The Disrupted-in-Schizophrenia-1 Ser704Cys polymorphism and brain neurodevelopmental markers in schizophrenia and healthy subjects

• Published in: Progress in neuro-psychopharmacology & biological psychiatry Vol. 56; pp. 11 - 17
• Main Authors: Takahashi, Tsutomu, Nakamura, Mihoko, Nakamura, Yukako, Aleksic, Branko, Kido, Mikio, Sasabayashi, Daiki, Takayanagi, Yoichiro, Furuichi, Atsushi, Nishikawa, Yumiko, Noguchi, Kyo, Ozaki, Norio, Suzuki, Michio
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 02.01.2015
• Subjects: Adult; Analysis of Variance; Brain - metabolism; Brain - pathology; Cavum septi pellucidi; Chi-Square Distribution; Cysteine - genetics; DISC1; Female; Functional Laterality; Genotype; Humans; Magnetic Resonance Imaging; Male; Nerve Tissue Proteins - genetics; Neurodevelopment; Orbitofrontal cortex; Polymorphism, Single Nucleotide - genetics; Psychiatric Status Rating Scales; Schizophrenia; Schizophrenia - genetics; Schizophrenia - pathology; Serine - genetics; Young Adult; VBM; CSP; Orbitofrontal cortex; MRI; AI; Schizophrenia; CASH; OFC; MOS; ANCOVA; LOS; SNP; ANOVA; SANS; HWE; SAPS; Neurodevelopment; TOS; DISC1; Cavum septi pellucidi
• ISSN: 0278-5846; 1878-4216; 1878-4216
• DOI: 10.1016/j.pnpbp.2014.07.005

Increasing evidence has implicated the role of Disrupted-in-Schizophrenia-1 (DISC1), a potential susceptibility gene for schizophrenia, in early neurodevelopmental processes. However, the effect of its genotype variation on brain morphologic changes related to neurodevelopmental abnormalities in schizophrenia remains largely unknown. This magnetic resonance imaging study examined the association between DISC1 Ser704Cys polymorphism and a range of brain neurodevelopmental markers [cavum septi pellucidi (CSP), adhesio interthalamica (AI), olfactory sulcus depth, and sulcogyral pattern (Types I, II, III, and IV) in the orbitofrontal cortex (OFC)] in an all Japanese sample of 75 schizophrenia patients and 87 healthy controls. The Cys carriers had significantly larger CSP than the Ser homozygotes for both schizophrenia patients and healthy controls. The Cys carriers also exhibited a reduction in the Type I pattern of the right OFC in the healthy controls, but not in the schizophrenia patients. The DISC1 Ser704Cys polymorphism did not affect the AI and olfactory sulcus depth in either group. These results suggested a possible role of the DISC1 genotype in the early neurodevelopment of human brains, but failed to show its specific role in the neurodevelopmental pathology of schizophrenia. •The DISC1 genotype effect on neurodevelopmental markers was examined using MRI.•The subjects were schizophrenia patients and healthy controls.•The genotype affected the CSP and gyral pattern predominantly in healthy controls.•The DISC1 genotype did not affect the adhesio interthalamica or olfactory sulcus.•The genotype alone cannot explain the neurodevelopmental pathology of schizophrenia.