Current developments and controversies: does the serotonin transporter gene-linked polymorphic region (5-httlpr) modulate the association between stress and depression?
Abstract
PURPOSE OF REVIEW: Human observational studies have shown that, in interaction with life stress, the short or S-allele of the serotonin transporter gene-linked polymorphic region (5-HTTLPR) is associated with an enhanced risk for depression. However, this gene-by-environment interaction (G×E) has recently been questioned by two meta-analyses. We aim to provide an overview and appraisal of recent developments and controversies. RECENT FINDINGS: The statistical approach of the meta-analyses aimed at a very strict replication of the initial finding and, accordingly, included only a minority of all available studies. Furthermore, the negative results of the meta-analyses appear to be predominantly driven by a few large studies that used retrospective, self-report measures of life stress. In contrast, among 19 studies using interview-based or more objective measures of stress, there were 13 replications, five part-replications and only one nonreplication. Finally, a broader approach based on evidence from different research fields and methodologies supports a 5-HTTLPR by stress interaction. SUMMARY: Whereas there is no doubt that the meta-analyses are methodologically sound, it appears that this technique is only in part suitable for appraising all of the available evidence. Furthermore, convergent evidence is accumulating from different research fields that 5-HTTLPR is indeed closely associated with different biological pathways associated with stress regulation and depression.
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A genetic polymorphism that downregulates the serotonin reuptake transporter predisposes towards depression and other related mood disorders.
“On the other hand, a genetic polymorphism that downregulates the very same serotonin reuptake transporter, thus acting in the same direction as the drugs, has the opposite effect on mood, predisposing towards depression and other related mood disorders ([30]; though see also [31] for a discussion of replication failures).”
From Bonsai trees in your head: how the pavlovian system sculpts goal-directed choices by pruning decision trees (2012) · cites this paper as [31]
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- Authors
- Wankerl, M., Wüst, S., & Otte, C.
- Affiliations
- Maastricht University (NL)
- Central Institute of Mental Health (DE)
- University Medical Center Hamburg-Eppendorf (DE)
- Corresponding author
- Otte, Christian
- Venue
- Current Opinion in Psychiatry
- Published
- 2010-11
- Volume
- 23
- Issue
- 6
- Pages
- 582-587
- ISSN
- 0951-7367 (ISSN-L)
- OpenAlex
- W2065220020
- Cited by
- 49
- References
- 59
- Citations by year
- 2025: 2 · 2023: 2 · 2022: 3 · 2019: 1 · 2018: 1 · 2016: 3 · 2015: 5 · 2014: 5 · 2013: 5 · 2012: 11
- FWCI
- 0.78
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Current Opinion in Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- 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
- 5-HTTLPR, serotonin transporter gene, gene-environment interaction, life events, depression risk, S-alleles, stress measurement methods, stress regulation, genetic susceptibility to depression
- MeSH terms
- Depressive Disorder, Humans, Polymorphism, Genetic, Stress, Psychological, Meta-Analysis as Topic, Genetic Predisposition to Disease, Serotonin Plasma Membrane Transport Proteins
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