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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

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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.

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References

  • Alexopoulos GS (2005) Depression in the elderly. Lancet 365(9475):1961–1970

    Article  PubMed  Google Scholar 

  • 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):670–682

    Article  Google Scholar 

  • 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):1160–1173

    Article  PubMed  Google Scholar 

  • Beck JS (1995) Cognitive therapy. Wiley Online Library, Chichester

    Google Scholar 

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

    Article  PubMed  Google Scholar 

  • Belsky J, Jonassaint C, Pluess M, Stanton M, Brummett B, Williams R (2009) Vulnerability genes or plasticity genes quest. Mol Psychiatry 14(8):746–754

    Article  PubMed  PubMed Central  Google Scholar 

  • 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):34–43

    Article  PubMed  PubMed Central  Google Scholar 

  • 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):471–478

    Article  PubMed  Google Scholar 

  • 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):386–389

    Article  PubMed  Google Scholar 

  • 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):748–755

    Article  PubMed  Google Scholar 

  • 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:14104803

  • 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):561–565

    Article  Google Scholar 

  • 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):830–833

    Article  Google Scholar 

  • 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):1219–1239

    Article  PubMed  PubMed Central  Google Scholar 

  • CIDR (2012) CIDR health and retirement study: imputation report—1000 genomes project reference panel, University of Washington, Seattle, pp 1–25

  • Consortium GP (2012) An integrated map of genetic variation from 1092 human genomes. Nature 491(7422):56–65

    Article  Google Scholar 

  • 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):71–79

    Article  PubMed  Google Scholar 

  • Delaneau O, Zagury J-F, Marchini J (2013) Improved whole-chromosome phasing for disease and population genetic studies. Nat Methods 10(1):5–6

    Article  PubMed  Google Scholar 

  • 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):214–220

    PubMed  Google Scholar 

  • 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):7

    Article  PubMed  Google Scholar 

  • Fiske A, Wetherell JL, Gatz M (2009) Depression in older adults. Annu Rev Clin Psychol 5:363–389

    Article  PubMed  PubMed Central  Google Scholar 

  • 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):179–183

    Article  Google Scholar 

  • 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):243–246

    Article  PubMed  Google Scholar 

  • 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):101–111

    Article  PubMed  Google Scholar 

  • 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):260–269

    Article  PubMed  PubMed Central  Google Scholar 

  • 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):220–224

    Article  PubMed  Google Scholar 

  • 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):25

    Article  PubMed  PubMed Central  Google Scholar 

  • 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):1068

  • 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):2621–2624

    Article  PubMed  Google Scholar 

  • 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):e1000529

    Article  PubMed  PubMed Central  Google Scholar 

  • 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

  • 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

  • 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):8–16

    Article  PubMed  Google Scholar 

  • 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):815–826

    Article  PubMed  PubMed Central  Google Scholar 

  • 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):933–939

    Article  PubMed  PubMed Central  Google Scholar 

  • 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):989–996

    Article  PubMed  Google Scholar 

  • 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 1–43

  • 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  PubMed  PubMed Central  Google Scholar 

  • 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):833–842

    Article  PubMed  Google Scholar 

  • Kendler KS, Kuhn JW, Prescott CA (2004) Childhood sexual abuse, stressful life events and risk for major depression in women. Psychol Med 34(08):1475–1482

    Article  PubMed  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(5):529–535

    Article  PubMed  Google Scholar 

  • Keyes CL (2009) The Black-White paradox in health: flourishing in the face of social inequality and discrimination. J Pers 77(6):1677–1706

    Article  PubMed  Google Scholar 

  • 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):1693–1699

    Article  PubMed  Google Scholar 

  • Kim Y, Schulz R, Carver CS (2007) Benefit finding in the cancer caregiving experience. Psychosom Med 69(3):283–291

    Article  PubMed  Google Scholar 

  • 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):179–193

    Article  PubMed  Google Scholar 

  • 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–P94

    Article  Google Scholar 

  • Kraft JB, Slager SL, McGrath PJ, Hamilton SP (2005) Sequence analysis of the serotonin transporter and associations with antidepressant response. Biol Psychiatry 58(5):374–381

    Article  PubMed  Google Scholar 

  • 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):737–747

    Article  PubMed  Google Scholar 

  • 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):591–602

    Article  PubMed  PubMed Central  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(5292):1527–1531

    Article  PubMed  Google Scholar 

  • Li Y, Willer C, Sanna S, Abecasis G (2009) Genotype imputation. Annu Rev Genomics Hum Genet 10:387–406

    Article  PubMed  PubMed Central  Google Scholar 

  • Li JJ, Berk MS, Lee SS (2013) Differential susceptibility in longitudinal models of gene–environment interaction for adolescent depression. Dev Psychopathol 25(4pt1):991–1003

    Article  PubMed  Google Scholar 

  • Lotrich FE, Pollock BG, Ferrell RE (2003) Serotonin transporter promoter polymorphism in African Americans. Am J Pharmacogenomics 3(2):145–147

