Clinical symptoms and performance on the continuous performance test in children with attention deficit hyperactivity disorder between subtypes: a natural follow-up study for 6 months

<p>Abstract</p> <p>Background</p> <p>The aims of this study were to determine the time course of improvements in attention deficit hyperactivity disorder (ADHD) clinical symptoms and neurocognitive function in a realistic clinical setting, and the differences in ADHD symptom improvement using different classifications of ADHD subtypes.</p> <p>Methods</p> <p>The Child Behavior Checklist (CBCL) was completed by parents of ADHD children at the initial visit. The computerized Continuous Performance Test (CPT), Swanson, Nolan, and Pelham, and Version IV Scale for ADHD (SNAP-IV), and ADHD Rating Scale (ADHD-RS) were performed at baseline, one month, three months, and six months later, respectively. Patient care including drug therapy was performed at the discretion of the psychiatrist. The ADHD patients were divided into DSM-IV subtypes (Inattentive, Hyperactive-impulsive and Combined type), and were additionally categorized into aggressive and non-aggressive subtypes by aggression scale in CBCL for comparisons.</p> <p>Results</p> <p>There were 50 ADHD patients with a mean age of 7.84 ± 1.64 years; 15 of them were inattentive type, 11 were hyperactive-impulsive type, and 24 were combined type. In addition, 28 of the ADHD patients were grouped into aggressive and 22 into non-aggressive subtypes. There were significant improvements in clinical symptoms of hyperactivity and inattention, and impulsivity performance in CPT during the 6-month treatment. The clinical hyperactive symptoms were significantly different between ADHD patients sub-grouping both by DSM-IV and aggression. Non-aggressive patients had significantly greater changes in distraction and impulsivity performances in CPT from baseline to month 6 than aggressive patients.</p> <p>Conclusions</p> <p>We found that ADHD symptoms, which included impulsive performances in CPT and clinical inattention and hyperactivity dimensions, had improved significantly over 6 months under pragmatic treatments. The non-aggressive ADHD patients might have a higher potential for improving in CPT performance than aggressive ones. However, it warrant further investigation whether the different classifications of ADHD patients could be valid for predicting the improvements in ADHD patients' clinical symptoms and neurocognitive performance.</p

Complexity in the genetic architecture of leukoaraiosis in hypertensive sibships from the GENOA Study

<p>Abstract</p> <p>Background</p> <p>Subcortical white matter hyperintensity on magnetic resonance imaging (MRI) of the brain, referred to as leukoaraiosis, is associated with increased risk of stroke and dementia. Hypertension may contribute to leukoaraiosis by accelerating the process of arteriosclerosis involving penetrating small arteries and arterioles in the brain. Leukoaraiosis volume is highly heritable but shows significant inter-individual variability that is not predicted well by any clinical covariates (except for age) or by single SNPs.</p> <p>Methods</p> <p>As part of the Genetics of Microangiopathic Brain Injury (GMBI) Study, 777 individuals (74% hypertensive) underwent brain MRI and were genotyped for 1649 SNPs from genes known or hypothesized to be involved in arteriosclerosis and related pathways. We examined SNP main effects, epistatic (gene-gene) interactions, and context-dependent (gene-environment) interactions between these SNPs and covariates (including conventional and novel risk factors for arteriosclerosis) for association with leukoaraiosis volume. Three methods were used to reduce the chance of false positive associations: 1) false discovery rate (FDR) adjustment for multiple testing, 2) an internal replication design, and 3) a ten-iteration four-fold cross-validation scheme.</p> <p>Results</p> <p>Four SNP main effects (in <it>F3</it>, <it>KITLG</it>, <it>CAPN10</it>, and <it>MMP2</it>), 12 SNP-covariate interactions (including interactions between <it>KITLG </it>and homocysteine, and between <it>TGFB3 </it>and both physical activity and C-reactive protein), and 173 SNP-SNP interactions were significant, replicated, and cross-validated. While a model containing the top single SNPs with main effects predicted only 3.72% of variation in leukoaraiosis in independent test samples, a multiple variable model that included the four most highly predictive SNP-SNP and SNP-covariate interactions predicted 11.83%.</p> <p>Conclusion</p> <p>These results indicate that the genetic architecture of leukoaraiosis is complex, yet predictive, when the contributions of SNP main effects are considered in combination with effects of SNP interactions with other genes and covariates.</p

Investigating neuromagnetic brain responses against chromatic flickering stimuli by wavelet entropies

