Variation in DISC1 affects hippocampal structure and function and increases risk for schizophrenia
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- Joseph H. Callicott
- Genes, Cognition, and Psychosis Program, Clinical Brain Disorders Branch, Division of Intramural Research, National Institute of Mental Health, National Institutes of Health, and Department of Health and Human Services, Bethesda, MD 20892
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- Richard E. Straub
- Genes, Cognition, and Psychosis Program, Clinical Brain Disorders Branch, Division of Intramural Research, National Institute of Mental Health, National Institutes of Health, and Department of Health and Human Services, Bethesda, MD 20892
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- Lukas Pezawas
- Genes, Cognition, and Psychosis Program, Clinical Brain Disorders Branch, Division of Intramural Research, National Institute of Mental Health, National Institutes of Health, and Department of Health and Human Services, Bethesda, MD 20892
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- Michael F. Egan
- Genes, Cognition, and Psychosis Program, Clinical Brain Disorders Branch, Division of Intramural Research, National Institute of Mental Health, National Institutes of Health, and Department of Health and Human Services, Bethesda, MD 20892
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- Venkata S. Mattay
- Genes, Cognition, and Psychosis Program, Clinical Brain Disorders Branch, Division of Intramural Research, National Institute of Mental Health, National Institutes of Health, and Department of Health and Human Services, Bethesda, MD 20892
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- Ahmad R. Hariri
- Genes, Cognition, and Psychosis Program, Clinical Brain Disorders Branch, Division of Intramural Research, National Institute of Mental Health, National Institutes of Health, and Department of Health and Human Services, Bethesda, MD 20892
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- Beth A. Verchinski
- Genes, Cognition, and Psychosis Program, Clinical Brain Disorders Branch, Division of Intramural Research, National Institute of Mental Health, National Institutes of Health, and Department of Health and Human Services, Bethesda, MD 20892
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- Andreas Meyer-Lindenberg
- Genes, Cognition, and Psychosis Program, Clinical Brain Disorders Branch, Division of Intramural Research, National Institute of Mental Health, National Institutes of Health, and Department of Health and Human Services, Bethesda, MD 20892
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- Rishi Balkissoon
- Genes, Cognition, and Psychosis Program, Clinical Brain Disorders Branch, Division of Intramural Research, National Institute of Mental Health, National Institutes of Health, and Department of Health and Human Services, Bethesda, MD 20892
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- Bhaskar Kolachana
- Genes, Cognition, and Psychosis Program, Clinical Brain Disorders Branch, Division of Intramural Research, National Institute of Mental Health, National Institutes of Health, and Department of Health and Human Services, Bethesda, MD 20892
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- Terry E. Goldberg
- Genes, Cognition, and Psychosis Program, Clinical Brain Disorders Branch, Division of Intramural Research, National Institute of Mental Health, National Institutes of Health, and Department of Health and Human Services, Bethesda, MD 20892
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- Daniel R. Weinberger
- Genes, Cognition, and Psychosis Program, Clinical Brain Disorders Branch, Division of Intramural Research, National Institute of Mental Health, National Institutes of Health, and Department of Health and Human Services, Bethesda, MD 20892
書誌事項
- 公開日
- 2005-06-06
- DOI
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- 10.1073/pnas.0500515102
- 公開者
- National Academy of Sciences
この論文をさがす
説明
<jats:p> Disrupted-in-schizophrenia 1 (DISC1) is a promising schizophrenia candidate gene expressed predominantly within the hippocampus. We typed 12 single-nucleotide polymorphisms (SNPs) that covered the DISC1 gene. A three-SNP haplotype [hCV219779 (C)-rs821597 (G)-rs821616 (A)] spanning 83 kb of the gene was associated with schizophrenia in a family-based sample ( <jats:italic>P</jats:italic> = 0.002). A common nonconservative SNP (Ser704Cys) (rs821616) within this haplotype was associated with schizophrenia ( <jats:italic>P</jats:italic> = 0.004). Based on primary expression of DISC1 in hippocampus, we hypothesized that allelic variation at Ser704Cys would have a measurable impact on hippocampal structure and function as assayed via specific hippocampus-related intermediate phenotypes. In addition to overtransmission in schizophrenia, the Ser allele was associated with altered hippocampal structure and function in healthy subjects, including reduced hippocampal gray matter volume and altered engagement of the hippocampus during several cognitive tasks assayed with functional magnetic resonance imaging. These convergent data suggest that allelic variation within DISC1, either at Ser704Cys or haplotypes monitored by it, increases the risk for schizophrenia and that the mechanism of this effect involves structural and functional alterations in the hippocampal formation. </jats:p>
収録刊行物
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- Proceedings of the National Academy of Sciences
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Proceedings of the National Academy of Sciences 102 (24), 8627-8632, 2005-06-06
National Academy of Sciences
