Neuromechanistic Pathways Underlying Mindfulness-Based Interventions for Core Post-Traumatic Stress Disorder Symptoms: A Systematic Review
Abstract
Background: Prior reviews indicate mindfulness-based interventions (MBIs) alleviate PTSD symptoms through fear extinction and cognitive restructuring, yet critical gaps remain in clarifying their neural mechanisms. Objective: This systematic review integrates empirical evidence on the neural correlates of standardized MBIs (e.g., MBSR, MBCT) in ameliorating core PTSD symptoms (intrusions, avoidance, and negative cognitions) to inform clinical translation and future research. Method: The review systematically searched PubMed, Web of Science, and Google Scholar (2015–2025) for English-language studies examining neurobiological mechanisms of MBIs for PTSD, using terms PTSD, mindfulness interventions, and neurobiological measures. Results: MBIs reduced intrusive symptoms by regulating limbic hyperactivity, enhancing prefrontal control over traumatic memory activation, strengthening amygdala-prefrontal connectivity, and attenuating autonomic reactivity. For avoidance behaviors, MBIs increased insular and temporoparietal junction (TPJ) activation during emotion regulation, restored connectivity between default mode, salience, and executive control networks, and modulated FKBP5 methylation to optimize hypothalamic-pituitary-adrenal (HPA) axis function. MBIs alleviated negative cognitions by optimizing neural oscillations (theta, alpha) and cortisol dynamics, reducing hypervigilance and cognitive rigidity.
References
Yehuda R, Hoge CW, McFarlane AC, et al., 2015, Post-traumatic Stress Disorder. Nature Reviews Disease Primers, 1(1): 15057. http://doi.org/10.1038/nrdp.2015.57
American Psychiatric Association, 2022, Diagnostic and Statistical Manual of Mental Disorders (5th ed., text rev.). https://doi.org/10.1176/appi.books.9780890425787
Goldstein RB, Smith SM, Chou SP, et al., 2016, The Epidemiology of DSM-5 Posttraumatic Stress Disorder in the United States: Results from the National Epidemiologic Survey on Alcohol and Related Conditions-III. Social Psychiatry and Psychiatric Epidemiology, 51(8): 1137–1148. https://doi.org/10.1007/s00127-016-1208-5
Iribarren J, Prolo P, Neagos N, et al., 2005, Post-Traumatic Stress Disorder: Evidence-Based Research for the Third Millennium. Evid. Based Complement. Alternative Medicine, 2005(2): 503–512. https://doi.org/10.1093/ecam/neh127
Agbaria L, Mirzaei F, A’amar NO, et al., 2025, The Neuroscientific Basis of Post-traumatic Stress Disorder (PTSD): From Brain to Treatment. Progress in Brain Research, 2025(291): 427–468. https://doi.org/10.1016/bs.pbr.2025.01.009
Simone MB, Giulia B, Daniela P, 2017, Appetitive and Aversive Motivation in Dysphoria: A Time-domain and Time-Frequency Study of Response Inhibition. Biological Psychology, 2017(125): 12–27. https://doi.org/10.1016/j.biopsycho.2017.02.007
Lanius RA, Williamson PC, Bluhm RL, et al., 2005, Functional Connectivity of Dissociative Responses in Posttraumatic Stress Disorder: A Functional Magnetic Resonance Imaging Investigation. Biological Psychiatry, 2005(57): 873–884. https://doi.org/10.1016/j.biopsych.2005.01.011
Kunimatsu A, Yasaka K, Akai H, et al., 2020, MRI Findings in Posttraumatic Stress Disorder. Journal of Magnetic Resonance Imaging, 52(2): 380–396. https://doi.org/10.1002/jmri.26929