    Article  PubMed  Google Scholar 

  • 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):297–304

    Article  PubMed  Google Scholar 

  • 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):750–755

    Article  PubMed  PubMed Central  Google Scholar 

  • 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):294–301

    Article  PubMed  Google Scholar 

  • 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):142

    Article  PubMed  PubMed Central  Google Scholar 

  • Monroe SM, Reid MW (2008) Gene-environment interactions in depression research: genetic polymorphisms and life-stress polyprocedures. Psychol Sci 19(10):947–956

    Article  PubMed  Google Scholar 

  • Munafò MR, Durrant C, Lewis G, Flint J (2009) Gene × environment interactions at the serotonin transporter locus. Biol Psychiatry 65(3):211–219

    Article  PubMed  Google Scholar 

  • 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):32–38

    Article  PubMed  Google Scholar 

  • 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 164:1379–1384

    Article  PubMed  PubMed Central  Google Scholar 

  • 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):91–99

    Article  PubMed  Google Scholar 

  • 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):953

    Article  PubMed  PubMed Central  Google Scholar 

  • 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):525–535

    Article  PubMed  Google Scholar 

  • 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):886–887

    Article  PubMed  Google Scholar 

  • Radloff LS (1977) The Ces-D scale. Appl Psychol Meas 1(3):385–401

    Article  Google Scholar 

  • Radloff LS (1991) The use of the center for epidemiologic studies depression scale in adolescents and young-adults. J Youth Adolesc 20(2):149–166

    Article  PubMed  Google Scholar 

  • RAND (2014) RAND enhanced fat files. Center for the Study of Aging, RAND Corporation, Santa Monica

    Google Scholar 

  • 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):398–402

    Article  PubMed  Google Scholar 

  • 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):2462–2471

    Article  PubMed  PubMed Central  Google Scholar 

  • 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):1281

    Article  PubMed  PubMed Central  Google Scholar 

  • Santor DA, Coyne JC (1997) Shortening the CES–D to improve its ability to detect cases of depression. Psychol Assess 9(3):233

    Article  Google Scholar 

  • 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):453–464

    Article  PubMed  Google Scholar 

  • 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):1–13

    Article  PubMed  Google Scholar 

  • 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):332–339

    Article  PubMed  PubMed Central  Google Scholar 

  • 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):1165–1176

    Article  PubMed  PubMed Central  Google Scholar 

  • 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 27:105–389

    Google Scholar 

  • 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):443–449

    Article  PubMed  Google Scholar 

  • Steffick DE (2002) Mental health and labor market outcomes. University of Michigan, Ann Arbor

    Google Scholar 

  • 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):224–229

    Article  PubMed  Google Scholar 

  • 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):671–676

    Article  PubMed  Google Scholar 

  • Tennant C (2002) Life events, stress and depression: a review of recent findings. Aust N Z J Psychiatry 36(2):173–182

    Article  PubMed  Google Scholar 

  • 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):139–148

    Article  PubMed  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(1):18–22

    Article  PubMed  Google Scholar 

  • 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):1073

  • 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 16:191–196

    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(3):224–226

    Article  PubMed  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(3):210–215

    Article  PubMed  Google Scholar 

  • 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 28:533–541

    Article  PubMed  Google Scholar 

  • 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):51–57

    Article  PubMed  Google Scholar 

  • 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):468–476

    Article  PubMed  PubMed Central  Google Scholar 

  • 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):217–225

    Article  Google Scholar 

  • Zammit S, Owen MJ (2006) Stressful life events, 5-HTT genotype and risk of depression. Br J Psychiatry 188:199–201

    Article  PubMed  Google Scholar 

  • Zimmerman M, Coryell W (1994) Screening for major depressive disorder in the community: a comparison of measures. Psychol Assess 6(1):71

    Article  Google Scholar 

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Acknowledgments

This research was supported by the National Institute on Aging, of the National Institutes of Health, under Award Numbers F32AG048681 and P30AG17265. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Note: The Health and Retirement Study genetic data is sponsored by the National Institute on Aging (Grant Numbers U01AG009740, RC2AG036495, and RC4AG039029) and was conducted by the University of Michigan.

Conflict of Interest

T.E. Arpawong, J. Lee, D.F. Phillips, E.M. Crimmins, C.A. Prescott declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For this type of study, formal consent is not required.

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Authors and Affiliations

  1. Department of Psychology, University of Southern California, 3620 South McClintock Ave, SGM 501 MC 1061, Los Angeles, CA, 90089-1061, USA

    Thalida E. Arpawong & Carol A. Prescott

  2. Dornsife Center for Economic and Social Research, University of Southern California, Los Angeles, CA, USA

    Jinkook Lee & Drystan F. Phillips

  3. RAND Corporation, Santa Monica, CA, USA

    Jinkook Lee & Drystan F. Phillips

  4. Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA

    Eileen M. Crimmins & Carol A. Prescott

  5. Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA, USA

    Morgan E. Levine

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  1. Thalida E. Arpawong
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Correspondence to Thalida E. Arpawong.

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Arpawong, T.E., Lee, J., Phillips, D.F. et al. 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 (2016). https://doi.org/10.1007/s10519-015-9740-8

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  • DOI: https://doi.org/10.1007/s10519-015-9740-8

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