Archival ReportBrain Cannabinoid CB2 Receptor in Schizophrenia
Section snippets
Participants in the Association Study
Consensual diagnosis of schizophrenia was made according to the DSM-IV. Control subjects had no history of mental illness, and second-degree relatives were free of psychosis in a brief psychiatric interview. The first screening group of subjects (East Japan) comprised 1152 unrelated Japanese patients with schizophrenia and 1194 control subjects. The second group of subjects (West Japan) for replication analysis comprised 768 unrelated Japanese patients with schizophrenia and 726 control
Results
Table 1 shows the distribution of the genotypes of the tag SNPs in the CNR2 gene region, and Figure 1 shows the LD pattern within those tag SNPs. None of the SNPs deviated significantly from the expected Hardy-Weinberg equilibrium. Nominally, significant differences were found in allele frequencies of rs12744386 (p = .05, odds ratio [OR] = 1.13 with 95% confidence interval [CI]: 1.00–1.27) and rs2501432 (R63Q) (p = .003, OR = 1.19, 95% CI: 1.06–1.34) between schizophrenic and control subjects
Discussion
We found two SNPs in and near the CNR2 gene associated with schizophrenia in Japanese populations. One of these two SNPs, rs12744386, was found to be associated with gene expression levels (the risk allele was associated with low levels of CNR2) and another, rs2501432, was a missense R63Q. By the transfection experiments, we showed that, compared with the protective allele, the risk allele of the missense polymorphism had a poor response to CB2 ligands. Therefore, it was thought that both risk
References (45)
- et al.
Cannabis and schizophreniaA longitudinal study of Swedish conscripts
Lancet
(1987) - et al.
Cannabis use and brain structural alterations in first episode schizophrenia—A region of interest, voxel based morphometric study
Schizophr Res
(2008) - et al.
Activation of cannabinoid-1 receptors disrupts sensory gating and neuronal oscillation: Relevance to schizophrenia
Biol Psychiatry
(2008) - et al.
Female schizophrenia patients have prepulse inhibition deficits
Biol Psychiatry
(2005) - et al.
Cannabinoid CB2 receptors: Immunohistochemical localization in rat brain
Brain Res
(2006) - et al.
The effects of an early stressful life event on sensorimotor gating in adult rats
Schizophr Res
(1998) - et al.
Early maternal deprivation and prepulse inhibition: The role of the postdeprivation environment
Pharmacol Biochem Behav
(2002) - et al.
The effects of early maternal deprivation on auditory information processing in adult Wistar rats
Biol Psychiatry
(2004) - et al.
Early maternal deprivation reduces prepulse inhibition and impairs spatial learning ability in adulthood: No further effect of post-pubertal chronic corticosterone treatment
Behav Brain Res
(2007) - et al.
Early life tactile stimulation changes adult rat responsiveness to amphetamine
Pharmacol Biochem Behav
(2006)
Self reported cannabis use as a risk factor for schizophrenia in Swedish conscripts of 1969: Historical cohort study
BMJ
Cerebrospinal anandamide levels are elevated in acute schizophrenia and are inversely correlated with psychotic symptoms
Neuropsychopharmacology
Effects of cannabidiol on schizophrenia-like symptoms in people who use cannabis
Br J Psychiatry
Endocannabinoid signalling in the blood of patients with schizophrenia
Lipids Health Dis
Elevated endogenous cannabinoids in schizophrenia
Neuroreport
Expression of CB1 cannabinoid receptor in the anterior cingulate cortex in schizophrenia, bipolar disorder, and major depression
J Neural Transm
Determination and characterization of a cannabinoid receptor in rat brain
Mol Pharmacol
Nucleotide sequence of a human cannabinoid receptor cDNA
Nucleic Acids Res
Structure of a cannabinoid receptor and functional expression of the cloned cDNA
Nature
Cannabinoid receptor 1 gene (CNR1) and susceptibility to a quantitative phenotype for hebephrenic schizophrenia
Am J Med Genet B Neuropsychiatr Genet
Schizophrenia and the cannabinoid receptor type 1 (CB1): Association study using a single-base polymorphism in coding exon 1
Am J Med Genet
(AAT)n repeat in the cannabinoid receptor gene, CNR1: Association with schizophrenia in a Spanish population
Eur Arch Psychiatry Clin Neurosci
Cited by (156)
Cannabinoid CB2 receptors and hypersensitivity to methamphetamine: Vulnerability to schizophrenia
2024, Progress in Neuro-Psychopharmacology and Biological PsychiatryHU-910, a CB2 receptor agonist, reverses behavioral changes in pharmacological rodent models for schizophrenia
2022, Progress in Neuro-Psychopharmacology and Biological PsychiatryCitation Excerpt :Cannabis use is a well-known risk factor for schizophrenia, and elevated levels of anandamide in the cerebrospinal fluid have been described in the prodromal stage of the disease and antipsychotic-naïve acute schizophrenia patients (Giuffrida et al., 2004; Hall and Degenhardt, 2008; Koethe et al., 2009). Moreover, genetic associations between polymorphisms of cannabinoid CB1 and CB2 receptors may be related to a higher susceptibility to schizophrenia and response to antipsychotic drugs (Bae et al., 2014; Hamdani et al., 2008; Ishiguro et al., 2010; Legge et al., 2019; Ujike et al., 2002). CB2 receptors modulate dopaminergic neurotransmission and dopamine-related behaviors (Canseco-Alba et al., 2019; Manzanares et al., 2018; Xi et al., 2011).
Development of high-affinity fluorinated ligands for cannabinoid subtype 2 receptor, and in vitro evaluation of a radioactive tracer for imaging
2022, European Journal of Medicinal ChemistryNabilone Impairs Spatial and Verbal Working Memory in Healthy Volunteers
2024, Cannabis and Cannabinoid ResearchGoods and Bads of the Endocannabinoid System as a Therapeutic Target: Lessons Learned after 30 Years
2023, Pharmacological ReviewsCannabis Use and Endocannabinoid Receptor Genes: A Pilot Study on Their Interaction on Brain Activity in First-Episode Psychosis
2023, International Journal of Molecular Sciences