Proteomic analysis of blood serum in bipolar disorder

TL;DR

This study identifies potential blood serum protein biomarkers for bipolar disorder, which could aid in diagnosis and treatment.

Contribution

The study presents novel proteomic biomarkers specific to bipolar disorder using blood serum samples.

Findings

21 neurospecific proteins showed differential expression in bipolar disorder patients compared to healthy controls.

Several identified proteins are involved in neuronal proliferation, differentiation, and synaptic transmission.

The findings suggest these proteins could serve as potential targets for new diagnostic methods and therapies.

Abstract

Bipolar disorder (BD) often has symptoms similar to other mental disorders (BD), and there are no paraclinical criteria for differential diagnosis. (Geoffroy et al. Bip Dis 2017; 5 7). Published work on MD proteomics is scarce and focused on schizophrenia. (Dmitrieva et al. PeerJ. 2022; 10 e13907). Therefore, it is important to study potential biomarkers of BD using easily accessible material—blood serum (Rhee et al. Transl Psy 2023; 13 44). Identification of proteins involved in the pathogenesis of BD will help in the study of the pathogenetic mechanisms of BD, the development of differential diagnostic methods and pathogenetically based drugs.

Carrying out a comparative proteomic analysis of blood serum from patients with BD and healthy individuals to identify potential biomarkers

We analyzed the protein spectrum of the blood serum of 14 patients with BD who were admitted during a depressive episode at the age of 32 [21;52] years with a disease duration of 8[5;11] years. The control group consisted of 10 mentally and somatically healthy individuals corresponding to the gender and age of the BD group. Blood serum was purified from 14 major proteins using affinity chromatography and separated by electrophoresis using the Laemmli method. After trypsinolysis, proteins were identified using HPLC/mass spectrometry on an Orbitrap instrument. Mass spectrometric analysis was performed on the Advanced Mass Spectrometry Core Facility of Skolkovo Institute of Science and Technology. Protein identification was carried out using the UniProtKB database using the Mascot search engine. The results were tested for significance using the nonparametric Fisher exact test with Yates correction.

In patients with BD, qualitative mass spectrometry revealed differential expression of 21 neurospecific proteins. Among them: Protein dispatched homolog 3, Ceroid-lipofuscinosis neuronal protein 6, SWI/SNF complex subunit SMARCC1, Neurogenic differentiation factor 4, Protein furry homolog-like, REST corepressor 1 – are involved in the proliferation, development and differentiation of neurons; Hemicentin-2, Dystrophin, Voltage-dependent L-type calcium channel subunit alpha-1D, Syntaxin-binding protein 5, Small conductance calcium-activated potassium channel protein 1– participate in synaptic transmission of ion transport and form receptors.

Studying the role of these proteins in BD and their quantitative content in a larger number of patients is promising. This will help in the development of new diagnostic criteria and targets for drug therapy for BD.

Support by the Russian Science Foundation grant No. 23-75-00023.

None Declared