Changes in DNA Methylation Associated With Psychobehavioral Interventions: A Scoping Literature Review.

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Learn more: PMC Disclaimer | PMC Copyright Notice Biol Res Nurs . 2025 May 31;27(4):666–682. doi: 10.1177/10998004251346179 Changes in DNA Methylation Associated With Psychobehavioral Interventions: A Scoping Literature Review Karen L Saban 1, ✉ , Linda Janusek 1 , Paula de la Pena 1 , Sueyeon Lee 1 , Dina Tell 1 , Herbert Mathews 2 , Alexandra L Nowak 1 , Alexandria Nyembwe 3 , Jacquelyn Y Taylor 4 Author information Article notes Copyright and License information 1 Marcella Niehoff School of Nursing, Loyola University Chicago, Maywood, IL, USA 2 Stritch School of Medicine, Loyola University Chicago, Maywood, IL, USA 3 Sue & Bill Gross School of Nursing, University of California, Irvine, CA, USA 4 Columbia University School of Nursing, New York, NY, USA ✉ Karen L. Saban, PhD, RN, CNRN, FAHA, FAAN, Marcella Niehoff School of Nursing, Loyola University Chicago, 2160 S. First Ave, Center for Translational Research and Education, Office #349, Maywood, IL 60153, USA. Email: Ksaban@luc.edu Received 2025 Mar 17; Revised 2025 May 13; Accepted 2025 May 14; Collection date 2025 Oct. © The Author(s) 2025 PMC Copyright notice PMCID: PMC12571133  NIHMSID: NIHMS2116656 PMID: 40448426 Abstract Background: DNA methylation (DNAm) is an epigenetic process of addition or reduction of methyl groups to genes that modify gene expression and can alter the physiological response to psychological stress. DNAm associated with psychological stress is malleable, making it a prime target for psychobehavioral interventions. Research is beginning to examine changes in DNAm in response to psychobehavioral interventions, such as mindfulness-based stress reduction, cognitive behavioral therapy, and yoga. A better understanding of the current evidence may provide direction for future research. Objective: The purpose of this scoping review is to summarize current studies, identify knowledge gaps, and make recommendations for further research related to examining alterations in DNAm in response to psychobehavioral interventions. Methods: A scoping review was conducted based on the methods recommended by Arksey and O’Malley (2005). Studies examining response of blood or saliva DNAm to psychobehavioral interventions in adult humans were reviewed. Results: Twenty-one studies met the inclusion criteria. Although many studies were inadequately powered, several reported differences in DNAm in response to a psychobehavioral intervention across a variety of genes, including genes related to stress and inflammation. However, the studies varied with respect to participant health status, type and duration of psychobehavioral interventions evaluated, biospecimens examined, and method of DNA analysis. Conclusions: The evaluation of DNAm in response to psychobehavioral interventions is a growing area of research. Future research is needed to address design limitations of existing investigations, evaluate the biological importance of observations, and link the DNAm response to physiological and psychological outcomes of the interventions. Keywords: DNA methylation, epigenetics, stress reduction, intervention Epigenetics refers to the processes that regulate genomic information by dynamically modifying the patterns of transcription of genes without changing the underlying DNA sequence, while the epigenome refers to the collection of chemical changes that comprise the epigenetic landscape of an individual’s DNA ( Matosin et al., 2017 ). Across the lifespan there is a dynamic interplay between the epigenome and the external environment surrounding a person and the internal environment of cells and tissues. Environmental input can induce epigenetic modifications to influence gene expression and subsequently produce changes in physiology (e.g., psychobehavioral state, microbiome, inflammation) and/or behavior (e.g., stress reactivity, social interaction). In turn these changes may influence the epigenome. Importantly, epigenetic modification is context dependent. It is modulated by both positive and negative input, including early life experiences, resilience, social support, health behaviors, genetic predisposition, and health status ( Kanherkar et al., 2014 ). The most studied epigenetic process is DNA methylation (DNAm) in which methyl groups are added to specific DNA sequences. The location and extent of methylation (hypo/hypermethylation) modulates gene expression and protein production. The functional implications of hypo- or hypermethylation are complex and vary depending upon the particular genes and genomic regions affected (i.e., regulatory regions, protein coding exons, or non-coding regions). For example. Methylation of critical regulatory regions of genes (promotors, enhancers, and transcription start sites) generally results in silencing gene expression by blocking transcription factor access needed to transcribe the genes ( Suzuki & Bird, 2008 ). In contrast, increased methylation of intragenic regions (exons or introns) results in a proportionate increase in transcription rate, while the reverse, decreased methylation of these gene regions, results in reduced transcription (Suzuki & Bird). Growing evidence suggests changes in DNAm may be one of the earliest cellular events in disease onset ( Matosin et al., 2017 ). Epigenetic changes are associated with psychological factors, including stress experienced in early childhood ( Park et al., 2019 ) and higher stress burden ( Skinner et al., 2024 ). Changes in DNAm are also linked to chronic stress ( Duman & Canli, 2015 ), depressive symptoms (( Na et al., 2014 ; Olsson et al., 2010 ; Uddin et al., 2011 ), and work stress ( Alasaari et al., 2012 ). Growing evidence suggests that early life adversity ( Fiacco et al., 2019 ; Kundakovic et al., 2015 ; Turecki & Meaney, 2016 ), social stress ( Draper et al., 2022 ), post-traumatic stress disorder (PTSD; Smith et al., 2011 ; Uddin et al., 2010 ), perceived discrimination ( de Mendoza et al., 2018 ; van der Laan et al., 2020 ), and history of trauma ( Kang et al., 2019 ; Matosin et al., 2017 ) are associated with modifications in DNAm, such as hypermethylation, hypomethylation, and DNAm age acceleration. DNAm associated with psychosocial stress is malleable ( Szyf et al., 2016 ), suggesting that interventions may potentially buffer the impact of psychological stress at the epigenetic level ( Stoffel et al., 2020 ). A key question in behavioral epigenetics is whether psychobehavioral interventions can attenuate or reverse adverse epigenetic marks, which may help explain individual variability in treatment response or outcomes. Emerging studies report potentially beneficial changes (i.e., reduced hypomethylation of tumor necrosis factor (TNF) region, modification of binding sites for transcription factors related to inflammation and immunity) in DNAm associated with psychobehavioral interventions such as yoga ( Harkess et al., 2016 ), mindfulness ( Garcia-Campayo et al., 2018 ), psychotherapy ( Xulu et al., 2021 ), and meditation ( Chaix et al., 2020 ). However, the possible impact of these interventions on DNAm has not been comprehensively reviewed. In this scoping review, we summarize studies evaluating whether psychobehaviroal interventions may modify DNAm, identify limitations and knowledge gaps of existing studies, and make recommendations for further research. Methods The method for the scoping review was based on Arksey and O’Malley’s framework Arksey and O'Malley (2005) which includes five phases: (1) identifying the research question, (2) identifying relevant studies, (3) selecting studies, (4) tabulating the findings, and (5) summarizing gaps in the field. This review was guided by the research question, “What is the current knowledge regarding DNAm response to psychobehavioral interventions?” Eligibility Criteria This scoping review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Table 1 lists inclusion and exclusion criteria. Psychobehavioral interventions were considered to be structured interventions that integrate psychological and behavioral strategies to promote mental and physical well-being. Examples include mindfulness-based interventions (MBIs), yoga, cognitive behavioral therapy (CBT), and dialectical behavioral therapy (DBT), all of which emphasize self-regulation, awareness, and adaptive behavior change. We intentionally limited our scoping review to adult populations to reduce heterogeneity and improve the interpretability of findings. Yoga interventions were included because they often incorporate mindfulness and meditation and are typically considered to be low activity. We excluded studies focused solely on DNA methylation age acceleration because our review aimed to examine locus-specific or genome-wide