Association Between 5HT1b Receptor Gene and Methamphetamine Dependence

H Ujike,M Kishimoto,M Kodama,N Uchimura,N Iwata,M Takaki,M Yamada,I Sora,M Iyo,T Inada,N Ozaki,Y Okahisa

doi:10.2174/157015911795017137

Abstract

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.

Highlights

And twin studies have provided evidence that genetic factors can influence individual differences in vulnerability to substance abuse and dependence [1, 2]
We previously reported that patients with methamphetamine use disorders showed substantial individual differences in psychotomimetic and psychotogenic effects of methamphetamine consumption, e.g., intensity of subjective euphoric effects, latency to onset of methamphetamine-induced psychosis, and prognosis of psychosis after discontinuance of methamphetamine use [3], whose clinical variations should be affected by individual genetic background
The patients with methamphetamine dependence and/or psychosis were divided into subgroups according to several clinical phenotypes that may indicate indirectly the severity of and liability to dependence and psychosis: 1) age at first abuse of methamphetamine: younger than 20 years old, which is underage in Japan, or older; 2) latency to onset of psychotic state after initial methamphetamine consumption: divided into two groups by median latency of 3 years; 3) Duration of psychotic state after discontinuance of abuse and therapy with antipsychotics: transient type and prolonged type, which were defined as psychosis that subsides within one month or lasts longer than one month, respectively; 4) complication of spontaneous psychosis after remission of methamphetamine-induced psychosis, and 5) multisubstance abuse status

Summary

INTRODUCTION

And twin studies have provided evidence that genetic factors can influence individual differences in vulnerability to substance abuse and dependence [1, 2]. Previous genetic studies indicated that the 5HT1b receptor gene (HTR1B, MIM 182131) was associated with drug dependence and related behaviors. 164 Current Neuropharmacology, 2011, Vol 9, No 1 coholism with antisocial behaviors [11, 12], whole alcoholism [13, 14], substance dependence [15] and heroin addiction [16], there were several inconsistent reports [17, 18]. In order to investigate the roles of HTR1B in substance dependence, we examined a possible genetic association of HTR1B with methamphetamine dependence in a Japanese population

METHODS

RESULTS

DISCUSSION