Profiling of the Peripheral Blood Mononuclear Cell Proteome in Schizophrenia and Mood Disorders for the Discovery of Discriminatory Biomarkers: A Proof-of-Concept Study.

Current diagnoses in psychiatry are solely based on the evaluation of clinical presentation by the treating psychiatrist. This results in a high percentage of misdiagnosis and consequential inefficient treatment; especially regarding major depressive disorder (MDD), depression in the context of bipolar disorder (BD-D), bipolar disorder with manic symptoms (BD-M), and psychosis in the context of schizophrenia (SZ). Objective biomarkers allowing for accurate discriminatory diagnostics are therefore urgently needed. Peripheral blood mononuclear cell (PBMC) proteomes of patients with MDD (n = 5) , BD-D (n = 3), BD-M (n = 4), and SZ (n = 4), and also of healthy controls (HC; n = 6) were analyzed by state-of-the-art mass spectrometry. Proteins with a differential expression of a >2 standard deviation (SD) expression fold change from that of the HC and between either MDD versus BD-D or BD-M versus SZ were subsequently identified as potential discriminatory biomarkers. In total, 4,271 individual proteins were retrieved from the HC. Of these, about 2,800 were detected in all patient and HC samples. For objective discrimination between MDD and BD-D, 66 candidate biomarkers were found. In parallel, 72 proteins might harbor a biomarker capacity for differential diagnostics of BD-M and SZ. A single biomarker was contraregulated versus HC in each pair of comparisons. With this work, we provide a register of candidate biomarkers with the potential to objectively discriminate MDD from BD-D, and BD-M from SZ. Although concerning a proof-of-concept study with limited sample size, these data provide a stepping-stone for follow-up research on the validation of the true discriminatory potential and feasibility of clinical implementation of the discovered biomarker candidates.

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