Social Adversity, the Serotonin Transporter (5-HTTLPR) Polymorphism and Major Depressive Disorder
Abstract
Background Recent evidence has suggested that the short allele of the serotonin transporter (5-HTT) gene-linked polymorphic region (5-HTTLPR of the human serotonin gene [SLC6A4]) is associated with increased risk of depressive disorder but only among individuals exposed to social adversity. We report an investigation designed to replicate this finding. Methods Data were available from a non-clinical sample of 4,175 adult men and women, ages 41-80 years, selected from participants in the European Prospective Investigation into Cancer and Nutrition in Norfolk (EPIC-Norfolk, United Kingdom) study. Evidence of past-year prevalent episodic major depressive disorder (MDD), defined by restricted DSM-IV diagnostic criteria, was assessed through questionnaire. Adverse experiences in childhood and in adulthood (during the five years preceding assessment) were also assessed through self-report. The 5-HTTLPR variant was genotyped according to published protocols. Results One-year prevalent MDD criteria were met by 298 study participants. The experience of social adversity (both in childhood and adulthood) was strongly associated with increased rates of past-year prevalent MDD. No gene by environment (GxE) interactions between the 5-HTTLPR genotype, social adversity, and MDD were observed. Conclusions This study has not replicated a previous finding of a GxE interaction between the 5-HTTLPR genotype, social adversity, and depression.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
There is commonly a dose-response relationship between the number of types of adversity and the magnitude of risk for depression.
“Moreover, there is commonly a dose-response relationship between the number of types of adversity associated and the magnitude of the risk for depression.4-11”
From Early life adversity and the epigenetic programming of hypothalamic-pituitary-adrenal function (2014) · cites this paper as [7]
Cites
Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene
Caspi, A., Sugden, K., Moffitt, T. E., Taylor, A., Craig, I. W., Harrington, H., McClay, J., Mill, J., Martin, J., Braithwaite, A., et al. (2003) · Science · doi:10.1126/science.1083968 · Cited by 8,120 · see citing works
Brugha, T. S., & Cragg, D. (1990) · Acta Psychiatrica Scandinavica · doi:10.1111/j.1600-0447.1990.tb01360.x · Cited by 883 · see citing works
Kendler, K. S., Thornton, L. M., & Gardner, C. O. (2000) · American Journal of Psychiatry · doi:10.1176/appi.ajp.157.8.1243 · Cited by 721 · see citing works
Phenotype-genotype relationships in monogenic disease: lessons from the thalassaemias
Weatherall, D. J. (2001) · Nature Reviews Genetics · doi:10.1038/35066048 · Cited by 692 · see citing works
Childhood adversity, gender and depression over the life-course
Wainwright, N. W. J., & Surtees, P. G. (2002) · Journal of Affective Disorders · doi:10.1016/s0165-0327(01)00420-7 · Cited by 109 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Beyond diathesis stress: differential susceptibility to environmental influences
Belsky, J., & Pluess, M. (2009) · Psychological Bulletin · doi:10.1037/a0017376 · Cited by 3,039 · see citing works
Risch, N., Herrell, R., Lehner, T., Liang, K.-Y., Eaves, L., Hoh, J., Griem, A., Kovacs, M., Ott, J., & Merikangas, K. R. (2009) · JAMA · doi:10.1001/jama.2009.878 · Cited by 1,655 · see citing works
Gene–environment interactions in psychiatry: joining forces with neuroscience
Caspi, A., & Moffitt, T. E. (2006) · Nature Reviews Neuroscience · doi:10.1038/nrn1925 · Cited by 1,300 · see citing works
Epigenetics and the biological definition of gene×environment interactions
Meaney, M. J. (2010) · Child Development · doi:10.1111/j.1467-8624.2009.01381.x · Cited by 1,239 · see citing works
Long story short: the serotonin transporter in emotion regulation and social cognition
Canli, T., & Lesch, K.-P. (2007) · Nature Neuroscience · doi:10.1038/nn1964 · Cited by 1,034 · see citing works