DNAm changes that may be directly attributable to psychobehavioral interventions. Table 1. Inclusion and Exclusion Criteria. Inclusion criteria Exclusion criteria Participants Adults ≥18 Interventions Psychobehavioral interventions include Pharmacological interventions Mindfulness-based interventions (MBIs) Exercise interventions Yoga Nutritional/dietary interventions Cognitive behavioral therapy (CBT) Dialectical behavioral therapy (DBT) Outcomes Measure of DNA methylation Epigenetic aging measures Study design RCTs, non RCTs, cross-sectional studies Qualitative, study protocols Dissemination Published in peer-reviewed journals Published as reviews, case report, conference proceedings, or letters Open in a new tab Note. RCT = randomized controlled trial. Information Sources A systematic literature search of PubMed, Scopus, and PsycINFO was conducted between October 2024 and January 2025. Search terms included “DNA methylation,” “mindfulness,” “mindfulness-based stress reduction,” “yoga,” “cognitive behavioral therapy,” “dialectical behavioral therapy,” and “psychobehavioral intervention.” Additionally, ancestry searching was performed manually to identify additional studies. Selection Process Two authors independently screened titles and abstracts for full-text retrieval eligibility. Full texts of potentially eligible studies were assessed, and any discrepancies were resolved through discussion and consensus. After selection, another author independently reviewed the selected studies for eligibility. Figure 1 displays the PRISMA flow chart of study selection. Figure 1. Open in a new tab PRISMA diagram ( Page et al., 2021 ). Results Participant Characteristics Twenty-one studies met inclusion criteria ( Table 2 ). Studies were published between 2013 and 2023, with 62% published between 2019 and 2023. The sample size of the 21 studies ranged from 11 to 181 participants. Most participants experienced various physical and psychological conditions. Physical conditions included chronic low back pain ( Adhikari et al., 2022 ) and polycystic ovarian syndrome ( Dema et al., 2023 ). Psychological conditions were obsessive-compulsive disorder ( Schiele et al., 2020 ), PTSD or exposure to trauma ( Bishop et al., 2018 , 2021 ; Hummel et al., 2022 ; Vinkers et al., 2021 ; Wilker et al., 2023 ; Xulu et al., 2021 ; Yehuda et al., 2013 ), panic disorder with anxiety symptoms ( Moser et al., 2022 ; Ziegler et al., 2016 ), major depressive disorder ( Van Assche et al., 2023 ), borderline personality disorder ( Knoblich et al., 2018 ; Perroud et al., 2013 ) and agoraphobia or specific phobias ( Roberts et al., 2019 ). Other studies enrolled healthy adults to evaluate mindfulness interventions ( Pragya et al., 2023 ; Stoffel et al., 2019 ) or to compare long-term meditators to non-meditators ( Chaix et al., 2020 ; Cozzolino et al., 2017 ; Garcia-Campayo et al., 2018 ). Five studies ( Dema et al., 2023 ; Harkess et al., 2016 ; Hummel et al., 2022 ; Schiele et al., 2020 ; Ziegler et al., 2016 ) included only women. Table 2. Summary of Literature Reviewed. Article Sample Purpose/Intervention Description of intervention Tissue and method of DNA methylation analysis Findings – DNA methylated genes Adhikari et al. (2022) 11 participants with chronic low back pain To assess the feasibility and acceptability of a yoga intervention on pain and DNA methylation (DNAm) 12-week yoga intervention Blood collected just prior to and after the yoga -Differential gene expression in 94 genes (76 genes were upregulated and 18 downregulated) Intervention -Differential methylation analysis showed the induced increased expression of antisense genes (pain genes) and a total of 282 with 5 hypermethylated and 277 hypomethylated positions White blood cells isolated and analyzed -Out of 282, only 33 genes were associated with hypomethylated positions by twofold, with enrichment of genes involved in NIK/NF-kB signaling NGS * (RRBS-seq) Illumina NextSeq 550 Bishop et al. (2018) 22 veterans with post-traumatic stress disorder (PTSD) To examine DNAm levels of SLC6A4 and FKBP5 in veterans with PTSD who responded to mindfulness-based stress reduction (MBSR) treatment compared with non-responders 9-week MBSR intervention Blood collected prior to and following the intervention -Significant time x responder group interaction for methylation in FKBP5 intron 7 bin 2. Responders had an increase in methylation and non-responders had a decrease in methylation from before to after treatment in this region Bishop et al. (2021) (corrigendum) NGS (Illumina MiSeq) -Analyses of the three CpG sites within bin 2 revealed a significant time x responder group interaction for CpG_35558513 which resides in a known glucocorticoid response element (GRE) White blood cells isolated and analyzed Chaix et al. (2020) 18 long-term meditators and 20 meditation-naïve controls To examine the influence of a day long (8hr) meditation in long-term meditators compared to an 8hr leisure activity in naïve controls on DNAm of Intrinsic Epigenetic age acceleration genes Day-long session of MBSR intervention program, control group engaged in intentional activities Blood collected prior to and at completion of one-day intensive meditation -No differences between groups at baseline Peripheral blood mononuclear cells (PBMCs) isolated and analyzed -After MBSR 61 meditation-sensitive differentially methylated sites showed increased DNAm (55 located at known genes) 450K array -Methylated sites were more often found in CpG Islands Cozzolino et al. (2017) 20 participants enrolled in a mind-body therapeutic protocol (MBT-T) To examine the epigenetic response to MBT-T measuring DNAm prior to treatment, 1 hour and 24 hours after treatment MBT-T protocol based on four-stage creative process, ultradian rhythms, basic rest-activity cycle (BRAC), and neuronal and biological plasticity Samples collected at baseline, 1 hour after and 24 hours after treatment -Prior to treatment subject DNAm profiles were heterogeneous; after MBT-T treatment, DNAm profiles converged to a homogenous status Type of tissue not identified Restriction enzyme; methylation sensitive amplification polymorphism (MSAP) analysis Dema et al. (2023) 42 women with polycystic ovarian syndrome (PCOS). women were randomly assigned to an MBSR program ( n = 21) or a control group ( n = 21) To determine the effect of MBSR on anthropometric, measurements, mental health, and alterations in DNAm in peripheral blood 8-week MBSR program Blood collected at baseline and 6 months after the 8-week intervention -Statistically significant two-way interaction between time and group on DNAm Whole blood analyzed MBSR group had an ↑DNAm for COMT_4, FKBP51_1, MAOA_2 and a ↓ DNAm for FST_1 NGS (Illumina MiniSeq) Garcia-Campayo et al. (2018) 17 long-term (>10 years) mindfulness meditators (MMs), 17 controls recruited from healthy relatives and friends of MMs To profile genome wide DNAm patterns in peripheral blood leukocytes of long-term meditators non-meditators (known groups design) MMs practice 60min/day of formal practice of open-monitoring meditation Blood collected in long term meditators and control group of non-meditators −64 differentially methylated regions (DMRs) passed statistical threshold (β difference ≤.05 and minimum p value ≤.05), corresponding to 43 genes Buffy coat analyzed -Mean length of mindfulness related DMRS was 499.6bp, encompassed an average of 4.3 differentially methylated CpG sites per region 450 K array −45 DMRs (70.3%) were hypomethylated in MM compared to 19 DMRs (29.7%) in controls were hypermethylated Harkess et al. (2016) Women with psychological distress ( n = 28)—Subsample of larger clinical trial ( N = 116) To examine whether participation in a yoga intervention is associated with altered levels of estimated global DNAm (LINE-1) or changes to DNAm patterns of IL6 , TNF and CRP genes 1 hour yoga class 2x week for 8 weeks Blood collected at baseline, completion of intervention and post-intervention -No between-group differences in mean methylation of CRP or IL-6 Note – no baseline measure of DNAm. Only post yoga measure of DNAm - Women in yoga group demonstrated a 4.5% lower level of methylation relative to the waitlist control group Whole blood analyzed -Decreased methylation at post-yoga time point for TNF CpG site 1 and 4/5/6 -No effect on IL-6 or CRP methylation Mass array -Correlation between LINE-1 methylation and perceived stress Hummel et al. (2022) 60 females with PTSD between the ages of 20 and 60 To replicate DNA methylation changes associated with therapy for PTSD in 60 women with PTSD and identify novel genomic regions with changes in DNA methylation post-treatment by completing whole-genome bisulfite sequencing in 2 women with PTSD. Inpatient treatment for PTSD treatment consisted of one session per week of CBT, three sessions of trauma group therapy, two