Plasma homocysteine, folate and B12 in chronic schizophrenia

Elevated plasma levels of the amino acid homocysteine have been associated with schizophrenia, particularly in young male patients. Among other factors, low folate and vitamin B12 levels have been implicated in the increase in homocysteine. In order to investigate this association, we determined plasma homocysteine, folate and B12 levels in 97 (67 males and 30 females) inpatients with chronic schizophrenia and 103 (46 males and 57 females) controls. Patients and controls did not differ in folate or B12 levels, after adjusting for age. Patients with schizophrenia had higher plasma homocysteine than controls (mean=15.42 micromol/l in cases versus 11.54 micromol/l in controls: F(1,195)=17.978; p<0.001). This difference persisted after controlling for folate and B12 concentrations. Both male and female patients had increased plasma homocysteine compared to controls [(males: mean=16.61 micromol/l in cases versus mean=13.72 in controls: F(1,110)=5.54; p=0.020) (females: mean=12.78 micromol/l in cases versus mean=9.79 micromol/l in controls: F(1,84)=13.54; p<0.001)]. When dividing our sample into two age groups (age < and > or =50 years), both young and older females and younger males with schizophrenia had increased plasma homocysteine compared to controls. We therefore suggest that homocysteinemia is a general risk factor for schizophrenia. We further suggest that it is not limited to young male patients and is not necessarily associated with low folate or B12 levels.     

急性脑梗死患者血浆同型半胱氨酸、叶酸、维生素B12水平的测定及其临床意义

目的 探讨血浆同型半胱氨酸(Hcy)在急性脑梗死发病过程中的临床意义以及与病情、伴发症、叶酸、维生素B_(12)之间的关系。方法 采用化学发光法测定急性脑梗死患者血浆Hcy、叶酸、维生素B_(12)水平,并与对照组进行比较。结果急性脑梗死组血浆Hcy水平明显高于对照组(P<0.001),叶酸明显低于对照组(P<0.001);重型患者血浆Hcy水平明显高于中型及轻型患者(P<0.01,0.01),叶酸明显低于中型及轻型患者(P<0.01,0.05);伴发高血压病的患者血浆Hcy水平明显高于非高血压病的患者(P<0.05);急性脑梗死组血浆Hcy与叶酸、维生素B_(12)呈负相关(P<0.01,0.01);对照组血浆Hcy与叶酸呈负相关(P<0.05)。结论高Hcy血症是脑梗死的一个新的重要危险因素;Hcy水平与病情密切相关,与叶酸、维生素B_(12)呈负相关。     

Plasma homocysteine levels in young male patients in the exacerbation and remission phase of schizophrenia

High levels of homocysteine (Hcy) were suggested to contribute to the pathogenesis of schizophrenia. Recent investigations have shown that treatment with folic acid, vitamin B-12 and pyridoxine are effective in reducing Hcy levels while concomitantly reducing the score of positive and negative symptoms in schizophrenic patients. In addition to the availability of nutrients (mainly folate, vitamins B6 and B12), plasma Hcy concentrations are dependent on complex metabolic regulation that could be disrupted in schizophrenia.This study was designed to test the influence of disease activity on plasma Hcy levels. Plasma Hcy concentrations were measured in male chronic schizophrenic patients with a predominantly positive (SCH (+)) or predominantly negative (SCH (−)) syndrome in schizophrenia immediately upon admission to the hospital (exacerbation phase) and one month later (remission phase). During this period patients received antipsychotic medications without vitamin therapy. The effects of age, duration of illness, folate and B12 concentrations, as well as smoking and coffee consumption habits on the observed changes were evaluated. Age- and sex-matched subjects were included in the control group. In the control group plasma Hcy concentration was 8.75 ± 1.84 μmol/L. In the exacerbation phase plasma Hcy concentrations were significantly increased both in SCH (+) (14.91 ± 6.19 μmol/L) and SCH (−) groups (12.8 ± 3.27 μmol/L). There was no difference in plasma Hcy concentrations between SCH (+) and SCH (−) patients. Serum folate and B12 concentrations were not significantly different in any of the investigated groups of subjects. The plasma Hcy concentrations could not be correlated with age, duration of illness, the score of positive symptoms or the concentration of folate and vitamin B12. A positive correlation was found between plasma Hcy level and score of negative symptoms in both groups of patients. No correlation was found between smoking or coffee consumption habits and plasma Hcy concentrations. All patients exhibited decreased plasma Hcy levels in the remission phase of the illness, with a mean decrease of 2.68 ± 1.57 μmol/L. Folate and B12 levels did not differ in the exacerbation and remission phases of the illness.The significant decrease of plasma Hcy levels, without changes in folate and vitamin B12 concentrations in the remission phase of schizophrenia, could indicate an influence of a pathogenetic process involved in schizophrenia on Hcy metabolism.     

