Pituitary adenylate cyclase-activating polypeptide is associated with schizophrenia

被引：122

作者：

Hashimoto, R.

Hashimoto, H.

Shintani, N.

Chiba, S.

Hattori, S.

Okada, T.

Nakajima, M.

Tanaka, K.

Kawagishi, N.

Nemoto, K.

Mori, T.

Ohnishi, T.

Noguchi, H.

Hori, H.

Suzuki, T.

Iwata, N.

Ozaki, N.

Nakabayashi, T.

Saitoh, O.

Kosuga, A.

Tatsumi, M.

Kamijima, K.

Weinberger, D. R.

Kunugi, H.

Baba, A.

机构：

[1] Osaka Univ, Grad Sch Med, Osaka Hamamatsu Joint Res, Ctr Child & Mental Dev, Suita, Osaka 565, Japan

[2] Natl Ctr Neurol & Psychiat, Natl Inst Neurosci, Dept Mental Disorder Res, Kodaira, Tokyo 187, Japan

[3] Osaka Univ, Grad Sch Pharmaceut Sci, Osaka Hamamatsu Joint Res, Lab Mol Neuropharmacol, Suita, Osaka 565, Japan

[4] Natl Ctr Hosp Mental Nervous & Muscular Disorders, Natl Ctr Neurol & Psychiat, Dept Radiol, Kodaira, Tokyo, Japan

[5] Fujita Hlth Univ, Sch Med, Dept Psychiat, Toyoake, Aichi 47011, Japan

[6] Nagoya Univ, Grad Sch Med, Dept Psychiat, Nagoya, Aichi, Japan

[7] Natl Ctr Neurol & Psychiat, Natl Ctr Hosp Mental Nervous & Muscular Disorders, Dept Psychiat, Kodaira, Tokyo, Japan

[8] Showa Univ, Sch Med, Dept Psychiat, Shinagawa Ku, Tokyo 142, Japan

[9] NIH, NIMH, Clin Brain Disorders Branch, Cognit & Psychosis Program, Bethesda, MD 20892 USA

来源：

MOLECULAR PSYCHIATRY | 2007年 / 12卷 / 11期

基金：

日本科学技术振兴机构; 日本学术振兴会;

关键词：

schizophrenia; PACAP; SNP; hippocampus; memory; PPI;

D O I：

10.1038/sj.mp.4001982

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Pituitary adenylate cyclase- activating polypeptide (PACAP, ADCYAP1: adenylate cyclaseactivating polypeptide 1), a neuropeptide with neurotransmission modulating activity, is a promising schizophrenia candidate gene. Here, we provide evidence that genetic variants of the genes encoding PACAP and its receptor, PAC1, are associated with schizophrenia. We studied the effects of the associated polymorphism in the PACAP gene on neurobiological traits related to risk for schizophrenia. This allele of the PACAP gene, which is overrepresented in schizophrenia patients, was associated with reduced hippocampal volume and poorer memory performance. Abnormal behaviors in PACAP knockout mice, including elevated locomotor activity and deficits in prepulse inhibition of the startle response, were reversed by treatment with an atypical antipsychotic, risperidone. These convergent data suggest that alterations in PACAP signaling might contribute to the pathogenesis of schizophrenia.

引用

页码：1026 / 1032

页数：7

共 26 条

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