电休克治疗用于精神分裂症的激越症状:随机对照试验的meta分析（英文）

背景:躁动在精神分裂症治疗中是一个重大挑战。电休克疗法(ECT)对各种精神疾病是一种快速、有效、和安全的治疗,但ECT对精神分裂症的躁动治疗的相关meta分析还尚未报道。目标:系统地评估单一使用ECT或ECT合并使用其他抗精神病药物(APs)的对精神分裂症的躁动治疗的有效性和安全性。方法:进行随机对照试验(RCT)的系统文献搜索。两名独立评估者筛选研究、提取结果数据与现有数据的安全性、进行质量评估和数据合成。采用建议、评估、开发、和评价的工作组等级(GRADE)来判断主要成果的证据的总体水平。结果:一共确定了中国有七个RCTs,包括ECT单一使用(4个RCTs有5个治疗组,n=240)和ECT-APs合并使用(3个RCTs,n=240)。研究对象平均年龄34.3(4.5)岁,平均治疗时间为4.3(3.1)周。所有7个RCTs非盲法,并且根据Jadad量表7项RCTs均被评为低质量。样本的Meta分析发现与APs单一治疗相比,单一使用ECT或ECT-APs合并使用阳性和阴性症状量表(PANSS)的躁动子因子评分改善均无显著性差异(ECT单一使用:weighted mean difference(WMD)=-0.90,95%confidence interval(CI):(-2.91,1.11),p=0.38;ECT-APs合并使用:WMD=-1.34,(95%CI:-4.07,1.39),p=0.33)。然而,PANSS总分(WMD=-7.13,I^2=0%,p=0.004)和兴奋子因子评分(WMD=-1.97,p<0.0001)、ECT治疗14天后的PANSS总分(WMD=-7.13,I^2=0%,p=0.004)和第7天和第14天的兴奋子因子评分(WMD=-1.97to-1.92,p=0.002 to 0.0001)均显示单一使用ECT优于APs单一治疗。ECT-APs合并治疗结束时(WMD=-10.40,p=0.03)和治疗后7天(WMD=-5.01,p=0.02)的PANSS总分显示均优于APs单药治疗。头痛(p=0.0001,number-needed-to-harm(NNH)=3,95%CI=2-4)是唯一的ECT单一治疗后不良反应,并且ECT单一治疗组比APs单药治疗发生的更频繁。根据GRADE方法,主要结果的证据水平被评为"非常低"(37.5%)和"低"(50%)。结论:基于中国7个RCTs合并的数据发现ECT单一治疗或ECT-APs合并治疗在精神分裂症患者的躁动治疗中并没有优势。然而,ECT单一治疗或ECT-APs合并治疗均与PANSS总分减低显著有关。需要高质量的RCTs验证目前的解释。

AB016.Cholinergic enhancement reduces the temporary shift in perceptual eye dominance induced by a few hours of monocular occlusion

Background:A few hours of monocular deprivation with a diffuser eye patch temporarily strengthens the contribution of the deprived eye to binocular vision.This shift in favour of the deprived eye is characterized as a form of adult visual plasticity.Studies in animal and human models suggest that neuromodulators can enhance adult brain plasticity in general.Specifically,acetylcholine has been shown to improve certain aspects of visual function and plasticity in adulthood.We investigated whether a single administration of donepezil(a cholinesterase inhibitor)could further augment the temporary shift in perceptual eye dominance that occurs after two hours of monocular patching.Methods:We conducted three experiments to investigate whether donepezil enhances the shift in perceptual eye dominance induced by monocular patching.In each experiment,healthy adults completed two experimental sessions while taking either donepezil(5 mg,oral)or a placebo(lactose)pill.In experiment 1 we patched the non-dominant eye for 2 hours and measured ocular balance with a binocular phase combination task.In experiment 2 we patched for one hour to investigate whether donepezil shortens the amount of time necessary to observe a shift in ocular dominance.In experiment 3 we patched for 2 hours and measured ocular balance with a binocular rivalry task to see if the effect of donepezil was comparable across the two tasks.We calculated AUCs for the shift in perceptual eye dominance across five time points after removing the patch to compare our treatment conditions in each experiment.Results:Donepezil significantly reduces the magnitude and duration of the shift in perceptual eye dominance produced by both 2(P<0.01)and 1 hours(P<0.05)of monocular patching when measuring ocular balance with a binocular phase combination task.Donepezil also reduces the magnitude of the shift in ocular dominance when measuring balance with a binocular rivalry task.Conclusions:Previous studies have demonstrated that cholinergic potentiation enhances adult brain plasticity.Because of this,we hypothesized donepezil would further augment the strength of the deprived eye after patching.Our study demonstrates that enhanced cholinergic potentiation actually interferes with the consolidation of the perceptual eye dominance plasticity induced by several hours of monocular deprivation.These results contribute to the growing evidence that cholinergic potentiation enhances certain forms of adult brain plasticity at the expense of others.

