Metabolome in schizophrenia and other psychotic disorders: A general population-based study

Matej Oresic (Corresponding Author), Jing Tang, Tuulikki Seppänen-Laakso, Ismo Mattila, S. E. Saarni, S. I. Saarni, J. Lönnqvist, Marko Sysi-Aho, Tuulia Hyötyläinen, J. Perälä, J. Suvisaari

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Abstract

BackgroundPersons 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.MethodsWe 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).ResultsCompared 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.ConclusionsOur 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.
Original languageEnglish
JournalGenome Medicine
Volume3
Issue number19
DOIs
Publication statusPublished - 2011
MoE publication typeA1 Journal article-refereed

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Metabolome
Psychotic Disorders
Schizophrenia
Metabolomics
Proline
Psychotic Affective Disorders
Population
Lipids
Mass Spectrometry
Serum
Branched Chain Amino Acids
Glucose Intolerance
Hypertriglyceridemia
Disease Susceptibility
HDL Lipoproteins
Finland
Pyruvic Acid
Phenylalanine
LDL Lipoproteins
Liquid Chromatography

Cite this

Oresic, Matej ; Tang, Jing ; Seppänen-Laakso, Tuulikki ; Mattila, Ismo ; Saarni, S. E. ; Saarni, S. I. ; Lönnqvist, J. ; Sysi-Aho, Marko ; Hyötyläinen, Tuulia ; Perälä, J. ; Suvisaari, J. / Metabolome in schizophrenia and other psychotic disorders : A general population-based study. In: Genome Medicine. 2011 ; Vol. 3, No. 19.
@article{d61fe121c2304ba386718ff8c2894ed7,
title = "Metabolome in schizophrenia and other psychotic disorders: A general population-based study",
abstract = "BackgroundPersons 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.MethodsWe 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).ResultsCompared 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.ConclusionsOur 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.",
author = "Matej Oresic and Jing Tang and Tuulikki Sepp{\"a}nen-Laakso and Ismo Mattila and Saarni, {S. E.} and Saarni, {S. I.} and J. L{\"o}nnqvist and Marko Sysi-Aho and Tuulia Hy{\"o}tyl{\"a}inen and J. Per{\"a}l{\"a} and J. Suvisaari",
year = "2011",
doi = "10.1186/gm233",
language = "English",
volume = "3",
journal = "Genome Medicine",
issn = "1756-994X",
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Oresic, M, Tang, J, Seppänen-Laakso, T, Mattila, I, Saarni, SE, Saarni, SI, Lönnqvist, J, Sysi-Aho, M, Hyötyläinen, T, Perälä, J & Suvisaari, J 2011, 'Metabolome in schizophrenia and other psychotic disorders: A general population-based study', Genome Medicine, vol. 3, no. 19. https://doi.org/10.1186/gm233

Metabolome in schizophrenia and other psychotic disorders : A general population-based study. / Oresic, Matej (Corresponding Author); Tang, Jing; Seppänen-Laakso, Tuulikki; Mattila, Ismo; Saarni, S. E.; Saarni, S. I.; Lönnqvist, J.; Sysi-Aho, Marko; Hyötyläinen, Tuulia; Perälä, J.; Suvisaari, J.

In: Genome Medicine, Vol. 3, No. 19, 2011.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Metabolome in schizophrenia and other psychotic disorders

T2 - A general population-based study

AU - Oresic, Matej

AU - Tang, Jing

AU - Seppänen-Laakso, Tuulikki

AU - Mattila, Ismo

AU - Saarni, S. E.

AU - Saarni, S. I.

AU - Lönnqvist, J.

AU - Sysi-Aho, Marko

AU - Hyötyläinen, Tuulia

AU - Perälä, J.

AU - Suvisaari, J.

PY - 2011

Y1 - 2011

N2 - BackgroundPersons 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.MethodsWe 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).ResultsCompared 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.ConclusionsOur 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.

AB - BackgroundPersons 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.MethodsWe 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).ResultsCompared 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.ConclusionsOur 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.

U2 - 10.1186/gm233

DO - 10.1186/gm233

M3 - Article

VL - 3

JO - Genome Medicine

JF - Genome Medicine

SN - 1756-994X

IS - 19

ER -