期刊
BIOLOGICAL PSYCHIATRY
卷 69, 期 10, 页码 1006-1008出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.biopsych.2010.10.031
关键词
Dopamine; efficiency; fMRI; glutamate; prefrontal; working memory
资金
- National Institutes of Health, Bethesda, Maryland
Background: Accumulating evidence indicates that genetic polymorphisms of D-amino acid oxidase activator (DAOA) (M24; rs1421292; T-allele) and catechol-O-methyltransferase (COMT) (Val(158)Met; rs4680) likely enhance susceptibility to schizophrenia. Previously, clinical association between DAOA M24 (T-allele) and a functionally inefficient 3-marker COMT haplotype (that included COMT Val(158)Met) uncovered epistatic effects on risk for schizophrenia. Therefore, we projected that healthy control subjects with risk genotypes for both DAOA M24 (T/T) and COMTVal(158)Met (Val/Val) would produce prefrontal inefficiency, a critical physiological marker of the dorsolateral prefrontal cortex (DLPFC) in schizophrenic patients influenced by both familial and heritable factors. Methods: With 3T blood oxygen level dependent functional magnetic resonance imaging data, we analyzed in SPM5 the proposed interaction of DAOA and COMT in 82 healthy volunteers performing an N-back executive working memory paradigm (2-back > 0-back). Results: As predicted, we detected a functional gene x gene interaction between DAOA and COMT in the DLPFC. Conclusions: The neuroimaging findings here of inefficient information processing in the prefrontal cortex seem to echo prior statistical epistasis between risk alleles for DAOA and COMT, albeit within a small sample. These in vivo results suggest that deleterious genotypes for DAOA and COMT might contribute to the pathophysiology of schizophrenia, perhaps through combined glutamatergic and dopaminergic dysregulation.
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