Serotonin Transporter (5-HTTLPR) Genotype and Amygdala Activation: A Meta-Analysis
Munafò, M. R., Brown, S. M., & Hariri, A. R. (2008) · Biological Psychiatry · doi:10.1016/j.biopsych.2007.08.016 · Cited by 789 · see citing works
Gene×environment interactions at the serotonin transporter locus
Munafò, M. R., Durrant, C., Lewis, G., & Flint, J. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2008.06.009 · Cited by 576 · see citing works
Self-citationGatt, J. M., Nemeroff, C. B., Dobson-Stone, C., Paul, R. H., Bryant, R. A., Schofield, P. R., Gordon, E., Kemp, A. H., & Williams, L. M. (2009) · Molecular Psychiatry · doi:10.1038/mp.2008.143 · Cited by 525 · see citing works
Leucht, S., Arbter, D., Engel, R. R., Kissling, W., & Davis, J. M. (2009) · Molecular Psychiatry · doi:10.1038/sj.mp.4002136 · Cited by 489 · see citing works
Taylor, S. E., Way, B. M., Welch, W. T., Hilmert, C. J., Lehman, B. J., & Eisenberger, N. I. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.04.019 · Cited by 432 · see citing works
Sen, S., Kranzler, H. R., Krystal, J. H., Speller, H., Chan, G., Gelernter, J., & Guille, C. (2010) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2010.41 · Cited by 411 · see citing works
Philibert, R. A., Sandhu, H., Hollenbeck, N., Gunter, T., Adams, W., & Madan, A. (2008) · American Journal of Medical Genetics Part B: Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30657 · Cited by 300 · see citing works
Hosang, G. M., Shiles, C., Tansey, K. E., McGuffin, P., & Uher, R. (2014) · BMC Medicine · doi:10.1186/1741-7015-12-7 · Cited by 292 · see citing works
Kim, J.-M., Stewart, R., Kim, S.-W., Yang, S.-J., Shin, I.-S., Kim, Y.-H., & Yoon, J.-S. (2007) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.11.020 · Cited by 282 · see citing works
Gene–environment interactions: early life stress and risk for depressive and anxiety disorders
Nugent, N. R., Tyrka, A. R., Carpenter, L. L., & Price, L. H. (2011) · Psychopharmacology · doi:10.1007/s00213-010-2151-x · Cited by 269 · see citing works
“…Cicchetti et al. 2007; Eley et al. 2004; Gibb et al. 2009; Hammen et al. 2010; Kaufman et al. 2004, 2006; Laucht et al. 2009; Nobile et al. 2009; Ritchie et al. 2009; Sjoberg et al. 2006; Stein et al. 2008; Surtees et al. 2006; Taylor et al. 2006; Wichers et al. 2008; Xie et al. 2009) (Table 1).”
BackgroundMethodInfluentialXie, P., Kranzler, H. R., Poling, J., Stein, M. B., Anton, R. F., Brady, K., Weiss, R. D., Farrer, L., & Gelernter, J. (2009) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2009.153 · Cited by 264 · see citing works
Structural MRI correlates for vulnerability and resilience to major depressive disorder
Amico, F. (2011) · Journal of Psychiatry & Neuroscience · doi:10.1503/jpn.090186 · Cited by 256 · see citing works
Stein, M. B., Schork, N. J., & Gelernter, J. (2008) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301422 · Cited by 247 · see citing works
Early life adversity and the epigenetic programming of hypothalamic-pituitary-adrenal function
Anacker, C., O'Donnell, K. J., & Meaney, M. J. (2014) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2014.16.3/canacker · Cited by 237 · see citing works
Oldehinkel, A. J., & Bouma, E. M. C. (2011) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2010.10.013 · Cited by 225 · see citing works
Interaction between CRHR1 gene and stressful life events predicts adolescent heavy alcohol use
Blomeyer, D., Treutlein, J., Esser, G., Schmidt, M. H., Schumann, G., & Laucht, M. (2008) · Biological Psychiatry · doi:10.1016/j.biopsych.2007.04.026 · Cited by 211 · see citing works
McCormack, K., Newman, T. K., Higley, J. D., Maestripieri, D., & Sanchez, M. M. (2009) · Hormones and Behavior · doi:10.1016/j.yhbeh.2009.01.009 · Cited by 161 · see citing works
“Although a recent study failed to replicate these findings (Surtees et al., 2006), other groups have found similar gene by environment effects, such as Kaufman et al.”
