Abstract
Schizophrenia is a severe mental disorder which leads to functional deterioration. Early detection and intervention are vital for better prognosis. However, the diagnosis of schizophrenia still depends on clinical observation to date. Without reliable biomarkers, schizophrenia is difficult to detect in its early phase. Further, there is no approved medication for prodromal schizophrenia because current antipsychotics fail to show satisfactory efficacy and safety. Therefore, to develop an effective early diagnostic and therapeutic approach for schizophrenia, especially in its prodromal phase, is crucial. Glutamate signaling dysfunction and dysregulation of oxidative stress have been considered to play important roles in schizophrenic prodrome. The N-methyl-D-aspartate receptor (NMDAR) is one of three types of ionotropic glutamate receptors. In this article, we reviewed literature regarding NMDAR hypofunction, oxidative stress, and the linkage between both in prodromal schizophrenia. The efficacy of NMDAR enhancers such as D-amino acid oxidase inhibitor was addressed. Finally, we highlighted potential biomarkers related to NMDAR and oxidative stress regulation, and therefore suggested the strategies of early detection and intervention of prodromal schizophrenia. Future larger-scale studies combining biomarkers and novel drug development for early psychosis are warranted.
Highlights
Schizophrenia is a high-morbidity and high-mortality brain disorder
We reviewed literature regarding N-methyl-D-aspartate receptor (NMDAR) hypofunction, oxidative stress, and the linkage between both in prodromal schizophrenia
Many subjects in the study carried severe depressive symptoms, hampering the conclusion of the study. These findings suggest that oxidative stress levels may be a biomarker of schizophrenia risk and response to adjunctive antioxidant treatment
Summary
Schizophrenia is a high-morbidity and high-mortality brain disorder. Globally 1% population suffered from this disorder. Clinical manifestation of schizophrenia consists of three domains: positive symptoms (such as hallucinations or delusions), negative symptoms (such as flattening affect or social withdrawal), and cognitive deficits (such as impaired memory, attention, and executive functions) [1,2,3,4]. Glutamate and Oxidative Stress in Early Psychosis [5,6,7,8,9]. The deterioration of cognitive function in patients with schizophrenia will lead to impairment of self-care, social, and occupational function [12]. Oxidative stress and genetic/environmental factors converge during neurodevelopment, leading to the impairment of neural connectivity and synchronization, as well as to cognitive deficits in early psychosis patients [16]. This review highlights a recent development surrounding N-methyl-D-aspartate receptor (NMDAR) modulators and antioxidants, paving the way for biomarker guided early detection and intervention of high-risk individuals [17]
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