Vitamin B12, folate, and homocysteine in depression: the Rotterdam Study. Five year changes in mental health and associations with vitamin B12/folate status of elderly Europeans. Predictive value of folate, vitamin B12 and homocysteine levels in late-life depression. The B-VITAGE trial: A randomized trial of homocysteine lowering treatment of depression in later life Dietary factors and depression in older people. Longitudinal association of vitamin B-6, folate, and vitamin B-12 with depressive symptoms among older adults over time. Nutritional Factors Associated with Antenatal Depressive Symptoms in the Early Stage of Pregnancy Among Urban South Indian Women Micronutrient supplementation may reduce symptoms of depression in Guatemalan women. Dietary folate and vitamin B12 intake and cognitive decline among community-dwelling older persons. Folate Augmentation of Treatment--Evaluation for Depression (FolATED): randomised trial and economic evaluation. Nutritional Status in Relation to Balance and Falls in the Elderly Effects of dietary supplements on depressive symptoms in older patients: a randomised double-blind placebo-controlled trial. B vitamins to enhance treatment response to antidepressants in middle-aged and older adults: results from the B-VITAGE randomised, double-blind, placebo-controlled trial. Correlations between cognitive, behavioural and psychological findings and levels of vitamin B12 and folate in patients with dementia. Serum folate, vitamin B12, and homocysteine in major depressive disorder, Part 1: predictors of clinical response in fluoxetine-resistant depression. Randomized multicenter investigation of folate plus vitamin B12 supplementation in schizophrenia. Serum Vitamin B12, C and Folate Concentrations in the New Mexico Elder Health Survey: Correlations with Cognitive and Affective Functions
OBJECTIVE The associations of vitamin B(12 ) , folate , and homocysteine with depression were examined in a population -based study . METHOD 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 r and omly selected reference subjects . Adjustments were made for age , gender , cardiovascular disease , and functional disability . RESULTS 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 . CONCLUSIONS 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 OBJECTIVE To describe 5-year changes of mental health in SENECA participants , and to examine whether mental health is associated with the status of vitamin B12 and folate . DESIGN A longitudinal , multicentre study including a Baseline study , a Follow-up study , and a Finale study . SUBJECTS Inhabitants of 11 European towns , born between 1913 and 1918 , were r and omly selected at baseline to participate in the SENECA study . Of the 1099 enrolled subjects in the Follow-up study , 586 participated in the Finale study . INTERVENTION Mental health status was assessed by the  Mini-Mental State Examination ( MMSE , cognitive impairment defined as MMSE<23 ) and the  15-item Geriatric Depression Scale  ( GDS , depression defined as GDS>5 ) . RESULTS In the Finale study , mean overall MMSE score was 26.1 for men and 25.6 for women , while mean overall GDS score was 3.1 for men and 4.1 for women . Among subjects that participated in both the Follow-up and the Finale study , MMSE scores decreased with 0.9 points ( P<0.0001 ) and 1.0 points ( P<0.0001 ) among men and women respectively . The GDS scores decreased with 0.7 points ( P<0.0001 ) for men and 0.8 points ( P<0.0001 ) for women . Among subjects that participated in the Finale study , no significant correlations have been observed between mental health and vitamin B12/folate status . CONCLUSION In the Finale study , mental health of the majority of the SENECA participants remained intact . In contrast to the Follow-up study , no associations between mental health and vitamin B12/folate status were emerged BACKGROUND The role of folate , vitamin B(12 ) and homocysteine levels in depression is not clear . AIMS To investigate cross-sectional and prospect i ve associations between folate , B(12 ) and homocysteine levels and late-life depression . METHOD A total of 732 Korean people aged 65 years or over were evaluated at baseline . Of the 631 persons who were not depressed , 521 ( 83 % ) were followed over a period of 2 - 3 years and incident depression was ascertained with the Geriatric Mental State schedule .  