D-cycloserine in Schizophrenia: New Strategies for Improving Clinical Outcomes by Enhancing Plasticity

Title:D-cycloserine in Schizophrenia: New Strategies for Improving Clinical Outcomes by Enhancing Plasticity

Volume: 15 Issue: 1

Author(s): Donald C. Goff

Affiliation:

Keywords: Cognition, D-cycloserine, glutamate, memory, NMDA, pharmacology, plasticity, schizophrenia.

Abstract: Background: Dysregulation of N-methyl D-aspartate (NMDA) receptor signaling is strongly implicated in schizophrenia. Based on the ketamine model of NMDA receptor hypoactivity, therapeutic approaches designed to maintain a sustained increase in agonist activity at the glycine site of the NMDA receptor have produced promising, although inconsistent, efficacy for negative symptoms.

Methods: A review of the published literature on D-cycloserine (DCS) pharmacology in animal models and in clinical studies was performed. Findings relevant to DCS effects on memory and plasticity and their potential clinical application to schizophrenia were summarized.

Results: Studies in animals and clinical trials in patients with anxiety disorders have demonstrated that single or intermittent dosing with DCS enhances memory consolidation. Preliminary trials in patients with schizophrenia suggest that intermittent dosing with DCS may produce persistent improvement of negative symptoms and enhance learning when combined with cognitive behavioral therapy for delusions or with cognitive remediation. The pharmacology of DCS is complex, since it acts as a “super agonist” at NMDA receptors containing GluN2C subunits and, under certain conditions, it may act as an antagonist at NMDA receptors containing GluN2B subunits.

Conclusions: There are preliminary findings that support a role for D-cycloserine in schizophrenia as a strategy to enhance neuroplasticity and memory. However, additional studies with DCS are needed to confirm these findings. In addition, clinical trials with positive and negative allosteric modulators with greater specificity for NMDA receptor subtypes are needed to identify the optimal strategy for enhancing neuroplasticity in schizophrenia.

Cite this article as:

Goff C. Donald, D-cycloserine in Schizophrenia: New Strategies for Improving Clinical Outcomes by Enhancing Plasticity, Current Neuropharmacology 2017; 15 (1) . https://dx.doi.org/10.2174/1570159X14666160225154812

DOI https://dx.doi.org/10.2174/1570159X14666160225154812	Print ISSN 1570-159X
Publisher Name Bentham Science Publisher	Online ISSN 1875-6190