Speaker 2: Kazutaka Ikeda, Japan

Genetic studies on METH abuse and METH psychosis are influential in the fields of comorbidity of substance abuse, etiological models of schizophrenia, and the nosology of prolonged or chronic substance-induced psychosis. Most data of genetic markers associated with METH abuse or METH psychosis derived from Asian samples. Previous studies on Meth abuse and Meth psychosis have identified many potential genetic markers. However, most of the genetic associations are not replicated. Among few replicated genetic associations, BDNF rs6465 is concluded to be associated with METH dependence, whereas SOD2 gene is associated with METH psychosis. A genome-wide association studies (GWAS) of independent pooled DNA samples of METH users from Taiwan and Japan show that variants in the “METH dependence” genes are likely to alter cell adhesion, enzymatic functions, transcription, cell structure, as well as DNA, RNA, and/or protein handling or modification. The GWAS findings from individual DNA samples suggest shared genetic risk between Meth psychosis and schizophrenia. Speaker 2: Kazutaka Ikeda, Japan Genetic polymorphisms commonly associated with sensitivity to addictive substances Kazutaka Ikeda1, Daisuke Nishizawa1, Ken-ichi Fukuda1,2, Masakazu Hayashida1,3, Susumu Higuchi1,4, Haruhiko Sugimura5, Ichiro Sora1,6 1Tokyo Metropolitan Institute of Medical Science 2Tokyo Dental College 3Juntendo University School of Medicine 4National Hospital Organization Kurihama Medical and Addiction Center 5Hamamatsu University School of Medicine 6Kobe University Graduate School of Medicine Abstract Sensitivity to addictive substance is well known to vary widely among individual subjects, which hampers effective prevention and treatment of addiction. Many genetic and environmental factors are involved in sensitivity to addictive substances including opioids, methamphetamine, alcohol, and nicotine. Interestingly, we recently found that several single nucleotide polymorphisms (SNPs) which are associated with sensitivity to an addictive substance are also associated with sensitivity to other addictive substances. Firstly, we found that the rs2952768 SNP neighboring the CREB1gene was strongly associated with the requirements for postoperative opioid analgesics after painful cosmetic surgery in a genome wide association study (GWAS), and consistent results were obtained in patients who underwent abdominal surgery. The SNP was also associated with vulnerability to severe drug dependence in patients with methamphetamine (METH) dependence, alcohol dependence, and eating disorders and a lower “Reward Dependence” score on a personality questionnaire in healthy subjects. These results demonstrate that the SNP affects both the efficacy of opioid analgesics and liability to severe substance dependence. Secondly, we found that the nonsynonymous rs2653349 SNP (located on the gene that encodes orexin [hypocretin] receptor 2; Val308Ile) was associated with the Fagerström Test for Nicotine Dependence (FTND) score in a GWAS. This SNP was also associated with the initiation of METH use in patients with METH dependence. Thirdly, we found that the rs2835859 SNP (located on gene that encodes G-protein-activated inwardly rectifying potassium (GIRK) channel 2 subunit) was associated with opioid analgesic sensitivity and the result was corroborated in further confirmatory study. Moreover, this SNP was also associated with susceptibility to nicotine dependence and successful smoking cessation. The results indicate that this SNP in the GIRK2 (KCNJ6) gene could serve as a marker that predicts sensitivity to analgesic and susceptibility to nicotine dependence. These SNPs commonly associated with sensitivity to addictive substances suggest common mechanisms among vulnerabilities to addiction due to different addictive substances. Our findings may provide valuable information for the personalized prevention and treatment of addiction.Sensitivity to addictive substance is well known to vary widely among individual subjects, which hampers effective prevention and treatment of addiction. Many genetic and environmental factors are involved in sensitivity to addictive substances including opioids, methamphetamine, alcohol, and nicotine. Interestingly, we recently found that several single nucleotide polymorphisms (SNPs) which are associated with sensitivity to an addictive substance are also associated with sensitivity to other addictive substances. Firstly, we found that the rs2952768 SNP neighboring the CREB1gene was strongly associated with the requirements for postoperative opioid analgesics after painful cosmetic surgery in a genome wide association study (GWAS), and consistent results were obtained in patients who underwent abdominal surgery. The SNP was also associated with vulnerability to severe drug dependence in patients with methamphetamine (METH) dependence, alcohol dependence, and eating disorders and a lower “Reward Dependence” score on a personality questionnaire in healthy subjects. These results demonstrate that the SNP affects both the efficacy of opioid analgesics and liability to severe substance dependence. Secondly, we found that the nonsynonymous rs2653349 SNP (located on the gene that encodes orexin [hypocretin] receptor 2; Val308Ile) was associated with the Fagerström Test for Nicotine Dependence (FTND) score in a GWAS. This SNP was also associated with the initiation of METH use in patients with METH dependence. Thirdly, we found that the rs2835859 SNP (located on gene that encodes G-protein-activated inwardly rectifying potassium (GIRK) channel 2 subunit) was associated with opioid analgesic sensitivity and the result was corroborated in further confirmatory study. Moreover, this SNP was also associated with susceptibility to nicotine dependence and successful smoking cessation. The results indicate that this SNP in the GIRK2 (KCNJ6) gene could serve as a marker that predicts sensitivity to analgesic and susceptibility to nicotine dependence. These SNPs commonly associated with sensitivity to addictive substances suggest common mechanisms among vulnerabilities to addiction due to different addictive substances. Our findings may provide valuable information for the personalized prevention and treatment of addiction.