Dysregulation of synaptic-related genes within neuroimmune networks of peripheral blood mononuclear cells in major depressive disorder

Anny Silva Adri; Adriel Leal Nóbile; Débora Gomes de Alburquerque; Pedro Marçal Barcelos; Fernando Yuri Nery do Vale; Ian Antunes Ferreira Bahia; Paula Paccielli Freire; Roseane Galdioli Nava; Yohan Lucas Gonçalves Corrêa; Gustavo Cabral‐Miranda; Rodrigo Juliani Siqueira Dalmolin; Lena F. Schimke; Dennyson Leandro M. Fonseca; Igor Salerno Filgueiras; Helder Imoto Nakaya; Rafael Machado Rezende; Haroldo Dutra Dias; Otávio Cabral-Marques

doi:10.1101/2024.11.13.623441

BioinformaticsbioRxivNov 13, 2024

Preprint

Dysregulation of synaptic-related genes within neuroimmune networks of peripheral blood mononuclear cells in major depressive disorder

Anny Silva Adri iD, Adriel Leal Nóbile iD, Débora Gomes de Alburquerque, Pedro Marçal Barcelos iD, Fernando Yuri Nery do Vale iD, Ian Antunes Ferreira Bahia iD, Paula Paccielli Freire iD, Roseane Galdioli Nava iD, Yohan Lucas Gonçalves Corrêa iD, Gustavo Cabral‐Miranda iD, Rodrigo Juliani Siqueira Dalmolin iD, Lena F. Schimke iD, Dennyson Leandro M. Fonseca iD, Igor Salerno Filgueiras iD, Helder Imoto Nakaya iD, Rafael Machado Rezende iD, Haroldo Dutra Dias iD, Otávio Cabral-Marques iD

Abstract

Major depressive disorder (MDD) involves complex neuroimmune interactions linked to gene modulation. Our study investigates synaptic-related gene dysregulation in peripheral blood mononuclear cells (PBMCs) from MDD patients, showing how these immune cells mirror neural processes. Using RNA-seq data, we identified 1,383 differentially expressed genes (DEGs) related to neuroimmune crosstalk, with 49 DEGs effectively distinguishing MDD patients from controls based on synaptic functions. Synaptic genes, enriched for roles like vesicle transport, suggest mechanistic links between immune cells and neural signaling. Eleven synaptic-related DEGs were shared between PBMCs and brain regions involved in mood regulation, highlighting a common molecular signature. Among them, ADORA3 and RPS28 emerged as potential biomarkers. These findings highlight the potential of PBMCs in the diagnosis and treatment of MDD, reinforcing the development of future neuroimmune-targeted therapies for depression.

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