Olanzapine-induced weight gain plays a key role in the potential cardiovascular risk: evidence from heart rate variability analysis.
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ABSTRACT:
SUBMITTER: Wang J
PROVIDER: S-EPMC4260225 | biostudies-other | 2014 Dec
REPOSITORIES: biostudies-other
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Project description:Weight gain and metabolic disturbances, potentially influenced by increased appetite, are common effects of olanzapine treatment in patients with schizophrenia. In this study, we explored the association between olanzapine-induced weight gain and metabolic effects with increased appetite. Drug-naïve, first-episode schizophrenia patients were treated with olanzapine for 12 weeks. Assessments included time to increased appetite, body weight, body mass index, biochemical indicators of blood glucose and lipids, proportion of patients who gained more than 7% or 10% of their baseline weight upon treatment conclusion, patients who developed dyslipidemia, and Positive and Negative Syndrome Scale scores. In total, 33 patients with schizophrenia receiving olanzapine were enrolled and 31 completed the study. During the 12-week olanzapine treatment, 77.4% (24/31) patients had increased appetite with 58.1% (18/31) patients having increased appetite within the first 4 weeks. The mean time for increased appetite was 20.3 days. More patients in the increased appetite group increased their initial body weight by more than 7% after 12 weeks when compared to patients with unchanged appetite (22/24 [91.7%] vs. 3/7 [42.9%], p = 0.004). Earlier increased appetite led to more weight gain during the following month. Overall, 50% of patients in the increased appetite group had dyslipidemia after 12 weeks. Our results demonstrated that olanzapine induced significantly appetite increase in first-episode patients with schizophrenia and appetite increase played a key role in olanzapine-induced weight gain and dyslipidemia. Clinical Trial Registration:NCT03451734. Registered March 2, 2018 (retrospectively registered).
| S-EPMC7256453 | biostudies-literature
Project description:In France, new cancer cases keep on increasing with around 150 000 deaths yearly. Cancer therapy research is constantly evolving. Indeed, several studies explore new treatments or their combination with conventional cancer treatments. But, at the same time, complementary and alternative medicines, as osteopathy, remain little explored upon their role in the combination with conventional therapy.
Several studies showed indirect interaction between vagus nerve and cancer. Firstly, vagus nerve regulates homeostasis and immunity by reducing systemic inflammation while maintaining local inflammation and antitumor effects. Secondly, vagus nerve stimulation increases Heart Rate Variability (HRV). Moreover, a higher HRV is associated with an improvement of vital prognosis in cancer patients. Vagus nerve could be stimulated by noninvasive osteopathic manipulations.
This prospective, monocentric and randomized study is a collaboration between the Centre Hospitalier d’Avignon and the Institut de Formation en Ostéopathie du Grand Avignon. It focuses on using noninvasive osteopathic mobilizations to stimulate vagus nerve. Indeed, this study aims to evaluate effects of vagus nerve osteopathic stimulations on HRV in patients with lung cancer, colorectal cancer, Non Hodgkin Lymphoma or Multiple Myeloma. More specifically, this study will tell us whether vagus nerve noninvasive osteopathic stimulations induce increase of HRV associated with a decrease of systemic inflammation and an improvement of patient’s quality of life.
| 2364606 | ecrin-mdr-crc
Project description:Olanzapine is a first line medication for the treatment of schizophrenia, but it is also one of the atypical antipsychotics carrying the highest risk of weight gain. Metformin was reported to produce significant attenuation of antipsychotic-induced weight gain in patients, while the study of preventing olanzapine-induced weight gain in an animal model is absent. Berberine, an herbal alkaloid, was shown in our previous studies to prevent fat accumulation in vitro and in vivo. Utilizing a well-replicated rat model of olanzapine-induced weight gain, here we demonstrated that two weeks of metformin or berberine treatment significantly prevented the olanzapine-induced weight gain and white fat accumulation. Neither metformin nor berberine treatment demonstrated a significant inhibition of olanzapine-increased food intake. But interestingly, a significant loss of brown adipose tissue caused by olanzapine treatment was prevented by the addition of metformin or berberine. Our gene expression analysis also demonstrated that the weight gain prevention efficacy of metformin or berberine treatment was associated with changes in the expression of multiple key genes controlling energy expenditure. This study not only demonstrates a significant preventive efficacy of metformin and berberine treatment on olanzapine-induced weight gain in rats, but also suggests a potential mechanism of action for preventing olanzapine-reduced energy expenditure.
