Homocysteine-Reducing Strategies Improve Symptoms in Chronic Schizophrenic Patients with Hyperhomocysteinemia

Levine, Joseph; Stahl, Ziva; Sela, Ben‐Ami; Ruderman, Vladimir; Shumaico, Oleg; Babushkin, Ivgeny; Osher, Yamima; Bersudsky, Yuly; Belmaker, R.H.

doi:10.1016/j.biopsych.2005.10.009

Cited by 115 publications

(85 citation statements)

References 14 publications

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“…Hyperhomocysteinemia did not appear to impact global DNA methylation in leukocytes of patients (Bromberg et al, 2008) or in mice with artificially elevated levels of homocysteine (Bromberg et al, 2011). Archived maternal serum samples assayed for levels of homocysteine during pregnancy indicate that an elevated homocysteine level, particularly during the third trimester, is associated with a greater than twofold increase in risk for SZ (Brown et al, 2007 supplementation has been used in clinical studies of SZ patients to alleviate negative symptoms with somewhat mixed results (Levine et al, 2006;Hill et al, 2011).…”

Section: One Carbon Metabolism and Szmentioning

confidence: 99%

The Dynamics of DNA Methylation in Schizophrenia and Related Psychiatric Disorders

Grayson

Guidotti

2012

Neuropsychopharmacol

239

214

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Major psychiatric disorders such as schizophrenia (SZ) and bipolar disorder (BP) with psychosis (BP+ ) express a complex symptomatology characterized by positive symptoms, negative symptoms, and cognitive impairment. Postmortem studies of human SZ and BP+ brains show considerable alterations in the transcriptome of a variety of cortical structures, including multiple mRNAs that are downregulated in both inhibitory GABAergic and excitatory pyramidal neurons compared with non-psychiatric subjects (NPS). Several reports show increased expression of DNA methyltransferases in telencephalic GABAergic neurons. Accumulating evidence suggests a critical role for altered DNA methylation processes in the pathogenesis of SZ and related psychiatric disorders. The establishment and maintenance of CpG site methylation is essential during central nervous system differentiation and this methylation has been implicated in synaptic plasticity, learning, and memory. Atypical hypermethylation of candidate gene promoters expressed in GABAergic neurons is associated with transcriptional downregulation of the corresponding mRNAs, including glutamic acid decarboxylase 67 (GAD67) and reelin (RELN). Recent reports indicate that the methylation status of promoter proximal CpG dinucleotides is in a dynamic balance between DNA methylation and DNA hydroxymethylation. Hydroxymethylation and subsequent DNA demethylation is more complex and involves additional proteins downstream of 5-hydroxymethylcytosine, including members of the base excision repair (BER) pathway. Recent advances in our understanding of altered CpG methylation, hydroxymethylation, and active DNA demethylation provide a framework for the identification of new targets, which may be exploited for the pharmacological intervention of the psychosis associated with SZ and possibly BP+ .

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Section: One Carbon Metabolism and Szmentioning

confidence: 99%

The Dynamics of DNA Methylation in Schizophrenia and Related Psychiatric Disorders

Grayson

Guidotti

2012

Neuropsychopharmacol

239

214

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“…One potential lead is that mifepristone (RU-486), a corticosteroid receptor antagonist, was associated with 20% improvement in spatial working memory, with little change in ratings of depression, in a small, double-blind, crossover study in depressed BPD patients (72). Also of potential interest, a randomized, doubleblind, placebo-controlled, crossover study reduced serum homocysteine concentrations in schizophrenia patients with oral folic acid, vitamin B12, and pyridoxine and found improvements in executive functioning as well as possibly confounding symptomatic status (73). These highly preliminary observations suggest that selective beneficial effect on some aspects of cognition, independent of mood-altering actions in BPD, may be feasible.…”

Section: Psychopharmacologic Effects On Neurocognitionmentioning

confidence: 99%

Neurocognitive impairment in bipolar disorder patients: functional implications

2009

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Growing evidence suggests that bipolar disorder (BPD) patients experience prominent neurocognitive impairment not only during acute mood episodes (1-3) but also during euthymia (1,(4)(5)(6)(7)(8)(9)(10)(11)(12). A recent meta-analytic review of 39 studies comparing neurocognitive functioning in 948 euthymic BPD patients and 1,128 normal controls, matched for age, sex, education, and estimated premorbid IQ, found medium-to-large effect sizes (ES, as group differences ⁄ variance) for impaired attention and processing speed (ES = 0.60-0.79), episodic memory (ES = 0.43-0.81), and executive functioning (ES = 0.47-0.71) in the BPD patients (11). Another meta-analytic review of 20 studies, also comparing neurocognitive performance in euthymic BPD patients to matched normal controls, found deficits of similar magnitude in measures of executive functions, verbal learning, immediate Background: Functional recovery among treated bipolar disorder (BPD) patients is far less likely than syndromal and even symptomatic recovery. We hypothesized that increasingly well-documented aspects of cognitive impairment may contribute to poor functional outcomes in BPD patients, and reviewed the available research on the topic.Methods: Computerized literature searching identified 12 studies with 13 comparisons that simultaneously evaluated cognitive and functional status in euthymic (n = 8) or non-euthymic (n = 5 comparisons) adult BPD patients versus otherwise similar healthy controls.Results: In 6 ⁄ 8 studies of euthymic BPD patients and 5 ⁄ 5 studies of non-euthymic BPD patients, neurocognitive impairment was significantly associated with impaired psychosocial functioning, even after adjusting for residual mood symptoms and relevant demographic and clinical variables. Cognitive status was consistently assessed with standardized, performance-based neuropsychological tests, but functional status usually was based on subjective self-appraisals. Approximately 55% of BPD patients were unemployed.Conclusions: Available studies are limited by subjective assessments of functional status rather than objective, performance-based measures. Nevertheless, they support the hypothesis that enduring aspects of cognitive impairment found even in euthymic BPD patients are associated with inferior functioning. These findings encourage further studies with better assessment methods and greater rehabilitative efforts in BPD patients.

