Genetic Variation Throughout the Folate Metabolic Pathway Influences Negative Symptom Severity in Schizophrenia

Roffman, Joshua L.; Brohawn, David G.; Nitenson, Adam Z; Macklin, Eric A.; Smoller, Jordan W.; Goff, Donald C.

doi:10.1093/schbul/sbr150

Cited by 66 publications

(51 citation statements)

References 43 publications

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“…Additionally, it has been demonstrated that polymorphisms in the MTHFR gene are associated with negative symptoms severity [45, 46]. The exact mechanism of the correlation between Hcy levels and the severity of negative symptoms remains unknown.…”

Section: Discussionmentioning

confidence: 99%

Effects of second-generation antipsychotics on selected markers of one-carbon metabolism and metabolic syndrome components in first-episode schizophrenia patients

Misiak

Frydecka

Łaczmański

et al. 2014

Eur J Clin Pharmacol

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PurposeAlterations in one-carbon metabolism (OCM) have been repeatedly reported in schizophrenia. However, there is a scarcity of studies addressing the effects of antipsychotics on selected OCM markers in schizophrenia and provided results are inconsistent.MethodsWe recruited 39 first-episode schizophrenia (FES) patients and determined serum profile of total homocysteine (tHcy), folate, vitamin B12, lipoproteins and glucose at baseline and after 12 weeks of treatment with second-generation antipsychotics (SGA) including olanzapine and risperidone in monotherapy.ResultsAfter 12 weeks of treatment, all patients had significantly higher body mass index (BMI), serum levels of total cholesterol (TC), low-density lipoproteins (LDL), triglycerides (TG) and tHcy together with significantly lower levels of folate and vitamin B12. The analysis of differences between SGA revealed the same biochemical alterations in patients treated with olanzapine as in the whole group, while those receiving risperidone had no statistically significant changes in serum folate, vitamin B12 and TG. There was a significantly higher increase in BMI and TC in patients treated with olanzapine in comparison with those treated with risperidone. Patients receiving olanzapine had a higher decrease in vitamin B12 than those assigned to the treatment with risperidone. Changes in folate, vitamin B12, tHcy and TC levels were significant only in males, even after Bonferroni correction. Multiple regression analysis revealed that changes in tHcy levels are associated with gender and baseline metabolic parameters (BMI, glucose, TC, LDL and HDL) but not with selected SGA.ConclusionsThese results indicate that SGA may influence OCM, especially in first-episode schizophrenia (FES) males.Electronic supplementary materialThe online version of this article (doi:10.1007/s00228-014-1762-2) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Effects of second-generation antipsychotics on selected markers of one-carbon metabolism and metabolic syndrome components in first-episode schizophrenia patients

Misiak

Frydecka

Łaczmański

et al. 2014

Eur J Clin Pharmacol

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“…Moreover, the efficacy of supplementing a nutrient antioxidant such as folic acid in improving the enzymatic defense system demonstrates its potential application as a prophylactic treatment (Wu et al, 2013). New research in both humans and animals is needed to establish precise protocols, better costs, and thus identify patients who will actually benefit from this supplementation (Roffman et al, 2013b).…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Effect of folic acid on oxidative stress and behavioral changes in the animal model of schizophrenia induced by ketamine

Zugno

Canever

Heylmann

et al. 2016

Journal of Psychiatric Research

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“…Therefore, MTRR may regulate the expression of genes after antipsychotic treatment and thus variants in these genes may affect the way in which patients respond to treatment. Although MTRR itself has not yet been implicated in antipsychotic treatment response, MTHFR, which along with MTRR, is an important enzyme in the folate metabolism pathway, has been associated previously with antipsychotic treatment response outcomes [39,40]. Of particular interest to the findings of this study, it has been reported that the rs1801133 variant (677T-allele) in MTHFR is associated with less severe positive symptoms in schizophrenia patients [40,41].…”

Section: Discussionmentioning

confidence: 72%

“…MTRR forms part of the folate metabolism pathway and it has been suggested that variants affecting genes in this pathway may affect downstream methylation activities and gene expression levels [39]. Therefore, MTRR may regulate the expression of genes after antipsychotic treatment and thus variants in these genes may affect the way in which patients respond to treatment.…”

Section: Discussionmentioning

confidence: 99%

The identification of novel genetic variants associated with antipsychotic treatment response outcomes in first-episode schizophrenia patients

Drögemöller

Emsley

Chiliza

et al. 2016

Pharmacogenetics and Genomics

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The use of whole-exome sequencing in a subset of patients from a well-characterized cohort of first-episode schizophrenia patients, for whom longitudinal depot treatment response data were available, allowed for (i) the removal of confounding factors related to treatment progression and compliance and (ii) the identification of two genetic variants that have not been associated previously with antipsychotic treatment response outcomes and whose results were applicable across different classes of antipsychotics. Although the genes that are affected by these variants are involved in pathways that have been related previously to antipsychotic treatment outcomes, the identification of these novel genes will play an important role in improving our understanding of the specific variants involved in antipsychotic treatment response outcomes.

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Genetic Variation Throughout the Folate Metabolic Pathway Influences Negative Symptom Severity in Schizophrenia

Cited by 66 publications

References 43 publications

Effects of second-generation antipsychotics on selected markers of one-carbon metabolism and metabolic syndrome components in first-episode schizophrenia patients

Effects of second-generation antipsychotics on selected markers of one-carbon metabolism and metabolic syndrome components in first-episode schizophrenia patients

Effect of folic acid on oxidative stress and behavioral changes in the animal model of schizophrenia induced by ketamine

The identification of novel genetic variants associated with antipsychotic treatment response outcomes in first-episode schizophrenia patients

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