title: Brain cannabinoid CB2 receptor in schizophrenia.
abstract: BACKGROUND
  Neural endocannabinoid function appears to be involved in schizophrenia. Two endocannabinoid receptors, CB1 and CB2, are found in the brain and elsewhere in the body. We investigated roles of CB2 in schizophrenia.
  
  
  METHODS
  An association study was performed between tag single nucleotide polymorphisms (SNPs) in the CNR2 gene encoding the CB2 receptor and schizophrenia in two independent case-control populations. Allelic differences of associated SNPs were analyzed in human postmortem brain tissues and in cultured cells. Prepulse inhibition and locomotor activity in C57BL/6JJmsSlc mice with CB2 receptor antagonist AM630 administration was examined.
  
  
  RESULTS
  The analysis in the first population revealed nominally significant associations between schizophrenia and two SNPs, and the associations were replicated in the second population. The R63 allele of rs2501432 (R63Q) (p = .001), the C allele of rs12744386 (p = .005) and the haplotype of the R63-C allele (p = 5 x 10(-6)) were significantly increased among 1920 patients with schizophrenia compared with 1920 control subjects in the combined population. A significantly lower response to CB2 ligands in cultured CHO cells transfected with the R63 allele compared with those with Q63, and significantly lower CB2 receptor mRNA and protein levels found in human brain with the CC and CT genotypes of rs12744386 compared with TT genotype were observed. AM630 exacerbated MK-801- or methamphetamine-induced disturbance of prepulse inhibition and hyperactivity in C57BL/6JJmsSlc mice.
  
  
  CONCLUSIONS
  These findings indicate an increased risk of schizophrenia for people with low CB2 receptor function.
authors.affiliation: Department of Medical Genetics, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan. hishigur@md.tsukuba.ac.jp
authors.forename: Hiroki
authors.initials: H
authors.lastname: Ishiguro
authors.forename: Yasue
authors.initials: Y
authors.lastname: Horiuchi
authors.forename: Maya
authors.initials: M
authors.lastname: Ishikawa
authors.forename: Minori
authors.initials: M
authors.lastname: Koga
authors.forename: Keiko
authors.initials: K
authors.lastname: Imai
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Miyuki
authors.initials: M
authors.lastname: Morikawa
authors.forename: Toshiya
authors.initials: T
authors.lastname: Inada
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Makoto
authors.initials: M
authors.lastname: Takahashi
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Someya
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ujike
authors.forename: Nakao
authors.initials: N
authors.lastname: Iwata
authors.forename: Norio
authors.initials: N
authors.lastname: Ozaki
authors.forename: Emmanuel S
authors.initials: ES
authors.lastname: Onaivi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kunugi
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Sasaki
authors.forename: Masanari
authors.initials: M
authors.lastname: Itokawa
authors.forename: Makoto
authors.initials: M
authors.lastname: Arai
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Niizato
authors.forename: Shyuji
authors.initials: S
authors.lastname: Iritani
authors.forename: Izumi
authors.initials: I
authors.lastname: Naka
authors.forename: Jun
authors.initials: J
authors.lastname: Ohashi
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Kakita
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Takahashi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nawa
authors.forename: Tadao
authors.initials: T
authors.lastname: Arinami
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D016466:CHO Cells; D016022:Case-Control Studies; D006224:Cricetinae; D003412:Cricetulus; D000242:Cyclic AMP / Q000378:metabolism; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D020641:Polymorphism, Single Nucleotide; D043885:Receptor, Cannabinoid, CB2 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D013216:Reflex, Startle / Q000187:drug effects; D012559:Schizophrenia / Q000235:genetics* / Q000378:metabolism*
chemical_list: D007211:Indoles; D043885:Receptor, Cannabinoid, CB2; D000242:Cyclic AMP; C094023:iodopravadoline; C402944:JHW 015