Dataset Information

Orexin-A Levels in Relation to the Risk of Metabolic Syndrome in Patients with Schizophrenia Taking Antipsychotics.

ABSTRACT: Background:The role of orexin-A in regulating metabolic homeostasis has been recognized, but its association with antipsychotic-induced metabolic abnormalities remains unclear. We investigated the association between orexin-A levels and metabolic syndrome in patients with schizophrenia treated with clozapine or less obesogenic antipsychotics compared with nonpsychiatric controls. Methods:Plasma orexin-A levels and metabolic parameters were determined in 159 patients with schizophrenia: 109 taking clozapine; 50 taking aripiprazole, amisulpride, ziprasidone, or haloperidol; and 60 nonpsychiatric controls. Results:Orexin-A levels were significantly higher in the group taking less obesogenic antipsychotics, followed by the clozapine group and the controls (F=104.6, P<.01). Higher orexin-A levels were correlated with better metabolic profiles in the patient groups but not in the controls. Regression analyses revealed that the patients with higher orexin-A levels had significantly lower risk of metabolic syndrome (adjusted odds ratio [OR]=0.04, 95% CI: 0.01-0.38 for the 2nd tertile; OR=0.04, 95% CI: 0.01-0.36 for the 3rd tertile, compared with the first tertile), after adjustment for age, sex, smoking history, types of antipsychotics (clozapine vs less obesogenic antipsychotics), duration of antipsychotic treatment, and disease severity. Conclusions:Our results revealed that the orexin-A level was upregulated in patients with schizophrenia treated with antipsychotics, especially for the group taking less obesogenic antipsychotics. Furthermore, higher orexin-A levels were independently associated with better metabolic profiles. These observations suggest that an upregulation of orexin-A has a protective effect against the development of metabolic abnormalities in patients with schizophrenia receiving antipsychotic treatment.

SUBMITTER: Chen PY

PROVIDER: S-EPMC6313111 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Orexin-A Levels in Relation to the Risk of Metabolic Syndrome in Patients with Schizophrenia Taking Antipsychotics.

Chen Po-Yu PY Chen Chun-Hsin CH Chang Chin-Kuo CK Kao Chung-Feng CF Lu Mong-Liang ML Lin Shih-Ku SK Huang Ming-Chyi MC Hwang Ling-Ling LL Mondelli Valeria V

The international journal of neuropsychopharmacology 20190101 1

<h4>Background</h4>The role of orexin-A in regulating metabolic homeostasis has been recognized, but its association with antipsychotic-induced metabolic abnormalities remains unclear. We investigated the association between orexin-A levels and metabolic syndrome in patients with schizophrenia treated with clozapine or less obesogenic antipsychotics compared with nonpsychiatric controls.<h4>Methods</h4>Plasma orexin-A levels and metabolic parameters were determined in 159 patients with schizophr ...[more]

PMID: 30204875

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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.

Project description:STUDY OBJECTIVE Patients with schizophrenia are known to have higher rates of metabolic disease than the general population. Contributing factors likely include lifestyle and atypical antipsychotic (AAP) use, but the underlying mechanisms are unknown. The objective of this study was to identify metabolomics variability in adult patients with schizophrenia who were taking AAPs and grouped by fasting insulin concentration, our surrogate marker for metabolic risk. DESIGN Metabolomics analysis. PARTICIPANTS Ninety-four adult patients with schizophrenia who were taking an AAP for at least 6 months, with no changes in their antipsychotic regimen for the previous 8 weeks, and who did not require treatment with insulin. Twenty age- and sex-matched nonobese (10 subjects) and obese (10 subjects) controls without cardiovascular disease or mental health diagnoses were used to match the body mass index range of the patients with schizophrenia to account for metabolite concentration differences attributable to body mass index. MEASUREMENTS AND MAIN RESULTS Existing serum samples were used to identify aqueous metabolites (to differentiate fasting insulin concentration quartiles) and fatty acids with quantitative nuclear magnetic resonance (NMR) and gas chromatography (GC) methods, respectively. To exclude metabolites from our pathway mapping analysis that were due to variability in weight, we also subjected serum samples from the nonobese and obese controls to the same analyses. Patients with schizophrenia had a median age of 47.0 (interquartile range 41.0-52.0) years. Using a false discovery rate threshold of <25%, 10 metabolites, not attributable to weight, differentiated insulin concentration quartiles in patients with schizophrenia and identified variability in one-carbon metabolism between groups. Patients with higher fasting insulin concentrations (quartiles 3 and 4) also trended toward having higher levels of saturated fatty acids compared with patients with lower fasting insulin concentrations (quartiles 1 and 2). CONCLUSION These results illustrate the utility of metabolomics to identify pathways underlying variable fasting insulin concentration in patients with schizophrenia. Importantly, no significant difference in AAP exposure was observed among groups, suggesting that current antipsychotic use may not be a primary factor that differentiates middle-aged adult patients with schizophrenia by fasting insulin concentration. This article is protected by copyright. All rights reserved. As published in Pharmacotherapy. 2018 Jun;38(6):638-650.

