Elevated levels of plasma phenylalanine in schizophrenia: a guanosine triphosphate cyclohydrolase-1 metabolic pathway abnormality?
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.
Mood and Anxiety Program, University of Maryland School of Medicine, Baltimore, Maryland, United States of America ; Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston, Houston, Texas, United States of America.
Olaoluwa
O
Okusaga
Mood and Anxiety Program, University of Maryland School of Medicine, Baltimore, Maryland, United States of America.
Olesja
O
Muravitskaja
Division of Biological Chemistry, Biocenter Innsbruck Medical University, Innsbruck, Austria.
Dietmar
D
Fuchs
Mood and Anxiety Program, University of Maryland School of Medicine, Baltimore, Maryland, United States of America.
Ayesha
A
Ashraf
Mood and Anxiety Program, University of Maryland School of Medicine, Baltimore, Maryland, United States of America.
Sarah
S
Hinman
Section of Molecular and Clinical Neurobiology, Ludwig Maximilians University, Munich, Germany.
Ina
I
Giegling
Section of Molecular and Clinical Neurobiology, Ludwig Maximilians University, Munich, Germany.
Annette M
AM
Hartmann
Section of Molecular and Clinical Neurobiology, Ludwig Maximilians University, Munich, Germany.
Bettina
B
Konte
Section of Molecular and Clinical Neurobiology, Ludwig Maximilians University, Munich, Germany.
Marion
M
Friedl
Department of Psychology, University of Maryland, Baltimore, Maryland, United States of America.
Jason
J
Schiffman
Maryland Psychiatric Research Center (MPRC), Department of Psychiatry, University of Maryland School of Medicine, Baltimore, Maryland, United States of America.
Elliot
E
Hong
Division of Child and Adolescent Psychiatry, University of Maryland School of Medicine, Baltimore, Maryland, United States of America ; University of Maryland Child and Adolescent Mental Health Innovations Center, Baltimore, Maryland, United States of America.
Gloria
G
Reeves
University of South Florida, Tampa, Florida, United States of America.
Maureen
M
Groer
The University of Texas, MD Anderson Cancer Center, Houston, Texas, United States of America.
Robert
R
Dantzer
Section of Molecular and Clinical Neurobiology, Ludwig Maximilians University, Munich, Germany ; Department of Psychiatry, University of Halle-Wittenberg, Halle, Germany.
Dan
D
Rujescu
Mood and Anxiety Program, University of Maryland School of Medicine, Baltimore, Maryland, United States of America ; University of Maryland Child and Adolescent Mental Health Innovations Center, Baltimore, Maryland, United States of America ; VISN 5 Capitol Health Care Network Mental Illness Research Education and Clinical Center (MIRECC), Baltimore, Maryland, United States of America ; VISN 19 MIRECC, Denver, Colorado, United States of America.
Teodor T
TT
Postolache
D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D003710:Demography; D005260:Female; D006136:GTP Cyclohydrolase / Q000378:metabolism*; D006801:Humans; D008297:Male; D053858:Metabolic Networks and Pathways; D008875:Middle Aged; D010649:Phenylalanine / Q000097:blood*; D012559:Schizophrenia / Q000097:blood* / Q000175:diagnosis / Q000201:enzymology*; D014443:Tyrosine / Q000097:blood; D055815:Young Adult
D014443:Tyrosine; D010649:Phenylalanine; D006136:GTP Cyclohydrolase