Plasma homocysteine, vitamin B12 and folate in Alzheimer's patients and healthy Arabs in Israel

High plasma homocysteine (tHcy) is a risk factor for cardiovascular disease and stroke and Alzheimer's disease (AD). An inverse relationship has been reported between tHcy and plasma B12 and folate levels. Seventy-nine AD patients and 156 controls from three Arab villages in northern Israel participated. Plasma tHcy, B12 and folate levels were determined. Data were analyzed using univariate statistical tests and logistical regression with confounders. tHcy was significantly higher in AD patients (20.6+/-8.7 micromol/l) than in controls (16.4+/-6.5 micromol/l) (p=0.03) after correction for year of birth, gender and smoking status. Plasma B12 (322.9+/-136.0/350.5+/-175.3 pmol/l) and plasma folate (4.5+/-3.8/4.9+/-2.6 nmol/l) levels did not differ significantly between AD patients and controls. Subjects in the highest tHcy tertile or in the lowest B12 and folate tertiles did not have greater risk to develop AD. In this population residing in Arab villages in northern Israel, tHcy levels were significantly higher among AD patients than in controls. Plasma B12 and folate levels were lower among cases but were not significant. There was not a significant association between plasma tHcy, B12 and folate levels in controls or AD patients. High levels of tHcy may suggest the need for folate and vitamin B12 supplementation in this population.     

No association between global leukocyte DNA methylation and homocysteine levels in schizophrenia patients

Meta-analysis recently suggested that a 5 μM increase in homocysteine is associated with a 70% higher risk for schizophrenia. Elevated homocysteine is reported to alter macromolecule methylation. We studied whether elevated plasma homocysteine levels in schizophrenia are associated with altered leukocyte global DNA methylation. DNA was extracted from peripheral blood leukocytes of 28 schizophrenia patients vs. 26 matched healthy controls. Percent of global genome DNA methylation was measured using the cytosine-extension method. Homocysteine levels were higher in schizophrenia patients than in controls. No difference in global DNA methylation between schizophrenia patients and control subjects was found (74.0% ± 14.8 vs. 69.4 ± 22.0, p = 0.31). A significant interaction between diagnosis and smoking on DNA methylation was obtained (F = 6.8, df = 1,47, p = 0.032). Although leukocytes may be a useful cell model to evaluate epigenetic changes such as global DNA methylation in brain, future studies should compare global DNA methylation in peripheral tissue vs. brain in laboratory animals.     

Serum folate and homocysteine levels in patients with obsessive-compulsive disorder

Previous studies have shown that folate deficiency, increased homocysteine, impaired metylation have been identified in depressive disorder. Recently, growing research has resulted in the biological association between obsessive-compulsive disorder (OCD) and affective disorders. Therefore, in the present study it was evaluated whether or not folate and homocysteine levels changed. Serum folate and homocysteine concentrations were measured in 23 patients with OCD and in same number of controls. In addition, all patients were assessed by Yale-Brown Obsession Compulsion Scale (Y-BOCS). Serum folate values were significantly lower in OCD patients than in controls, while homocysteine concentrations were higher in patients compared with controls. Serum folate values were significantly and negatively related to Y-BOCS scores. Total serum homocysteine concentrations were positively correlated to Y-BOCS scores and the duration of illness. There was a trend toward a negative correlation between the concentrations of serum folate and homocysteine. In conclusion, we identified that a group of patients with OCD might have folate deficiency, higher homocysteine levels and probable impaired metylation and monoamine metabolism.     

