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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Psychiatry | doi: 10.3389/fpsyt.2019.00394

Childhood Adversity Moderates the Effects of HTR2A Epigenetic Regulatory Polymorphisms on Rumination

 Nora Eszlari1, 2*, Peter Petschner2,  Xenia Gonda3, Daniel Baksa2,  Rebecca Elliott4, Ian M. Anderson4,  Bill Deakin4, Gyorgy Bagdy2 and Gabriella Juhasz2
  • 1Semmelweis University, Hungary
  • 2Department of Pharmacodynamics, Faculty of Pharmacy, Semmelweis University, Hungary
  • 3Department of Psychiatry and Psychotherapy, Faculty of Medicine, Semmelweis University, Hungary
  • 4Division of Neuroscience and Experimental Psychology, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, United Kingdom

The serotonin system has been suggested to moderate the association between childhood maltreatment and rumination, with the latter in its turn reported to be a mediator in the depressogenic effect of childhood maltreatment. Therefore, we investigated whether the associations of two epigenetic regulatory polymorphisms in the HTR2A serotonin receptor gene with Ruminative Responses Scale rumination and its two subtypes, brooding and reflection, are moderated by childhood adversity (derived from the Childhood Trauma Questionnaire) among 1501 European white adults. We tested post hoc whether the significant associations are due to depression. We also tested the replicability of the significant results within the two subsamples of Budapest and Manchester. We revealed two significant models: both the association of methylation site rs6311 with rumination and that of miRNA binding site rs3125 (supposed to bind miR-1270, miR-1304, miR-202, miR-539 and miR-620) with brooding were a function of childhood adversity, and both interaction findings were significantly present both in the never-depressed and in the ever-depressed group. Moreover, the association of rs3125 with brooding could be replicated across the separate subsamples, and remained significant even when controlling for lifetime depression and the Brief Symptom Inventory depression score. These findings indicate the crucial importance of involving stress factors when considering endophenotypes, and suggest that brooding is a more promising endophenotype than a broader measure of rumination. Transdiagnostic relevance of the brooding endophenotype and the potential of targeting epigenetic regulatory polymorphisms of HTR2A in primary and secondary prevention of depression and possibly of other disorders are also discussed.

Keywords: childhood stress; rumination; brooding; serotonin system; perseverative thought, Childhood stress, rumination, brooding, Serotonin system, perseverative cogniton

Received: 04 Mar 2019; Accepted: 17 May 2019.

Edited by:

Divya Mehta, Queensland University of Technology, Australia

Reviewed by:

Gabriel R. Fries, University of Texas Health Science Center at Houston, United States
Ludwig Stenz, Université de Genève, Switzerland  

Copyright: © 2019 Eszlari, Petschner, Gonda, Baksa, Elliott, Anderson, Deakin, Bagdy and Juhasz. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Ms. Nora Eszlari, Semmelweis University, Budapest, Hungary,