Takahashi Hitoshi, Higuchi Hisashi, Sato Kazuhiro, Kamata Mitsuhiro, Yoshida Keizo, Nishimura Katsuji
Department of Neuropsychiatry, Tokyo Women's Medical University School of Medicine, Shinjuku-ku.
Suzuki Jikoh Hospital, Ome-shi, Tokyo.
Neuropsychiatr Dis Treat. 2017 Jun 7;13:1463-1469. doi: 10.2147/NDT.S123708. eCollection 2017.
We investigated the association between serotonin- or 5-hydroxytryptamine (5-HT)-related gene polymorphisms and response to antidepressant treatment in a specific symptom cluster of major depression by using the three-factor model of the Montgomery-Åsberg Depression Rating Scale (MADRS), ie, dysphoria (items of sadness, pessimistic thoughts, and suicidal thoughts), retardation (items of lassitude, inability to feel, apparent sadness, and concentration difficulties), and vegetative symptoms (items of reduced sleep, reduced appetite, and inner tension).
This study was an open-label and nonrandomized trial. A total of 160 patients with baseline MADRS scores of ≥21, who were treated with fluvoxamine or milnacipran for 6 weeks, were included in the statistical analysis. Polymorphisms within a 5-HT transporter (5-HTT) gene-linked polymorphic region (5-HTTLPR), a variable number of tandem repeats in the second intron of the 5-HTT gene (5-HTTVNTR), and 5HT2A receptor (1438G/A) were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).
The 5-HTTLPR polymorphisms affected the MADRS score change in dysphoria, but not in retardation, vegetative, or total symptoms. Dysphoria scores significantly decreased in patients with the S/S genotype compared to those in patients with the short (S)/long (L) + L/L genotype. However, 5-HTTVNTR and 1438G/A polymorphisms were not significantly associated with the treatment response to any cluster of depressive symptoms. When a Bonferroni correction was made, however, our results did not reach the criteria for statistical significance.
The use of a single total depression rating scale may not be sufficient to accurately estimate the clinical response to antidepressants. Analyzing a subset of symptoms in psychological scales could be important when performing pharmacogenetic studies.
我们采用蒙哥马利-Åsberg抑郁评定量表（MADRS）的三因素模型，即烦躁不安（悲伤、悲观想法和自杀念头等条目）、迟缓（疲倦、感觉迟钝、明显悲伤和注意力不集中等条目）以及躯体症状（睡眠减少、食欲减退和内心紧张等条目），研究血清素或5-羟色胺（5-HT）相关基因多态性与重度抑郁症特定症状群对抗抑郁治疗反应之间的关联。
本研究为开放标签、非随机试验。共有160例基线MADRS评分≥21且接受氟伏沙明或米那普明治疗6周的患者纳入统计分析。通过聚合酶链反应-限制性片段长度多态性（PCR-RFLP）测定5-羟色胺转运体（5-HTT）基因连锁多态性区域（5-HTTLPR）、5-HTT基因第二内含子中可变数目的串联重复序列（5-HTTVNTR）以及5HT2A受体（1438G/A）的多态性。
5-HTTLPR多态性影响烦躁不安症状群中MADRS评分的变化，但不影响迟缓、躯体症状或总症状评分。与短（S）/长（L）+L/L基因型患者相比，S/S基因型患者的烦躁不安评分显著降低。然而，5-HTTVNTR和1438G/A多态性与任何抑郁症状群的治疗反应均无显著关联。不过，进行Bonferroni校正后，我们的结果未达到统计学显著性标准。
使用单一的总体抑郁评定量表可能不足以准确评估对抗抑郁药的临床反应。在进行药物遗传学研究时，分析心理量表中的症状子集可能很重要。