Homocysteine,vitamin B12 and folate levels in Iranian patients with Multiple Sclerosis: A case control study

Background

Recently, homocysteine (Hcy), folate, and vitamin B12 have been proposed to have several roles on MS pathogenesis.

Objective

We performed this study to determine the role of serum levels of Hcy, vitamin B12, and folate in patients with relapsing remitting MS (RRMS) and compared them with healthy controls.

Methods

We recruited 75 RRMS patients and 75 subjects as controls with the same age and sex. Homocysteine was measured using fluorimetric high-performance liquid chromatography. Plasma folate and vitamin B12 levels were measured through ion-capture method.

Results

Mean plasma levels of vitamin B12, folate, and Hcy in cases were 342.64 ± 210.66 pg/ml, 9.74 ± 4.77 ng/ml, and 22.73 ± 11.63 μM/L, respectively, which showed significant difference in comparison with the controls. In addition, there were significant correlations between mean serum Hcy levels and duration of disease (r = 0.2, p = 0.05) and treatment with interferon (r = 0.21, p = 0.01). In cases, Hcy level was higher among those on β interferon (24.56 ± 11.87 vs. 19.71 ± 10.75, p = 0.01).

Conclusions

We concluded that serum levels of vitamin B12 and folate decreased in RRMS patients, but Hcy levels increased significantly. It seems necessary to conduct prospective trials to determine whether the treatment with supplements and correct biomarker levels in the early stage of the disease can change the course of the disease. We recommend regular checking of the serum level of Hcy in patients who use disease-modifying drugs.     

抑郁症患者血清同型半胱氨酸水平的研究

目的　探讨同型半胱氨酸 (Homocysteine ,Hcy)在抑郁症发病中的作用。方法　采用荧光偏振免疫法 (FPLA)检测 2 2例抑郁症患者 (抑郁症组 )和 2 0名正常人 (对照组 )的血清Hcy水平 ,以 μmol/l计。 结果　抑郁症组血清Hcy水平高于对照组 [(16 .37± 6 .4 5 ) μmol/l比 (11.6 2± 4 .0 7) μmol/l,P <0 .0 1]。抑郁症组高同型半胱氨酸血症 (Hyperhomocysteinemia ,HHcy) (血清Hcy水平 >16 .0 0 μmlo/l)的发生率明显高于对照组 (4 5 .4 5 %比 10 .0 0 % ,oddsratio ,7.5 ;95 %可信区间 ,1.5 9～ 35 .39,P <0 .0 5 )。结论　抑郁症患者的血清Hcy水平升高 ,提示Hcy在抑郁症的发病中起一定作用。     

Elevated homocysteine level in siblings of patients with schizophrenia

Increased homocysteine plasma levels were reported in patients with schizophrenia and Levine et al. (2002) suggested that such increase characterizes mainly males. In the following study we examined whether such increased levels also characterize male siblings of schizophrenia patients. Forty-four pairs of schizophrenia patients and their corresponding healthy male siblings were recruited and sampled for homocysteine. We also had age-matched controls for each of the sibling. The median homocysteine plasma level for patients was 13.0 µMol/L and 11.7 µMol/L for their male siblings compared with a median of 10.9 µMol/L for the siblings' controls. There was no significant difference between homocysteine plasma level in patients and their siblings. Significant difference was found for homocysteine plasma level between the siblings' group and their matched controls. A partial correlation of Ln plasma homocysteine level between patients and their siblings was found to be close to a zero correlation of −0.089, p=0.57 for the whole study group and −0.15, p=0.38 in the male–male patient-sibling pairs. Our results show that elevated homocysteine plasma level may characterize schizophrenia patients' male siblings, a finding that seems to agree with previous studies suggesting elevated homocysteine level as a risk factor for developing schizophrenia.     

