期刊論文
| 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 | en_US |
| ISSN | 0006-3223 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 | 是 |
| 國別 | USA |
| 公開徵稿 | |
| 出版型式 | ,電子版,紙本 |
| 相關連結 |
機構典藏連結 ( http://tkuir.lib.tku.edu.tw:8080/dspace/handle/987654321/93104 ) |