Article

ISSN 0006-2979, Biochemistry (Moscow), 2026, Vol. 91, No. 5, pp. 780-788 © The Author(s) 2026. This article is an open access publication.

780

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

Ekaterina V. Mikhalitskaya

1,a

*, Lyudmila A. Levchuk

Anastasia S. Boiko

, Natalya M. Vyalova

, Elena V. Epimakhova

Diana Z. Paderina

, Olga V. Roschina

, German G. Simutkin

Nikolay A. Bokhan

1,2

, and Svetlana A. Ivanova

1,2

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

634014 Tomsk, Russia

Department of Psychiatry, Addictology, and Psychotherapy, Siberian State Medical University,

634050 Tomsk, Russia

e-mail: uzen63@mail.ru

Received February 3, 2026

Revised March 3, 2026

Accepted March 10, 2026

Abstract— Cytokines play a critical role in brain functioning by modulating neurotransmitter and energy

metabolism, neuroplasticity, and neuronal activity. Dysregulated or excessive cytokine production can dis-

rupt neuronal metabolic processes and contribute to brain dysfunction. Among the proposed mechanisms

underlying the development and progression of affective disorders (ADs), the cytokine hypothesis empha-

sizes 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 mono-

nuclear 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 mech-

anisms underlying development of ADs.

DOI: 10.1134/S0006297926600304

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

* To whom correspondence should be addressed.

INTRODUCTION

Among the existing concepts on the etiology and

progression of affective disorders (ADs), the cytokine

hypothesis emphasizes inflammatory factors as key

contributors in the AD pathogenesis [1-3]. This hy-

pothesis is based on the observation that elevated

levels of inflammatory markers can induce alterations

in brain neurotransmitter systems, including seroto-

nergic, dopaminergic, and glutamatergic pathways, as

well as in tryptophan metabolism [4]. These changes

can also affect energy metabolism and neuroplasticity

CYTOKINES IL-1β, IL-13, TNF-β, TGF-α IN AFFECTIVE DISORDERS 781

BIOCHEMISTRY (Moscow) Vol. 91 No. 5 2026

and influence neuronal activity through astrocytes

and microglia, as commonly observed during depres-

sive episodes in patients with AD.

Excessive cytokine production disrupts neuronal

metabolism and leads to brain dysfunction, while cy-

tokine-mediated activation of microglia contributes to

the development of neuroinflammatory and neurode-

generative cascades and oligodendrocyte death[5, 6].

Microglia, represented by resident immune effec-

tor cells of the central nervous system (CNS), plays

a central role in the regulation of neuroimmune re-

sponses and participates in the bidirectional commu-

nication with the serotonergic system. Cytokines can

activate the microglia and perivascular macrophages

in the brain parenchyma, thus contributing to alter-

ations in serotonin synthesis and reuptake. Activation

of microglia toward a pro-inflammatory phenotype

can disrupt serotonergic neurotransmission by al-

tering the expression and function of the serotonin

transporter (SERT) and modulating downstream sig-

naling pathways mediated by 5-HT receptors. Con-

versely, serotonergic neurotransmission mediated by

5-HT1A, 5-HT2A/2B, and 5-HT7 receptors can regulate

microglial phenotypic polarization and cytokine pro-

duction, thereby shaping the inflammatory environ-

ment and affecting CNS homeostasis [7].

The involvement of central and peripheral in-

flammation in the pathogenesis and prognosis of

major depressive disorder (MDD) has been increas-

ing recognized. Sarmin et  al. [8] reported elevated

levels of cytokines, such as interleukins  12 (IL-12)

and  4 (IL-4), and their association with the severity

of depression. Increased levels of cytokines, includ-

ing tumor necrosis factor alpha (TNF-α), IL-1β, IL-2,

and IL-6, in the cerebrospinal fluid and peripheral

blood [9-11] in individuals with depression may trig-

ger peripheral inflammation and neuroinflammatory

processes in the brain. Meta-analysis showed that

elevated baseline levels of inflammatory markers,

in particular, C-reactive protein (CRP) and IL-6, are

predictive risk factors for the MDD development[10].

Patients with MDD and elevated levels of pro-inflam-

matory biomarkers are less likely to respond to anti-

depressant therapy, whereas new immunotherapeutic

drugs may potentially offer improved efficacy in this

patient subgroup [10]. In a previous pilot study [12],

we observed elevated serum levels of the pro-inflam-

matory cytokine interferon alpha (IFNα) and reduced

levels of the anti-inflammatory cytokine IL-1 receptor

antagonist (IL-1RA) in patients with AD compared to

healthy individuals [12].

