Early developmental pathways to childhood symptoms of attention-deficit hyperactivity disorder (ADHD), anxiety, and autism spectrum disorder (ASD)

Background Children with autism spectrum disorder (ASD) often have co-occurring symptoms of attention-deficit/hyperactivity disorder (ADHD) and/or anxiety. It is unclear whether these disorders arise from shared or distinct developmental pathways. We explored this question by testing the specificity of early-life (infant and toddler) predictors of mid-childhood ADHD and anxiety symptoms compared to ASD symptoms. Methods Infants (n = 104) at high and low familial risk for ASD took part in research assessments at 7, 14, 24, and 38 months and 7 years of age. Symptoms of ASD, ADHD, and anxiety were measured by parent report at age 7. Activity levels and inhibitory control, also measured by parent report, in infancy and toddlerhood were used as early-life predictors of ADHD symptoms. Fearfulness and shyness measured in infancy and toddlerhood were used as early-life predictors of anxiety symptoms. Correlations and path analysis models tested associations between early-life predictors and mid-childhood ADHD and anxiety symptoms compared to mid-childhood ASD symptoms, and the influence of controlling for ASD symptoms on those associations. Results Increased activity levels and poor inhibitory control were correlated with ADHD symptoms and not ASD or anxiety; these associations were unchanged in path models controlling for risk-group and ASD symptoms. Increased fearfulness and shyness were correlated with anxiety symptoms, but also ASD symptoms. When controlling for risk-group in path analysis, the association between shyness and anxiety became non-significant, and when further controlling for ASD symptoms the association between fearfulness and anxiety became marginal. Conclusions The specificity of early-life predictors to ADHD symptoms suggests early developmental pathways to ADHD might be distinct from ASD. The overlap in early-life predictors of anxiety and ASD suggests that these disorders are difficult to differentiate early in life, which could reflect the presence of common developmental pathways or convergence in early behavioural manifestations of these disorders. Keywords ASD, ADHD, anxiety, comorbidity, early developmental pathwaysWe are very grateful for the important contributions BASIS families have made towards this study. The research was supported by the BASIS funding consortium led by Autistica (www.basisnetwork.org), Autism Speaks, a UK Medical Research Council Programme Grant (G0701484) to M.H. Johnson, and the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Trust and King’s College London. R. Bedford is supported by a Sir Henry Wellcome Postdoctoral Fellowship. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. The authors have no conflicts of interests

A study of segregation and mobility in an urban community

Thesis (M.A.)--University of Kansas, Sociology, 1925

The Role of Teachers in Peace-Building in Rwanda and South Africa

In 1994, both Rwanda and South Africa emerged from a long and protracted history of colonisation, conflict, genocide, and apartheid which left lasting scars on their education systems. Both countries have undertaken educational reforms to try to strengthen social cohesion. Research led by the University of Sussex in collaboration with the University of Rwanda and the Cape Peninsula University of Technology, Cape Town examined how education policy interventions have helped teachers to become active agents of peace-building. It found that more professional development, policy direction, and support are needed.ESRC-DFI

Electrophysiological correlates of learning and cognitive control in children with tics with and without ADHD symptoms

The aims of this study were to explore the nature of comorbid Tourette syndrome and attention-deficit/hyperactivity disorder (TS+ADHD), in particular whether additive, independent or symptomatic phenocopy models of comorbidity can explain the co-occurrence of these two conditions, and to investigate the impact of comorbid ADHD symptoms on cognitive functions related to the control of tic symptoms in young people with TS. Electrophysiological activity and behavioural performance were measured during three cognitive tasks designed to assess goal-directed reinforcement learning, habit-based reinforcement learning, and cognitive control and were compared between young people with TS, ADHD, TS+ADHD and unaffected young people aged 9 to 17 years. The extent to which severity of tics, ADHD and comorbid oppositional-defiant disorder (ODD) symptoms predicted behavioural and electrophysiological correlates of reinforcement learning and cognitive control was also examined. The TS+ADHD and ADHD groups were impaired in goal-directed learning and modification of new behaviours using reinforcement feedback. ADHD symptoms were negatively associated with adaptive changes in the feedback-related negativity (FRN) ERP that were indicative of compensatory strategies employed to improve learning in the TS+ADHD group. In contrast, the TS+ADHD and ADHD groups showed intact habit-learning performance compared with unaffected controls. The TS+ADHD and ADHD groups were impaired in the ability to withhold inappropriate responses to Nogo stimuli during the Go/Nogo cognitive control task compared with TS and controls. Both ADHD groups also showed greater intra-individual variability than TS and controls. Concurrently, the TS+ADHD group were enhanced in the ability to withhold inappropriate Nogo responses and showed enhancement of the error-related negativity (ERN) ERP relative to the ADHD group. The TS group exhibited enhanced ERN ERPs and post-error slowing, a measure of the ability to adjust performance following errors. These findings are consistent with an additive, but interactive, model of comorbidity, and indicate that comorbid ADHD symptoms introduce impairments in young people with TS that will negatively impact upon the ability to control tics

