期刊
AMERICAN JOURNAL OF PSYCHIATRY
卷 169, 期 9, 页码 982-990出版社
AMER PSYCHIATRIC PUBLISHING, INC
DOI: 10.1176/appi.ajp.2012.11101585
关键词
-
类别
资金
- German Federal Ministry of Education and Research [01GS08144, 01GS08147]
- German Research Foundation [FOR926, BI 1227/3-1, SFB779-TPA08, GRK 793]
- Alfried Krupp von Bohlen und Halbach-Stiftung
- Seventh Framework Programme of the European Union (ADAMS project) [HEALTH-F4-2009-242257]
- NIH [1RC2MH089921-01, 1RC2MH090047-01, 1RC2MH089929-01]
Objective: Genome-wide association has been reported between the NCAN gene and bipolar disorder. The aims of this study were to characterize the clinical symptomatology most strongly influenced by NCAN and to explore the behavioral phenotype of Ncan knockout (Ncan(-/-)) mice. Method: Genotype/phenotype correlations were investigated in patients with bipolar disorder (N=641) and the genetically related disorders major depression (N=597) and schizophrenia (N=480). Principal components and genotype association analyses were used to derive main clinical factors from 69 lifetime symptoms and to determine which of these factors were associated with the NCAN risk allele. These analyses were then repeated using the associated factor(s) only in order to identify the more specific clinical sub-dimensions that drive the association. Ncan(-/-) mice were tested using diverse paradigms, assessing a range of behavioral traits, including paradigms corresponding to bipolar symptoms in humans. Results: In the combined patient sample, the NCAN risk allele was significantly associated with the mania factor, in particular the subdimension overactivity. Ncan(-/-) mice were hyperactive and showed more frequent risk-taking and repetitive behaviors, less depression-like conduct, impaired prepulse inhibition, amphetamine hypersensitivity, and increased saccharin preference. These aberrant behavioral responses normalized after the administration of lithium. Conclusions: NCAN preferentially affected mania symptoms in humans. Ncan(-/-) mice showed behavioral abnormalities that were strikingly similar to those of the human mania phenotype and may thus serve as a valid mouse model.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据