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“…In a small double blind placebocontrol study, Godfrey et al, [49] showed symptom and social recovery in 17 schizophrenia patients with baseline low folate levels who received daily methylfolate supplementation (15 mg/day) for six months in addition to standard pharmacologic treatment. Levine and colleagues [50] demonstrated symptom improvement in schizophrenic patients supplemented with folic acid (2 mg/day), vitamin B6 (25 mg/day) and vitamin B12 (400 mcg/day) in addition to regular antipsychotic treatment. According to Firth's.…”

Section: Discussionmentioning

confidence: 99%

“…Supplementation with both folate and vitamin B12 can be beneficial, especially in improving negative symptoms. [50,52] Vitamin and mineral supplements can be important in cases of substance and alcohol abuse. [53,54] The results of the studies suggested that some drug treatments might lead to a decrease in folic acid levels.…”

Section: Discussionmentioning

confidence: 99%

Determination of vitamin B12, folate, and ferritin levels of inpatients in a psychiatry clinic: A one-year retrospective study

Örüm¹

2018

FNG & Bilim Tıp Dergisi

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Objectives:This study aims to compare the vitamin B12, folate, and ferritin levels of inpatients in a psychiatry clinic. Materials and methods:The study included 286 inpatients (178 males, 108 females; mean age 35.4±12.9 years; range, 15 to 76 years) treated in Adiyaman University Training and Research Hospital psychiatry clinic between 01 January 2017 and 31 December 2017. Patients' diagnoses and vitamin B12, folate, and ferritin levels were examined retrospectively. Results:The most common diagnoses were schizophrenia (23.4%), bipolar affective disorder (23.1%), and major depressive disorder (11.5%). While there was no significant difference in vitamin B12 levels according to sex (p=0.850), folate level was significantly lower in males (p=0.001) and ferritin level was significantly lower in females (p=0.001). No difference was detected in the levels of vitamin B12, folate and ferritin in the comparison between diagnoses. Conclusion: Deficiency in vitamin B12, folate, and ferritin levels may cause psychiatric symptoms. Due to the high number of patients with low vitamin B12 levels in our study, more attention may be paid to vitamin B12 replacement. Ferritin deficiency in females and folate deficiency in males are noteworthy. Further research are needed to identify more specific and detailed algorithms related to vitamin B12, folate, and ferritin to support the findings of this study and optimize the care given to patients suffering from psychiatric syndromes. Bulgular: En sık görülen tanılar şizofreni (%23.4), bipolar affektif bozukluk (%23.1) ve majör depresif bozukluk (%11.5) idi. Cinsiyete göre B12 vitamini düzeylerinde anlamlı farklılık yokken (p=0.850) erkeklerde folat düzeyi (p=0.001) ve kadınlarda ferritin düzeyi (p=0.001) anlamlı olarak düşük idi. Tanılar arasındaki karşılaştırmada; B12 vitamini, folat ve ferritin düzeyleri arasında farklılık tespit edilmedi. Sonuç: B12 vitamini, folat ve ferritin düzeylerinde eksiklik psikiyatrik semptomlara neden olabilir. Çalışmamızda B12 vitamini düzeyi düşük olan hasta sayısının fazla olmasına bağlı olarak B12 vitamini replasmanında daha dikkatli olunabilir. Kadınlardaki ferritin eksikliği ve erkeklerdeki folat eksikliği dikkat çekicidir. Bu çalışmanın bulgularını desteklemek ve psikiyatrik sendromu olan hastalara verilen bakımın optimize edilmesi için B12 vitamini, folat ve ferritine ilişkin daha spesifik ve ayrıntılı algoritmaları belirlemek amacıyla ileri araştırmalar gerekmektedir.Anahtar sözcükler: Ferritin; folik asit; yatan hastalar; psikiyatri; retrospektif çalışma; B12 vitamini.

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Homocysteine-Reducing Strategies Improve Symptoms in Chronic Schizophrenic Patients with Hyperhomocysteinemia

Cited by 115 publications

References 14 publications

The Dynamics of DNA Methylation in Schizophrenia and Related Psychiatric Disorders

The Dynamics of DNA Methylation in Schizophrenia and Related Psychiatric Disorders

Neurocognitive impairment in bipolar disorder patients: functional implications

Determination of vitamin B12, folate, and ferritin levels of inpatients in a psychiatry clinic: A one-year retrospective study

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