Diagnostic model development for schizophrenia based on peripheral blood mononuclear cell subtype-specific expression of metabolic markers.

A significant proportion of the personal and economic burden of schizophrenia can be attributed to the late diagnosis or misdiagnosis of the disorder. A novel, objective diagnostic approaches could facilitate the early detection and treatment of schizophrenia and improve patient outcomes. In the present study, we aimed to identify robust schizophrenia-specific blood biomarkers, with the goal of developing an accurate diagnostic model.

Exploring cellular markers of metabolic syndrome in peripheral blood mononuclear cells across the neuropsychiatric spectrum.

Recent evidence suggests that comorbidities between neuropsychiatric conditions and metabolic syndrome may precede and even exacerbate long-term side-effects of psychiatric medication, such as a higher risk of type 2 diabetes and cardiovascular disease, which result in increased mortality. In the present study we compare the expression of key metabolic proteins, including the insulin receptor (CD220), glucose transporter 1 (GLUT1) and fatty acid translocase (CD36), on peripheral blood mononuclear cell subtypes from patients across the neuropsychiatric spectrum, including schizophrenia, bipolar disorder, major depression and autism spectrum conditions (n = 25/condition), relative to typical controls (n = 100). This revealed alterations in the expression of these proteins that were specific to schizophrenia.

Proteomic Profiling as a Diagnostic Biomarker for Discriminating Between Bipolar and Unipolar Depression.

Introduction: Affective disorders are a major global burden, with approximately 15% of people worldwide suffering from some form of affective disorder. In patients experiencing their first depressive episode, in most cases it cannot be distinguished whether this is due to bipolar disorder (BD) or major depressive disorder (MDD). Valid fluid biomarkers able to discriminate between the two disorders in a clinical setting are not yet available.

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.

Applications of blood-based protein biomarker strategies in the study of psychiatric disorders.

Major psychiatric disorders such as schizophrenia, major depressive and bipolar disorders are severe, chronic and debilitating, and are associated with high disease burden and healthcare costs. Currently, diagnoses of these disorders rely on interview-based assessments of subjective self-reported symptoms. Early diagnosis is difficult, misdiagnosis is a frequent occurrence and there are no objective tests that aid in the prediction of individual responses to treatment.

Proteomic changes in serum of first onset, antidepressant drug-naïve major depression patients.

Major depressive disorder (MDD) is a complex and multi-factorial disorder. Although genetic factors and other molecular aspects of MDD have been widely studied, the underlying pathological mechanisms are still mostly unknown. We sought to investigate the pathophysiology of MDD by identifying and characterising serum molecular differences and their correlation to symptom severity in first onset, antidepressant drug-naïve MDD patients.

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.

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.