BACKGROUND: Photosensitive epilepsy is a type of reflexive epilepsy triggered by various visual stimuli including colourful ones. Despite the ubiquitous presence of colorful displays, brain responses against different colour combinations are not properly studied. METHODOLOGY/PRINCIPAL FINDINGS: Here, we studied the photosensitivity of the human brain against three types of chromatic flickering stimuli by recording neuromagnetic brain responses (magnetoencephalogram, MEG) from nine adult controls, an unmedicated patient, a medicated patient, and two controls age-matched with patients. Dynamical complexities of MEG signals were investigated by a family of wavelet entropies. Wavelet entropy is a newly proposed measure to characterize large scale brain responses, which quantifies the degree of order/disorder associated with a multi-frequency signal response. In particular, we found that as compared to the unmedicated patient, controls showed significantly larger wavelet entropy values. We also found that Renyi entropy is the most powerful feature for the participant classification. Finally, we also demonstrated the effect of combinational chromatic sensitivity on the underlying order/disorder in MEG signals. CONCLUSIONS/SIGNIFICANCE: Our results suggest that when perturbed by potentially epileptic-triggering stimulus, healthy human brain manages to maintain a non-deterministic, possibly nonlinear state, with high degree of disorder, but an epileptic brain represents a highly ordered state which making it prone to hyper-excitation. Further, certain colour combination was found to be more threatening than other combinations

Predicting sulfotyrosine sites using the random forest algorithm with significantly improved prediction accuracy

addresses: School of Biosciences, University of Exeter, Exeter EX4 5DE, UK. [email protected]: PMCID: PMC2777180types: Journal Article; Research Support, Non-U.S. Gov't© 2009 Yang; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Tyrosine sulfation is one of the most important posttranslational modifications. Due to its relevance to various disease developments, tyrosine sulfation has become the target for drug design. In order to facilitate efficient drug design, accurate prediction of sulfotyrosine sites is desirable. A predictor published seven years ago has been very successful with claimed prediction accuracy of 98%. However, it has a particularly low sensitivity when predicting sulfotyrosine sites in some newly sequenced proteins

Facts, values, and Attention-Deficit Hyperactivity Disorder (ADHD): an update on the controversies

The Hastings Center, a bioethics research institute, is holding a series of 5 workshops to examine the controversies surrounding the use of medication to treat emotional and behavioral disturbances in children. These workshops bring together clinicians, researchers, scholars, and advocates with diverse perspectives and from diverse fields. Our first commentary in CAPMH, which grew out of our first workshop, explained our method and explored the controversies in general. This commentary, which grows out of our second workshop, explains why informed people can disagree about ADHD diagnosis and treatment. Based on what workshop participants said and our understanding of the literature, we make 8 points. (1) The ADHD label is based on the interpretation of a heterogeneous set of symptoms that cause impairment. (2) Because symptoms and impairments are dimensional, there is an inevitable "zone of ambiguity," which reasonable people will interpret differently. (3) Many other variables, from different systems and tools of diagnosis to different parenting styles and expectations, also help explain why behaviors associated with ADHD can be interpreted differently. (4) Because people hold competing views about the proper goals of psychiatry and parenting, some people will be more, and others less, concerned about treating children in the zone of ambiguity. (5) To recognize that nature has written no bright line between impaired and unimpaired children, and that it is the responsibility of humans to choose who should receive a diagnosis, does not diminish the significance of ADHD. (6) Once ADHD is diagnosed, the facts surrounding the most effective treatment are complicated and incomplete; contrary to some popular wisdom, behavioral treatments, alone or in combination with low doses of medication, can be effective in the long-term reduction of core ADHD symptoms and at improving many aspects of overall functioning. (7) Especially when a child occupies the zone of ambiguity, different people will emphasize different values embedded in the pharmacological and behavioral approaches. (8) Truly informed decision-making requires that parents (and to the extent they are able, children) have some sense of the complicated and incomplete facts regarding the diagnosis and treatment of ADHD

IMPRoving Outcomes for children exposed to domestic ViolencE (IMPROVE): an evidence synthesis

