5-HT3 receptor influences the washing phenotype and visual organization in obsessive-compulsive disorder supporting 5-HT3 receptor antagonists as novel treatment option

A role of the HTR3A-E genes in obsessive-compulsive disorder (OCD) can be expected based on promising effects of 5-HT3 receptor antagonists as adjunctive treatment of OCD. We therefore genotyped six common coding or promoter variants within the HTR3A-E genes in a case-control-sample consisting of N=236 OCD patients and N=310 control subjects and in N=58 parent–child-trios. Given the heterogeneous OCD phenotype, we also investigated OCD symptom dimensions and cognitive endophenotypes in subsamples. OCD patients scoring high for the washing subtype were significantly more likely to carry the c.256G-allele of the HTR3E variant rs7627615 (p=0.0001) as compared to OCD patients low for this symptom dimension. Visual organization was impaired in OCD patients and unaffected relatives as compared to healthy control subjects and carriers of the HTR3E c.256G/c.256G-genotype performed significantly worse (p=0.007). The case-control analyses revealed a nominal significant association of the HTR3D variant rs1000592 (p.H52R) with OCD (p=0.029) which was also evident after combination of the case-control and the trio-results (p=0.024). In male subjects, the variant rs6766410 (p.N163K) located in the HTR3C was significantly associated with OCD (p=0.007). The association findings of the HTR3C and the HTR3E remained significant after correction for the number of variants investigated. These findings indicate a role of common variants of the HTR3A-E genes in OCD and OCD-related phenotypes and further support the use of 5-HT3 receptor antagonists as novel treatment options. The HTR3E gene is a novel candidate gene impacting on the individual expression of OC symptoms and OCD-related cognitive dysfunction.     

内化心理障碍患者错误相关负波的对照研究

目的 探讨内化心理障碍患者错误相关负波特征和诊断价值.方法 从门诊和住院患者中筛选符合DSM-Ⅳ焦虑或抑郁障碍患者55人（内化障碍组）,选择正常对照20人（对照组）.以Eriksen任务和Simon任务作为诱发刺激,应用加拿大Stellate-64导EEG/ERP分析仪和BESA5.2软件获取错误相关负波（ERN）,同时收集一般资料、临床症状、反应时和错误率等行为资料.结果 （1）在Eriksen任务和Si-mon任务上,内化障碍组正确反应时[（377.5±98.8）ms]和错误反应时[（337.3±96.6） ms]显著长于对照组[（288.5±105.9） ms和（281.9±94.3） ms],其它指标组间差异无统计学意义（P＞0.05）;（2）内化障碍组Eriksen任务6个位点的ERN波幅[（Fz=（4.97±5.74） μV,F3=（5.50±4.59） μV,F4=（6.26±6.79） μV,Cz=（4.74±5.51） μV,C3=（5.44±4.80） μV,C4=（5.50±5.28） μV]均显著大于对照组[（1.17±1.47） μV,（2.22±3.95） μV,（3.40±2.55） μV,（2.28± 1.41） μV,（3.05±2.47） μV,（3.16± 2.51） μμV],在Simon任务中仅Fz位点[（5.43±6.61） μV]和F4位点[（6.00±5.50） μV]的ERN波幅显著大于对照组[（2.05±2.34） μV,（3.09±2.86） μV],其它位点组间差异无统计学意义（P＞0.05）;（3）内化障碍组Simon任务Fz和F4位点ERN潜伏期[（87.6±34.4） ms和（84.9± 34.8） ms]显著长于对照组[（54.0±46.5） ms和（36.3±42.4） ms],其它位点组间差异无统计学意义（P＞0.05）.结论 内化心理障碍患者错误相关负波增大,提示患者存在内部错误监控缺陷,ERN可能是内化心理障碍的内表型指标.     

