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Abstract An increasing number of large-scale multi-modal research initiatives has been conducted in the typically developing population, e.g. Dev. Cogn. Neur. 32:43-54, 2018; PLoS Med. 12(3):e1001779, 2015; Elam and Van Essen, Enc. Comp. Neur., 2013, as well as in psychiatric cohorts, e.g. Trans. Psych. 10(1):100, 2020; Mol. Psych. 19:659–667, 2014; Mol. Aut. 8:24, 2017; Eur. Child and Adol. Psych. 24(3):265–281, 2015. Missing data is a common problem in such datasets due to the difficulty of assessing multiple measures on a large number of participants. The consequences of missing data accumulate when researchers aim to integrate relationships across multiple measures. Here we aim to evaluate different imputation strategies to fill in missing values in clinical data from a large (total N = 764) and deeply phenotyped (i.e. range of clinical and cognitive instruments administered) sample of N = 453 autistic individuals and N = 311 control individuals recruited as part of the EU-AIMS Longitudinal European Autism Project (LEAP) consortium. In particular, we consider a total of 160 clinical measures divided in 15 overlapping subsets of participants. We use two simple but common univariate strategies—mean and median imputation—as well as a Round Robin regression approach involving four independent multivariate regression models including Bayesian Ridge regression, as well as several non-linear models: Decision Trees (Extra Trees., and Nearest Neighbours regression. We evaluate the models using the traditional mean square error towards removed available data, and also consider the Kullback–Leibler divergence between the observed and the imputed distributions. We show that all of the multivariate approaches tested provide a substantial improvement compared to typical univariate approaches. Further, our analyses reveal that across all 15 data-subsets tested, an Extra Trees regression approach provided the best global results. This not only allows the selection of a unique model to impute missing data for the LEAP project and delivers a fixed set of imputed clinical data to be used by researchers working with the LEAP dataset in the future, but provides more general guidelines for data imputation in large scale epidemiological studies.

Introduction Methylphenidate is the most frequently used medication for the treatment of attention-deficit/hyperactivity disorder (ADHD) in Europe. Following concerns about its safety, the European Commission called for research into the long-term effects of methylphenidate on children and adolescents with ADHD. The Attention Deficit Hyperactivity Disorder Drugs Use Chronic Effects (ADDUCE) research programme was designed to address this call. At the heart of this programme is a 2-year longitudinal naturalistic pharmacovigilance study being conducted in 27 European sites.Methods and analysis 3 cohorts of children and adolescents (aged 6–17) living in the UK, Germany, Italy and Hungary are being recruited:Group 1 (Medicated ADHD): 800 ADHD medication-naive children and adolescents with a clinical diagnosis of ADHD about to start methylphenidate treatment for the first time.Group 2 (Unmedicated ADHD): 400 children and adolescents with a clinical diagnosis of ADHD who have never been treated with ADHD medication and have no intention of beginning medication.Group 3 (Non-ADHD): 400 children and adolescents without ADHD who are siblings of individuals in either group 1 or 2.All participants will be assessed 5 times during their 2-year follow-up period for growth and development, psychiatric, neurological and cardiovascular health. The primary outcome measure will be the height velocity SD score.Ethics and dissemination Ethical approval for the study has been granted by the East of Scotland Research Ethics Service. Following this approval, patient information leaflets and consent forms were translated as necessary and submissions made by lead sites in each of the other 3 countries to their own ethics committees. Following ethical approval in each country, local ethical permissions at each site were sought and obtained as needed. The study's website (http://www.adhd-adduce.org/page/view/2/Home) provides information for researchers, participants and the general public.Trial registration number NCT01470261.

Background. We investigated the links between familial loading, preadolescent temperament, and internalizing and externalizing problems in adolescence, hereby distinguishing effects on maladjustment in general versus dimension-specific effects on either internalizing or externalizing problems.Method. In a population-based sample of 2230 preadolescents (10–11 years) familial loading (parental lifetime psychopathology) and offspring temperament were assessed at baseline by parent report, and offspring psychopathology at 2·5-years follow-up by self-report, teacher report and parent report. We used purified measures of temperament and psychopathology and partialled out shared variance between internalizing and externalizing problems.Results. Familial loading of internalizing psychopathology predicted offspring internalizing but not externalizing problems, whereas familial loading of externalizing psychopathology predicted offspring externalizing but not internalizing problems. Both familial loadings were associated with Frustration, low Effortful Control, and Fear. Frustration acted as a general risk factor predicting severity of maladjustment; low Effortful Control and Fear acted as dimension-specific risk factors that predicted a particular type of psychopathology; whereas Shyness, High-Intensity Pleasure, and Affiliation acted as direction markers that steered the conditional probability of internalizing versus externalizing problems, in the event of maladjustment. Temperament traits mediated one-third of the association between familial loading and psychopathology. Findings were robust across different composite measures of psychopathology, and applied to girls as well as boys.Conclusions. With regard to familial loading and temperament, it is important to distinguish general risk factors (Frustration) from dimension-specific risk factors (familial loadings, Effortful Control, Fear), and direction markers that act as pathoplastic factors (Shyness, High-Intensity Pleasure, Affiliation) from both types of risk factors. About one-third of familial loading effects on psychopathology in early adolescence are mediated by temperament. [ABSTRACT FROM AUTHOR]

Background. A lack of inhibitory control has been suggested to be the core deficit in children with attention deficit hyperactivity disorder (ADHD). This means that a primary deficit in behavioral inhibition mediates a cascade of secondary deficits in other executive functions, such as arousal regulation. Clinical observations have revealed that with increasing age symptoms of hyperactivity and impulsivity decline at a higher rate than those of inattention. This might imply that a deficit in attention rather than a lack of inhibitory control is the major feature in adult ADHD.Method. To study whether an attentional or inhibitory deficit predominates, the stop-signal task and the stop-change task were presented to 24 adults with ADHD combined subtype and 24 controls.Results. Relative to controls, the stop-signal reaction time (SSRT) was significantly more prolonged than the go-stimulus reaction time (RT) in patients with ADHD. This disproportionate elongation of the SSRT was comparable across tasks, even though the stop-change task exerted more complex (or at least different) demands on the inhibitory system than the stop-signal task. ADHD patients had a higher proportion of choice errors, possibly reflecting more premature responses. Specifically in the stop-change task, patients had more variable choice responses and made more inappropriate change responses, which may also reflect enhanced impulsivity.Conclusions. The results support a core deficit in behavioral inhibition in adults with ADHD. We further suggest that there is more evidence for a critical role of deficient inhibitory control in adults than in children with ADHD. [ABSTRACT FROM AUTHOR]