HTR1A Gene Polymorphisms and 5-HT1A Receptor Partial Agonist Antipsychotics Efficacy in Schizophrenia
HTR1A Gene Polymorphisms and 5-HT1A Receptor Partial Agonist Antipsychotics Efficacy in Schizophrenia
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DOI：
10.1097/jcp.0000000000000304
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发表时间：
2015-06
影响因子：
2.9
通讯作者：
Y. Takekita;C. Fabbri;Masaki Kato;S. Nonen;S. Sakai;N. Sunada;Y. Koshikawa;M. Wakeno;G. Okugawa;T. Kinoshita;A. Serretti
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文献类型：
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作者：
Y. Takekita;C. Fabbri;Masaki Kato;S. Nonen;S. Sakai;N. Sunada;Y. Koshikawa;M. Wakeno;G. Okugawa;T. Kinoshita;A. Serretti
摘要 血清素 1A (5-HT1A) 受体的个体差异可能导致对 5-HT1A 受体部分激动的抗精神病药物的不同反应。我们研究了日本精神分裂症患者中 5-HT1A 受体基因 (HTR1A) 单核苷酸多态性 (SNP) 与 5-HT1A 受体部分激动抗精神病药物疗效之间的关系。在一项随机对照研究中，100 名精神分裂症患者接受了哌罗螺酮或阿立哌唑治疗。候选 SNP 为 rs6295（影响 HTR1A 表达和功能）、rs1364043、rs878567 和 rs10042486。使用阳性和阴性综合征量表 (PANSS) 5 因素分量表（兴奋/敌意、抑郁/焦虑、认知、阳性和阴性）评估治疗第 12 周的疗效。 Rs1364043 T 等位基因与 PANSS 5 因子阴性评分的百分比变化相关 (P < 0.01)。单倍型分析显示，rs10042486-rs6295-rs1364043 T-C-G单倍型与较差的负分改善相关（单倍型频率，0.675；P=0.014），而相对罕见的T-G-T单倍型与较好的疗效相关（单倍型频率，0.05；P=0.031）。这是第一项表明 rs10042486-rs6295-rs1364043 HTR1A 变异可能与 5-HT1A 部分激动剂抗精神病药治疗期间 PANSS 5 因子阴性评分改善相关的研究。有必要进行更大样本量和不同种族群体的研究。
Abstract Individual differences in serotonin 1A (5-HT1A) receptor may result in variable response to antipsychotics with 5-HT1A receptor partial agonism. We investigated the relationship between 5-HT1A receptor gene (HTR1A) single nucleotide polymorphisms (SNPs) and efficacy of antipsychotics with 5-HT1A receptor partial agonism in Japanese patients with schizophrenia. Perospirone or aripiprazole was administered to 100 patients with schizophrenia in a randomized controlled study. Candidate SNPs were rs6295 (which affects HTR1A expression and function), rs1364043, rs878567, and rs10042486. Efficacy at week 12 of treatment was evaluated using the Positive and Negative Syndrome Scale (PANSS) 5-factor subscales (excitement/hostility, depression/anxiety, cognition, positive, and negative). Rs1364043 T allele was correlated with the percent change in the PANSS 5-factor negative score (P < 0.01). Haplotype analysis showed that the rs10042486-rs6295-rs1364043 T-C-G haplotype was correlated with worse negative score improvement (haplotype frequency, 0.675; P = 0.014), and the relatively rare T-G-T haplotype correlated with better efficacy (haplotype frequency, 0.05; P = 0.031). This is the first study to show that rs10042486-rs6295-rs1364043 HTR1A variants may be correlated with the improvement of the PANSS 5-factor negative score during treatment with 5-HT1A partial agonist antipsychotics. Studies with larger sample sizes and in different ethnic groups are warranted.