TY - JOUR
T1 - Impaired learning, memory, and extinction in posttraumatic stress disorder
T2 - translational meta-analysis of clinical and preclinical studies
AU - Sep, Milou S. C.
AU - Geuze, Elbert
AU - Joëls, Marian
N1 - Funding Information: We thank Lara Oblak and Sophie Heijnen for their help with screening and data-extraction. We also thank Valeria Bonapersona for her statistical advice and valuable discussions. This work is supported by the Dutch Ministry of Defence. MS is supported by a personal grant which is part of the Graduate Program (project #022.003.003) of The Netherlands Organization of Scientific Research NWO. MS and MJ were supported by the Consortium on Individual Development (CID), which is funded through the Gravitation program of the Dutch Ministry of Education, Culture, and Science and Netherlands Organization for Scientific Research (project #024.001.003). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. This manuscript is shared as preprint on medRxiv. Publisher Copyright: © 2023, The Author(s).
PY - 2023/12/1
Y1 - 2023/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85178906571&partnerID=8YFLogxK
U2 - https://doi.org/10.1038/s41398-023-02660-7
DO - https://doi.org/10.1038/s41398-023-02660-7
M3 - Review article
C2 - 38062029
SN - 2158-3188
VL - 13
SP - 376
JO - Translational Psychiatry
JF - Translational Psychiatry
IS - 1
M1 - 376
ER -