sessions of trauma stabilization group therapy and one session of skills group, two sessions of kinesiotherapy, two session of art therapy, physiotherapy, clinical rounds and brief session with nurse Blood collected upon admission and discharge from inpatient treatment -No intervention related changes found in DNA methylation of monocytes in target genes ( NR3C1, FKBP5, SLC6A4, OXTR ) CD14 + monocytes isolated from blood -WGBS in 2 participants demonstrated a limited number of candidate genes that suggest changes in therapy related DNA methylation but were not able to be replicated in full cohort Cell type heterogeneity controlled for Targeted deep bisulfite sequencing (DBS) in 60 participants of candidate genes ( NR3C1, SLC6A4, FKBP5, OXTR ) and whole-genome bisulfite sequencing (WGBS) in 2 participants. New candidate genes validated by DBS Knoblich et al. (2018) 44 participants with bipolar disorder (BPD) and 44 matched healthy controls To examine the role of DNA methylation of APBA3 and MCF2 as predictors of treatment outcome of BPD. 12 weeks of dialectical behavior therapy (DBT) Whole blood collected during the first week of the intervention and during the last week of the 12- week DBT program -No differences between participants who participated in DBT versus healthy controls Whole blood analyzed - -Greater methylation of APBA3 and MCF2 prior to therapy in responders to therapy Pyrosequencing -Suggests possible epigenetic marker predictive of therapy response Moser et al. (2022) 42 with diagnosis of panic disorder and Hamilton anxiety scale (HAMA) score of >14 To investigate the changes in DNAm and proportion of immune cell-type during and post CBT intervention −12 CBT session (1–2 per week over 6–8 weeks), 2 “booster” sessions after 2- and 4-month mark Blood collected at baseline, after the 4 th therapy session, completion of therapy (6–8 weeks), and 2 months after completion of therapy -cg01586609 ( HTR3A ) was differentially methylated during fear exposure and regulated at gene expression level with significant differences between remitters and non-remitters -Session 5 and 7 were in vivo exposure (outside of clinical setting to expose to fear) Whole blood analyzed 450K array -cg01699630 ( ARG1 ) was differently methylated at the end of therapy as compared to the beginning Perroud et al. (2013) 115 participants with borderline personality disorder (BPD) and 52 controls To examine BDNF methylation and protein levels in individuals with BPD receiving intensive DBT (I-DBT) 4-week intensive DBT Blood (PBMCs) samples collected 1 week prior to beginning I-DBT and on last day of treatment -Baseline BDNF higher in BPD patients than controls Peripheral blood leukocytes analyzed -DNAm of BDNF ↑in non-responders and ↓in responders to therapy High-resolution melt analysis -Changes in methylation status over time were correlated with changes in measures of depression, hopelessness and impulsivity Pragya et al. (2023) 34 college students To examine the molecular and cellular effects of Preksha Dhyana meditation (PM) on the DNA methylome 8-week PM meditation and yoga sessions (60 min) Blood collected at baseline and at completion of 8-week intervention -PM meditation affects the DNA methylation profile of novice and healthy college students 8 weeks postintervention: 470 CpG sites were nominally differentially methylated between baseline and 8 weeks postintervention with 180 sites hypermethylated and 290 sites hypomethylated Whole blood analyzed -The most significant differences in methylation changes are in the 10 probes: cg14193459, cg15251779, cg21830259, cg09463055, cg19220607, cg03701082, cg01297639, cg09105687, cg20672131, and cg08355228 EPIC 850K array -Changes were related to in brain and metabolic signaling pathways Roberts et al. (2019) 111 with agoraphobia (with or without panic disorder) or specific phobias To examine the association between changes in DNAm in two regions of FKBP5 and therapy outcome at posttreatment and follow-up Exposure based CBT (4 plans) based on level of dental anxiety/fear Blood collected at baseline, completion of treatment and approximately 6 months following conclusion of treatment -Change in DNAm from pre- to posttreatment at CpG 5 of intron 7 of FKBP5; ↓ DNAm associated with greater response to therapy Whole blood analyzed -Percentage reduction in CGI severity associated with change in percentage -DNAm from pre- to post-treatment Mass array -Decreasing DNAm at one CpG site of intron 7 of FKBP5 was strongly associated with decreasing anxiety severity following exposure-based CBT. Schiele et al. (2020) 12 women with OCD (non-medicated) and 14 healthy female controls To investigate the impact of psychotherapies on MAOA methylation in patients with obsessive compulsive disorder (OCD) 8–10-week OCD specific CBT -Psychoeducation, exposure therapy, in vivo exposure (“flooding”), and response prevention and management techniques Blood collected prior to CBT and 8–10 weeks after intervention -Lower DNAm levels in OCD patients compared to controls Whole blood analyzed -Decreases in obsessive-compulsive disorder correlated with increases in MAOA methylation levels ( n = 7) Direct sequencing of MAOA Stoffel et al. (2019) 74 healthy medical students To explore the association of MBI and DNAm of SLC6A4 Intervention: 3-month MBI or control group Blood collected 1 day prior to intervention and one day after the conclusion of the intervention -Between group differences of SLC6A4 DNAm of 56 CpG sites Whole blood analyzed -Group-by-time interactions showed changes in mindfulness Pyrosequencing -Decreases in mean SLC6A4 DNAm of MBI group practicing mindfulness everyday -self-reported feelings of reduced stress after the MBI associated with a higher decrease in mean SLC6A4 DNAm Van Assche et al. (2023) 90 patients with major depressive disorder (Secondary analysis) To compare individuals with and without cognitive impairment at baseline and after a cognitive intervention 8-week personalized cognitive training intervention (16 treatment sessions designed to improve cognition, emotion processing, and social cognition) Blood collected at baseline and 8 weeks into the treatment -Analyses at baseline and at week 8 did not show any genome-wide significant CpGs comparing patients with and without cognitive impairment Whole blood analyzed -At baseline, of the top 12 CpGs, 3 had a DNAm difference of >2%. The most significant CpG comparing the groups with and without cognitive is located in an open sea region with predominantly regulatory qualities (cg10962945) EPIC 850k Array -At 8 weeks, the most significant CpG was located in open sea, though in exon 13 of the NTRK2-gene, linked to the BDNF pathway (cg13620631) Vinkers et al. (2021) Patients that obtained remission from PTSD ( n = 21), non-remission from PTSD ( n = 23) and trauma-exposed military controls ( n = 23). In addition, examined the extent to which differentially methylated regions (DMRs) were relevant for the development of PTSD in prospective cohort of 85 participants To examine longitudinal changes in genome-wide DNA methylation associated with trauma focused therapy for PTSD. Trauma-focused psychotherapy for PTSD, including eye movement desensitization reprocessing (EMDR) and trauma focused cognitive behavioral therapy Blood collected at baseline and 6–8 months later following therapy -Successful treatment of PTSD was associated with significant changes in DNA methylation in 12 DMRs in the genes: APOB, MUC4, EDN2, ZFP57, GPX6, CFAP45, AFF3, TP73, UBCLP1, RPL13P and two intergenic regions Whole blood analyzed -Only ZFP57 methylation was found to be associated with the development and successful treatment of PTSD. Genome-wide DNA methylation – Infinium MethylationEPIC BeadChip Wilker et al. (2023) 153 conflict survivors from Northern Uganda with PTSD. To investigate the relationship between methylation at the glucocorticoid receptor gene ( NR3C1 ) and PTSD treatment success of evidence-based psychotherapy 12 sessions of narrative exposure therapy (NET): Exposure-based psychotherapy for PTSD. Saliva collected at baseline and 4 and 10 months after completion of intervention -Treatment responders had a significant cg25535999 methylation increase after treatment with NET. Saliva analyzed -The strong reduction of PTSD symptoms over time was accompanied by an increase of NR3C1 cg25535999 methylation EPIC 850K array Xulu et al. (2021) 29 south African men with chronic exposure to trauma To investigate epigenetic signatures of psychotherapy for PTSD and appetitive aggression symptoms (AAS) CBT, narrative exposure therapy for forensic offender rehabilitation (FORNET) versus controls Saliva samples collected at baseline, 8 months, and 16 months following the intervention -Increased methylation of NR4A2 (and AUTS2 associated with reduced PTSD symptom severity in participants