Resick PA, Wachen JS, Mintz J, et al., 2015, A Randomized Clinical Trial of Group Cognitive Processing Therapy Compared with Group Present-centered Therapy for PTSD among Active Duty Military Personnel. Journal of Consulting and Clinical Psychology, 83(6): 1058–1068. https://doi.org/10.1037/ccp0000016
Frost ND, Laska KM, Wampold BE, 2014, The Evidence for Present-centered Therapy as a Treatment for Posttraumatic Stress Disorder. Journal of Traumatic Stress, 27(1): 1–8. https://doi.org/10.1002/jts.21881
Kearney DJ, McDermott K, Malte C, et al., 2013, Effects of Participation in a Mindfulness Program for Veterans with Posttraumatic Stress Disorder: A Randomized Controlled Pilot Study. Journal of Clinical Psychology, 69(1): 14–27. https://doi.org/10.1002/jclp.21911
Alsubaie M, Abbott R, Dunn B, et al., 2017, Mechanisms of Action in Mindfulness-based Cognitive Therapy (MBCT) and Mindfulness-based Stress Reduction (MBSR) in People with Physical and/or Psychological Conditions: A Systematic Review. Clinical Psychology Review, 2017(55): 74–91. https://doi.org/10.1016/j.cpr.2017.04.008
Lloyd A, White R, Eames C, et al., 2018, The Utility of Home-practice in Mindfulness-based Group Interventions: A Systematic Review. Mindfulness, 9(3): 673–692. https://doi.org/10.1007/s12671-017-0813-z
Berghoff CR, Tull MT, 2019, Third-wave Behavioral Therapies for the Co-occurrence of PTSD and Substance Use Disorders, in Posttraumatic Stress and Substance Use Disorders. Routledge, London, 260–282. https://doi.org/10.4324/9781315442648-14
Goldberg SB, Riordan KM, Sun S, et al., 2020, Efficacy and Acceptability of Mindfulness-based interventions for Military Veterans: A Systematic Review and Meta-analysis. Journal of Psychosomatic Research, 2020(138): 110232. https://doi.org/10.1016/j.jpsychores.2020.110232
Boyd JE, Lanius RA, McKinnon MC, 2018, Mindfulness-based Treatments for Posttraumatic Stress Disorder: A Review of the Treatment Literature and Neurobiological Evidence. Journal of Psychiatry and Neuroscience, 43(1): 7–25. https://doi.org/10.1503/jpn.170021
Mak BSW, Zhang D, Powell CLYM, et al., 2024, Effects of Mindfulness-based Cognitive Therapy for Chinese Adults with PTSD Symptoms: Protocol for a Randomised Controlled Trial. BMC Psychiatry, 24(1): 400. https://doi.org/10.1186/s12888-024-05840-x
Powers A, Lathan EC, Dixon HD, et al., 2023, Primary Care-based Mindfulness Intervention for Posttraumatic Stress Disorder and Depression Symptoms among Black Adults: A Pilot Feasibility and Acceptability Randomized Controlled Trial. Psychological Trauma: Theory, Research, Practice, and Policy, 15(5): 858–867. https://doi.org/10.1037/tra0001390
Bishop JR, Lee AM, Mills LJ, et al., 2018, Methylation of FKBP5 and SLC6A4 in Relation to Treatment Response to Mindfulness Based Stress Reduction for Posttraumatic Stress Disorder. Frontiers in Psychiatry, 2018(9): 418. https://doi.org/10.3389/fpsyt.2018.00418
Eyni S, Musavi SE, Shoae Ardabili H, 2024, Acceptance of Chronic Pain in Veterans with PTSD Based on Post-traumatic Growth and Pain Catastrophizing: The Mediating Role of Mindfulness. European Journal of Trauma & Dissociation, 8(2): 100398. https://doi.org/10.1016/j.ejtd.2024.100398
Lee A, Thuras P, Baller J, et al., 2024, Serotonin Transporter (SLC6A4) and FK506-binding Protein 5 (FKBP5) Genotype and Methylation Relationships with Response to Meditation in Veterans with PTSD. Molecular Neurobiology, 61(11): 9608–9622. https://doi.org/10.1007/s12035-024-04096-6
Hölzel BK, Carmody J, Vangel M, et al., 2011, Mindfulness Practice Leads to Increases in Regional Brain Gray Matter Density. Psychiatry Research, 191(1): 36–43. https://doi.org/10.1016/j.pscychresns.2010.08.006
