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Effect of interleukin-1β gene functional polymorphism on dorsolateral prefrontal cortex activity in schizophrenic patients

Authors

  • Sergi Papiol,

    Corresponding author
    1. Departament de Biologia Animal, Unitat d'Antropologia, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain
    • Departament de Biologia Animal, Unitat d'Antropologia, Facultat de Biologia, Universitat de Barcelona, Av. Diagonal 645, 08028 Barcelona, Spain.
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  • Vicente Molina,

    1. Department of Psychiatry, Hospital Clínico de Salamanca, Salamanca, Spain
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  • Araceli Rosa,

    1. Departament de Biologia Animal, Unitat d'Antropologia, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain
    2. Unitat de Biologia Evolutiva. Facultat de Ciències de la Salut i de la Vida. Universitat Pompeu Fabra. Barcelona, Spain
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  • Javier Sanz,

    1. Department of Psychiatry, Hospital Doce de Octubre, Edificio de Medicina Comunitaria, Madrid, Spain
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  • Tomás Palomo,

    1. Department of Psychiatry, Hospital Doce de Octubre, Edificio de Medicina Comunitaria, Madrid, Spain
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  • Lourdes Fañanás

    1. Departament de Biologia Animal, Unitat d'Antropologia, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain
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  • Please cite this article as follows: Papiol S, Molina V, Rosa A, Sanz J, Palomo T, Fañanás L. 2007. Effect of Interleukin-1β Gene Functional Polymorphism on Dorsolateral Prefrontal Cortex Activity in Schizophrenic Patients. Am J Med Genet Part B 144B:1090–1093.

Abstract

Hypoactivity of the dorsolateral prefrontal cortex (DLPFC) during cognitive tasks is among the most consistent findings in schizophrenia. The biological factors contributing to this hypofrontality are only partially known. Previous reports have shown the influence of genes mapped to IL-1 cluster (i) in the risk to develop schizophrenia and (ii) on brain morphological abnormalities in these patients. Moreover, Interleukin-1β (IL-1β), encoded by IL-1B gene (IL-1 cluster, chromosome 2q13) has a key role in dopaminergic differentiation and dendrite growth in developing cortical neurons. The authors explored the role of a genetic functional polymorphism at IL-1B gene in relation to DLPFC activity. DLPFC (left and right) metabolic activity was measured in a sample of 19 DSM-IV diagnosed schizophrenic patients of Spanish origin using a procedure based on MRI/PET image fusion. During PET studies, subjects performed a contingent Continuous Performance Test aiming to activate DLPFC. Functional promoter polymorphism −511 C/T (rs16944) of IL-1B gene was genotyped in these patients. Those patients who were allele 2 (−511 T) carriers showed a lower metabolic activity in the left DLPFC with respect to patients homozygous for allele 1 (−511 C) (U = 16, z = −2.32, P = 0.02). Our results suggest that hypofrontality reported in some schizophrenic patients might be explained, at least in part, by this functional polymorphism at IL-1B gene. Genetic variants with influence on brain functionality may account for the neurocognitive heterogeneity observed in schizophrenic patients. © 2007 Wiley-Liss, Inc.

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