receiving FORNET Saliva analyzed -Positive association between AAS and methylation of TFAM . NGS (EpiTect methyl II array) Yehuda et al. (2013) 16 veterans with PTSD To determine the extent to which cytosine methylation in promoter regions of the glucocorticoid related genes ( NR3C1 and FKBP51 ) are associated with prolonged exposure psychotherapy treatment outcomes Prolonged exposure therapy Blood samples collected at baseline, after 12 weeks of treatment, and 3- months after completion of treatment Methylation of the NR3C1 exon 1F promoter at baseline predicted treatment outcome but was not altered in responders or non-responders at post-treatment or follow up PBMCs analyzed Methylation of NRC1 exon 1F promoter correlated with both post treatment PTSD symptom severity and change in pre to post treatment symptom severity Bisulfite genomic sequencing of bacterial clones Methylation of FKBP5 gene exon 1 promoter region did not predict treatment response but decreased in correlation with recovery Ziegler et al. (2016) 28 participants with panic disorder and 28 matched healthy controls To examine methylation changes of monoamine oxidase A ( MAOA ) gene following 6 weeks of CBT in participants with panic disorder 6-week CBT Whole blood was collected at baseline and at completion of 6-week CBT -Participants with panic disorder had lower MAOA methylation than health controls at baseline Whole blood analyzed -Greater panic disorder severity was associated with lower MAOA at baseline Bisulfite genomic sequencing - MAOA methylation increased to the level of controls in CBT responders Open in a new tab Note. *NGS = Next Generation Sequencing; PBMC = peripheral blood mononuclear cells. Intervention Characteristics The psychobehavioral interventions in 18 of the studies were categorized into five types: mindfulness or meditation-based intervention (MBI; n = 6), cognitive behavioral therapy (CBT; n = 5), trauma or exposure therapy ( n = 3), dialectical behavioral therapy (DBT; n = 2) and yoga ( n = 2). In addition, one study ( Pragya et al., 2023 ) evaluated an intervention combining mindfulness (meditation) and yoga, and two studies combined CBT with trauma therapy ( Hummel et al., 2022 ; Xulu et al., 2021 ). MBIs included relaxation exercises, such as meditation and breathing, as well as mind-body therapy for facilitating resilience and resourcefulness. They were performed for 8–9 weeks ( Bishop et al., 2018 , 2021 ; Dema et al., 2023 ; Pragya et al., 2023 ), 3 months ( Cozzolino et al., 2017 ), or intensively for one day ( Chaix et al., 2020 ). Most interventions consisted of 7–12 sessions conducted for 6–10 weeks. Various yoga poses were performed for 1 hour, 1 or 2 times per week, over 8–12 weeks. Sampling and Methods of DNA Methylation Analysis DNA was obtained from blood samples in 18 studies. DNA was sampled from peripheral blood mononuclear cells (PBMCs; n = 2; Chaix et al., 2017 ; Yehuda et al., 2013 ), white blood cells ( n = 2; Adhikari et al., 2022 ; Perroud et al., 2013 ), CD14 + monocytes ( n = 1; Hummel et al., 2022 ) and buffy coat ( n = 1; Garcia-Campayo et al., 2018 ). The remaining studies using blood samples analyzed DNAm in whole blood or did not identify blood cell type. One study identified blood cell type counts in their samples ( Hummel et al., 2022 ). Two studies ( Wilker et al., 2023 ; Xulu et al., 2021 ) sampled DNA from saliva, and one study ( Cozzolino et al., 2017 ) did not state whether the DNA samples were obtained from saliva or blood. Most studies limited the evaluation of DNAm at baseline (pre-intervention) and at the completion of the intervention, precluding understanding of the temporal pattern of DNAm changes, and whether observed changes in DNAm are stable over time, and/or if they associate with the dynamics of psychological outcomes. Several studies, however, did include one or two additional follow-up assessments beyond the immediate post-intervention sampling time point ( Dema et al., 2023 ; Moser et al., 2022 ; Roberts et al., 2019 ; Schiele et al., 2020 ; Vinkers et al., 2021 ; Wilker et al., 2023 ; Xulu et al., 2021 ; Yehuda et al., 2013 ). These follow-up times ranged from 2 months to 16 months. Of note, one cross-sectional study did not apply an intervention but compared DNAm profiles between a group practicing MBI and a control group without MBI experience ( Garcia-Campayo et al., 2018 ). The DNAm analysis used a variety of techniques to capture the complexity of DNAm patterns. Most used BeadChip arrays, namely the Illumina Infinium ® 450k array ( Chaix et al., 2020 ; Garcia-Campayo et al., 2018 ; Moser et al., 2022 ) and the Illumina Infinium ® EPIC 850k array ( Pragya et al., 2023 ; Van Assche et al., 2023 ; Wilker et al., 2023 ). Other methods included pyrosequencing ( Knoblich et al., 2018 ; Stoffel et al., 2019 ), bisulfite genomic sequencing ( Yehuda et al., 2013 ; Ziegler et al., 2016 ), and mass array techniques ( Harkess et al., 2016 ; Roberts et al., 2019 ). One study used high resolution melt analysis ( Perroud et al., 2013 ). Two studies used restriction enzyme methods—EpiTect Methyl II Array ( Xulu et al., 2021 ) and methylation-sensitive amplification polymorphism (MSAP) analysis ( Cozzolino et al., 2017 ). One study used targeted deep bisulfite sequencing and whole genomic bisulfite sequencing ( Hummel et al., 2022 ) and another used genome-wide DNA methylation with the Infinium MethylationEPIC BeadChip ( Vinkers et al., 2021 ). Finally, three studies used next generation sequencing (NGS) methods including the Illumina MiniSeq ( Dema et al., 2023 ), NextSeq 550 ( Adhikari et al., 2022 ), and MiSeq ( Bishop et al., 2018 , 2021 )) sequencers. Findings of DNA Methylation Genes A diverse set of candidate genes were evaluated across studies, including genes associated with stress, mood, immunity, inflammation, pain, and diseases such as psychiatric, cardiovascular, neurologic, metabolic, and cancer ( Table 2 ). Many of the genes showed DNAm changes in response to the interventions. For example, using a genome-wide DNA methylation approach, one study identified significant changes in DNAm in 12 gene regions, APOB, MUC4, EDN2, ZFP57, GPX6, CFAP45. AFF3, TP73, UBCLP1, RPL13P and two intergenic regions in individuals who exhibited PTSD symptom reduction after trauma focused psychotherapy ( Vinkers et al., 2021 ). One group of studies evaluated modification of DNAm of genes associated with the hypothalamic-pituitary adrenal (HPA) stress response system ( Table 2 ). These genes included NR3C1, the gene coding for the glucocorticoid receptor, FKBP5 a gene that decreases affinity of cortisol, for the glucocorticoid receptor, and GRE (glucocorticoid response element), a DNA sequence that binds to the GR to regulate gene transcription ( Timmermans et al., 2019 ). Findings related to these genes revealed differential DNAm in responders to an intervention compared to nonresponders. For example, individuals with PTSD who responded to narrative exposure therapy exhibited a pre- to post-intervention increase in methylation of the glucocorticoid receptor gene, NRC31 Wilker et al. (2023) ; Yehuda et al. (2013) found pre-treatment levels of methylation of NR3C1 predicted treatment outcome in veterans with PTSD undergoing exposure therapy, and that methylation status of FKBP5 correlated with treatment outcome ( Yehuda et al., 2013 ). Others showed that veterans with PTSD who responded to MBI exhibited an increase in methylation of FKBP5 and GRE from pre to post-intervention ( Bishop et al., 2018 , 2021 ). In contrast, individuals with agoraphobia who responded more positively to CBT exhibited a reduction in methylation of FKBP5 , while non-responders had either no change or an increase in DNAm ( Roberts et al., 2019 ). Methylation of genes which regulate mood, such as the serotonin transporter gene, SLC6A4, and the gene coding for the serotonin receptor, HTR3A, were also evaluated ( Table 2 ). For example, following a 3-month MBI program, healthy medical students exhibited decreased methylation of SLC6A4 post-MBI compared to a control group ( Stoffel et al., 2019 ). Other studies focused upon genes involved in neurotransmission such as the gene coding for monoamine oxidase (MAOA) a key enzyme regulating degradation of biogenic amines, like serotonin and dopamine, and catechol-o-methyltransferase (COMT), an enzyme which catalyzes the degradation of catecholamine neurotransmitters. An evaluation of MAOA methylation in women with panic disorder found lower methylation of MAOA at baseline compared to healthy controls, while after a CBT intervention the women responding to CBT exhibited MAOA methylation levels similar to that of controls ( Ziegler et al., 2016 ). In addition, women with polycystic ovary disease who completed an MBSR program had greater methylation of MAOA and COMT compared to a control group ( Dema