Erythrocyte membrane phospholipids in psychotic patients

Keshavan, Matcheri S.; Mallinger, Alan G.; Pettegrew, Jay W.; Dippold, Christine

doi:10.1016/0165-1781(93)90032-c

Cited by 89 publications

(28 citation statements)

References 16 publications

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“…No significant changes were seen within the five other lipid classes. These findings are consistent with and substantially add to the previous reports of decrease in phospholipids in red blood cells (RBC) of psychotic patients 37 and medication-free schizophrenic patients; 38 in fibroblasts from neuroleptic-naïve schizophrenic patients; 39 in platelet membranes of drug-naïve patients with schizophrenia 40 and in post-mortem brain tissue from patients with schizophrenia. 41,42 There is also convincing evidence for abnormal central phospholipid metabolism in first-episode and chronic schizophrenic patients.…”

Section: Phospholipid Alterations In Schizophreniasupporting

confidence: 91%

Metabolomic mapping of atypical antipsychotic effects in schizophrenia

Kaddurah‐Daouk

McEvoy

Baillie³

et al. 2007

Mol Psychiatry

239

181

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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.

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Section: Phospholipid Alterations In Schizophreniasupporting

confidence: 91%

Metabolomic mapping of atypical antipsychotic effects in schizophrenia

Kaddurah‐Daouk

McEvoy

Baillie³

et al. 2007

Mol Psychiatry

239

181

View full text Add to dashboard Cite

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“…Decrease in membrane phospholipids in blood cells of psychotic patients [167,168] and fibroblasts from drug-naïve patients [169] and in post-mortem brain [170] were indeed reported. It has been also suggested that peripheral membrane anomalies correlate with abnormal central phospholipid metabolism in first-episode and chronic schizophrenia patients [171,172].…”

Section: Polyunsaturated Fatty Acidsmentioning

confidence: 86%

Redox Dysregulation and Oxidative Stress in Schizophrenia: Nutrigenetics as a Challenge in Psychiatric Disease Prevention

Conus²,

Cuénod³

2010

J Nutrigenet Nutrigenomics

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“…Whereas the evidence for reduced EFAs, increased activity of the calcium-independent PLA2 (probably the cytosolic 85 kDa group IVA PLA2), decreased activity of calcium dependent PLA2 and altered lipid transport proteins (ApoD) seems to be quite robust, measures of GPL composition of the cell membrane seem to be less conclusive (Ripova, Strunecka, Nemcova, & Farska, 1997;Keshavan, Mallinger, Pettegrew, & Dippold, 1993;Rotrosen & Wolkin, 1987). Initial reports found a marked increase in phosphatidylserine (PtdSer) (up to 50%) and a decrease in phosphatidylethanolamine (PtdEtn) (9-47%) and phosphatidylcholine (Henn, 1980;Stevens, 1972) leading to the proposal that the ratio of PtdEtn to PtdSer might be a biochemical marker for schizophrenia (Keshavan et al, 1993;Ripova et al, 1997;Rotrosen & Wolkin, 1987), although two groups (Hitzemann, Hirschowitz, & Garver, 1984;Lautin et al, 1982) failed to replicate these findings.…”

Section: Altered Glycerophospholipid (Gpl) Membrane Composition In Scmentioning

confidence: 99%

“…Initial reports found a marked increase in phosphatidylserine (PtdSer) (up to 50%) and a decrease in phosphatidylethanolamine (PtdEtn) (9-47%) and phosphatidylcholine (Henn, 1980;Stevens, 1972) leading to the proposal that the ratio of PtdEtn to PtdSer might be a biochemical marker for schizophrenia (Keshavan et al, 1993;Ripova et al, 1997;Rotrosen & Wolkin, 1987), although two groups (Hitzemann, Hirschowitz, & Garver, 1984;Lautin et al, 1982) failed to replicate these findings. Significantly lower amounts of PtdEtn and PtdCho were found in post mortem brain tissue from patients with schizophrenia (Yao et al, 2000b), even after accounting for potential confounds.…”

Section: Altered Glycerophospholipid (Gpl) Membrane Composition In Scmentioning

confidence: 99%

Bioactive lipids in schizophrenia

Berger

Smesny

Amminger

2006

International Review of Psychiatry

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SummaryBioactive lipids, in particular arachidonic acid (AA), are vital for monoaminergic neurotransmission, brain development and synaptic plasticity. Phospholipases A2 (PLA2) are key-enzymes in AA metabolism and are activated during monoaminergic neurotransmission. Reduced membrane AA levels, and an altered activity of PLA2 have been found in peripheral membranes of drug-naïve patients with schizophrenia with some conflicting results in more chronic patient populations. Furthermore, in vivo brain phosphorus-31 magnetic resonance spectroscopy suggests reduced lipid membrane precursors (phosphomonoesters) and increased membrane breakdown products (phosphodiesters) in drug-naïve or early treated firstepisode schizophrenia patients compared to age-matched controls or chronic populations and these changes were correlated with peripheral red blood cell membrane AA levels. We postulate that processes modulating membrane lipid metabolism are associated with psychotic illnesses and might partially explain the mechanism of action of antipsychotic agents, as well as experimental agents such as purified ethyl-eicosapentaenoic acid (E-EPA). Recent supplementation trials suggest that E-EPA is a modestly effective augmentation treatment resulting in reduced doses of antipsychotic medication in acutely ill patients with schizophrenia (but not in residual-type schizophrenia). This review investigates the role of bioactive lipids in schizophrenia and its treatment, as well as its potential use in prevention.

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Erythrocyte membrane phospholipids in psychotic patients

Cited by 89 publications

References 16 publications

Metabolomic mapping of atypical antipsychotic effects in schizophrenia

Metabolomic mapping of atypical antipsychotic effects in schizophrenia

Redox Dysregulation and Oxidative Stress in Schizophrenia: Nutrigenetics as a Challenge in Psychiatric Disease Prevention

Bioactive lipids in schizophrenia

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