Altered DNA Methylation of the Serotonin Transporter Gene Associated with Early Life Stress and White Matter Microalterations in Korean Patients with Panic Disorder
Abstract
INTRODUCTION: Changes in the DNA methylation of 5-HTTLPR are associated with the pathophysiology of panic disorder (PD). This study was conducted to investigate the association between stressful life events and the level of 5-HTTLPR methylation in patients with PD. We also examined whether these factors were associated with white matter alterations in psychological trauma-related regions. METHODS: The participants comprised 232 patients with PD and 93 healthy adults of Korean descent. DNA methylation levels of five cytosine-phosphate-guanine (CpG) sites in the 5-HTTLPR region were analyzed. Voxel-wise statistical analysis of diffusion tensor imaging data was performed within the trauma-related regions. RESULTS: PD patients showed significantly lower levels of the DNA methylation at 5-HTTLPR 5 CpG sites than healthy controls. In patients with PD, the DNA methylation levels at 5-HTTLPR 5 CpG sites showed significant negative association with the parental separation-related psychological distress, and positive correlations with the fractional anisotropy values of the superior longitudinal fasciculus (SLF) which might be related to trait anxiety. CONCLUSION: Early life stress was significantly associated with DNA methylation levels at 5-HTTLPR related to the decreased white matter integrity in the SLF region in PD. Decreased white matter connectivity in the SLF might be related to trait anxiety and is vital to the pathophysiology of PD.
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Early life stress has been significantly associated with DNA methylation levels at the 5-HTTLPR site, correlating with decreased white matter integrity in individuals with panic disorder.
“In humans, early life stress has been significantly associated with DNA methylation levels at the 5-HTTLPR site, correlating with decreased white matter integrity in individuals with panic disorder.”
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Chronic social defeat (CSD) in mice reveals that while cis-regulatory mechanisms predominantly control gene expression in the prefrontal cortex and amygdala, trans-regulatory mechanisms become more prominent in the amygdala under stress.
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From Comprehensive review of chronic stress pathways and the efficacy of behavioral stress reduction programs (BSRPs) in managing diseases. (2024) · cites this paper as [47]
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- Authors
- Kim, H.-J., Bang, M., Park, C. I., & Lee, S.-H.
- Affiliations
- CHA University Bundang Medical Center (KR)
- Venue
- Neuropsychobiology
- Publisher
- S. Karger AG
- Published
- 2023
- Volume
- 82
- Issue
- 4
- Pages
- 210-219
- ISSN
- 0302-282X (ISSN-L)
- 1423-0224
- OpenAlex
- W4378349614
- Cited by
- 2
- References
- 54
- Citations by year
- 2024: 1 · 2023: 1
- FWCI
- 0.18
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuropsychobiology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Keywords
- panic disorder, DNA methylation, 5-HTTLPR, serotonin transporter gene, early life stress, white matter microstructure, superior longitudinal fasciculus, fractional anisotropy, parental separation, psychological trauma, trait anxiety, epigenetics, Korean patients
- MeSH terms
- Adverse Childhood Experiences, Adult, Humans, Panic Disorder, DNA Methylation, Serotonin Plasma Membrane Transport Proteins, Diffusion Tensor Imaging, Republic of Korea, White Matter
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