Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Curr Neuropharmacol. 2011 Mar;9(1):163-8. doi: 10.2174/157015911795017137.
Several lines of evidence implicate serotonergic dysfunction in diverse psychiatric disorders including anxiety, depression, and drug abuse. Mice with a knock-out of the 5HT1b receptor gene (HTR1B) displayed increased locomotor response to cocaine and elevated motivation to self-administer cocaine and alcohol. Previous genetic studies showed significant associations of HTR1B with alcohol dependence and substance abuse, but were followed by inconsistent results. We examined a case-control genetic association study of HTR1B with methamphetamine-dependence patients in a Japanese population. The subjects were 231 patients with methamphetamine dependence, 214 of whom had a co-morbidity of methamphetamine psychosis, and 248 age- and sex-matched healthy controls. The three single nucleotide polymorphisms (SNPs), rs130058 (A-165T), rs1228814 (A-700C) and rs1228814 (A+1180G) of HTR1B were genotyped. There was no significant difference in allelic and genotypic distributions of the SNPs between methamphetamine dependence and the control. Genetic associations of HTR1B were tested with several clinical phenotypes of methamphetamine dependence and/or psychosis, such as age at first abuse, duration of latency from the first abuse to onset of psychosis, prognosis of psychosis after therapy, and complication of spontaneous relapse of psychotic state. There was, however, no asscocation between any SNP and the clinical phenotypes. Haplotype analyses showed the three SNPs examined were within linkage disequilibrium, which implied that the three SNPs covered the whole HTR1B, and distribution of estimated haplotype frequency was not different between the groups. The present findings may indicate that HTR1B does not play a major role in individual susceptibility to methamphetamine dependence or development of methamphetamine-induced psychosis.
有几条证据表明 5-羟色胺能功能障碍与各种精神疾病有关，包括焦虑、抑郁和药物滥用。5-HT1b 受体基因（HTR1B）敲除的小鼠对可卡因的运动反应增加，对可卡因和酒精的自我给药动机也升高。先前的遗传研究表明 HTR1B 与酒精依赖和物质滥用有显著关联，但随后的结果不一致。我们在日本人群中检查了 HTR1B 与甲基苯丙胺依赖患者的病例对照遗传关联研究。研究对象为 231 例甲基苯丙胺依赖患者，其中 214 例合并有甲基苯丙胺精神病，248 例年龄和性别匹配的健康对照。对 HTR1B 的三个单核苷酸多态性（SNP），rs130058（A-165T）、rs1228814（A-700C）和 rs1228814（A+1180G）进行了基因分型。SNP 在甲基苯丙胺依赖和对照组中的等位基因和基因型分布无显著差异。对 HTR1B 的遗传关联进行了测试，涉及甲基苯丙胺依赖和/或精神病的几种临床表型，如首次滥用的年龄、首次滥用至精神病发作的潜伏期持续时间、治疗后精神病的预后以及精神病自发复发的并发症。然而，没有 SNP 与任何临床表型相关。单体型分析表明，所研究的三个 SNP 处于连锁不平衡状态，这意味着这三个 SNP 涵盖了整个 HTR1B，并且群体之间估计的单体型频率分布没有差异。目前的研究结果可能表明 HTR1B 对个体对甲基苯丙胺依赖的易感性或甲基苯丙胺引起的精神病的发展没有主要作用。
