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Lipidomics reveals early metabolic changes in subjects with schizophrenia: effects of atypical antipsychotics.

ABSTRACT: There is a critical need for mapping early metabolic changes in schizophrenia to capture failures in regulation of biochemical pathways and networks. This information could provide valuable insights about disease mechanisms, trajectory of disease progression, and diagnostic biomarkers. We used a lipidomics platform to measure individual lipid species in 20 drug-naïve patients with a first episode of schizophrenia (FE group), 20 patients with chronic schizophrenia that had not adhered to prescribed medications (RE group), and 29 race-matched control subjects without schizophrenia. Lipid metabolic profiles were evaluated and compared between study groups and within groups before and after treatment with atypical antipsychotics, risperidone and aripiprazole. Finally, we mapped lipid profiles to n3 and n6 fatty acid synthesis pathways to elucidate which enzymes might be affected by disease and treatment. Compared to controls, the FE group showed significant down-regulation of several n3 polyunsaturated fatty acids (PUFAs), including 20:5n3, 22:5n3, and 22:6n3 within the phosphatidylcholine and phosphatidylethanolamine lipid classes. Differences between FE and controls were only observed in the n3 class PUFAs; no differences where noted in n6 class PUFAs. The RE group was not significantly different from controls, although some compositional differences within PUFAs were noted. Drug treatment was able to correct the aberrant PUFA levels noted in FE patients, but changes in re patients were not corrective. Treatment caused increases in both n3 and n6 class lipids. These results supported the hypothesis that phospholipid n3 fatty acid deficits are present early in the course of schizophrenia and tend not to persist throughout its course. These changes in lipid metabolism could indicate a metabolic vulnerability in patients with schizophrenia that occurs early in development of the disease.

SUBMITTER: McEvoy J

PROVIDER: S-EPMC3722141 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Lipidomics reveals early metabolic changes in subjects with schizophrenia: effects of atypical antipsychotics.

McEvoy Joseph J Baillie Rebecca A RA Zhu Hongjie H Buckley Peter P Keshavan Matcheri S MS Nasrallah Henry A HA Dougherty George G GG Yao Jeffrey K JK Kaddurah-Daouk Rima R

PloS one 20130724 7

There is a critical need for mapping early metabolic changes in schizophrenia to capture failures in regulation of biochemical pathways and networks. This information could provide valuable insights about disease mechanisms, trajectory of disease progression, and diagnostic biomarkers. We used a lipidomics platform to measure individual lipid species in 20 drug-naïve patients with a first episode of schizophrenia (FE group), 20 patients with chronic schizophrenia that had not adhered to prescrib ...[more]

PMID: 23894336

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Project description:BackgroundIn many countries of the industrialised world second generation (atypical) antipsychotics have become first line drug treatments for people with schizophrenia. The question as to whether, and if so how much, the effects of the various second generation antipsychotics differ is a matter of debate. In this review we examine how the efficacy and tolerability of amisulpride differs from that of other second generation antipsychotics.ObjectivesTo evaluate the effects of amisulpride compared with other atypical antipsychotics for people with schizophrenia and schizophrenia-like psychoses.Search strategyWe searched the Cochrane Schizophrenia Group Trials Register (April 2007) which is based on regular searches of BIOSIS, CINAHL, EMBASE, MEDLINE and PsycINFO.Selection criteriaWe included randomised, at least single-blind, trials comparing oral amisulpride with oral forms of aripiprazole, clozapine, olanzapine, quetiapine, risperidone, sertindole, ziprasidone or zotepine in people with schizophrenia or schizophrenia-like psychoses.Data collection and analysisWe extracted data independently. For continuous data we calculated weighted mean differences (MD), for dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a random effects model. We calculated numbers needed to treat/harm (NNT/NNH) where appropriate.Main resultsThe review currently includes ten short to medium term trials with 1549 participants on three comparisons: amisulpride versus olanzapine, risperidone and ziprasidone. The overall attrition rate was considerable (34.7%) with no significant difference between groups. Amisulpride was similarly effective as olanzapine and risperidone and more effective than ziprasidone (leaving the study early due to inefficacy: n=123, 1 RCT, RR 0.21 CI 0.05 to 0.94, NNT 8 CI 5 to 50). Amisulpride induced less weight gain than risperidone (n=585, 3 RCTs, MD -0.99 CI -1.61 to -0.37) or olanzapine (n=671, 3 RCTs, MD -2.11 CI -2.94 to -1.29). Olanzapine was also associated with a higher increase of glucose (n=406, 2 RCTs, MD -7.30 CI -7.62 to -6.99). There was no difference in terms of cardiac effects and extra pyramidal symptoms (EPS) compared with olanzapine (akathisia: n= 587, 2 RCTs, RR 0.66 CI 0.36 to 1.21), compared with risperidone (akathisia: n=586, 3 RCTs, RR 0.80 CI 0.58 to 1.11) and compared with ziprasidone (akathisia: n=123, 1 RCT, RR 0.63, CI 0.11 to 3.67).Authors' conclusionsThere is little randomised evidence comparing amisulpride with other second generation antipsychotic drugs. We could only find trials comparing amisulpride with olanzapine, risperidone and ziprasidone. We found amisulpride may be somewhat more effective than ziprasidone, and more tolerable in terms of weight gain and other associated problems than olanzapine and risperidone. These data, however, are based on only ten short to medium term studies and therefore too limited to allow for firm conclusions.

Dataset Information

Lipidomics reveals early metabolic changes in subjects with schizophrenia: effects of atypical antipsychotics.

Publications

Lipidomics reveals early metabolic changes in subjects with schizophrenia: effects of atypical antipsychotics.

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