Immunoinflammatory Markers in Patients with Affective Disorders: Genetic Polymorphisms, Peripheral Cytokine Levels, and Expression of IL-1β, IL-13, TNF-β, and TGF-α in Peripheral Blood Mononuclear Cells

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Ekaterina V. Mikhalitskaya^1,a*, Lyudmila A. Levchuk¹, Anastasia S. Boiko¹, Natalya M. Vyalova¹, Elena V. Epimakhova¹, Diana Z. Paderina¹, Olga V. Roschina¹, German G. Simutkin¹, Nikolay A. Bokhan^1,2, and Svetlana A. Ivanova^1,2

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

²Department of Psychiatry, Addictology, and Psychotherapy, Siberian State Medical University, 634050 Tomsk, Russia

^* To whom correspondence should be addressed.

Received: February 3, 2026; Revised: March 3, 2026; Accepted: March 10, 2026

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Cytokines play a critical role in brain functioning by modulating neurotransmitter and energy metabolism, neuroplasticity, and neuronal activity. Dysregulated or excessive cytokine production can disrupt neuronal metabolic processes and contribute to brain dysfunction. Among the proposed mechanisms underlying the development and progression of affective disorders (ADs), the cytokine hypothesis emphasizes the role of inflammatory markers as key factors in the development of depressive pathologies. The aim of this study was to investigate molecular characteristics of selected immunoinflammatory markers in patients with AD. The study included 239 patients diagnosed with AD and 205 healthy controls. Polymorphic variants of the immunoinflammatory genes IL1B (rs16944, rs1143627), IL13 (rs1295686), TNFB (rs2229094), and TGFA (rs2166975) were analyzed, and cytokine levels in the blood serum and peripheral blood mononuclear cells were measured. As association was identified between the rs2229094 polymorphism of the TNFB gene and AD: the carriage of the A allele and the AA genotype of this variant was associated with an increased risk of AD. Furthermore, the levels of TGF-α and IL-13 in peripheral blood mononuclear cells and the serum content of TNF-β were significantly elevated in patients with AD compared with healthy controls. These pilot findings suggest that the studied cytokines may contribute to the pathogenetic mechanisms underlying development of ADs.

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KEY WORDS: affective disorders, cytokines, IL-1β, IL-13, TNF-β, TGF-α

DOI: 10.1134/S0006297926600304

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