Serum Homocysteine and Folate Levels in Korean Schizophrenic Patients

Department of Psychiatry, Research Institute of Medical Science, Konkuk University School of Medicine, Chungju, Korea.
Psychiatry investigation (Impact Factor: 1.28). 06/2011; 8(2):134-40. DOI: 10.4306/pi.2011.8.2.134
Source: PubMed


This study was conducted to confirm the results of the authors' previous research on schizophrenia manifesting high serum homocysteine and low folate levels. This study is anchored on a theory that a high serum homocysteine concentration affects schizophrenia by virtue of a neurotoxic mechanism, and on a report that some schizophrenia patients with high homocysteine levels benefited from high folate ingestion.
The serum homocysteine, folate, and vitamin B(12) levels of 236 normal-control-group subjects and 234 schizophrenia subjects who met the diagnostic criteria based on DSM-IV-TR were compared. The homocysteine levels were measured via fluorescence polarization immunoassay, and the folate and vitamin B(12) levels were determined via radioimmunoassay.
The homocysteine levels of the patient group were significantly higher than those of the normal control group. The homocysteine level was more negatively correlated with the folate level in the schizophrenia group than in the control group. The percentages of female and male schizophrenia subjects manifesting high homocysteine levels were 33.8 and 51.5%, respectively. The percentage of schizophrenia subjects with low folate levels was 66.2%. In the low- and normal-folate-level groups, the patient group showed significantly higher homocysteine levels than the normal control group. The low-folate-level patient group particularly showed significantly higher homocysteine levels than the low-folate-level normal control group.
Some schizophrenia patients with high serum homocysteine levels may have the genetic defect of having low folate serum levels. In such cases, folate ingestion may be a good management modality for clinical improvement.

