The Hypothesis of NMDA Receptor Hypofunction for Schizophrenia

精神分裂症之NMDA受體功能低下假說

10.29478/TJP.201209.0003

張慧貞(Huey-Jen Chang)；藍先元(Hsien-Yuan Lane)；蔡果荃(Guo-Chuan E. Tsai)

Schizophrenia ； NMDA receptor hypofunction ； negative symptoms ； cognitive function

台灣精神醫學

26卷3期（2012 / 09 / 01）

147 - 161

英文

Schizophrenia, a multifactorial mental disorder with polygenic inheritance as well as environmental influences, encompasses a characteristic group of symptoms and neurocognitive deficits. Cognitive function, a major determinant of quality of life and overall function in schizophrenia, contributes more to the prognosis of the disease than positive symptoms, such as delusions or hallucinations. Although its exact etiological mechanisms remain relatively unknown, extensive studies are ongoing to explore. Among them, one of the primary causal factors is dysfunction of the N-methyl-D-aspartate (NMDA)-type glutamate receptors. This article reviews the clinical limitations of current antipsychotics in treating the core symptoms of schizophrenia and the trend in the reconceptualization of the disease nature and treatment modalities. The NMDA receptor model plays a critical role in the revolution of pharmaceutical industry as a new set of drug targets in addition to those based on the traditional monoaminergic models is proposed. The evidence of NMDA receptor hypofunction in schizophrenia is accumulating from the investigations on the modulation of glutamatergic system, particularly the intrinsic NMDA/glycine site, through genetic research and various clinical trials. A group of ”NMDA-enhancing agents,” being used either as adjuncts to typical/atypical antipsychotics or as monotherapy, in schizophrenic patients, particularly those with refractory negative and cognitive symptoms, offer efficacy in preclinical and early clinical trials. Novel therapeutic agents acting as NMDA enhancers show promise as the next wave of drug development for schizophrenia.

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