Cited by 170Schizophrenia research and treatmentMemory and Neural MechanismsNeurotransmitter Receptor Influence on Behavior

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Extinction Memory Is Impaired in Schizophrenia

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Holt, Daphne J., Lebron-Milad, Kelimer, Milad, Mohammed R., Rauch, Scott L., Pitman, Roger K., Orr, Scott P., Cassidy, Brittany S., Walsh, Jared P., Goff, Donald C.·2009·Biological Psychiatry

DOI 10.1016/j.biopsych.2008.09.017PMC PMC3740529

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Abstract

Background Schizophrenia is associated with abnormalities in emotional processing and social cognition, which might result from disruption of the underlying neural mechanism(s) governing emotional learning and memory. To investigate this possibility, we measured the acquisition and extinction of conditioned fear responses and delayed recall of extinction in schizophrenia and control subjects.Methods Twenty-eight schizophrenia and 18 demographically matched control subjects underwent a 2-day fear conditioning, extinction learning, and extinction recall procedure, in which skin conductance response (SCR) magnitude was used as the index of conditioned responses.Results During fear acquisition, 83% of the control subjects and 57% of the patients showed autonomic responsivity ("responders"), and the patients showed larger SCRs to the stimulus that was not paired with the unconditioned stimulus (CS-) than the control subjects. Within the responder group, there was no difference between the patients and control subjects in levels of extinction learning; however, the schizophrenia patients showed significant impairment, relative to the control subjects, in context-dependent recall of the extinction memory. In addition, delusion severity in the patients correlated with baseline skin conductance levels.Conclusions These data are consistent with prior evidence for a heightened neural response to innocuous stimuli in schizophrenia and elevated arousal levels in psychosis. The finding of deficient extinction recall in schizophrenia patients who showed intact extinction learning suggests that schizophrenia is associated with a disturbance in the neural processes supporting emotional memory.

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Authors: Holt, D. J., Lebron-Milad, K., Milad, M. R., Rauch, S. L., Pitman, R. K., Orr, S. P., Cassidy, B. S., Walsh, J. P., & Goff, D. C.
Affiliations: Harvard University (US)
McLean Hospital (US)
Massachusetts General Hospital (US)
Corresponding author: Holt, Daphne J.
ORCID: Holt, Daphne J.
Milad, Mohammed R.
Rauch, Scott L.
Pitman, Roger K.
Orr, Scott P.
Cassidy, Brittany S.
Walsh, Jared P.
Goff, Donald C.
Venue: Biological Psychiatry
Publisher: Elsevier BV
Published: 2009-03
Volume: 65
Issue: 6
Pages: 455-463
ISSN: 0006-3223 (ISSN-L)
DOI: 10.1016/j.biopsych.2008.09.017
PMC: PMC3740529
OpenAlex: W2076938137
Cited by: 170
References: 93
Citations by year: 2026: 5 · 2025: 4 · 2024: 9 · 2023: 8 · 2022: 8 · 2021: 8 · 2020: 7 · 2019: 10 · 2018: 15 · 2017: 8 · 2016: 11 · 2015: 10 · 2014: 8 · 2013: 16 · 2012: 19
FWCI: 5.62
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Biological Psychiatry (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Institute of Mental Health (K23MH076054, K24MH002025)
Topics: Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords: schizophrenia, memory extinction, fear conditioning, extinction learning, extinction recall, emotional memory, emotional learning, skin conductance response, delusions, contextual memory
MeSH terms: Adult, Conditioning, Psychological, Extinction, Psychological, Fear, Female, Galvanic Skin Response, Humans, Male, Memory, Schizophrenic Psychology, Case-Control Studies

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Extinction Memory Is Impaired in Schizophrenia

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