Biomarkers of Pathological Dissociation: A Systematic Review
Open accessAbstract
Pathological dissociation is a severe, debilitating and transdiagnostic psychiatric symptom. This review identifies biomarkers of pathological dissociation in a transdiagnostic manner to recommend the most promising research and treatment pathways in support of the precision medicine framework. A total of 205 unique studies that met inclusion criteria were included. Studies were divided into four biomarker categories, namely neuroimaging, psychobiological, psychophysiological and genetic biomarkers. The dorsomedial and dorsolateral prefrontal cortex, bilateral superior frontal regions, (anterior) cingulate, posterior association areas and basal ganglia are identified as neurofunctional biomarkers of pathological dissociation and decreased hippocampal, basal ganglia and thalamic volumes as neurostructural biomarkers. Increased oxytocin and prolactin and decreased tumor necrosis factor alpha (TNF-α) are identified as psychobiological markers. Psychophysiological biomarkers, including blood pressure, heart rate and skin conductance, were inconclusive. For the genetic biomarker category studies related to dissociation were limited and no clear directionality of effect was found to warrant identification of a genetic biomarker. Recommendations for future research pathways and possible clinical applicability are provided.
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Three neuromodulatory and neurotransmitter systems may play a role in generating dissociative experiences.
“In this section, we briefly overview three neuromodulatory and neurotransmitter systems that may play a role in generating dissociative experiences (see [105–107] for reviews, and [108] for recent discussion).”
From Treatment of dissociative identity disorder: leveraging neurobiology to optimize success (2024) · cites this paper as [106]
Section 4.5.1 (page unavailable) reviews associations between dissociative symptoms and several neurochemical measures, including oxytocin, norepinephrine, and glutamate. That supports a possible neurochemical role, but the review does not identify three neuromodulatory or neurotransmitter systems as generating dissociative experiences; its findings concern biomarkers and associations. (LLM, conf=0.77)
Experimental — accuracy not yet measuredA recent extensive systematic review confirmed the present findings, citing inconclusive results due to most studies reporting no effects.
“This review confirmed our findings, citing inconclusive results due to most studies reporting no effects.”
From Trauma-related dissociation and the autonomic nervous system: a systematic literature review of psychophysiological correlates of dissociative experiencing in PTSD patients (2022) · cites this paper as Roydeva & Reinders, 2021
Section 4.5 (page not available) reports mixed findings and says most studies found no correlation between psychophysiological responses and dissociative symptoms; null findings were also most frequent in the genetic studies. But this does not establish that most studies across the entire review found no effects. Section 4.6.2 says the authors found some convergence and proposed diagnostic biomarkers, so the claim overgeneralizes the review’s conclusions. (LLM, conf=0.84)
Experimental — accuracy not yet measuredThe authors of that review concluded that none of the reviewed physiological measures could be recommended as a biomarker of pathological dissociation.
“The authors further concluded that none of the reviewed physiological measures could be recommended as a biomarker of pathological dissociation (Roydeva & Reinders, 2021).”
From Trauma-related dissociation and the autonomic nervous system: a systematic literature review of psychophysiological correlates of dissociative experiencing in PTSD patients (2022) · cites this paper as Roydeva & Reinders, 2021
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Neural and Behavioral Correlates of Peritraumatic Dissociation in an Acutely Traumatized Sample
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EEG Studies of Two Multiple Personalities and a Control
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Neuroimaging in functional neurological disorder: State of the field and research agenda
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“As recommended by Roydeva and Reinders (2021), future research should aim to increase the specificity of biomarkers to PTSD-related dissociation, for instance by testing the robustness of these psychophysiological correlates across other psychopathologies (e.g. depression or anxiety).”
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Persistent Dissociation and Its Neural Correlates in Predicting Outcomes After Trauma Exposure
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Deconstructing dissociation: a triple network model of trauma-related dissociation and its subtypes
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Self-citationDissociation, trauma, and borderline personality disorder
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Self-citationVissia, E. M., Lawrence, A. J., Chalavi, S., Giesen, M. E., Draijer, N., Nijenhuis, E. R. S., Aleman, A., Veltman, D. J., & Reinders, A. A. T. S. (2022) · BJPsych Open · doi:10.1192/bjo.2022.22 · Cited by 28 · see citing works
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Dissociation in patients with epilepsy and functional seizures: A narrative review of the literature
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Treatment of dissociative identity disorder: leveraging neurobiology to optimize success
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“Second, we cover recent neurobiological findings specific to DID (for recent reviews see [17,105]).”
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The Molecular Genetics of Dissociative Symptomatology: A Transdiagnostic Literature Review
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Dissociative Symptoms and Interoceptive Integration
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Normal amygdala morphology in dissociative identity disorder
Reinders, A. A. T. S., Dimitrova, L. I., Schlumpf, Y. R., Vissia, E. M., Nijenhuis, E. R. S., Jäncke, L., Chalavi, S., & Veltman, D. J. (2022) · BJPsych Open · doi:10.1192/bjo.2022.36 · Cited by 10 · see citing works
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The Induction of Dissociative States: A Meta-Analysis
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Pedunculopontine-induced cortical decoupling as the neurophysiological locus of dissociation.
