Pituitary adenylate cyclase-activating polypeptide is associated with schizophrenia.
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.
Hashimoto
R
R
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
Hashimoto
H
H
Shintani
N
N
Chiba
S
S
Hattori
S
S
Okada
T
T
Nakajima
M
M
Tanaka
K
K
Kawagishi
N
N
Nemoto
K
K
Mori
T
T
Ohnishi
T
T
Noguchi
H
H
Hori
H
H
Suzuki
T
T
Iwata
N
N
Ozaki
N
N
Nakabayashi
T
T
Saitoh
O
O
Kosuga
A
A
Tatsumi
M
M
Kamijima
K
K
Weinberger
D R
DR
Kunugi
H
H
Baba
A
A
D000328:Adult; D000483:Alleles; D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage; D001522:Behavior, Animal; D016009:Chi-Square Distribution; D004195:Disease Models, Animal; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008875:Middle Aged; D009043:Motor Activity / Q000187:drug effects / Q000235:genetics; D009433:Neural Inhibition / Q000187:drug effects / Q000235:genetics; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000172:deficiency / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I / Q000235:genetics; D018967:Risperidone / Q000008:administration & dosage; D012559:Schizophrenia / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology
C495401:ADCYAP1 protein, human; C495503:ADCYAP1R1 protein, human; D014150:Antipsychotic Agents; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; D018967:Risperidone