Publications

Recent genetic studies have revealed that the interleukin-1 beta gene (IL1B) is associated with the risk for schizophrenia; however the underlying biological mechanisms of this association are still unclear. The integration of genetic data with functional magnetic resonance imaging (fMRI) enables the study of the effect of variability at IL1B gene on brain systems underlying specific brain activity and working memory deficits manifested in schizophrenia. The aim of the present study was to examine the role of a functional polymorphisms at IL1B gene promoter (-511C/T; rs16944) on the brain activity in 48 schizophrenia patients and 46 controls. All subjects underwent fMRI while performing the n-back task. In the pooled sample, genetic variability at the examined locus was associated with differential brain activation at dorsolateral prefrontal cortex (DLPFC). Interestingly, when the belonging to patients or control group was considered in interaction with the genotypic effect, a disease-genetic interaction effect emerged also in bilateral DLPFC. Hence, while the IL1B polymorphism does not seem to modulate the DLPFC activation during the performance of the n-back task in healthy subjects, it does modulate the DLPFC function in patients. Specifically, CC schizophrenia patients presented significantly lower mean activation scores than T carriers, with healthy subjects presenting intermediate mean activation values among both patients’ groups. This findings indicate that the -511C/T variant may exert a disease-specific effect on brain’s response to specific environmental stimuli such as a working memory task, suggesting the involvement of IL1B gene in the abnormal regulation of DLPFC activity classically associated to schizophrenia.