期刊
ARCHIVES OF GENERAL PSYCHIATRY
卷 65, 期 3, 页码 298-+出版社
AMER MEDICAL ASSOC
DOI: 10.1001/archgenpsychiatry.2007.48
关键词
-
类别
资金
- NIDA NIH HHS [DA15105, K24 DA015105, DA12690, DA12849, R01 DA012849, R01 DA012690] Funding Source: Medline
- NIMH NIH HHS [K-08 MH01770, R01 MH65413, K24 MH64122, R01MH47077-11] Funding Source: Medline
Context: Although anxiety disorders are heritable, their genetic and phenotypic complexity has made the identification of susceptibility genes difficult. Well-validated animal models and intermediate phenotypes provide crucial tools for genetic dissection of anxiety. The gene encoding regulator of G protein signaling 2 ( Rgs2) is a quantitative trait gene that influences mouse anxiety behavior, making its human ortholog ( RGS2) a compelling candidate gene for human anxiety phenotypes. Objective: To examine whether variation in RGS2 is associated with intermediate phenotypes for human anxiety disorders. Design: Family-based and case-control association analysis of single-nucleotide polymorphisms at the RGS2 locus in 3 independent samples. Setting: Massachusetts General Hospital, University of California, San Diego, and San Diego State University. Participants: Study participants included a family-based sample ( n=119 families) of children who underwent laboratory-based assessments of temperament ( behavioral inhibition), a sample of 744 unrelated adults who completed assessments of extraversion and introversion, and 55 unrelated adults who underwent functional magnetic resonance imaging measures of response to emotional faces. Main Outcome Measures: Laboratory-based behavioral measures of childhood temperament, self-report measure of personality, and functional magnetic resonance imaging response to emotion processing. Results: Markers spanning RGS2 were associated with childhood behavioral inhibition, a temperamental precursor of social anxiety disorder ( haplotype P= 3 x 10(-5); odds ratio, 2.99 in complete trios). In independent samples, RGS2 markers, including rs4606, which has previously been associated with RGS2 expression, were also associated with introversion ( a core personality trait in social anxiety disorder) and with increased limbic activation ( insular cortex and amygdala) during emotion processing ( brain phenotypes correlated with social anxiety). The genotype at rs4606 explained 10% to 15% of the variance in amygdala and insular cortex activation to emotional faces. Conclusions: These results provide the first evidence that a gene that influences anxiety in mice is associated with intermediate phenotypes for human anxiety disorders across multiple levels of assessment, including childhood temperament, adult personality, and brain function. This translational research suggests that some genetic influences on anxiety are evolutionarily conserved and that pharmacologic modulation of RGS2 function may provide a novel therapeutic approach for anxiety disorders.
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