Stimulant drug effects on attention deficit/hyperactivity disorder: a review of the effects of age and sex of patients

Objective: As dopamine functioning varies by sex and age it might be expected that the effects of methylphenidate or amfetamine, the psychostimulants used for the treatment of Attention Deficit /Hyperactivity Disorder (ADHD), will also be moderated by these factors. Here we review the published literature on whether stimulant effects in ADHD symptoms vary by age and sex. Method: We searched for studies published from 1989 until October 2009. Databases searched included U. S. National Library of Medicine (PubMed), Medline, EMBASE, PsycINFO and ISI Web of Knowledge. Firstly, we reviewed the effects of stimulant drugs on male and female patients and also patients of pre-school, middle childhood, adolescence and adulthood. Secondly, we reviewed studies that directly tested the moderating effect of age and sex on stimulant treatment outcome. Results: Randomised controlled trials confirm that stimulant medication is efficacious for, and well tolerated by, males and females and patients across the age range; although preschoolers appear to have a less beneficial response and more side effects. Few studies that specifically examined the moderating effect of age and/or sex were identified. For sex, no effects on overall response were found, although one study reported that sex moderated methylphenidate pharmacodynamics. The few effects found for age were small and inconsistent. Conclusions: The available evidence suggests that stimulant medication, when appropriately administered, has efficacy as an ADHD treatment for both sexes and across all ages. There are currently too few published papers examining the effects of sex and age to draw strong conclusions about moderation. Further studies of the pharmacodynamics of stimulants on symptoms measured using objective tests in the laboratory or classroom setting need to be undertaken

Using qualitative models to define sustainable management for the commons in data poor conditions

Acknowledgments This work was funded by the University of Aberdeen and Scottish Natural Heritage (SNH) and their support is gratefully acknowledged. We thank MASTS (the Marine Alliance for Science and Technology for Scotland) for their role in funding this work and B. Leyshon and F. Manson (SNH) for fruitful discussion.Peer reviewedPostprin

The social sciences and the web : From ‘Lurking’ to interdisciplinary ‘Big Data’ research

Acknowledgements This research is supported by the award made by the RCUK Digital Economy theme to the dot.rural Digital Economy Hub (award reference: EP/G066051/1) and the UK Economic & Social Research Council (ESRC) (award reference: ES/M001628/1).Peer reviewedPublisher PD

Using social media to quantify spatial and temporal dynamics of nature-based recreational activities

Data Availability: All the data and R scripts are available at https://github.com/FrancescaMancini/Flickr-API and https://github.com/FrancescaMancini/Flickr-Statistical-Analysis. Funding: This work was supported by the University of Aberdeen, Scottish Natural Heritage through a Dominic Counsell PhD studentship, and the Marine Alliance for Science and Technology for Scotland (MASTS). The funders had no role in study design, data collection and analysis, decision to publish, or preparation.Peer reviewedPublisher PD

Post hoc analyses of the impact of previous medication on the efficacy of lisdexamfetamine dimesylate in the treatment of attention-deficit/hyperactivity disorder in a randomized, controlled trial

David R Coghill,1 Tobias Banaschewski,2 Michel Lecendreux,3 César Soutullo,4 Alessandro Zuddas,5 Ben Adeyi,6 Shaw Sorooshian7 1Division of Neuroscience, University of Dundee, Dundee, UK; 2Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany; 3Paediatric Sleep Centre and National Reference Centre for Orphan Diseases: Narcolepsy, Idiopathic Hypersomnia and Kleine-Levin Syndrome, Robert-Debré University Hospital, Paris, France; 4Child and Adolescent Psychiatry Unit, Department of Psychiatry and Medical Psychology, University of Navarra Clinic, Pamplona, Spain; 5Department of Biomedical Sciences, Section of Neuroscience and Clinical Pharmacology, University of Cagliari, Cagliari, Italy; 6Shire, Wayne, PA, USA; 7Shire, Eysins, Switzerland Background: Following the approval of lisdexamfetamine dimesylate (LDX) in several European countries for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children and adolescents with an inadequate response to methylphenidate (MPH) treatment, the aim of the present analysis was to establish the response to LDX in subgroups of patients with different ADHD medication histories. Methods: This was a post hoc subgroup analysis of data from a 7-week, European, double-blind, dose-optimized, Phase III study. Patients aged 6–17 years were randomized 1:1:1 to LDX, placebo, or osmotic-release oral system methylphenidate (OROS-MPH). OROS-MPH was included as a reference arm rather than as a direct comparator. Efficacy was assessed in patients categorized according to their ADHD medication history using the ADHD Rating Scale IV and Clinical Global Impressions-Improvement (CGI-I) scores. Results: The difference between active drug and placebo in least-squares mean change from baseline to endpoint in ADHD Rating Scale IV total score (95% confidence interval) was similar between the overall study population (n=317; LDX, -18.6 [-21.5, -15.7]; OROS- MPH, -13.0 [-15.9, -10.2]) and treatment-naïve individuals (n=147; LDX, -15.1 [-19.4, -10.9]; OROS-MPH, -12.7 [-16.8, -8.5]) or patients previously treated with any ADHD medication (n=170; LDX, -21.5 [-25.5, -17.6]; OROS-MPH, -14.2 [-18.1, -10.3]). In addition, similar proportions of patients receiving active treatment were categorized as improved based on CGI-I score (CGI-I of 1 or 2) in the overall study population and among treatment-naïve individuals or patients previously treated with any ADHD medication. Conclusion: In these post hoc analyses, the response to LDX treatment, and to the reference treatment OROS-MPH, was similar to that observed for the overall study population in subgroups of patients categorized according to whether or not they had previously received ADHD medication. Keywords: attention-deficit/hyperactivity disorder, lisdexamfetamine dimesylate, methylphenidate, central nervous system stimulant

