DNA methylation signatures in panic disorder
Open accessAbstract
Panic disorder (PD) affects about four million Europeans, with women affected twice as likely as men, causing substantial suffering and high economic costs. The etiopathogenesis of PD remains largely unknown, but both genetic and environmental factors contribute to risk. An epigenome-wide association study (EWAS) was conducted to compare medication-free PD patients (n = 89) with healthy controls (n = 76) stratified by gender. Replication was sought in an independent sample (131 cases, 169 controls) and functional analyses were conducted in a third sample (N = 71). DNA methylation was assessed in whole blood using the Infinium HumanMethylation450 BeadChip. One genome-wide association surviving FDR of 5% (cg07308824, P = 1.094 × 10-7, P-adj = 0.046) was identified in female PD patients (N = 49) compared to controls (N = 48). The same locus, located in an enhancer region of the HECA gene, was also hypermethylated in female PD patients in the replication sample (P = 0.035) and the significance of the association improved in the meta-analysis (P-adj = 0.004). Methylation at this CpG site was associated with HECA mRNA expression in another independent female sample (N = 71) both at baseline (P = 0.046) and after induction by dexamethasone (P = 0.029). Of 15 candidates, 5 previously reported as associated with PD or anxiety traits also showed differences in DNA methylation after gene-wise correction and included SGK1, FHIT, ADCYAP1, HTR1A, HTR2A. Our study examines epigenome-wide differences in peripheral blood for PD patients. Our results point to possible sex-specific methylation changes in the HECA gene for PD but overall highlight that this disorder is not associated with extensive changes in DNA methylation in peripheral blood.
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Altered DNA methylation patterns have been found in GAD, PD, and adolescents with anxiety disorder.
“altered DNA methylation patterns in GAD (Gottschalk & Domschke, 2017), PD (Iurato et al., 2017) or adolescents with anxiety disorder (Bortoluzzi et al., 2018) have been found.”
From Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders (2019) · cites this paper as Iurato et al., 2017
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Self-citationCzamara, D., Neufang, A., Dieterle, R., Iurato, S., Arloth, J., Martins, J., Ising, M., Binder, E. E., & Erhardt, A. (2022) · Figshare · doi:10.6084/m9.figshare.19670077
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Self-citationCzamara, D., Neufang, A., Dieterle, R., Iurato, S., Arloth, J., Martins, J., Ising, M., Binder, E. E., & Erhardt, A. (2022) · Figshare · doi:10.6084/m9.figshare.19670074
Self-citationCzamara, D., Neufang, A., Dieterle, R., Iurato, S., Arloth, J., Martins, J., Ising, M., Binder, E. E., & Erhardt, A. (2022) · Figshare · doi:10.6084/m9.figshare.19670089
Self-citationCzamara, D., Neufang, A., Dieterle, R., Iurato, S., Arloth, J., Martins, J., Ising, M., Binder, E. E., & Erhardt, A. (2022) · Figshare · doi:10.6084/m9.figshare.19670062
Self-citationCzamara, D., Neufang, A., Dieterle, R., Iurato, S., Arloth, J., Martins, J., Ising, M., Binder, E. E., & Erhardt, A. (2022) · Figshare · doi:10.6084/m9.figshare.19670083
Self-citationCzamara, D., Neufang, A., Dieterle, R., Iurato, S., Arloth, J., Martins, J., Ising, M., Binder, E. E., & Erhardt, A. (2022) · Figshare · doi:10.6084/m9.figshare.19670065
