Fear learning in unmedicated patients with anxiety disorders: a comparison of delay conditioning, fear reversal, and trace conditioning.
Overview
14 affiliations
- Institut d’Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain
- Department of Medicine, Institute of Neurosciences, University of Barcelona, Barcelona, Spain
- University of Vic – Central University of Catalonia, C. Sagrada Família, 7, 08500 Vic Barcelona, Spain
- Department of Theoretical and Applied Sciences, eCampus University, Novedrate (Como), Italy
- Psychiatry and Mental Health Group, Neuroscience Program, Institut d’Investigació Biomèdica de Bellvitge (IDIBELL), L’Hospitalet de Llobregat, Barcelona, Spain
- Department of Clinical Sciencies, Universitat de Barcelona, Barcelona, Spain
- Network Center for Biomedical Research on Mental Health (CIBERSAM), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Radiology Department, Hospital Universitari de Bellvitge, L’Hospitalet de Llobregat, Carrer de Feixa Llarga SN, 08907 Barcelona, Spain
- Sant Pau Mental Health Research Group, Institut de Recerca Sant Pau (IR SANT PAU), Barcelona, Spain
- Department of Psychology, University of Maryland, College Park, MD 20742 US
- Neuroscience and Cognitive Science Program, University of Maryland, College Park, MD 20742 US
- Maryland Neuroimaging Center, University of Maryland, College Park, MD 20742 US
- Department of Social Psychology and Quantitative Psychology, Institute of Neurosciences, Universitat de Barcelona (UB), and Institut d’Investigació Biomèdica de Bellvitge (IDIBELL) and CIBERSAM, Barcelona, Spain
- Adult Psychiatry and Psychology Department, Institute of Neurosciences, Hospital Clinic, Barcelona, Spain
Abstract
Anxiety disorders are common and impairing, yet their underlying mechanisms remain incompletely understood. Fear learning provides a critical translational framework for investigating pathological anxiety, bridging laboratory models and clinical phenomena. Prior studies have been limited by important methodological issues, including the inclusion of non-anxiety diagnoses, high comorbidity, and medication use. Here we examined three forms of fear learning— delay conditioning, fear reversal, and trace conditioning—in unmedicated adults with minimally comorbid primary anxiety disorders (Generalized Anxiety Disorder and Social Anxiety Disorder; n = 34) and demographically matched controls (n = 102). Individuals with anxiety disorders showed greater psychophysiological arousal (skin conductance responses) and reduced brain activation (assessed using functional magnetic resonance imaging) in the left dorsolateral prefrontal cortex to the learned safety cue (CS − ) during the early phase of delay conditioning. Differences between individuals with anxiety disorders and controls were not evident for the learned threat versus learned safety (CS+ versus CS − ) contrasts during delay conditioning, fear-reversal, or trace conditioning in psychophysiological arousal, brain activation, or subjective ratings. Taken together, these observations underscore the selectivity of Pavlovian learning deficits among unmedicated individuals with anxiety disorders and highlight differences in learning or using safety-related information to adaptively regulate fear.
Reproduced under the paper's license (CC BY), from the paper cited above.
Code
The paper says that its authors' code is available on request: it was not published with the paper, so there is nothing to verify.
Code availability
The code that supports the findings of this study is available from the corresponding author upon reasonable request.
Reproduced under the paper's license (CC BY), from the paper cited above.
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Data availability
The data that support the findings of this study are available from the corresponding author, upon reasonable request.
Reproduced under the paper's license (CC BY), from the paper cited above.
Versions
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Version 2, 28 September 2026
- Funding: added Ministerio de Ciencia e Innovación: 13039/501100011033, 501100011033, PID2022; Fundação Bial: 235/22; National Institutes of Health: 1r01aa031261-01a1, MH131264, AA030042, MH121409; Agència de Gestió d'Ajuts Universitaris i de Recerca: 13039/501100011033; Instituto de Salud Carlos III: PI16/, PI22/00261, PI19/01171, PI19/00272, PI16/00889, PI16/00144; European Regional Development Fund: 13039/501100011033, PI16/00144, PI16/00889, 501100011033; Agencia Estatal de Investigación: 501100011033, 13039, 13039/501100011033
Version 1, 28 September 2026: the first record
Recorded: type, language, journal, volume, issue, pages, dates, 11 authors, 3 keywords, 14 MeSH terms, 57 references.
Cite
This paper
Vilajosana, E., Battaglia, S., Chavarría-Elizondo, P., Martínez‑Zalacaín, I., Juaneda-Seguí, A., Saiz-Masvidal, C., De la Peña-Arteaga, V., Shackman, A. J., Radua, J., Soriano-Mas, C., & Fullana, M. A. (2026). Fear learning in unmedicated patients with anxiety disorders: a comparison of delay conditioning, fear reversal, and trace conditioning. Translational psychiatry, 16(1), 274. https://
BibTeX
@article{vilajosana2026f
author = {Vilajosana, Enric and Battaglia, Simone and Chavarría-Elizondo, Pamela and Martínez‑Zalacaín, Ignacio and Juaneda-Seguí, Asier and Saiz-Masvidal, Cristina and De la Peña-Arteaga, Víctor and Shackman, Alexander J and Radua, Joaquim and Soriano-Mas, Carles and Fullana, Miquel A},
title = {{Fear learning in unmedicated patients with anxiety disorders: a comparison of delay conditioning, fear reversal, and trace conditioning}},
journal = {Translational psychiatry},
year = {2026},
month = apr,
volume = {16},
number = {1},
pages = {274},
publisher = {Nature Publishing Group},
issn = {2158-3188},
doi = {10.1038/
url = {https://
pmid = {41927553},
pmcid = {PMC13184327}
}
RIS
TY - JOUR
AU - Vilajosana, Enric
AU - Battaglia, Simone
AU - Chavarría-Elizondo, Pamela
AU - Martínez‑Zalacaín, Ignacio
AU - Juaneda-Seguí, Asier
AU - Saiz-Masvidal, Cristina
AU - De la Peña-Arteaga, Víctor
AU - Shackman, Alexander J
AU - Radua, Joaquim
AU - Soriano-Mas, Carles
AU - Fullana, Miquel A
TI - Fear learning in unmedicated patients with anxiety disorders: a comparison of delay conditioning, fear reversal, and trace conditioning
T2 - Translational psychiatry
J2 - Transl Psychiatry
PY - 2026
DA - 2026/
VL - 16
IS - 1
SP - 274
SN - 2158-3188
PB - Nature Publishing Group
DO - 10.1038/
UR - https://
LA - en
ER -
CSL-JSON
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