Background: Observational studies have shown that low folate status induces depression. Here we studied the effects of folic acid supplementation on depression scores of Japanese women with depression-susceptible gene polymorphisms: methylenetetrahydrofolate reductase (MTHFR), serotonin transporter (5-HTT), and dopamine D4 receptor (DRD4).
Design: This was a 16-wk randomized, double-blind, crossover study of a group of Japanese women. Forty-six women (mean age 20 years; range: 18-26) were included in the study. First it was determined if the subjects had one of the following depression-susceptible gene polymorphisms: MTHFR, 5-HTT, or DRD4. The subjects then consumed bread with or without folic acid (200 μg/d) during two 4-wk diet periods separated by an 8-wk washout period. Serum folate and serum total homocysteine (tHcy) concentrations were measured before and after each intervention. Depressive symptoms using the Center for Epidemiologic Studies Depression Scale (CES-D) were determined.
Results:In the folic acid period, serum folate concentration increased from 14.2 nmol/L (median, 25th-75th percentiles: 10.6-17.5) to 23.1 nmol/L (16.4-27.8 p < 0.001); tHcy was reduced from 6.6 µmol/L (5.6-7.5) to 5.7 µmol/L (4.8-6.6, p < 0.001) and CES-D score decreased from 10.0 (3.0-13.0) to 5.0 (2.0-10.0, p < 0.001). In the control period, these changes were either insignificant or reversed. CES-D score significantly decreased by supplementing with folic acid in subjects with depression-susceptible genotypes common among Japanese, namely homozygotes of the "S" allele of 5-HTT and the "4" allele of DRD4View Pdf and Full Text
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