Serum folate , serum vitamin B(12 ) and plasma homocysteine levels were assayed at both baseline and follow-up . RESULTS Lower levels of folate and vitamin B(12 ) and higher homocysteine levels at baseline were associated with a higher risk of incident depression at follow-up . Incident depression was associated with a decline in vitamin B(12 ) and an increase in homocysteine levels over the follow-up period . CONCLUSIONS Lower folate , lower vitamin B(12 ) and raised homocysteine levels may be risk factors for late-life depression Background Depression is a leading cause of disability worldwide and depressive symptoms are common in later life . Observational evidence suggests that depression is more prevalent among people with high plasma homocysteine ( tHcy ) , but the results of r and omized trials to date have been unable to show that lowering tHcy through the supplementation of vitamins B6 , B12 and folate benefits depressive symptoms . We design ed the B-VITAGE trial to determine whether adjunctive treatment with vitamins B6 , B12 and folate increases the efficacy of st and ard antidepressant treatment . Methods / Design The B-VITAGE trial is a 12-month r and omized , double-blind , placebo-controlled trial of daily citalopram ( 20 to 40 mg ) plus B12(0.4 mg ) , B6 ( 25 mg ) and folic acid ( 2 mg ) or citalopram ( 20 to 40 mg ) plus placebo for the treatment of depression in later life . The trial aims to recruit over 300 older adults with major depression ( DSM-IV ) and has been powered to detect the impact of an intervention associated with moderate effect size . Depressive symptoms will be rated with the Montgomery-Åsberg Depression Rating Scale ( MADRS ) . The trial has two main outcomes of interest : a reduction of 50 % or more in the MADRS total score between baseline and week 12 and the remission of the depressive episode at weeks 12 , 26 and 52 according to DSM-IV criteria . We hypothesize that subjects r and omly allocated to the vitamin arm of the study will be more likely to show a clinical ly significant improvement and achieve and maintain remission of symptoms at 12 , 26 and 52 weeks . Secondary outcomes of interest include compliance with treatment , reduction in the severity of depressive symptoms , switching to different antidepressants , the use of non-pharmacological antidepressant treatments , response to treatment according to MTHFRC677 T genotype , and changes in cognitive function over 52 weeks . Conclusions The results of this trial will clarify whether the systematic use of B-vitamins improves the response of older adults to st and ard antidepressant treatment . We anticipate that our findings will have implication s for clinical practice and health policy development . Trial Registration The trial is registered with the Australian Clinical Trials Registry , trial number ( ())ACTRN12609000256279 Depression is one of the most prevalent mental health conditions and can affect people of all ages , but it is becoming more common among the older population with increasing life expectancy . Observational studies have found poor micronutrient status ( particularly folate and vitamin B12 ) to be associated with an increased risk of  depression in older people .  Supplementation with folic acid has been shown to enhance anti-depressant drug treatment and there is preliminary evidence that supplementation with certain micronutrients may help improve depressive symptoms in older patients . There has also been a lot of interest in the role of long-chain omega-3 fatty acids in depression . However , the evidence from r and omized controlled trials is limited and difficult to evaluate owing to considerable variability between studies . The research highlights the importance of a healthy diet and lifestyle to help maintain good mental health into old age and health professionals should try to support older people in trying to achieve this BACKGROUND B-vitamin deficiencies have been associated with depression ; however , there is very little prospect i ve evidence from population -based studies of older adults . OBJECTIVE We examined whether dietary intakes of vitamins B-6 , folate , or vitamin B-12 were predictive of depressive symptoms over an average of 7.2 y in a community-based population of older adults . DESIGN The study sample consisted of 3503 adults from the Chicago Health and Aging project , an ongoing , population -based , biracial ( 59 % African American ) study in adults aged > or = 65 y.  