TY - JOUR
T1 - Prevalence of MTHFR C677T and MS A2756G polymorphisms in major depressive disorder, and their impact on response to fluoxetine treatment
AU - Mischoulon, David
AU - Lamon-Fava, Stefania
AU - Selhub, Jacob
AU - Katz, Judith
AU - Papakostas, George I.
AU - Iosifescu, Dan V.
AU - Yeung, Albert S.
AU - Dording, Christina M.
AU - Farabaugh, Amy H.
AU - Clain, Alisabet J.
AU - Baer, Lee
AU - Alpert, Jonathan E.
AU - Nierenberg, Andrew A.
AU - Fava, Maurizio
PY - 2012/6
Y1 - 2012/6
N2 - 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.
AB - 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.
KW - A2756G
KW - Antidepressant
KW - C677T
KW - Depression
KW - Fluoxetine
KW - MS
KW - MTHFR
KW - Methionine Synthase
KW - Methylene Tetrahydrofolate Reductase
UR - http://www.scopus.com/inward/record.url?scp=84869225065&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84869225065&partnerID=8YFLogxK
U2 - 10.1017/S1092852912000430
DO - 10.1017/S1092852912000430
M3 - Article
C2 - 22789065
AN - SCOPUS:84869225065
SN - 1092-8529
VL - 17
SP - 76
EP - 86
JO - CNS spectrums
JF - CNS spectrums
IS - 2
ER -