et al., 2023 ). A few studies evaluated genes related to the immune and inflammatory response ( Table 2 ). For example, adults with chronic low back pain who completed a 12-week yoga intervention exhibited hypomethylation of genes from the nuclear factor-kappa B (NF-κB) inducing kinase (NIK/NF-κB) inflammatory signaling pathway ( Adhikari et al., 2022 ). Another study found women with psychological stress who completed an 8-week yoga program exhibited pre to post decreases in methylation of specific CpG sites for the TNF gene compared to a wait-list control group ( Harkess et al., 2016 ). In addition, long-term meditators were found to have greater methylation of genes related to transcription factors regulating the immune inflammatory response after a 1-day intensive MBI intervention compared to a meditation-naive group ( Chaix et al., 2020 ). Several studies focused on genes linked to diseases such as psychiatric, cardiovascular, neurologic, metabolic, and cancer ( Table 2 ). For example, a study evaluating an 8-week yoga and meditation intervention for college students ( Pragya et al., 2023 ) revealed that 470 CpG sites were differentially methylated from pre to post-intervention, with 290 sites with hypomethylation and 180 with hypermethylation in genes related to metabolic and brain function signaling pathways. Others showed hypomethylation of disease-related genes in long-term meditators compared to non-meditators ( Garcia-Campayo et al., 2018 ). Other studies found no changes in DNAm in response to treatment for PTSD ( Hummel et al., 2022 ) and DBT for bipolar disorder ( Knoblich et al., 2018 ). However, the latter study did find that greater methylation of APBA3 and MCF2 prior to treatment predicted a better psychobehavioral response to therapy ( Knoblich et al., 2018 ). Findings of DNA Methylation Related to Other Variables DNAm exhibited associations with stress and disease symptoms. For example, a greater decrease in DNAm in immune genes (LINE-1) and SLC6A4 was related to reduced stress following yoga and MBI, respectively ( Harkess et al., 2016 ; Stoffel et al., 2019 ). In individuals with PTSD, decreased symptoms were associated with increased DNAm in NRC31 ( Wilker et al., 2023 ), NR4A2, and AUTS2 genes ( Xulu et al., 2021 ). Additionally, decreased obsessive-compulsive disorder symptoms were associated with increased DNAm in MAOA ( Schiele et al., 2020 ), while decreased anxiety severity correlated with reduced DNAm in FKBP5 ( Roberts et al., 2019 ). Discussion Although most of the reviewed studies are pilot in nature, collectively the findings provide preliminary evidence supporting the concept that psychobehavioral interventions may be associated with changes in DNAm patterns. A variety of interventions were evaluated with most studies reporting a change in DNAm in response to the intervention. Further, for nearly half of the studies, differential DNAm was observed in those participants who exhibited improvement of symptoms (i.e., responders) post-intervention, as opposed to non-responders. In addition, some studies found pre-treatment methylation levels predicted the response to treatment ( Bishop et al., 2018 , 2021 ; Knoblich et al., 2018 ; Yehuda et al., 2013 ). These findings suggest that epigenetic profile may in the future provide clinical insight as to individual differences in response to therapy. Across the studies, those genes influenced by psychobehavioral interventions comprise a few broad functional categories, each having psychobehavioral relevance. These categories include genes regulating the HPA stress response and glucocorticoid action ( NR3C1, FKBP5 ), genes modulating mood ( SLC6A4, HTR3A ), genes promoting positive social interaction and emotions (OXTR), genes regulating neurotransmitter degradation activity ( COMT, MAOA ), and genes regulating the inflammatory and/or the immune response ( NIK/NFkB, TNF, ARG1 ). Moreover, the genes found responsive to psychobehavioral interventions have psychosocial relevance in that their methylation status is linked to early life adversity, adult stress reactivity, and risk for mental health disorders, like depression and PTSD ( Palma-Gudiel et al., 2015 ; Parade et al., 2021 ; Wang et al., 2018 ). For example, Yehuda et al. (2013) and Wilker et al. (2023) found adults with PTSD who responded to exposure therapy exhibited increased methylation of NR3C1 , the glucocorticoid receptor gene, which regulates the HPA axis by modulating the availability of the stress hormone, cortisol ( Palma-Gudiel et al., 2015 ). Methylation of FKBP51, which codes for the glucocorticoid binding protein and modulates the HPA stress response ( Zannas et al., 2016 ) , was found to decease in PTSD patients in association with recovery after exposure therapy ( Yehuda et al., 2013 ). Similarly, a decrease in methylation of FKBP5 was associated with a greater response to CBT exposure therapy for adults with agoraphobia ( Roberts et al., 2019 ). Differential methylation of genes regulating the serotonin neurotransmitter system, a key regulator of mood and stress, was reported for the serotonin transporter gene ( SLC6A4 ) in response to a yoga intervention for stressed medical students ( Stoffel et al., 2019 ) and for the serotonin receptor gene ( HTR3A ) following CBT in adults with panic disorder ( Moser et al., 2022 ). Methylation of MAOA, which regulates the degradation of biogenic amines (serotonin and dopamine), was increased in those with panic disorder who responded to CBT ( Ziegler et al., 2016 ), while an increase in MAOA methylation correlated with a decrease in obsessive-compulsive disorder symptoms in response to CBT ( Schiele et al., 2020 ). Dema et al. (2023) found an increase in methylation (hypermethylation) of both MAOA and COMT genes ( which code for enzymes that regulate catecholamine degradation) in women following a mindfulness-based stress reduction program compared to women randomized to a control group. Stress exposure results in heightened inflammation and an altered immune response, which can increase risk for psychopathology ( Ravi et al., 2021 ), and a few studies evaluated inflammatory/immune related genes. Following a yoga intervention, individuals with chronic back pain exhibited differential methylation of NIK/NFkB inflammatory signaling genes ( Adhikari et al., 2022 ), while stressed women exhibited differential methylation for the proinflammatory TNF gene after completion of a yoga program ( Harkess et al., 2016 ). Of note, Yehuda et al. (2013) did not find changes in NFkB methylation in either responders or non-responders following exposure therapy for PTSD; however, pretreatment methylation levels of NFkB predicted treatment outcome. Others found differential methylation of a macrophage effector gene ( ARG1) ( Kieler et al., 2021 ), after CBT for adults with panic disorder ( Moser et al., 2022 ). Most studies evaluated DNAm in a heterogeneous population of cells from whole blood without accounting for cell type. One study ( Hummel et al., 2022 ) isolated CD14 + monocytes from blood. Cell composition is dynamic over time, and immune cell distribution changes in association with stress levels ( Dhabhar, 2006 ), confounding the interpretation of DNAm changes. Further, assessing DNAm in a mixed population of cells is limited in that this approach is incapable of differentiating heterogeneous methylation patterns in different cells present within samples. Future analysis of single cell DNAm may transform our understanding of the epigenetic response to psychobehavioral interventions. It is noteworthy that two studies measured DNAm in saliva ( Wilker et al., 2023 ; Xulu et al., 2021 ), which offers distinct advantages. Collection is non-invasive and saliva DNAm correlates well with DNAm in blood ( Langie et al., 2016 , 2017 ; Thompson et al., 2013 ). Importantly, saliva DNAm demonstrates more similar patterns of DNAm to brain tissue as compared to blood ( Braun et al., 2019 ; Smith et al., 2015 ), and it correlates with front limbic brain function ( Chiarella et al., 2020 ; Ismaylova et al., 2018 ). Like blood, saliva is composed of several cell types, but it may be a better choice for investigating whether psychobehavioral interventions alter DNAm and improve psychological outcomes (Chiarella et al.; Ismaylova et al.). Currently, there is no consensus as to how long it takes for methylation changes to occur in response to psychobehavioral interventions or how long it takes for methylation changes to produce neuropsychological changes. Hence, more frequent assessment and longer-term follow-up may better capture the temporal dynamics of the psycho-biological response to interventions and the durability of the response. Multiple assessments over time may also provide greater ability to uncover individual differences in response to an intervention, and may explain, in