ArticlePloS one2012
Peripheral SLC6A4 DNA methylation is associated with in vivo measures of human brain serotonin synthesis and childhood physical aggression.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers.
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Who cites it
89 citing papers in PubMed, 210 citations in OpenAlex.
- Trial
- Epigenetics of generalized internet use disorder including data on overuse of social media: a closer look at the SLC6A4, NR3C1 and OXT genes.BMC psychiatry · 2026Article
- Epigenetic Regulation of Modulatory Neurotransmitter System Integrity in the Aging Brain: A Scoping Review Across the Lifespan.Life (Basel, Switzerland) · 2026Review
- Understanding attenuated positive facial expression in depressed women: central role of dorsal raphe network alterations and associated serotonin transporter methylation.Scientific reports · 2026Article
- Correlation of non-suicidal self-injury with SLC6A4 promoter DNA methylation in children and adolescents with bipolar depression.Frontiers in psychiatry · 2026Article
- Updated Freudian drive theory: childhood trauma, epigenetics, serotonin and beta endorphin.Frontiers in psychiatry · 2026Article
- Prematurity and Epigenetic Regulation ofBiomedicines · 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
- A Comprehensive Review of the Role of the Microbiota-Gut-Brain Axis via Neuroinflammation: Advances and Therapeutic Implications for Ischemic Stroke.Biomolecules · 2025Review
- Phytochemicals Modulate Biosynthesis and Function of Serotonin, Dopamine, and Norepinephrine for Treatment of Monoamine Neurotransmission-Related Psychiatric Diseases.International journal of molecular sciences · 2025Review
- No association between peripheral serotonin-gene-related DNA methylation and brain serotonin neurotransmission in the healthy and depressed state.Clinical epigenetics · 2024Article
- 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
- Mild internet use is associated with epigenetic alterations of key neurotransmission genes in salivary DNA of young university students.Scientific reports · 2023Article
- Endocannabinoid signaling and epigenetics modifications in the neurobiology of stress-related disorders.Neuronal signaling · 2023Review
- Epigenetic modifications and obsessive-compulsive disorder: what do we know?Brain structure & function · 2023Review
- Prevalence of Common Alleles of Some Stress Resilience Genes among Adolescents Born in Different Periods Relative to the Socioeconomic Crisis of the 1990s in Russia.Current issues in molecular biology · 2022Article
- Methylation of the serotonin reuptake transporter gene and non-motor symptoms in dystonia patients.Clinical epigenetics · 2022Article
- Chimpanzee Extraversion scores vary with epigenetic modification of dopamine receptor gene D2 (Epigenetics · 2022Article
- Current understanding of the genetics of tourette syndrome.Biomedical journal · 2022Review
- Prenatal maternal stress and offspring aggressive behavior: Intergenerational and transgenerational inheritance.Frontiers in behavioral neuroscience · 2022Review
29 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
The main challenge in addressing the role of DNA methylation in human behaviour is the fact that the brain is inaccessible to epigenetic analysis in living humans. Using positron emission tomography (PET) measures of brain serotonin (5-HT) synthesis, we found in a longitudinal sample that adult males with high childhood-limited aggression (C-LHPA) had lower in vivo 5-HT synthesis in the orbitofrontal cortex (OBFC). Here we hypothesized that 5-HT alterations associated with childhood aggression were linked to differential DNA methylation of critical genes in the 5-HT pathway and these changes were also detectable in peripheral white blood cells. Using pyrosequencing, we determined the state of DNA methylation of SLC6A4 promoter in T cells and monocytes isolated from blood of cohort members (N = 25) who underwent a PET scan, and we examined whether methylation status in the blood is associated with in vivo brain 5-HT synthesis. Higher levels of methylation were observed in both T cells and monocytes at specific CpG sites in the C-LHPA group. DNA methylation of SLC6A4 in monocytes appears to be associated more reliably with group membership than T cells. In both cell types the methylation state of these CpGs was associated with lower in vivo measures of brain 5-HT synthesis in the left and right lateral OBFC (N = 20) where lower 5-HT synthesis in C-LHPA group was observed. Furthermore, in vitro methylation of the SLC6A4 promoter in a luciferase reporter construct suppresses its transcriptional activity supporting a functional role of DNA methylation in SLC6A4 promoter regulation. These findings indicate that state of SLC6A4 promoter methylation is altered in peripheral white blood cells of individuals with physical aggression during childhood. This supports the relevance of peripheral DNA methylation for brain function and suggests that peripheral SLC6A4 DNA methylation could be a marker of central 5-HT function.
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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.