ResultEpigenetic regulation of serotonin transporter expression and behavior in infant rhesus macaques
Kinnally, E. L., Capitanio, J. P., Leibel, R., Deng, L., LeDuc, C., Haghighi, F., & Mann, J. J. (2010) · Genes, Brain and Behavior · doi:10.1111/j.1601-183x.2010.00588.x · Cited by 155 · see citing works
Ressler, K. J., Bradley, B., Mercer, K. B., Deveau, T. C., Smith, A. K., Gillespie, C. F., Nemeroff, C. B., Cubells, J. F., & Binder, E. B. (2010) · American Journal of Medical Genetics Part B: Neuropsychiatric Genetics · doi:10.1002/ajmg.b.31052 · Cited by 140 · see citing works
Choi, S., Han, K.-M., Won, E., Yoon, B.-J., Lee, M.-S., & Ham, B.-J. (2015) · Journal of Affective Disorders · doi:10.1016/j.jad.2014.09.042 · Cited by 111 · see citing works
Karg, K., Burmeister, M., Shedden, K., & Sen, S. (2011) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2010.189 · Cited by 87 · see citing works
Kagan, J. (2007) · Perspectives on Psychological Science · doi:10.1111/j.1745-6916.2007.00049.x · Cited by 84 · see citing works
Chipman, P., Jorm, A. F., Prior, M., Sanson, A., Smart, D., Tan, X., & Easteal, S. (2007) · American Journal of Medical Genetics Part B: Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30480 · Cited by 81 · see citing works
Brody, G. H., Beach, S. R. H., Chen, Y.-F., Obasi, E., Philibert, R. A., Kogan, S. M., & Simons, R. L. (2011) · Development and Psychopathology · doi:10.1017/s0954579411000046 · Cited by 56 · see citing works
Depressão e estresse: existe um endofenótipo?
Mello, A. F., Juruena, M. F., Pariante, C. M., Tyrka, A. R., Price, L. H., Carpenter, L. L., & Del Porto, J. A. (2007) · Revista Brasileira de Psiquiatria · doi:10.1590/s1516-44462007000500004 · Cited by 56 · see citing works
Wankerl, M., Wüst, S., & Otte, C. (2010) · Current Opinion in Psychiatry · doi:10.1097/yco.0b013e32833f0e3a · Cited by 49 · see citing works
Childhood maltreatment and stress-related psychopathology: the epigenetic memory hypothesis
Lutz, P.-E., Almeida, D., Fiori, L., & Turecki, G. (2015) · Current Pharmaceutical Design · doi:10.2174/1381612821666150105124928 · Cited by 44 · see citing works
Cognitive Control as a 5-HT1A-Based Domain That Is Disrupted in Major Depressive Disorder
Langenecker, S. A., Mickey, B. J., Eichhammer, P., Sen, S., Elverman, K. H., Kennedy, S. E., Heitzeg, M. M., Ribeiro, S. M., Love, T. M., Hsu, D. T., et al. (2019) · Frontiers in Psychology · doi:10.3389/fpsyg.2019.00691 · Cited by 18 · see citing works
- Authors
- Surtees, P. G., Wainwright, N. W. J., Willis-Owen, S. A. G., Luben, R., Day, N. E., & Flint, J.
- Affiliations
- University of Cambridge (GB)
- Corresponding author
- Surtees, Paul G.
- ORCID
- Luben, Robert
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2006-02
- Volume
- 59
- Issue
- 3
- Pages
- 224-229
- ISSN
- 0006-3223 (ISSN-L)
- OpenAlex
- W2002996606
- Cited by
- 265
- References
- 5
- Citations by year
- 2026: 2 · 2024: 2 · 2023: 1 · 2022: 5 · 2020: 2 · 2019: 3 · 2018: 3 · 2017: 13 · 2016: 7 · 2015: 8 · 2014: 9 · 2013: 12 · 2012: 16
- FWCI
- 10.16
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Cancer Research UK (C865/A2883)
- Stroke Association
- Wellcome Trust
- European Commission
- British Heart Foundation
- Food Standards Agency
- Medical Research Council (G9502233, G0300128)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- serotonin transporter gene, 5-HTTLPR polymorphism, major depressive disorder, social adversity, gene-environment interaction, childhood adversity, genetic susceptibility to depression, replication
- MeSH terms
- Adult, Aged, Depressive Disorder, Major, Major Depressive Disorder, England, Europe, Female, Genotype, Humans, Life Change Events, Male, Middle Aged, Polymorphism, Genetic, Social Environment, Genetic Variation, Risk Assessment, Genetic Predisposition to Disease, Serotonin Plasma Membrane Transport Proteins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
