Pharmacogenetics of Antidepressants: Is There a Magic Bullet for Treating Depression?

抗憂鬱劑的藥物基因學：治療憂鬱症的仙丹妙藥是否存在？

李敏秀(Min-Soo Lee)

《台灣精神醫學》 30卷2期 (2016/06) Pp. 79-90+ii

摘要

憂鬱症是現今社會最常見的精神疾患之一。已有許多精神醫學領域的研究者投身於憂鬱症病因的研究，但臨床上對於抗憂鬱劑治療反應的個體差異問題仍持續存在。為了更順利地進入本文主題，筆者將會先介紹單胺假說、血清素在造成臨床憂鬱症的角色、以及抗憂鬱劑的問世（簡短描述三環抗憂鬱劑、選擇性血清素回收抑制劑，及其他新型抗憂鬱劑），接下來再介紹藥物基因學的概念與候選基因(candidate genes)。 筆者認為，基因因素被視為對藥物反應有獨立的影響，並舉四個基因研究為例：血清素轉運體 (5-HTT/SLC6A4) 與血清素受體2A (HTR2A)、G 蛋白β3 次單元 (GNB3)、腦源性神經滋養因子 (BDNF)、及色胺酸水解酶(TPH)。值得注意的是，其中有些候選基因研究的結果是不一致的。2009 年起，全基因體關聯性研究 (Genome-wide Association Studies, GWAS) 提供了更進一步的基礎以瞭解抗憂鬱劑及憂鬱症治療的藥物基因學機轉，但更多的研究及技術的發展仍是需要的。

關鍵字

抗憂鬱劑 ； 單胺 ； 藥物基因學 ； 全基因體關聯性研究 (GWAS)

並列摘要

Depression is one of the most common mental disorders nowadays. Many researchers in psychiatry have investigated the cause of depression. Unfortunately, the problem of individual differences in response to antidepressant treatment still lingers in the clinical fi eld. For setting up the stage for the main topics in the later part of this overview, I start introducing the topics of monoamine hypothesis, the rôle of serotonin in causing clinical depression, as well as advents of antidepressants (briefl y describing tricyclic antidepressants, the arrival of selective serotoninreuptake inhibitor, and novel antidepressants). Then, I introduce the concept of pharmacogenetics, the candidate genes. Afterwards, I consider that genetic factors are recognized to have an independent effect on drug responses. To demonstrate, I highlight fi ve gene studies-serotonin transporter (5-HTT/SLC6A4), serotonin receptor 2A (HTR2A), G-protein β3 subunit (GNB3), brain-derived neurotrophic factor (BDNF), and tryptophan hydroxylase (TPH). But some of candidate gene studies have been conducted, but results were not consistent. Since 2009, Genomewide Association Studies (GWAS) has provided further grounds for understanding the pharmacogenetic mechanisms of antidepressants and depression treatment. Further research and technological development are still needed.

並列關鍵字

antidepressants ； monoamines ； pharmacogenetics ； Genome-wide Association Studies (GWAS)

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