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 journalArticlepeer-review

115 Scopus citations


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 (US)
Pages (from-to)1026-1032
Number of pages7
JournalMolecular psychiatry
Issue number11
StatePublished - Nov 2007
Externally publishedYes


  • Hippocampus
  • Memory
  • PPI
  • SNP
  • Schizophrenia

ASJC Scopus subject areas

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


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