Dietary assessment was made by food-frequency question naire . Incident depression was measured by the presence of > or = 4 depressive symptoms from the 10-item version of the Center for Epidemiologic Studies Depression scale . RESULTS The logistic regression models , which used generalized estimating equations , showed that higher total intakes , which included supplementation , of vitamins B-6 and B-12 were associated with a decreased likelihood of incident depression for up to 12 y of follow-up , after adjustment for age , sex , race , education , income , and antidepressant medication use . For example , each 10 additional milligrams of vitamin B-6 and 10 additional micrograms of vitamin B-12 were associated with 2 % lower odds of depressive symptoms per year . There was no association between depressive symptoms and food intakes of these vitamins or folate . These associations remained after adjustment for smoking , alcohol use , widowhood , caregiving status , cognitive function , physical disability , and medical conditions . CONCLUSION Our results support the hypotheses that high total intakes of vitamins B-6 and B-12 are protective of depressive symptoms over time in community-residing older adults Many women of reproductive age from developing countries have poor nutritional status , and the prevalence of depression during pregnancy is high . The objective of the present study was to assess the prevalence of antenatal depressive symptoms in early pregnancy , and to identify the demographic and nutritional factors associated with these symptoms in a sample of urban South Indian pregnant women . This cross-sectional study was the baseline assessment of a prospect i ve r and omized controlled trial of vitamin B12 supplementation in urban pregnant south Indian women between the ages of 18 and 40 years ( www . clinical trials.gov : NCT00641862 ) . 365 women in their first trimester of pregnancy were screened for depressive symptoms at an urban clinic in Karnataka , South India , using the Kessler Psychological Distress Scale ( K-10 ) . Nutritional , clinical and biochemical factors were also assessed . Mean ( SD ) age of the cohort was 22.6 ( 3.7 ) years and mean ( SD ) BMI was 20.4 ( 3.3 ) kg/m2 . 121 ( 33 % ) of the women in the 1st trimester had symptoms consistent with depression ( K-10 score > 6 ) . In multivariate log binomial regression analysis , presence of antenatal depressive symptoms in the first trimester were positively associated with vomiting , prevalence ratio ( PR ) = 1.54 ( 95 % CI 1.10 , 2.16 ) and negatively with anemia , PR = 0.67 ( 95 % CI 0.47 , 0.96 ) . Nutrient intakes , serum vitamin B12 , methylmalonic acid , homocysteine and red cell folate levels were not associated with measures of depression . Antenatal depressive symptoms in early pregnancy are highly prevalent in urban Indian women and are more common in women with vomiting and without anemia . In this cross-sectional data , blood concentrations of vitamin B12 and folate were not associated with depressive symptoms . The relationship between nutritional status and depressive symptoms may require larger and longitudinal studies Evidence for the impact of micronutrient supplementation trials on  depression in women from developing countries is limited . This study examines this association and compares the impact of weekly versus daily combinations of micronutrient supplements on symptoms of depression . A r and omized , positive-controlled trial was conducted in Guatemala . A total of 459 women were assigned r and omly to 4 groups to receive weekly ( 5,000 or 2,800 microg ) or daily ( 400 or 200 microg ) folic acid ( FA ) plus iron , zinc and vitamin B-12 for 12 weeks . Depression was measured using the Center for Epidemiologic Studies -Depression 20-item Scale ( CES-D ) . A score = 16 was used as an indication of depression . The association between micronutrient status and depression was assessed using baseline data . Generalized linear regression models were used to assess treatment effects . The baseline mean CES-D score was 17.1 + /- 8.5 and the prevalence of depression was 49.3 % . Women in the lowest tertile of red blood cell folate ( RBC ) were 1.7 times more likely to be depressed than those in the highest tertile ( OR=1.71 ; 95 % CI : 0.91 , 3.18 ) . There were no associations between depression and serum folate , homocysteine , vitamin B-12 , hemoglobin , ferritin or zinc ( p > 0.05 ) . Mean depression scores decreased by 2.3 points post-intervention and depression decreased to 37.7 % , with no differences in degree of improvement by group ( p = 0.64 ) . Low RBC folate was associated with elevated symptoms of depression at baseline . Supplementation with FA-containing micronutrients may be equally efficacious in improving symptoms of depression when provided daily or weekly . Our findings that poor folate status may increase depression needs to be further investigated BACKGROUND Deficiencies in folate and vitamin B12 have been associated with neurodegenerative disease . OBJECTIVE To examine the association between rates of age-related cognitive change and dietary intakes of folate and vitamin B12 . DESIGN Prospect i ve study performed from 1993 to 2002 . SETTING Geographically defined biracial community in Chicago , Ill. PARTICIPANTS A total of 3718 residents , 65 years and older , who completed 2 to 3 cognitive assessment s and a food frequency question naire .  