Summary

J Psychiatr Res. 2018 Apr;99:142-150. doi: 10.1016/j.jpsychires.2018.01.019. Epub 2018 Feb 3.

13C-phenylalanine breath test and serum biopterin in schizophrenia, bipolar disorder and major depressive disorder.

Abstract:

Phenylalanine is required for the synthesis of the neurotransmitters dopamine, noradrenaline, and adrenaline. The rate-limiting step for phenylalanine metabolism is catalyzed by phenylalanine hydroxylase (PAH) and its cofactor tetrahydrobiopterin. We aimed to detect altered phenylalanine metabolism in major psychiatric disorders using the l-[1-13C]phenylalanine breath test (13C-PBT) and serum biopterin levels. We also investigated association of PAH mutations with schizophrenia and phenylalanine metabolism. 13C-phenylalanine (100 mg) was orally administered, and the breath 13CO2/12CO2 ratio was monitored for 120 min in four groups: 103 patients with schizophrenia (DSM-IV), 39 with bipolar disorder, 116 with major depressive disorder (MDD), and 241 healthy controls. Serum biopterin levels were measured by high performance liquid chromatography. Mutation screening of PAH exons was performed by direct sequencing in 46 schizophrenia patients. Association analysis was performed using six tag single nucleotide polymorphisms and the PAH Arg53His mutation by TaqMan assays in 616 schizophrenia patients and 1194 healthy controls. Analyses of covariance controlling for age, sex, and body weight showed that the index for the amount of exhaled 13CO2 was significantly lower in the schizophrenia group than in the other three groups (all p < 0.05). Biopterin levels in schizophrenia and MDD were significantly lower than those in controls. Biopterin levels correlated with 13C-PBT indices in controls. PAH polymorphisms were not associated with schizophrenia or 13C-PBT indices. 13C-PBT revealed reduced phenylalanine metabolism in schizophrenia, though we obtained no evidence of involvement of PAH polymorphism. Serum biopterin levels were lower in schizophrenia and MDD, warranting further investigation.

日本語要旨:

本研究では、統合失調症、大うつ病、躁うつ病の患者さんを対象にフェニルアラニン呼気検査と血中ビオプテリン濃度測定を行いました。その結果、統合失調症ではフェニルアラニンの代謝低下、また統合失調症と大うつ病におきまして血中ビオプテリン濃度の低下が認められました

PMID:  29454221

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