Qualitative kinematics of planar robots: Intelligent connection

AbstractThis paper proposes a qualitative representation for robot kinematics in order to close the gap, raised by the perception–action problem, with a focus on intelligent connection of qualitative states to their corresponding numeric data in a robotic system. First, qualitative geometric primitives are introduced by combining a qualitative orientation component and qualitative translation component using normalisation techniques. A position in Cartesian space can be mathematically described by the scalable primitives. Secondly, qualitative robot kinematics of an n-link planar robot is derived in terms of the qualitative geometry primitives. Finally, it shows how to connect quantitativeness and qualitativeness of a robotic system. On the one hand, the integration of normalisation and domain knowledge generates normalised labels to introduce the meaningful parameters into the proposed representation. On the other hand, the normalised labels of this representation can be converted to a quantitative description using aggregation operators, whose numeric outputs can be used to generate desired trajectories based on mature interpolation techniques

Disentangling ADHD's Presentation-Related Decision-Making-A Meta-Analytic Approach on Predominant Presentations

Background: Deficient decision-making (DM) in attention deficit/hyperactivity disorder (ADHD) is marked by altered reward sensitivity, higher risk taking, and aberrant reinforcement learning. Previous meta-analysis aggregate findings for the ADHD combined presentation (ADHD-C) mostly, while the ADHD predominantly inattentive presentation (ADHD-I) and the predominantly hyperactive/impulsive presentation (ADHD-H) were not disentangled. The objectives of the current meta-analysis were to aggregate findings from DM for each presentation separately. Methods: A comprehensive literature search of the PubMed (Medline) and Web of Science Database took place using the keywords "ADHD," "attention-deficit/hyperactivity disorder," "decision-making," "risk-taking," "reinforcement learning," and "risky." Random-effects models based on correlational effect-sizes were conducted. Heterogeneity analysis and sensitivity/outlier analysis were performed, and publication biases were assessed with funnel-plots and the egger intercept. Results: Of 1,240 candidate articles, seven fulfilled criteria for analysis of ADHD-C (N = 193), seven for ADHD-I (N = 256), and eight for ADHD-H (N = 231). Moderate effect-size were found for ADHD-C (r = 0.34; p = 0.0001; 95% CI = [0.19, 0.49]). Small effect-sizes were found for ADHD-I (r = 0.09; p = 0.0001; 95% CI = [0.008, 0.25]) and for ADHD-H (r = 0.1; p = 0.0001; 95% CI = [-0.012, 0.32]). Heterogeneity was moderate for ADHD-H. Sensitivity analyses show robustness of the analysis, and no outliers were detected. No publication bias was evident. Conclusion: This is the first study that uses a meta-analytic approach to investigate the relationship between the different presentations of ADHD separately. These findings provide first evidence of lesser pronounced impairment in DM for ADHD-I and ADHD-I compared to ADHD-C. While the exact factors remain elusive, the current study can be considered as a starting point to reveal the relationship of ADHD presentations and DM more detailed

Cognitive Function of Children and Adolescents with Attention-Deficit/Hyperactivity Disorder in a 2-Year Open-Label Study of Lisdexamfetamine Dimesylate

