Cognition in Schizophrenia: Modeling the Interplay between Interleukin-1β C-511T Polymorphism, Metabolic Syndrome, and Sex

Abstract

<b><i>Introduction:</i></b> Cognitive deficits and metabolic disturbances are among the main determinants of functional impairment and reduced life expectancy in patients with schizophrenia, and they may share underlying biological mechanisms. Among these, interleukin-1β (IL-1β), a key mediator of inflammatory response, is of particular interest. IL-1β C-511T polymorphism has been associated with neuropsychiatric conditions and, in the general population, with cognitive and metabolic alterations. This study aims to evaluate the effects of the IL-1β C-511T polymorphism on both cognition and metabolic syndrome in a sample of patients affected by schizophrenia, with a focus on sex differences. <b><i>Methods:</i></b> 138 patients with schizophrenia were assessed for metabolic parameters and neurocognitive measures by means of the Brief Assessment of Cognition Scale. The effects of IL-1β C-511T polymorphism on cognition and metabolic syndrome were evaluated in the context of general linear models. <b><i>Results:</i></b> The analysis showed a significant interaction between IL-1β genotype and sex on 2 core cognitive domains. In detail, among CC homozygous, females outperformed males on processing speed, while among T carriers, males outperformed females on executive functions. A significant interaction also emerged between metabolic syndrome, sex, and IL-1β genotype for executive functions, with worse performance for T carrier females with metabolic syndrome. No significant direct effect was observed for metabolic syndrome on cognition. <b><i>Conclusion:</i></b> These findings support the hypothesis that IL-1β polymorphism could play a key role in mediating the complex and refined relationship between metabolic syndrome and cognitive performance.

Association Between Metabolic Risk Factors and Cognitive Impairment in Schizophrenia Based on Sex

“…A few studies have examined associations between metabolic risk factors and neurocognitive function in schizophrenia by sex. The study by Bosia et al [ 41 ] showed that MetS was only closely related to executive function in female patients with schizophrenia. One study indicated that BMI was only correlated with male patients’ cognitive functions, including language, visuospatial skill, and attention [ 27 ].…”

Hyperexpression of Proinflammatory Cytokines in Blood as a Biomarker of Systemic Inflammatory Response in Schizophrenia: Scoping Review

“…The IL-1β C-511T polymorphism is associated with higher IL-1β plasma concentrations, on the one hand, there is evidence suggesting that levels of IL-1β may vary with clinical status along with the concentration of other cytokines, such as IL-6 and TGFβ. Specifically, acute exacerbations seem to create an increase in their values [35]. Also, a significant association founds between serum levels of IL-1β and negative rather than positive Sch symptoms [36][37].…”