Department of Psychiatry and Psychotherapy, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn, Germany.
Eur Arch Psychiatry Clin Neurosci. 2011 Nov;261 Suppl 2:S161-5. doi: 10.1007/s00406-011-0256-9. Epub 2011 Sep 20.
Mutations of the transcription factor 4 (TCF4) gene cause mental retardation with or without associated facial dysmorphisms and intermittent hyperventilation. Subsequently, a polymorphism of TCF4 was shown in a genome-wide association study to slightly increase the risk of schizophrenia. We have further analysed the impact of this TCF4 variant rs9960767 on early information processing and cognitive functions in schizophrenia patients. We have shown in a sample of 401 schizophrenia patients that TCF4 influences verbal memory in the Rey Auditory Verbal Learning Test. Contrary to expectations, carriers of the schizophrenia-associated allele showed better recognition, thus indicating that while TCF4 influences verbal memory, the TCF4-mediated schizophrenia risk is not determined by the influence of TCF4 on verbal memory. TCF4 does not impact on various other cognitive functions belonging to the domains of attention and executive functions. Moreover, in a pharmacogenetic approach, TCF4 does not modulate the improvement of positive or negative schizophrenia symptoms during treatment with antipsychotics. Finally, we have assessed a key electrophysiological endophenotype of schizophrenia, sensorimotor gating. As measured by prepulse inhibition, the schizophrenia risk allele C of TCF4 rs9960767 reduces sensorimotor gating. This indicates that TCF4 influences key mechanisms of information processing, which may contribute to the pathogenesis of schizophrenia.
转录因子 4（TCF4）基因突变可导致伴有或不伴有相关面部畸形和间歇性过度通气的智力障碍。随后，一项全基因组关联研究显示 TCF4 的多态性略微增加了精神分裂症的风险。我们进一步分析了 TCF4 变体 rs9960767 对精神分裂症患者早期信息处理和认知功能的影响。我们在 401 名精神分裂症患者的样本中表明，TCF4 影响 Rey 听觉言语学习测试中的言语记忆。出乎意料的是，携带与精神分裂症相关等位基因的个体表现出更好的识别能力，这表明尽管 TCF4 影响言语记忆，但 TCF4 介导的精神分裂症风险并非由 TCF4 对言语记忆的影响决定。TCF4 不影响属于注意力和执行功能领域的各种其他认知功能。此外，在药物遗传学方法中，TCF4 不会调节抗精神病药物治疗期间阳性或阴性精神分裂症症状的改善。最后，我们评估了精神分裂症的一个关键电生理内表型，即感觉运动门控。通过前脉冲抑制测量，TCF4 rs9960767 的精神分裂症风险等位基因 C 降低了感觉运动门控。这表明 TCF4 影响信息处理的关键机制，这可能有助于精神分裂症的发病机制。