Eye-voice span during rapid automatized naming: evidence of reduced automaticity in individuals with autism spectrum disorder and their siblings

Background

Individuals with autism spectrum disorder (ASD) and their parents demonstrate impaired performance in rapid automatized naming (RAN), a task that recruits a variety of linguistic and executive processes. Though the basic processes that contribute to RAN differences remain unclear, eye-voice relationships, as measured through eye tracking, can provide insight into cognitive and perceptual processes contributing to RAN performance. For example, in RAN, eye-voice span (EVS), the distance ahead the eyes are when articulation of a target item''s label begins, is an indirect measure of automaticity of the processes underlying RAN. The primary objective of this study was to investigate automaticity in naming processes, as indexed by EVS during RAN. The secondary objective was to characterize RAN difficulties in individuals with ASD and their siblings.

Methods

Participants (aged 15–33 years) included 21 individuals with ASD, 23 siblings of individuals with ASD, and 24 control subjects, group-matched on chronological age. Naming time, frequency of errors, and EVS were measured during a RAN task and compared across groups.

Results

A stepwise pattern of RAN performance was observed, with individuals with ASD demonstrating the slowest naming across all RAN conditions, controls demonstrating the fastest naming, and siblings demonstrating intermediate performance. Individuals with ASD exhibited smaller EVSs than controls on all RAN conditions, and siblings exhibited smaller EVSs during number naming (the most highly automatized type of naming). EVSs were correlated with naming times in controls only, and only in the more automatized conditions.

Conclusions

These results suggest that reduced automaticity in the component processes of RAN may underpin differences in individuals with ASD and their siblings. These findings also provide further support that RAN abilities are impacted by genetic liability to ASD. This study has important implications for understanding the underlying skills contributing to language-related deficits in ASD.     

Are Brain Responses to Emotion a Reliable Endophenotype of Schizophrenia? An Image-Based Functional Magnetic Resonance Imaging Meta-analysis

BackgroundImpaired emotion processing constitutes a key dimension of schizophrenia and a possible endophenotype of this illness. Empirical studies consistently report poorer emotion recognition performance in patients with schizophrenia as well as in individuals at enhanced risk of schizophrenia. Functional magnetic resonance imaging studies also report consistent patterns of abnormal brain activation in response to emotional stimuli in patients, in particular, decreased amygdala activation. In contrast, brain-level abnormalities in at-risk individuals are more elusive. We address this gap using an image-based meta-analysis of the functional magnetic resonance imaging literature.MethodsFunctional magnetic resonance imaging studies investigating brain responses to negative emotional stimuli and reporting a comparison between at-risk individuals and healthy control subjects were identified. Frequentist and Bayesian voxelwise meta-analyses were performed separately, by implementing a random-effect model with unthresholded group-level T-maps from individual studies as input.ResultsIn total, 17 studies with a cumulative total of 677 at-risk individuals and 805 healthy control subjects were included. Frequentist analyses did not reveal significant differences between at-risk individuals and healthy control subjects. Similar results were observed with Bayesian analyses, which provided strong evidence for the absence of meaningful brain activation differences across the entire brain. Region of interest analyses specifically focusing on the amygdala confirmed the lack of group differences in this region.ConclusionsThese results suggest that brain activation patterns in response to emotional stimuli are unlikely to constitute a reliable endophenotype of schizophrenia. We suggest that future studies instead focus on impaired functional connectivity as an alternative and promising endophenotype.     

特应性皮炎的临床表型和内表型

【摘要】 特应性皮炎患者的临床表型及内表型多样，明确不同临床表型及内表型的特征，对协助诊断并实施针对性治疗有重要意义。本文从特应性皮炎不同发病年龄、种族背景及疾病严重程度等方面综述其临床表型差异，概述内表型及相关生物标志物的临床意义。     

Priming Deficiency in Male Subjects at Risk for Alcoholism: The N4 During a Lexical Decision Task

