Dataset Information

A hypomethylating variant of MTHFR, 677C>T, blunts the neural response to errors in patients with schizophrenia and healthy individuals.

ABSTRACT: 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%.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.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

ACCESS DATA

Publications

A hypomethylating variant of MTHFR, 677C>T, blunts the neural response to errors in patients with schizophrenia and healthy individuals.

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]

PMID: 21980405

Similar Datasets

Project description:BackgroundGenetic polymorphisms can explain some of the population- and individual-based variations in nutritional status biomarkers.ObjectiveWe sought to screen the entire human genome for common genetic polymorphisms that influence folate-status biomarkers in healthy individuals.DesignWe carried out candidate gene analyses and genome-wide association scans in 2232 young, healthy Irish subjects to evaluate which common genetic polymorphisms influence red blood cell folate, serum folate, and plasma total homocysteine.ResultsThe 5,10-methylenetetrahydrofolate reductase (MTHFR) 677C→T (rs1801133) variant was the major genetic modifier of all 3 folate-related biomarkers in this Irish population and reached genome-wide significance for red blood cell folate (P = 1.37 × 10-17), serum folate (P = 2.82 × 10-11), and plasma total homocysteine (P = 1.26 × 10-19) concentrations. A second polymorphism in the MTHFR gene (rs3753584, P = 1.09 × 10-11) was the only additional MTHFR variant to exhibit any significant independent effect on red blood cell folate. Other MTHFR variants, including the 1298A→C variant (rs1801131), appeared to reach genome-wide significance, but these variants shared linkage disequilibrium with MTHFR 677C→T and were not significant when analyzed in MTHFR 677CC homozygotes. No additional non-MTHFR modifiers of red blood cell or plasma folate were detected. Two additional genome-wide significant modifiers of plasma homocysteine were found in the region of the dipeptidase 1 (DPEP1) gene on chromosome 16 and the Twist neighbor B (TWISTNB) gene on chromosome 7.ConclusionsThe MTHFR 677C→T variant is the predominant genetic modifier of folate status biomarkers in this healthy Irish population. It is not necessary to determine MTHFR 677C→T genotype to evaluate folate status because its effect is reflected in concentrations of standard folate biomarkers. The MTHFR 1298A→C variant had no independent effect on folate status biomarkers. To our knowledge, this is the first genome-wide association study report on red blood cell folate and the first report of an association between homocysteine and TWISTNB.

Dataset Information

A hypomethylating variant of MTHFR, 677C>T, blunts the neural response to errors in patients with schizophrenia and healthy individuals.

Publications

A hypomethylating variant of MTHFR, 677C>T, blunts the neural response to errors in patients with schizophrenia and healthy individuals.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

A hypomethylating variant of MTHFR, 677C>T, blunts the neural response to errors in patients with schizophrenia and healthy individuals.

Publications

A hypomethylating variant of MTHFR, 677C&gt;T, blunts the neural response to errors in patients with schizophrenia and healthy individuals.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

A hypomethylating variant of MTHFR, 677C>T, blunts the neural response to errors in patients with schizophrenia and healthy individuals.