Dementia Research Centre, UCL Institute of Neurology, University College London, London, UK.
Alzheimers Res Ther. 2012 Aug 13;4(5):42. doi: 10.1186/alzrt145. eCollection 2012.
An expanded hexanucleotide repeat in the C9ORF72 gene has recently been identified as an important cause of frontotemporal dementia and motor neuron disease; however, the phenotypic spectrum of this entity and its pathophysiologic basis have yet to be fully defined. Psychiatric features may be early and prominent, although a putative cortico-thalamo-cerebellar network has been implicated in the pathogenesis of the clinical phenotype. Differentiation of self from others is a core cognitive operation that could potentially link network disintegration with neuropsychiatric symptoms in C9ORF72-associated frontotemporal dementia.
We undertook a detailed behavioral analysis of self-other attribution in a 67-year-old male patient with behavioral variant frontotemporal dementia (bvFTD) due to the C9ORF72 expansion by using a novel paradigm requiring differentiation of the effects of self- and non-self-generated actions. The patient's performance was assessed in relation to two older male patients with bvFTD not attributable to the C9ORF72 expansion and four healthy older male subjects.
Compared with the healthy control group, the patient with the C9OFR72 mutation showed a deficit of self-other differentiation that was disproportionate to his otherwise relatively indolent clinical phenotype. The performance of the other patients with bvFTD was similar to that of healthy subjects.
We propose that impaired self-other differentiation is a candidate mechanism for neuropsychiatric decline in association with the C9ORF72 expansion. We offer this preliminary observation as a stimulus to further work.
最近，C9ORF72 基因中的六核苷酸重复扩增被确定为额颞叶痴呆和运动神经元病的重要病因；然而，该实体的表型谱及其病理生理基础尚未完全确定。精神症状可能是早期和突出的，尽管皮质-丘脑-小脑网络被认为与临床表型的发病机制有关。自我与他人的区分是一种核心认知操作，它可能将网络解体与 C9ORF72 相关额颞叶痴呆的神经精神症状联系起来。
我们通过使用一种需要区分自我和非自我产生的动作的影响的新范式，对一位 67 岁的男性患者（由于 C9ORF72 扩展而患有行为变异额颞叶痴呆 bvFTD）进行了自我与他人归因的详细行为分析。我们评估了该患者的表现与两位归因于 C9ORF72 扩展之外的 bvFTD 患者和四位健康的老年男性进行了比较。
与健康对照组相比，C9OFR72 突变患者的自我与他人区分缺陷与其相对惰性的临床表型不成比例。其他 bvFTD 患者的表现与健康受试者相似。
我们提出，自我与他人区分的受损是与 C9ORF72 扩展相关的神经精神下降的候选机制。我们提供这一初步观察结果作为进一步研究的动力。
