A Hypomethylating Variant of MTHFR, 677C>T, Blunts the Neural Response to Errors in Patients with Schizophrenia and Healthy Individuals
2011

A Schizophrenia Gene Influences Error Processing

Sample size: 56 publication 10 minutes Evidence: moderate

Author Information

Author(s): 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.

Primary Institution: Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School

Hypothesis

Does the MTHFR 677C>T genetic variant affect the neural response to errors in individuals with schizophrenia and healthy individuals?

Conclusion

The MTHFR 677C>T variant blunts the neural response to errors in both schizophrenia patients and healthy individuals.

Supporting Evidence

  • The 677T allele reduces MTHFR activity by 35%.
  • Carriers of the 677T allele showed blunted error-related activation in the dACC.
  • Error-related dACC activation was disrupted among carriers of the 677T allele.
  • Both schizophrenia patients and healthy participants exhibited similar patterns of dACC activation.
  • Genotype effects on error processing were consistent across different diagnostic groups.

Takeaway

A gene linked to schizophrenia affects how people respond to mistakes, making it harder for them to learn from errors.

Methodology

Participants underwent functional MRI while performing an antisaccade task to measure brain activation related to error processing.

Potential Biases

Potential population stratification artifact due to the racially admixed cohort.

Limitations

The study could not directly measure MTHFR genotype effects on methylation in vivo, and dietary folate levels were not assessed.

Participant Demographics

31 outpatients with chronic schizophrenia and 25 demographically matched healthy subjects.

Statistical Information

P-Value

p=0.001

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1371/journal.pone.0025253

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