ArticleBiology of mood & anxiety disorders2015
Influence of life stress, 5-HTTLPR genotype, and SLC6A4 methylation on gene expression and stress response in healthy Caucasian males.
Article in Biology of mood & anxiety disorders, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 3 of them syntheses that pooled it.
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Who cites it
53 citing papers in PubMed, 3 syntheses or guidelines pooled it, 130 citations in OpenAlex.
- Exploring the association between serotonin transporter promoter region methylation levels and depressive symptoms: a systematic review and multi-level meta-analysis.Translational psychiatry · 2025Pooled it
- Adverse Childhood Events and Health Biomarkers: A Systematic Review.Frontiers in public health · 2021Pooled it
- Physiological responses to acute psychological stress as a biomarker for depression: A systematic review and meta-analysis.Psychological bulletinPooled it
- Eight weeks of high-intensity interval training increases peripheral serotonin transporter expression independently of promoter methylation changes.European journal of applied physiology · 2026Article
- Adrenarche as a regulator of sensitivity to early adversity.Journal of neuroendocrinology · 2026Review
- Epigenetics, Resilience, Protective Factors and Factors Promoting Positive Outcomes: A Scoping Review.International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience · 2025Article
- Changes in DNA Methylation Associated With Psychobehavioral Interventions: A Scoping Literature Review.Biological research for nursing · 2025Article
- Serotonin transporter gene methylation and cortisol reactivity to acute stress: modeling the pathogenetic and therapeutic effects of stress-related disorders?Journal of neural transmission (Vienna, Austria : 1996) · 2025Article
- Clinical characteristics of obsessive-compulsive disorder comorbid with obsessive -compulsive personality disorder: subtype implications.Frontiers in psychiatry · 2025Article
- Associations Between Loneliness, Epigenetic Aging, and Multimorbidity Through Older Adulthood.The journals of gerontology. Series B, Psychological sciences and social sciences · 2024Article
- Serotonin Transporter (SLC6A4) and FK506-Binding Protein 5 (FKBP5) Genotype and Methylation Relationships with Response to Meditation in Veterans with PTSD.Molecular neurobiology · 2024Article
- Socioeconomic Status, Knee Pain, and Epigenetic Aging in Community-Dwelling Middle-to-Older Age Adults.The journal of pain · 2024Article
- Biomarker-Guided Tailored Therapy in Major Depression.Advances in experimental medicine and biology · 2024Review
- A Bibliometric and Visual Analysis of Single Nucleotide Polymorphism Studies in Depression.Current neuropharmacology · 2024Article
- Mental health and the effects on methylation of stress-related genes in front-line versus other health care professionals during the second wave of COVID-19 pandemic: an Italian pilot study.European archives of psychiatry and clinical neuroscience · 2023Article
- Increased academic stress is associated with decreased plasma BDNF in Chilean college students.PeerJ · 2023Article
- Novel Antidepressant-Like Properties of the Iron Chelator Deferiprone in a Mouse Model of Depression.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2022Article
- Correlation between intestinal microbiotal imbalance and 5-HT metabolism, immune inflammation in chronic unpredictable mild stress male rats.Genes, brain, and behavior · 2022Article
- Evaluating the challenges and reproducibility of studies investigating DNA methylation signatures of psychological stress.Epigenomics · 2022Review
- No long-term effects of antenatal synthetic glucocorticoid exposure on epigenetic regulation of stress-related genes.Translational psychiatry · 2022Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPrevious research reported that individual differences in the stress response were moderated by an interaction between individuals' life stress experience and the serotonin transporter-linked polymorphic region (5-HTTLPR), a common polymorphism located in the promoter region of the serotonin transporter gene (SLC6A4). Furthermore, this work suggested that individual differences in SLC6A4 DNA methylation could be one underlying mechanism by which stressful life events might regulate gene expression. The aim of this study was to understand the relation between early and recent life stress experiences, 5-HTTLPR genotype, and SLC6A4 methylation. In addition, we aimed to address how these factors influence gene expression and cortisol response to an acute psychosocial stressor, operationalized as the Trier Social Stress Test (TSST). In a sample of 105 Caucasian males, we collected early and recent life stress measures and blood samples to determine 5-HTTLPR genotype and SLC6A4 methylation. Furthermore, 71 of these participants provided blood and saliva samples before and after the TSST to measure changes in SLC6A4 and NR3C1 gene expression and cortisol response.
resultsCompared to S-group individuals, LL individuals responded with increased SLC6A4 mRNA levels to the TSST (t(66) = 3.71, P < .001) and also showed increased global methylation as a function of ELS (r (32) = .45, P = .008) and chronic stress (r (32) = .44, P = .010). Compared to LL individuals, S-group individuals showed reduced SLC6A4 mRNA levels (r (41) = -.31, P = .042) and increased F3 methylation (r (67) = .30, P = .015) as a function of ELS; as well as increased F1 methylation as a function of chronic stress and recent depressive symptoms (r = .41, P < .01), which correlated positively with NR3C1 expression (r (42) = .31, P = .040).
conclusionsBoth early and recent life stress alter DNA methylation as a function of 5-HTTLPR genotype. Some of these changes are also reflected in gene expression and cortisol response, differentially affecting individuals' stress response in a manner that may confer susceptibility or resilience for psychopathology upon experiencing stressful life events.
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