¹Department of Neuropsychiatry, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan

²Zikei Hospital, Okayama, Japan

³Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, USA

⁴Takami Hospital, Okayama, Japan

⁵Takaoka Hospital, Himeji, Japan

⁶Kasaoka Hospital, Kasaoka, Japan

Correspondence to: H Ujike, MD, PhD, Department of Neuropsychiatry, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama 700-8558, Japan. E-mail: hujike@cc.okayama-u.ac.jp

To examine the cannabinoid hypothesis for pathogenesis of schizophrenia, we examined two kinds of polymorphisms of the CNR1 gene, which encodes human CB1 receptor, a subclass of central cannabinoid receptors, in schizophrenics and age-matched controls in the Japanese population. Allelic and genotypic 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 1359G/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% CI (1.91-2.69)), and decreased rate of the 17 repeat allele (P = 0.011, OR = 0.208, 95% CI (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.

Molecular Psychiatry (2002) 7, 515-518. doi:10.1038/ sj.mp.4001029

CNR1 gene; cannabinoid receptor; schizophrenia; hebephrenic type; Japanese; association study