Krug Axel, Markov Valentin, Eggermann Thomas, Krach Sören, Zerres Klaus, Stöcker Tony, Shah N Jon, Schneider Frank, Nöthen Markus M, Treutlein Jens, Rietschel Marcella, Kircher Tilo
Department of Psychiatry and Psychotherapy, RWTH Aachen University, Pauwelsstr. 30, 52074 Aachen, Germany.
Neuroimage. 2008 Oct 1;42(4):1569-76. doi: 10.1016/j.neuroimage.2008.05.058. Epub 2008 Jun 12.
Working memory dysfunctions are a prominent feature in schizophrenia. These impairments have been linked to alterations in prefrontal brain activation with studies reporting hypo- and hyperactivations. Since schizophrenia has a high heritability, it is of interest whether susceptibility genes modulate working memory and its neural correlates. The aim of the present study was to test the influence of the NRG1 schizophrenia susceptibility gene on working memory and its neural correlates in healthy subjects. 429 healthy individuals performed a verbal and a spatial working memory task. A subsample of 85 subjects performed a 2-back version of the Continuous Performance Test (CPT) in a functional MRI study. The NRG1 SNP8NRG221533 (rs35753505) carrier status was determined and correlated with working memory performance and brain activation. There were no effects of genetic status on behavioural performance in the working memory tasks in the 429 subjects and in the fMRI task (n=85). A linear effect of NRG1 SNP8NRG221533 carrier status on neuronal activation emerged in the fMRI experiment. Hyperactivation of the superior frontal gyrus (BA 10) was correlated with the number of risk alleles. The fMRI data suggest that performance measures between groups did not differ due to a compensational activation of BA 10 in risk-allele carriers. Our results are in line with functional imaging studies in patients with schizophrenia, which also showed a differential activation in lateral prefrontal areas.
工作记忆功能障碍是精神分裂症的一个突出特征。这些损害与前额叶脑激活的改变有关，研究报告了激活不足和过度激活的情况。由于精神分裂症具有较高的遗传度，因此易感性基因是否调节工作记忆及其神经关联值得关注。本研究的目的是测试NRG1精神分裂症易感基因对健康受试者工作记忆及其神经关联的影响。429名健康个体进行了言语和空间工作记忆任务。在一项功能磁共振成像研究中，85名受试者的子样本进行了2-back版本的连续性能测试（CPT）。确定了NRG1 SNP8NRG221533（rs35753505）的携带者状态，并将其与工作记忆表现和脑激活相关联。在429名受试者的工作记忆任务和功能磁共振成像任务（n = 85）中，基因状态对行为表现均无影响。在功能磁共振成像实验中，出现了NRG1 SNP8NRG221533携带者状态对神经元激活的线性影响。额上回（BA 10）的过度激活与风险等位基因的数量相关。功能磁共振成像数据表明，由于风险等位基因携带者中BA 10的代偿性激活，各组之间的表现测量没有差异。我们的结果与精神分裂症患者的功能成像研究一致，该研究也显示外侧前额叶区域存在差异激活。
