Impaired learning, memory, and extinction in posttraumatic stress disorder: translational meta-analysis of clinical and preclinical studies
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Abstract
Current evidence-based treatments for post-traumatic stress disorder (PTSD) are efficacious in only part of PTSD patients. Therefore, novel neurobiologically informed approaches are urgently needed. Clinical and translational neuroscience point to altered learning and memory processes as key in (models of) PTSD psychopathology. We extended this notion by clarifying at a meta-level (i) the role of information valence, i.e. neutral versus emotional/fearful, and (ii) comparability, as far as applicable, between clinical and preclinical phenotypes. We hypothesized that cross-species, neutral versus emotional/fearful information processing is, respectively, impaired and enhanced in PTSD. This preregistered meta-analysis involved a literature search on PTSD+Learning/Memory+Behavior, performed in PubMed. First, the effect of information valence was estimated with a random-effects meta-regression. The sources of variation were explored with a random forest-based analysis. The analyses included 92 clinical ( N = 6732 humans) and 182 preclinical ( N = 6834 animals) studies. A general impairment of learning, memory and extinction processes was observed in PTSD patients, regardless of information valence. Impaired neutral learning/memory and fear extinction were also present in animal models of PTSD. Yet, PTSD models enhanced fear/trauma memory in preclinical studies and PTSD impaired emotional memory in patients. Clinical data on fear/trauma memory was limited. Mnemonic phase and valence explained most variation in rodents but not humans. Impaired neutral learning/memory and fear extinction show stable cross-species PTSD phenotypes. These could be targeted for novel PTSD treatments, using information gained from neurobiological animal studies. We argue that apparent cross-species discrepancies in emotional/fearful memory deserve further in-depth study; until then, animal models targeting this phenotype should be applied with utmost care.
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Methylation differences in NTRK2 have been linked to variation in recognition memory performance and lifetime PTSD risk.
“Methylation differences in NTRK2, a gene involved in synaptic signaling and memory formation, have been linked to variation in recognition memory performance and lifetime PTSD risk (92).”
From Epigenetic changes associated with multi-generational trauma: characterization, mechanisms, and therapeutics (2026) · cites this paper as [92]
The Results section reports impaired neutral and emotional memory in PTSD patients, but does not link memory performance or lifetime PTSD risk to NTRK2 methylation. Searches for NTRK2 methylation, recognition memory performance, and lifetime PTSD risk found no passage addressing that link in our copy; page numbers were not provided. (LLM, conf=0.76)
Experimental — accuracy not yet measuredGenocide exposure has been associated with epigenetic variation in pathways involved in neurodevelopment and memory processing.
“Genocide exposure has also been associated with epigenetic variation in pathways involved in neurodevelopment and memory processing.”
From Epigenetic changes associated with multi-generational trauma: characterization, mechanisms, and therapeutics (2026) · cites this paper as [92]
The Introduction (page unavailable) discusses individual differences in learning and memory after traumatic stress, but does not address genocide exposure or epigenetic variation. Searches for genocide exposure and epigenetic or methylation variation found no passage in our copy supporting that association. (LLM, conf=0.76)
Experimental — accuracy not yet measuredMethylation differences in survivors of the Tutsi genocide and related conflicts have been reported in genes regulating synaptic plasticity, neurotrophic signaling, and early developmental programming.
“Methylation differences in survivors of the Tutsi genocide and related conflicts have been reported in genes regulating synaptic plasticity, neurotrophic signaling, and early developmental programming (88–92).”
From Epigenetic changes associated with multi-generational trauma: characterization, mechanisms, and therapeutics (2026) · cites this paper as [92]
The Methods and Results passages describe a meta-analysis of learning, memory, and extinction in PTSD, not methylation differences in conflict survivors. Searches for Tutsi genocide, Rwanda, and methylation found no passage addressing the claimed genes or population. The Discussion mentions synaptic plasticity as a possible target for extinction therapies, but does not link it to methylation. (LLM, conf=0.76)
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Neurobiological aspects of the post-traumatic stress disorders. Systematic review
Bashirzadeм, K. A., & Narov, M. (2026) · Медицинский вестник МВД · doi:10.52341/20738080_2026_144_5_37
- Authors
- Sep, M. S. C., Geuze, E., & Joëls, M.
- Affiliations
- Utrecht University (NL)
- University Medical Center Groningen (NL)
- Corresponding author
- Sep, Milou S. C.
- Venue
- Translational Psychiatry
- Published
- 2023-12-07
- Volume
- 13
- Issue
- 1
- Pages
- 376-376
- ISSN
- 2158-3188 (ISSN-L)
- PMC
- PMC10703817
- OpenAlex
- W4389428451
- Cited by
- 39
- References
- 142
- Citations by year
- 2026: 16 · 2025: 13 · 2024: 8 · 2022: 1 · 2019: 1
- FWCI
- 1.88
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Translational Psychiatry (publishedVersion, cc-by)
- medRxiv (acceptedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, cc-by)
- Funders
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (022.003.003, 024.001.003)
- Dutch Ministry of Defence
- Topics
- Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory Processes and Influences
- Keywords
- post-traumatic stress disorder, fear extinction, learning and memory impairment, emotional memory, information valence, animal model of PTSD, fear memory, translational neuroscience
- MeSH terms
- Animals, Extinction, Psychological, Fear, Humans, Learning, Memory, Memory Disorders, Stress Disorders, Post-Traumatic
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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