Prevalence of MTHFR C677T and MS A2756G polymorphisms in major depressive disorder, and their impact on response to fluoxetine treatment

David Mischoulon, Stefania Lamon-Fava, Jacob Selhub, Judith Katz, George I. Papakostas, Dan V. Iosifescu, Albert S. Yeung, Christina M. Dording, Amy H. Farabaugh, Alisabet J. Clain, Lee Baer, Jonathan E. Alpert, Andrew A. Nierenberg, Maurizio Fava

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Objective. To examine the prevalence of the C677T polymorphism of the methylene tetrahydrofolate reductase (MTHFR) gene and the A2756G polymorphism of methionine synthase (MS), and their impact on antidepressant response. Methods. We screened 224 subjects (52% female, mean age 39 ± 11 years) with SCID-diagnosed major depressive disorder (MDD), and obtained 194 genetic samples. 49 subjects (49% female, mean age 36 ± 11 years) participated in a 12-week open clinical trial of fluoxetine 20-60 mg/day. Association between clinical response and C677T and A2756G polymorphisms, folate, B12, and homocysteine was examined. Results. Prevalence of the C677T and A2756G polymorphisms was consistent with previous reports (C/C=41%, C/T=47%, T/T=11%, A/A=66%, A/G=29%, G/G=4%). In the fluoxetine-treated subsample (n=49), intent-to-treat (ITT) response rates were 47% for C/C subjects and 46% for pooled C/T and T/T subjects (nonsignificant). ITT response rates were 38% for A/A subjects and 60% for A/G subjects (nonsignificant), with no subjects exhibiting the G/G homozygote. Mean baseline plasma B12 was significantly lower in A/G subjects compared to A/A, but folate and homocysteine levels were not affected by genetic status. Plasma folate was negatively associated with treatment response. Conclusion. The C677T and A2756G polymorphisms did not significantly affect antidepressant response. These preliminary findings require replication in larger samples.

Original languageEnglish (US)
Pages (from-to)76-86
Number of pages11
JournalCNS Spectrums
Volume17
Issue number2
DOIs
StatePublished - Jun 1 2012
Externally publishedYes

Keywords

  • A2756G
  • Antidepressant
  • C677T
  • Depression
  • Fluoxetine
  • MS
  • MTHFR
  • Methionine Synthase
  • Methylene Tetrahydrofolate Reductase

ASJC Scopus subject areas

  • Clinical Neurology
  • Psychiatry and Mental health

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    Mischoulon, D., Lamon-Fava, S., Selhub, J., Katz, J., Papakostas, G. I., Iosifescu, D. V., Yeung, A. S., Dording, C. M., Farabaugh, A. H., Clain, A. J., Baer, L., Alpert, J. E., Nierenberg, A. A., & Fava, M. (2012). Prevalence of MTHFR C677T and MS A2756G polymorphisms in major depressive disorder, and their impact on response to fluoxetine treatment. CNS Spectrums, 17(2), 76-86. https://doi.org/10.1017/S1092852912000430