Healthy young women with serotonin transporter SS polymorphism show a pro-inflammatory bias under resting and stress conditions
Open accessAbstract
The study of functionally relevant biological effects of serotonin transporter gene promoter region (5-HTTLPR) polymorphisms is especially important given the current controversy about the clinical relevance of these polymorphisms. Here we report an intrinsic immunobiological difference between individuals carrying two short (SS) versus long (LL) 5-HTTLPR alleles, that is observed in healthy subjects reporting low exposure to life stress. Given that 5-HTTLPR polymorphisms are thought to influence susceptibility to depression and are associated with robust neurobiological effects, that depression is associated with higher pro-inflammatory and lower anti-inflammatory cytokines, and that acute stressors increase circulating concentrations of pro-inflammatory cytokines, we hypothesized that compared to LL individuals, SS individuals may show a pro-inflammatory bias under resting conditions and/or during stress. 15 LL and 11 SS individuals participated in the Trier Social Stress Test (TSST). Serum IL-6 and IL-10 were quantified at baseline and 30, 60, 90, and 120min after beginning the 20-min stress test. Compared to LL individuals, SS individuals showed a higher IL-6/IL-10 ratio at baseline and during stress. Importantly, this pro-inflammatory bias was observed despite both groups being healthy, reporting similar intensities of stress and negative emotionality during the TSST, and reporting similar low exposures to early and recent life stress. To our knowledge, this is the first report of a pro-inflammatory bias/phenotype in individuals carrying the SS genotype of 5-HTTLPR. Thus, healthy SS individuals may be chronically exposed to a pro-inflammatory physiological burden under resting and stress conditions, which could increase their vulnerability to disorders like depression and other diseases that can be facilitated/exacerbated by a chronic pro-inflammatory state.
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Genetic polymorphisms moderate associations between ELA and various outcomes.
“Genetic polymorphisms found to moderate associations between ELA and various outcomes”
From Biological embedding of childhood adversity: from physiological mechanisms to clinical implications (2017) · cites this paper as [88]
The Introduction (page unavailable) reports that the 5-HTTLPR polymorphism may modify depression risk after stressful life events and discusses studies assessing early and recent life stressors. It also mentions other outcomes after life stress. The paper does not establish the broader claim that genetic polymorphisms generally moderate associations between early-life adversity and various outcomes; it notes mixed replication results for the specific polymorphism discussed. (LLM, conf=0.82)
Experimental — accuracy not yet measuredWomen who carry two short alleles of the 5-HTTLPR present a higher IL-6/IL-10 ratio when dealing with stress.
“women who carry two short alleles of the 5-HTTLPR present a higher IL-6/IL-10 ratio when dealing with stress (198).”
From Epigenetic Modifications in Stress Response Genes Associated With Childhood Trauma (2019) · cites this paper as [198]
ELA effects are modified by genetics, child sex and/or gender, exposure features (e.g., timing, nature, and intensity), and the presence of other risks or protective factors.
“Some observed modifiers of ELA effects include genetics [25, 87–89], child sex and/or gender [19, 90, 91], exposure features (e.g., timing, nature, and intensity) [21, 25], and the presence of other risks or protective factors [36].”
From Biological embedding of childhood adversity: from physiological mechanisms to clinical implications (2017) · cites this paper as [88]
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- Authors
- Fredericks, C. A., Drabant, E. M., Edge, M. D., Tillie, J. M., Hallmayer, J., Ramel, W., Kuo, J. R., Mackey, S., Gross, J. J., & Dhabhar, F. S.
- Affiliations
- Stanford University (US)
- Stanford Medicine (US)
- Corresponding author
- Dhabhar, Firdaus S.
- ORCID
- Venue
- Brain, Behavior, and Immunity
- Publisher
- Elsevier BV
- Published
- 2010-03
- Volume
- 24
- Issue
- 3
- Pages
- 350-357
- ISSN
- 0889-1591 (ISSN-L)
- PMC
- PMC2826575
- OpenAlex
- W2167848374
- Cited by
- 74
- References
- 77
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 1 · 2023: 1 · 2022: 4 · 2021: 1 · 2020: 2 · 2019: 1 · 2018: 4 · 2017: 3 · 2016: 3 · 2015: 5 · 2014: 8 · 2013: 10 · 2012: 11
- FWCI
- 2.94
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Brain Behavior and Immunity (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (R01 # MH58147)
- Carl & Elizabeth Naumann Fund Startup
- NARSAD Young Investigator Award (34676)
- National Center for Research Resources (M01 RR-00070)
- National Institutes of Health
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- serotonin transporter gene, 5-HTTLPR polymorphism, SS genotype, interleukin-6, IL-10, IL-6/IL-10 ratio, acute psychological stress, Trier Social Stress Test, inflammation, depression vulnerability, healthy young women
- MeSH terms
- Adolescent, Affect, DNA, Female, Genotype, Humans, Inflammation, Polymorphism, Genetic, Rest, Stress, Psychological, Interleukin-6, Interleukin-10, Reverse Transcriptase Polymerase Chain Reaction, Serotonin Plasma Membrane Transport Proteins, Young Adult
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