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
Open accessAbstract
Background There is ongoing interest in the possible interaction of the serotonin-transporter-linked polymorphic region (5-HTTLPR) with environmental factors in determining Major Depressive Disorder (MDD). The current study contributes to this research area by comprehensively examining the interaction-effects and direct-effects of 5-HTTLPR and five environmental factors on MDD prevalence and course in a well-characterized longitudinal sample.Methods The sample consisted of 1625 patients with a CIDI-confirmed diagnosis of MDD and 1698 screened controls from the Netherlands. Four MDD outcomes were studied as dependent variables: one main MDD prevalence-outcome (all MDD), two more severe MDD prevalence-outcomes (suicidal and chronic MDD), and one MDD course outcome (chronic versus non-chronic MDD). Because SNP rs25531 modifies the effect of 5-HTTLPR, haplotypes of 5-HTTLPR and rs25531 were measured. For the four MDD outcome measures, we examined the direct effects of 5-HTTLPR/rs25531-haplotypes, five environmental factors (lifetime and recent stressful life-events, sexual abuse, low educational attainment, and childhood trauma) and their interaction in logistic regression models.Results The environmental factors had large and consistent effects on all four MDD outcomes, including course of MDD. The 5-HTTLPR/rs25531-haplotype had a suggestive effect on course of MDD, but not on presence of MDD. Gene-by-environment interaction was significant (<0.05) for one of the 20 tests performed, which is not more than expected by chance.Limitations Environmental factors were not assessed before the onset of MDD.Conclusions Environmental factors had a strong impact on the presence and course of MDD, but no evidence for gene-by-environment interaction was found.
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From Childhood maltreatment and characteristics of adult depression: Meta-analysis (2017) · cites this paper as [23]
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References 43 · Cited by 31
- Authors
- Peyrot, W. J., Middeldorp, C. M., Jansen, R., Smit, J. H., de Geus, E. J. C., Hottenga, J.-J., Willemsen, G., Vink, J. M., Virding, S., Barragan, I., Ingelman-Sundberg, M., Sim, S. C., Boomsma, D. I., & Penninx, B. W. J. H.
- Affiliations
- Amsterdam Neuroscience (NL)
- Amsterdam UMC Location University of Amsterdam (NL)
- Vrije Universiteit Amsterdam (NL)
- Karolinska Institutet (SE)
- University Medical Center Groningen (NL)
- Corresponding author
- Peyrot, Wouter J.
- ORCID
- Venue
- Journal of Affective Disorders
- Publisher
- Elsevier BV
- Published
- 2013-03
- Volume
- 146
- Issue
- 1
- Pages
- 91-99
- ISSN
- 0165-0327 (ISSN-L)
- OpenAlex
- W1965957925
- Cited by
- 31
- References
- 43
- Citations by year
- 2024: 2 · 2023: 1 · 2022: 1 · 2021: 2 · 2020: 3 · 2019: 4 · 2017: 3 · 2016: 6 · 2015: 2 · 2014: 4 · 2013: 2
- FWCI
- 1.05
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Affective Disorders (publishedVersion)
- PubMed (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- VU Research Portal (publishedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Leiden Repository (Leiden University) (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Funders
- European Science Foundation (2001-01254, EU/QLRT-2001-01254, HEALTH-F4-2007-201413)
- ZonMw (985-10-002, 400‐05‐717, 56-464-14192, 904-61-193, 904-61-090, 480‐04‐004, 10‐000‐1002)
- Vrije Universiteit Amsterdam (FP7/2007-2013, 2008.024)
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (10-000-1002, 400‐05‐717, 904-61-193, 904-61-090, FP7 2007-2013, 912-100-20, 56‐464‐14192, 230374, Spinozapremie 56-464-14192, 985-10002, 14192, 480-04-004)
- Vetenskapsrådet (FP7/2007-2013)
- Norwegian Biodiversity Information Centre
- European Social Fund (2007–2013, FP7/2007-2013)
- 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
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- major depressive disorder, 5-HTTLPR, serotonin transporter gene, gene-environment interaction, rs25531, haplotypes, environmental risk factors, life events, childhood trauma, sexual abuse, educational attainment, chronic depression, suicidal depression, course of depression, depression prevalence
- MeSH terms
- Adult, Major Depressive Disorder, Educational Status, Female, Haplotypes, Humans, Life Change Events, Longitudinal Studies, Male, Middle Aged, Netherlands, Risk Factors, Sex Offenses, Prevalence, Case-Control Studies, Polymorphism, Single Nucleotide, Serotonin Plasma Membrane Transport Proteins, Adult Survivors of Child Abuse, Gene-Environment Interaction
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