The DNA methylome in panic disorder: A case-control and longitudinal psychotherapy-epigenetic study
Open accessAbstract
In panic disorder (PD), epigenetic mechanisms such as DNA methylation of candidate genes have been suggested to play a key role at the intersection of genetic and environmental factors. On an epigenome-wide level, however, only two studies in PD patients have been published so far, while to date no study has intra-individually analyzed dynamic epigenetic correlates of treatment-response in PD on a DNA methylome level. Here, an epigenome-wide association study (EWAS) was performed in a sample of 57 PD patients and matched healthy controls using the Illumina MethylationEPIC BeadChip, along with a longitudinal approach assessing changes on the DNA methylome level corresponding to clinical effects of a manualized six-week cognitive-behavioral therapy (CBT) in PD. While no epigenome-wide significant hits could be discerned, top suggestive evidence was observed for decreased methylation in PD at cg19917903 in the Cilia and Flagella Associated Protein 46 (CFAP46) gene, and for an increase in methylation after CBT at cg06943668 in the Interleukin 1 Receptor Type 1 (IL1R1) gene in treatment responders to CBT. Additional exploratory analyses based on biological validity and a combined statistical/biological ranking point to further new potential PD risk genes such as the CCL4L1 or GMNN genes, and suggest dynamic methylation of, e.g., the ZFP622 and the SLC43A2 genes along with response to CBT. These EWAS and first longitudinal epigenome-wide pilot data in PD add to the emerging candidate gene-based body of evidence for epigenetic mechanisms to be involved in PD pathogenesis and to possibly constitute dynamic biological correlates of therapeutic interventions.
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IL1R1 methylation is increased post-CBT.
“↑ IL1R1 methylation post-CBT”
From The applied implications of epigenetics in anxiety, affective and stress-related disorders - A review and synthesis on psychosocial stress, psychotherapy and prevention (2020) · cites this paper as Ziegler et al., 2019
The Results (Treatment-response analysis) report a suggestive increase in methylation at an IL1R1 CpG site after CBT in patients who responded to treatment, but not in non-responders. The claim omits that restriction and the paper's qualification that the finding did not reach epigenome-wide significance (Discussion, Longitudinal psychotherapy-epigenetic study). (LLM, conf=0.88)
Experimental — accuracy not yet measuredSuggestive evidence was discerned for an increase in methylation directly after CBT at cg06943668 in the IL1R1 gene in treatment responders, suggesting a potentially immunomodulatory effect of successful CBT.
“Suggestive evidence was discerned for an increase in methylation directly after CBT at cg06943668 in the interleukin 1 receptor type 1 (IL1R1) gene in treatment responders suggesting a potentially immunomodulatory effect of successful CBT (Ziegler et al., 2019).”
From The applied implications of epigenetics in anxiety, affective and stress-related disorders - A review and synthesis on psychosocial stress, psychotherapy and prevention (2020) · cites this paper as Ziegler et al., 2019
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- Authors
- Ziegler, C., Grundner-Culemann, F., Schiele, M. A., Schlosser, P., Kollert, L., Mahr, M., Gajewska, A., Lesch, K.-P., Deckert, J., Köttgen, A., & Domschke, K.
- Affiliations
- University of Freiburg (DE)
- University of Würzburg (DE)
- Sechenov University (RU)
- Corresponding author
- Domschke, Katharina
- ORCID
- Venue
- Translational Psychiatry
- Published
- 2019-11-21
- Volume
- 9
- Issue
- 1
- Pages
- 314-314
- ISSN
- 2158-3188 (ISSN-L)
- PMC
- PMC6872551
- OpenAlex
- W2991154961
- Cited by
- 47
- References
- 59
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 5 · 2023: 12 · 2022: 5 · 2021: 5 · 2020: 10
- FWCI
- 1.65
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Translational Psychiatry (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research Publications (Maastricht University) (publishedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Research Publications (Maastricht University) (submittedVersion, other-oa)
- Funders
- Deutsche Forschungsgemeinschaft (44541416, CRC 992, KO 3598/3-1, KO 3598/5-1)
- Bundesministerium für Bildung und Forschung (01EE1402A)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Maternal Mental Health During Pregnancy and Postpartum
- Keywords
- panic disorder, DNA methylation, epigenome-wide association study, cognitive behavioral therapy, treatment response, IL1R1, candidate genes
- MeSH terms
- Adult, Female, Humans, Longitudinal Studies, Male, Cognitive Behavioral Therapy, Case-Control Studies, Panic Disorder, CpG Islands, DNA Methylation, Epigenesis, Genetic, Gene Regulatory Networks, Genome-Wide Association Study, Young Adult
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