Metabolomic profiling to identify potential serum biomarkers for schizophrenia and risperidone action

J Proteome Res. 2011 Dec 2;10(12):5433-43. doi: 10.1021/pr2006796. Epub 2011 Nov 8.

Abstract

Despite recent advances in understanding the pathophysiology of schizophrenia and the mechanisms of antipsychotic drug action, the development of biomarkers for diagnosis and therapeutic monitoring in schizophrenia remains challenging. Metabolomics provides a powerful approach to discover diagnostic and therapeutic biomarkers by analyzing global changes in an individual's metabolic profile in response to pathophysiological stimuli or drug intervention. In this study, we performed gas chromatography-mass spectrometry based metabolomic profiling in serum of unmedicated schizophrenic patients before and after an 8-week risperidone monotherapy, to detect potential biomarkers associated with schizophrenia and risperidone treatment. Twenty-two marker metabolites contributing to the complete separation of schizophrenic patients from matched healthy controls were identified, with citrate, palmitic acid, myo-inositol, and allantoin exhibiting the best combined classification performance. Twenty marker metabolites contributing to the complete separation between posttreatment and pretreatment patients were identified, with myo-inositol, uric acid, and tryptophan showing the maximum combined classification performance. Metabolic pathways including energy metabolism, antioxidant defense systems, neurotransmitter metabolism, fatty acid biosynthesis, and phospholipid metabolism were found to be disturbed in schizophrenic patients and partially normalized following risperidone therapy. Further study of these metabolites may facilitate the development of noninvasive biomarkers and more efficient therapeutic strategies for schizophrenia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers / analysis
  • Biomarkers / blood
  • Case-Control Studies
  • Citric Acid / blood
  • Energy Metabolism
  • Female
  • Gas Chromatography-Mass Spectrometry
  • Humans
  • Male
  • Metabolic Networks and Pathways
  • Metabolome*
  • Middle Aged
  • Palmitic Acid / blood
  • Principal Component Analysis
  • Risperidone / therapeutic use*
  • Schizophrenia / blood*
  • Schizophrenia / diagnosis*
  • Schizophrenia / drug therapy
  • Uric Acid / blood

Substances

  • Biomarkers
  • Uric Acid
  • Citric Acid
  • Palmitic Acid
  • Risperidone