Bremner JD, Mishra S, Campanella C, et al., 2017, A Pilot Study of the Effects of Mindfulness-Based Stress Reduction on Post-traumatic Stress Disorder Symptoms and Brain Response to Traumatic Reminders of Combat in Operation Enduring Freedom/Operation Iraqi Freedom Combat Veterans with Post-traumatic Stress Disorder. Frontiers in psychiatry, 2017(8): 157. https://doi.org/10.3389/fpsyt.2017.00157
Maruyama BA, Abrams G, Kornblith E, et al., 2023, Improvement in Executive Functioning after Goal-Oriented Attentional Self-regulation Training is Associated with Reduction in PTSD Hyperarousal Symptoms among Veterans with Comorbid PTSD and Mild TBI. Applied Neuropsychology: Adult, 30(5): 503–511. https://doi.org/10.1080/23279095.2021.1960531
Ghaedi-Heidari F, Izadi M, Seyedbagheri S, et al., 2024, The Effect of Mindfulness on Posttraumatic Growth of Mothers of Premature Infants Admitted to Neonatal Intensive Care Unit. Journal of Clinical Psychology in Medical Settings, 31(1): 19–25. https://doi.org/10.1007/s10880-023-09961-5
Somohano VC, Kaplan J, Newman AG, et al., 2022, Formal Mindfulness Practice Predicts Reductions in PTSD Symptom Severity Following a Mindfulness-based Intervention for Women with Co-occurring PTSD and Substance Use Disorder. Addiction Science & Clinical Practice, 17(1): 51. https://doi.org/10.1186/s13722-022-00333-2
Bedford CE, Nakamura Y, Marchand WR, et al., 2022, Heightened Autonomic Reactivity to Negative Affective Stimuli among Active Duty Soldiers with PTSD and Opioid-treated Chronic Pain. Psychiatry Research, 2022(309): 114394. https://doi.org/10.1016/j.psychres.2022.114394
Guendelman S, Bayer M, Prehn K, et al., 2022, Towards a Mechanistic Understanding of Mindfulness-based Stress Reduction (MBSR) using an RCT Neuroimaging Approach: Effects on Regulating own Stress in Social and non-social Situations. Neuroimage, 2022(254): 119059. https://doi.org/10.1016/j.neuroimage.2022.119059
Molteni L, Gosling CJ, Fagan HA, et al., 2024, Effects of Mindfulness-based Interventions on Symptoms and Interoception in Trauma-related Disorders and Exposure to Traumatic Events: Systematic Review and Meta-analysis. Psychiatry Research, 2024(336): 115897. https://doi.org/10.1016/j.psychres.2024.115897
Yue WL, Ng KK, Koh AJ, et al., 2023, Mindfulness-based Therapy Improves Brain Functional Network Reconfiguration Efficiency. Translational Psychiatry, 13(1): 345. https://doi.org/10.1038/s41398-023-02642-9
Gallegos AM, Heffner KL, Cerulli C, et al., 2020, Effects of Mindfulness Training on Posttraumatic Stress Symptoms from a Community-based Pilot Clinical Trial Among Survivors of Intimate Partner Violence. Psychological Trauma: Theory, Research, Practice, and Policy, 12(8): 859–868. https://doi.org/10.1037/tra0000975
Kang SS, Sponheim SR, Lim KO, 2022, Interoception Underlies Therapeutic Effects of Mindfulness Meditation for Posttraumatic Stress Disorder: A Randomized Clinical Trial. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, 7(8): 793–804. https://doi.org/10.1016/j.bpsc.2021.10.005
Shapira I, Richman J, Pace TWW, et al., 2022, Biomarker Response to Mindfulness Intervention in Veterans Diagnosed with Post-traumatic Stress Disorder. Mindfulness, 13(10): 2448–2460. https://doi.org/10.1007/s12671-022-01969-6
Best RD, Ozmeral A, Grinberg AS, et al., 2024, Pain Acceptance as a Change Mechanism for Mindfulness-based Cognitive Therapy for Migraine. Journal of Behavioral Medicine, 47(3): 471–482. https://doi.org/10.1007/s10865-024-00475-5
