A study of the association between polymorphisms in the genes for interleukins IL-6 and IL-10 and negative symptoms subdomains in schizophrenia

Indian J Psychiatry. 2022 Sep-Oct;64(5):484-488. doi: 10.4103/indianjpsychiatry.indianjpsychiatry_212_22. Epub 2022 Oct 12.

Abstract

Background: Schizophrenia is a severe mental illness manifested by various symptoms. Negative symptoms (NS) are associated with disability and poor function of patients. The study of NS neurobiology is complicated by their heterogeneity. Factor analysis revealed two distinct NS subdomains with different pathophysiological mechanisms: volitional pathology, including avolition and apathy (AA), and diminished expression (DE). Inflammation is one mechanism that may underlie NS, including their heterogeneity.

Aims: To search for the association between genes for interleukins (IL-6 -174 G/C, IL-10 -592 C/A, and IL-10 -1082 G/A) and NS subdomains.

Materials and methods: The study included 275 patients with schizophrenia. NS factors were calculated based on the Positive and Negative Syndromes Scale.

Results: There was a significant main effect of IL-10 polymorphisms on the AA, but not the DE subdomain. Mean score on the AA subdomain was higher in the IL-10 -592 AA compared to the CC genotype. Differences between IL-10 -1082 G/A genotypes were dose dependent. The lowest score was observed for the IL-10 -1082 GG genotype. The association between the IL-6 -174 G/C polymorphism and AA scores was close to the level of significance. Patients with the IL-6 -174 GG genotype had higher score compared to the AA genotype.

Conclusion: The results provide further neurobiological evidence for the validity of the NS factor categorization. An imbalance between pro-inflammatory and anti-inflammatory cytokines because of genetic variations is associated with the AA NS subdomain that is supposed to be a more severe aspect of psychopathology compared to the DE.

Keywords: Inflammatory imbalance; negative symptoms heterogeneity; schizophrenia severity.