@article{5fcc3b6cf7ba43839c17aa19ab3d80ed,
title = "DNA methylation in the 5-HTT regulatory region is associated with CO2-induced fear in panic disorder patients",
abstract = "A polymorphism in the gene encoding the serotonin (5-HT) transporter (5-HTT) has been shown to moderate the response to CO2 inhalation, an experimental model for panic attacks (PAs). Recurrent, unpredictable PAs represent, together with anticipatory anxiety of recurring attacks, the core feature of panic disorder (PD) and significantly interfere with patients' daily life. In addition to genetic components, accumulating evidence suggests that epigenetic mechanisms, which regulate gene expression by modifying chromatin structure, also play a fundamental role in the etiology of mental disorders. However, in PD, epigenetic mechanisms have barely been examined to date. In the present study, we investigated the relationship between methylation at the regulatory region of the gene encoding the 5-HTT and the reactivity to a 35% CO2 inhalation in PD patients. We focused on four specific CpG sites and found a significant association between the methylation level of one of these CpG sites and the fear response. This suggests that the emotional response to CO2 inhalation might be moderated by an epigenetic mechanism, and underlines the implication of the 5-HT system in PAs. Future studies are needed to further investigate epigenetic alterations in PD and their functional consequences. These insights can increase our understanding of the underlying pathophysiology and support the development of new treatment strategies. (c) 2020 Elsevier B.V. and ECNP. All rights reserved.",
keywords = "Panic attacks, Serotonin transporter, Epigenetics, Carbon dioxide, CARBON-DIOXIDE, COMT PROMOTER, HYPOMETHYLATION, SEROTONIN, TRAITS, SALIVA",
author = "Leibold, {N. K.} and Weidner, {M. T.} and C. Ziegler and G. Ortega and K. Domschke and Lesch, {K. P.} and {Van den Hove}, {D. L.} and Schruers, {K. R.}",
note = "Funding Information: Klaus-Peter Lesch (KPL) and his team are supported by the Deutsche Forschungsgemeinschaft (DFG: CRU 125, CRC TRR 58 A1/A5, No. 44,541,416), the European Union's Horizon 2020 Research and Innovation Programme under Grant No. 728,018 (Eat2beNICE), ERA-Net NEURON/RESPOND,No. 01EW1602B, and 5–100 Russian Academic Excellence Project. Katharina Domschke (KD) received funding by the German Research Foundation (DFG) – project no. 44,541,416 – TRR 58 , subprojects C02 and Z02. The funders had no role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. Funding Information: Klaus-Peter Lesch (KPL) and his team are supported by the Deutsche Forschungsgemeinschaft (DFG: CRU 125, CRC TRR 58 A1/A5, No. 44,541,416), the European Union's Horizon 2020 Research and Innovation Programme under Grant No. 728,018 (Eat2beNICE), ERA-Net NEURON/RESPOND,No. 01EW1602B, and 5?100 Russian Academic Excellence Project. Katharina Domschke (KD) received funding by the German Research Foundation (DFG) ? project no. 44,541,416 ? TRR 58, subprojects C02 and Z02. The funders had no role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. KRS designed the study and wrote the protocol. NKL did the experiments. NKL, MTW, CZ, OG, designed and did the epigenetic analysis. NKL and MTW undertook the statistical analysis, and NKL wrote the first draft of the manuscript. DvdH, KD, and KPL contributed to overall discussion. All authors contributed to and have approved the final manuscript. KPL served as a speaker for Eli Lilly and received research support from Medice, and travel support from Shire, all outside the submitted work. Other authors declare no conflict of interest. None. Publisher Copyright: {\textcopyright} 2020",
year = "2020",
month = jul,
doi = "10.1016/j.euroneuro.2020.04.011",
language = "English",
volume = "36",
pages = "154--159",
journal = "European Neuropsychopharmacology",
issn = "0924-977X",
publisher = "Elsevier B.V.",
}