Effect of the Interleukin-1β Gene on Dorsolateral Prefrontal Cortex Function in Schizophrenia: A Genetic Neuroimaging Study

• Published in: Biological psychiatry (1969) 2012-11, Vol.72 (9), p.758-765
• Main Authors: Fatjó-Vilas, Mar, Pomarol-Clotet, Edith, Salvador, Raymond, Monté, Gemma C, Gomar, Jesús J, Sarró, Salvador, Ortiz-Gil, Jordi, Aguirre, Candibel, Landín-Romero, Ramón, Guerrero-Pedraza, Amalia, Papiol, Sergi, Blanch, Josep, McKenna, Peter J, Fañanás, Lourdes
• Format: Article
• Language: English
• Subjects: Adult; Adult and adolescent clinical studies; Biological and medical sciences; Case-Control Studies; Dorsolateral prefrontal cortex; European Continental Ancestry Group - genetics; European Continental Ancestry Group - psychology; Female; fMRI; Functional Neuroimaging - methods; Functional Neuroimaging - psychology; Genotype; Humans; Interleukin-1beta - genetics; Interleukin-1beta - physiology; interleukin-1β gene; Magnetic Resonance Imaging - methods; Magnetic Resonance Imaging - psychology; Male; Medical sciences; Memory, Short-Term - physiology; Middle Aged; neuroimaging genetics; Neuropsychological Tests; Polymorphism, Genetic; Prefrontal Cortex - physiopathology; Psychiatry; Psychology. Psychoanalysis. Psychiatry; Psychomotor Performance - physiology; Psychopathology. Psychiatry; Psychoses; Schizophrenia; Schizophrenia - genetics; Schizophrenia - physiopathology; Schizophrenic Psychology; working memory
• ISSN: 0006-3223; 1873-2402
• DOI: 10.1016/j.biopsych.2012.04.035

Background Genetic studies have found that the interleukin-1β gene ( IL1B, 2q13) influences the risk for schizophrenia, but the underlying biological mechanisms of the association are still unclear. Investigation of the effects of genetic variability in this gene on brain function could provide more information about its role in the disorder. Methods The present study examined the effects of a functional polymorphism at IL1B gene promoter (−511C/T; rs16944) on brain correlates of working memory performance in schizophrenia. Forty-eight schizophrenia patients and 46 control subjects underwent functional magnetic resonance imaging while performing the n-back task. Results In the pooled sample, genetic variability at this locus was associated with differential brain activation in a bilateral frontal region including the dorsolateral prefrontal cortex. There was also a significant diagnosis × genotype interaction effect in an overlapping frontal region: the IL1B polymorphism did not affect activation in the control subjects in this area, but the schizophrenia patients who were T carriers showed significantly higher activation than the CC homozygotes. Conclusions The findings support a role for IL1B variability in the dorsolateral prefrontal cortex dysfunction classically associated with schizophrenia.