D-cycloserine facilitation of cognitive behavioral therapy for delusions in schizophrenia
Open accessAbstract
Glutamatergic N-methyl-D-aspartate (NMDA) receptor hypofunction has been proposed as a mechanism underlying psychosis. D-cycloserine, a partial agonist at the glycine site of the NMDA receptor, enhances learning in animal models, although tachyphylaxis develops with repeated dosing. Once-weekly dosing of D-cycloserine produces persistent improvement when combined with cognitive behavioral therapy (CBT) in anxiety disorders. Delusional beliefs can be conceptualized as a learning deficit, characterized by the failure to use contradictory evidence to modify the belief. CBT techniques have been developed with modest success to facilitate such reality-testing (or new learning) in delusional beliefs. The current study evaluated whether D-cycloserine could potentiate beneficial effects of CBT on delusional severity. Twenty-one outpatients with schizophrenia or schizoaffective disorder and moderately severe delusions were randomized in a double-blind cross-over design to receive a single-dose of either D-cycloserine 50mg or placebo in a counterbalanced order on two consecutive weeks 1h prior to a CBT intervention involving training in the generation of alternative beliefs. Assessments were completed at baseline, 7 days following the first study drug administration and 7 days following the second study drug administration. Contrary to prediction, there was no significant d-cycloserine treatment effect on delusional distress or severity as measured by the SAPS or PSYRATS. An unexpected finding was an order effect, whereby subjects who received D-cycloserine first had significantly reduced delusional severity, distress, and belief conviction on PSYRATS compared to subjects who received placebo first. However, this finding is consistent with animal models in which D-cycloserine enhances learning only when accompanying the first exposure to training.
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In a 2011 study, participants who received D-cycloserine after cognitive behavioural therapy showed greater adoption of new explanatory beliefs than those who received placebo.
“In a 2011 investigation 24 , participants given D-cycloserine (which boosts NMDA receptor function) after cognitive behavioural therapy showed an enhanced adoption of new explanatory beliefs compared with those who received placebo.”
From Computational psychiatry: a Rosetta Stone linking the brain to mental illness (2014) · cites this paper as [24]
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- Authors
- Gottlieb, J. D., Cather, C., Shanahan, M., Creedon, T., Macklin, E. A., & Goff, D. C.
- Affiliations
- Massachusetts General Hospital (US)
- Harvard University (US)
- Corresponding author
- Gottlieb, Jennifer D.
- ORCID
- Venue
- Schizophrenia Research
- Publisher
- Elsevier BV
- Published
- 2011-09
- Volume
- 131
- Issue
- 1-3
- Pages
- 69-74
- ISSN
- 0920-9964 (ISSN-L)
- PMC
- PMC3389827
- OpenAlex
- W2052868558
- Cited by
- 73
- References
- 26
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 1 · 2023: 5 · 2022: 1 · 2021: 5 · 2020: 4 · 2019: 3 · 2018: 7 · 2017: 2 · 2016: 6 · 2015: 7 · 2014: 10 · 2013: 7 · 2012: 9
- FWCI
- 5.91
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Schizophrenia Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (P50MH060450, K24MH002025, 5 P50 MH60450-11)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Social Sciences › Arts and Humanities › Philosophy › Mental Health and Psychiatry
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- D-cycloserine, cognitive behavioral therapy
- MeSH terms
- Adolescent, Adult, Aged, Antimetabolites, Culture, Cycloserine, Delusions, Double-Blind Method, Female, Follow-Up Studies, Humans, Male, Middle Aged, Psychiatric Status Rating Scales, Psychotic Disorders, Retrospective Studies, Schizophrenia, Cognitive Behavioral Therapy, Young Adult
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