Physical Activity and Fitness in Children with Developmental Disorder

Introduction: Developmental coordination disorder (DCD) is a prevalent condition characterized by poor motor proficiency that interferes with a child‟s activities of daily living. Children with DCD often experience compromised health-related fitness components such as cardiorespiratory fitness (CRF). Purpose: To better understand the physical activity and fitness characteristics of children with probable DCD (pDCD), with a particular focus on CRF. Specifically: (1) to present a synopsis of current literature; (2) to determine the longitudinal trajectories of CRF; (3) to compare the submaximal CRF of children with and without pDCD. Methods: A comprehensive, systematic literature review was conducted of the recent available data on fitness and physical activity and pDCD (Chapter 2). This review provided the background for the other two studies included in this thesis. In Chapter 3, a prospective cohort design was used to assess how CRF in children with pDCD changes over time (56 months) relative to a group of typically developing controls. Using a nested-case control design, 63 subjects with pDCD and 63 matched controls from the larger sample were recruited to participate in the lab-based component of the study (Chapter 4). In this investigation CRF was examined using the oxygen cost of work (VO2) during an incremental test on a cycle ergometer. Results: The literature review showed that fitness parameters, including CRF and physical activity levels, were consistently reduced in children with pDCD. Chapter 3 demonstrated that the difference in CRF between children with pDCD and typically developing children is substantial, and that it tends to increase over time. Results from VO2 assessments showed that children with pDCD utilized more oxygen to sustain the same submaximal workloads compared to typically developing children. Conclusions: Findings from this thesis have made several important contributions to our understanding of children with pDCD. Since differences in CRF between children with and without pDCD tend to worsen over time, this adds to the argument that interventions intended to improve CRF may be appropriate for children with motor difficulties. This thesis also presented the first evidence suggesting that DCD involves higher energy expenditure, and could help explain why children with pDCD perform poorly on tasks requiring CRF.

Developmental disorder associated with increased cellular nucleotidase activity

Four unrelated patients are described with a syndrome that included developmental delay, seizures, ataxia, recurrent infections, severe language deficit, and an unusual behavioral phenotype characterized by hyperactivity, short attention span, and poor social interaction. These manifestations appeared within the first few years of life. Each patient displayed abnormalities on EEG. No unusual metabolites were found in plasma or urine, and metabolic testing was normal except for persistent hypouricosuria. Investigation of purine and pyrimidine metabolism in cultured fibroblasts derived from these patients showed normal incorporation of purine bases into nucleotides but decreased incorporation of uridine. De novo synthesis of purines and cellular phosphoribosyl pyrophosphate content also were moderately decreased. The distribution of incorporated purines and pyrimidines did not reveal a pattern suggestive of a deficient enzyme activity. Assay of individual enzymes in fibroblast lysates showed no deficiencies. However, the activity of cytosolic 5′-nucleotidase was elevated 6- to 10-fold. Based on the possibility that the observed increased catabolic activity and decreased pyrimidine salvage might be causing a deficiency of pyrimidine nucleotides, the patients were treated with oral pyrimidine nucleoside or nucleotide compounds. All patients showed remarkable improvement in speech and behavior as well as decreased seizure activity and frequency of infections. A double-blind placebo trial was undertaken to ascertain the efficacy of this supplementation regimen. Upon replacement of the supplements with placebo, all patients showed rapid regression to their pretreatment states. These observations suggest that increased nucleotide catabolism is related to the symptoms of these patients, and that the effects of this increased catabolism are reversed by administration of uridine.

Childhood auditory processing disorder as a developmental disorder:the case for a multi-professional approach to diagnosis and management

Auditory processing disorder (APD) is diagnosed when a patient presents with listening difficulties which can not be explained by a peripheral hearing impairment or higher-order cognitive or language problems. This review explores the association between auditory processing disorder (APD) and other specific developmental disorders such as dyslexia and attention-deficit hyperactivity disorder. The diagnosis and aetiology of APD are similar to those of other developmental disorders and it is well established that APD often co-occurs with impairments of language, literacy, and attention. The genetic and neurological causes of APD are poorly understood, but developmental and behavioural genetic research with other disorders suggests that clinicians should expect APD to co-occur with other symptoms frequently. The clinical implications of co-occurring symptoms of other developmental disorders are considered and the review concludes that a multi-professional approach to the diagnosis and management of APD, involving speech and language therapy and psychology as well as audiology, is essential to ensure that children have access to the most appropriate range of support and interventions.

The lived experience of mothering a child with autism: a hermeneutic phenomenological understanding

Autism Spectrum Disorder is a complex developmental disorder with increasing prevalence. Despite the significant role of mothers, often seen as primary caregivers, there is limited understanding of this experience. The purpose of this study was to explore the everyday experience of mothers with children with autism. Accounts of lived experience were collected through research conversations with six mothers and analyzed using van Manen’s (1990) orientation to hermeneutic phenomenology. The main themes include: It Can’t Be Autism, The Womb is Extended, The Locus of Other, and The Womb is Now and is Forever. The findings suggest that mothers experienced a transformation from mother to mother with a child with autism; one that mirrors the transformation from woman to mother (Bergum, 1989). In this transformation, mothers move from suspicion of the potential diagnosis to acceptance that they are mothers with children whose needs define them and potentially, mothers whose wombs are forever extended.