| S-EPMC3965561 | biostudies-literature
Project description:Statistical, spectral, multi-resolution and non-linear methods were applied to heart rate variability (HRV) series linked with classification schemes for the prognosis of cardiovascular risk. A total of 90 HRV records were analyzed: 45 from healthy subjects and 45 from cardiovascular risk patients. A total of 52 features from all the analysis methods were evaluated using standard two-sample Kolmogorov-Smirnov test (KS-test). The results of the statistical procedure provided input to multi-layer perceptron (MLP) neural networks, radial basis function (RBF) neural networks and support vector machines (SVM) for data classification. These schemes showed high performances with both training and test sets and many combinations of features (with a maximum accuracy of 96.67%). Additionally, there was a strong consideration for breathing frequency as a relevant feature in the HRV analysis.
| S-EPMC3046173 | biostudies-literature
Project description:Psychological stress is a well-established risk factor for cardiovascular disease (CVD). Heart rate variability (HRV)-biofeedback could significantly reduce stress levels and improve autonomic nervous system function and cardiovascular endpoints. We aimed to systematically review the literature to investigate the impact of HRV modulation through HRV-biofeedback on clinical outcomes in patients with CVD. A literature search was performed in the following databases: MEDLINE (PubMed), Embase, and Cochrane from the inception until 1 October 2021. Patients in the HRV-biofeedback group had significantly lower rates of all-cause readmissions than patients who received psychological education (respectively, p = 0.028 and p = 0.001). Heart failure following HRV-biofeedback displayed an inverse association with stress and depression (respectively, p = 0.022 and p = 0.033). When stratified according to left ventricular ejection fraction (LVEF), patients with LVEF ≥ 31% showed improved values of the 6 min walk test after HRV-biofeedback interventions (p = 0.05). A reduction in systolic and diastolic blood pressure associated with HRV-biofeedback was observed (p < 0.01) in pre-hypertensive patients. HRV-biofeedback had beneficial effects on different cardiovascular diseases documented in clinical trials, such as arterial hypertension, heart failure, and coronary artery disease. A standard breathing protocol should be applied in future studies to obtain equivalent results and outcomes. However, data regarding mortality in patients with coronary artery disease are scarce and need further research.
| S-EPMC8700170 | biostudies-literature
Project description:Olanzapine is the one of first line antipsychotic drug for schizophrenia and other serious mental illness. However, it is associated with troublesome metabolic side-effects, particularly body weight gain and obesity. The antagonistic affinity to histamine H1 receptors (H1R) of antipsychotic drugs has been identified as one of the main contributors to weight gain/obesity side-effects. Our previous study showed that a short term (2 weeks) combination treatment of betahistine (an H1R agonist and H3R antagonist) and olanzapine (O+B) reduced (-45%) body weight gain induced by olanzapine in drug-naïve rats. A key issue is that clinical patients suffering with schizophrenia, bipolar disease and other mental disorders often face chronic, even life-time, antipsychotic treatment, in which they have often had previous antipsychotic exposure. Therefore, we investigated the effects of chronic O+B co-treatment in controlling body weight in female rats with chronic and repeated exposure of olanzapine. The results showed that co-administration of olanzapine (3 mg/kg, t.i.d.) and betahistine (9.6 mg/kg, t.i.d.) significantly reduced (-51.4%) weight gain induced by olanzapine. Co-treatment of O+B also led to a decrease in feeding efficiency, liver and fat mass. Consistently, the olanzapine-only treatment increased hypothalamic H1R protein levels, as well as hypothalamic pAMPKα, AMPKα and NPY protein levels, while reducing the hypothalamic POMC, and UCP1 and PGC-1α protein levels in brown adipose tissue (BAT). The olanzapine induced changes in hypothalamic H1R, pAMPKα, BAT UCP1 and PGC-1α could be reversed by co-treatment of O+B. These results supported further clinical trials to test the effectiveness of co-treatment of O+B for controlling weight gain/obesity side-effects in schizophrenia with chronic antipsychotic treatment.
| S-EPMC4118967 | biostudies-literature
Project description:Atypical antipsychotics such as olanzapine often induce excessive weight gain and type 2 diabetes. However, the mechanisms underlying these drug-induced metabolic perturbations remain poorly understood. Here, we used an experimental model that reproduces olanzapine-induced hyperphagia and obesity in female C57BL/6 mice. We found that olanzapine treatment acutely increased food intake, impaired glucose tolerance, and altered physical activity and energy expenditure in mice. Furthermore, olanzapine-induced hyperphagia and weight gain were blunted in mice lacking the serotonin 2C receptor (HTR2C). Finally, we showed that treatment with the HTR2C-specific agonist lorcaserin suppressed olanzapine-induced hyperphagia and weight gain. Lorcaserin treatment also improved glucose tolerance in olanzapine-fed mice. Collectively, our studies suggest that olanzapine exerts some of its untoward metabolic effects via antagonism of HTR2C.
