Open Access Research

The Frizzled 3 gene is associated with methamphetamine psychosis in the Japanese population

Makiko Kishimoto1, Hiroshi Ujike12*, Yuko Okahisa1, Tatsuya Kotaka1, Manabu Takaki1, Masafumi Kodama1, Toshiya Inada23, Mitsuhiko Yamada24, Naohisa Uchimura25, Nakao Iwata26, Ichiro Sora27, Masaomi Iyo28, Norio Ozaki29 and Shigetoshi Kuroda1

Author Affiliations

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

2 JGIDA (Japanese Genetics Initiative for Drug Abuse), Japan

3 Institute of Neuropsychiatry, Seiwa Hospital, Tokyo, Japan

4 Department of Psychogeriatrics, National Institute of Mental Health, National Center of Neurology and Psychiatry, Kodaira, Japan

5 Department of Neuropsychiatry, Kurume University Graduate School of Medicine, Kurume, Japan

6 Department of Psychiatry, Fujita Health University School of Medicine, Houmei, Japan

7 Department of Neuroscience, Division of Psychobiology, Tohoku University Graduate School of Medicine, Sendai, Japan

8 Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba, Japan

9 Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Japan

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Behavioral and Brain Functions 2008, 4:37  doi:10.1186/1744-9081-4-37

Published: 15 August 2008



Frizzled 3 (Fzd3) is a receptor required for the Wnt-signaling pathway, which has been implicated in the development of the central nervous system, including synaptogenesis and structural plasticity. We previously found a significant association between the FZD3 gene and susceptibility to schizophrenia, but subsequent studies showed inconsistent findings. To understand the roles of the FZD3 gene in psychotic disorders further, it should be useful to examine FZD3 in patients with methamphetamine psychosis because the clinical features of methamphetamine psychosis are similar to those of schizophrenia.


Six SNPs of FZD3, rs3757888 in the 3' flanking region, rs960914 in the intron 3, rs2241802, a synonymous SNP in the exon5, rs2323019 and rs352203 in the intron 5, and rs880481 in the intron 7, were selected based on the previous schizophrenic studies and analyzed in 188 patients with methamphetamine psychosis and 240 age- and gender-matched controls.


A case-control association analyses revealed that two kinds of FZD3 haplotypes showed strong associations with methamphetamine psychosis (p < 0.00001). Having the G-A-T-G or A-G-C-A haplotype of rs2241802-rs2323019-rs352203-rs880481 was a potent negative risk factor (odds ratios were 0.13 and 0.086, respectively) for methamphetamine psychosis.


Our present and previous findings indicate that genetic variants of the FZD3 gene affect susceptibility to two analogous but distinct dopamine-related psychoses, endogenous and substance-induced psychosis.