期刊
SCHIZOPHRENIA RESEARCH
卷 131, 期 1-3, 页码 69-74出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.schres.2011.05.029
关键词
NMDA receptor hypofunction; D-cycloserine; Cognitive-behavioral therapy; Psychosis; Delusions; Schizophrenia
类别
资金
- Harvard Medical School [K24 MH002025, P50 MH60450]
- NIMH [5K24 MH002025-10]
- NIMH Neuroscience Center [5 P50 MH60450-11]
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 50 mg or placebo in a counterbalanced order on two consecutive weeks 1 h 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. (C) 2011 Elsevier B.V. All rights reserved.
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