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Association between the blood concentrations of ammonia and carnitine/amino acid of schizophrenic patients treated with valproic acid

BACKGROUND: Administration of valproic acid (VPA) is complicated with approximately 0.9% of patients developing hyperammonemia, but the pathogenesis of this adverse effect remains to be clarified. The aim of the present study was to search for mechanisms associated with VPA-induced hyperammonemia in...

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Autores principales: Ando, Masazumi, Amayasu, Hideaki, Itai, Takahiro, Yoshida, Hisahiro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5497353/
https://www.ncbi.nlm.nih.gov/pubmed/28690671
http://dx.doi.org/10.1186/s13030-017-0101-0
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author Ando, Masazumi
Amayasu, Hideaki
Itai, Takahiro
Yoshida, Hisahiro
author_facet Ando, Masazumi
Amayasu, Hideaki
Itai, Takahiro
Yoshida, Hisahiro
author_sort Ando, Masazumi
collection PubMed
description BACKGROUND: Administration of valproic acid (VPA) is complicated with approximately 0.9% of patients developing hyperammonemia, but the pathogenesis of this adverse effect remains to be clarified. The aim of the present study was to search for mechanisms associated with VPA-induced hyperammonemia in the light of changes in serum amino acids concentrations associated with the urea cycle of schizophrenic patients. METHOD: Blood samples (10 mL) were obtained from 37 schizophrenic patients receiving VPA for the prevention of violent behaviors in the morning after overnight fast. Blood concentrations of ammonia, VPA, free carnitine, acyl-carnitine, and 40 amino acids including glutamate and citrulline were measured for each patient. Univariate and multivariate regression analyses were performed to identify amino acids or concomitantly administered drugs that were associated with variability in the blood concentrations of ammonia. RESULT: The blood ammonia level was positively correlated with the serum glutamate concentration (r = 0.44, p < 0.01) but negatively correlated with glutamine (r = −0.41, p = 0.01), citrulline (r = −0.42, p = 0.01), and glycine concentrations (r = −0.54, p < 0.01). It was also revealed that the concomitant administration of the mood stabilizers (p = 0.04) risperidone (p = 0.03) and blonanserin (p < 0.01) was positively associated with the elevation of the blood ammonia level. CONCLUSION: We hypothisized that VPA would elevate the blood ammonia level of schizophrenic patients. The observed changes in serum amino acids are compatible with urea cycle dysfunction, possibly due to reduced carbamoyl-phosphate synthase 1 (CPS1) activity. We conclude that VPA should be prudently prescribed to schizophrenic patients, particularly those receiving mood stabilizers or certain antipsychotics.
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spelling pubmed-54973532017-07-07 Association between the blood concentrations of ammonia and carnitine/amino acid of schizophrenic patients treated with valproic acid Ando, Masazumi Amayasu, Hideaki Itai, Takahiro Yoshida, Hisahiro Biopsychosoc Med Research BACKGROUND: Administration of valproic acid (VPA) is complicated with approximately 0.9% of patients developing hyperammonemia, but the pathogenesis of this adverse effect remains to be clarified. The aim of the present study was to search for mechanisms associated with VPA-induced hyperammonemia in the light of changes in serum amino acids concentrations associated with the urea cycle of schizophrenic patients. METHOD: Blood samples (10 mL) were obtained from 37 schizophrenic patients receiving VPA for the prevention of violent behaviors in the morning after overnight fast. Blood concentrations of ammonia, VPA, free carnitine, acyl-carnitine, and 40 amino acids including glutamate and citrulline were measured for each patient. Univariate and multivariate regression analyses were performed to identify amino acids or concomitantly administered drugs that were associated with variability in the blood concentrations of ammonia. RESULT: The blood ammonia level was positively correlated with the serum glutamate concentration (r = 0.44, p < 0.01) but negatively correlated with glutamine (r = −0.41, p = 0.01), citrulline (r = −0.42, p = 0.01), and glycine concentrations (r = −0.54, p < 0.01). It was also revealed that the concomitant administration of the mood stabilizers (p = 0.04) risperidone (p = 0.03) and blonanserin (p < 0.01) was positively associated with the elevation of the blood ammonia level. CONCLUSION: We hypothisized that VPA would elevate the blood ammonia level of schizophrenic patients. The observed changes in serum amino acids are compatible with urea cycle dysfunction, possibly due to reduced carbamoyl-phosphate synthase 1 (CPS1) activity. We conclude that VPA should be prudently prescribed to schizophrenic patients, particularly those receiving mood stabilizers or certain antipsychotics. BioMed Central 2017-07-05 /pmc/articles/PMC5497353/ /pubmed/28690671 http://dx.doi.org/10.1186/s13030-017-0101-0 Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Ando, Masazumi
Amayasu, Hideaki
Itai, Takahiro
Yoshida, Hisahiro
Association between the blood concentrations of ammonia and carnitine/amino acid of schizophrenic patients treated with valproic acid
title Association between the blood concentrations of ammonia and carnitine/amino acid of schizophrenic patients treated with valproic acid
title_full Association between the blood concentrations of ammonia and carnitine/amino acid of schizophrenic patients treated with valproic acid
title_fullStr Association between the blood concentrations of ammonia and carnitine/amino acid of schizophrenic patients treated with valproic acid
title_full_unstemmed Association between the blood concentrations of ammonia and carnitine/amino acid of schizophrenic patients treated with valproic acid
title_short Association between the blood concentrations of ammonia and carnitine/amino acid of schizophrenic patients treated with valproic acid
title_sort association between the blood concentrations of ammonia and carnitine/amino acid of schizophrenic patients treated with valproic acid
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5497353/
https://www.ncbi.nlm.nih.gov/pubmed/28690671
http://dx.doi.org/10.1186/s13030-017-0101-0
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