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

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...

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Bibliographic Details
Published in:Journal of psychiatric research 2018-04, Vol.99, p.142
Main Authors: Teraishi, Toshiya, Kajiwara, Masahiro, Hori, Hiroaki, Sasayama, Daimei, Hidese, Shinsuke, Matsuo, Junko, Ishida, Ikki, Kajiwara, Yasuhiro, Ozeki, Yuji, Ota, Miho, Hattori, Kotaro, Higuchi, Teruhiko, Kunugi, Hiroshi
Format: Article
Language:English
Subjects:
Adult
Biopterins - blood
Bipolar Disorder - blood
Bipolar Disorder - genetics
Bipolar Disorder - metabolism
Breath Tests
Carbon Isotopes - metabolism
Depressive Disorder, Major - blood
Depressive Disorder, Major - genetics
Depressive Disorder, Major - metabolism
Female
Genetic Association Studies
Humans
Male
Middle Aged
Phenylalanine - metabolism
Phenylalanine Hydroxylase - genetics
Polymorphism, Single Nucleotide
Schizophrenia - blood
Schizophrenia - genetics
Schizophrenia - metabolism
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Summary: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- C]phenylalanine breath test ( C-PBT) and serum biopterin levels. We also investigated association of PAH mutations with schizophrenia and phenylalanine metabolism. C-phenylalanine (100 mg) was orally administered, and the breath CO / CO 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 CO was significantly lower in the schizophrenia group than in the other three groups (all p 
ISSN:1879-1379