Papiol Sergi, Molina Vicente, Rosa Araceli, Sanz Javier, Palomo Tomás, Fañanás Lourdes
Departament de Biologia Animal, Unitat d'Antropologia, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain.
Am J Med Genet B Neuropsychiatr Genet. 2007 Dec 5;144B(8):1090-3. doi: 10.1002/ajmg.b.30542.
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-1beta (IL-1beta), 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.
背外侧前额叶皮质（DLPFC）在认知任务期间的活动减退是精神分裂症中最一致的发现之一。导致这种前额叶功能减退的生物学因素仅部分为人所知。先前的报告显示，定位于白细胞介素-1（IL-1）基因簇的基因（i）对精神分裂症发病风险的影响以及（ii）对这些患者脑形态异常的影响。此外，由IL-1B基因（IL-1基因簇，位于2号染色体q13）编码的白细胞介素-1β（IL-1β）在发育中的皮质神经元的多巴胺能分化和树突生长中起关键作用。作者探讨了IL-1B基因的一个基因功能多态性与DLPFC活动的关系。使用基于MRI/PET图像融合的程序，对19名诊断为DSM-IV的西班牙裔精神分裂症患者样本的DLPFC（左、右）代谢活动进行了测量。在PET研究期间，受试者进行了一个偶然连续操作测试，旨在激活DLPFC。对这些患者的IL-1B基因功能启动子多态性-511 C/T（rs16944）进行了基因分型。与等位基因1（-511 C）纯合的患者相比，那些等位基因2（-511 T）携带者的患者左DLPFC代谢活动较低（U = 16，z = -2.32，P = 0.02）。我们的结果表明，一些精神分裂症患者中报告的前额叶功能减退可能至少部分地由IL-1B基因的这种功能多态性所解释。影响脑功能的基因变异可能解释了在精神分裂症患者中观察到的神经认知异质性。
