Devenney Emma M, Landin-Romero Ramon, Irish Muireann, Hornberger Michael, Mioshi Eneida, Halliday Glenda M, Kiernan Matthew C, Hodges John R
Neuroscience Research Australia, Barker Street, Sydney, NSW 2031, Australia; University of New South Wales, Sydney, NSW 2031, Australia; Brain and Mind Research Institute, Camperdown, Sydney, NSW 2050, Australia; ARC Centre of Excellence in Cognition and its Disorders, Macquarie University, Sydney, NSW 2109, Australia.
Neuroscience Research Australia, Barker Street, Sydney, NSW 2031, Australia; University of New South Wales, Sydney, NSW 2031, Australia; ARC Centre of Excellence in Cognition and its Disorders, Macquarie University, Sydney, NSW 2109, Australia.
Neuroimage Clin. 2016 Dec 2;13:439-445. doi: 10.1016/j.nicl.2016.11.028. eCollection 2017.
This present study aims to address the gap in the literature regarding the severity and underlying neural correlates of psychotic symptoms in frontotemporal dementia with and without the gene expansion.
Fifty-six patients with behavioural variant frontotemporal dementia (20 with concomitant amyotrophic lateral sclerosis) and 23 healthy controls underwent neuropsychological assessments, detailed clinical interview for assessment of psychosis symptoms, brain MRI and genetic testing. Carers underwent a clinical interview based upon the neuropsychiatric inventory. Patients were assessed at ForeFront, the Frontotemporal Dementia Research Group at Neuroscience Research Australia or at the Brain and Mind Centre, between January 2008 and December 2013. An index of psychosis was calculated, taking into account the degree and severity of psychosis in each case. Voxel-based morphometry analyses were used to explore relationships between the psychosis index and grey matter changes.
Thirty-four percent of frontotemporal dementia patients showed psychotic features. expansion cases were more likely to exhibit psychotic symptoms than non-carriers (64% vs. 26%; = 0.006), which were also more severe (psychotic index 23.1 vs. 8.1; = 0.002). Delusions comprised persecutory, somatic, jealous and grandiose types and were present in 57% of carriers and 19% of non-carriers ( = 0.006). Auditory, visual or tactile hallucinations were present in 36% of carriers and 17% of non-carriers ( = 0.13). Increased psychotic symptoms in expansion carriers correlated with atrophy in a distributed cortical and subcortical network that included discrete regions of the frontal, temporal and occipital cortices, as well as the thalamus, striatum and cerebellum.
This study underlines the need to consider and assess for psychotic symptoms in the frontotemporal dementia-amyotrophic lateral sclerosis continuum particularly in those with gene expansions. The network of brain regions identified in this study is strikingly similar to that identified in other psychotic disorders such as schizophrenia, which suggests that treatment strategies in psychiatry may be beneficial for the management of psychotic symptoms in frontotemporal dementia.
本研究旨在填补文献中关于伴有或不伴有该基因扩增的额颞叶痴呆中精神症状的严重程度及潜在神经关联方面的空白。
56例行为变异型额颞叶痴呆患者（20例伴有肌萎缩侧索硬化）和23名健康对照者接受了神经心理学评估、用于评估精神症状的详细临床访谈、脑部磁共振成像及基因检测。照料者接受了基于神经精神科问卷的临床访谈。患者于2008年1月至2013年12月期间在澳大利亚神经科学研究所的额颞叶痴呆研究组ForeFront或脑与心智中心接受评估。计算了一个精神病指数，该指数考虑了每个病例中精神病的程度和严重程度。基于体素的形态学分析用于探究精神病指数与灰质变化之间的关系。
34%的额颞叶痴呆患者表现出精神症状特征。基因扩增病例比非携带者更易出现精神症状（64%对26%；P = 0.006），且症状也更严重（精神病指数23.1对8.1；P = 0.002）。妄想包括被害妄想、躯体妄想、嫉妒妄想和夸大妄想，57%的基因扩增携带者和19%的非携带者存在妄想（P = 0.006）。36%的基因扩增携带者和17%的非携带者存在听幻觉、视幻觉或触幻觉（P = 0.13）。基因扩增携带者中精神症状增加与包括额叶、颞叶和枕叶皮质的离散区域以及丘脑、纹状体和小脑在内的分布式皮质和皮质下网络萎缩相关。
本研究强调了在额颞叶痴呆 - 肌萎缩侧索硬化连续体中需要考虑并评估精神症状，尤其是在那些有该基因扩增的患者中。本研究中确定的脑区网络与在其他精神障碍如精神分裂症中确定的网络惊人地相似，这表明精神病学中的治疗策略可能有助于管理额颞叶痴呆中的精神症状。
