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失调结合蛋白基因(DTNBP1)与甲基苯丙胺所致精神障碍有关。

The dysbindin gene (DTNBP1) is associated with methamphetamine psychosis.

作者信息

Kishimoto Makiko, Ujike Hiroshi, Motohashi Yasuko, Tanaka Yuji, Okahisa Yuko, Kotaka Tatsuya, Harano Mutsuo, Inada Toshiya, Yamada Mitsuhiko, Komiyama Tokutaro, Hori Toru, Sekine Yoshimoto, Iwata Nakao, Sora Ichiro, Iyo Masaomi, Ozaki Norio, Kuroda Shigetoshi

机构信息

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

出版信息

Biol Psychiatry. 2008 Jan 15;63(2):191-6. doi: 10.1016/j.biopsych.2007.03.019. Epub 2007 Jun 6.

Abstract

BACKGROUND

The dysbindin (DTNBP1 [dystrobrevin-binding protein 1]) gene has repeatedly been shown to be associated with schizophrenia across diverse populations. One study also showed that risk haplotypes were shared with a bipolar disorder subgroup with psychotic episodes, but not with all cases. DTNBP1 may confer susceptibility to psychotic symptoms in various psychiatric disorders besides schizophrenia.

METHODS

Methamphetamine psychosis, the psychotic symptoms of which are close to those observed in schizophrenia, was investigated through a case (n = 197)-control (n = 243) association analyses of DTNBP1.

RESULTS

DTNBP1 showed significant associations with methamphetamine psychosis at polymorphisms of P1635 (rs3213207, p = .00003) and SNPA (rs2619538, p = .049) and the three-locus haplotype of P1655 (rs2619539)-P1635-SNPA (permutation p = .0005). The C-A-A haplotype, which was identical to the protective haplotype previously reported for schizophrenia and psychotic bipolar disorders, was a protective factor (p = .0013, odds ratio [OR] = .62, 95% confidence interval [CI] .51-.77) for methamphetamine psychosis. The C-G-T haplotype was a risk for methamphetamine psychosis (p = .0012, OR = 14.9, 95% CI 3.5-64.2).

CONCLUSIONS

Our genetic evidence suggests that DTNBP1 is involved in psychotic liability not only for schizophrenia but also for other psychotic disorders, including substance-induced psychosis.

摘要

背景

失调结合蛋白(DTNBP1 [肌萎缩蛋白结合蛋白1])基因在不同人群中反复被证明与精神分裂症有关。一项研究还表明,风险单倍型与伴有精神病性发作的双相情感障碍亚组共有,但并非所有病例都有。除精神分裂症外,DTNBP1可能使各种精神障碍易患精神病性症状。

方法

通过对DTNBP1进行病例(n = 197)-对照(n = 243)关联分析,研究了甲基苯丙胺精神病,其精神病性症状与精神分裂症中观察到的症状相似。

结果

DTNBP1在P1635(rs3213207,p = .00003)和SNPA(rs2619538,p = .049)的多态性以及P1655(rs2619539)-P1635-SNPA的三位点单倍型与甲基苯丙胺精神病显著相关(置换p = .0005)。C-A-A单倍型与先前报道的精神分裂症和精神病性双相情感障碍的保护性单倍型相同,是甲基苯丙胺精神病的保护因素(p = .0013,优势比[OR] = .62,95%置信区间[CI].51-.77)。C-G-T单倍型是甲基苯丙胺精神病的风险因素(p = .0012, OR = 14.9, 95% CI 3.5-64.2)。

结论

我们的遗传学证据表明,DTNBP1不仅参与精神分裂症的精神病易感性,还参与包括物质所致精神病在内的其他精神病性障碍

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