Disrupted-in-Schizophrenia-1 (DISC1): A key susceptibility factor for major mental illnesses

Naoya Sawamura*, Akira Sawa


研究成果: Conference contribution

29 被引用数 (Scopus)


Here we overview Disrupted-in-Schizophrenia-1 (DISC1), a promising lead in studying the pathophysiology of major mental conditions. Genetic association studies reproducibly suggest involvement of DISC1 in both schizophrenia and bipolar disorder in several ethnic groups. Different from several other susceptibility genes for schizophrenia, such as neuregulin-1 and dysbindin, there are two independent pedigrees in which genetic variations of DISC1 directly segregate with major mental conditions. This uniqueness has facilitated neurobiology of DISC1, which may hopefully lead to an important breakthrough in understanding of pathophysiology of major mental conditions. DISC1 is a multifunctional protein that plays a role in neurodevelopment and cell signaling. In autopsied brains from patients with psychosis and substance abuse, change in subcellular distribution of DISC1 is observed. DISC1 interacts with phosphodiesterase (PDE) 4B that degrades cyclic AMP (cAMP), which may be a regulatory molecule for working memory in the prefrontal cortex. Knockdown expression of DISC1 in developing cerebral cortex in mouse brains leads to changes that resemble, at least in part, the pathology found in patients with schizophrenia. These results support involvement of DISC1 in the pathophysiology of major mental conditions, including schizophrenia, in several mechanisms.

ホスト出版物のタイトルIntegrated Molecular Medicine for Neuronal and Neoplastic Disorders
出版社Blackwell Publishing Inc.
ISBN(印刷版)1573316555, 9781573316552
出版ステータスPublished - 2006 11月


名前Annals of the New York Academy of Sciences

ASJC Scopus subject areas

  • 神経科学(全般)
  • 生化学、遺伝学、分子生物学(全般)
  • 科学史および科学哲学


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