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Association of the Ser 704 Cys DISC1 polymorphism with human hippocampal formation gray matter and function during memory encoding
Author(s) -
Di Giorgio Annabella,
Blasi Giuseppe,
Sambataro Fabio,
Rampino Antonio,
Papazacharias Apostolos,
Gambi Francesco,
Romano Raffaella,
Caforio Grazia,
Rizzo Miriam,
Latorre Valeria,
Popolizio Teresa,
Kolachana Bhaskar,
Callicott Joseph H,
Nardini Marcello,
Weinberger Daniel R,
Bertolino Alessandro
Publication year - 2008
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2008.06482.x
Subject(s) - disc1 , hippocampal formation , single nucleotide polymorphism , neuroscience , white matter , allele , prefrontal cortex , psychology , genetics , biology , genotype , medicine , magnetic resonance imaging , gene , cognition , radiology
A common nonsynonymous single nucleotide polymorphism leading to a serine‐to‐cysteine substitution at amino acid 704 (Ser 704 Cys) 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 Ser 704 Cys 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 Ser 704 Cys 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.