Increased homocysteine levels in valproate-treated patients with epilepsy: a meta-analysis

Ni, Guanzhong; Qin, Jiaming; Fang, Ziyan; Chen, Yishu; Chen, Ziyi; Zhou, Jueqian; Zhou, Liemin

doi:10.1136/bmjopen-2014-004936

Cited by 23 publications

(16 citation statements)

References 29 publications

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“…In this study, we found that the concentration of Hcy in serum was significantly increased in prenatal VPA‐exposed mice, in accordance with that observed in autism patients. Previous studies have shown that VPA monotherapy is associated with increased plasma Hcy levels in epilepsy patients, suggesting that VPA could influence the metabolism of Hcy. Here we found that the expression of BHMT was reduced in the liver of VPA mice.…”

Section: Discussionmentioning

confidence: 97%

Betaine ameliorates prenatal valproic‐acid‐induced autism‐like behavioral abnormalities in mice by promoting homocysteine metabolism

Huang

Chen

Jiang

et al. 2019

Psychiatry Clin Neurosci

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Aim Abnormally high levels of homocysteine (Hcy) are associated with autism spectrum disorder. Betaine is a methyl group donor in Hcy metabolism, and is known to prevent noxious Hcy accumulation. This study explored whether betaine could influence Hcy metabolism in a mouse model of autism and ameliorate behavioral abnormalities. Methods Pregnant ICR mice were administered valproic acid (VPA) intraperitoneally on Embryonic Day 12.5. Serum Hcy concentrations in the offspring were measured by enzyme‐linked immunosorbent assay. Expressions of Hcy‐metabolism‐related enzymes, betaine‐Hcy methyltransferase, cystathionine β‐synthase, and methionine synthase, were measured by quantitative reverse transcription polymerase chain reaction and western blotting. Offspring were treated by either betaine or saline at the age of 8 weeks and serum Hcy concentrations were measured. Social behaviors were assessed by sniff‐duration test and three‐chamber test. Repetitive behavior was evaluated by marble‐burying test. Tail‐flick test was performed to measure nociceptive sensitivity. Results Prenatal VPA‐exposed mice showed significantly elevated Hcy concentrations and decreased betaine‐Hcy methyltransferase expression. Treatment with betaine could reduce Hcy level in VPA‐exposed mice, attenuate social impairment and repetitive behavior, and normalize nociceptive sensitivity in this model. Conclusion Betaine could ameliorate autism‐like features and play a beneficial role in a mouse autism model induced by prenatal VPA exposure.

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Section: Discussionmentioning

confidence: 97%

Betaine ameliorates prenatal valproic‐acid‐induced autism‐like behavioral abnormalities in mice by promoting homocysteine metabolism

Huang

Chen

Jiang

et al. 2019

Psychiatry Clin Neurosci

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“…However, previous studies have demonstrated that the effects of valproate on serum folate and Hcy levels are contradictory. Most studies have shown that valproate reduced folic acid levels and increased the levels of Hcy (Gorjipour, Asadi, K Osguei, Effatkhah, & Samadikuchaksaraei, ; Ni et al, ; Sharma, Vardey, & Sitaraman, ), whereas other studies have found that valproic acid use was significantly associated with elevated Hcy level only in children with epilepsy (Dinç & Schulte, ). The results of adult patients with epilepsy were contradictory (Dinç & Schulte, ).…”

Section: Discussionmentioning

confidence: 99%

Sex differences in the prevalence and clinical correlates of hyperhomocysteinemia in patients with bipolar disorder

Lin

Huang

et al. 2020

Human Psychopharmacology

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Objective Sex differences in bipolar disorder are well recognized but little attention has been paid to sex differences in homocysteine or hyperhomocysteinemia in bipolar patients. This study compared gender differences in homocysteine levels and rates of hyperhomocysteinemia in Chinese inpatients with bipolar disorder. Methods A total of 198 BD patients and 84 healthy controls were enrolled. The Young Mania Rating Scale, Hamilton Depression Rating Scale, and the Clinical Global Impressions–Severity scale were used to assess the affective symptomatology. Fasting plasma Hcy levels were measured by high‐performance liquid chromatography. Results Men had higher homocysteine levels than women and the prevalence of hyperhomocysteinemia in male patients was approximately twice that in female patients. Logistic regression analyses showed that HHcy was associated with less frequent use of valproate in males and being overweight in females. Further correlation analysis and multivariate regression analysis demonstrated that Hcy levels were inversely correlated with valproate treatment in men and positively associated with overweight in women. Conclusions In bipolar patients, there are significant differences between sexes in the levels of homocysteine and prevalence of hyperhomocysteinemia. This appears to be associated with lower prevalence of valproate prescribing in men and with being overweight in women.

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“…83,84 However, evaluations of Hcy levels in patients with epilepsy treated with mood stabilizers do not present consistent results. A study published by Gidal et al 85 did not show increased Hcy levels in patients with epilepsy treated with sodium valproate and lamotrigine, but the meta-analysis published by Ni et al 86 associated sodium valproate monotherapy with increased levels of Hcy in patients with epilepsy. Genetic background related to enzymes involved in 1-carbon metabolism could explain the increased Hcy in bipolar patients on mood stabilizers therapy or even indicate Hcy as an independent risk factor for the development of bipolar disorder.…”

Section: Major Depressive Disordermentioning

confidence: 96%

Homocysteine and Psychiatric Disorders

Silva

Oliveira

D’Almeida

2017

Journal of Inborn Errors of Metabolism and Screening

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Psychiatric disorders are highly prevalent all over the world with a great impact on public health. Altered homocysteine metabolism is implicated in the pathogenesis of many of these disorders, as it can interfere in normal methylation of subcellular components, promote neuroexcitotoxicity, and induce oxidative stress and inflammation. There are cumulative data implicating these mechanisms in the development of autism, schizophrenia, depression, bipolar disorder, and Alzheimer disease. Altered homocysteine metabolism is multifactorial in its origin. On one hand, genetic factors act as predisposing factors through brain development and function, and on the other hand, environmental factors give the opportunity for nutritional interventions improving metabolic status and possibly also clinical parameters. This article provides a review on the association of 1-carbon metabolism and autism, schizophrenia, depression, bipolar disorder, and dementia and goes through studies on the role of different cofactors and metabolites involved in this pathway.

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Increased homocysteine levels in valproate-treated patients with epilepsy: a meta-analysis

Cited by 23 publications

References 29 publications

Betaine ameliorates prenatal valproic‐acid‐induced autism‐like behavioral abnormalities in mice by promoting homocysteine metabolism

Betaine ameliorates prenatal valproic‐acid‐induced autism‐like behavioral abnormalities in mice by promoting homocysteine metabolism

Sex differences in the prevalence and clinical correlates of hyperhomocysteinemia in patients with bipolar disorder

Homocysteine and Psychiatric Disorders

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