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Proposition of Two Subtypes of Patients at Risk of Suicide: Pain Hypersensitive Vs. Dissociative
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Neurostructural brain imaging study of trait dissociation in healthy children
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Self-citationHow-To Study Dissociative Symptoms in a Broad Range of Mental Disorders: A Methodological Primer
Danböck, S. K., Mertens, Y. L., Kulla, P., Seitz, K. I., & Schalinski, I. (2025) · Journal of Trauma & Dissociation · doi:10.1080/15299732.2025.2481474 · Cited by 4 · see citing works
Dissociative Symptoms and Disorders in Patients With Bipolar Disorders: A Scoping Review
Rajkumar, R. P. (2022) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2022.925983 · Cited by 4 · see citing works
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“…a dysfunctional neurophysiological profile characterized by top-down inhibition of activity in the prefrontal cortex and limbic emotional responses (Roydeva & Reinders, 2021), which in unimpaired individuals serves an evolutionary function (i.e., to minimize anxiety whilst maintaining behavioral…”
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CATT haplotype of the FKBP5 gene and dissociative phenomenology
Moser, S., Knoblauch, H., Müller‐Myhsok, B., Katrinli, Ş., Mekawi, Y., Gillespie, C. F., Fani, N., Bradley, B., Michopoulos, V., Stevens, J. S., et al. (2025) · Scientific Reports · doi:10.1038/s41598-025-13865-9 · Cited by 3 · see citing works
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The role of the immune system in depersonalisation disorder
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Dissociative experiences alter resting state functional connectivity after childhood abuse
von Schröder, C., Nkrumah, R. O., Demirakça, T., Ende, G., & Schmahl, C. G. (2025) · Scientific Reports · doi:10.1038/s41598-024-79023-9 · Cited by 3 · see citing works
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Dissociation and Brain Rhythms: Pitfalls and Promises
Grent-‘t-Jong, T., Melloni, L., & Uhlhaas, P. J. (2021) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2021.790372 · Cited by 3 · see citing works
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Dissociation As a Mechanism of Risk for Interpersonal Victimization Among Adolescent Girls
Kouri, N. A., Simon, V. A., & Partridge, T. (2024) · Journal of Interpersonal Violence · doi:10.1177/08862605241248431 · Cited by 2 · see citing works
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Does Dissociation Have an Emotion-Regulation Function? Evidence From Daily Life and the Laboratory
Heekerens, J. B., Gross, J. J., Kreibig, S. D., Ober, H., Eichentopf, R., Dittrich, T., Lebovitz, J. G., Hellmann‐Regen, J., Wingenfeld, K., & Roepke, S. (2026) · Clinical Psychological Science · doi:10.1177/21677026251396803 · Cited by 2 · see citing works
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Assessing malingering and personality styles in dissociative identity disorder: a case study
Lanfranco, R. C., Martínez-Aguayo, J. C., & Marcelo Arancibia, M. (2023) · Neurocase · doi:10.1080/13554794.2024.2348218 · Cited by 3 · see citing works
Dissociative Disorders: Neuroimaging as a New Narrative
Modesti, M. N., & CASALE, A. D. (2025) · Springer eBooks · doi:10.1007/978-3-031-73368-0_47 · Cited by 2 · see citing works
Shaw, S. B., Terpou, B. A., Densmore, M., Théberge, J., Frewen, P., McKinnon, M. C., & Lanius, R. A. (2022) · doi:10.31234/osf.io/b6kdm · Cited by 2 · see citing works
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A network analysis of peritraumatic dissociation and subsequent intrusive memories
Maccallum, F., Gutmann, H., Creamer, M. C., O'Donnell, M. L., Forbes, D., McFARLANE, A. C., Silove, D. M., & Bryant, R. A. (2025) · European Journal of Psychotraumatology · doi:10.1080/20008066.2025.2555793 · Cited by 1 · see citing works
Dissociation in functional/dissociative seizures: Alignment with neurobiology across the lifespan
Hingray, C., Popkirov, S., Kozlowska, K., Pretorius, C., Sarudiansky, M., El‐Hage, W., Zhou, D., Ertan, D., LaFrance, W. C., Jr., & Reuber, M. (2026) · Epilepsia · doi:10.1111/epi.70032 · Cited by 1 · see citing works
The heart of the self: An interoceptive perspective on the psychotherapeutic process
Hauke, G., & Critchley, H. (2026) · Consciousness and Cognition · doi:10.1016/j.concog.2026.104032 · Cited by 1 · see citing works
