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BioPsychoSocial Medicine
Published in: BioPsychoSocial Medicine 1/2017

Open Access 01-12-2017 | Research

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

Authors: Masazumi Ando, Hideaki Amayasu, Takahiro Itai, Hisahiro Yoshida

Published in: BioPsychoSocial Medicine | Issue 1/2017

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Abstract

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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Metadata
Title
Association between the blood concentrations of ammonia and carnitine/amino acid of schizophrenic patients treated with valproic acid
Authors
Masazumi Ando
Hideaki Amayasu
Takahiro Itai
Hisahiro Yoshida
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BioPsychoSocial Medicine / Issue 1/2017
Electronic ISSN: 1751-0759
DOI
https://doi.org/10.1186/s13030-017-0101-0

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