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


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.


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



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.

Supplementary material

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


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© 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

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