Cornoni-Huntley J (1993) Two shorter forms of the CES-D depression symptoms index. J Aging Health 5(2):179–193PubMedCrossRefGoogle Scholar
  46. Kraaij V, Arensman E, Spinhoven P (2002) Negative life events and depression in elderly persons a meta-analysis. J Gerontol Ser B 57(1):P87–P94CrossRefGoogle Scholar
  47. Kraft JB, Slager SL, McGrath PJ, Hamilton SP (2005) Sequence analysis of the serotonin transporter and associations with antidepressant response. Biol Psychiatry 58(5):374–381PubMedCrossRefGoogle Scholar
  48. Laucht M, Treutlein J, Blomeyer D, Buchmann AF, Schmid B, Becker K, Zimmermann US, Schmidt MH, Esser G, Rietschel M (2009) Interaction between the 5-HTTLPR serotonin transporter polymorphism and environmental adversity for mood and anxiety psychopathology: evidence from a high-risk community sample of young adults. Int J Neuropsychopharmacol 12(6):737–747PubMedCrossRefGoogle Scholar
  49. Laurie CC, Doheny KF, Mirel DB, Pugh EW, Bierut LJ, Bhangale T, Boehm F, Caporaso NE, Cornelis MC, Edenberg HJ (2010) Quality control and quality assurance in genotypic data for genome-wide association studies. Genet Epidemiol 34(6):591–602PubMedPubMedCentralCrossRefGoogle Scholar
  50. 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(5292):1527–1531PubMedCrossRefGoogle Scholar
  51. Li Y, Willer C, Sanna S, Abecasis G (2009) Genotype imputation. Annu Rev Genomics Hum Genet 10:387–406PubMedPubMedCentralCrossRefGoogle Scholar
  52. Li JJ, Berk MS, Lee SS (2013) Differential susceptibility in longitudinal models of gene–environment interaction for adolescent depression. Dev Psychopathol 25(4pt1):991–1003PubMedCrossRefGoogle Scholar
  53. Lotrich FE, Pollock BG, Ferrell RE (2003) Serotonin transporter promoter polymorphism in African Americans. Am J Pharmacogenomics 3(2):145–147PubMedCrossRefGoogle Scholar
  54. Mazure CM, Maciejewski PK, Jacobs SC, Bruce ML (2002) Stressful life events interacting with cognitive/personality styles to predict late-onset major depression. Am J Geriatr Psychiatry 10(3):297–304PubMedCrossRefGoogle Scholar
  55. Medland SE, Nyholt DR, Painter JN, McEvoy BP, McRae AF, Zhu G, Gordon SD, Ferreira MA, Wright MJ, Henders AK (2009) Common variants in the trichohyalin gene are associated with straight hair in Europeans. Am J Hum Genet 85(5):750–755PubMedPubMedCentralCrossRefGoogle Scholar
  56. Middeldorp CM, de Geus EJ, Beem AL, Lakenberg N, Hottenga J-J, Slagboom PE, Boomsma DI (2007) Family based association analyses between the serotonin transporter gene polymorphism (5-HTTLPR) and neuroticism, anxiety and depression. Behav Genet 37(2):294–301PubMedCrossRefGoogle Scholar
  57. Ming Q, Zhang Y, Q-l C, H-y C, C-j H, M-c W, Y-p W, Cai L, X-z Z, J-y Y (2013) Interaction between a serotonin transporter gene promoter region polymorphism and stress predicts depressive symptoms in Chinese adolescents: a multi-wave longitudinal study. BMC Psychiatry 13(1):142PubMedPubMedCentralCrossRefGoogle Scholar
  58. Monroe SM, Reid MW (2008) Gene-environment interactions in depression research: genetic polymorphisms and life-stress polyprocedures. Psychol Sci 19(10):947–956PubMedCrossRefGoogle Scholar
  59. Munafò MR, Durrant C, Lewis G, Flint J (2009) Gene × environment interactions at the serotonin transporter locus. Biol Psychiatry 65(3):211–219PubMedCrossRefGoogle Scholar
  60. Nakamura M, Ueno S, Sano A, Tanabe H (2000) The human serotonin transporter gene linked polymorphism (5-HTTLPR) shows ten novel allelic variants. Mol Psychiatry 5(1):32–38PubMedCrossRefGoogle Scholar
  61. Otte C, McCaffery J, Ali S, Whooley MA (2007) Association of a serotonin transporter polymorphism (5-HTTLPR) with depression, perceived stress, and norepinephrine in patients with coronary disease: the heart and soul study. Am J Psychiatry 164:1379–1384PubMedPubMedCentralCrossRefGoogle Scholar
