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Association of the PPAR-? Gene with Altered Glucose Levels and Psychosis Profile in Schizophrenia Patients Exposed to Antipsychotics.

ABSTRACT: OBJECTIVE:Metabolic abnormalities, e.g., diabetes, are common among schizophrenia patients. Peroxisome proliferator activated receptor-? (PPAR-?) regulates glucose/lipid metabolisms, and schizophrenia like syndrome may be induced by actions involving retinoid X receptor-?/PPAR-? heterodimers. We examined a possible role of the PPAR-? gene in metabolic traits and psychosis profile in schizophrenia patients exposed to antipsychotics. METHODS:Single nucleotide polymorphisms (SNPs) of the PPAR-? gene and a serial of metabolic traits were determined in 394 schizophrenia patients, among which 372 were rated with Positive and Negative Syndrome Scale (PANSS). RESULTS:SNP-10, -12, -18, -19, -20 and -26 were associated with glycated hemoglobin (HbA1c) whereas SNP-18, -19, -20 and -26 were associated with fasting plasma glucose (FPG). While SNP-23 was associated with triglycerides, no associations were identified between the other SNPs and lipids. Further haplotype analysis demonstrated an association between the PPAR-? gene and psychosis profile. CONCLUSION:Our study suggests a role of the PPAR-? gene in altered glucose levels and psychosis profile in schizophrenia patients exposed to antipsychotics. Although the Pro12Ala at exon B has been concerned an essential variant in the development of obesity, the lack of association of the variant with metabolic traits in this study should not be treated as impossibility or a proof of error because other factors, e.g., genes regulated by PPAR-?, may have complicated the development of metabolic abnormalities. Whether the PPAR-? gene modifies the risk of metabolic abnormalities or psychosis, or causes metabolic abnormalities that lead to psychosis, remains to be examined.

SUBMITTER: Liu YR

PROVIDER: S-EPMC4023093 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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Association of the PPAR-γ Gene with Altered Glucose Levels and Psychosis Profile in Schizophrenia Patients Exposed to Antipsychotics.

Liu Yun-Ru YR Hu Tsung-Ming TM Lan Tsuo-Hung TH Chiu Hsien-Jane HJ Chang Yung-Han YH Chen Shuo-Fei SF Yu Yen-Hsin YH Chen Cheng-Chung CC Loh El-Wui el-W

Psychiatry investigation 20140411 2

<h4>Objective</h4>Metabolic abnormalities, e.g., diabetes, are common among schizophrenia patients. Peroxisome proliferator activated receptor-γ (PPAR-γ) regulates glucose/lipid metabolisms, and schizophrenia like syndrome may be induced by actions involving retinoid X receptor-α/PPAR-γ heterodimers. We examined a possible role of the PPAR-γ gene in metabolic traits and psychosis profile in schizophrenia patients exposed to antipsychotics.<h4>Methods</h4>Single nucleotide polymorphisms (SNPs) of ...[more]

PMID: 24843374

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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.

Project description:Objective:Second-generation antipsychotics (SGAs) have a high risk of causing metabolic syndrome (MetS). There is accumulating evidence supporting the fact that the activation of inflammatory pathway contributes to the development of MetS and further aggravates cognitive impairment. This study aimed to investigate the relationship between interleukin-6 (IL-6), cognitive function, and MetS in schizophrenia patients treated with SGAs. Methods:One hundred and seventy-four patients with schizophrenia using SGAs were divided into MetS and non-MetS group, based on the criteria of the National Cholesterol Education Program's Adult Treatment Panel III. Cognitive function was measured using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). A total of 138 patients and 29 healthy controls were examined in the plasma IL-6 levels. Results:The prevalence of MetS in schizophrenia patients treated with SGAs was 33% in this study. There were no significant differences in cognitive functions (both RBANS total score and subscale score) between MetS and non-Mets patients (P>0.05). Patients with MetS had higher plasma levels of IL-6 compared to non-MetS patients (P=0.019). However, such difference was only found in male patients (male: P=0.012; female: P=0.513). The partial correlational analysis further showed that IL-6 levels were notably negative related to the HDL levels in male schizophrenia patients after age, years of education, body mass index (BMI), age of onset, total disease course, and equal dose of olanzapine were controlled (male: P=0.009; female: P=0.450). In addition, the multiple regression analysis (stepwise model) performed in the male patient subgroup showed that IL-6 (beta =-0.283, t=-2.492, P=0.015) was an independent contributor to the HDL levels. However, the IL-6 was not an independent contributor to the HDL levels in female patients. Conclusion:Our findings provide evidence suggesting that the immune-inflammatory effect of IL-6 on SGAs-induced MetS may be in a gender manner.

Dataset Information

Association of the PPAR-? Gene with Altered Glucose Levels and Psychosis Profile in Schizophrenia Patients Exposed to Antipsychotics.

Publications

Association of the PPAR-γ Gene with Altered Glucose Levels and Psychosis Profile in Schizophrenia Patients Exposed to Antipsychotics.

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