Association of the SerCys DISC1 polymorphism with human hippocampal formation gray matter and function during memory encoding.
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.
Di Giorgio
Annabella
A
Psychiatric Neuroscience Group, Section on Mental Disorders, Department of Neurological and Psychiatric Sciences, University of Bari, Bari, Italy.
Blasi
Giuseppe
G
Sambataro
Fabio
F
Rampino
Antonio
A
Papazacharias
Apostolos
A
Gambi
Francesco
F
Romano
Raffaella
R
Caforio
Grazia
G
Rizzo
Miriam
M
Latorre
Valeria
V
Popolizio
Teresa
T
Kolachana
Bhaskar
B
Callicott
Joseph H
JH
Nardini
Marcello
M
Weinberger
Daniel R
DR
Bertolino
Alessandro
A
D000328:Adult; D000483:Alleles; D000595:Amino Acid Sequence / Q000235:genetics; D019943:Amino Acid Substitution / Q000235:genetics; D003545:Cysteine / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics; D005838:Genotype; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008568:Memory / Q000502:physiology*; D008569:Memory Disorders / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics*; D009434:Neural Pathways / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D011110:Polymorphism, Genetic / Q000235:genetics*; D017397:Prefrontal Cortex / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D012559:Schizophrenia / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D012694:Serine / Q000235:genetics; D055815:Young Adult
C412476:DISC1 protein, human; D009419:Nerve Tissue Proteins; D012694:Serine; D003545:Cysteine