Self-citationCzamara, D., Neufang, A., Dieterle, R., Iurato, S., Arloth, J., Martins, J., Ising, M., Binder, E. E., & Erhardt, A. (2022) · Figshare · doi:10.6084/m9.figshare.19670059
Self-citationCzamara, D., Neufang, A., Dieterle, R., Iurato, S., Arloth, J., Martins, J., Ising, M., Binder, E. E., & Erhardt, A. (2022) · Figshare · doi:10.6084/m9.figshare.19670056
Self-citationCzamara, D., Neufang, A., Dieterle, R., Iurato, S., Arloth, J., Martins, J., Ising, M., Binder, E. E., & Erhardt, A. (2022) · Figshare · doi:10.6084/m9.figshare.19670086
Self-citationCzamara, D., Neufang, A., Dieterle, R., Iurato, S., Arloth, J., Martins, J., Ising, M., Binder, E. E., & Erhardt, A. (2022) · Figshare · doi:10.6084/m9.figshare.19670092
Self-citationAdditional file 2 of Altered immune phenotype and DNA methylation in panic disorder
Petersen, C. L., Chen, J.-Q., Salas, L. A., & Christensen, B. C. (2020) · Figshare · doi:10.6084/m9.figshare.13257575
Czamara, D., Neufang, A., Dieterle, R., Iurato, S., Arloth, J., Martins, J., Ising, M., Binder, E. E., & Erhardt, A. (2022) · Figshare · doi:10.6084/m9.figshare.19670053
Self-citationCzamara, D., Neufang, A., Dieterle, R., Iurato, S., Arloth, J., Martins, J., Ising, M., Binder, E. E., & Erhardt, A. (2022) · Figshare · doi:10.6084/m9.figshare.19670044
Self-citationCzamara, D., Neufang, A., Dieterle, R., Iurato, S., Arloth, J., Martins, J., Ising, M., Binder, E. E., & Erhardt, A. (2022) · Figshare · doi:10.6084/m9.figshare.19670050
Self-citationCzamara, D., Neufang, A., Dieterle, R., Iurato, S., Arloth, J., Martins, J., Ising, M., Binder, E. E., & Erhardt, A. (2022) · Figshare · doi:10.6084/m9.figshare.19670071
Self-citationVellame, D. S., Castanho, I., Dahir, A., Mill, J. S., & Hannon, E. J. (2021) · Figshare · doi:10.6084/m9.figshare.14782453
Epigenetic processes in depressive and anxiety disorders
Breton, É., Booij, L., & Nemoda, Z. (2026) · Handbook of clinical neurology · doi:10.1016/b978-0-443-19043-8.00032-3
- Authors
- Iurato, S., Carrillo-Roa, T., Arloth, J., Czamara, D., Diener-Hölzl, L., Lange, J., Müller-Myhsok, B., Binder, E. B., & Erhardt, A.
- Affiliations
- Max Planck Institute of Psychiatry (DE)
- Emory University (US)
- Corresponding author
- Iurato, Stella
- Erhardt, Angelika
- Venue
- Translational Psychiatry
- Published
- 2017-12-18
- Volume
- 7
- Issue
- 12
- Pages
- 1287-1287
- ISSN
- 2158-3188 (ISSN-L)
- PMC
- PMC5802688
- OpenAlex
- W2775629207
- Cited by
- 70
- References
- 87
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 4 · 2023: 9 · 2022: 27 · 2021: 5 · 2020: 10 · 2019: 7 · 2018: 2
- FWCI
- 2.12
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Translational Psychiatry (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Publication Server of the Catholic University Eichstätt-Ingolstadt (Catholic University of Eichstätt-Ingolstadt) (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Electronic Theses of LMU Munich (Ludwig-Maximilians-Universität München) (submittedVersion)
- Max Planck Digital Library (submittedVersion, other-oa)
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- panic disorder, DNA methylation, epigenome-wide association study, sex differences, hypermethylation, enhancers, peripheral blood, anxiety disorders, SGK1, FHIT, ADCYAP1, 5-HT1A receptor, HTR2A
- MeSH terms
- Adult, Female, Humans, Male, Middle Aged, Anti-Anxiety Agents, Panic Disorder, DNA Methylation, Gene Expression Profiling, Genome-Wide Association Study, Genetic Loci, Epigenomics
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