Response inhibition is essential for navigating everyday life. Its derailment is considered integral to numerous neurological and psychiatric disorders, and more generally, to a wide range of behavioral and health problems. Response-inhibition efficiency furthermore correlates with treatment outcome in some of these conditions. The stop-signal task is an essential tool to determine how quickly response inhibition is implemented. Despite its apparent simplicity, there are many features (ranging from task design to data analysis) that vary across studies in ways that can easily compromise the validity of the obtained results. Our goal is to facilitate a more accurate use of the stop-signal task. To this end, we provide 12 easy-to-implement consensus recommendations and point out the problems that can arise when they are not followed. Furthermore, we provide user-friendly open-source resources intended to inform statistical-power considerations, facilitate the correct implementation of the task, and assist in proper data analysis.

Individuals who are at risk for autosomal dominant polycystic kidney disease are often screened by ultrasound using diagnostic criteria derived from individuals with mutations in PKD1. Families with mutations in PKD2 typically have less severe disease, suggesting a potential need for different diagnostic criteria. In this study, 577 and 371 at-risk individuals from 58 PKD1 and 39 PKD2 families, respectively, were assessed by renal ultrasound and molecular genotyping. Using sensitivity data derived from genetically affected individuals and specificity data derived from genetically unaffected individuals, various diagnostic criteria were compared. In addition, data sets were created to simulate the PKD1 and PKD2 case mix expected in practice to evaluate the performance of diagnostic criteria for families of unknown genotype. The diagnostic criteria currently in use performed suboptimally for individuals with mutations in PKD2 as a result of reduced test sensitivity. In families of unknown genotype, the presence of three or more (unilateral or bilateral) renal cysts is sufficient for establishing the diagnosis in individuals aged 15 to 39 y, two or more cysts in each kidney is sufficient for individuals aged 40 to 59 y, and four or more cysts in each kidney is required for individuals Ն60 yr. Conversely, fewer than two renal cysts in at-risk individuals aged Ն40 yr is sufficient to exclude the disease. These unified diagnostic criteria will be useful for testing individuals who are at risk for autosomal dominant polycystic kidney disease in the usual clinical setting in which molecular genotyping is seldom performed.

No abstract

We conclude that cigarette smoke decreases the expression of CFTR gene, protein, and function in vitro and that acquired CFTR deficiency occurs in the nasal respiratory epithelium of cigarette smokers. We suggest that acquired CFTR deficiency may contribute to the physiopathology of cigarette-induced diseases such as chronic bronchitis.

Response inhibition, defined as the ability to withhold a response, is considered to be a core deficit in various mental illnesses. Measures of response inhibition have been used to define functional deficits, as markers of genetic risk, in neuroimaging studies, and for diagnostic purposes in these disorders. However, the magnitude of the deficit across psychopathologies has not been systematically assessed. We conducted a systematic review and meta-analysis of performance on commonly used measures of the ability to withhold a response: go/no-go task, Conners' continuous performance task (CCPT), and sustained attention to response task (SART). The primary variable of interest in each of these tasks was commission errors (CE), which provides an index of one's ability to correctly withhold a response. In addition, we examined omission errors (OE) which are an index of sustained attention; and mean reaction time (RT; MRT). Three-hundred and 18 studies in 11 different psychiatric disorders met inclusion criteria. Weighted mean effect sizes (ESs) were calculated to measure the magnitude of the deficit. In general, we found low-to-medium ESs for commission errors ranging from g = -0.10 for anxiety disorder to medium ESs of g = 0.52 for bipolar disorder. Small-to-medium deficits in withholding were found in various disorders. Results indicate that deficits in withholding are insufficiently sensitive or specific to be used individually as a diagnostic measure or biomarker in most disorders.