Neuroinflammation causes changes in tryptophan

metabolism, leading to reduced serotonin synthesis

and decreased expression of brain-derived neuro-

trophic factor (BDNF), thereby disrupting brain neu-

roplasticity mechanisms [13]. In parallel, inflamma-

tory processes contribute to the glutamate-mediated

excitotoxicity[14]. Through these pathways, cytokines

can affect neuronal connectivity in brain circuits that

regulate mood, motivation, motor activity, and anx-

iety, ultimately contributing to the development of

depressive symptoms.

Because immunoinflammatory processes in AD

are systemic, many studies assess cytokine levels in

peripheral blood, which have been shown to reflect,

to some extent, processes occurring in the CNS [15].

For example, peripheral inflammation has been as-

sociated with changes in the volume of brain white

matter and severity of depressive symptoms [16].

In addition to a significant role of protein compo-

nents of systemic inflammation in the AD pathogen-

esis, lipid mediators derived from polyunsaturated

fatty acids, particularly ω-3 and ω-6 fatty acids, have

also been implicated as contributors to chronic in-

flammation in AD [17, 18].

The studies of metabolic processes in the brain

of patients with mental disorders have certain lim-

itations and are often conducted using postmortem

material only. In this context, peripheral blood mono-

nuclear cells (PBMCs) represent a practical and ac-

cessible model for biomarker research. Recent stud-

ies have shown a correlation between peripheral

markers and the molecular state of cells in the CNS.

Gladkevich et al. [19] argued that blood lymphocytes

can be considered a convenient model, albeit for

investigating a limited number of cellular functions

(e.g., protein and gene expression). Numerous studies

have shown similarities in receptor expression and

signal transduction mechanisms in nervous system

cells (neurons and glia) and lymphocytes. In several

mental disorders, changes in metabolism and cellular

functions in the CNS, as well as disruptions in major

neurotransmitter and hormonal systems, are accom-

panied by changes in the function and metabolism

of blood lymphocytes. According to some authors, as-

sessment of cytokine levels in PBMCs (which reflect

the ability of cells to produce cytokines) is one of the

most informative methods for evaluating the func-

tional state of immune cells. This approach is consid-

ered comparable to other established assays, such as

lymphocyte blast transformation assay or assessment

of cellular phagocytic activity [20, 21].

Polymorphisms in cytokine-encoding genes may

influence the structure and function of the encoded

proteins and are associated with depressive disor-

ders and their clinical manifestations [22]. The most

frequently confirmed and significant associations in

depression have been found for polymorphisms of

the IL1B, IL6, and TNFA genes [23]. Previously, we

demonstrated an association between the rs2069840

polymorphism of the IL6 gene and clinical severity of

AD symptoms [24].

MIKHALITSKAYA et al.782

BIOCHEMISTRY (Moscow) Vol. 91 No. 5 2026

The aim of the present study was to identify the

molecular characteristics of several immunoinflam-

matory markers in patients with AD to provide data

on changes in protein and genetic markers of sys-

temic inflammation, thereby supporting the hypoth-

esis that AD development is accompanied by immu-

noinflammatory activation at various levels of cellular

organization.

MATERIALS AND METHODS

Study design. The study compared biomarkers

in patients with established diagnoses of mood (af-

fective) disorders (ICD-10: F31-F33) and experiencing

a current depressive episode (DE) and healthy vol-

unteers. All patients underwent genetic analysis for

cytokine gene polymorphisms. To assess intracellular

cytokine content in PBMCs and corresponding serum

levels, a subsample matched for sex, age, and clinical

diagnosis was formed from the overall patient group.

Patients. The study included 239 patients treat-

ed at the Affective States Department of the Mental

Health Research Institute, Tomsk National Research

Medical Center, who were experiencing current DEs

(including single DE, recurrent depressive disorder

(RDD), or bipolar disorder (BD)) (ICD-10: F31-F33)

(Table  1). To determine the eligibility, the patients

were screened for affective pathology via clinical

examination on the first day of hospitalization. The

comparison group included 205 healthy individuals

(women, 50.5%), matched for age to the patient group.

