Epigenetic, psychological, and EEG changes after a 1-week retreat based on mindfulness and compassion for stress reduction: Study protocol of a cross-over randomized controlled trial

Introduction The main objective of the study will be to evaluate the effects of two widely used standardized mindfulness-based programs [Mindfulness-Based Stress Reduction (MBSR) and Compassion Cultivation Training (CCT)], on epigenetic, neurobiological, psychological, and physiological variables. Methods The programs will be offered in an intensive retreat format in a general population sample of healthy volunteer adults. During a 7-day retreat, participants will receive MBSR and CCT in a crossover design where participants complete both programs in random order. After finishing their first 3-day training with one of the two programs, participants will be assigned to the second 3-day training with the second program. The effects of the MBSR and CCT programs, and their combination, will be measured by epigenetic changes (i.e., DNA methylation biomarkers), neurobiological and psychophysiological measures (i.e., EEG resting state, EKG, respiration patterns, and diurnal cortisol slopes), self-report questionnaires belonging to different psychological domains (i.e., mindfulness, compassion, well-being, distress, and general functioning), and stress tasks (i.e., an Arithmetic Stress Test and the retrieval of negative autobiographical memories). These measures will be collected from both groups on the mornings of day 1 (pre-program), day 4 (after finishing the first program and before beginning the second program), and day 7 (post-second program). We will conduct a 3-month follow-up using only the set of self-report measures. Discussion This study aims to shed light on the neurobiological and psychological mechanisms linked to meditation and compassion in the general population. The protocol was registered at [clinicaltrials.gov][1] (Identifier: [NCT05516355][2]; August 23, 2022). ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial Clinicaltrials.gov ([NCT05516355][2]) ### Funding Statement CV: Ministry of Science PID2019-108711GB-I00 RMZ:Spanish Ministry of Science FPI predoctoral fellowship (PRE2020-092011) GD: Mindfulness and Cognitive Science Chair of Complutense University of Madrid. The funders did not and will not have a role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: University Ethics Committee (Ref. 22/449-E, July 2022 Hospital Clinico Universitario San Carlos) I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All relevant data from this study will be made available upon study completion. [1]: http://clinicaltrials.gov [2]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT05516355&atom=%2Fmedrxiv%2Fearly%2F2023%2F03%2F05%2F2023.03.03.23286782.atom