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Dietary, lifestyle and pharmacogenetic factors associated with arteriole endothelial-dependent vasodilatation in schizophrenia patients treated with atypical antipsychotics (AAPs).

ABSTRACT: PURPOSE:Within schizophrenia cardiovascular disease (CVD) is highly prevalent secondary to atypical antipsychotic (AAP) use. Thorough assessments of diet, lifestyle, and endothelial functioning have not been done in this population. Omega 3 Fatty Acids (N-3 FAs) have garnered attention in relation to psychopathology as well as cardioprotection. This study examined the status of endothelial function within the schizophrenia population and determined pharmacogenetic, medication, dietary, and lifestyle factors associated with this functioning. METHODS:Schizophrenia subjects were screened for the metabolic syndrome along with physical activity, smoking, and variants related to folate pharmacogenetics in this cross-sectional analysis. Arteriole endothelial-dependent vasodilatation was measured using non-invasive peripheral arterial tonometry (RH-PAT, EndoPAT2000). A 24h dietary food recall was used to construct intake profiles using the Nutrition Data Systems for Research software (NDSR). We examined associations between AAP use and RH-PAT values, and the influence of N-3 FA dietary intake on this measure. Preliminary data are reported in 83 subjects with a mean age (±s.d.) of 45.89 (±11.49), 64% were Caucasian (n=53), 64% were male (n=53), and 77% were receiving AAP treatment (n=63). RESULTS:A significant positive relationship was found between RH-PAT values and N-3 FA intake (F=17.7(1,16), p=0.0007) in subjects not receiving AAPs. This relationship was lost in those treated with AAPs (F=0.25(1,43), p>0.6). Regression analysis confirmed the interaction effect of AAP treatment on the relationship between RH-PAT and N-3 FAs (p=0.0105). Endothelial dysfunction was also related to folate pharmacogenetic variants. CONCLUSIONS:AAPs may counteract some vascular health benefits of a diet high in N-3 FAs. AAP use may necessitate a higher N-3 FA dose to regain these effects, but additional research is necessary to strengthen the preliminary findings. Pharmacogenetic variants related to folate and homocysteine metabolism may also increase endothelial dysfunction risk.

SUBMITTER: Ellingrod VL

PROVIDER: S-EPMC3139795 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature

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Dietary, lifestyle and pharmacogenetic factors associated with arteriole endothelial-dependent vasodilatation in schizophrenia patients treated with atypical antipsychotics (AAPs).

Ellingrod Vicki L VL Taylor Stephan F SF Brook Robert D RD Evans Simon J SJ Zöllner Sebastian K SK Grove Tyler B TB Gardner Kristen M KM Bly Michael J MJ Pop-Busui Rodica R Dalack Gregory G

Schizophrenia research 20110419 1-3

<h4>Purpose</h4>Within schizophrenia cardiovascular disease (CVD) is highly prevalent secondary to atypical antipsychotic (AAP) use. Thorough assessments of diet, lifestyle, and endothelial functioning have not been done in this population. Omega 3 Fatty Acids (N-3 FAs) have garnered attention in relation to psychopathology as well as cardioprotection. This study examined the status of endothelial function within the schizophrenia population and determined pharmacogenetic, medication, dietary, a ...[more]

PMID: 21504842

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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: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:OBJECTIVE:The objective of this study was to compare persistence, costs, and healthcare resource utilization in patients with schizophrenia and cardiometabolic comorbidities treated with once-monthly paliperidone palmitate or an oral atypical antipsychotic. METHODS:Medicaid data from six states (07/2009-03/2015) were used to identify adults with schizophrenia and cardiometabolic comorbidities initiated on once-monthly paliperidone palmitate or an oral atypical antipsychotic (index date) on 01/2010 or after. Persistence to index medication at 12 months (no gap ≥ 90 days) was compared between patients taking once-monthly paliperidone palmitate and an oral atypical antipsychotic using Chi-squared tests. The 12-month post-index healthcare costs and healthcare resource utilization were compared using multivariate ordinary least squares and Poisson regression, respectively. RESULTS:Selected patients taking once-monthly paliperidone palmitate (n = 371) were younger (mean age: 45.0 vs. 47.5 years, standardized difference = 24%) than patients taking oral atypical antipsychotics (n = 8296). Persistence at 12 months was higher in patients taking once-monthly paliperidone palmitate (40 vs. 33%, p = 0.006). Adjusted all-cause medical costs were lower in patients taking once-monthly paliperidone palmitate vs. patients taking oral atypical antipsychotics (mean monthly cost differences = US $ - 369, p = 0.004) while all-cause pharmacy costs were higher (mean monthly cost differences = US $279, p < 0.001), resulting in no significant difference in total costs (mean monthly cost differences = US $ - 90, p = 0.357). No significant difference was observed in cardiometabolic comorbidity-related pharmacy or medical costs. Compared with patients taking oral atypical antipsychotics, patients taking once-monthly paliperidone palmitate had more schizophrenia-related outpatient visits (incidence rate ratio = 1.44, p < 0.001) but fewer cardiometabolic comorbidity-related inpatient admissions (incidence rate ratio = 0.73, p < 0.001) with shorter lengths of stay (incidence rate ratio = 0.72, p = 0.020), and fewer cardiometabolic comorbidity-related long-term care admissions (incidence rate ratio = 0.56, p = 0.016). CONCLUSIONS:Medicaid beneficiaries with schizophrenia and cardiometabolic comorbidities who were initiated on once-monthly paliperidone palmitate had similar 12-month total healthcare costs compared with oral atypical antipsychotics. Cardiometabolic comorbidity-related utilization of inpatient and long-term care services was lower in patients taking once-monthly paliperidone palmitate.

Dataset Information

Dietary, lifestyle and pharmacogenetic factors associated with arteriole endothelial-dependent vasodilatation in schizophrenia patients treated with atypical antipsychotics (AAPs).

Publications

Dietary, lifestyle and pharmacogenetic factors associated with arteriole endothelial-dependent vasodilatation in schizophrenia patients treated with atypical antipsychotics (AAPs).

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