Vitamin B 12 , Folate, and Homocysteine in Depression: The Rotterdam Study

Department of Psychiatry, Erasmus MC, Rotterdam, South Holland, Netherlands
American Journal of Psychiatry (Impact Factor: 12.3). 01/2003; 159(12):2099-101. DOI: 10.1176/appi.ajp.159.12.2099
Source: PubMed


The associations of vitamin B(12), folate, and homocysteine with depression were examined in a population-based study.
The authors screened 3,884 elderly people for depressive symptoms. Subjects with positive screening results had psychiatric workups. Folate, vitamin B(12), and homocysteine blood levels were compared in 278 persons with depressive symptoms, including 112 with depressive disorders, and 416 randomly selected reference subjects. Adjustments were made for age, gender, cardiovascular disease, and functional disability.
Hyperhomocysteinemia, vitamin B(12) deficiency, and to a lesser extent, folate deficiency were all related to depressive disorders. For folate deficiency and hyperhomocysteinemia, the association with depressive disorders was substantially reduced after adjustment for functional disability and cardiovascular disease, but for vitamin B(12) this appeared independent.
The association of vitamin B(12) and folate with depressive disorders may have different underlying mechanisms. Vitamin B(12) may be causally related to depression, whereas the relation with folate is due to physical comorbidity.

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Available from: Henning Tiemeier, Oct 06, 2015
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    • "It was shown in several large studies that elevated plasma or serum homocysteine concentrations and folate and vitamin B 12 deficiency are all significantly associated with depressive disorders (Tiemeier et al. 2002; Gu et al. 2012) or with increased risk of depression (Tolmunen et al. 2004; Refsum et al. 2006; Gilbody et al. 2007; Almeida et al. 2008). Approximately one third of patients with a depression diagnosis showed low concentrations of folate and elevated concentrations of homocysteine in serum or erythrocytes (Carney et al. 1990; Bottiglieri et al. 2000). "
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    ABSTRACT: Objective: Elevated homocysteine is associated with a variety of diseases, including Alzheimer's disease (AD) and depressive disorder. This study was designed to detect an association between plasma homocysteine and AD with or without co-morbid depressive symptoms. Methods: Plasma homocysteine concentrations were measured in 85 AD patients (36 of them with depressive symptoms), 33 non-AD patients with a depression diagnosis and 44 healthy controls, all aged above 50 years. Results: Positive correlation between age and homocysteine was confirmed. Significantly higher mean plasma homocysteine was found in AD patients, but not in depressive patients, when compared with controls. We confirmed significant correlation between homocysteine concentration and the degree of cognitive impairment in AD patients. There was no incremental effect of concurrent depressive symptoms on homocysteine concentration in AD patients. Conclusion: The association of high homocysteine with degree of cognitive impairment or stage of dementia in AD indicate potential role of high plasma homocysteine as a biomarker of the disease and/or indicator of brain damage during the progression of AD dementia.
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    • "Low levels of the B vitamins have been linked to depression, with different B vitamins implicated in particular study populations . While vitamin B12 (cobalamin) showed a strong correlation with depression in elderly population (Robinson et al., 2011; Tiemeier et al., 2002), correlations between folate and depression have been reported in adult and adolescent populations (Beydoun et al., 2010; Murakami et al., 2010). Proposed mechanisms for these associations include the neuronal hypothesis, which suggests decreased synthesis of neurotransmitters serotonin, dopamine and noradrenaline as a consequence of the low levels of these B vitamins, and the 'vascular' hypothesis, which implicates hyperhomocysteinaemia associated vascular damage and chronic inflammation, stemming from deficiency in the B vitamins (Ellsworth-Bowers and Corwin, 2012). "
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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.
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    • "Comparatively few studies aimed to investigate a possible involvement of HCY in depression (Gu et al., 2012). Data from the Rotterdam study (Tiemeier et al., 2002) argued for a relationship of an impaired HCY pathway in depression and the Hordaland HCY Study (Bjelland et al., 2003) showed that homocysteinemia as well as the MTHFR C677T variant are related to depression in a large non-clinical population. Most importantly, those studies were conducted mainly in elderly subjects, which are reasonable when pertinent concepts of vascular dysfunctioning in late-onset depression are taken into account (''vascular depression''; (Naismith et al., 2012)). "
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