Background:  While there is extensive literature on the relationship between the P3 component of event-related potentials (ERPs) and risk for alcoholism, there are few published studies regarding other potentially important ERP components. One important candidate is the N4(00) component in the context of semantic processing, as abnormalities in this component have been reported for adult alcoholics.
Method:  A semantic priming task was administered to nonalcohol dependent male offspring (18 to 25 years) of alcoholic fathers [high risk (HR) n  = 23] and nonalcoholic fathers [low risk (LR) n  = 28] to study whether the 2 groups differ in terms of the N4 component. Subjects were presented with 150 words and 150 nonwords. Among the words, 50 words (primed) were preceded by their antonyms (prime, n  = 50), whereas the remaining 50 words were unprimed. For the analysis, N4 amplitude and latency as well as behavioral measures for the primed and unprimed words were considered.
Results:  A significant interaction effect was observed between semantic condition and group, where HR subjects did not show N4 attenuation for primed stimuli.
Conclusion:  The lack of N4 attenuation to primed stimuli and/or inability to differentiate between primed and unprimed stimuli, without latency and reaction time being affected, suggest deficits in semantic priming, especially in semantic expectancy and/or postlexical semantic processing in HR male offspring. Further, it indicates that it might be an electrophysiological endophenotype that reflects genetic vulnerability to develop alcoholism.     

Performance monitoring is altered in adult ADHD: A familial event-related potential investigation

Background

Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder that starts in childhood and frequently persists in adults. Electrophysiological studies in children with ADHD provide evidence for abnormal performance monitoring processes and familial association of these processes with ADHD. It is not yet known whether these processes show the same abnormalities and familial effects in adults.

Method

We investigated event-related potential (ERP) indices of performance monitoring in adults with ADHD compared to age matched control participants. We subsequently investigated whether the ERP indices showed a familial association with ADHD by investigating these processes in first degree relatives of children with ADHD. This was achieved using an arrow flanker task presented to 21 adults with ADHD, 20 fathers of children with ADHD and 20 control participants.

Results

Compared to the control group, both adults with ADHD and fathers of children with ADHD displayed significantly weaker error and conflict monitoring, as indexed by the smaller error negativity (Ne) and the N2 components. These two components were highly correlated within each of the three groups (r = 0.53–0.65). The groups did not differ on the error positivity (Pe).

Conclusions

These findings closely resemble those previously found in children with ADHD, suggesting that conflict monitoring and early error processing are also abnormal in adults with ADHD; and share familial influences with ADHD throughout the lifespan. The relationship between different indices of performance monitoring may suggest partly common underlying mechanisms or modulators.     

Neural representation of reward in recovered depressed patients

Introduction  Anhedonia, a loss of interest and pleasure in normally rewarding stimuli, is a key diagnostic criterion for major depression. It has been suggested that deficits in the processing of reward-relevant stimuli could represent an endophenotype for depression. We hypothesized that people at risk of depression by virtue of a personal history of the illness would show impaired neural responses to a primary rewarding stimulus. Materials and methods  Using functional magnetic resonance imaging, we measured the neural response to the sight and flavor of chocolate, and their combination, in 13 unmedicated recovered patients with a history of major depression and 14 healthy controls matched for age and gender. We also examined a control aversive condition consisting of the sight of moldy strawberries and a corresponding unpleasant taste. Participants simultaneously recorded subjective ratings of “pleasantness,” “intensity,” and “wanting.” Results and discussion  Despite no differences between the groups in stimulus ratings, patients showed decreased neural responses to the pleasant stimulus in the ventral striatum and increases in the caudate nucleus to the aversive stimulus. Furthermore, patients had a diminished neural supralinearity response (the potentiation produced by simultaneous presentation of the sight and flavor of the stimuli) in the prefrontal cortex for both aversive and pleasant conditions. Patients recovered from depression appear to have deficits in the neural basis of reward and may also have impairments in the cross-modal integration of sensory stimuli. Conclusion  These findings support the view that abnormal neural responses to reward may be an endophenotype for depression and a potential target for intervention and prevention strategies.