复发—缓解型多发性硬化患者血清中CRP及Hcy水平分析

目的探讨复发—缓解型多发性硬化(RRMS)患者血清中C反应蛋白(CRP)、同型半胱氨酸(Hcy)、维生素B_(12)及叶酸水平,并探讨上述因子与RRMS发病的关系。方法选取21例急性期的RRMS患者作为RRMS组,21例同期住院的神经性头痛患者作为对照组,测定其血清中CRP、Hcy、叶酸及维生素B_(12)水平,并比较两组之间的水平差异;并比较RRMS组中不同性别、不同残疾程度组之间的血清CRP、Hcy、叶酸及维生素B_(12)水平。结果 RRMS组患者血清中CRP及Hcy水平高于对照组,而叶酸及维生素B_(12)水平低于对照组,(P0.05)。而扩展残疾状况评分量表评分(EDSS)4分的RRMS患者血清中Hcy及CRP水平高于EDSS评分≤4分的RRMS患者,(P0.05)。结论血清中高CRP、Hcy水平可能与RRMS发病及残疾程度有关。     

Gene--nutrition interactions in coronary artery disease: correlation between the MTHFR C677T polymorphism and folate and homocysteine status in a Korean population

INTRODUCTION: Elevated plasma total homocysteine is a major risk for coronary artery disease (CAD). Methyltetrahydrofolate reductase (MTHFR) is a main regulatory enzyme in homocysteine metabolism; a common C677T mutation in the MTHFR gene results in decreased enzyme activity, and contributes to increased homocysteine levels and decreased folate levels. We investigated the frequency of MTHFR C677T alleles in a Korean population, determined the genotype-specific threshold levels of folate or vitamin B12, and investigated the relationship between the TT genotype and the risk of CAD. MATERIALS AND METHODS: We enrolled a study population of 163 CAD patients and 50 control subjects, and screened the MTHFR C677T polymorphism using real-time PCR with melting point analysis. Levels of plasma homocysteine, folate and vitamin B12 were also determined. We then defined the genotype-specific threshold values of folate and vitamin B12 required to keep homocysteine levels in a normal range for individuals of each MTHFR C677T genotype. RESULTS: The frequency of the TT genotype was 18% in control subjects and 26% in patients group (P>0.05). Individuals homozygous for the TT genotype had significantly elevated homocysteine levels (P<0.05). The genotype-specific folate threshold level was significantly higher in TT individuals than in the CC or CT genotypes. The OR of individuals with low folate status and the TT genotype to estimate the relative risk of CAD was 2.2 and the OR of those with high folate status and the TT genotype was 1.5 (95% CI, 0.5-9.6 and 0.7-3.2, respectively). CONCLUSION: We were able to define a gene-nutrient interaction that shows a higher risk for CAD based on specific threshold folate levels required by different MTHFR C677T genotypes in a Korean population.     

Serum vitamin D and folate levels in children with autism spectrum disorders

It has recently proposed that vitamin D and folate may be involved in the aetiology of autism. We investigated the serum levels of vitamin D, calcium (Ca), phosphorus (P), alkaline phosphatase (ALP) and folate in 54 young children, aged 3–8 years, with autism spectrum disorders (ASD) and in 54 age and gender matched normal controls. Vitamin D, Ca, P, ALP and folate levels in children with ASD were not different from control group. The correlational analysis in children with ASD revealed that Aberrant Behaviour Checklist, Autism Behaviour Checklist, and Childhood Autism Rating Scale scores and the level of cognitive development were not correlated with these laboratory findings. Our findings do not support the idea that serum levels of vitamin D and folate might be low in children with ASD. Nevertheless, it is possible that vitamin D and folate deficiency may be playing a role in development of ASD at earlier ages or during prenatal period.     

高同型半胱氨酸血症与血管性痴呆相关性研究

目的:探讨血浆同型半胱氨酸(Hcy)水平与血管性痴呆(VD)的相关性。方法:应用全自动生化分析仪用循环酶法检测37例VD患者的血浆Hcy浓度,并与39例非痴呆脑梗死患者作为同龄对照组血浆Hcy浓度进行比较,同时测定血浆叶酸及VitB12浓度,根据简易精神状态检查量表(MMSE)评分划分VD患者严重程度,分为轻度(20～24分),中度(10～19分),重度(10分以下)。结果:VD组血浆Hcy水平显著高于非痴呆脑梗死组(P<0.05),VD组血浆叶酸水平显著低于非痴呆脑梗死组(P<0.05),两组间VitB12水平无显著性差异(P>0.05),不同程度VD患者血浆Hcy、叶酸水平有显著性差异(p<0.05),VitB12水平无显著性差异(p>0.05)。结论:高同型半胱氨酸血症可能是VD发病的一个新的危险因素。     