MAIN OUTCOME MEASURE Change in cognitive function measured at baseline and 3-year and 6-year follow-ups , using the average z score of 4 tests : the East Boston Tests of immediate and delayed recall , the Mini-Mental State Examination , and the Symbol Digit Modalities Test . RESULTS High folate intake was associated with a faster rate of cognitive decline in mixed models adjusted for multiple risk factors . The rate of cognitive decline among persons in the top fifth of total folate intake ( median , 742 microg/d ) was more than twice that of those in the lowest fifth of intake ( median , 186 microg/d ) , a statistically significant difference of 0.02 st and ardized unit per year ( P = .002 ) . A faster rate of cognitive decline was also associated with high folate intake from food ( P for trend = .04 ) and with folate vitamin supplementation of more than 400 microg/d compared with nonusers ( beta = -.03 , P<.001 ) . High total B12 intake was associated with slower cognitive decline only among the oldest participants . CONCLUSIONS High intake of folate may be associated with  cognitive decline in older persons . These unexpected findings call for further study of the cognitive implication s of high levels of dietary folate in older population BACKGROUND Folate deficiency is associated with depression . Despite the biological plausibility of a causal link , the evidence that adding folate enhances antidepressant treatment is weak . OBJECTIVES ( 1 ) Estimate the clinical effectiveness and cost-effectiveness of folic acid as adjunct to antidepressant medication ( ADM ) . ( 2 ) Explore whether baseline folate and homocysteine predict response to treatment . ( 3 ) Investigate whether response to treatment depends on genetic polymorphisms related to folate metabolism . DESIGN FolATED ( Folate Augmentation of Treatment - Evaluation for Depression ) was a double-blind and placebo-controlled , but otherwise pragmatic , r and omised trial including cost-utility analysis . To yield 80 % power of detecting st and ardised difference on the Beck Depression Inventory version 2 ( BDI-II ) of 0.3 between groups ( a ' small ' effect ) ,  FolATED trialists sought to analyse 358 participants . To allow for an estimated loss of 21 % of participants over three time points , we planned to r and omise 453 . SETTING S Clinical - Three centres in Wales - North East Wales , North West Wales and Swansea . Trial management - North Wales Organisation for R and omised Trials in Health in Bangor University . Biochemical analysis - University Hospital of Wales , Cardiff . Genetic analysis - University of Liverpool . PARTICIPANTS Four hundred and seventy-five adult patients presenting to primary or secondary care with confirmed moderate to severe depression for which they were taking or about to start ADM , and able to consent and complete assessment s , but not ( 1 ) folate deficient , vitamin B12 deficient , or taking folic acid or anticonvulsants ; ( 2 ) misusing drugs or alcohol , or suffering from psychosis , bipolar disorder , malignancy or other unstable or terminal illness ; ( 3 ) ( planning to become ) pregnant ; or ( 4 ) participating in other clinical research . INTERVENTIONS Once a day for 12 weeks experimental participants added 5 mg of folic acid to their ADM , and control participants added an indistinguishable placebo . All participants followed pragmatic management plans initiated by a trial psychiatrist and maintained by their general medical practitioners . MAIN OUTCOME MEASURES Assessed at baseline , and 4 , 12 and 25 weeks thereafter , and analysed by ' area under curve ' ( main ) ; by analysis of covariance at each time point ( secondary ) ; and by multi-level repeated measures ( sensitivity analysis ): Mental health - BDI-II ( primary ) , Clinical Global Impression ( CGI ) , Montgomery-Åsberg Depression Rating Scale ( MADRS ) , UKU side effects scale , and Mini International Neuropsychiatric Interview ( MINI ) suicidality subscale ; General health - UK 12-item Short Form Health Survey ( SF-12 ) , European Quality of Life scale - 5 Dimensions ( EQ-5D ) ; Biochemistry - serum folate , B12 , homocysteine ; Adherence - Morisky Question naire ; Economics - re source use . RESULTS Folic acid did not significantly improve any of these measures . For example it gained a mean of just 2.9 quality -adjusted life-days [ 95 % confidence interval ( CI ) from -12.7 to 7.0 days ] and saved a mean of just £ 48 ( 95 % CI from -£292 to £ 389 ) . In contrast it significantly reduced mental health scores on the SF-12 by 3.0 % ( 95 % CI from -5.2 % to -0.8 % ) . CONCLUSIONS The FolATED trial generated no evidence that folic acid was clinical ly effective or cost-effective in augmenting ADM . This negative finding is consistent with improving underst and ing of the one-carbon folate pathway suggesting that methylfolate is a better c and i date for augmenting ADM . Hence the findings of FolATED undermine treatment guidelines that advocate folic acid for treating depression , and suggest future trials of methylfolate to augment ADM . TRIAL REGISTRATION Current Controlled Trials IS RCT N37558856 . FUNDING This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol . 18 , No. 48 . See the HTA programme website for further project information Background / Aim : In elderly persons , fall-related injury is a serious public health problem . We investigated the impact of essential nutritional elements on falls in the elderly . Methods : Clinical function , balance , gait and disability tests and health and nutritional status assessment s were performed . All subjects were interviewed regarding the occurrence of falls in the last year . Blood tests for serum vitamin D , folate and B12 were conducted among a r and omly selected sub sample of 54 participants in the same month . Results : One hundred 65- to 91-year-old volunteers participated in the study , and 29 of them fell at least once during the past year .  The depression score was higher ( indicating more depressive symptoms ) among fallers compared with non-fallers ( 4.0 ± 3.2 vs. 2.5 ± 2.3 , respectively ) . The overall function score ( indicating better function ) was marginally higher in non-fallers . Subsequent comparisons between fallers and non-fallers were adjusted for overall function and depression scores . Serum folate  was significantly lower in fallers ( 9.5 ± 7.1 vs. 16.2 ± 6.7 ng/ml , p = 0.02 ) . Dietary intake  was equal in both groups . Correlation analyses indicate a significant association between vitamin D and the functional measurements : timed get up and go ( negative ) , Berg balance test , overall functional score , lower extremity score and limitation score ( positive correlation coefficients ) . Serum folate was highly and negatively associated with the number of falls and with prescribed medications and was the only protective factor against falls in a multivariate analysis . Conclusions : Vitamin D was related to most functional and balance measurements . Serum folate was protective against falls . For every 1 ng/ml increase in serum folate the occurrence of falls decreased by 19 % BACKGROUND & AIMS The effect of nutritional supplements on mental health in older patients has received little attention so far . The aims of this trial were therefore to test the effect of nutritional support on older patient 's depressive symptoms and cognitive function . METHODS In this prospect i ve , double-blind , placebo-controlled study , we r and omly assigned 225 hospitalised acutely ill older patients to receive either normal hospital diet plus 400 mL oral nutritional supplements ( 106 subjects ) or normal hospital diet plus a placebo ( 119 subjects ) daily for 6 weeks . The composition of the supplement was such as to provide 995 kcal for energy and 100 % of the Reference Nutrient Intakes for a healthy old person for vitamins and minerals . Outcome measures were 6 weeks and 6 months changes in nutritional status , depressive symptoms and cognitive state . RESULTS R and omisation to the supplement group led to a significant increase in red-cell folate and plasma vitamin B12 concentrations , in contrast to a decrease seen in the placebo group . There were significant differences in symptoms of depression scores in the supplement group compared with the placebo group at 6 months ( p = 0.021 for between groups difference ) . The effect of supplement was seen in all patient groups including those with no symptoms of depression , mild depression and those with severe depression ( p = 0.007 ) . There was no evidence of a difference in cognitive function scores at 6 months . CONCLUSION Oral nutritional supplementation of hospitalised acutely ill older patients led to a statistically significant benefit on depressive symptoms BACKGROUND Depression is common and the efficacy of antidepressants is suboptimal . High plasma homocysteine has been consistently associated with depression , and treatment with certain B vitamins demonstrably reduces its concentration . AIMS To determine whether vitamins B6 , B12 and folic acid enhance response to antidepressant treatment  over 52 weeks . METHOD R and omised , double-blind , placebo-controlled trial of citalopram ( 20 - 40 g ) together with 0.5 mg of vitamin B12 , 2 mg of folic acid and 25 mg of vitamin B6 for 52 weeks ( Australian and New Zeal and Clinical Trials Registry : 12609000256279 ) . Participants were community-dwelling adults aged 50 years or over with DSM-IV-TR major depression . We measured severity of symptoms with the Montgomery-Åsberg Depression Rating Scale ( MADRS ) . The primary outcome was remission of the depressive episode after 12 , 26 and 52 weeks . Secondary outcomes included reduction of MADRS scores over time and relapse of major depression after recovery by week 12 . Results In total , 153 people were r and omised ( 76 placebo , 77 vitamins ) .  