Pituitary adenylate cyclase-activating polypeptide is associated with schizophrenia

R. Hashimoto; H. Hashimoto; N. Shintani; S. Chiba; S. Hattori; T. Okada; M. Nakajima; K. Tanaka; N. Kawagishi; K. Nemoto; T. Mori; T. Ohnishi; H. Noguchi; H. Hori; T. Suzuki; N. Iwata; N. Ozaki; T. Nakabayashi; O. Saitoh; A. Kosuga; M. Tatsumi; K. Kamijima; D. R. Weinberger; H. Kunugi; A. Baba

doi:10.1038/sj.mp.4001982

Pituitary adenylate cyclase-activating polypeptide is associated with schizophrenia

R. Hashimoto, H. Hashimoto, N. Shintani, S. Chiba, S. Hattori, T. Okada, M. Nakajima, K. Tanaka, N. Kawagishi, K. Nemoto, T. Mori, T. Ohnishi, H. Noguchi, H. Hori, T. Suzuki, N. Iwata, N. Ozaki, T. Nakabayashi, O. Saitoh, A. KosugaM. Tatsumi, K. Kamijima, D. R. Weinberger, H. Kunugi, A. Baba

Research output: Contribution to journal › Article › peer-review

115 Scopus citations

Abstract

Pituitary adenylate cyclase-activating polypeptide (PACAP, ADCYAP1: adenylate cyclase-activating 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.

Original language	English (US)
Pages (from-to)	1026-1032
Number of pages	7
Journal	Molecular psychiatry
Volume	12
Issue number	11
DOIs	https://doi.org/10.1038/sj.mp.4001982
State	Published - Nov 2007
Externally published	Yes

Keywords

Hippocampus
Memory
PACAP
PPI
SNP
Schizophrenia

ASJC Scopus subject areas

Molecular Biology
Cellular and Molecular Neuroscience
Psychiatry and Mental health

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10.1038/sj.mp.4001982

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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., ... Baba, A. (2007). Pituitary adenylate cyclase-activating polypeptide is associated with schizophrenia. Molecular psychiatry, 12(11), 1026-1032. https://doi.org/10.1038/sj.mp.4001982

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, DR, Kunugi, H & Baba, A 2007, 'Pituitary adenylate cyclase-activating polypeptide is associated with schizophrenia', Molecular psychiatry, vol. 12, no. 11, pp. 1026-1032. https://doi.org/10.1038/sj.mp.4001982

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title = "Pituitary adenylate cyclase-activating polypeptide is associated with schizophrenia",

abstract = "Pituitary adenylate cyclase-activating polypeptide (PACAP, ADCYAP1: adenylate cyclase-activating 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.",

keywords = "Hippocampus, Memory, PACAP, PPI, SNP, Schizophrenia",

author = "R. Hashimoto and H. Hashimoto and N. Shintani and S. Chiba and S. Hattori and T. Okada and M. Nakajima and K. Tanaka and N. Kawagishi and K. Nemoto and T. Mori and T. Ohnishi and H. Noguchi and H. Hori and T. Suzuki and N. Iwata and N. Ozaki and T. Nakabayashi and O. Saitoh and A. Kosuga and M. Tatsumi and K. Kamijima and Weinberger, {D. R.} and H. Kunugi and A. Baba",

note = "Funding Information: We thank Ms Tomoko Shizuno, Keiko Okada and Akiko Murakami for technical assistance and staff of the National Center of Neurology and Psychiatry for recruiting patients and healthy subjects. This work was supported in part by Grants-in-Aid from the Japanese Ministry of Health, Labor and Welfare (H18-kokoro-005, H17-kokoro-001, H17-kokoro-007 and H16-kokoro-002); the Japanese Ministry of Education, Culture, Sports, Science and Technology; Japan Society for the Promotion of Science; CREST (Core Research for Evolutional Science and Technology) of JST (Japan Science and Technology Agency); Japan Foundation for Neuroscience and Mental Health; the Sankyo Foundation of Life Science; and Taisho Pharmaceutical Co Ltd.",

year = "2007",

month = nov,

doi = "10.1038/sj.mp.4001982",

language = "English (US)",

volume = "12",

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AU - Hashimoto, R.

AU - Hashimoto, H.

AU - Shintani, N.

AU - Chiba, S.

AU - Hattori, S.

AU - Okada, T.

AU - Nakajima, M.

AU - Tanaka, K.

AU - Kawagishi, N.

AU - Nemoto, K.

AU - Mori, T.

AU - Ohnishi, T.

AU - Noguchi, H.

AU - Hori, H.

AU - Suzuki, T.

AU - Iwata, N.

AU - Ozaki, N.

AU - Nakabayashi, T.

AU - Saitoh, O.

AU - Kosuga, A.

AU - Tatsumi, M.

AU - Kamijima, K.

AU - Weinberger, D. R.

AU - Kunugi, H.

AU - Baba, A.

N1 - Funding Information: We thank Ms Tomoko Shizuno, Keiko Okada and Akiko Murakami for technical assistance and staff of the National Center of Neurology and Psychiatry for recruiting patients and healthy subjects. This work was supported in part by Grants-in-Aid from the Japanese Ministry of Health, Labor and Welfare (H18-kokoro-005, H17-kokoro-001, H17-kokoro-007 and H16-kokoro-002); the Japanese Ministry of Education, Culture, Sports, Science and Technology; Japan Society for the Promotion of Science; CREST (Core Research for Evolutional Science and Technology) of JST (Japan Science and Technology Agency); Japan Foundation for Neuroscience and Mental Health; the Sankyo Foundation of Life Science; and Taisho Pharmaceutical Co Ltd.

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N2 - Pituitary adenylate cyclase-activating polypeptide (PACAP, ADCYAP1: adenylate cyclase-activating 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.

AB - Pituitary adenylate cyclase-activating polypeptide (PACAP, ADCYAP1: adenylate cyclase-activating 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.

KW - Hippocampus

KW - Memory

KW - PACAP

KW - PPI

KW - SNP

KW - Schizophrenia

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ER -

Pituitary adenylate cyclase-activating polypeptide is associated with schizophrenia

Abstract

Keywords

ASJC Scopus subject areas

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