Integrative analysis of peripheral leukocytes as neuroimmune modulators and signatures associated with synaptic dysfunction in major depressive disorder

• Grant number: 24/21635-9
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: October 01, 2025
• End date: October 31, 2027
• Field of knowledge: Biological Sciences - Immunology
• Principal Investigator: Otávio Cabral Marques
• Grantee: Anny Silva Adri
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Psychiatric disorders such as major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SCH) affect millions of people globally, and are a major cause of morbidity and disability. Although distinct in clinical manifestations, these disorders share profound biological alterations. MDD is characterized by persistent sadness, anhedonia, and cognitive deficits; BD involves alternating episodes of mania and depression, often marked by severe emotional instability; and SCH involves hallucinations, cognitive deficits, and disorganized thinking. These conditions share underlying mechanisms, such as synaptic dysfunction and neuroinflammation, that connect the central nervous system (CNS) to the periphery. In this context, since recent studies demonstrate that leukocytes communicate cellularly via neurotransmitters and their respective receptors, PBMCs (peripheral blood mononuclear cells) emerge as valuable tools to explore the bidirectional relationship between the CNS and the immune system. These peripheral cells have the potential to reflect synaptic and neuroinflammatory alterations present in the brain, in addition to being modulated by these same processes. Synaptic dysfunctions, widely recognized as a central axis in the pathophysiology of psychiatric disorders, are influenced by neuroimmune factors, such as pro-inflammatory cytokines, which contribute to cognitive and emotional deficits. The present study proposes an integrative approach using transcriptomic data from both PBMCs and brain regions associated with MDD, BD and Scz. This analysis will deepen the understanding of synaptic and immunological processes, expanding the understanding of the bidirectional connections between the nervous and immune systems in these psychiatric disorders.