MAPK/ERK Signaling Pathway in Schizophrenia: Expression Levels of Regulatory Proteins in Peripheral Blood Mononuclear Cells

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Anastasiia S. Boiko^1,a*, Ivan S. Kopnov^1,2, Elena V. Epimakhova¹, Elena G. Kornetova¹, and Svetlana A. Ivanova^1,2

¹Mental Health Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, 634014 Tomsk, Russia

²Siberian State Medical University, 634050 Tomsk, Russia

^* To whom correspondence should be addressed.

Received: September 30, 2025; Revised: November 17, 2025; Accepted: December 4, 2025

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Schizophrenia is a severe mental disorder whose molecular mechanisms remain poorly understood. Investigating brain-derived neurotrophic factor (BDNF)-dependent signaling pathways and their contribution to schizophrenia pathogenesis is a promising research direction in schizophrenia research. BDNF activates multiple intracellular cascades, among which the MAPK/ERK pathway plays a central role. In this study, expression levels of key regulatory proteins of the MAPK/ERK signaling pathway (ERK1/2, STAT3, STAT5, NF-κB, IGF1R, IRS1, IR, TSC2, and CREB1) were examined in lysates of peripheral blood mononuclear cells (PBMCs) from schizophrenia patients using multiplex analysis. The study group included 58 patients diagnosed with schizophrenia (F20); the control group included 60 healthy individuals. The results revealed significantly increased expression of ERK1/2 and STAT3, along with decreased NF-κB levels, in PBMCs from schizophrenia patients compared to controls. Moreover, patients with leading positive symptoms exhibited elevated expression of CREB1 and ERK1/2. These findings suggest that dysregulation of the MAPK/ERK signaling may play a significant role in the pathogenesis schizophrenia. BDNF-dependent signaling pathways may therefore represent promising targets for diagnostics and therapy of this disorder.

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KEY WORDS: schizophrenia, MAPK/ERK signaling pathway, regulatory proteins, brain-derived neurotrophic factor

DOI: 10.1134/S0006297925603466

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