BackgroundExposure to domestic violence and abuse (DVA) during childhood and adolescence increases the risk of negative outcomes across the lifespan.ObjectivesTo synthesise evidence on the clinical effectiveness, cost-effectiveness and acceptability of interventions for children exposed to DVA, with the aim of making recommendations for further research.Design(1) A systematic review of controlled trials of interventions; (2) a systematic review of qualitative studies of participant and professional experience of interventions; (3) a network meta-analysis (NMA) of controlled trials and cost-effectiveness analysis; (4) an overview of current UK provision of interventions; and (5) consultations with young people, parents, service providers and commissioners.SettingsNorth America (11), the Netherlands (1) and Israel (1) for the systematic review of controlled trials of interventions; the USA (4) and the UK (1) for the systematic review of qualitative studies of participant and professional experience of interventions; and the UK for the overview of current UK provision of interventions and consultations with young people, parents, service providers and commissioners.ParticipantsA total of 1345 children for the systematic review of controlled trials of interventions; 100 children, 202 parents and 39 professionals for the systematic review of qualitative studies of participant and professional experience of interventions; and 16 young people, six parents and 20 service providers and commissioners for the consultation with young people, parents, service providers and commissioners.InterventionsPsychotherapeutic, advocacy, parenting skills and advocacy, psychoeducation, psychoeducation and advocacy, guided self-help.Main outcome measuresInternalising symptoms and externalising behaviour, mood, depression symptoms and diagnosis, post-traumatic stress disorder symptoms and self-esteem for the systematic review of controlled trials of interventions and NMA; views about and experience of interventions for the systematic review of qualitative studies of participant and professional experience of interventions and consultations.Data sourcesMEDLINE, Cumulative Index to Nursing and Allied Health Literature, PsycINFO, EMBASE, Cochrane Central Register of Controlled Trials, Science Citation Index, Applied Social Sciences Index and Abstracts, International Bibliography of the Social Sciences, Social Services Abstracts, Social Care Online, Sociological Abstracts, Social Science Citation Index, World Health Organization trials portal and clinicaltrials.gov.Review methodsA narrative review; a NMA and incremental cost-effectiveness analysis; and a qualitative synthesis.ResultsThe evidence base on targeted interventions was small, with limited settings and types of interventions; children were mostly &lt; 14 years of age, and there was an absence of comparative studies. The interventions evaluated in trials were mostly psychotherapeutic and psychoeducational interventions delivered to the non-abusive parent and child, usually based on the child’s exposure to DVA (not specific clinical or broader social needs). Qualitative studies largely focused on psychoeducational interventions, some of which included the abusive parent. The evidence for clinical effectiveness was as follows: 11 trials reported improvements in behavioural or mental health outcomes, with modest effect sizes but significant heterogeneity and high or unclear risk of bias. Psychoeducational group-based interventions delivered to the child were found to be more effective for improving mental health outcomes than other types of intervention. Interventions delivered to (non-abusive) parents and to children were most likely to be effective for improving behavioural outcomes. However, there is a large degree of uncertainty around comparisons, particularly with regard to mental health outcomes. In terms of evidence of cost-effectiveness, there were no economic studies of interventions. Cost-effectiveness was modelled on the basis of the NMA, estimating differences between types of interventions. The outcomes measured in trials were largely confined to children’s mental health and behavioural symptoms and disorders, although stakeholders’ concepts of success were broader, suggesting that a broader range of outcomes should be measured in trials. Group-based psychoeducational interventions delivered to children and non-abusive parents in parallel were largely acceptable to all stakeholders. There is limited evidence for the acceptability of other types of intervention. In terms of the UK evidence base and service delivery landscape, there were no UK-based trials, few qualitative studies and little widespread service evaluation. Most programmes are group-based psychoeducational interventions. However, the funding crisis in the DVA sector is significantly undermining programme delivery.ConclusionsThe evidence base regarding the acceptability, clinical effectiveness and cost-effectiveness of interventions to improve outcomes for children exposed to DVA is underdeveloped. There is an urgent need for more high-quality studies, particularly trials, that are designed to produce actionable, generalisable findings that can be implemented in real-world settings and that can inform decisions about which interventions to commission and scale. We suggest that there is a need to pause the development of new interventions and to focus on the systematic evaluation of existing programmes. With regard to the UK, we have identified three types of programme that could be justifiably prioritised for further study: psycho-education delivered to mothers and children, or children alone; parent skills training in combination with advocacy: and interventions involving the abusive parent/caregiver. We also suggest that there is need for key stakeholders to come together to explicitly identify and address the structural, practical and cultural barriers that may have hampered the development of the UK evidence base to date.Future work recommendationsThere is a need for well-designed, well-conducted and well-reported UK-based randomised controlled trials with cost-effectiveness analyses and nested qualitative studies. Development of consensus in the field about core outcome data sets is required. There is a need for further exploration of the acceptability and effectiveness of interventions for specific groups of children and young people (i.e. based on ethnicity, age, trauma exposure and clinical profile). There is also a need for an investigation of the context in which interventions are delivered, including organisational setting and the broader community context, and the evaluation of qualities, qualifications and disciplines of personnel delivering interventions. We recommend prioritisation of psychoeducational interventions and parent skills training delivered in combination with advocacy in the next phase of trials, and exploratory trials of interventions that engage both the abusive and the non-abusive parent.Study registrationThis study is registered as PROSPERO CRD42013004348 and PROSPERO CRD420130043489.FundingThe National Institute for Health Research Public Health Research programme.</jats:sec

