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

Published online by Cambridge University Press:  04 May 2012

David Mischoulon ,
Stefania Lamon-Fava ,
Jacob Selhub ,
Judith Katz ,
George I. Papakostas ,
Dan V. Iosifescu ,
Albert S. Yeung ,
Christina M. Dording ,
Amy H. Farabaugh  and
Alisabet J. Clain
...Show all authors
David Mischoulon*
Affiliation:
Depression Clinical and Research Program, Massachusetts General Hospital and Harvard Medical School, Boston, MA
Stefania Lamon-Fava
Affiliation:
Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA
Jacob Selhub
Affiliation:
Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA
Judith Katz
Affiliation:
Depression Clinical and Research Program, Massachusetts General Hospital and Harvard Medical School, Boston, MA
George I. Papakostas
Affiliation:
Depression Clinical and Research Program, Massachusetts General Hospital and Harvard Medical School, Boston, MA
Dan V. Iosifescu
Affiliation:
Depression Clinical and Research Program, Massachusetts General Hospital and Harvard Medical School, Boston, MA
Albert S. Yeung
Affiliation:
Depression Clinical and Research Program, Massachusetts General Hospital and Harvard Medical School, Boston, MA
Christina M. Dording
Affiliation:
Depression Clinical and Research Program, Massachusetts General Hospital and Harvard Medical School, Boston, MA
Amy H. Farabaugh
Affiliation:
Depression Clinical and Research Program, Massachusetts General Hospital and Harvard Medical School, Boston, MA
Alisabet J. Clain
Affiliation:
Depression Clinical and Research Program, Massachusetts General Hospital and Harvard Medical School, Boston, MA
Lee Baer
Affiliation:
Depression Clinical and Research Program, Massachusetts General Hospital and Harvard Medical School, Boston, MA
Jonathan E. Alpert
Affiliation:
Depression Clinical and Research Program, Massachusetts General Hospital and Harvard Medical School, Boston, MA
Andrew A. Nierenberg
Affiliation:
Depression Clinical and Research Program, Massachusetts General Hospital and Harvard Medical School, Boston, MA
Maurizio Fava
Affiliation:
Depression Clinical and Research Program, Massachusetts General Hospital and Harvard Medical School, Boston, MA
*
*Address correspondence to: David Mischoulon, MD, PhD, 1 Bowdoin Square, 6th Floor, Massachusetts General Hospital, Boston, MA 02114, Tel. 617-724-5198; Fax 617-724-3028. (Email dmischoulon@partners.org)
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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.

Keywords

Methylene Tetrahydrofolate ReductaseMTHFRMethionine SynthaseMSC677TA2756Gdepressionantidepressantfluoxetine
Type
Original Research
Information
CNS Spectrums , Volume 17 , Issue 2 , June 2012 , pp. 76 - 86
Copyright
Copyright © Cambridge University Press 2012

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