Association between Genetic Polymorphisms of Pro- and Anti-Inflammatory Cytokines and C-Reactive Protein and Syndrome-Based Subtypes of Unipolar Depression

Background: systemic inflammation plays a central role in pathogenesis of unipolar depression. In most studies focusing on inflammatory markers, unipolar depressive disorders are regarded as a single nosological category without subtype differentiation although the extent to which inflammatory mechanisms are involved varies across syndrome-based subtypes. Genetic polymorphisms affecting the expression of pro- and anti-inflammatory cytokines IL-4, IL-10, IL-6, IL-1B and C-reactive protein (CRP) may determine the syndrome-based structure of unipolar depressive disorders. The aim of study was to investigate functionally significant single-nucleotide polymorphisms (SNPs) of IL-4, IL-10, IL-6, IL-1B and CRP genes in patients with unipolar depressive disorders and their potential associations with syndrome-based subtypes. Patients, Materials and Methods: the study enrolled patients aged 18–65 years with a verified diagnosis of unipolar depression (ICD-10 codes F32, F33, F34.1, DSM-5 codes 296.2, 296.3, 300.4) who were they undergoing treatment from May 2021 to April 2024. Genetic analysis was conducted at the Laboratory of Clinical Genetics of the FSBSI “Mental Health Research Centre”. The allocation to each syndrome-based subtype was carried out in line with the leading symptoms according to ICD-10 and DSM-5 criteria (melancholic, atypical and anxious). Genotyping was performed using the High-Resolution Melting method (HRM) run on the Applied Biosystems QuantStudio 7 Flex Real-Time PCR System (ThermoFisher, the US). Statistical analysis was conducted using the R software. Results: a total of 93 patients (n = 93) were divided into three groups by syndrome-based subtype: melancholic (n = 34; 36.5%), atypical (n = 19; 20.4%) and anxious (n = 40; 43%). The A-allele of IL-10 (rs1800872) was associated with the melancholic subtype (OR = 1.95, adjusted р = 0.0247). The C/C genotype of IL-4 (rs2243250) and the A/A genotype of CRP (rs2794521) were both associated with the atypical subtype (OR = 3.61, adjusted p = 0.0121 and OR = 3.35, adjusted p = 0.0037, respectively). The anxious subtype was associated with the T/T genotype of IL-4 (rs2243250) as well as the C/C and the C/G genotypes of IL-6 (rs1800795). Notably, carriers of the IL-6 (rs1800795) genotypes were either at a higher or a lower risk of developing anxious depression depending on their ethnicity (OR = 6.33; adjusted p = 0.013; OR = 0.004, adjusted p = 0.006). None of the syndrome-based subtypes were associated with the IL-1B rs16944 polymorphism. Conclusions: genetic polymorphisms of IL-10, IL-4, IL-6 and CRP were shown to be significantly associated with the melancholic, atypical and anxious subtypes of unipolar depression. Further research into these polymorphisms may contribute to the development of personalized diagnostic strategies and treatments for patients with unipolar depressive disorders.

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