[Frontiers in Bioscience E3, 308-314, January 1, 2011]

Alterations of primary fatty acid amides in serum of patients with severe mental illness

Emanuel Schwarz1, Phil Whitfield2, Sven Nahnsen3, Lan Wang1, Hilary Major4, F. Markus Leweke5, Dagmar Koethe5, Pietro Lio6, Sabine Bahn1

1Institute of Biotechnology, University of Cambridge, Cambridge CB2 1QT, UK, 2Proteomics and Functional Genomics Research Group, Faculty of Veterinary Science, University of Liverpool, Liverpool, UK, 3Division for Simulation of Biological Systems, Center for Bioinformatics, Eberhard-Karls University, 72076 Tuebingen, Germany, 4Waters Corporation, Atlas Park, Manchester, M22 5PP, UK, 5Central Institute of Mental Health, University of Heidelberg, Mannheim, Germany 6Computer Laboratory, University of Cambridge, Cambridge CB3 0FD, UK

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Material and Methods
3.1. Clinical Samples
3.2. Preparation of serum samples
3.3. Liquid Chromatography
3.4. Mass spectrometry
3.5. Data Processing
3.6. Statistical analysis
4. Results
4.1. Characterization of serum metabolite changes
4.2. Effects of antipsychotic treatment and cannabis consumption on the extracted metabolic network
4.3. Alteration of the extracted metabolic network in affective disorder and sleep deprived healthy volunteers
5. Discussion
5.1. Effects of antipsychotic treatment on the pFAA metabolic network
5.2. Alteration of the pFAA metabolic network in affective disorder
6. Conculsion
7. Acknowledgement
8. References

1. ABSTRACT

Cannabis consumption is a well known risk factor for the onset of schizophrenia and evidence accumulates that the endocannabinoid system may play a central role in the disease etiology. Using a clinical bioinformatics approach, we have previously found primary fatty acid amides, which are linked to the endocannabinoid system, to be elevated in drug naive schizophrenia and affective disorder. Here, we provide a detailed description of these findings and expand the investigation by analyzing serum from 74 patients after short term treatment with antipsychotic medication using a liquid chromatography-mass spectrometry (LC-MS) metabolomics approach. We show that primary fatty acid amide (pFAA) levels normalize after treatment with typical but not after treatment with atypical antipsychotic medication. Also, the comparison of pFAA levels in schizophrenia patients to those of sleep deprived healthy volunteers suggests that pFAA abnormalities were not related to changes in the sleep architecture of patients with mental illness. Our findings support the involvement of the endocannabinoid system in the pathology of schizophrenia.