Association of the Ser704Cys DISC1 polymorphism with human hippocampal formation gray matter and function during memory encoding

Annabella Di Giorgio, Giuseppe Blasi, Fabio Sambataro, Antonio Rampino, Apostolos Papazacharias, Francesco Gambi, Raffaella Romano, Grazia Caforio, Miriam Rizzo, Valeria Latorre, Teresa Popolizio, Bhaskar Kolachana, Joseph H. Callicott, Marcello Nardini, Daniel R. Weinberger, Alessandro Bertolino

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2129-2136
Number of pages8
JournalEuropean Journal of Neuroscience
Volume28
Issue number10
DOIs
StatePublished - Nov 2008
Externally publishedYes

Keywords

  • DISC1
  • Gray matter
  • Hippocampus
  • Memory encoding
  • Phenotypic variance
  • fMRI

ASJC Scopus subject areas

  • Neuroscience(all)

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