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

Naoya Sawamura, Akira Sawa

Research output: Chapter in Book/Report/Conference proceedingConference contribution

28 Citations (Scopus)

Abstract

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.

Original languageEnglish
Title of host publicationAnnals of the New York Academy of Sciences
Pages126-133
Number of pages8
Volume1086
DOIs
Publication statusPublished - 2006 Nov

Publication series

NameAnnals of the New York Academy of Sciences
Volume1086
ISSN (Print)00778923
ISSN (Electronic)17496632

Fingerprint

Brain
Schizophrenia
Type 4 Cyclic Nucleotide Phosphodiesterase
Neuregulin-1
Cell signaling
Pathology
Cyclic AMP
Genes
Data storage equipment
Molecules
Proteins
Neurobiology
Genetic Association Studies
Pedigree
Prefrontal Cortex
Bipolar Disorder
Short-Term Memory
Ethnic Groups
Cerebral Cortex
Lead

Keywords

  • Bipolar disorder
  • DISC1
  • Schizophrenia

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Sawamura, N., & Sawa, A. (2006). Disrupted-in-Schizophrenia-1 (DISC1): A key susceptibility factor for major mental illnesses. In Annals of the New York Academy of Sciences (Vol. 1086, pp. 126-133). (Annals of the New York Academy of Sciences; Vol. 1086). https://doi.org/10.1196/annals.1377.018

Disrupted-in-Schizophrenia-1 (DISC1) : A key susceptibility factor for major mental illnesses. / Sawamura, Naoya; Sawa, Akira.

Annals of the New York Academy of Sciences. Vol. 1086 2006. p. 126-133 (Annals of the New York Academy of Sciences; Vol. 1086).

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Sawamura, N & Sawa, A 2006, Disrupted-in-Schizophrenia-1 (DISC1): A key susceptibility factor for major mental illnesses. in Annals of the New York Academy of Sciences. vol. 1086, Annals of the New York Academy of Sciences, vol. 1086, pp. 126-133. https://doi.org/10.1196/annals.1377.018
Sawamura N, Sawa A. Disrupted-in-Schizophrenia-1 (DISC1): A key susceptibility factor for major mental illnesses. In Annals of the New York Academy of Sciences. Vol. 1086. 2006. p. 126-133. (Annals of the New York Academy of Sciences). https://doi.org/10.1196/annals.1377.018
Sawamura, Naoya ; Sawa, Akira. / Disrupted-in-Schizophrenia-1 (DISC1) : A key susceptibility factor for major mental illnesses. Annals of the New York Academy of Sciences. Vol. 1086 2006. pp. 126-133 (Annals of the New York Academy of Sciences).
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