Schizophrenia and bipolar disorder include patients with different characteristics, which may hamper the definition of biomarkers.  https://www.selleckchem.com/products/s-gsk1349572.html  One of the dimensions with greater heterogeneity among these patients is cognition. Recent studies support the identification of different patients' subgroups along the cognitive domain using cluster analysis. Our aim was to validate clusters defined on the basis of patients' cognitive status and to assess its relation with demographic, clinical and biological measurements. We hypothesized that subgroups characterized by different cognitive profiles would show differences in an array of biological data. Cognitive data from 198 patients (127 with chronic schizophrenia, 42 first episodes of schizophrenia and 29 bipolar patients) were analyzed by a K-means cluster approach and were compared on several clinical and biological variables. We also included 155 healthy controls for further comparisons. A two-cluster solution was selected, including a severely impaired group and a moderately impaired group. The severely impaired group was associated with higher illness duration and symptoms scores, lower thalamus and hippocampus volume, lower frontal connectivity and basal hypersynchrony in comparison to controls and the moderately impaired group. Moreover, both patients' groups showed lower cortical thickness and smaller functional connectivity modulation than healthy controls. This study supports the existence of different cognitive subgroups within the psychoses with different neurobiological underpinnings.
  There is growing evidence for a shared genetic basis between schizophrenia risk and cardiovascular disease. Reduced efferent vagal activity, indexed by reduced heart rate variability (HRV), has been consistently described in patients with schizophrenia and may potentially contribute to the increased cardiovascular risk in these patients. In this study, we tested the hypothesis whether the established schizophrenia risk variant HCN1 rs16902086 (A>G) is associated with reduced HRV.
 
  We analyzed the risk status of HCN1 rs16902086 (AG/GG vs. AA genotype) in 83 unmedicated patients with schizophrenia and 96 healthy controls and investigated genotype-related impacts on various HRV parameters.
 
  We observed significantly increased resting heart rates and a marked decrease of vagal modulation in our patient cohort. Strikingly, HCN1 rs16902086 (A>G) was associated with reduced HRV parameters in patients only. A trend towards more pronounced HRV deviations was observed in homozygous (GG) compared to heterozygous patients (AG).
 
  We present first evidence for a genetic risk factor that is associated with decreased vagal modulation in unmedicated patients with schizophrenia. Moreover, our findings suggest that HCN1 might be involved in reduced vagal modulation and possibly in increased cardiac mortality in schizophrenia patients. Thus, our data indicate that reduced vagal modulation might be an endophenotype of schizophrenia.
 We present first evidence for a genetic risk factor that is associated with decreased vagal modulation in unmedicated patients with schizophrenia. Moreover, our findings suggest that HCN1 might be involved in reduced vagal modulation and possibly in increased cardiac mortality in schizophrenia patients. Thus, our data indicate that reduced vagal modulation might be an endophenotype of schizophrenia.
  Nonadherence to antipsychotics may cause relapse and hospitalizations in patients with psychotic disorders. The purpose was to quantify and compare the outpatient's nonadherence rates of atypical antipsychotics by objective detection in blood samples.
 
  Totally, 13,217 outpatients with therapeutic drug monitoring (TDM) data of atypical antipsychotics were included. An event of complete nonadherence was defined as an occurrence of undetectable level of a prescribed antipsychotic in the blood sample submitted for TDM. Patients with such an event(s) were defined as nonadherent of the respective drug treatment (outcome). The rates of nonadherence patients were compared between the drugs by logistic regression.
 
  In the study population, 70.2% of the patients were prescribed doses compliant with a schizophrenia diagnosis. The mean olanzapine equivalent dose in the population was 13.4mg (95% confidence interval (CI) 13.3, 13.6). The frequency of nonadherence patients, regardless of drug, was 3.7% (CI 3.4-4.0). Thificantly higher during olanzapine treatment compared to other atypical antipsychotics. Further studies should investigate if this reflects drug differences in tolerability or other causal relationships.
  The advent of direct-acting antiviral agents for treating hepatitis C virus infection has made hepatitis C virus elimination possible. Rural patients with hepatitis C virus infection may be less likely to access direct-acting antiviral agents, but the real-world evidence is scarce on urban-rural disparities in direct-acting antiviral agent utilization.
 
  This retrospective cohort study was conducted in 2019-2020 using Medicare data to examine urban-rural disparities in direct-acting antiviral agent utilization among newly diagnosed patients with hepatitis C virus infection in 2014-2016. Direct-acting antiviral agent use was defined as filling ≥1 prescription for direct-acting antiviral agents during 2014-2017, and patient's urban-rural status was classified on the basis of their ZIP code of residence. This study evaluated the associations between multilevel factors and direct-acting antiviral agent use with a focus on urban-rural disparities. It also assessed changes over time in urban-rural disparities in al disparities in direct-acting antiviral agent utilization. Enhancing direct-acting antiviral agent uptake in rural populations with hepatitis C virus infection will help reduce hepatitis C virus‒related health disparities and reach the national goal of eliminating hepatitis C virus infection.
 This study reveals important gaps in hepatitis C virus treatment and suggests increasing urban-rural disparities in direct-acting antiviral agent utilization. Enhancing direct-acting antiviral agent uptake in rural populations with hepatitis C virus infection will help reduce hepatitis C virus‒related health disparities and reach the national goal of eliminating hepatitis C virus infection.