Saliva flow rate, buffer capacity, and pH of autistic individuals

The objective of the study was to evaluate saliva flow rate, buffer capacity, pH levels, and dental caries experience (DCE) in autistic individuals, comparing the results with a control group (CG). The study was performed on 25 noninstitutionalized autistic boys, divided in two groups. G1 composed of ten children, ages 3-8. G2 composed of 15 adolescents ages 9-13. The CG was composed of 25 healthy boys, randomly selected and also divided in two groups: CG3 composed of 14 children ages 4-8, and CG4 composed of 11 adolescents ages 9-14. Whole saliva was collected under slight suction, and pH and buffer capacity were determined using a digital pHmeter. Buffer capacity was measured by titration using 0.01 N HCl, and the flow rate expressed in ml/min, and the DCE was expressed by decayed, missing, and filled teeth (permanent dentition [DMFT] and primary dentition [dmft]). Data were plotted and submitted to nonparametric (Kruskal-Wallis) and parametric (Student`s t test) statistical tests with a significance level less than 0.05. When comparing G1 and CG3, groups did not differ in flow rate, pH levels, buffer capacity, or DMFT. Groups G2 and CG4 differ significantly in pH (p = 0.007) and pHi = 7.0 (p = 0.001), with lower scores for G2. In autistic individuals aged 3-8 and 9-13, medicated or not, there was no significant statistical difference in flow rate, pH, and buffer capacity. The comparison of DCE among autistic children and CG children with deciduous (dmft) and mixed/permanent decayed, missing, and filled teeth (DMFT) did not show statistical difference (p = 0.743). Data suggest that autistic individuals have neither a higher flow rate nor a better buffer capacity. Similar DCE was observed in both groups studied.

Targeting the mitochondrial electron transport chain in autism, a systematic review and synthesis of a novel therapeutic approach

Autism is a complex developmental disorder with an unknown etiology and without any curative treatment. The mitochondrial electron transfer chains play a major role in the production of ATP, and the generation and management of reactive oxidative stress (ROS). This paper is a systematic review of the role of the mitochondrial electron transport chain in autism, and a consequent hypothesis for treating autism is synthesized.

An electronic search with pre-specified inclusion criteria was conducted in order to retrieve all the published articles about the mitochondrial electron transport chain in autism. The two databases of PUBMED and Google Scholar were searched.

Genetic background of bipolar disorder and related cognitive impairments

Bipolar disorder (BP) is a complex psychiatric disorder characterized by episodes of mania and depression. BP affects approximately 1% of the world’s population and shows no difference in lifetime prevalence between males and females. BP arises from complex interactions among genetic, developmental and environmental factors, and it is likely that several predisposing genes are involved in BP. The genetic background of BP is still poorly understood, although intensive and long-lasting research has identified several chromosomal regions and genes involved in susceptibility to BP. This thesis work aims to identify the genetic variants that influence bipolar disorder in the Finnish population by candidate gene and genome-wide linkage analyses in families with many BP cases. In addition to diagnosis-based phenotypes, neuropsychological traits that can be seen as potential endophenotypes or intermediate traits for BP were analyzed. In the first part of the thesis, we examined the role of the allelic variants of the TSNAX/DISC1 gene cluster to psychotic and bipolar spectrum disorders and found association of distinct allelic haplotypes with these two groups of disorders. The haplotype at the 5’ end of the Disrupted-in-Schizophrenia-1 gene (DISC1) was over-transmitted to males with psychotic disorder (p = 0.008; for an extended haplotype p = 0.0007 with both genders), whereas haplotypes at the 3’ end of DISC1 associated with bipolar spectrum disorder (p = 0.0002; for an extended haplotype p = 0.0001). The variants of these haplotypes also showed association with different cognitive traits. The haplotypes at the 5’ end associated with perseverations and auditory attention, while the variants at the 3’ end associated with several cognitive traits including verbal fluency and psychomotor processing speed. Second, in our complete set of BP families with 723 individuals we studied six functional candidate genes from three distinct signalling systems: serotonin-related genes (SLC6A4 and TPH2), BDNF -related genes (BDNF, CREB1 and NTRK2) and one gene related to the inflammation and cytokine system (P2RX7). We replicated association of the functional variant Val66Met of BDNF with BP and better performance in retention. The variants at the 5’ end of SLC6A4 also showed some evidence of association among males (p = 0.004), but the widely studied functional variants did not yield any significant results. A protective four-variant haplotype on P2RX7 showed evidence of association with BP and executive functions: semantic and phonemic fluency (p = 0.006 and p = 0.0003, respectively). Third, we analyzed 23 bipolar families originating from the North-Eastern region of Finland. A genome-wide scan was performed using the 6K single nucleotide polymorphism (SNP) array. We identified susceptibility loci at chromosomes 7q31 with a LOD score of 3.20 and at 9p13.1 with a LOD score of 4.02. We followed up both linkage findings in the complete set of 179 Finnish bipolar families. The finding on chromosome 9p13 was supported (maximum LOD score of 3.02), but the susceptibility gene itself remains unclarified. In the fourth part of the thesis, we wanted to test the role of the allelic variants that have associated with bipolar disorder in recent genome-wide association studies (GWAS). We could confirm findings for the DFNB31, SORCS2, SCL39A3, and DGKH genes. The best signal in this study comes from DFNB31, which remained significant after multiple testing corrections. Two variants of SORCS2 were allelic replications and presented the same signal as the haplotype analysis. However, no association was detected with the PALB2 gene, which was the most significantly associated region in the previous GWAS. Our results indicate that BP is heterogeneous and its genetic background may accordingly vary in different populations. In order to fully understand the allelic heterogeneity that underlies common diseases such as BP, complete genome sequencing for many individuals with and without the disease is required. Identification of the specific risk variants will help us better understand the pathophysiology underlying BP and will lead to the development of treatments with specific biochemical targets. In addition, it will further facilitate the identification of environmental factors that alter risk, which will potentially provide improved occupational, social and psychological advice for individuals with high risk of BP.