Endophenotypes or intermediate phenotypes are of great interest in neuropsychiatric genetics because of their potential for facilitating gene discovery. We evaluated response inhibition, latency and variability measures derived from the stop task as endophenotypes of ADHD by testing whether they were related to ADHD traits in the general population, heritable and shared genetic risk with ADHD traits. Participants were 16,099 children and adolescents, ages 6 to 18 years who visited a local science center. We measured ADHD traits using the Strengths and Weaknesses of ADHD-symptoms and Normal-Behavior (SWAN) rating scale and performance on the stop signal task (SST)—response inhibition (SSRT), response latency (GoRT), and response variability (GoRTSD). Regression analysis was used to assess the relationship of cognitive measures and ADHD traits while controlling for family, age, sex, ethnicity, socioeconomic status and treatment status. Heritability of ADHD and cognitive traits was estimated using SOLAR in 7,483 siblings from 3,507 families that included multiple siblings. Bivariate relationships between pairs of variables were examined. Individuals with greater ADHD trait scores had worse response inhibition, slower response latency, and greater variability. Younger participants and girls had inferior performance although the gender effects were minimal and evident in youngest participants. Inhibition, latency, variability, total ADHD traits, inattention and hyperactivity-impulsivity scores were significantly heritable. ADHD traits and inhibition, but not latency or variability were coheritable. In the largest study in the general population, we found support for the validity of response inhibition as an endophenotype of ADHD.Electronic supplementary materialThe online version of this article (doi:10.1007/s10802-012-9693-9) contains supplementary material, which is available to authorized users.

Duchenne muscular dystrophy is a progressive neuromuscular condition that has a high rate of cognitive and learning disabilities as well as neurobehavioral disorders, some of which have been associated with disruption of dystrophin isoforms. Retrospective cohort of 59 boys investigated the cognitive and neurobehavioral profile of boys with Duchenne muscular dystrophy. Full-scale IQ of < 70 was seen in 27%; learning disability in 44%, intellectual disability in 19%; attention-deficit/hyperactivity disorder in 32%; autism spectrum disorders in 15%; and anxiety in 27%. Mutations affecting Dp260 isoform and 5'untranslated region of Dp140 were observed in 60% with learning disability, 50% intellectual disability, 77% with autism spectrum disorders, and 94% with anxiety. No statistically significant correlation was noted between comorbidities and dystrophin isoforms; however, there is a trend of cumulative loss of dystrophin isoforms with declining full-scale IQ. Enhanced psychology testing to include both cognitive and neurobehavioral disorders is recommended for all individuals with Duchenne muscular dystrophy.

The aim of this study was to evaluate the construct validity and feasibility of a multidimensional electronic pain diary (e-Ouch(c)) in adolescents with juvenile idiopathic arthritis (JIA). Two descriptive studies with repeated measures were conducted between January and December 2005. Participants were drawn from a large metropolitan rheumatology clinic in a university affiliated pediatric tertiary care centre. In Study 1, 76 adolescents with active arthritis recorded their pain three times a day for 2weeks using the e-Ouch(c). In Study 2, 36 adolescents recorded their pain three times a day for 1week before and 2weeks after joint injections. Adolescents in both studies completed multiple measures to determine the construct validity and feasibility of the e-Ouch(c). Adolescents reported mild levels of pain intensity, unpleasantness, and interference as well as stiffness, and mild to moderate levels of fatigue. e-Ouch(c) average weekly pain unpleasantness and interference scores were higher in adolescents with higher pain intensity scores. Correlations between average weekly pain ratings on the e-Ouch(c) and scores from: (a) recalled least, average and worst weekly pain, (b) health-related quality of life and pain coping, and (c) disease activity were as predicted. Pain ratings were significantly lower following joint injections with effect sizes in the low to moderate and moderate to high ranges at the first and second week post-injection, respectively. These findings provide evidence of the construct validity and feasibility of the e-Ouch(c) electronic diary in adolescents with JIA. Use of real-time data capture approaches should be considered in future studies of chronic arthritis.