Serum Folate, Vitamin B-12, and Homocysteine and Their Association With Depressive Symptoms Among U.S. Adults

National Institute on Aging, National Institutes of Health/Intramural Research Program, Baltimore, Maryland 21224, USA.
Psychosomatic Medicine (Impact Factor: 3.47). 11/2010; 72(9):862-73. DOI: 10.1097/PSY.0b013e3181f61863
Source: PubMed


To examine, in a nationally representative sample of U.S. adults, the associations of serum folate, vitamin B-12, and total homocysteine (tHcy) levels with depressive symptoms. Several nutritional and physiological factors have been linked to depression in adults, including low folate and vitamin B-12 and elevated tHcy levels.
Data on U.S. adults (age, 20-85 years; n = 2524) from the National Health and Nutrition Examination Survey during the period 2005 to 2006 were used. Depressive symptoms were measured with the Patient Health Questionnaire (PHQ), and elevated symptoms were defined as a PHQ total score of ≥10. Serum folate, vitamin B-12, and tHcy were mainly expressed as tertiles. Multiple ordinary least square (OLS), logistic, and zero-inflated Poisson regression models were conducted in the main analysis.
Overall, mean PHQ score was significantly higher among women compared with men. Elevated depressive symptoms (PHQ score of ≥10) were inversely associated with folate status, particularly among women (fully adjusted odds ratio [tertiles T(3) versus T(1)] = 0.37; 95% confidence interval, 0.17-0.86), but not significantly related to tHcy or vitamin B-12. No interaction was noted between the three exposures in affecting depressive symptoms. In older adults (≥50 years) and both sexes combined, tHcy was positively associated with elevated depressive symptoms (fully adjusted odds ratio [tertiles T(2) versus T(1)] = 3.01; 95% confidence interval, 1.01-9.03), although no significant dose-response relationship was found.
Future interventions to improve mental health outcomes among U.S. adults should take into account dietary and other factors that would increase levels of serum folate.

