Elevated Levels of Plasma Phenylalanine in Schizophrenia: a Guanosine Triphosphate Cyclohydrolase-1 Metabolic Pathway Abnormality?

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2014 Jan 28

PMID 24465804

Citations 11

Authors

Olaoluwa Okusaga

Olesja Muravitskaja

Dietmar Fuchs

Ayesha Ashraf

Sarah Hinman

Ina Giegling

Annette M Hartmann

Bettina Konte

Marion Friedl

Jason Schiffman

Elliot Hong

Gloria Reeves

Maureen Groer

Robert Dantzer

Dan Rujescu

Teodor T Postolache

Affiliations

Soon will be listed here.

Abstract

Background: Phenylalanine and tyrosine are precursor amino acids required for the synthesis of dopamine, the main neurotransmitter implicated in the neurobiology of schizophrenia. Inflammation, increasingly implicated in schizophrenia, can impair the function of the enzyme Phenylalanine hydroxylase (PAH; which catalyzes the conversion of phenylalanine to tyrosine) and thus lead to elevated phenylalanine levels and reduced tyrosine levels. This study aimed to compare phenylalanine, tyrosine, and their ratio (a proxy for PAH function) in a relatively large sample of schizophrenia patients and healthy controls.

Methods: We measured non-fasting plasma phenylalanine and tyrosine in 950 schizophrenia patients and 1000 healthy controls. We carried out multivariate analyses to compare log transformed phenylalanine, tyrosine, and phenylalanine:tyrosine ratio between patients and controls.

Results: Compared to controls, schizophrenia patients had higher phenylalanine (p<0.0001) and phenylalanine: tyrosine ratio (p<0.0001) but tyrosine did not differ between the two groups (p = 0.596).

Conclusions: Elevated phenylalanine and phenylalanine:tyrosine ratio in the blood of schizophrenia patients have to be replicated in longitudinal studies. The results may relate to an abnormal PAH function in schizophrenia that could become a target for novel preventative and interventional approaches.

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