A spontaneous dissociative episode during an EEG experiment
Jamieson, G. A., Cardeña, E., & Pascalis, V. D. (2023) · Brain and Cognition · doi:10.1016/j.bandc.2023.106121 · Cited by 1 · see citing works
Dissociation and Post-traumatic Complexity in the Forensic Assessment of Psychological Injury
Bailey, T. D., Benincasa, C. A., & Boyer, S. M. (2025) · Springer eBooks · doi:10.1007/978-3-031-69734-0_6 · Cited by 1 · see citing works
Turkish adaptation of the scale of dissociative activities
Yılmaz, F., & Akcan, G. (2022) · European Journal of Trauma & Dissociation · doi:10.1016/j.ejtd.2022.100270 · Cited by 1 · see citing works
Imaging dissociation in post-traumatic stress disorder
Quidé, Y. (2023) · BJPsych Open · doi:10.1192/bjo.2023.25 · Cited by 1 · see citing works
Lynn, S. J., Sleight, F. G., Merckelbach, H. L. G. J., Condon, L. P., Lilienfeld, S. O., & der Kloet, D. V. H. (2023) · Elsevier eBooks · doi:10.1016/b978-0-323-91497-0.00181-8 · Cited by 1 · see citing works
Aksen, D. E., & Lynn, S. J. (2025) · Cambridge University Press eBooks · doi:10.1017/9781009086264.008 · Cited by 1 · see citing works
la Rie, D., & Wageningen, S.-V. (2022) · Bohn Stafleu van Loghum eBooks · doi:10.1007/978-90-368-2711-9_2
Heekerens, J. B., Gross, J. J., Kreibig, S. D., Wingenfeld, K., & Röpke, S. (2023) · doi:10.31234/osf.io/aq63g
Garcia, S., Coetzee, S., & Belaunzaran, M. (2023) · Springer eBooks · doi:10.1007/978-3-031-39854-4_43
Fisher, K. A., & Adrian, T. (2023) · Springer eBooks · doi:10.1007/978-3-031-39854-4_5
Genetics and Dissociative Identity Disorder (DID)
Bonsu, N., Sreeram, V., & Hasan, F. M. (2023) · Springer eBooks · doi:10.1007/978-3-031-39854-4_22
Psikotravmatoloji ve Dissosiyatif Bozukluklar
Özen, Y. (2024) · Akademisyen Kitabevi eBooks · doi:10.37609/akya.3079
Aktuelle Forschungsergebnisse zur Neuropsychologie dissoziativer Anfälle
Jungilligens, J., Hoppe, C., & Reuner, G. (2024) · Clinical Epileptology · doi:10.1007/s10309-024-00681-w
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Jungilligens, J., Hoppe, C., & Reuner, G. (2024) · Clinical Epileptology · doi:10.1007/s10309-024-00707-3
Dissociative Disorders: Neuroimaging as a New Narrative
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Dissociation in Borderline Personality Disorder
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Grundlagen der Diagnostik und Therapie
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Dissociative Disorders: Symptomatology and Genes
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Bibliometric and Visualization Analysis of Dissociation in English Literature Based on CiteSpace
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Dissociative Disorders: Symptomatology and Genes
Rajkumar, R. P. (2025) · Springer eBooks · doi:10.1007/978-3-031-73368-0_48
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- Authors
- Roydeva, M. I., & Reinders, A. A. T. S.
- Affiliations
- King's College London (GB)
- Corresponding author
- Reinders, Antje A.T.S.
- Venue
- Neuroscience & Biobehavioral Reviews
- Publisher
- Elsevier BV
- Published
- 2021-04
- Volume
- 123
- Pages
- 120-202
- ISSN
- 0149-7634 (ISSN-L)
- OpenAlex
- W3107607617
- Cited by
- 116
- References
- 350
- Citations by year
- 2026: 12 · 2025: 25 · 2024: 31 · 2023: 25 · 2022: 19 · 2021: 4
- FWCI
- 1.98
- Type
- journal article
- Language
- en
- Open access
- green
- kclpure.kcl.ac.uk
- Licence
- Locations
- Neuroscience & Biobehavioral Reviews (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion, other-oa)
- Funders
- National Institute for Health Research
- King's College London
- King’s College London
- South London and Maudsley NHS Foundation Trust
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Psychosomatic Disorders and Their Treatments
- Social Sciences › Psychology › Clinical Psychology › Psychoanalysis and Psychopathology Research
- Social Sciences › Arts and Humanities › Philosophy › Mental Health and Psychiatry
- Keywords
- pathological dissociation, transdiagnostic psychiatry, neuroimaging biomarkers, oxytocin, prolactin, TNF-α, genetic biomarkers, prefrontal cortex, hippocampus, basal ganglia, thalamus, precision medicine
- MeSH terms
- Mental Disorders, Frontal Lobe, Hippocampus, Humans, Biomarkers, Neuroimaging
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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