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    • "There is also evidence suggesting that vitamin B6 (Bjelland et al., 2003; Morris et al., 2003) and vitamin B12 (Skarupski et al., 2010) may be associated with MDD-symptomatology. Nevertheless, thus far, no consistent associations are found between these 1-C-cycle components and MDD-symptomatology (Beydoun et al., 2010; Kamphuis et al., 2008; Lindeman et al., 2000; Morris et al., 2003; Penninx et al., 2000). "
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    ABSTRACT: Background An important biological factor suggested in the pathophysiology of (recurrent) Major Depressive Disorder (MDD) concerns a polymorphism in a gene encoding for the MTHFR-enzyme of the one-carbon (1-C)-metabolism. Integratively investigating key 1-C-components (folate, homocysteine, vitamin B6 and B12), including the possible effects of antidepressant medication and depressive state, could provide more insight in the possible association between the MTHFR-polymorphism and recurrent MDD. Methods We compared the MTHFR C677T-polymorphism together with the key 1-C-components in clinically ascertained patients with recurrent MDD (n=137) to age- and gender-matched healthy controls (n=73). Results First, patients had lower folate (t=2.25; p=.025) as compared to controls; a difference that resolved after correction for demographics (t=1.22; p=.223). Second, patients that were depressed during sampling had lower vitamin B6 (t=−2.070; p=.038) and higher homocysteine (t=2.404; p=.016) compared to those in remission. Finally, current use of antidepressants had no influence on the 1-C-components. Conclusions Despite investigation of a specific recurrently depressed patient population, we found no clear associations with the 1-C-cycle, except for higher homocysteine and lower vitamin B6 during the depressed state. This suggests that 1-C-cycle alterations in MDD are state-associated, possibly resulting from high levels of acute (psychological) stress, and may provide a treatment target to reduce cardiovascular risk in this population.
    Journal of Affective Disorders 09/2014; 166:115–123. DOI:10.1016/j.jad.2014.04.048 · 3.38 Impact Factor
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    • "Our study is suggesting that the relationships between folate, vitamin B12 and antenatal depression in mothers are consistent to studies performed in the general population. Data from U.S. adults aged 20e85 years (n ¼ 2524) showed that elevated depressive symptoms, measured by the Patient Health Questionnaire, were inversely associated with (serum) folate status, particularly among women, but not associated with serum vitamin B12 (Beydoun et al., 2010). Similarly, folate intake was inversely associated with depressive symptoms, measured by a Center for Epidemiologic Studies Depression Scale, in a cross-sectional study of Japanese adolescent boys and girls (n ¼ 6517), with no clear association between vitamin B12 intake and depressive symptoms seen (Murakami et al., 2010). "
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    ABSTRACT: Studies in the general population have proposed links between nutrition and depression, but less is known about the perinatal period. Depletion of nutrient reserves throughout pregnancy and delayed postpartum repletion could increase the risk of perinatal depression. We examined the relationships of plasma folate and vitamin B12 concentrations during pregnancy with perinatal depression. At 26th-28th weeks of gestation, plasma folate and vitamin B12 were measured in women from the GUSTO mother-offspring cohort study in Singapore. Depressive symptoms were measured with the Edinburgh Postnatal Depression Scale (EPDS) during the same period and at 3-month postpartum. EPDS scores of ≥15 during pregnancy or ≥13 at postpartum were indicative of probable depression. Of 709 women, 7.2% (n = 51) were identified with probable antenatal depression and 10.4% (n = 74) with probable postnatal depression. Plasma folate concentrations were significantly lower in those with probable antenatal depression than those without (mean ± SD; 27.3 ± 13.8 vs 40.4 ± 36.5 nmol/L; p = 0.011). No difference in folate concentrations was observed in those with and without probable postnatal depression. In adjusted regression models, the likelihood of probable antenatal depression decreases by 0.69 for every unit variation (increase) in folate (OR = 0.69 per SD increase in folate; 95% CI: 0.52, 0.94). Plasma vitamin B12 concentrations were not associated with perinatal depression. Lower plasma folate status during pregnancy was associated with antenatal depression, but not with postnatal depression. Replication in other studies is needed to determine the direction of causality between low folate and antenatal depression. NCT01174875.
    Journal of Psychiatric Research 04/2014; 55. DOI:10.1016/j.jpsychires.2014.04.006 · 3.96 Impact Factor
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    • "All the previous studies showing positive relationships between vitamin B12 levels and DS or depressive disorders have been conducted among older populations [15-18]. On the other hand, most previous population-based studies not showing an association between vitamin B12 levels and depressive disorders or DS have been conducted on younger populations than that in our study [20,21,23]. Exceptions are an American and an Australian study that failed to detect this association among older populations [19,22]. "
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    ABSTRACT: Background An association between vitamin B12 levels and depressive symptoms (DS) has been reported in several epidemiological studies. The purpose of this study was to evaluate vitamin B12 levels in population-based samples with melancholic or non-melancholic DS as the relationship between vitamin B12 levels and different subtypes of DS has not been evaluated in previous studies. Methods Subjects without previously known type 2 diabetes, aged 45–74 years were randomly selected from the National Population Register as a part of the Finnish diabetes prevention programme (FIN-D2D). The study population (N = 2806, participation rate 62%) consisted of 1328 men and 1478 women. The health examinations were carried out between October and December 2007 according to the WHO MONICA protocol. The assessment of DS was based on the Beck Depression Inventory (BDI, cut-off ≥10 points). A DSM-IV- criteria based summary score of melancholic items in the BDI was used in dividing the participants with DS (N = 429) into melancholic (N = 138) and non-melancholic DS (N = 291) subgroups. In the statistical analysis we used chi-squared test, t-test, permutation test, analysis of covariance, multivariate logistic regression analysis and multinomial regression model. Results The mean vitamin B12 level was 331±176 pmol/L in those without DS while the subjects with non-melancholic DS had a mean vitamin B12 level of 324 ± 135 pmol/L, and those with melancholic DS had the lowest mean vitamin B12 level of 292±112 pmol/L (p < 0.001 after adjusted for age, sex, use of antidepressive medication and chronic diseases sum index). The adjusted difference of vitamin B12 levels between the non-melancholic and the melancholic group was 33 pmol/L (95%CI 8 to 57, p = 0.008). Melancholic DS and vitamin B12 levels showed an independent linearly inverse association. The relative risk ratio (RRR) for melancholic DS was 2.75 (95%CI 1.66 to 4.56) in the lowest vitamin B12 level tertile versus the highest (p for linearity <0.001) when those without DS formed the reference group. The RRR in the non-melancholic subgroup was nonsignificant. Conclusions The vitamin B12 level was associated with melancholic DS but not with non-melancholic DS.
    BMC Psychiatry 05/2013; 13(1):145. DOI:10.1186/1471-244X-13-145 · 2.21 Impact Factor
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