Association between the blood concentrations of ammonia and carnitine-amino acid of schizophrenic patients treated with valproic acidReport as inadecuate




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BioPsychoSocial Medicine

, 11:19

First Online: 05 July 2017Received: 11 December 2016Accepted: 29 May 2017

Abstract

BackgroundAdministration 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.

MethodBlood 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.

ResultThe 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.

ConclusionWe 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.

KeywordsHyperammonemia Valproic acid Carnitine Glutamate Glycine CPS1 Mood stabilizer Antipsychotics AbbreviationsVPAValproic acid

NAGN-acetyl glutamic acid

NAGSN-acetyl glutamic acid synthase

CPS1carbamoyl-phosphate synthase 1

NMDAN-methyl-D-aspartate

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Author: Masazumi Ando - Hideaki Amayasu - Takahiro Itai - Hisahiro Yoshida

Source: https://link.springer.com/



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