Metabolomic mapping of atypical antipsychotic effects in schizophrenia

R. Kaddurah-Daouk, Joseph Patrick McEvoy, R. A. Baillie, D. Lee, J. K. Yao, P. M. Doraiswamy, K. R.R. Krishnan

Research output: Contribution to journalArticle

178 Citations (Scopus)

Abstract

Schizophrenia is associated with impairments in neurotransmitter systems and changes in neuronal membrane phospholipids. Several atypical antipsychotic drugs induce weight gain and hypertriglyceridemia. To date, there has not been a comprehensive evaluation and mapping of global lipid changes in schizophrenia, and upon treatment with antipsychotics. Such mapping could provide novel insights about disease mechanisms and metabolic side effects of therapies used for its treatment. We used a specialized metabolomics platform 'lipidomics' that quantifies over 300 polar and nonpolar lipid metabolites (across seven lipid classes) to evaluate global lipid changes in schizophrenia and upon treatment with three commonly used atypical antipsychotics. Lipid profiles were derived for 50 patients with schizophrenia before and after treatment for 2-3 weeks with olanzapine (n=20), risperidone (n=14) or aripiprazole (n=16). Patients were recruited in two cohorts (study I, n=27 and study II, n=23) to permit an internal replication analyses. The change from baseline to post-treatment was then compared among the three drugs. Olanzapine and risperidone affected a much broader range of lipid classes than aripiprazole. Approximately 50 lipids tended to be increased with both risperidone and olanzapine and concentrations of triacylglycerols increased and free fatty acids decreased with both drugs but not with aripiprazole. Phosphatidylethanolamine concentrations that were suppressed in patients with schizophrenia were raised by all three drugs. Drug specific differences were also detected. A principal component analysis (PCA) identified baseline lipid alterations, which correlated with acute treatment response. A more definitive long-term randomized study of these drugs correlating global lipid changes with clinical outcomes could yield biomarkers that define drug-response phenotypes.

Original languageEnglish (US)
Pages (from-to)934-945
Number of pages12
JournalMolecular Psychiatry
Volume12
Issue number10
DOIs
StatePublished - Oct 1 2007
Externally publishedYes

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Metabolomics
Antipsychotic Agents
Schizophrenia
olanzapine
Lipids
Risperidone
Pharmaceutical Preparations
Therapeutics
Pharmacological Biomarkers
Hypertriglyceridemia
Metabolic Diseases
Principal Component Analysis
Nonesterified Fatty Acids
Weight Gain
Neurotransmitter Agents
Phospholipids
Triglycerides
Cohort Studies
Phenotype
Membranes

Keywords

  • Antipsychotics
  • Lipidomics
  • Metabolic profiling
  • Metabolomics
  • Schizophrenia

ASJC Scopus subject areas

  • Molecular Biology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

Cite this

Kaddurah-Daouk, R., McEvoy, J. P., Baillie, R. A., Lee, D., Yao, J. K., Doraiswamy, P. M., & Krishnan, K. R. R. (2007). Metabolomic mapping of atypical antipsychotic effects in schizophrenia. Molecular Psychiatry, 12(10), 934-945. https://doi.org/10.1038/sj.mp.4002000

Metabolomic mapping of atypical antipsychotic effects in schizophrenia. / Kaddurah-Daouk, R.; McEvoy, Joseph Patrick; Baillie, R. A.; Lee, D.; Yao, J. K.; Doraiswamy, P. M.; Krishnan, K. R.R.

In: Molecular Psychiatry, Vol. 12, No. 10, 01.10.2007, p. 934-945.

Research output: Contribution to journalArticle

Kaddurah-Daouk, R, McEvoy, JP, Baillie, RA, Lee, D, Yao, JK, Doraiswamy, PM & Krishnan, KRR 2007, 'Metabolomic mapping of atypical antipsychotic effects in schizophrenia', Molecular Psychiatry, vol. 12, no. 10, pp. 934-945. https://doi.org/10.1038/sj.mp.4002000
Kaddurah-Daouk R, McEvoy JP, Baillie RA, Lee D, Yao JK, Doraiswamy PM et al. Metabolomic mapping of atypical antipsychotic effects in schizophrenia. Molecular Psychiatry. 2007 Oct 1;12(10):934-945. https://doi.org/10.1038/sj.mp.4002000
Kaddurah-Daouk, R. ; McEvoy, Joseph Patrick ; Baillie, R. A. ; Lee, D. ; Yao, J. K. ; Doraiswamy, P. M. ; Krishnan, K. R.R. / Metabolomic mapping of atypical antipsychotic effects in schizophrenia. In: Molecular Psychiatry. 2007 ; Vol. 12, No. 10. pp. 934-945.
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