Multiple brain networks support processing speed abilities of patients with multiple sclerosis

Objectives: Many people affected by multiple sclerosis (MS) experience cognitive impairment, especially decreases in information processing speed (PS). Neural disconnection is thought to represent the neural marker of this symptom, although the role played by alterations of specific functional brain networks still remains unclear. The aim is to investigate and compare patterns of association between PS-demanding cognitive performance and functional connectivity across two MS phenotypes.

Methods: Forty patients with relapsing-remitting MS (RRMS) and 25 with secondary progressive MS (SPMS) had neuropsychological and MRI assessments. Multiple regression models were used to investigate the relationship between performance on tests of visuomotor and verbal PS, and on the verbal fluency tests, and functional connectivity of four cognitive networks, i.e. left and right frontoparietal, salience and default-mode, and two control networks, i.e. visual and sensorimotor.

Results: Patients with SPMS were older and had longer disease history than patients with RRMS and presented with worse overall clinical conditions: higher disease severity, total lesion volume, and cognitive impairment rates. However, in both patient samples, cognitive performance across tests was negatively correlated with functional connectivity of the salience and default-mode networks, and positively with connectivity of the left frontoparietal network. Only the visuomotor PS scores of the RRMS group were also associated with connectivity of the sensorimotor network.

Conclusions: PS-demanding cognitive performance in patients with MS appears mainly associated with strength of functional connectivity of frontal networks involved in the evaluation and manipulation of information, as well as the default mode network. These results are in line with the hypothesis that multiple neural networks are needed to support normal cognitive performance across MS phenotypes. However, different PS measures showed partially different patterns of association with functional connectivity. Therefore, further investigations are needed to clarify the contribution of inter-network communication to specific cognitive deficits due to MS.     

Cognitive, language and social-cognitive skills of individuals with fragile X syndrome with and without autism

Background It is not known whether those with co‐morbid fragile X syndrome (FXS) and autism represent a distinct subtype of FXS; whether the especially severe cognitive delays seen in studies of young children with co‐morbid FXS and autism compared with those with only FXS continue into adolescence and young adulthood; and whether autism in those with FXS is ‘true autism’, i.e. reflects the same underlying problems as idiopathic autism. Method We compared the non‐verbal IQ of adolescents and young adults with co‐morbid FXS and autism (n = 10) with those with only FXS (n = 44). We then created a subsample of those with FXS only, matched on non‐verbal IQ, mental age and gender (n = 21) to the subsample of those with co‐morbid FXS and autism. We compared the two groups on measures of expressive language, receptive language (lexical, grammatical morphology and syntactic patterns), and a theory of mind task. Results Those with co‐morbid FXS and autism had lower non‐verbal IQs than those with only FXS. The participants with co‐morbid FXS and autism did not perform as well as the cognitive ability‐ and gender‐matched participants with only FXS on the three measures of receptive language or the theory of mind task; there were no differences on the expressive language measure. Conclusions Our findings support the notion that those with co‐morbid FXS and autism represent a distinct subtype of FXS, with more impairment in receptive language and theory of mind even when controlling for their lower non‐verbal IQ relative to those with only FXS. The greater cognitive impairments observed in those with co‐morbid FXS and autism continues into adolescence and young adulthood; and the autism seen in those with FXS appears to be the same as idiopathic autism.     

基于两样本孟德尔随机化方法探讨睡眠与痛风的关联

[目的] 通过两样本孟德尔随机化设计,探讨睡眠与痛风之间的关联。[方法] 从一项包含763 813名参与者的全基因组关联研究(genome-wide association study,GWAS)中获取痛风遗传关联数据。以与打鼾、睡眠时间、睡眠类型、失眠及白日困倦程度等睡眠表型相关的单核苷酸多态性(single nucleotide polymorphism,SNP)作为工具变量,采用逆方差加权(inverse variance weighted,IVW)评估遗传学预测的不同睡眠表型与痛风发生风险的关系。采用MR-Egger回归和孟德尔随机多态性残差和离群值(MR pleiotropy residual sum and outlier,MR-PRESSO)检验进行敏感性分析,以评估工具变量的多效性。进一步采用加权中位数法、简单中位数法、最大似然比法等分析方法检验结果的稳健性与可靠性。[结果] IVW结果显示,遗传学预测的打鼾[优势比(odds ratio,OR)=3.12,95%置信区间(confidence interval,CI)(1.21～8.05),PFDR=0.045]和失眠[OR=1.09,95%CI(1.04～1.15),PFDR=0.005]与痛风发生风险呈正相关,而睡眠时间、睡眠类型及白日困倦程度与痛风发生之间不存在统计学关联。MR-Egger回归提示上述因果关联未受到水平多效性影响,加权中位数法、简单中位数法、最大似然比法得出与IVW相似的结果。[结论] 打鼾、失眠与痛风发生风险呈正相关,纠正打鼾和失眠可能对痛风有一定的预防作用。     