进展性卒中患者血浆同型半胱氨酸和叶酸的水平测定

目的探讨进展性卒中（PS）与同型半胱氨酸（Hcy）的关系。方法选取PS患者33例，稳定性脑梗死患者30例，分别测定血浆Hcy和叶酸浓度。结果PS组比稳定性脑梗死组的血浆Hcy水平明显升高，叶酸水平明显降低（P〈0．05）。结论高Hcy与进展性脑卒中关系密切。     

Serum homocysteine, folate level and methylenetetrahydrofolate reductase 677, 1298 gene polymorphism in Korean schizophrenic patients

High homocysteine serum level has been regarded as one of the important factors that influence the development of schizophrenia. Genetic variations of methylenetetrahydrofolate reductase, which is a main enzyme reducing homocysteine level, are reported in schizophrenic patients. We measured the serum level of homocysteine/folate and methylenetetrahydrofolate reductase C677T/A1298C gene polymorphism in 235 patients with schizophrenia. Plasma homocysteine levels were higher and folate levels were lower in patients than in comparison subjects. Variations of C677T were more frequent in patients than in comparison subjects. Patients with the 677TT genotype showed higher homocysteine levels than patients with the CC and CT genotypes. These findings suggest that folate supplement may be beneficial to some schizophrenic patients with homocysteinemia due to the genetic defect of methylenetetrahydrofolate reductase.     

Serum BDNF levels and weight gain in schizophrenic patients on long-term treatment with antipsychotics

Several lines of evidence suggest that central brain-derived neurotrophic factor (BDNF) modulates food intake, metabolism, and increases in body weight. Reports have also shown that serum BDNF is altered in schizophrenic patients treated with antipsychotics. This study aimed to determine if there was a relationship between BDNF and antipsychotic-induced weight gain in patients with chronic schizophrenia. Serum BDNF was measured in 124 schizophrenia patients chronically treated with clozapine (n = 57), risperidone (n = 23) or typical antipsychotics (n = 44) and 50 healthy control subjects. To further assess group differences in serum BDNF, additional analyses were performed in a subset of patients and controls individually matched for body mass index (BMI). BDNF levels were lower in patients with schizophrenia than normal controls. However, this difference was not present when controlling for current BMI. In the individually BMI-matched sample, no differences in serum BDNF levels were observed in schizophrenic patients compared to BMI-matched healthy controls. BDNF levels negatively correlated with BMI gain in female but not in male patients when gender was considered. Antipsychotic class exerted differential effects over BDNF levels and BMI gain. Our findings suggest that decreased BDNF levels may be associated with weight gain in female schizophrenic patients on long-term antipsychotic treatment.     

叶酸、维生素B_(12)治疗高同型半胱氨酸血症对颈动脉粥样硬化的影响

目的观察叶酸、维生素B12治疗高同型半胱氨酸(Hcy)血症脑梗死患者对颈动脉粥样硬化的影响。方法高同型半胱氨酸脑梗死患者122例,随机分为研究组(65例),对照组(57例),研究组每日给予叶酸5mg,维生素B12500ug干预治疗,对照组不给予叶酸和维生素B12治疗,分别于入院时、治疗12、24及36个月测定血清Hcy、叶酸和维生素B12浓度,并进行颈动脉斑块积分及斑块类型超声检查。结果 (1)研究组第12、24、36个月血清Hcy水平较治疗前显著降低(p<0.01),叶酸及维生素B12浓度较治疗前显著性升高(p<0.01),对照组血清同型半胱氨酸、叶酸、维生素B12浓度无明显变化(p>0.05),两组间同一时期比较有显著性差异(p<0.01);(2)研究组随着疗程延长,颈动脉斑块积分减少且有显著性差异(p<0.05,),对照组颈动脉斑块积分增加且有显著性差异(p<0.05);两组间同期颈动脉斑块积分比较有显著性差异(p<0.01);(3)研究组随着疗程延长,颈动脉不稳定性斑块率呈下降趋势,有显著性差异(p<0.05);对照组颈动脉不稳定性斑块率呈上升趋势,有显著性差异(p<0.05);研究组与对照组第12、24及36个月相比不稳定斑块率差异有显著性(p<0.05、p<0.01)。结论叶酸、维生素B12可降低高同型半胱氨酸脑梗死患者同型半胱氨酸水平,可改善颈动脉粥样硬化程度,有稳定斑块作用。     

