Associations between IL-10, IL-4, IL-6, IL-1B-511, C-reactive protein and brain-derived neurotrophic factor genetic polymorphisms and syndrome-based subtypes of unipolar depression

Background

The clinical heterogeneity of unipolar depression may be attributed to differences in the pathogenetic mechanisms of its syndrome-based subtypes, including the degree of inflammatory activation and the severity of neurotrophic factor deficiency, such as that of brain-derived neurotrophic factor (BDNF). Functional polymorphisms in the genes encoding pro- and anti-inflammatory interleukins, as well as C-reactive protein (CRP) and BDNF, may have specific associations with different syndrome-based subtypes of the disease.

Aims

The aim of this study was to explore functional polymorphisms of the IL-10, IL-4, IL-6, IL-1B-511, CRP, and BDNF genes in patients with unipolar depression and to identify their potential associations with syndrome-based subtypes of the disease.

Methods

The study involved patients aged 18–65 years with a verified diagnosis of unipolar depressive disorder (ICD-10: F32, F33, F34.1; DSM-5: 296.2, 296.3, 300.4) who were treated at the Psychosomatic Medicine Clinic and the S.S. Korsakov Psychiatric Clinic of the Clinical Hospital No. 3 (Sechenov University) as well as the Psychiatric Hospital No. 1 named after N. A. Alexeev from May 2021 to April 2024. Genetic analysis was performed at the Clinical Genetics Laboratory of the FSBI “Mental Health Research Centre”. Depression subtyping was carried out based on the leading symptoms in line with ICD-10 and DSM-5 criteria (melancholic, atypical, or anxious type). Genotyping was performed using the high-resolution melting polymerase chain reaction (HRM-PCR) assay. Statistical analysis was conducted using the R software.

Results

A total of 93 patients (n=93) with unipolar depression were enrolled in the study and divided into three groups based on depression subtype: melancholic (n=34; 36.5%), atypical (n=19; 20.4%), and anxious (n=40; 43.0%). Carriage of the IL-10 (rs1800872) and BDNF (Val66Met) A-alleles was associated with the melancholic subtype (OR=1.95, p=0.0247 and OR=2.08, p=0.0144, respectively), whereas carriage of the IL-4 (rs2243250) C/C genotype and the CRP (rs2794521) A/A genotype was associated with the atypical subtype (OR=3.61, p=0.0121 and OR=3.35, p=0.0037, respectively). For anxious depression, an association was found with the IL-4 (rs2243250) T/T genotype (OR=6.33, p=0.013) and the IL-6 (rs1800795) C/C and C/G genotypes. Notably, the effect of IL-6 genotype carriage was dependent on participants’ ethnicity, with Russian patients being at increased risk of anxious depression and non-Russian patients showing the opposite trend (OR=2.86, p=0.034 and OR=0.004, p=0.006, respectively). No significant associations between IL-1B-511 genetic polymorphisms and syndrome-based unipolar depression subtypes were identified.

Conclusions

Statistically significant associations were established between IL-10, IL-4, IL-6, CRP, and BDNF genetic polymorphisms and the three syndrome-based subtypes of unipolar depression, while no association was found for IL-1B-511 genetic polymorphisms. Our findings support the hypothesis of differential roles of inflammatory mechanisms and neuroplasticity among these subtypes. Further research into these polymorphisms may facilitate the identification of specific genetic markers for syndrome-based subtypes of unipolar depression, contributing to more personalized diagnosis and treatment.

References

No references.