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    • "We found that the patient group had significantly lower serum levels of folate and BDNF and higher serum levels of Hcy compared to the healthy control group. Our results are consistent with the findings from some of previous studies (Kale et al., 2010; Kim and Moon, 2011; Rizos et al., 2011). However, some studies reported elevated blood levels of BDNF in patients with schizophrenia (Rizos et al., 2008; Jindal et al., 2010; Sotiropoulou et al., 2013). "
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    ABSTRACT: Objective The present study was to examine serum levels of brain-derived neurotrophic factor (BDNF), folate, homocysteine (Hcy), and their relationships with hippocampal volume and psychopathology in drug naïve, first episode schizophrenia. Method Drug naïve, first episode schizophrenia patients and healthy controls were enrolled in the study. Serum levels of BDNF, folate and Hcy were measured using enzyme-linked immunosorbent assay (ELISA), electrochemiluminescence immunoassay (ECLIA), and enzymatic cycling method respectively. Hippocampus was parcellated and bilateral hippocampal volumes were measured using FreeSurfer. Results Forty-six patients with drug naïve, first episode schizophrenia (SZ group) and 30 healthy controls (control group) were enrolled. The SZ group had significantly lower serum levels of BDNF and folate, and significantly higher serum levels of Hcy compared with the control group (p = 0.013, p < 0.001, p = 0.003 respectively). There were no significant differences in hippocampal volumes between the two groups (ps > 0.2). Within the SZ group, there were significant positive relationships between serum levels of BDNF and both left and right hippocampal volumes (r = 0.327, p = 0.026; r = 0.338, p = 0.022 respectively). In contrast, such relationships did not exist in the control group. Within the SZ group, there were significant negative relationships between serum levels of folate and PANSS-total scores and PANSS-negative symptom scores (r = 0.319, p = 0.031; r = 0.321, p = 0.030 respectively); and there was a positive relationship between serum levels of Hcy and PANSS-total scores (r = 0.312, p = 0.035). Controlling for potential confounding variables resulted in similar findings. Conclusions Drug naïve, first episode schizophrenia presents decreased serum levels of BDNF, folate and increased serum levels of Hcy, which may play an important role in the neurodevelopmental process and clinical manifestation of schizophrenia.
    Full-text · Article · Oct 2014 · Schizophrenia Research
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    • "Though Goff et al.,[20] too found that association with schizophrenia, and further a correlation with severity of extrapyramidal symptoms, this study had serious flaws in study design such as poor age matching and non-uniformity in Hcys assays. Kim and Moon,[47] Lee et al.,[21] and Feng et al.,[26] also reported this association irrespective of age, in oriental populations. Petronijevi et al.,[25] noted that the Hcys levels rise in schizophrenia subjects during exacerbations in both the groups of patients, those with predominantly positive or negative syndrome. "
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    ABSTRACT: Hyperhomocysteinemia has been associated with psychiatric diseases in non-Indian populations. We aimed to determine if total plasma Homocysteine (Hcys) is associated with schizophrenia or depression in South Indian Tamil patients and if so, to correlate their severity and phenomenology to Hcys levels. 40 patients each with schizophrenia and depression and 40 healthy controls were recruited from the psychiatry department of a quaternary referral centre. Association between Hcys and psychiatric disorders was determined using a Case- control design. Hcys levels were correlated with age, gender and severity and duration of the disease by appropriate statistical methods using SPSS17. Schizophrenia and depression were defined using ICD10 DCR version. Severity of depression was assessed by Hamilton Depression Rating Scale and that of schizophrenia using Positive and Negative Schizophrenia scales (PANSS). Hcys levels were determined using automated chemiluminiscence immunoassay (74-76). Differences between the mean values of plasma homocysteine levels among schizophrenia, depression and control groups were compared using analysis of variants. The association between the severity and duration of schizophrenia and depression and the plasma homocysteine levels were determine using Pearson correlation. In Tamilian population, schizophrenia and depression are associated with total plasma Hcys levels which correlated with the duration and severity of psychosis.
    Full-text · Article · Mar 2014 · Indian Journal of Psychiatry
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    • "Elevated concentrations of homocysteine in human tissues, definied as hyperhomocysteinemia have been correlated with some diseases, such as cardiovascular, neurodegenerative, and kidney disorders. The elevated level of homocysteine has been repeatedly observed in patients with schizophrenia [6, 22–24]. Molecular-genetic studies revealed tha association between schizophrenia and polymorphisms of two genes—methylenetetrahydrofolate reductase and cystathionine-beta-synthase involved in the conversion of homocysteine to methionine and cysteine, respectively [23]. "
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    ABSTRACT: The mechanisms of oxidative stress in schizophrenic patients are not fully understood. In the present study, we investigated the effect of elevated level of homocysteine (Hcys) on some parameters of oxidative stress, namely thiobarbituric acid reactive substances (TBARS), an index of lipid peroxidation in plasma, the level of carbonyl groups in plasma proteins, as well as the amount of 3-nitrotyrosine in plasma proteins isolated from schizophrenic patients. Patients hospitalised in I and II Psychiatric Department of Medical University in Lodz, Poland were interviewed with special questionnaire (treatment, course of diseases, dyskinesis and other EPS). According to DSM-IV criteria all patients had diagnosis of paranoid type. They were treated with antipsychotic drugs (clozapine, risperidone, olanzapine). Mean time of schizophrenia duration was about 5 years. High-performance liquid chromatography was used to analyse the total level of homocysteine in plasma. Levels of carbonyl groups and 3-nitrotyrosine residues in plasma proteins were measured by ELISA and a competition ELISA, respectively. The lipid peroxidation in plasma was measured by the level of TBARS. Our results showed that in schizophrenic patients the amount of homocysteine in plasma was higher in comparison with the control group. We also observed a statistically increased level of biomarkers of oxidative/nitrative stress such as carbonyl groups or 3-nitrotyrosine in plasma proteins from schizophrenic patients. Moreover, our experiments indicate that the correlation between the increased amount of homocysteine and the oxidative stress exists. Considering the data presented in this study, we suggest that the elevated Hcys in schizophrenic patients may stimulate the oxidative stress.
    Preview · Article · Jan 2012 · Neurochemical Research
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