Pulmonary and respiratory muscle function in response to 10 marathons in 10 days

Purpose: Marathon and ultramarathon provoke respiratory muscle fatigue and pulmonary dysfunction; nevertheless, it is unknown how the respiratory system responds to multiple, consecutive days of endurance exercise. Methods: Nine trained individuals (six male) contested 10 marathons in 10 consecutive days. Respiratory muscle strength (maximum static inspiratory and expiratory mouth-pressures), pulmonary function (spirometry), perceptual ratings of respiratory muscle soreness (Visual Analogue Scale), breathlessness (dyspnea, modified Borg CR10 scale), and symptoms of Upper Respiratory Tract Infection (URTI), were assessed before and after marathons on days 1, 4, 7, and 10. Results: Group mean time for 10 marathons was 276 ± 35 min. Relative to pre-challenge baseline (159 ± 32 cmH2O), MEP was reduced after day 1 (136 ± 31 cmH2O, p = 0.017), day 7 (138 ± 42 cmH2O, p = 0.035), and day 10 (130 ± 41 cmH2O, p = 0.008). There was no change in pre-marathon MEP across days 1, 4, 7, or 10 (p > 0.05). Pre-marathon forced vital capacity was significantly diminished at day 4 (4.74 ± 1.09 versus 4.56 ± 1.09 L, p = 0.035), remaining below baseline at day 7 (p = 0.045) and day 10 (p = 0.015). There were no changes in FEV1, FEV1/FVC, PEF, MIP, or respiratory perceptions during the course of the challenge (p > 0.05). In the 15-day post-challenge period, 5/9 (56%) runners reported symptoms of URTI, relative to 1/9 (11%) pre-challenge. Conclusions: Single-stage marathon provokes acute expiratory muscle fatigue which may have implications for health and/or performance, but 10 consecutive days of marathon running does not elicit cumulative (chronic) changes in respiratory function or perceptions of dyspnea. These data allude to the robustness of the healthy respiratory system

Attention-induced deactivations in very low frequency EEG oscillations: differential localisation according to ADHD symptom status

Background: the default-mode network (DMN) is characterised by coherent very low frequency (VLF) brain oscillations. The cognitive significance of this VLF profile remains unclear, partly because of the temporally constrained nature of the blood oxygen-level dependent (BOLD) signal. Previously we have identified a VLF EEG network of scalp locations that shares many features of the DMN. Here we explore the intracranial sources of VLF EEG and examine their overlap with the DMN in adults with high and low ADHD ratings.Methodology/Principal Findings: DC-EEG was recorded using an equidistant 66 channel electrode montage in 25 adult participants with high- and 25 participants with low-ratings of ADHD symptoms during a rest condition and an attention demanding Eriksen task. VLF EEG power was calculated in the VLF band (0.02 to 0.2 Hz) for the rest and task condition and compared for high and low ADHD participants. sLORETA was used to identify brain sources associated with the attention-induced deactivation of VLF EEG power, and to examine these sources in relation to ADHD symptoms. There was significant deactivation of VLF EEG power between the rest and task condition for the whole sample. Using s-LORETA the sources of this deactivation were localised to medial prefrontal regions, posterior cingulate cortex/precuneus and temporal regions. However, deactivation sources were different for high and low ADHD groups: In the low ADHD group attention-induced VLF EEG deactivation was most significant in medial prefrontal regions while for the high ADHD group this deactivation was predominantly localised to the temporal lobes.Conclusions/Significance: attention-induced VLF EEG deactivations have intracranial sources that appear to overlap with those of the DMN. Furthermore, these seem to be related to ADHD symptom status, with high ADHD adults failing to significantly deactivate medial prefrontal regions while at the same time showing significant attenuation of VLF EEG power in temporal lobe