Ontology highlight
ABSTRACT: Background
Responding to errors is a critical first step in learning from mistakes, a process that is abnormal in schizophrenia. To gain insight into the neural and molecular mechanisms of error processing, we used functional MRI to examine effects of a genetic variant in methylenetetrahydrofolate reductase (MTHFR 677C>T, rs1801133) that increases risk for schizophrenia and that has been specifically associated with increased perseverative errors among patients. MTHFR is a key regulator of the intracellular one-carbon milieu, including DNA methylation, and each copy of the 677T allele reduces MTHFR activity by 35%.Methodology/principal findings
Using an antisaccade paradigm, we found that the 677T allele induces a dose-dependent blunting of dorsal anterior cingulate cortex (dACC) activation in response to errors, a pattern that was identical in healthy individuals and patients with schizophrenia. Further, the normal relationship between dACC activation and error rate was disrupted among carriers of the 677T allele.Conclusions/significance
These findings implicate an epigenetic mechanism in the neural response to errors, and provide insight into normal cognitive variation through a schizophrenia risk gene.
SUBMITTER: Roffman JL
PROVIDER: S-EPMC3182200 | biostudies-literature | 2011
REPOSITORIES: biostudies-literature
Roffman Joshua L JL Nitenson Adam Z AZ Agam Yigal Y Isom Marlisa M Friedman Jesse S JS Dyckman Kara A KA Brohawn David G DG Smoller Jordan W JW Goff Donald C DC Manoach Dara S DS
PloS one 20110928 9
<h4>Background</h4>Responding to errors is a critical first step in learning from mistakes, a process that is abnormal in schizophrenia. To gain insight into the neural and molecular mechanisms of error processing, we used functional MRI to examine effects of a genetic variant in methylenetetrahydrofolate reductase (MTHFR 677C>T, rs1801133) that increases risk for schizophrenia and that has been specifically associated with increased perseverative errors among patients. MTHFR is a key regulator ...[more]