  62. Peyrot WJ, Middeldorp CM, Jansen R, Smit JH, de Geus EJ, Hottenga JJ, Willemsen G, Vink JM, Virding S, Barragan I, Ingelman-Sundberg M, Sim SC, Boomsma DI, Penninx BW (2013) Strong effects of environmental factors on prevalence and course of major depressive disorder are not moderated by 5-HTTLPR polymorphisms in a large Dutch sample. J Affect Disord 146(1):91–99PubMedCrossRefGoogle Scholar
  63. Phillips-Bute B, Mathew JP, Blumenthal JA, Morris RW, Podgoreanu MV, Smith M, Stafford-Smith M, Grocott HP, Schwinn DA, Newman MF (2008) Relationship of genetic variability and depressive symptoms to adverse events after coronary artery bypass graft surgery. Psychosom Med 70(9):953PubMedPubMedCentralCrossRefGoogle Scholar
  64. Poulin C, Hand D, Boudreau B, Santor D (2005) Gender differences in the association between substance use and elevated depressive symptoms in a general adolescent population. Addiction 100(4):525–535PubMedCrossRefGoogle Scholar
  65. Power T, Stewart R, Ancelin M-L, Jaussent I, Malafosse A, Ritchie K (2010) 5-HTTLPR genotype, stressful life events and late-life depression: no evidence of interaction in a French population. Neurobiol Aging 31(5):886–887PubMedCrossRefGoogle Scholar
  66. Radloff LS (1977) The Ces-D scale. Appl Psychol Meas 1(3):385–401CrossRefGoogle Scholar
  67. Radloff LS (1991) The use of the center for epidemiologic studies depression scale in adolescents and young-adults. J Youth Adolesc 20(2):149–166PubMedCrossRefGoogle Scholar
  68. RAND (2014) RAND enhanced fat files. Center for the Study of Aging, RAND Corporation, Santa MonicaGoogle Scholar
  69. Rees M, Norton N, Jones I, McCandless F, Scourfield J, Holmans P, Moorhead S, Feldman E, Sadler S, Cole T (1997) Association studies of bipolar disorder at the human serotonin transporter gene (hSERT; 5HTT). Mol Psychiatry 2(5):398–402PubMedCrossRefGoogle Scholar
  70. Risch N, Herrell R, Lehner T, Liang K-Y, Eaves L, Hoh J, Griem A, Kovacs M, Ott J, Merikangas KR (2009) Interaction between the serotonin transporter gene (5-HTTLPR), stressful life events, and risk of depression: a meta-analysis. JAMA 301(23):2462–2471PubMedPubMedCentralCrossRefGoogle Scholar
  71. Ritchie K, Jaussent I, Stewart R, Dupuy A-M, Courtet P, Ancelin M-L, Malafosse A (2009) Association of adverse childhood environment and 5-HTTLPR genotype with late-life depression. J Clin Psychiatry 70(9):1281PubMedPubMedCentralCrossRefGoogle Scholar
  72. Santor DA, Coyne JC (1997) Shortening the CES–D to improve its ability to detect cases of depression. Psychol Assess 9(3):233CrossRefGoogle Scholar
  73. Scheid J, Holzman C, Jones N, Friderici K, Nummy K, Symonds L, Sikorskii A, Regier M, Fisher R (2007) Depressive symptoms in mid-pregnancy, lifetime stressors and the 5-HTTLPR genotype. Genes Brain Behav 6(5):453–464PubMedCrossRefGoogle Scholar
  74. Schild AH, Nader IW, Pietschnig J, Voracek M (2014) Ethnicity moderates the association between 5-HTTLPR and national suicide rates. Arch Suicide Res 18(1):1–13PubMedCrossRefGoogle Scholar
  75. Seneviratne C, Huang W, Ait-Daoud N, Li MD, Johnson BA (2009) Characterization of a functional polymorphism in the 3′ UTR of SLC6A4 and its association with drinking intensity. Alcohol Clin Exp Res 33(2):332–339PubMedPubMedCentralCrossRefGoogle Scholar
  76. Seneviratne C, Franklin J, Beckett K, Ma JZ, Ait-Daoud N, Payne TJ, Johnson BA, Li MD (2013) Association, interaction, and replication analysis of genes encoding serotonin transporter and 5-HT3 receptor subunits A and B in alcohol dependence. Hum Genet 132(10):1165–1176PubMedPubMedCentralCrossRefGoogle Scholar
  77. Sharpley CF, Palanisamy SK, Glyde NS, Dillingham PW, Agnew LL (2014) An update on the interaction between the serotonin transporter promoter variant (5-HTTLPR), stress and depression, plus an exploration of non-confirming findings. Behav Brain Res 27:105–389Google Scholar
