ArticleSchizophrenia bulletin2020
Promoter Activity-Based Case-Control Association Study on SLC6A4 Highlighting Hypermethylation and Altered Amygdala Volume in Male Patients With Schizophrenia.
Article in Schizophrenia bulletin, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 4 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
18 citing papers in PubMed, 4 syntheses or guidelines pooled it, 35 citations in OpenAlex.
- Japanese Cohort Study Identifies an Association Between the Serotonin Transporter-Linked Polymorphic Region and Suicide Death.Neuropsychopharmacology reports · 2026Pooled it
- Japanese Cohort Study and Meta-Analysis Demonstrate Significant Association Between Serotonin Transporter-Linked Polymorphic Region and Schizophrenia.Neuropsychopharmacology reports · 2026Pooled it
- Pooled it
- DNA methylation and histone modifications associated with antipsychotic treatment: a systematic review.Molecular psychiatry · 2025Pooled it
- Eight weeks of high-intensity interval training increases peripheral serotonin transporter expression independently of promoter methylation changes.European journal of applied physiology · 2026Article
- Molecular Mechanisms of Depression: The Interplay Between Genes and Receptors.International journal of molecular sciences · 2025Review
- Development of a method for the imputation of the multi-allelic serotonin-transporter-linked polymorphic region (5-HTTLPR) in the Japanese population.Journal of human genetics · 2025Article
- The Role of the 5-HTTLPR Gene Variation of the SLC6A4 Serotonergic System in the Development of Addictive Disorders: A Narrative Review.Consortium psychiatricum · 2025Review
- Epigenome Defines Aberrant Brain Laterality in Major Mental Illnesses.Brain sciences · 2024Review
- Methylation of serotonin regulating genes in cord blood cells: association with maternal metabolic parameters and correlation with methylation in peripheral blood cells during childhood and adolescence.Clinical epigenetics · 2024Article
- Prediction of treatment response to antipsychotic drugs for precision medicine approach to schizophrenia: randomized trials and multiomics analysis.Military Medical Research · 2023Article
- Methylation of the serotonin transporter gene moderates the depressive subjective effect of cocaine.Behavioural brain research · 2022Article
- Serotonin transporter functional polymorphisms potentially increase risk of schizophrenia separately and as a haplotype.Scientific reports · 2022Article
- Trends in big data analyses by multicenter collaborative translational research in psychiatry.Psychiatry and clinical neurosciences · 2022Review
- Surface area in the insula was associated with 28-month functional outcome in first-episode psychosis.NPJ schizophrenia · 2021Article
- Stress and the Role of the Gut-Brain Axis in the Pathogenesis of Schizophrenia: A Literature Review.International journal of molecular sciences · 2021Review
- Cataloging recent advances in epigenetic alterations in major mental disorders and autism.Epigenomics · 2021Article
- Identification and functional characterization of the extremely long allele of the serotonin transporter-linked polymorphic region.Translational psychiatry · 2021Article
Corrections and comments
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Authors and funding
28 authors at 12 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Associations between altered DNA methylation of the serotonin transporter (5-HTT)-encoding gene SLC6A4 and early life adversity, mood and anxiety disorders, and amygdala reactivity have been reported. However, few studies have examined epigenetic alterations of SLC6A4 in schizophrenia (SZ). We examined CpG sites of SLC6A4, whose DNA methylation levels have been reported to be altered in bipolar disorder, using 3 independent cohorts of patients with SZ and age-matched controls. We found significant hypermethylation of a CpG site in SLC6A4 in male patients with SZ in all 3 cohorts. We showed that chronic administration of risperidone did not affect the DNA methylation status at this CpG site using common marmosets, and that in vitro DNA methylation at this CpG site diminished the promoter activity of SLC6A4. We then genotyped the 5-HTT-linked polymorphic region (5-HTTLPR) and investigated the relationship among 5-HTTLPR, DNA methylation, and amygdala volume using brain imaging data. We found that patients harboring low-activity 5-HTTLPR alleles showed hypermethylation and they showed a negative correlation between DNA methylation levels and left amygdala volumes. These results suggest that hypermethylation of the CpG site in SLC6A4 is involved in the pathophysiology of SZ, especially in male patients harboring low-activity 5-HTTLPR alleles.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.