An index of 5-HT synthesis changes during early antidepressant treatment:: α-[11C]methyl-L-tryptophan PET study
An index of 5-HT synthesis changes during early antidepressant treatment:: α-[11C]methyl-L-tryptophan PET study
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DOI：
10.1016/j.neuint.2007.08.021
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发表时间：
2008-03-01
影响因子：
4.2
通讯作者：
Diksic, Mirko
中科院分区：
文献类型：
--
作者：
Berney, Alexandre;Nishikawa, Masami;Diksic, Mirko
抗抑郁药选择性5-羟色胺转运体抑制剂（SSRIs）在延迟几周后具有临床活性。事实上，SSRIs引起的血清素（5-HT）的快速增加会刺激5-HT 1A自身受体，从而对5-HT神经传递产生负反馈。只有当自身受体脱敏时，SSRIs才能发挥其治疗活性。5-HT 1A受体拮抗剂吲哚洛尔可通过抑制负反馈作用来加速抗抑郁药的临床疗效。使用α-[C-11]甲基-L-色氨酸/正电子发射断层扫描（PET），本双盲、随机研究的目的是比较接受SSRI西酞普兰（20 mg/天）加安慰剂治疗的单相抑郁症患者与接受西酞普兰加吲哚（7.5 mg/天）治疗的患者的α-[C-11]甲基-L-色氨酸捕获（5-羟色胺合成的一个指标）的变化。在基线、抗抑郁药治疗10 d和24 d时进行PET和汉密尔顿抑郁量表（HDRS-17）检查。结果显示，与单独的西酞普兰相比，西酞普兰加吲哚的组合显示出前额叶皮层中5-HT合成指数（BA 9）的更快和更大的增加。这项研究是第一项人体PET研究，证明24天后，SSRIs加吲哚洛尔的组合会使前额叶皮层中5-羟色胺的代谢增加，这是一个与抑郁症状相关的区域。(C)2007爱思唯尔有限公司保留所有权利。
The antidepressant selective serotonin transporter inhibitors (SSRIs) are clinically active after a delay of several weeks. Indeed, the rapid increase of serotonin (5-HT) caused by SSRIs, stimulates the 5-HT1A autoreceptors, which exert a negative feedback on the 5-HT neurotransmission. Only when autoreceptors are desensitized, can SSRIs exert their therapeutic activity. The 5-HT1A receptor antagonist pindolol has been used to accelerate the clinical effects of antidepressant by preventing the negative feedback. Using the alpha-[C-11]methyl-L-tryptophan/positron emission tomography (PET), the goal of the present double-blind, randomized study was to compare the changes in alpha-[C-11]methyl-L-tryptophan trapping, an index of serotonin synthesis, in patients suffering from unipolar depression treated with the SSRI citalopram (20 mg/day) plus placebo versus patients treated with citalopram plus pindol (7.5 mg/day). PET and Hamilton depression rating scale (HDRS-17) were performed at baseline, and after 10 and 24 days of antidepressant treatment. Results show that the combination citalopram plus pindol, compared to citalopram alone shows a more rapid and greater increase of an index of 5-HT synthesis in prefrontal cortex (BA 9). This research is the first human PET study demonstrating that, after 24 days, the combination SSRIs plus pindolol produces a greater increase of the metabolism of serotonin in the prefrontal cortex, an area associated to depressive symptoms. (C) 2007 Elsevier Ltd. All rights reserved.