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Mol Psychiatry. 2007 Nov;12(11):1026-32. Epub 2007 Mar 27.

Pituitary adenylate cyclase-activating polypeptide is associated with schizophrenia.

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1
The Osaka-Hamamatsu Joint Research Center for Child Mental Development, Osaka University Graduate School of Medicine, Yamadaoka, Suita, Osaka, Japan. hashimor@psy.med.osaka-u.ac.jp

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.

PMID:
17387318
DOI:
10.1038/sj.mp.4001982
[Indexed for MEDLINE]
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