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

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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 languageEnglish
Pages (from-to)1026-1032
Number of pages7
JournalMolecular Psychiatry
Volume12
Issue number11
DOIs
Publication statusPublished - 11-2007

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

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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