BACKGROUND: SPD489-404 was the first 2-year safety study of lisdexamfetamine dimesylate in the treatment of attention-deficit/hyperactivity disorder in children and adolescents. In accordance with advice from the European Medicines Agency, assessment of cognitive function was a predefined safety outcome in SPD489-404. OBJECTIVE: The objective of this study was to assess cognitive function over 2 years in study SPD489-404, using the Cambridge Neuropsychological Test Automated Battery (CANTAB). METHODS: Participants aged 6-17 years received dose-optimised open-label lisdexamfetamine dimesylate (30, 50 or 70 mg/day) for 104 weeks. Cognition was assessed using four CANTAB tasks; Delayed Matching to Sample (DMS), Spatial Working Memory (SWM), Stop Signal Task (SST) and Reaction Time (RTI). Key and additional variables were pre-specified for each CANTAB task; groupwise mean percentage changes in key variables from baseline of > 5% were considered potentially clinically significant. RESULTS: All 314 enrolled participants received lisdexamfetamine dimesylate and were included in the safety population, and 191 (60.8%) completed the study. No potentially clinically significant deteriorations from baseline were observed in any key CANTAB variable over the 2 years of the study. Based on predefined thresholds, potentially clinically significant improvements from baseline were observed at 6 months (DMS median reaction time, mean per cent change, - 6.6%; SWM total between-search errors, - 22.8%; SST stop signal reaction time, -18.9%), and at the last on-treatment assessment (DMS median reaction time, - 6.5%; SWM total between-search errors, - 32.6%; SST stop signal reaction time, - 25.7%). CONCLUSIONS: Lisdexamfetamine dimesylate treatment for 2 years was not associated with deterioration of cognitive function in children and adolescents with attention-deficit/hyperactivity disorder. Although improvements in some cognitive measures were observed, lack of a control group makes interpretation of the findings difficult. Further studies of the impact of stimulants on cognition are required

Heterogeneity in hyperkinetic disorder

It is increasingly recognised that the broadly defined behavioural phenotype of attention deficit – hyperactivity disorder (ADHD) is a heterogeneous condition and that this heterogeneity is seen across all levels of analysis from the genetic and environmental causes to the associated neuropsychological deficits, the clinical presentation and response to treatment. This work investigated whether the more restrictive and clinically homogeneous hyperkinetic disorder (HKD) phenotype is associated with reduced neuropsychological heterogeneity compared with the broader ADHD phenotype. Using a well known, broad based battery of neuropsychological tasks from the Cambridge Neuropsychological Test Automated Battery (CANTAB) and a computerised Go/NoGo task in a large well described group of boys with rigorously diagnosed HKD who were stimulant medication naïve at baseline, it was demonstrated that the neuropsychological heterogeneity in the HKD boys was very similar to that seen previously in children with ADHD. Interestingly, and contrary to popular opinion, the strongest associations were with more simple recognition memory tasks with a low executive demand. Although there were significant associations between HKD and deficits on a range of tasks with high executive demands these were less strong. Could this neuropsychological heterogeneity be a function of different developmental issues or comorbidity? With respect to development there was evidence that boys with HKD lagged behind the healthy boys with respect to the development of their neuropsychological performance. However the pattern of development was similar with the performance of the HKD boys paralleling that of the healthy boys, suggesting that the neuropsychological heterogeneity seen in HKD is not accounted for by developmental issues. With respect to the relationship between neuropsychological functioning and comorbidity, the impact of comorbid oppositional defiant disorder (ODD) and conductdisorder (CD), it was found that all three clinical groups (pure HKD, HKD + ODD and HKD + CD) demonstrated deficits on several tasks compared with the healthy boys. Compared with healthy boys each of the three clinical groups was associated with at least one unique neuropsychological deficit. This suggests that comorbidity between HKD and both ODD and CD may contribute to the neuropsychological heterogeneity in the HKD boys. Is there an association between clinical and neuropsychological responses to the treatment of HKD with the stimulant drug methylphenidate (MPH)? Detailed analyses were conducted to investigate heterogeneity of clinical and neuropsychological response in these boys to MPH. As predicted in previous studies there is evidence for clinical heterogeneity in response with between 68 and 78% of boys with HKD responding to MPH treatment at either one or both of the doses. The precise proportion responding was dependent on the scale and definition of response used. Clinical response was not predicted by age but was predicted to a degree by severity of symptoms at baseline and it was generally true that better response was predicted by lower (better) scores at baseline. Baseline performance on a component reflecting recognition memory performance at baseline predicted clinical response to the lower (0.3 mg/kg/dose), but not the higher (0.6, mg/kg/dose) dose of MPH with poorer baseline neuropsychological performance predicting a better clinical response. Whilst there was improvement on some neuropsychological measures following administration of MPH there was little association between clinical and neuropsychological responses to medication. Clinical response was only associated with neuropsychological response on a single measure from a single task (Go/NoGo Block 2 Errors to Distractors), a task that did not itself discriminate between the HKD boys and healthy Controls at baseline.EThOS - Electronic Theses Online ServiceGBUnited Kingdo