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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:ObjectiveIncreasing evidence indicated that schizophrenia and obesity are associated with altered mitochondrial and immune function. In this study, we investigated the levels of CRP (C-reactive protein) and mitochondrial lymphocytes in chronically treated schizophrenia patients with atypical antipsychotic medications and further explored the relationship between mitochondrial lymphocyte and weight gain as well as cognitive function in these patients.MethodsWe evaluated the mitochondrial lymphocyte count of 97 patients (53 overweight, 44 non-overweight) and 100 healthy controls using mitochondrial fluorescence staining and flow cytometry (NovoCyte, Agilent Technologies, US). The serum CRP was measured by high-sensitivity enzyme-linked immunosorbent assay (ELISA). Clinical symptoms and cognitive function of the patients were assessed using the Positive and Negative Syndrome Scale (PANSS) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).ResultsThe results showed that mitochondrial lymphocyte counts of CD3+ T, CD3+CD4+ T, and CD3+CD8+ T cells in schizophrenia patients were higher than in the control group (p < 0.05). Additionally, overweight patients had significantly higher mitochondrial lymphocyte counts of CD3+ T and CD3+CD4+ T cells compared to schizophrenia patients with normal weight. Stratified analysis by gender revealed that there was a statistically significant difference in CD3+CD4+ mitochondrial lymphocyte count in male patients (p = 0.014) and a marginal trend toward significance in female patients (p = 0.058). Furthermore, the mitochondrial lymphocyte counts of CD3+ T and CD3+CD4+ T cells, as well as CRP levels, were positively correlated with BMI in schizophrenia patients, but the mitochondrial lymphocyte counts of CD3+CD4+ T cells were negatively correlated with the language scale in the RBANS.ConclusionOur study results provide evidence for the association between altered mitochondrial T lymphocyte and weight gain as well as cognitive impairment in schizophrenia patients treated with atypical antipsychotic medications.

Project description:ImportanceEvidence for improved clinical outcomes with long-acting injectable antipsychotics (LAIAs) vs oral antipsychotics (OAs) is limited in Asian populations and special patient groups, including older people (>65 years), people with substance use, and early initiators of LAIAs.ObjectiveTo compare the risk of disease relapse, health care use, and adverse events associated with the use of LAIAs vs OAs among people in Hong Kong with schizophrenia.Design, setting, and participantsIn this self-controlled case series study, individuals with a diagnosis of schizophrenia who were prescribed LAIAs and OAs between January 1, 2004, and December 31, 2019, were identified from the Clinical Database Analysis and Reporting System of the Hong Kong Hospital Authority. Data analysis was conducted from May to August in 2021.ExposuresUse of LAIAs vs OAs.Main outcomes and measuresRisk of disease relapse (hospitalizations for psychiatric disorders, hospitalizations for schizophrenia, and suicide attempts), health care use (all-cause emergency department visits and hospitalizations), and adverse events (hospitalizations for somatic disorders, hospitalizations for cardiovascular diseases, and extrapyramidal symptoms) between the period in which patients were treated with LAIAs and the period in which patients were treated with OAs were compared using Poisson regression.ResultsOf the 70 396 individuals with schizophrenia (37 200 women [52.8%]; mean [SD] age, 44.2 [15.8] years), 23 719 (33.7%) were prescribed both LAIAs and OAs. Compared with OAs, LAIAs were associated with a lower risk of hospitalizations for any cause (n = 20 973; incidence rate ratio [IRR], 0.63 [95% CI, 0.61-0.65]), hospitalizations for psychiatric disorders (n = 19 283; IRR, 0.52 [95% CI, 0.50-0.53]), hospitalizations for schizophrenia (n = 18 385; IRR, 0.53 [95% CI, 0.51-0.55]), and incident suicide attempts (n = 1453; IRR, 0.56 [95% CI, 0.44-0.71]). During full treatment with LAIAs, there was a reduction in hospitalizations for somatic disorders (n = 15 396; IRR, 0.88 [95% CI, 0.85-0.91]), hospitalizations for cardiovascular diseases (n = 3710; IRR, 0.88 [95% CI, 0.81-0.96]), and extrapyramidal symptoms (n = 22 182; IRR, 0.86 [95% CI, 0.82-0.91]) compared with full treatment with OAs. No significant difference was found for emergency department visits. Similar associations were observed during the subsequent treatment periods (beyond 90 days) and among older people and those with substance use, except for an increased risk of extrapyramidal symptoms among older people when initiating LAIAs (first 90 days). Compared with late initiators, early LAIA initiators had a greater reduction in these outcome events.Conclusions and relevanceThis self-controlled case series study of people in Hong Kong with schizophrenia suggests that LAIAs were associated with a lower risk of disease relapse and hospitalization than OAs, without an increased risk of adverse events. Clinicians should more broadly consider the long-term use of LAIAs for Chinese people with schizophrenia, especially early in the course of illness.

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.

Similar Datasets

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