part, variability in findings across studies. Although most of the reviewed studies limited assessments to pre- and post-intervention, several studies also included one or two follow-up time points post-intervention (range 2–16 months post-intervention). The clinical relevance of extending study follow-up is exemplified by the findings of Wilker et al. (2023) who captured distinct NR3C1 DNAm profile dynamics from completion of intervention to 10 months after intervention in therapy responders compared to non-responders. Overall, the findings of the reviewed studies are promising, despite research design limitations. Most enrolled a small number of participants, limiting statistical power. About half included a control group, with only one using randomization to groups ( Dema et al., 2023 ). None used an active control group. These limitations increase error related to time, engagement with an interventionist, and sample characteristics. Only a few studies measured gene expression levels and/or the associated gene protein products, both of which verify that changes in DNAm correlate with expected gene expression patterns and/or protein production, adding to functional/clinical relevance. Of those studies, Stoffel et al. (2019) observed decreases in SL6A4 methylation post-MBI in stressed medical students, which was associated with an increase in SL6A4 expression. Also, Yehuda et al. (2013) found decreased methylation of the FKBP5 gene ( FKBP51) exon 1 promoter region associated with recovery after PTSD exposure therapy, with responders exhibiting a corresponding higher FKBP5 gene expression at post-treatment than non-responders. Conclusions and Directions for Future Research Although assessment of DNAm as a marker of epigenetic changes associated with psychobehavioral interventions is in its infancy, it is a growing area of research with increasing studies being published over the past five years, and others currently in progress ( Saban et al., 2025 ; Taylor et al., 2024 ). Understanding whether psychobehavioral interventions alter DNAm may provide mechanistic insight as to how these interventions improve health. Moreover, findings of differential DNAm in those responding to an intervention relative to non-responders suggest DNAm may serve as a biologic marker of psycho-therapeutic success with potential to guide individualized treatment in the future. As costs for epigenome-wide association study analysis are reduced, there will be opportunities to identify novel DNAm areas of interest associated with psychobehavioral interventions. To address limitations of existing studies, large randomized controlled trials, ideally using an active control group with long term follow up, are needed. The individual characteristics and experiences of the sample (e.g., demographics, health, medication use, lifestyle factors, past trauma, underlying inflammation) need to be to be considered within the broader epigenetic regulatory network, as such biological and contextual variables can be integral to shaping the psycho-biological and DNAm response to an intervention. Lastly, to achieve functional relevance and biologic validity, it is critical that future studies assess the extent to which psychological outcomes are associated with changes in DNAm, as well as with corresponding changes in gene expression and gene protein products. Footnotes The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. Funding: The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Funding for this project was provided by the following grants: (R01AGO81251) to Saban & Taylor, (T32HL007343) to Taylor & Nyembwe, (K23MD019315) for Nowak, (ITM TL1) for De La Pena. ORCID iDs Karen L. Saban https://orcid.org/0000-0001-5767-5453 Linda Janusek https://orcid.org/0000-0003-2673-2296 Paula de la Pena https://orcid.org/0000-0001-9083-0136 Sueyeon Lee https://orcid.org/0000-0002-8532-7074 Dina Tell https://orcid.org/0000-0002-8141-7187 Herbert Mathews https://orcid.org/0009-0004-4033-9065 Alexandra L. Nowak https://orcid.org/0000-0003-3457-593X Alexandria Nyembwe https://orcid.org/0000-0002-6302-0899 References Adhikari B., Starkweather A., Xu W., Acabchuk R. L., Ramesh D., Eze B., Yang Y., Yang G. S., Walker J., Laubenbacher R., Park C. L. (2022). A feasibility study on yoga’s mechanism of action for chronic low back pain: Psychological and neurophysiological changes, including global gene expression and DNA methylation, following a yoga intervention for chronic low back pain. Pilot and feasibility studies, 8(1), 142. 10.1186/s40814-022-01103-2 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] Alasaari J. S., Lagus M., Ollila H. M., Toivola A., Kivimäki M., Vahtera J., Kronholm E., Härmä M., Puttonen S., Paunio T. (2012). Environmental stress affects DNA methylation of a CpG rich promoter region of serotonin transporter gene in a nurse cohort. PLoS One, 7(9), Article e45813. 10.1371/journal.pone.0045813 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] Arksey H., O'Malley L. (2005). Scoping studies: Towards a methodological framework. International Journal of Social Research Methodology, 8(1), 19–32. 10.1080/1364557032000119616 [ DOI ] [ Google Scholar ] Bishop J. R., Lee A. M., Mills L. J., Thuras P. D., Eum S., Clancy D., Erbes C. R., Polusny M. A., Lamberty G. J., Lim K. O. (2018). Methylation of FKBP5 and SLC6A4 in relation to treatment response to mindfulness based stress reduction for posttraumatic stress disorder. Frontiers in Psychiatry, 9, 418. 10.3389/fpsyt.2018.00418 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] Bishop J. R., Lee A. M., Mills L. J., Thuras P. D., Eum S., Clancy D., Erbes C. R., Polusny M. A., Lamberty G. J., Lim K. O. (2021). Corrigendum: Methylation of FKBP5 and SLC6A4 in relation to treatment response to mindfulness based stress reduction for posttraumatic stress disorder. Frontiers in Psychiatry, 12, Article 642245. 10.3389/fpsyt.2021.642245 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] Braun P. R., Han S., Hing B., Nagahama Y., Gaul L. N., Heinzman J. T., Grossbach A. J., Close L., Dlouhy B. J., Howard M. A., Kawasaki H., Potash J. B., Shinozaki G. (2019). Genome-wide DNA methylation comparison between live human brain and peripheral tissues within individuals. Translational Psychiatry, 9(1), 47. 10.1038/s41398-019-0376-y [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] Chaix R., Alvarez-López M. J., Fagny M., Lemee L., Regnault B., Davidson R. J., Lutz A., Kaliman P. (2017). Epigenetic clock analysis in long-term meditators. Psychoneuroendocrinology, 85, 210–214. 10.1016/j.psyneuen.2017.08.016 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] Chaix R., Fagny M., Cosin-Tomás M., Alvarez-López M., Lemee L., Regnault B., Davidson R. J., Lutz A., Kaliman P. (2020). Differential DNA methylation in experienced meditators after an intensive day of mindfulness-based practice: Implications for immune-related pathways. Brain, Behavior, and Immunity, 84(350), 36–44. 10.1016/j.bbi.2019.11.003 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] Chiarella J., Schumann L., Pomares F. B., Frodl T., Tozzi L., Nemoda Z., Yu P., Szyf M., Khalid-Khan S., Booij L. (2020). DNA methylation differences in stress-related genes, functional connectivity and gray matter volume in depressed and healthy adolescents. Journal of Affective Disorders, 271(3), 160–168. 10.1016/j.jad.2020.03.062 [ DOI ] [ PubMed ] [ Google Scholar ] Cozzolino M., Guarino F., Castiglione S., Cicatelli A., Celia G. (2017). Pilot study on epigenetic response to A mind-body treatment. Translational medicine @ UniSa, 17(7), 40–44. [ PMC free article ] [ PubMed ] [ Google Scholar ] Dema H., Videtič Paska A., Kouter K., Katrašnik M., Jensterle M., Janež A., Oblak A., Škodlar B., Bon J. (2023). Effects of mindfulness-based therapy on clinical symptoms and DNA methylation in patients with polycystic ovary syndrome and high metabolic risk. Current Issues in Molecular Biology, 45(4), 2717–2737. 10.3390/cimb45040178 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] de Mendoza V. B., Huang Y., Crusto C. A., Sun Y. V., Taylor J. Y. (2018). Perceived racial discrimination and DNA methylation among african American women in the InterGEN study. Biological Research For Nursing, 20(2), 145–152. 10.1177/1099800417748759 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] Dhabhar F. S. (2006). Stress-induced changes in immune cell distribution and trafficking: Implications for immunoprotection versus immunopathology. In Welsh C. J., Meagher M. W., Sternberg E. M. (Eds.), Neural and neuroendocrine mechanisms in host defense and autoimmunity. Springer. 10.1007/978-0-387-48334-4_2 [ DOI ] [ Google Scholar ] Draper B., Yee W. L., Pedrana A., Kyi K. P., Qureshi H., Htay H., Naing W., Thompson A. J., Hellard M., Howell J. (2022). Reducing liver disease-related deaths in the asia-pacific: The important role of decentralised and non-specialist led hepatitis C treatment for cirrhotic patients. The Lancet regional health. Western Pacific, 20(5), Article 100359. 