Budget impact analysis of continuous glucose monitoring in individuals with type 2 diabetes on insulin treatment in England.

Introduction: In 2022, updated guidance from NICE expanded the options for self-monitoring of blood glucose for patients with type 2 diabetes (T2DM), to include continuous glucose monitoring (CGM). In this budget impact analysis, the cost impact of CGM was compared with traditional self-monitoring of blood glucose (SMBG) in adults with T2DM over 1 year from the commissioner perspective in England.

Research Design And Methods: The NICE-eligible T2DM cohort was split into 4 subgroups to enable nuanced costing by insulin administration frequency: basal human insulin, premixed insulin, basal-bolus insulin and bolus insulin.

Multiplex immunoassay analysis of plasma shows differences in biomarkers related to manic or mixed mood states in bipolar disorder patients.

Background: The molecular understanding of bipolar disorder (BD) aetiology has advanced over the last years through the identification of peripheral disease biomarkers. Here, we have attempted to identify plasma biomarkers associated with distinct BD mood states.

Methods: Plasma from BD patients with either a current manic (n=29) or mixed (n=17) mood state and healthy controls (n=53) were analysed using a multiplex immunoassay platform.

Distinct proteomic profiles in post-mortem pituitary glands from bipolar disorder and major depressive disorder patients.

Disturbances of the hypothalamic-pituitary-adrenal axis have been implicated in the pathophysiology of bipolar disorder (BD) and major depressive disorder (MDD). To examine this further, we carried out proteomic profiling of post-mortem pituitaries from 13 BD and 14 MDD patients, in comparison to 15 controls. Liquid chromatography-mass spectrometry (LC-MS(E)) analysis showed that BD patients had significantly increased levels of the major pituitary hormones pro-opiomelanocortin (POMC) and galanin.

Multiplex immunoassay analysis of plasma shows prominent upregulation of growth factor activity pathways linked to GSK3β signaling in bipolar patients.

Background: Our understanding of bipolar disorder (BD) aetiology has advanced in recent years but our ability to translate this to improve patient care in the clinic is still limited.

Methods: In this study, we have measured the concentrations of 190 different molecules using sensitive multiplex immunoassays in plasma of 17 BD patients compared to 46 matched control subjects.

Results: The analyses led to the identification of 26 dysregulated proteins in BD patients compared to controls.

Application of meta-analysis methods for identifying proteomic expression level differences.

We present new statistical approaches for identification of proteins with expression levels that are significantly changed when applying meta-analysis to two or more independent experiments. We showed that the Euclidean distance measure has reduced risk of false positives compared to the rank product method. Our Ψ-ranking method has advantages over the traditional fold-change approach by incorporating both the fold-change direction as well as the p-value.

Proteomic profiling in schizophrenia: enabling stratification for more effective treatment.

Schizophrenia is a heterogeneous psychiatric disorder characterized by an array of clinical manifestations. Although the best known manifestations include serious effects on mood and behavior, patients can also display co-morbidities, including immune system or metabolic abnormalities. Thorough characterization of these conditions using proteomic profiling methods has increased our knowledge of these molecular differences and has helped to unravel the complexity and heterogeneity of this debilitating condition.

Challenges in drug target discovery in bipolar disorder.

Introduction: Misdiagnosis and subsequent inappropriate treatment of patients with bipolar disorder (BD) can worsen their clinical condition and outcome.

Areas Covered: This review focuses on the therapeutic targets which have been implicated in BD, including the glycogen synthase kinase 3 (GSK-3) and phosphoinositide signaling pathways. In addition, evidence is presented for potential new molecular strategies which involve targeting neuropeptide-converting endopeptidases, glutamatergic excitotoxicity, insulin signaling and dysfunctions in mitochondrial metabolism.

Analysis of serum and plasma identifies differences in molecular coverage, measurement variability, and candidate biomarker selection.

Purpose: To compare the use of serum and plasma in multiplex immunoassay analyses of 190 proteins and small molecules, and associated molecular pathways. We also tested whether differences between these biofluids can influence the identification of potential biomarkers in a preliminary study comparing bipolar disorder patients with controls.

Experimental Design: Using multiplexed immunoassay analyses, we compared the measurement levels and interindividual variation of 190 proteins and small molecules between serum and plasma collected from 21 healthy individuals.

The application of selective reaction monitoring confirms dysregulation of glycolysis in a preclinical model of schizophrenia.

Background: Establishing preclinical models is essential for novel drug discovery in schizophrenia. Most existing models are characterized by abnormalities in behavioral readouts, which are informative, but do not necessarily translate to the symptoms of the human disease. Therefore, there is a necessity of characterizing the preclinical models from a molecular point of view.

Behavioral and molecular biomarkers in translational animal models for neuropsychiatric disorders.

Modeling neuropsychiatric disorders in animals poses a significant challenge due to the subjective nature of diverse often overlapping symptoms, lack of objective biomarkers and diagnostics, and the rudimentary understanding of the pathophysiology. Successful translational research requires animal models that can inform about disease mechanisms and therapeutic targets. Here, we review behavioral and neurobiological findings from selected animal models, based on presumed etiology and risk factors, for schizophrenia, bipolar disorder, and major depressive disorder.

Translating potential biomarker candidates for schizophrenia and depression to animal models of psychiatric disorders.

Schizophrenia and major depressive disorder are severe mental illnesses, which are diagnosed based on patient interviews. Despite many years of extensive research, scientists have not yet fully deciphered how genetic and environmental factors interact to cause these illnesses. Biomarker tests that can confirm diagnoses of schizophrenia or depression are only now beginning to emerge, and could result in a paradigm shift in this field.

Differential expression of HINT1 in schizophrenia brain tissue.

Recent findings in the literature suggest a relation between histidine triad nucleotide-binding protein-1 (HINT1) and psychiatric disorders such as major depression, anxiety, and schizophrenia, although its physiological roles are not completely comprehended. Using Western blot, we compared HINT1 protein expression in the postmortem dorsolateral prefrontal cortex and thalamus of schizophrenia patients and healthy controls for contributing to elucidate the role of HINT1 in schizophrenia pathophysiology. HINT1 was found to be downregulated in the dorsolateral prefrontal cortex and upregulated in the thalamus.