Elevated levels of plasma phenylalanine in schizophrenia: a guanosine triphosphate cyclohydrolase-1 metabolic pathway abnormality?

PLoS One. 2014 Jan 21;9(1):e85945. doi: 10.1371/journal.pone.0085945. eCollection 2014.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Case-Control Studies
  • Demography
  • Female
  • GTP Cyclohydrolase / metabolism*
  • Humans
  • Male
  • Metabolic Networks and Pathways
  • Middle Aged
  • Phenylalanine / blood*
  • Schizophrenia / blood*
  • Schizophrenia / diagnosis
  • Schizophrenia / enzymology*
  • Tyrosine / blood
  • Young Adult

Substances

  • Tyrosine
  • Phenylalanine
  • GTP Cyclohydrolase

Grants and funding

Financial support was provided by a Standard Research Grant (PI Postolache, coPI Rujescu) and a Distinguished Investigator Award (PI Postolache) from the American Foundation for Suicide Prevention, VISN 5 Capitol Health Care Network Mental Illness Research Education and Clinical Center (MIRECC), Baltimore, MD, USA and VISN 19 MIRECC, Denver, Colorado, USA (Postolache), University of Maryland Child and Adolescent Mental Health Innovations Center, Baltimore, Maryland, USA (Postolache), and Department of Psychiatry and Behavioral Sciences, University of Texas Health Science Center at Houston (Okusaga). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.