  78. Sjöberg RL, Nilsson KW, Nordquist N, Öhrvik J, Leppert J, Lindström L, Oreland L (2006) Development of depression: sex and the interaction between environment and a promoter polymorphism of the serotonin transporter gene. Int J Neuropsychopharmacol 9(4):443–449PubMedCrossRefGoogle Scholar
  79. Steffick DE (2002) Mental health and labor market outcomes. University of Michigan, Ann ArborGoogle Scholar
  80. Surtees PG, Wainwright NW, Willis-Owen SA, Luben R, Day NE, Flint J (2006) Social adversity, the serotonin transporter (5-HTTLPR) polymorphism and major depressive disorder. Biol Psychiatry 59(3):224–229PubMedCrossRefGoogle Scholar
  81. Taylor SE, Way BM, Welch WT, Hilmert CJ, Lehman BJ, Eisenberger NI (2006) Early family environment, current adversity, the serotonin transporter promoter polymorphism, and depressive symptomatology. Biol Psychiatry 60(7):671–676PubMedCrossRefGoogle Scholar
  82. Tennant C (2002) Life events, stress and depression: a review of recent findings. Aust N Z J Psychiatry 36(2):173–182PubMedCrossRefGoogle Scholar
  83. Turvey CL, Wallace RB, Herzog R (1999) A revised CES-D measure of depressive symptoms and a DSM-based measure of major depressive episodes in the elderly. Int Psychogeriatr 11(02):139–148PubMedCrossRefGoogle Scholar
  84. 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(1):18–22PubMedCrossRefGoogle Scholar
  85. Vinkhuyzen AA, Dumenil T, Ryan L, Gordon SD, Henders AK, Madden PA, Heath AC, Montgomery GW, Martin NG, Wray NR (2011) Identification of tag haplotypes for 5HTTLPR for different genome-wide SNP platforms. Mol Psychiatry 16(11):1073Google Scholar
  86. Walsh K, Uddin M, Soliven R, Wildman DE, Bradley B (2014) Associations between the SS variant of 5-HTTLPR and PTSD among adults with histories of childhood emotional abuse: results from two African American independent samples. J Affect Disord 16:191–196Google Scholar
  87. 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(3):224–226PubMedCrossRefGoogle Scholar
  88. 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(3):210–215PubMedCrossRefGoogle Scholar
  89. Williams RB, Marchuk DA, Gadde K, Barefoot JC, Grichnik K, Helms MJ, Kuhn CM, Lewis JG, Schanberg SM, Stafford-Smith M (2003) Serotonin-related gene polymorphisms and central nervous system serotonin function. Neuropsychopharmacology 28:533–541PubMedCrossRefGoogle Scholar
  90. Wong M, Day N, Luan J, Chan K, Wareham N (2003) The detection of gene–environment interaction for continuous traits: should we deal with measurement error by bigger studies or better measurement? Int J Epidemiol 32(1):51–57PubMedCrossRefGoogle Scholar
  91. Wray NR, James MR, Gordon SD, Dumenil T, Ryan L, Coventry WL, Statham DJ, Pergadia ML, Madden PA, Heath AC (2009) Accurate, large-scale genotyping of 5HTTLPR and flanking single nucleotide polymorphisms in an association study of depression, anxiety, and personality measures. Biol Psychiat 66(5):468–476PubMedPubMedCentralCrossRefGoogle Scholar
  92. Yang Z, Seneviratne C, Wang S, Ma JZ, Payne TJ, Wang J, Li MD (2013) Serotonin transporter and receptor genes significantly impact nicotine dependence through genetic interactions in both European American and African American smokers. Drug Alcohol Depen 129(3):217–225CrossRefGoogle Scholar
  93. Zammit S, Owen MJ (2006) Stressful life events, 5-HTT genotype and risk of depression. Br J Psychiatry 188:199–201PubMedCrossRefGoogle Scholar
  94. Zimmerman M, Coryell W (1994) Screening for major depressive disorder in the community: a comparison of measures. Psychol Assess 6(1):71CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  1. 1.Department of PsychologyUniversity of Southern CaliforniaLos AngelesUSA
  2. 2.Dornsife Center for Economic and Social ResearchUniversity of Southern CaliforniaLos AngelesUSA
  3. 3.RAND CorporationSanta MonicaUSA
  4. 4.Davis School of GerontologyUniversity of Southern CaliforniaLos AngelesUSA
  5. 5.Human Genetics, David Geffen School of MedicineUniversity of CaliforniaLos AngelesUSA

Personalised recommendations