Marijuana receptor gene abnormality in sch...( NR1 gene which encodes human CB1 re...)

NR1 gene, which encodes human CB1 receptor, a subclass of central cannabinoid receptors, in schizophrenics and age-matched controls in the Japanese population. Allelic and genotype distributions of polymorphism 1359G/A at codon 453 in the coding region and AAT triplet repeats in the 3' flanking region in the Japanese population were quite different from those in Caucasians. Although the polymorphism 1359/A was not associated with schizophrenia, the triplet repeat polymorphism of the CNR1 gene was significantly associated with schizophrenia, especially the hebephrenic subtype (P = 0.0028). Hebephrenic schizophrenia showed significantly increased rate of the 9 repeat allele (P = 0.032, OR = 2.30, 95% Cl (191-2.69), and decreased rate of the 17 repeat allele (P = 0.011, OR = 0.208, 95% Cl (0.098-0.439)). The present findings indicated that certain alleles or genotypes of the CNR1 gene may confer a susceptibility of schizophrenia, especially of the hebephrenic type.

The hebephrenic type schizophrenia, which has been shown to be associated with the CNR1 gene in the present study, is characterized by predominant negative symptoms such as blunted affect, disorganized thought and deterioration of personality. Such symptomatic features of hebephrenic schizophrenia bear resemblance to chronic cannabinoid psychoses. Although acute use of cannabis can induce diverse types of psychotic state, such as panic reaction, confusional state, paranoid state and mania, chronic cannabis users often develop an 'amotivational syndrome typified by a diminution of ambition, productivity and motivation, which are often observed in hebephrenic schizophrenics. In addition, cannabinoid use affects cognitive function such as information processing and planning tasks. Such cognitive dysfunction is prominent in chronic schizophrenics like hebephrenics. Therefore, the endogenous cannabinoid system may
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Contact: Frank Sissingh
molecularpsychiatry@mednet.ucla.edu
310-206-6739
Molecular Psychiatry
1-Jul-2002

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