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Metabolome in schizophrenia and other psychotic disorders: a general population-based study
Örebro University, School of Medical Sciences. VTT Technical Research Centre of Finland, Espoo, Finland.ORCID iD: 0000-0002-2856-9165
VTT Technical Research Centre of Finland, Espoo, Finland.
VTT Technical Research Centre of Finland, Espoo, Finland.
VTT Technical Research Centre of Finland, Espoo, Finland.
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2011 (English)In: Genome Medicine, E-ISSN 1756-994X, Vol. 3, no 3, article id 19Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Persons with schizophrenia and other psychotic disorders have a high prevalence of obesity, impaired glucose tolerance, and lipid abnormalities, particularly hypertriglyceridemia and low high-density lipoprotein. More detailed molecular information on the metabolic abnormalities may reveal clues about the pathophysiology of these changes, as well as about disease specificity.

METHODS: We applied comprehensive metabolomics in serum samples from a general population-based study in Finland. The study included all persons with DSM-IV primary psychotic disorder (schizophrenia, n = 45; other non-affective psychosis (ONAP), n = 57; affective psychosis, n = 37) and controls matched by age, sex, and region of residence. Two analytical platforms for metabolomics were applied to all serum samples: a global lipidomics platform based on ultra-performance liquid chromatography coupled to mass spectrometry, which covers molecular lipids such as phospholipids and neutral lipids; and a platform for small polar metabolites based on two-dimensional gas chromatography coupled to time-of-flight mass spectrometry (GC × GC-TOFMS).

RESULTS: Compared with their matched controls, persons with schizophrenia had significantly higher metabolite levels in six lipid clusters containing mainly saturated triglycerides, and in two small-molecule clusters containing, among other metabolites, (1) branched chain amino acids, phenylalanine and tyrosine, and (2) proline, glutamic, lactic and pyruvic acids. Among these, serum glutamic acid was elevated in all psychoses (P = 0.0020) compared to controls, while proline upregulation (P = 0.000023) was specific to schizophrenia. After adjusting for medication and metabolic comorbidity in linear mixed models, schizophrenia remained independently associated with higher levels in seven of these eight clusters (P < 0.05 in each cluster). The metabolic abnormalities were less pronounced in persons with ONAP or affective psychosis.

CONCLUSIONS: Our findings suggest that specific metabolic abnormalities related to glucoregulatory processes and proline metabolism are specifically associated with schizophrenia and reflect two different disease-related pathways. Metabolomics, which is sensitive to both genetic and environmental variation, may become a powerful tool in psychiatric research to investigate disease susceptibility, clinical course, and treatment response.

Place, publisher, year, edition, pages
BioMed Central, 2011. Vol. 3, no 3, article id 19
National Category
Medical and Health Sciences Medical Genetics
Identifiers
URN: urn:nbn:se:oru:diva-63644DOI: 10.1186/gm233ISI: 000208627400019PubMedID: 21429189Scopus ID: 2-s2.0-79953072214OAI: oai:DiVA.org:oru-63644DiVA, id: diva2:1169209
Funder
EU, FP7, Seventh Framework Programme, FP7-KBBE-222639 FP7-KBBE-222720
Note

Funding agencies:

NARSAD Maltz Investigator

Award  Academy of Finland 129434 

Available from: 2017-12-22 Created: 2017-12-22 Last updated: 2024-07-04Bibliographically approved

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Oresic, MatejHyötyläinen, Tuulia

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