Journal
NEUROPSYCHOPHARMACOLOGY
Volume 43, Issue 2, Pages 342-353Publisher
SPRINGERNATURE
DOI: 10.1038/npp.2017.102
Keywords
-
Categories
Funding
- Helmholtz Zentrum Munchen-German Research Center for Environmental Health - German Federal Ministry of Education and Research (BMBF)
- State of Bavaria
- portfolio area metabolic dysfunction
- Helmholtz Association
- Munich Center of Health Sciences (MC-Health)
- Ludwig-Maximilians-Universitat, as part of LMUinnovativ
- Ministry of Science and Research of the State of North Rhine-Westphalia (MIWF NRW)
- German Federal Ministry of Health (BMG)
- German Federal Ministry of Education and Research (BMBF)
- ERA-NET NEURON (AnxBio)
- Marie-Sklodowska Curie fellowship (H2020) [653240]
- Dartmouth Clinical and Translational Science Institute from the National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health (NIH) [UL1TR001086]
- NATIONAL CANCER INSTITUTE [R25CA134286] Funding Source: NIH RePORTER
Ask authors/readers for more resources
Epigenetic regulation in anxiety is suggested, but evidence from large studies is needed. We conducted an epigenome-wide association study (EWAS) on anxiety in a population-based cohort and validated our finding in a clinical cohort as well as a murine model. In the KORA cohort, participants (n = 1522, age 32-72 years) were administered the Generalized Anxiety Disorder (GAD-7) instrument, whole blood DNA methylation was measured (Illumina 450K BeadChip), and circulating levels of hs-CRP and IL-18 were assessed in the association between anxiety and methylation. DNA methylation was measured using the same instrument in a study of patients with anxiety disorders recruited at the Max Planck Institute of Psychiatry (MPIP, 131 non-medicated cases and 169 controls). To expand our mechanistic understanding, these findings were reverse translated in a mouse model of acute social defeat stress. In the KORA study, participants were classified according to mild, moderate, or severe levels of anxiety (29.4%/6.0%/1.5%, respectively). Severe anxiety was associated with 48.5% increased methylation at a single CpG site (cg12701571) located in the promoter of the gene encoding Asb1 (beta-coefficient = 0.56 standard error (SE) = 0.10, p (Bonferroni) = 0.005), a protein hypothetically involved in regulation of cytokine signaling. An interaction between IL-18 and severe anxiety with methylation of this CpG cite showed a tendency towards significance in the total population (p = 0.083) and a significant interaction among women (p = 0.014). Methylation of the same CpG was positively associated with Panic and Agoraphobia scale (PAS) scores (beta = 0.005, SE = 0.002, p = 0.021, n = 131) among cases in the MPIP study. In a murine model of acute social defeat stress, Asb1 gene expression was significantly upregulated in a tissue-specific manner (p = 0.006), which correlated with upregulation of the neuroimmunomodulating cytokine interleukin 1 beta. Our findings suggest epigenetic regulation of the stress-responsive Asb1 gene in anxiety-related phenotypes. Further studies are necessary to elucidate the causal direction of this association and the potential role of Asb1-mediated immune dysregulation in anxiety disorders.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available