TY - JOUR
T1 - Association of the Ser704Cys DISC1 polymorphism with human hippocampal formation gray matter and function during memory encoding
AU - Di Giorgio, Annabella
AU - Blasi, Giuseppe
AU - Sambataro, Fabio
AU - Rampino, Antonio
AU - Papazacharias, Apostolos
AU - Gambi, Francesco
AU - Romano, Raffaella
AU - Caforio, Grazia
AU - Rizzo, Miriam
AU - Latorre, Valeria
AU - Popolizio, Teresa
AU - Kolachana, Bhaskar
AU - Callicott, Joseph H.
AU - Nardini, Marcello
AU - Weinberger, Daniel R.
AU - Bertolino, Alessandro
PY - 2008/11
Y1 - 2008/11
N2 - A common nonsynonymous single nucleotide polymorphism leading to a serine-to-cysteine substitution at amino acid 704 (Ser704Cys) in the DISC1 protein sequence has been recently associated with schizophrenia and with specific hippocampal abnormalities. Here, we used multimodal neuroimaging to investigate in a large sample of healthy subjects the putative association of the Ser704Cys DISC1 polymorphism with in vivo brain phenotypes including hippocampal formation (HF) gray matter volume and function (as assessed with functional MRI) as well as HF functional coupling with the neural network engaged during encoding of recognition memory. Individuals homozygous for DISC1 Ser allele relative to carriers of the Cys allele showed greater gray matter volume in the HF. Further, Ser/Ser subjects exhibited greater engagement of the HF together with greater HF-dorsolateral prefrontal cortex functional coupling during memory encoding, in spite of similar behavioral performance. These findings consistently support the notion that Ser704Cys DISC1 polymorphism is physiologically relevant. Moreover, they support the hypothesis that genetic variation in DISC1 may affect the risk for schizophrenia by modifying hippocampal gray matter and function.
AB - A common nonsynonymous single nucleotide polymorphism leading to a serine-to-cysteine substitution at amino acid 704 (Ser704Cys) in the DISC1 protein sequence has been recently associated with schizophrenia and with specific hippocampal abnormalities. Here, we used multimodal neuroimaging to investigate in a large sample of healthy subjects the putative association of the Ser704Cys DISC1 polymorphism with in vivo brain phenotypes including hippocampal formation (HF) gray matter volume and function (as assessed with functional MRI) as well as HF functional coupling with the neural network engaged during encoding of recognition memory. Individuals homozygous for DISC1 Ser allele relative to carriers of the Cys allele showed greater gray matter volume in the HF. Further, Ser/Ser subjects exhibited greater engagement of the HF together with greater HF-dorsolateral prefrontal cortex functional coupling during memory encoding, in spite of similar behavioral performance. These findings consistently support the notion that Ser704Cys DISC1 polymorphism is physiologically relevant. Moreover, they support the hypothesis that genetic variation in DISC1 may affect the risk for schizophrenia by modifying hippocampal gray matter and function.
KW - DISC1
KW - Gray matter
KW - Hippocampus
KW - Memory encoding
KW - Phenotypic variance
KW - fMRI
UR - http://www.scopus.com/inward/record.url?scp=55949127945&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=55949127945&partnerID=8YFLogxK
U2 - 10.1111/j.1460-9568.2008.06482.x
DO - 10.1111/j.1460-9568.2008.06482.x
M3 - Article
C2 - 19046394
AN - SCOPUS:55949127945
SN - 0953-816X
VL - 28
SP - 2129
EP - 2136
JO - European Journal of Neuroscience
JF - European Journal of Neuroscience
IS - 10
ER -