Early detection and novel intervention of schizophrenia: based upon DAOA/DAAO/NMDAR pathway


2020 神醫中心學術演講

日期 : 6月 23日
時間 : 上午11:00 
地點 : 國衛院竹南院區/ 行政大樓B1第6會議室
主題 : Early detection and novel intervention of schizophrenia: based upon DAOA/DAAO/NMDAR pathway
講師 : Hsien-Yuan Lane (藍先元), M.D., Ph.D.
精神醫學部主任/ 成癮醫學研究中心主任



While second-generation antipsychotics are increasingly used, treatment for schizophrenia remains a great challenge. NMDAR dysfunction plays vital roles in pathogenesis of schizophrenia. However, there have been lack of suitable biomarkers and enhancers for schizophrenia.

Previously, we have found that glycine transporter-1 (GlyT-1) antagonist, N-methylglycine (sarcosine), can improve symptoms of schizophrenia. This presentation will update the current status of the development of novel glutamate-related biomarkers and modulators, based upon DAOA/DAAO/NMDAR pathway, for early diagnosis and treatment of schizophrenia.

We will present data from clinical trials with benzoate, the pivotal D-amino acid oxidase (DAAO) inhibitor, in chronic- and treatment-resistant forms of schizophrenia. Results suggest that adjuvant benzoate therapy can improve cognitive function of patients, irrespective of clinical improvement, supporting cognition as an independent, primary outcome measure. Lately, we also found that adjuvant therapy improved symptomatology of patients with ultra-resistant (clozapine-resistant) schizophrenia

In addition, we will show findings suggesting that peripheral makers including DAAO activator (DAOA; or named G72) and cystine/glutamate antiporter system xc- may identify a unique subgroup of patients of schizophrenia who will be responsive to novel NMDA enhancers.

To sum up, this presentation, composed of several works on novel NMDAR-related biomarkers and modulators for early diagnosis and novel treatment, may help the development of pharmacotherapy and diagnosis for schizophrenia.



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