期刊
EUROPEAN NEUROPSYCHOPHARMACOLOGY
卷 23, 期 8, 页码 931-940出版社
ELSEVIER
DOI: 10.1016/j.euroneuro.2012.09.008
关键词
Glycine; NMDA receptor; Risk syndrome; Prodrome; Psychosis; Schizophrenia
资金
- Stanley Foundation [02T-175]
- NARSAD Distinguished Investigator Award
- Glytech Inc.
- Donaghue Foundation Early Schizophrenia Initiative
- National Institutes of Health [U01 MH74356]
- NATIONAL INSTITUTE OF MENTAL HEALTH [U01MH074356] Funding Source: NIH RePORTER
Patients meeting criteria for the risk syndrome for psychosis have treatment needs including positive and negative symptoms and cognitive impairment. These features could potentially respond to NMDA glycine-site agonists. The present objective was to determine which symptoms or domains of cognition promise to show the greatest response to glycine in risk syndrome patients. We conducted two short-term pilot studies of glycine used without adjunctive antipsychotic medication. In the first trial, 10 risk syndrome subjects received open-label glycine at doses titrated to 0.8 g/kg/d for 8 weeks, followed by discontinuation and 16 weeks of evaluation for durability of effects. In the second, 8 subjects were randomized to double-blind glycine vs. placebo for 12 weeks, followed by open-label glycine for another 12 weeks. Patients were evaluated every 1-2 weeks with the Scale Of Psychosis-risk Symptoms (SOPS) and before and after treatment with a neurocognitive battery. Within-group and between-group effect sizes were calculated. Effect sizes were large for positive (open-label within-group -1.10, double-blind between-group -1.11) and total (-1.39 and -1.15) symptoms and medium-to-large (-0.74 and -0.79) for negative symptoms. Medium or large effect sizes were also observed for several neurocognitive measures in the open-label study, although data were sparse. No safety concerns were identified. We conclude that glycine was associated with reduced symptoms with promising effect sizes in two pilot studies and a possibility of improvement in cognitive function. Further studies of agents that facilitate NMDA receptor function in risk syndrome patients are supported by these preliminary findings. (C) 2012 Elsevier B.V. and ECNP. All rights reserved.
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