The patient group contained 76.3% women,

which is consistent with a higher prevalence of AD

in the female population. The median age of partic-

ipants was 43 [28; 54] years. The median age of AD

onset was 28 [19; 44] years; the median duration of

a current DE was 5 [2; 9] months.

The inclusion criteria were as follows: provision

of informed consent to participate in the study; con-

firmed diagnosis of AD according to ICD-10 criteria

(F31-33); age between 18 and 60 years; and Cauca-

sian ethnicity. The exclusion criteria were refusal to

participate in the study at any stage; presence of de-

mentia, intellectual disability, or other severe organic

brain disorders accompanied by significant cognitive

impairment; chronic decompensated somatic diseases;

or acute-phase somatic illnesses.

Laboratory methods. Venous blood was collect-

ed in the morning after an overnight fasting (≥12  h)

prior to the initiation of active psychopharmacother-

apy. The blood was collected into tubes containing

anticoagulants (EDTA and lithium heparin), and clot

activator (SiO

Genomic DNA from patients and healthy vol-

unteers was extracted from whole blood using the

standard phenol–chloroform method. PBMCs were

isolated by Ficoll–Urografin density gradient centrif-

ugation. Cell lysates were prepared using MILLIPLEX

MAP Lysis Buffer for Multiplexing (Merck, Germany).

Serum was obtained by centrifugation under stan-

dard conditions while avoiding hemolysis.

Genotyping of polymorphic variants of the immu-

noinflammatory genes IL1B (rs16944, rs1143627), IL13

(rs1295686), TNFB (rs2229094), and TGFA (rs2166975)

was performed by qPCR with a QuantStudio™  5

Real-Time PCR System (Applied Biosystems, USA) and

DTprime real-time PCR System (DNA-Technology, Rus-

sia) using BioMaster UDG HS-qPCR Lo-ROX (2x) kits

(Biolabmix, Russia).

Cytokine levels in PBMCs and serum were as-

sessed using MAGPIX and Luminex 200 multiplex

analyzers (Luminex, USA) with HCYTMAG-60K-PX41

MILLIPLEX® Human Cytokine/Chemokine Magnet-

ic Bead Panel (Merck) and Magnetic Luminex Assay

Kit (Cloud-Clone, China). Intracellular cytokine levels

Table 1. Sociodemographic and clinical characteristics of the study groups

Parameter AD group (n  =  239) Control group (n  =  205) p, statistical test

Age 43  [28;  54] 39  [29;  51] 0.43; Mann–Whitney U  test

Sex ♀  –  76.3%

♂  –  23.7%

♀  –  50.5%

♂  –  49.5%

  =  31.9; p  <  0.001

ICD-10 diagnosis F31  –  33.8%

F32  –  30.4%

F33  –  35.8%

––

Age of AD onset (years) 28  [19;  44]

♀  –  29  [21;  47]

♂  –  23  [16;  42]

––

Duration of current AD

episode (months)

5  [2;  9] – –

CYTOKINES IL-1β, IL-13, TNF-β, TGF-α IN AFFECTIVE DISORDERS 783

BIOCHEMISTRY (Moscow) Vol. 91 No. 5 2026

were normalized to cell number and expressed as

concentrations in lysates corresponding to 10

cells

per mL. Final cytokine concentrations in the lysates

and serum were reported in pg/mL.

All laboratory experiments were conducted us-

ing the equipment of the Medical Genomics Center

for Collective Use (Tomsk National Research Medical

Center).

Statistical analysis was performed with Statis-

tica for Windows (v.12.0) using nonparametric tests

were applied, including the Mann–Whitney U  test,

Kruskal–Wallis test, and Pearson’s χ

  test. Odds ratios

with 95% confidence intervals (OR [95% CI]) were cal-

culated. Distribution of genotype was tested for com-

pliance with the Hardy–Weinberg equilibrium using

Pearson’s χ

  test.

RESULTS

Polymorphic variants of cytokine genes. The

frequencies of genotypes of the studied cytokine gene

polymorphisms were tested for compliance with the

Hardy–Weinberg equilibrium. All polymorphic vari-

ants were found to conform to the Hardy–Weinberg

equilibrium (p  >  0.05).

Comparative analysis of frequencies of genotypes

and alleles of polymorphisms in the cytokine genes

IL1B (rs16944, rs1143627), IL13 (rs1295686), TNFB

(rs2229094), and TGFA (rs2166975) revealed signif-

icant differences only for the rs2229094 polymor-

phism of the TNFB gene (χ

  =  51.42; p  <  0.001 for al-

leles and χ

  =  44.79; p  <  0.001 for genotypes) (Table  2).

