Journal
BIOLOGICAL PSYCHIATRY
Volume 69, Issue 10, Pages 1006-1008Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.biopsych.2010.10.031
Keywords
Dopamine; efficiency; fMRI; glutamate; prefrontal; working memory
Categories
Funding
- National Institutes of Health, Bethesda, Maryland
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available