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Marijuana receptor gene abnormality in schizophrenia

The cannabinoid hypothesis for the pathogenesis of schizophrenia is based on the clinical facts that abuse of cannabis (marijuana) could precipitate the psychotic state, with hallucinations and delusions resembling schizophrenia and worsen positive symptoms of schizophrenia, even under regular medication of antipsychotics. Cannabinoid consumption could result in poor outcome and liability to relapse for schizophrenics. In addition, heavy cannabis users may develop an amotivational syndrome, reminiscent of some of the negative symptoms of schizophrenia. A Swedish cohort study showed that cannabis use before 18 years of age raises the incident rate of schizophrenia six-fold. Another study showed that administration of delta-9-hydrocannabinol to normal volunteers induced cognitive impairment of three dimensions resembling closely that of schizophrenic patients. The hallucinogenic action of cannabis and marijuana mediated the central cannabinoid receptor, G-protein-coupled receptor CB1, which was discovered in 1988. CB1 receptors were expressed abundantly throughout the brain, especially in substantia nigra, globus pallidus, hippocampus and cerebellum. CB1 receptors are encoded by the CNR1 gene (MIM114610), which was cloned by Matsuda et al in 1992. CB1 is located at 6q14-q15, which was included in a schizophrenia susceptibility locus, 6q13-q26, revealed by Cao et al using two independent series of pedigrees, which was designated by Schizophrenia 5 (SCZ5, OMIM 603175). Recently, two polymorphisms, AAT repeats microsatellite in the 3' flanking region and 1359 G/A polymorphism at codon 453 in the coding exon of the CNR1 gene, were reported.

To examine the cannabinoid hypothesis for schizophrenia, the authors examined these two polymorphisms in the cannabinoid receptor 1 (CNR1) gene in the Japanese population. Specifically, they examined two kinds of polymorphisms of the C
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Contact: Frank Sissingh
molecularpsychiatry@mednet.ucla.edu
310-206-6739
Molecular Psychiatry
1-Jul-2002


Page: 1 2 3

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