Catechol-O-methyltransferase Val158Met genotype and the clinical responses to duloxetine treatment or plasma levels of 3-methoxy-4-hydroxyphenylglycol and homovanillic acid in Japanese patients with major depressive disorder
Catechol-O-methyltransferase Val158Met genotype and the clinical responses to duloxetine treatment or plasma levels of 3-methoxy-4-hydroxyphenylglycol and homovanillic acid in Japanese patients with major depressive disorder
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日本重度抑郁症患者儿茶酚-O-甲基转移酶 Val158Met 基因型与度洛西汀治疗或血浆 3-甲氧基-4-羟基苯基乙二醇和高香草酸水平的临床反应
DOI：
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发表时间：
2015
影响因子：
3.2
通讯作者：
J. Nakamura
中科院分区：
文献类型：
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作者：
K. Atake;R. Yoshimura;H. Hori;A. Katsuki;J. Nakamura
目的探讨血浆儿茶酚胺代谢物水平与度洛西汀治疗的临床反应以及COMT基因Val158Met多态性之间的关系。对象与方法招募64名患者和30名健康对照者。使用《精神障碍诊断与统计手册》第四版文本修订标准的结构化临床访谈对重度抑郁发作进行诊断。采用17项汉密尔顿抑郁量表（HAMD17）评估抑郁严重程度。HAMD17评分为15或更高的患者被纳入研究。于第0周和第8周采血并进行临床评价。采用高效液相色谱-电化学检测法测定血浆儿茶酚胺代谢物水平。采用直接测序进行基因分型。结果45例患者中有30例（67%）在8周的治疗期间对度洛西汀有效。在Val/Val基因型的重度抑郁症（MDD）患者中，3-甲氧基-4-羟基苯基乙二醇（MHPG）的基线血浆水平低于met携带者，而同型香草酸（HVA）的基线血浆水平则低于met携带者。MDD和Val/Val基因型患者，但非Met携带者，在接受度洛西汀治疗8周后，血浆中MHPG水平升高。Val/Val基因型健康对照者的血浆MHPG基线水平显著高于MDD患者。在Val/Val基因型MDD组受试者中，在接受度洛西汀治疗8周后，血浆MHPG水平升高程度与Val/Val基因型健康对照组相同。结论COMT Val158Met多态性、血浆儿茶酚胺代谢物水平与度洛西汀疗效之间的关系复杂。然而，我们的研究结果表明，重度抑郁症患者和Val/Val基因型患者对度洛西汀治疗对去甲肾上腺素能神经元的影响更为敏感。
Purpose This study investigated the relationships among the plasma levels of catecholamine metabolites, the clinical response to duloxetine treatment, and Val158Met polymorphism of the catechol-O-methyltransferase (COMT) gene. Subjects and methods Sixty-four patients and 30 healthy control subjects were recruited. Major depressive episodes were diagnosed using the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria. The severity of depression was evaluated using the 17-item Hamilton Rating Scale for Depression (HAMD17). Patients whose HAMD17 scores were 15 or greater were enrolled in the study. Blood sampling and clinical evaluation were performed at week 0 and week 8. The levels of plasma catecholamine metabolites were measured using high-performance liquid chromatography with electrochemical detection. Genotyping was performed using direct sequencing. Results Thirty of 45 patients (67%) responded to duloxetine treatment during the 8 weeks of treatment. The baseline plasma levels of 3-methoxy-4-hydroxyphenylglycol (MHPG), but not homovanillic acid (HVA), were lower in patients with major depressive disorder (MDD) who had the Val/Val genotype than in patients who were Met-carriers. Patients with MDD and the Val/Val genotype, but not Met carriers, had increased plasma levels of MHPG after 8 weeks of duloxetine treatment. The baseline plasma MHPG levels in healthy control subjects with the Val/Val genotype were significantly higher than those in patients with MDD. Among the subjects in the MDD group with the Val/Val genotype, the plasma MHPG levels increased to the same degree as in the healthy control subjects with the Val/Val genotype after 8 weeks of duloxetine treatment. Conclusion The relationship among the COMT Val158Met polymorphism, plasma levels of catecholamine metabolites, and responses to duloxetine is complex. Nevertheless, our results suggest that patients with MDD and the Val/Val genotype are more sensitive to the influence of noradrenergic neurons by duloxetine treatment.
DOI：
10.1097/00008571-199606000-00007
发表时间：
1996-06-01
期刊：
PHARMACOGENETICS
影响因子：
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作者：
Lachman, HM;Papolos, DF;Weinshilboum, RM
通讯作者：
Weinshilboum, RM