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The p250GAP gene is associated with risk for schizophrenia and schizotypal personality traits.

ABSTRACT: BACKGROUND: Hypofunction of the glutamate N-Methyl-d-aspartate (NMDA) receptor has been implicated in the pathophysiology of schizophrenia. p250GAP is a brain-enriched NMDA receptor-interacting RhoGAP. p250GAP is involved in spine morphology, and spine morphology has been shown to be altered in the post-mortem brains of patients with schizophrenia. Schizotypal personality disorder has a strong familial relationship with schizophrenia. Several susceptibility genes for schizophrenia have been related to schizotypal traits. METHODS: We first investigated the association of eight linkage disequilibrium-tagging single-nucleotide polymorphisms (SNPs) that cover the p250GAP gene with schizophrenia in a Japanese sample of 431 schizophrenia patients and 572 controls. We then investigated the impact of the risk genetic variant in the p250GAP gene on schizotypal personality traits in 180 healthy subjects using the Schizotypal Personality Questionnaire. RESULTS: We found a significant difference in genotype frequency between the patients and the controls in rs2298599 (?(2) = 17.6, p = 0.00015). The minor A/A genotype frequency of rs2298599 was higher in the patients (18%) than in the controls (9%) (?(2) = 15.5, p = 0.000083). Moreover, we found that subjects with the rs2298599 risk A/A genotype, compared with G allele carriers, had higher scores of schizotypal traits (F(1,178) = 4.08, p = 0.045), particularly the interpersonal factor (F(1,178) = 5.85, p = 0.017). DISCUSSION: These results suggest that a genetic variation in the p250GAP gene might increase susceptibility not only for schizophrenia but also for schizotypal personality traits. We concluded that the p250GAP gene might be a new candidate gene for susceptibility to schizophrenia.

SUBMITTER: Ohi K

PROVIDER: S-EPMC3329470 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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The p250GAP gene is associated with risk for schizophrenia and schizotypal personality traits.

Ohi Kazutaka K Hashimoto Ryota R Nakazawa Takanobu T Okada Takeya T Yasuda Yuka Y Yamamori Hidenaga H Fukumoto Motoyuki M Umeda-Yano Satomi S Iwase Masao M Kazui Hiroaki H Yamamoto Tadashi T Kano Masanobu M Takeda Masatoshi M

PloS one 20120418 4

<h4>Background</h4>Hypofunction of the glutamate N-Methyl-d-aspartate (NMDA) receptor has been implicated in the pathophysiology of schizophrenia. p250GAP is a brain-enriched NMDA receptor-interacting RhoGAP. p250GAP is involved in spine morphology, and spine morphology has been shown to be altered in the post-mortem brains of patients with schizophrenia. Schizotypal personality disorder has a strong familial relationship with schizophrenia. Several susceptibility genes for schizophrenia have be ...[more]

PMID: 22530067

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Project description:Perceptual organization (PO) difficulties have repeatedly been reported in people with schizophrenia, and in healthy individuals with high levels of schizotypy traits, who are at increased risk for schizophrenia. In particular, poor performance on the Embedded Figures Test (EFT) has been interpreted as an atypically strong preference for global over local processing, even though these processes cannot be clearly disambiguated on this test. Here we use two separate versions of the Radial Frequency Search Task (RFST), a new index of PO abilities, to selectively investigate global and local processing of shape information in trait schizotypy. Schizotypy traits were assessed using the Wisconsin Schizotypy Scales-Brief. Individuals selected for high and low levels of positive schizotypy [assessed with the Wisconsin Schizotypy Scales-Brief Perceptual Aberration (PAb) scale] completed the EFT, along with the Global RFST and the Local RFST, all of which require participants to find a target shape amongst distractor elements. The High PAb group (n = 83) were less efficient (i.e., reactions times slowed more as the set size increased) than the Low PAb group (n = 146) on the Global RFST (significant group differences for Target Absent conditions only), but not the Local RFST. High and Low PAb groups also differed on other schizotypy traits, so the specificity of the results to positive schizotypy cannot be assured. Unexpectedly, no group differences were observed on the EFT; however, there was a small, but significant, positive correlation between RFST search efficiency and EFT performance, indicating that they shared some common processes. Overall, the pattern of results suggests that global (but not local) processing difficulties may be contributing to the poorer perceptual organization observed in groups with high levels of schizotypy traits. In addition, the confinement of this result to the Target Absent condition suggests that the underlying mechanism involves differences in decisional processes on the RFST between high and low schizotypy groups. The RFST shows promise as a useful tool for measuring specific perceptual organization abilities in non-clinical, and potentially clinical, samples.

Dataset Information

The p250GAP gene is associated with risk for schizophrenia and schizotypal personality traits.

Publications

The p250GAP gene is associated with risk for schizophrenia and schizotypal personality traits.

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