| S-EPMC5669575 | biostudies-literature
Project description:BackgroundThere is consensus that Heart Rate Variability is associated with the risk of vascular events. However, Heart Rate Variability predictive value for vascular events is not completely clear. The aim of this study is to develop novel predictive models based on data-mining algorithms to provide an automatic risk stratification tool for hypertensive patients.MethodsA database of 139 Holter recordings with clinical data of hypertensive patients followed up for at least 12 months were collected ad hoc. Subjects who experienced a vascular event (i.e., myocardial infarction, stroke, syncopal event) were considered as high-risk subjects. Several data-mining algorithms (such as support vector machine, tree-based classifier, artificial neural network) were used to develop automatic classifiers and their accuracy was tested by assessing the receiver-operator characteristics curve. Moreover, we tested the echographic parameters, which have been showed as powerful predictors of future vascular events.ResultsThe best predictive model was based on random forest and enabled to identify high-risk hypertensive patients with sensitivity and specificity rates of 71.4% and 87.8%, respectively. The Heart Rate Variability based classifier showed higher predictive values than the conventional echographic parameters, which are considered as significant cardiovascular risk factors.ConclusionsCombination of Heart Rate Variability measures, analyzed with data-mining algorithm, could be a reliable tool for identifying hypertensive patients at high risk to develop future vascular events.
| S-EPMC4368686 | biostudies-literature
Project description:BACKGROUND:Cardiac mortality and electrophysiological dysfunction both increase with age. Heart rate variability (HRV) provides indices of autonomic function and electrophysiology that are associated with cardiac risk. How habitual physical activity among older adults prospectively relates to HRV, including nonlinear indices of erratic sinus patterns, is not established. We hypothesized that increasing the levels of both total leisure-time activity and walking would be prospectively associated with more favorable time-domain, frequency-domain, and nonlinear HRV measures in older adults. METHODS AND RESULTS:We evaluated serial longitudinal measures of both physical activity and 24-hour Holter HRV over 5 years among 985 older US adults in the community-based Cardiovascular Health Study. After multivariable adjustment, greater total leisure-time activity, walking distance, and walking pace were each prospectively associated with specific, more favorable HRV indices, including higher 24-hour standard deviation of all normal-to-normal intervals (Ptrend=0.009, 0.02, 0.06, respectively) and ultralow-frequency power (Ptrend=0.02, 0.008, 0.16, respectively). Greater walking pace was also associated with a higher short-term fractal scaling exponent (Ptrend=0.003) and lower Poincaré ratio (Ptrend=0.02), markers of less erratic sinus patterns. CONCLUSIONS:Greater total leisure-time activity, and walking alone, as well, were prospectively associated with more favorable and specific indices of autonomic function in older adults, including several suggestive of more normal circadian fluctuations and less erratic sinoatrial firing. Our results suggest potential mechanisms that might contribute to lower cardiovascular mortality with habitual physical activity later in life.
| S-EPMC4038662 | biostudies-literature
Project description:Olanzapine is a widely used atypical antipsychotic medication for treatment of schizophrenia and is often associated with serious metabolic abnormalities including weight gain and impaired glucose tolerance. These metabolic side effects are severe clinical problems but the underpinning mechanism remains poorly understood. Recently, growing evidence suggests that Wnt signaling pathway has a critical role in the pathogenesis of schizophrenia and molecular cascades of antipsychotics action, of which Wnt signaling pathway key effector TCF7L2 is strongly associated with glucose homeostasis. In this study, we aim to explore the characteristics of metabolic disturbance induced by olanzapine and to elucidate the role of TCF7L2 in this process. C57BL/6 mice were subject to olanzapine (4 mg/kg/day), or olanzapine plus metformin (150 mg/kg/day), or saline, respectively, for 8 weeks. Metabolic indices and TCF7L2 expression levels in liver, skeletal muscle, adipose, and pancreatic tissues were closely monitored. Olanzapine challenge induced remarkably increased body weight, fasting insulin, homeostasis model assessment-insulin resistance index, and TCF7L2 protein expression in liver, skeletal muscle, and adipose tissues. Notably, these effects could be effectively ameliorated by metformin. In addition, we found that olanzapine-induced body weight gain and insulin resistance actively influence the expression of TCF7L2 in liver and skeletal muscle, and elevated level of insulin determines the increased expression of TCF7L2 in adipose tissue. Our results demonstrate that TCF7L2 participates in olanzapine-induced metabolic disturbance, which presents a novel mechanism for olanzapine-induced metabolic disturbance and a potential therapeutic target to prevent the associated metabolic side effects.
| S-EPMC5911481 | biostudies-literature