French Validation of the Screen for Cognitive Impairment in Psychiatry (SCIP-F)

Background: Measuring cognition in clinical practice is clearly essential to the appropriate characterisation of patients’ clinical status and to the development of a personalised care plan. The Screen for Cognitive Impairment in Psychiatry (SCIP) has been developed in order to provide a brief and accessible tool allowing the evaluation of cognitive function in psychiatric conditions. Objective: We present a validation of a French version of the SCIP. Method: Translation from English into French is carried out using the accepted back-translation method. Seventy-two healthy volunteers are characterised by demographic questionnaires and a neuropsychological battery. The French version of the SCIP is then administered on two separate occasions separated by at least a one-week interval. Results: High internal consistencies as well as strong correlations with comparable neuropsychological tests are obtained. A normalised Cronbach’s α = 0.66 is obtained. Conclusions: The French version of the SCIP (SCIP-F) yields results comparable to the English version. The SCIP represents an essential tool for the preliminary evaluation of cognition. Its characteristics, brevity and the lack of need for a technological platform, allow for its integration into clinical practice. Further testing of SCIP-F in various psychiatric conditions will yield valuable information on its potential in clinical settings.

Perspectives on a collaborative Canada-China research program on diagnostic biomarkers for pre-dementia stages of Alzheimer’s disease

As biomarkers are important in the early diagnosis ofAlzheimer’s disease （AD）, the frst collab-orative work of recruiting early-onset familial AD （EO-FAD） families in Canada and China was initiated in 2012. The registration networks have collected hundreds of pedigrees, for which genetic screening, neuropsycholog-ical tests and amyloid and tau imaging was used to study diagnostic biomarkers for preclinical and mild cognitive impairment （MCI） stages of AD. Besides identifying ped-igrees with novel mutations in presenilins （PSENs）/amy-loid precursor protein （APP）, the program has benefted training of Chinese research fellows, AD clinical trials forprevention,the ethical concernsfor clinical fndings, and other collaborative projects with Chinese investiga-tors. Further research of the collaborative program may facilitate the testing and clinical use of novel treatments for EOFAD and late onset AD and contribute to dementia prevention strategies in Canada and China.

Impact of the biological definition of Alzheimer’s disease using amyloid, tau and neurodegeneration (ATN):what about the role of vascular changes,inflammation,Lewy body pathology?

Background:The NIA-AA research framework proposes a biological definition of Alzheimer’s disease,where asymptomatic persons with amyloid deposition would be considered as having this disease prior to symptoms.Discussion:Notwithstanding the fact that amyloid deposition in isolation is not associated with dementia,even the combined association of amyloid and tau pathology does not inevitably need to dementia over age 65.Other pathological factors may play a leading or an accelerating role in age-associated cognitive decline,including vascular small vessel disease,neuroinflammation and Lewy Body pathology.Conclusion:Research should aim at understanding the interaction between all these factors,rather than focusing on them individually.Hopefully this will lead to a personalized approach to the prevention of brain aging,based on individual biological,genetic and cognitive profiles.

Therapeutic response in children with ADHD: role of observers and settings

Background This study aims at characterizing the extent of correlation of treatment response (TR) obtained in various observation settings (home,school,clinic) by different observers (parents,teachers,clinicians).Methods Children with attention deficit hyperactivity disorder (ADHD) underwent a 2-week double-blind,randomized,cross-over clinical trial with methylphenidate and placebo,and various measures were obtained during the 2 weeks.Interrelationships of TR were examined using Pearson's correlation coefficients.Results The study included 526 children (420 male,106 female) with ADHD.TR between different observers shows a variable correlation between parents and teachers.No correlation is seen between parents/teacher evaluation of TR and laboratory-based measures (Continuous Performance Task;Restricted Academic Situation Scale).Conclusion The results firmly support the need to synthesize information from many sources in evaluating TR in ADHD.

In vivo tracking of tau pathology using positron emission tomography (PET) molecular imaging in small animals

Hyperphosphorylation of the tau protein leading to the formation of neurofibrillary tangles(NFTs)is a common feature in a wide range of neurodegenerative diseases known as tauopathies,which include Alzheimer’s disease(AD)and the frontotemporal dementias(FTDs).Although heavily investigated,the mechanisms underlying the pathogenesis and progression of tauopathies have yet to be fully understood.In this context,several rodent models have been developed that successfully recapitulate the behavioral and neurochemical features of tau pathology,aiming to achieve a better understanding of the link between tau and neurodegeneration.To date,behavioral and biochemical parameters assessed using these models have been conducted using a combination of memory tasks and invasive methods such as cerebrospinal fluid(CSF)sampling or post-mortem analysis.Recently,several novel positron emission tomography(PET)radiopharmaceuticals targeting tau tangles have been developed,allowing for non-invasive in vivo quantification of tau pathology.Combined with tau transgenic models and micro-PET,these tracers hold the promise of advancing the development of theoretical models and advancing our understanding of the natural history of AD and non-AD tauopathies.In this review,we briefly describe some of the most important insights for understanding the biological basis of tau pathology,and shed light on the opportunity for improved modeling of tau pathology using a combination of tau-radiopharmaceuticals and animal models.