The A allele was more frequent in the AD patient

Table 2. Allele and genotype frequencies of cytokine gene polymorphisms in patients with ADs and control group

SNP Genotypes/

alleles

AD patients, n (%) Control group, n (%) OR [95% CI] χ

rs16944 IL1B AA 24 (10.2%) 27 (13.6%) 0.72 [0.4-1.29] 1.277 0.528

AG 106 (44.9%) 87 (43.9%) 1.04 [0.71-1.52]

GG 106 (44.9%) 84 (42.4%) 1.11 [0.76-1.62]

A 154 (32.6%) 141 (35.6%) 0.88 [0.66-1.16] 0.852 0.356

G 318 (67.4%) 255 (64.4%) 1.14 [0.86-1.51]

rs1143627 IL1B AA 109 (45.6%) 89 (43.6%) 1.08 [0.74-1.58] 1.108 0.575

AG 106 (44.4%) 88 (43.1%) 1.05 [0.72-1.53]

GG 24 (10%) 27 (13.2%) 0.73 [0.41-1.31]

A 324 (67.8%) 266 (65.2%) 1.12 [0.85-1.49] 0.662 0.416

G 154 (32.2%) 142 (34.8%) 0.89 [0.67-1.18]

rs1295686 IL13 CC 132 (56.2%) 114 (55.9%) 1.01 [0.69-1.48] 1.975 0.372

CT 91 (38.7%) 73 (35.8%) 1.13 [0.77-1.67]

TT 12 (5.1%) 17 (8.3%) 0.59 [0.28-1.27]

C 355 (75.5%) 301 (73.8%) 1.1 [0.81-1.49] 0.357 0.550

T 115 (24.5%) 107 (26.2%) 0.91 [0.67-1.24]

rs2229094 TNFB AA 134 (56.1%) 59 (29.1%) 3.11 [2.10-4.63] 44.786 <0.001*

AG 86 (36%) 88 (43.3%) 0.73 [0.5-1.08]

GG 19 (7.9%) 56 (27.6%) 0.23 [0.13-0.4]

A 354 (74.1%) 206 (50.7%) 2.77 [2.09-3.68] 51.418 <0.001*

G 124 (25.9%) 200 (49.3%) 0.36 [0.27-0.48]

MIKHALITSKAYA et al.784

BIOCHEMISTRY (Moscow) Vol. 91 No. 5 2026

Table 2 (cont.)

SNP Genotypes/

alleles

AD patients, n (%) Control group, n (%) OR [95% CI] χ

rs2166975 TGFA AA 27 (11.4%) 17 (8.4%) 1.41 [0.75-2.68] 2.143 0.342

AG 97 (41.1%) 77 (37.9%) 1.14 [0.78-1.68]

GG 112 (47.5%) 109 (53.7%) 0.78 [0.53-1.13]

A 151 (32%) 111 (27.3%) 1.25 [0.93-1.67] 2.256 0.133

G 321 (68%) 295 (72.7%) 0.8 [0.6-1.07]

Note. χ

, Pearson’s criterion; * p < 0.05, statistically significant differences from the control group.

Table 3. Cytokine content in PBMCs

Cytokine

AD patients

(n = 30)

Control group

(n = 28)

M–U

IL-1β

4.46

[2.81; 5.96]

4.59

[2.31; 8.77]

0.51

TGF-α

0.34

[0.13; 0.96]

0.1

[0.05; 0.46]

0.042*

IL-13

6.84

[4.1; 10.64]

4.035

[2.85; 7.21]

0.015*

Note. Data are presented as median, lower, and upper quar-

tiles (Me [Q1; Q3]), pg/mL; *p < 0.05, statistically significant

differences between the patient and control groups; p

M–U

Mann–Whitney U test.