Goal-directed Leg Movements and Kicks in Infants with Spina Bifida

BACKGROUND AND PURPOSE: Infants with SB present with a known central nervous system lesion that often results in neurologic, orthopedic, and/or cognitive impairments. They usually learn to walk significantly later than typically developing (TD) infants. The delays they experience in learning to walk appear to be related to the fact that they move their legs and kick less often than infants who are TD. Only a small number of studies have reported strategies that therapists and parents may use to increase how often infants with SB move their legs and kick. The purpose of this study was to examine the impact conjugate reinforcement has on the frequency of leg movements (LMs) and kicks generated by infants with SB. METHODS: The LMs of 7 infants with lumbar or sacral SB were videotaped while they were supine in 3 conditions: Baseline; Acquisition (tethered to a mobile); and Extinction. The infants’ LMs were video-taped for two minutes in each condition which enabled us to capture their spontaneous and goal-directed LMs and kicks. The video-tape of each infant’s LMs were then behavior coded via a frame by frame analysis to identify how often each baby moved his or her legs and kicked in each condition as well as how often they generated 9 types of kicks. RESULTS: A significant correlation was observed between LMs and kicks (r= .976, p=0.00). These infants moved their tethered leg significantly more than their untethered leg (p=0.036). These infants generated more goal-directed LMs and kicks in the acquisition and extinction conditions; however, these differences only approached significance (p \u3c .05). Single kicks and parallel kicks were the most common types of kicks generated in each condition. CONCLUSION: The present results are consistent with the literature and suggest that increased kicks lead to stronger neural connections and increased strength, which ultimately leads to earlier onset of ambulation. Due to the significant correlation between LMs and kicks, increasing the frequency of LMs in infants may increase the amount of kicks. However, further research is needed. This study was limited by the small sample size and large standard deviations within group means

Electrophysiological correlates of learning and cognitive control in children with tics with and without ADHD symptoms

The aims of this study were to explore the nature of comorbid Tourette syndrome and attention-deficit/hyperactivity disorder (TS+ADHD), in particular whether additive, independent or symptomatic phenocopy models of comorbidity can explain the co-occurrence of these two conditions, and to investigate the impact of comorbid ADHD symptoms on cognitive functions related to the control of tic symptoms in young people with TS. Electrophysiological activity and behavioural performance were measured during three cognitive tasks designed to assess goal-directed reinforcement learning, habit-based reinforcement learning, and cognitive control and were compared between young people with TS, ADHD, TS+ADHD and unaffected young people aged 9 to 17 years. The extent to which severity of tics, ADHD and comorbid oppositional-defiant disorder (ODD) symptoms predicted behavioural and electrophysiological correlates of reinforcement learning and cognitive control was also examined. The TS+ADHD and ADHD groups were impaired in goal-directed learning and modification of new behaviours using reinforcement feedback. ADHD symptoms were negatively associated with adaptive changes in the feedback-related negativity (FRN) ERP that were indicative of compensatory strategies employed to improve learning in the TS+ADHD group. In contrast, the TS+ADHD and ADHD groups showed intact habit-learning performance compared with unaffected controls. The TS+ADHD and ADHD groups were impaired in the ability to withhold inappropriate responses to Nogo stimuli during the Go/Nogo cognitive control task compared with TS and controls. Both ADHD groups also showed greater intra-individual variability than TS and controls. Concurrently, the TS+ADHD group were enhanced in the ability to withhold inappropriate Nogo responses and showed enhancement of the error-related negativity (ERN) ERP relative to the ADHD group. The TS group exhibited enhanced ERN ERPs and post-error slowing, a measure of the ability to adjust performance following errors. These findings are consistent with an additive, but interactive, model of comorbidity, and indicate that comorbid ADHD symptoms introduce impairments in young people with TS that will negatively impact upon the ability to control tics

Neuroimaging and electroencephalographic (EEG) methods for investigating neural circuits in mental disorders

