Fallgatter Andreas J, Herrmann Martin J, Hohoff Christa, Ehlis Ann-Christine, Jarczok Tomasz A, Freitag Christine M, Deckert Jürgen
Laboratory for Psychophysiology and Functional Imaging, Department of Psychiatry, University of Würzburg, Würzburg, Bavaria, Germany.
Neuropsychopharmacology. 2006 Sep;31(9):2002-10. doi: 10.1038/sj.npp.1301003. Epub 2006 Jan 11.
DTNBP1 (dysbindin) is one of the several putative schizophrenia genes supported by association, neuroanatomical, and cellular studies. These suggest an involvement of DTNBP1 in the prefrontal cortex and cognitive functions mediated by interaction with neurotransmitter systems, in particular glutamate. The influence of DTNBP1 gene variation on prefrontal brain function at the systemic neurophysiological level, though, has not been characterized. The NoGo-anteriorization (NGA) as an event-related potential (ERP) measure elicited during the continuous performance test (CPT) has been established as a valid neurophysiological parameter for prefrontal brain function in healthy individuals and patients with schizophrenias. In the present study, we therefore investigated the influence of eight dysbindin gene variants on the NGA as a marker of prefrontal brain function in 48 healthy individuals. Two DTNBP1 polymorphisms previously linked to schizophrenia (P1765 and P1320) were found associated with changes in the NGA. Post hoc analysis showing an influence of genetic variation at these loci on the Go centroid and frontal amplitudes suggest that this might be due to modification of the execution of motor processes by the prefrontal cortex. This is the first report on a role of DTNBP1 gene variation for prefrontal brain function at a systemic neurophysiological level in healthy humans. Future studies will have to address the relevance of this observation for patients with schizophrenias.
DTNBP1（精神分裂症相关结合蛋白）是通过关联研究、神经解剖学研究和细胞研究得到支持的几种假定的精神分裂症基因之一。这些研究表明，DTNBP1参与前额叶皮层以及通过与神经递质系统（特别是谷氨酸）相互作用介导的认知功能。然而，DTNBP1基因变异在系统神经生理学水平上对前额叶脑功能的影响尚未得到明确描述。在持续操作测试（CPT）期间引出的作为事件相关电位（ERP）测量指标的不执行前冲（NGA），已被确立为健康个体和精神分裂症患者前额叶脑功能的有效神经生理学参数。因此，在本研究中，我们调查了48名健康个体中8种精神分裂症相关结合蛋白基因变异对作为前额叶脑功能标志物的NGA的影响。发现先前与精神分裂症相关的两种DTNBP1多态性（P1765和P1320）与NGA的变化有关。事后分析表明，这些位点的基因变异对“执行”波峰和额叶振幅有影响，这可能是由于前额叶皮层对运动过程执行的改变所致。这是关于DTNBP1基因变异在健康人类系统神经生理学水平上对前额叶脑功能作用的首次报道。未来的研究将必须探讨这一观察结果对精神分裂症患者的相关性。