Table 4. Cytokine concentration in blood serum

Cytokine

AD patients

(n = 35)

Control group

(n = 17)

M–U

IL-1β

1.45

[0.51; 2.02]

1.86

[0.23; 9.56]

0.62

TNF-β

129.6

[16.6; 250.6]

8.7

[6.0; 34.6]

0.039*

TGF-α

0.93

[0.40; 3.22]

1.30

[0.71; 3.30]

0.42

IL-13

18.8

[12.5; 119.3]

9.6

[3.2; 24.9]

0.09

Note. Data are presented as median, lower, and upper quar-

tiles (Me [Q1; Q3]), pg/mL; *p< 0.05, statistically significant

differences between the patient and control groups; p

M–U

Mann–Whitney U test.

group than in the control group (74.1% vs. 50.7%;

OR [95% CI]  =  2.77 [2.09-3.68]). The AA genotype was

also more frequent in AD patients than in the con-

trol group (56.1% vs. 29.1%; OR [95% CI]  =  3.11 [2.10-

4.63]). No other statistically significant differences in

the allele and genotype frequencies were detected for

the remaining studied polymorphisms (p  >  0.05).

Intracellular cytokine content. The cytokine

levels in PBMCs of AD patients are presented in

Table  3. Comparison between the patient and control

groups revealed statistically significant differences in

the levels of TGF-α (p  =  0.042) and IL-13 (p  =  0.015).

Specifically, the contents of TGF-α (0.34 [0.13; 0.96]

pg/mL) and IL-13 (6.84 [4.1; 10.64]  pg/mL) were high-

er in patients with AD than in healthy donors (0.1

[0.05; 0.46]  pg/mL and 4.035 [2.85; 7.21]  pg/mL, re-

spectively).

Cytokine concentration in blood serum. Com-

parative analysis of cytokine levels in the blood

serum of patients with AD and healthy individuals

(Table  4) demonstrated a significantly higher concen-

tration of TNF-β in the patients than in healthy donors

(129.6  [16.6; 250.6]  pg/mL vs. 8.7  [6.0; 34.6]  pg/mL, re-

spectively; p  =  0.039).

Correlation between the studied parameters.

The relationship between the cytokine levels in PBMCs,

cytokine concentrations in blood serum, and car-

riage of genotypes of polymorphic variants of the

IL1B (rs16944, rs1143627), IL13 (rs1295686), TNFB

(rs2229094), and TGFA (rs2166975) genes was eval-

uated using association and correlation analyses.

No statistically significant associations were identi-

fied between the cytokine concentrations in blood

serum and cytokine levels in PBMCs among carriers

of different genotypes, although a moderate positive

correlation (r  =  0.40) was found between the serum

levels of IL-1β and IL-13 in AD patients (p  <  0.05).

DISCUSSION

The compensatory and adaptive reactions initi-

ated by the immune system are aimed at maintain-

ing homeostasis and preventing the development of

pathological conditions [25,  26]. Hormonally stimu-

CYTOKINES IL-1β, IL-13, TNF-β, TGF-α IN AFFECTIVE DISORDERS 785

BIOCHEMISTRY (Moscow) Vol. 91 No. 5 2026

lated leukocytes circulating in the bloodstream can

either activate or suppress the immune response

through the secretion of pro- and anti-inflammatory

cytokines that can regulate brain activity and emo-

tions [27, 28]. Systemic inflammation is accompanied

by the disruption of cytokine balance and develop-

ment of neuroinflammation, which may ultimately

lead to the onset of mental pathologies, including de-

pressive symptoms.

Like many mental disorders, AD is a multifac-

torial disease caused by a combination of genetic,

ecological, psychological, and biological factors [29].

In this work, we performed a comprehensive study

of several cytokines (IL-1β, IL-13, TNF-β, and TGF-α)

involved in the development of neuroinflammation.

IL-1β is a pro-inflammatory cytokine encoded by

the IL1B gene located on chromosome 2q14.1. It had

been first discovered as a factor involved in the etiol-

ogy of behavioral disorders and was later associated

with depressive disorder [30]. Several studies have

demonstrated that IL-1β levels are significantly high-

er in patients with depression compared with healthy

individuals [31, 32]. Ferreira et al. [33] reported a

possible link between the rs16944 single nucleotide

polymorphism (SNP) in the IL1B gene and increased

susceptibility to depression in patients with multiple

sclerosis. However, in our study, we did not observe

any association between IL-1β levels (either in serum

or PBMCs) and AD, nor did we detect relationships

with polymorphic variants of the IL1B gene.

IL-13 is generally considered as an anti-inflam-

matory cytokine; however, its effects can be pleiotro-

pic. Under certain conditions, IL-13 may not contrib-

ute to the suppression of pro-inflammatory responses.