10.1016/j.lanwpc.2021.100359 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] Duman E. A., Canli T. (2015). Influence of life stress, 5-HTTLPR genotype, and SLC6A4 methylation on gene expression and stress response in healthy Caucasian males. Biology of Mood & Anxiety Disorders, 5(2), 2. 10.1186/s13587-015-0017-x [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] Fiacco S., Gardini E. S., Mernone L., Schick L., Ehlert U. (2019). DNA methylation in healthy older adults with a history of childhood adversity-findings from the women 40+ healthy aging study. Frontiers in Psychiatry, 10, 777. 10.3389/fpsyt.2019.00777 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] Garcia-Campayo J., Puebla-Guedea M., Labarga A., Urdanoz A., Roldan M., Pulido L., de Morentin X. M., Perdones-Montero A., Montero-Marin J., Mendioroz M. (2018). Epigenetic response to mindfulness in peripheral blood leukocytes involves genes linked to common human diseases [Health Psychology & Medicine 3360]. Mindfulness, 9(4), 1146–1159. 10.1007/s12671-017-0851-6 [ DOI ] [ Google Scholar ] Harkess K. N., Ryan J., Delfabbro P. H., Cohen-Woods S. (2016). Preliminary indications of the effect of a brief yoga intervention on markers of inflammation and DNA methylation in chronically stressed women. Translational Psychiatry, 6(11), Article e965. 10.1038/tp.2016.234 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] Hummel E., Elgizouli M., Sicorello M., Leitão E., Beygo J., Schröder C., Zeschnigk M., Müller S., Herpertz S., Moser D., Kessler H., Horsthemke B., Kumsta R. (2022). No evidence for intervention-associated DNA methylation changes in monocytes of patients with posttraumatic stress disorder. Scientific Reports, 12(1), Article 17347. 10.1038/s41598-022-22177-1 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] Ismaylova E., Lévesque M. L., Pomares F. B., Szyf M., Nemoda Z., Fahim C., Vitaro F., Brendgen M., Dionne G., Boivin M., Tremblay R. E., Booij L. (2018). Serotonin transporter promoter methylation in peripheral cells and neural responses to negative stimuli: A study of adolescent monozygotic twins. Translational Psychiatry, 8(1), 147. 10.1038/s41398-018-0195-6 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] Kang J. I., Kim T. Y., Choi J. H., So H. S., Kim S. J. (2019). Allele-specific DNA methylation level of FKBP5 is associated with post-traumatic stress disorder. Psychoneuroendocrinology, 103, 1–7. 10.1016/j.psyneuen.2018.12.226 [ DOI ] [ PubMed ] [ Google Scholar ] Kanherkar R. R., Bhatia-Dey N., Csoka A. B. (2014). Epigenetics across the human lifespan. Frontiers in Cell and Developmental Biology, 2, 49. 10.3389/fcell.2014.00049 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] Kieler M., Hofmann M., Schabbauer G. (2021). More than just protein building blocks: How amino acids and related metabolic pathways fuel macrophage polarization. FEBS Journal, 288(12), 3694–3714. 10.1111/febs.15715 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] Knoblich N., Gundel F., Brückmann C., Becker-Sadzio J., Frischholz C., Nieratschker V. (2018). DNA methylation of APBA3 and MCF2 in borderline personality disorder: Potential biomarkers for response to psychotherapy. European Neuropsychopharmacology: The Journal of the European College of Neuropsychopharmacology, 28(2), 252–263. 10.1016/j.euroneuro.2017.12.010 [ DOI ] [ PubMed ] [ Google Scholar ] Kundakovic M., Gudsnuk K., Herbstman J. B., Tang D., Perera F. P., Champagne F. A. (2015). DNA methylation of BDNF as a biomarker of early-life adversity. Proceedings of the National Academy of Sciences of the United States of America, 112(22), 6807–6813. 10.1073/pnas.1408355111 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] Langie S. A., Szarc Vel Szic K., Declerck K., Traen S., Koppen G., Van Camp G., Schoeters G., Vanden Berghe W., De Boever P. (2016). Whole-genome saliva and blood DNA methylation profiling in individuals with a respiratory allergy. PLoS One, 11(3), Article e0151109. 10.1371/journal.pone.0151109 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] Langie S. A. S., Moisse M., Declerck K., Koppen G., Godderis L., Vanden Berghe W., Drury S., De Boever P. (2017). Salivary DNA methylation profiling: Aspects to consider for biomarker identification. Basic and Clinical Pharmacology and Toxicology, 121(Suppl Suppl 3), 93-101. 10.1111/bcpt.12721 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] Matosin N., Cruceanu C., Binder E. B. (2017). Preclinical and clinical evidence of DNA methylation changes in response to trauma and chronic stress. Chronic Stress (Thousand Oaks), 1 Article 2470547017710764. 10.1177/2470547017710764 [ DOI ] [ PMC free article ] [ PubMed ] Moser S., Martins J., Czamara D., Lange J., Müller-Myhsok B., Erhardt A. (2022). DNA-methylation dynamics across short-term, exposure-containing CBT in patients with panic disorder. Translational Psychiatry, 12(1), 46. 10.1038/s41398-022-01802-7 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] Na K. S., Chang H. S., Won E., Han K. M., Choi S., Tae W. S., Yoon H. K., Kim Y. K., Joe S. H., Jung I. K., Lee M. S., Ham B. J. (2014). Association between glucocorticoid receptor methylation and hippocampal subfields in major depressive disorder. PLoS One, 9(1), Article e85425. 10.1371/journal.pone.0085425 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] Olsson C. A., Foley D. L., Parkinson-Bates M., Byrnes G., McKenzie M., Patton G. C., Morley R., Anney R. J., Craig J. M., Saffery R. (2010). Prospects for epigenetic research within cohort studies of psychological disorder: A pilot investigation of a peripheral cell marker of epigenetic risk for depression. Biological Psychology, 83(2), 159–165. 10.1016/j.biopsycho.2009.12.003 [ DOI ] [ PubMed ] [ Google Scholar ] Page M. J., McKenzie J. E., Bossuyt P. M., Boutron I., Hoffmann T. C., Mulrow C. D., et al. (2021). The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ, 372, n71. 10.1136/bmj.n71 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] Palma-Gudiel H., Córdova-Palomera A., Leza J. C., Fañanás L. (2015). Glucocorticoid receptor gene (NR3C1) methylation processes as mediators of early adversity in stress-related disorders causality: A critical review. Neuroscience & Biobehavioral Reviews, 55, 520–535. 10.1016/j.neubiorev.2015.05.016 [ DOI ] [ PubMed ] [ Google Scholar ] Parade S. H., Huffhines L., Daniels T. E., Stroud L. R., Nugent N. R., Tyrka A. R. (2021). A systematic review of childhood maltreatment and DNA methylation: Candidate gene and epigenome-wide approaches. Translational Psychiatry, 11(1), 134. 10.1038/s41398-021-01207-y [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] Park C., Rosenblat J. D., Brietzke E., Pan Z., Lee Y., Cao B., Zuckerman H., Kalantarova A., McIntyre R. S. (2019). Stress, epigenetics and depression: A systematic review. Neuroscience & Biobehavioral Reviews, 102, 139–152. 10.1016/j.neubiorev.2019.04.010 [ DOI ] [ PubMed ] [ Google Scholar ] Perroud N., Salzmann A., Prada P., Nicastro R., Hoeppli M. E., Furrer S., Ardu S., Krejci I., Karege F., Malafosse A. (2013). Response to psychotherapy in borderline personality disorder and methylation status of the BDNF gene. Translational Psychiatry, 3(1), Article e207. 10.1038/tp.2012.140 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] Pragya S. U., Pragya S. C., Griswold A. J., Gu E., Mehta N. D., Uddin P., Veeramachaneni P., Mehta N., Mehta D., Abomoelak B. (2023). Preksha dhyana meditation effect on the DNA methylation signature in college students. Journal of Integrative and Complementary Medicine, 29(4), 224–233. 10.1089/jicm.2022.0713 [ DOI ] [ PubMed ] [ Google Scholar ] Ravi M., Miller A. H., Michopoulos V. (2021). The immunology of stress and the impact of inflammation on the brain and behavior. BJPsych Advances, 27(Suppl 3), 158–165. 10.1192/bja.2020.82 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] Roberts S., Keers R., Breen G., Coleman J. R. I., Jöhren P., Kepa A., Lester K. J., Margraf J., Scheider S., Teismann T., Wannemüller A., Eley T. C., Wong C. C. Y. (2019). DNA methylation of FKBP5 and response to exposure-based psychological therapy. American Journal of Medical Genetics Part B, Neuropsychiatric Genetics: The Official Publication of the International Society of Psychiatric Genetics, 180(2), 150–158. 10.1002/ajmg.b.32650 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] Saban K. L., Joyce C., Nyembwe A., Janusek L., Tell D., De La Pena P., Motley D., Shawahin L., Prescott L., Potts-Thompson S., Taylor J. Y. (2025). The effectiveness of a race-based stress reduction intervention on improving stress-related symptoms and inflammation in african American women at risk for cardiometabolic disease. In Protocol for recruitment and intervention for a randomized controlled trial. JMIR. In press. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] Schiele M. A., Thiel C., Deckert J., Zaudig M., Berberich G., Domschke K. (2020). Monoamine oxidase A hypomethylation in obsessive-compulsive disorder: Reversibility by successful psychotherapy? The international journal of neuropsychopharmacology, 23(5), 319–323. 10.1093/ijnp/pyaa016 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] Skinner H. G., Palma-Gudiel H., Stewart J. D., Love S. A., Bhatti P., Shadyab A. H., Wallace R. B., Salmoirago-Blotcher E., Manson J. E., Kroenke C. H., Belsky D. W., Li Y., Whitsel E. A., Zannas A. S. (2024). Stressful life events, social support, and epigenetic aging in the Women's Health Initiative. Journal of the American Geriatrics Society, 72(2), 349–360. 10.1111/jgs.18726 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] Smith A. K., Conneely K. N., Kilaru V., Mercer K. B., Weiss T. E., Bradley B., Tang Y., Gillespie C. F., Cubells J. F., Ressler K. J. (2011). Differential immune system DNA methylation and cytokine regulation in post-traumatic stress disorder. American Journal of Medical Genetics Part B, Neuropsychiatric Genetics: The Official Publication of the International Society of Psychiatric Genetics, 156B(6), 700–708. 10.1002/ajmg.b.31212 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] Smith A. K., Kilaru V., Klengel T., Mercer K. B., Bradley B., Conneely K. N., Ressler K. J., Binder E. B. (2015). DNA extracted from saliva for methylation studies of psychiatric traits: Evidence tissue specificity and relatedness to brain. American Journal of Medical Genetics Part B, Neuropsychiatric Genetics: The Official Publication of the International Society of Psychiatric Genetics, 168b(1), 36–44. 10.1002/ajmg.b.32278 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] Stoffel M., Aguilar-Raab C., Rahn S., Steinhilber B., Witt S. H., Alexander N., Ditzen B. (2019). Effects of mindfulness-based stress prevention on serotonin transporter gene methylation. Psychotherapy and Psychosomatics, 88(5), 317–319. 10.1159/000501646 [ DOI ] [ PubMed ] [ Google Scholar ] Stoffel M., Gardini E., Ehrenthal J. C., Abbruzzese E., Ditzen B. (2020). Evaluation of stress management and stress prevention using epigenetic markers. Verhaltenstherapie, 30(1), 18–27. 10.1159/000505595 [ DOI ] [ Google Scholar ] Suzuki M. M., Bird A. (2008). DNA methylation landscapes: Provocative insights from epigenomics. Nature Reviews Genetics, 9(6), 465–476. 10.1038/nrg2341 [ DOI ] [ PubMed ] [ Google Scholar ] Szyf M., Tang Y. Y., Hill K. G., Musci R. (2016). The dynamic epigenome and its implications for behavioral interventions: A role for epigenetics to inform disorder prevention and health promotion. Translational behavioral medicine, 6(1), 55–62. 10.1007/s13142-016-0387-7 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] Taylor J. Y., Jones-Patten A., Prescott L., Potts-Thompson S., Joyce C., Tayo B., Saban K. (2024). The race-based stress reduction intervention (RiSE) study on African American women in NYC and Chicago: Design and methods for complex genomic analysis. PLoS One, 19(4 April), Article e0295293. 10.1371/journal.pone.0295293 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] Thompson T. M., Sharfi D., Lee M., Yrigollen C. M., Naumova O. Y., Grigorenko E. L. (2013). Comparison of whole-genome DNA methylation patterns in whole blood, saliva, and lymphoblastoid cell lines. Behavior Genetics, 43(2), 168–176. 10.1007/s10519-012-9579-1 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] Timmermans S., Souffriau J., Libert C. (2019). A general introduction to glucocorticoid biology. Frontiers in Immunology, 10, 1545. 10.3389/fimmu.2019.01545 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] Turecki G., Meaney M. J. (2016). Effects of the social environment and stress on glucocorticoid receptor gene methylation: A systematic review. Biological Psychiatry, 79(2), 87–96. 10.1016/j.biopsych.2014.11.022 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] Uddin M., Aiello A. E., Wildman D. E., Koenen K. C., Pawelec G., de los S. R., Goldmann E., Galea S. (2010). Epigenetic and immune function profiles associated with posttraumatic stress disorder. Proceedings of the National Academy of Sciences of the United States of America, 107(20), 9470–9475. 10.1073/pnas.0910794107 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] Uddin M., Koenen K. C., Aiello A. E., Wildman D. E., de los S. R., Galea S. (2011). Epigenetic and inflammatory marker profiles associated with depression in a community-based epidemiologic sample. Psychological Medicine, 41(5), 997–1007. 10.1017/S0033291710001674 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] Van Assche E., Hohoff C., Zang J., Knight M. J., Baune B. T. (2023). Epigenetic modification related to cognitive changes during a cognitive training intervention in depression. Progress in neuro-psychopharmacology & biological psychiatry, 127, Article , 110835. 10.1016/j.pnpbp.2023.110835 [ DOI ] [ PubMed ] [ Google Scholar ] van der Laan L. C., Meeks K. A. C., Chilunga F. P., Agyemang C., Venema A., Mannens M., Zafarmand M. H., Klipstein-Grobusch K., Smeeth L., Adeyemo A., Henneman P. (2020). Epigenome-wide association study for perceived discrimination among sub-Saharan African migrants in Europe - the RODAM study. Scientific Reports, 10(1), 4919. 10.1038/s41598-020-61649-0 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] Vinkers C. H., Geuze E., van Rooij S. J. H., Kennis M., Schür R. R., Nispeling D. M., Smith A. K., Nievergelt C. M., Uddin M., Rutten B. P. F., Vermetten E., Boks M. P. (2021). Successful treatment of post-traumatic stress disorder reverses DNA methylation marks. Molecular Psychiatry, 26(4), 1264–1271. 10.1038/s41380-019-0549-3 [ DOI ] [ PubMed ] [ Google Scholar ] Wang Q., Shelton R. C., Dwivedi Y. (2018). Interaction between early-life stress and FKBP5 gene variants in major depressive disorder and post-traumatic stress disorder: A systematic review and meta-analysis. Journal of Affective Disorders, 225, 422–428. 10.1016/j.jad.2017.08.066 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] Wilker S., Vukojevic V., Schneider A., Pfeiffer A., Inerle S., Pauly M., Elbert T., Papassotiropoulos A., de Quervain D., Kolassa I. T. (2023). Epigenetics of traumatic stress: The association of NR3C1 methylation and posttraumatic stress disorder symptom changes in response to narrative exposure therapy. Translational Psychiatry, 13(1), 14. 10.1038/s41398-023-02316-6 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] Xulu K. R., Womersley J. S., Sommer J., Hinsberger M., Elbert T., Weierstall R., Kaminer D., Malan-Müller S., Seedat S., Hemmings S. M. J. (2021). DNA methylation and psychotherapy response in trauma-exposed men with appetitive aggression. Psychiatry Research , 295, Article 113608. 10.1016/j.psychres.2020.113608 [ DOI ] [ PubMed ] [ Google Scholar ] Yehuda R., Daskalakis N. P., Desarnaud F., Makotkine I., Lehrner A. L., Koch E., Flory J. D., Buxbaum J. D., Meaney M. J., Bierer L. M. (2013). Epigenetic biomarkers as predictors and correlates of symptom improvement following psychotherapy in combat veterans with PTSD. Frontiers in Psychiatry, 4, 118. 10.3389/fpsyt.2013.00118 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] Zannas A. S., Wiechmann T., Gassen N. C., Binder E. B. (2016). Gene-stress-epigenetic regulation of FKBP5: Clinical and translational implications. Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology, 41(1), 261–274. 10.1038/npp.2015.235 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] Ziegler C., Richter J., Mahr M., Gajewska A., Schiele M. A., Gehrmann A., Schmidt B., Lesch K. P., Lang T., Helbig-Lang S., Pauli P., Kircher T., Reif A., Rief W., Vossbeck-Elsebusch A. N., Arolt V., Wittchen H. U., Hamm A. O., Deckert J., Domschke K. (2016). MAOA gene hypomethylation in panic disorder-reversibility of an epigenetic risk pattern by psychotherapy. Translational Psychiatry, 6(4), Article e773. 10.1038/tp.2016.41 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] Articles from Biological Research for Nursing are provided here courtesy of SAGE Publications ACTIONS View on publisher site PDF (816.2 KB) Cite Collections Permalink RESOURCES Similar articles Cited by other articles Links to NCBI Databases Follow NCBI NCBI on X (formerly known as Twitter) NCBI on Facebook NCBI on LinkedIn NCBI on GitHub NCBI RSS feed Connect with NLM NLM on X (formerly known as Twitter) NLM on Facebook NLM on YouTube National Library of Medicine 8600 Rockville Pike Bethesda, MD 20894 Web Policies FOIA HHS Vulnerability Disclosure Help Accessibility Careers NLM NIH HHS USA.gov Back to Top

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