Project description:STUDY OBJECTIVE Patients with schizophrenia are known to have higher rates of metabolic disease than the general population. Contributing factors likely include lifestyle and atypical antipsychotic (AAP) use, but the underlying mechanisms are unknown. The objective of this study was to identify metabolomic variability in adult patients with schizophrenia who were taking AAPs and grouped by fasting insulin concentration, our surrogate marker for metabolic risk. DESIGN Metabolomics analysis. PARTICIPANTS Ninety-four adult patients with schizophrenia who were taking an AAP for at least 6 months, with no changes in their antipsychotic regimen for the previous 8 weeks, and who did not require treatment with insulin. Twenty age- and sex-matched nonobese (10 subjects) and obese (10 subjects) controls without cardiovascular disease or mental health diagnoses were used to match the body mass index range of the patients with schizophrenia to account for metabolite concentration differences attributable to body mass index. MEASUREMENTS AND MAIN RESULTS Existing serum samples were used to identify aqueous metabolites (to differentiate fasting insulin concentration quartiles) and fatty acids with quantitative nuclear magnetic resonance (NMR) and gas chromatography (GC) methods, respectively. To exclude metabolites from our pathway mapping analysis that were due to variability in weight, we also subjected serum samples from the nonobese and obese controls to the same analyses. Patients with schizophrenia had a median age of 47.0 (interquartile range 41.0-52.0) years. Using a false discovery rate threshold of <25%, 10 metabolites, not attributable to weight, differentiated insulin concentration quartiles in patients with schizophrenia and identified variability in one-carbon metabolism between groups. Patients with higher fasting insulin concentrations (quartiles 3 and 4) also trended toward having higher levels of saturated fatty acids compared with patients with lower fasting insulin concentrations (quartiles 1 and 2). CONCLUSION These results illustrate the utility of metabolomics to identify pathways underlying variable fasting insulin concentration in patients with schizophrenia. Importantly, no significant difference in AAP exposure was observed among groups, suggesting that current antipsychotic use may not be a primary factor that differentiates middle-aged adult patients with schizophrenia by fasting insulin concentration. This article is protected by copyright. All rights reserved. As published in Pharmacotherapy. 2018 Jun;38(6):638-650.

Project description:BackgroundThe aim of this study was to evaluate the cardio-metabolic risk in schizophrenia patients treated by atypical antipsychotic drugs compared with that in those treated without atypical antipsychotic drugs using a nationwide insurance claims database and medical examination database in Japan.MethodsEligible patients were defined as those meeting the following two criteria: (i) A diagnosis of schizophrenia (ICD-10 code: F20) was made between 1 January 2005 and 31 December 2017, with data available for at least 6 months before the diagnosis was made (index month), and (ii) health check-up data were available within ±3 months of the index month. The primary endpoint was changes in cardio-metabolic risk based on the Suita score at 1 year, and the secondary endpoints were changes in medical examination data related to cardio-metabolic risk (total cholesterol [TC], triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, body mass index [BMI], and hemoglobin A1c) at 1 year. The primary endpoint was evaluated by multivariate analysis, with the cumulative chlorpromazine equivalent amount and the baseline Suita score added as covariates.ResultsOne-hundred eighty five pairs of propensity score (PS)-matched patients were evaluated. Patients receiving atypical antipsychotic drugs exhibited a greater change in the Suita score and a risk of coronary heart disease based on the Suita score of 0.530 and 0.098%, respectively, than patients not receiving atypical antipsychotic drugs, but there was no significant difference (p = 0.412 and 0.610). The significant changes in TC and BMI were determined as 6.525 mg/dL and 0.380 kg/m2 greater, respectively, in patients treated with atypical antipsychotic drugs (p = 0.037 and 0.011).ConclusionsThere were no significant increases in changes in the Suita score at 1 year by treatment with atypical antipsychotic drugs compared with treatment without atypical antipsychotic drugs. However, the TC and BMI were significantly higher in patients treated with atypical antipsychotic drugs.

Dataset Information

Orexin-A Levels in Relation to the Risk of Metabolic Syndrome in Patients with Schizophrenia Taking Antipsychotics.

Publications

Orexin-A Levels in Relation to the Risk of Metabolic Syndrome in Patients with Schizophrenia Taking Antipsychotics.

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