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

Abstract

Introduction: 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.

Methods: 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.

Results: 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.

Discussion: 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.

Keywords: Biomarker; Depression; Diagnosis; PBMC; Peripheral blood mononuclear cells; Schizophrenia.