The moderation by the serotonin transporter gene of environmental adversity in the etiology of depression: 2009 update

Uher, R; McGuffin, P

doi:10.1038/mp.2009.123

Cited by 424Neurotransmitter Receptor Influence on BehaviorGenetic Associations and EpidemiologyStress Responses and Cortisol

The moderation by the serotonin transporter gene of environmental adversity in the etiology of depression: 2009 update

Uher, R, McGuffin, P·2010·Molecular Psychiatry

DOI 10.1038/mp.2009.123

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Abstract

An updated review of 34 human observational studies indicates that the length polymorphism of the serotonin transporter gene moderates the effect of environmental adversity in the development of depression. This finding depends on the use of contextual or objective methods to assess environmental adversity and is attenuated when self-report instruments are used. Inconsistent findings in male adolescents suggest a developmental stage and sex-specific protective mechanism. These systematic relationships between method and results should be followed up to specify causal mechanisms leading to depression.

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Individuals with one or two copies of the short allele at 5-HTTLPR are at greater risk for MDD than their long-allele homozygous counterparts.
“individuals with one or two copies of the short allele at 5-HTTLPR are at greater risk for MDD than their long-allele homozygous counterparts”
From From stress to inflammation and major depressive disorder: A social signal transduction theory of depression. (2014) · cites this paper as Uher & McGuffin, 2010
Candidate gene studies need adequate numbers of subjects exposed and unexposed to the stressful environment to ensure adequate power.
“It is important that the study sample contains adequate numbers of subjects exposed and unexposed to the stressful environment to ensure adequate power”
From Gene–environment interactions: early life stress and risk for depressive and anxiety disorders (2011) · cites this paper as Uher and McGuffin 2010
Uher and McGuffin (2010) found that the 14 studies included in the Risch report showed a statistically significant bias toward negative findings.
“In a subsequent systematic review, the 14 studies (out of 34 possible studies) included in the Risch report were found to show a statistically significant bias toward negative findings (Uher and McGuffin 2010).”
From Gene–environment interactions: early life stress and risk for depressive and anxiety disorders (2011) · cites this paper as Uher and McGuffin 2010
Meta-analyses have not supported the MDD serotonin transporter gene-environment interaction finding.
“Meta-analyses have supported 111,112 and not supported 113,114 this finding.”
From Genetic architectures of psychiatric disorders: the emerging picture and its implications (2012) · cites this paper as [113]

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PERSPECTIVE
Uher, R., & Mcguffin, P. (2016)
Self-citation
The moderation by the serotonin transporter gene of environmental adversity in the aetiology of mental illness: review and methodological analysis
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Early Family Environment, Current Adversity, the Serotonin Transporter Promoter Polymorphism, and Depressive Symptomatology
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P.4.024 Serotonin transporter gene polymorphism as a possible modifying factor of individual response to stress
Алфимова, М. В., Коровайцева, Г. И., Abramova, L. I., Каледа, В. Г., & Голимбет, В. Е. (2005) · European Neuropsychopharmacology · doi:10.1016/s0924-977x(05)80377-3
G × E interaction and neurodevelopment II. Focus on adversities in paediatric depression: the moderating role of serotonin transporter
Bellani, M., Nobile, M., Bianchi, V., van Os, J., & Brambilla, P. (2012) · Epidemiology and Psychiatric Sciences · doi:10.1017/s2045796012000625 · Cited by 6 · see citing works

Authors: Uher, R., & McGuffin, P.
Affiliations: King's College London (GB)
Corresponding author: Uher, R
ORCID: Uher, R
Venue: Molecular Psychiatry
Publisher: Springer Science and Business Media LLC
Published: 2009-12-22
Volume: 15
Issue: 1
Pages: 18-22
ISSN: 1359-4184 (ISSN-L)
1476-5578
DOI: 10.1038/mp.2009.123
OpenAlex: W1989784453
Cited by: 424
References: 26
Citations by year: 2025: 2 · 2024: 5 · 2023: 5 · 2022: 6 · 2021: 7 · 2020: 31 · 2019: 21 · 2018: 9 · 2017: 25 · 2016: 26 · 2015: 33 · 2014: 40 · 2013: 53 · 2012: 49
FWCI: 22.11
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Molecular Psychiatry (publishedVersion)
PubMed (publishedVersion)
Research Portal (King's College London) (submittedVersion)
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, serotonin transporter, environmental adversity, etiology of depression, gene-environment interaction, length polymorphism, self-report measures, contextual assessment, adolescent boys, sex differences, developmental stages, protective mechanisms
MeSH terms: Depression, Environment, Humans, Polymorphism, Genetic, Meta-Analysis as Topic, Serotonin Plasma Membrane Transport Proteins

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The moderation by the serotonin transporter gene of environmental adversity in the etiology of depression: 2009 update

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