Doong et al. [34] found that the A allele of the IL13

gene (rs1295686) is associated with a complex of

symptoms, including pain, fatigue, sleep disturbances,

and depression. In contrast, we observed no such as-

sociation, which may be attributed to differences in

the patient populations, as Doong et al. examined

patients prior to breast cancer surgery, whereas our

study focused on individuals with AD without comor-

bid pathologies.

Several studies have reported elevated IL-13

levels in the serum of patients with MDD [35, 36].

The most likely explanation for this elevation is that

chronic stress associated with MDD causes a chronic

increase in cortisol levels, which, in turn, increases

IL-13 content in peripheral blood. Consistently, our

study found elevated IL-13 levels in PBMCs of patients

with AD.

TNF-β is a multifunctional pro-inflammatory cy-

tokine of the TNF superfamily. It is encoded by the

TNFB gene located on chromosome 6p21.33. Dunn

etal.[37] found an association between the rare Aal-

lele of rs2229094 of the TNFB gene and subsyndromal

depression. Consistent with this, we found that both

the allele and the genotype of rs2229094 are associ-

ated with AD. The A allele and the AA genotype oc-

curred more frequently in AD patients than in the

control group, suggesting that their presence consti-

tutes a risk factor for AD development. Furthermore,

Das et al. [38] demonstrated increase TNF levels in

MDD that correlated with the disease severity. In line

with these findings, we observed that patients with

AD exhibited higher TNF-β concentrations compared

to healthy controls.

TGFs are a family of polypeptide growth factors

including TGF-α and TGF-β. These cytokines play cru-

cial roles in embryonic development and regulation

of specific immune responses, particularly through

their ability to induce T-regulatory (Treg) cells. Bialek

et al. [39] demonstrated that the AG genotype of the

rs2166975 polymorphism in the TGFA gene is associ-

ated with an increased risk of developing depression,

whereas the GG genotype appears to confer a pro-

tective effect. In parallel, our findings indicated that

TGF-α levels in PBMCs are elevated in AD patients

compared to healthy controls.

It should be noted that the present study is the

first to report the results of a comprehensive investi-

gation of immunoinflammatory features across vari-

ous levels of molecular organization, including assess-

ment of genetic polymorphisms, protein expression in

PBMCs, and serum cytokine levels in patients with

AD compared to healthy individuals. At the same

time, our study has a number of limitations. Thus,

expression of cytokines was evaluated in PBMCs and

may not directly reflect processes occurring in the

brain. Goossens etal. [40] conducted a systematic re-

view and concluded that, despite inherent limitations,

heterogeneity in study designs, and a small number

of original studies, several characteristics of PBMCs,

particularly those related to inflammatory pathways

and cell viability, show potential as clinically relevant

biomarkers. However, caution should be exercised

when extrapolating findings from peripheral cells to

brain processes, as evidence regarding intracellular

signaling in the central nervous system remains lim-

ited and sometimes contradictory.

CONCLUSION

For the first time, an association has been iden-

tified between the rs2229094 polymorphism of the

TNFB gene and AD, along with elevated expression

of TGF-α and IL-13 in PBMCs and increased serum

levels of TNF-β in patients with AD. These findings

demonstrate the involvement of studied cytokines

in the pathophysiological mechanisms underlying

AD development.

MIKHALITSKAYA et al.786

BIOCHEMISTRY (Moscow) Vol. 91 No. 5 2026

Abbreviations

AD affective disorder

IL interleukin

MDD major depressive disorder

PBMCs peripheral blood mononuclear cells

TGF-α transforming growth factor alpha

TNF-β tumor necrosis factor beta

Contributions

L.A.L., S.A.I., E.V.M., and N.A.B. developed the concept

and supervised the study; E.V.M., A.S.B., E.V.E., N.M.V.,

D.Z.P., and O.V.R. conducted experiments; E.V.M. wrote

the text of the article; S.A.I., L.A.L., A.S.B., O.V.R., and

G.G.S. editing the manuscript.

Funding

This study was supported by the Russian Science Foun-

dation (project no. 23-15-00338; https://rscf.ru/project/

23-15-00338/).

Ethics approval and consent to participate

The study was conducted in accordance with the eth-

ical principles of human research and was approved

by the Biomedical Ethics Committee of the Mental

Health Research Institute, Tomsk National Research

Medical Center, and was in compliance with the Hel-

sinki Declaration for experiments involving humans

(protocol no.  164 from June  16,  2023). All patients

signed informed consent to participate in the study.

Conflict of interest

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