It is increasingly recognised that dysfunction in neural circuits plays a key role in the neurobiological basis of mental disorders.  The efficacy of pharmacological and behavioural treatments for mental disorders could therefore be improved by targeting dysfunctions in neurocircuits.  However, to achieve this, a better understanding of the specific alterations in neural circuits involved in different mental disorders is required.  Such understanding can be acquired by using advanced neuroscience methods to examine the pathways and function of neurocircuits in both typically developing individuals and in those with mental disorders.  This article provides an overview of currently available neuroscience methods of investigating neural circuits, including advantages and limitations of different techniques, and highlights the importance of using multi-modal imaging in future researchÉ cada vez mais reconhecido que a disfunção nos circuitos neurais desempenha um papel fundamental na base neurobiológica dos transtornos mentais. A eficácia dos tratamentos farmacológicos e comportamentais para os transtornos mentais pode, portanto, ser melhorada por direcionar as disfunções nos neurocircuitos. No entanto, para isso, é necessário um melhor entendimento das alterações específicas nos circuitos neurais envolvidos em diferentes transtornos mentais. Tal entendimento pode ser adquirido usando-se métodos avançados de neurociência para examinar as vias e a função dos neurocircuitos em indivíduos com desenvolvimento típico e naqueles com transtornos mentais. Este artigo fornece uma visão geral dos métodos da neurociência atualmente disponíveis na investigação de circuitos neurais, incluindo vantagens e limitações de diferentes técnicas, e destaca a importância do uso de imagens multimodais em pesquisas futura

Evaluation of a Drowning Prevention Campaign in a Vietnamese American Community

To address Washington State’s high pediatric fatal drowning rates in Asian children, especially Vietnamese, we conducted and evaluated a community water safety campaign for Vietnamese American families. Working with community groups, parks departments and public health, we disseminated three messages (learn to swim, swim with a lifeguard, and wear a life jacket) in Vietnamese media and at events, increased access to free/low cost swim lessons and availability of lifeguarded settings and life jackets in the community. Parents completed 168 pre- and 230 post-intervention self-administered, bilingual surveys. Significantly more post-intervention compared to pre-intervention respondents had heard water safety advice in the previous year, (OR 8.75 (5.07, 15.09)) and had used lifeguarded sites at lakes and rivers (OR 2.3 (1.04,5.08)). The campaign also increased community assets: availability of low-cost family swim lessons, free lessons at beaches, low cost life jacket sales, life jacket loan kiosks in multiple languages, and more Asian, including Vietnamese, lifeguards

Metabolomic and transcriptomic analyses of Fmo5-/- mice reveal roles for flavin-containing monooxygenase 5 (FMO5) in NRF2-mediated oxidative stress response, unfolded protein response, lipid homeostasis, and carbohydrate and one-carbon metabolism

Flavin-containing monooxygenase 5 (FMO5) is a member of the FMO family of proteins, best known for their roles in the detoxification of foreign chemicals and, more recently, in endogenous metabolism. We have previously shown that Fmo5-/- mice display an age-related lean phenotype, with much reduced weight gain from 20 weeks of age. The phenotype is characterized by decreased fat deposition, lower plasma concentrations of glucose, insulin and cholesterol, higher glucose tolerance and insulin sensitivity, and resistance to diet-induced obesity. In the present study we report the use of metabolomic and transcriptomic analyses of livers of Fmo5-/- and wild-type mice to identify factors underlying the lean phenotype of Fmo5-/- mice and gain insights into the function of FMO5. Metabolomics was performed by the Metabolon platform, utilising ultrahigh performance liquid chromatography-tandem mass spectroscopy. Transcriptomics was performed by RNA-Seq and results analysed by DESeq2. Disruption of the Fmo5 gene has wide-ranging effects on the abundance of metabolites and expression of genes in the liver. Metabolites whose concentration differed between Fmo5-/- and wild-type mice include several saturated and monounsaturated fatty acids, complex lipids, amino acids, one-carbon intermediates and ADP-ribose. Among the genes most significantly and/or highly differentially expressed are Apoa4, Cd36, Fitm1, Hspa5, Hyou1, Ide, Me1 and Mme. The results reveal that FMO5 is involved in upregulating the NRF2-mediated oxidative stress response, the unfolded protein response and response to hypoxia and cellular stress, indicating a role for the enzyme in adaptation to oxidative and metabolic stress. FMO5 also plays a role in stimulating a wide range of metabolic pathways and processes, particularly ones involved in lipid homeostasis, the uptake and metabolism of glucose, the generation of cytosolic NADPH, and in one-carbon metabolism. The results predict that FMO5 acts by stimulating the NRF2, XBP1, PPARA and PPARG regulatory pathways, while inhibiting STAT1 and IRF7 pathways

Measuring change

A change in the reporting of HbA1c is being adopted globally, including in Australia. It's anticipated that this change will, among other things, make it easier for doctors to educate their patients about the importance of glycaemic control. However, to understand how this change will help in practice, it's useful to firstly understand what HbA1c is and to know something of the history of how laboratories have measured the HbA1c assay