教師資料查詢 | 類別: 期刊論文 | 教師: 張玉坤 Yue-cune Chang (瀏覽個人網頁)

標題:Inhibition of Glycine Transporter-I as a Novel Mechanism for the Treatment of Depression
學年102
學期1
出版(發表)日期2013/11/01
作品名稱Inhibition of Glycine Transporter-I as a Novel Mechanism for the Treatment of Depression
作品名稱(其他語言)
著者Huang, Chih-Chia; Wei, I-Hua; Huang, Chieh-Liang; Chen, Kuang-Ti; Tsai, Mang-Hung; Tsai, Priscilla; Tun, Rene; Huang, Kuo-Hao; Chang, Yue-Cune; Lane, Hsien-Yuan; Tsai, Guochuan Emil
單位淡江大學數學學系
出版者Philadelphia: Elsevier Inc.
著錄名稱、卷期、頁數Biological Psychiatry 74(10), pp.734-741
摘要Background
Antidepressants, aiming at monoaminergic neurotransmission, exhibit delayed onset of action, limited efficacy, and poor compliance. Glutamatergic neurotransmission is involved in depression. However, it is unclear whether enhancement of the N-methyl-D-aspartate (NMDA) subtype glutamate receptor can be a treatment for depression.

Methods
We studied sarcosine, a glycine transporter-I inhibitor that potentiates NMDA function, in animal models and in depressed patients. We investigated its effects in forced swim test, tail suspension test, elevated plus maze test, novelty-suppressed feeding test, and chronic unpredictable stress test in rats and conducted a 6-week randomized, double-blinded, citalopram-controlled trial in 40 patients with major depressive disorder. Clinical efficacy and side effects were assessed biweekly, with the main outcomes of Hamilton Depression Rating Scale, Global Assessment of Function, and remission rate. The time course of response and dropout rates was also compared.

Results
Sarcosine decreased immobility in the forced swim test and tail suspension test, reduced the latency to feed in the novelty-suppressed feeding test, and reversed behavioral deficits caused by chronic unpredictable stress test, which are characteristics for an antidepressant. In the clinical study, sarcosine substantially improved scores of Hamilton Depression Rating Scale, Clinical Global Impression, and Global Assessment of Function more than citalopram treatment. Sarcosine-treated patients were much more likely and quicker to remit and less likely to drop out. Sarcosine was well tolerated without significant side effects.

Conclusions
Our preliminary findings suggest that enhancing NMDA function can improve depression-like behaviors in rodent models and in human depression. Establishment of glycine transporter-I inhibition as a novel treatment for depression waits for confirmation by further proof-of-principle studies.
關鍵字Anxiety; elevated plus maze; forced swimming test; glutamate; N-methyl-D-aspartate; sarcosine
語言英文(美國)
ISSN0006-3223;1873-2402
期刊性質國外
收錄於SCI;
產學合作
通訊作者Lane, Hsien-Yuan
審稿制度
國別美國
公開徵稿
出版型式,電子版,紙本
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