Depressive symptoms may explain elevated plasma levels of homocysteine in females with eating disorders

Elevated plasma homocysteine levels have been found in different psychiatric disorders, including major depression and eating disorders. The aim of the present study was to evaluate whether presence of depression or depressive symptoms is associated with elevated homocysteine levels in patients with eating disorders. Total plasma homocysteine levels were assessed in 44 females with anorexia nervosa (n = 21) or bulimia nervosa (n = 23). Comorbid major depressive disorder (MDD) was diagnosed according to DSM-IV criteria using a semi-structured interview (SCID-I). Furthermore, depressive symptoms were assessed using Beck's depression inventory (BDI). Presence of MDD was not associated with elevated homocysteine levels (t-test: T = 0.42; df = 42; P = 0.68). However, self-rated presence of clinically relevant depressive symptoms (BDI score18) was associated with elevated homocysteine (T = -2.8; df = 42; P = 0.008). Presence of depressive symptoms may explain elevated homocysteine levels previously reported in patients with eating disorders or vice versa. Longitudinal studies are needed to unravel this hen or egg problem.     

3-OMD and homocysteine plasma levels in parkinsonian patients

Summary. One main metabolizing pathway of levodopa is O-methylation to 3-O-methyldopa (3-OMD) by catechol-O-methyltransferase (COMT). Since COMT requires Mg²⁺ and S-adenosylmethionine as methyl donor for this transmethylating process, COMT converts S-adenosylmethionine to S-adenosylhomocysteine and subsequent homocysteine. Objective of this study was to demonstrate relations between plasma levodopa, 3-OMD and total homocysteine in treated parkinsonian subjects. We measured homocysteine, levodopa and 3-OMD by HPLC. We compared plasma homocysteine in two groups of treated parkinsonian subjects subdivided according to their 3-OMD level. Homocysteine was significantly (p = 0.002) elevated in the group with higher 3-OMD concentrations and positively (r = 0.52, p = 0.0006) correlated to 3-OMD. Homocysteine induces vascular disease. Previous studies showed an increase of ischaemic heart- and cerebrovascular disease in treated parkinsonian patients. Received November 20, 2000; accepted September 26, 2001     

首发精神分裂症的认知功能及其与血清同型半胱氨酸的关系

目的研究首发精神分裂症患者的认知功能及其与血清同型半胱氨酸(Hcy)水平的关系。方法采用词汇流畅测验、视觉再生测验、联想学习测验、数字广度测验、相似性测验、领悟测验、木块图测验、威斯康星卡片分类测验(WCST)8项神经心理测试工具,对57例首发精神分裂症患者于治疗前和非典型抗精神病药治疗8周后各评定认知功能1次,同时采用酶免疫法测定其血清Hcy水平,阳性与阴性症状量表(PANSS)评定临床症状。结果①治疗前,除WCST的随机错误数外,患者组各项认知功能指标均显著差于正常对照(P<0.01);血清Hcy水平明显高于正常对照(P<0.01);患者组中WCST的正确数、完成分类数与血清Hcy水平呈负相关(r=-0.376,P<0.01;r=-0.397,P<0.01),WCST的错误总数、持续错误数与血清Hcy水平呈正相关(r=0.376,P<0.01;r=0.298,P<0.05)。②治疗后,患者组PANSS总分显著下降(P<0.01);认知功能除WCST的随机错误数外较治疗前有所改善(P<0.05),但总体仍显著差于正常对照(P<0.01);血清Hcy水平无显著变化;患者组中WCST的正确数、完成分类数仍与血清Hcy水平呈负相关(r=-0.388,P<0.01;r=-0.383,P<0.01),WCST的错误总数、持续错误数仍与血清Hcy水平呈正相关(r=0.388,P<0.01;r=0.315,P<0.02)。结论精神分裂症患者存在认知损害,其执行功能损害可能与Hcy的代谢失衡有关。