Remission of symptoms was achieved by 78.1 and 79.4 % of participants treated with placebo and vitamins by week 12 ( P = 0.840 ) , by 76.5 and 85.3 % at week 26 and 75.8 and 85.5 % at week 52 ( effect of intervention over 52 weeks : odds ratio ( OR ) = 2.49 , 95 % CI 1.12 - 5.51 ) . Group differences in MADRS scores over time were not significant ( P = 0.739 ) . The risk of subsequent relapse among those who had achieved remission of symptoms at week 12 was lower in the vitamins than placebo group ( OR = 0.33 , 95 % CI 0.12 - 0.94 ) . CONCLUSIONS B vitamins did not increase the 12-week efficacy of antidepressant treatment , but enhanced and sustained antidepressant response over 1 year . Replication of these findings would m and ate that treatment guidelines adopt the adjunctive use of B vitamins as a safe and inexpensive strategy to manage major depression in middle-aged and older adults BACKGROUND Associations between low levels of folate and vitamin B12 and cognitive impairment in patients with dementia have been reported . Some studies revealed correlations between low levels of vitamin B12  and behavioural and psychological signs and symptoms of dementia ( BPSD ) in Alzheimer 's disease ( AD ) patients . Given the lack of studies in frontotemporal dementia ( FTD ) and on folate and given the method ological shortcomings of former publications , we set up a prospect i ve study . METHODS At inclusion , AD ( n=152 ) and FTD ( n=28 ) patients underwent a neuropsychological examination . Behaviour  was assessed using a battery of behavioural assessment scales . Determination of serum vitamin B12 and red cell folate levels  were performed within a time frame of two weeks of inclusion . RESULTS In both patient groups , significantly negative correlations between levels of serum vitamin B12 and red cell folate and the degree of cognitive deterioration were found . No correlations with BPSD were found in the AD patient group . In FTD patients , levels of vitamin B12 were negatively correlated with both hallucinations ( p=0.022 ) and diurnal rhythm disturbances ( p=0.036 ) . CONCLUSIONS The observed negative correlations between levels of vitamin B12 and folate and cognitive impairment in both AD and FTD patients , raise the possibility of a non-specific etiological role . Although levels of vitamin B12 and folate did not correlate with BPSD in AD patients , negative correlations between serum vitamin B12 levels and BPSD in FTD patients were revealed . Decreased serum vitamin B12 levels may predispose FTD patients to develop hallucinations and diurnal rhythm disturbances OBJECTIVE In the present study , we assessed the relationship between serum folate , vitamin B12 , and homocysteine levels and clinical response in patients with major depressive disorder ( MDD ) who had previously failed to respond to open treatment with fluoxetine 20 mg/day and were enrolled in a 4-week , double-blind trial of either ( 1 ) fluoxetine dose increase , ( 2 ) lithium augmentation of fluoxetine , or ( 3 ) desipramine augmentation of fluoxetine . METHOD Fifty-five out patients ( mean + /- SD age = 41.7 + /- 10.6 years ; 50.9 % women ) with MDD as assessed with the Structured Clinical Interview for DSM-III-R who were enrolled in the double-blind trial had  serum folate , vitamin B12 , and homocysteine measurements completed at baseline ( prior to fluoxetine treatment initiation ) . Folate levels were classified as either low ( < or = 2.5 ng/mL ) or normal . Vitamin B12 levels were classified as either low ( < or = 200 pg/mL ) or normal . Homocysteine levels were classified as either elevated ( > or = 13.2 micromol/L ) or normal . With the use of a logistic regression , we then assessed the relationship between ( 1 ) low or normal folate levels , ( 2 ) normal or low B12 levels , and ( 3 ) elevated or normal homocysteine levels and clinical response to double-blind treatment . The study was conducted from November 1992 to January 1999 . RESULTS Low serum folate levels ( chi2=3.626 , p = .04 ) , but not elevated homocysteine ( p > .05 ) or low vitamin B12 levels ( p > .05 ) , were associated with poorer response to treatment . The response rates for patients with ( N = 14 ) and without ( N = 38 ) low folate levels were 7.1 % versus 44.7 % , respectively . CONCLUSION Low serum