ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2018
Association of Serotonin Transporter Gene AluJb Methylation with Major Depression, Amygdala Responsiveness, 5-HTTLPR/rs25531 Polymorphism, and Stress.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 4 of them syntheses that pooled it.
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Who cites it
32 citing papers in PubMed, 4 syntheses or guidelines pooled it, 88 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
- Pooled it
- DNA methylation and brain structure and function across the life course: A systematic review.Neuroscience and biobehavioral reviews · 2020Pooled it
- DNA Methylation as a Biomarker of Treatment Response Variability in Serious Mental Illnesses: A Systematic Review Focused on Bipolar Disorder, Schizophrenia, and Major Depressive Disorder.International journal of molecular sciences · 2018Pooled it
- Transcutaneous auricular vagus nerve stimulation for major depressive disorder: current evidence and future research directions.Frontiers in psychiatry · 2026Review
- Epigenetic regulation in major depression and other stress-related disorders: molecular mechanisms, clinical relevance and therapeutic potential.Signal transduction and targeted therapy · 2023Review
- Epigenetic Gene-Regulatory Loci in Alu Elements Associated with Autism Susceptibility in the Prefrontal Cortex of ASD.International journal of molecular sciences · 2023Article
- Maternal Epigenetic Dysregulation as a Possible Risk Factor for Neurodevelopmental Disorders.Genes · 2023Article
- Article
- Quadrato Motor Training (QMT) is associated with DNA methylation changes at DNA repeats: A pilot study.PloS one · 2023Article
- Neuroinflammation and neuroprogression in depression: Effects of alternative drug treatments.Brain, behavior, & immunity - health · 2022Review
- The Role of Serotonergic Gene Methylation in Regulating Anxiety-Related Personality Traits in Chimpanzees.Biology · 2022Article
- Serotonin transporter in the temporal lobe, hippocampus and amygdala in SUDEP.Brain pathology (Zurich, Switzerland) · 2022Article
- Transposable Elements and Human Diseases: Mechanisms and Implication in the Response to Environmental Pollutants.International journal of molecular sciences · 2022Review
- Exploring the Structural and Functional Effects of Nonsynonymous SNPs in the Human Serotonin Transporter Gene ThroughBioinformatics and biology insights · 2022Article
- Epigenetic biotypes of post-traumatic stress disorder in war-zone exposed veteran and active duty males.Molecular psychiatry · 2021Article
- Modulation of Instagram Number of Followings by Avoidance in Close Relationships in Young Adults under a Gene x Environment Perspective.International journal of environmental research and public health · 2021Article
- Losing DNA methylation at repetitive elements and breaking bad.Epigenetics & chromatin · 2021Review
- Glucocorticoid Signaling and Epigenetic Alterations in Stress-Related Disorders.International journal of molecular sciences · 2021Review
- Clinical and Translational Considerations for Understanding Depression and Anxiety in Patients with Inflammatory Bowel Disease.Gastroenterology research and practice · 2021Review
Corrections and comments
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Authors and funding
23 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
DNA methylation profiles of the serotonin transporter gene (SLC6A4) have been shown to alter SLC6A4 expression, drive antidepressant treatment response and modify brain functions. This study investigated whether methylation of an AluJb element in the SLC6A4 promotor was associated with major depressive disorder (MDD), amygdala reactivity to emotional faces, 5-HTTLPR/rs25531 polymorphism, and recent stress. MDD patients (n=122) and healthy controls (HC, n=176) underwent fMRI during an emotional face-matching task. Individual SLC6A4 AluJb methylation profiles were ascertained and associated with MDD, amygdala reactivity, 5-HTTLPR/rs25531, and stress. SLC6A4 AluJb methylation was significantly lower in MDD compared to HC and in stressed compared to less stressed participants. Lower AluJb methylation was particularly found in 5-HTTLPR/rs25531 risk allele carriers under stress and correlated with less depressive episodes. fMRI analysis revealed a significant interaction of AluJb methylation and diagnosis in the amygdala, with MDD patients showing lower AluJb methylation associated with decreased amygdala reactivity. While no joint effect of AluJb methylation and 5-HTTLPR/rs25531 existed, risk allele carriers showed significantly increased bilateral amygdala activation. These findings suggest a role of SLC6A4 AluJb methylation in MDD, amygdala reactivity, and stress reaction, partly interwoven with 5-HTTLPR/rs25531 effects. Patients with low methylation in conjunction with a shorter MDD history and decreased amygdala reactivity might feature a more stress-adaptive epigenetic process, maybe via theoretically possible endogenous antidepressant-like effects. In contrast, patients with higher methylation might possibly suffer from impaired epigenetic adaption to chronic stress. Further, the 5-HTTLPR/rs25531 association with amygdala activation was confirmed in our large sample.
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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.