Abnormalities of the executive control network in multiple sclerosis phenotypes: An fMRI effective connectivity study

The Stroop interference task is a cognitively demanding task of executive control, a cognitive ability that is often impaired in patients with multiple sclerosis (MS). The aim of this study was to compare effective connectivity patterns within a network of brain regions involved in the Stroop task performance between MS patients with three disease clinical phenotypes [relapsing‐remitting (RRMS), benign (BMS), and secondary progressive (SPMS)] and healthy subjects. Effective connectivity analysis was performed on Stroop task data using a novel method based on causal Bayes networks. Compared with controls, MS phenotypes were slower at performing the task and had reduced performance accuracy during incongruent trials that required increased cognitive control. MS phenotypes also exhibited connectivity abnormalities reflected as weaker shared connections, presence of extra connections (i.e., connections absent in the HC connectivity pattern), connection reversal, and loss. In SPMS and the BMS groups but not in the RRMS group, extra connections were associated with deficits in the Stroop task performance. In the BMS group, the response time associated with correct responses during the congruent condition showed a positive correlation with the left posterior parietal → dorsal anterior cingulate connection. In the SPMS group, performance accuracy during the congruent condition showed a negative correlation with the right insula → left insula connection. No associations between extra connections and behavioral performance measures were observed in the RRMS group. These results suggest that, depending on the phenotype, patients with MS use different strategies when cognitive control demands are high and rely on different network connections. Hum Brain Mapp, 37:2293–2304, 2016. © 2016 Wiley Periodicals, Inc.     

睡眠性状与肠易激综合征的孟德尔随机化研究

目的 采用孟德尔随机化(MR)方法探索睡眠性状与肠易激综合征(IBS)的因果关系。方法 利用大规模全基因组关联研究汇总数据和芬兰生物银行数据(FinnGen),选择相互独立且与睡眠性状密切相关的遗传位点作为工具变量,通过逆方差加权法(MR-IVW)、加权中位数法、简单中位数法、稳健的调整轮廓评分法、MR多效性残差和与异质性法(MR-PRESSO)等MR方法,以比值比(OR值)作为评价指标对睡眠性状与IBS的因果关系进行探讨。结果 MR-IVW结果显示,过短睡眠和失眠分别导致IBS发病风险增高147%(OR=2.47, 95%CI:1.13～5.41)和18%(OR=1.18, 95%CI:1.14～1.22),早起型睡眠习惯会导致IBS发病风险降低12%(OR=0.88, 95%CI:0.84～0.92)。外部数据验证结果显示,仅失眠与IBS发病风险的关联有统计学意义(P<0.001)。多变量MR方法校正相关协变量后,失眠与IBS的关联效应仍有统计学意义(P<0.001)。结论 过短睡眠和失眠会增加IBS的发病风险。     

Dysbindin gene (DTNBP1) in major depressive disorder (MDD) patients: Lack of association with clinical phenotypes

Abstract

Objectives. Dystrobrevin binding protein 1 (Dysbindin) is a plausible candidate gene for major depressive disorders (MDD) due to its involvement in synaptic signaling, plasticity and localization in the brain. Methods. Two intronic SNPs of DTNBP1; rs760761 (P1320) and rs2619522 (P1763) were analyzed in 206 patients with DSM-IV MDD to investigate the functional impact of genotypes on susceptibility for depression and some clinical phenotypes. The Sequenom iPLEX assay (Sequenom, Cambridge, MA) was used for genotyping. Results and Conclusions. Despite the limited power of analysis, our results showed that these two SNPs in DTNPB1 gene were not related to clinical phenotypes such as melancholia, age at onset, suicidality and co-morbid anxiety disorders, as well as to treatment response phenotypes.     

Prediction of linkage phase by parental phenotypes

This paper answers the question as to which parental phenotypes are useful in prediction of the linkage phase of the progeny under conditions of linkage equilibrium. I demonstrate that (1) the parents with the same disease status or marker genotype carry no information about phase of the diheterozygous offspring; (2) the linkage phase can be inferred unambiguously only under recessive or dominant control of disease. In any other situations, only the probability of linkage phase is inferred. It has been shown that the relative difference between the probabilities of coupling phase and repulsion phase, ζ, which is regarded as a measure of accuracy of linkage phase prediction by parental phenotypes, is the same in all informative crosses and is dependent on the genetic model of the disease. Furthermore, ζ is the same for the di- and polyallelic marker genes. © 1996 Wiley-Liss, Inc.