folate levels were found to be associated with further treatment resistance among patients with fluoxetine-resistant MDD IMPORTANCE More effective treatments are needed for negative symptoms of schizophrenia , which are typically chronic , disabling , and costly . Negative symptoms have previously been associated with reduced blood folate levels , especially among patients with low-functioning variants in genes that regulate folate metabolism , suggesting the potential utility of folate supplementation . OBJECTIVES To determine whether folic acid plus vitamin B12 supplementation reduces negative symptoms of schizophrenia and whether functional variants in folate-related genes influence treatment response . DESIGN Parallel-group , r and omized , double-blind , placebo-controlled clinical trial of 16 weeks of treatment with 2 mg of folic acid and 400 μg of vitamin B12 . SETTING Three community mental health centers affiliated with academic medical centers in the United States . PARTICIPANTS Out patients with chronic schizophrenia who were psychiatrically stable but displayed persistent symptoms despite antipsychotic treatment . Eligible patients were 18 to 68 years old , were treated with an antipsychotic agent for 6 months or more at a stable dose for 6 weeks or more , and scored 60 or more on the Positive and Negative Syndrome Scale . INTERVENTION One hundred forty subjects were r and omized to receive daily oral folic acid plus vitamin B12 or placebo . MAIN OUTCOME MEASURES Change in negative symptoms ( Scale for the Assessment of Negative Symptoms [ SANS ] ) , as well as positive and total symptoms ( Positive and Negative Syndrome Scale ) . RESULTS Folate plus vitamin B12  improved negative symptoms significantly compared with placebo ( group difference , -0.33 change in SANS score per week ; 95 % CI , -0.62 to -0.05 ) when genotype was taken into account but not when genotype was excluded . An interaction of the 484C > T variant of FOLH1 ( rs202676 ) with treatment was observed ( P = .02 ) , where only patients homozygous for the 484 T allele demonstrated significantly greater benefit with active treatment ( -0.59 change in SANS score per week ; 95 % CI , -0.99 to -0.18 ) . In parallel , we observed an inverse relationship between red blood cell folate concentration at baseline and 484C allele load ( P = .03 ) , which persisted until 8 weeks of treatment . Change in positive and total symptoms did not differ between treatment groups . CONCLUSIONS Folate plus vitamin B12 supplementation can improve negative symptoms of schizophrenia , but treatment response is influenced by genetic variation in folate absorption . These findings support a personalized medicine approach for the treatment of negative symptoms . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00611806 Objectives : 1 ) To compare serum vitamin B12 , C and folate concentrations in a r and omly selected sample of elderly ( age 65 years or older ) male and female Hispanics and nonHispanic whites ( NHW ) and 2 ) to examine associations between serum B12 , C and folate concentrations compared to measures of cognitive and affective ( depression ) functions . Methods : Equal numbers of male and female Hispanics and NHW were r and omly sample d from the Health Care Financing Administration ( Medicare ) registrant list for Bernalillo County , New Mexico , and asked to volunteer for a paid home interview followed by a paid comprehensive interview/examination covering health and health-related issues . In addition to serum determinations of B12 , C and folate , associations were examined between these vitamins and measures of cognitive and affective functions . Results : Males and Hispanics had lower serum vitamin B12 , C and folate concentrations than females and NHW respectively . Participants taking a multivitamin supplement ( MVI ) had higher serum vitamin concentrations than those not taking MVI . There were significant associations between serum folate concentrations and measures of cognitive function , not seen with B12 or C , nor between any of the vitamins and affective function . Conclusions : Hispanics , even after adjustments for gender , age , vitamin supplementation , vitamin content of dietary foods , education and household income , had lower serum concentrations of B12 , C and folate than NHW . The most significant associations observed were those between serum folate and various measures of cognitive function , even after adjusting for presence of depression
Conclusion : Low folate and B12 serum levels seem to be associated with  depression in the aged .
Objectives : To systematic ally review and meta-analyse existing evidence on the association between folate/B12 , and depression among the aged people .