| Autor: |
Roffman, Joshua L., Nitenson, Adam Z., Agam, Yigal, Isom, Marlisa, Friedman, Jesse S., Dyckman, Kara A., Brohawn, David G., Smoller, Jordan W., Goff, Donald C., Manoach, Dara S. |
| Předmět: |
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| Zdroj: |
PLoS ONE; 2011, Vol. 6 Issue 9, p1-8, 8p |
| Abstrakt: |
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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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