Left ventricular structure in children with developmental coordination disorder

Developmental coordination disorder (p-DCD) is a neuro-developmental disorder featuring impairment in developing motor coordination. This study examined left ventricular mass (LVM) in children with p-DCD (n=63) and controls (n=63). LVM was measured using echocardiography. Body composition was determined using BOD POD and peak oxygen uptake (peak V02) was measured by a progressive exercise test. Height, weight and blood pressure were also measured. LVM was not significantly elevated in p-DCD compared to controls. Peak V02 was lower and SBP, BMI, HR, and BF(%) were significantly higher in p-DCD. They also demonstrated elevated stroke volume (SV), cardiac output (CO), end-diastolic volume, and ventricular diameter in diastole. In regression analyses, p-DCD was a significant predictor of SV and CO after accounting for height, FFM, V02FFM, and sex. These differences in children with p-DCD indicate obesity related changes in the left ventricle and may represent early stages of developing hypertrophy of the left ventricle.

Susceptibility genes and neurodevelopmental mechanisms in dyslexia

Developmental dyslexia is a specific reading disability, which is characterised by unexpected difficulty in reading, spelling and writing despite adequate intelligence, education and social environment. It is the most common childhood learning disorder affecting 5-10 % of the population and thus constitutes the largest portion of all learning disorders. It is a persistent developmental failure although it can be improved by compensation. According to the most common theory, the deficit is in phonological processing, which is needed in reading when the words have to be divided into phonemes, or distinct sound elements. This occurs in the lowest level of the hierarchy of the language system and disturbs processes in higher levels, such as understanding the meaning of words. Dyslexia is a complex genetic disorder and previous studies have found nine locations in the genome that associate with it. Altogether four susceptibility genes have been found and this study describes the discovery of the first two of them, DYX1C1 and ROBO1. The first clues were obtained from two Finnish dyslexic families that have chromosomal translocations which disrupt these genes. Genetic analyses supported their role in dyslexia: DYX1C1 associates with dyslexia in the Finnish population and ROBO1 was linked to dyslexia in a large Finnish pedigree. In addition a genome-wide scan in Finnish dyslexic families was performed. This supported the previously detected dyslexia locus on chromosome 2 and revealed a new locus on chromosome 7. Dyslexia is a neurological disorder and the neurobiological function of the susceptibility genes DYX1C1 and ROBO1 are consistent with this. ROBO1 is an axon guidance receptor gene, which is involved in axon guidance across the midline in Drosophila and axonal pathfinding between the two hemispheres via the corpus callosum, as well as neuronal migration in the brain of mice. The translocation and decreased ROBO1 expression in dyslexic individuals indicate that two functional copies of ROBO1 gene are required in reading. DYX1C1 was a new gene without a previously known function. Inhibition of Dyx1c1 expression showed that it is needed in normal brain development in rats. Without Dyx1c1 protein, the neurons in the developing brain will not migrate to their final position in the cortex. These two dyslexia susceptibility genes DYX1C1 and ROBO1 revealed two distinct neurodevelopmental mechanisms of dyslexia, axonal pathfinding and neuronal migration. This study describes the discovery of the genes and our research to clarify their role in developmental dyslexia.

Novo transtorno, velho problema: a identificação do TDAH pelo olhar do professor

No presente trabalho analisamos os desdobramentos do processo de expansão do Transtorno de Déficit de Atenção e Hiperatividade (TDAH) no cenário educacional brasileiro. O TDAH, considerado atualmente o transtorno de desenvolvimento que mais acomete crianças em idade escolar, vem sofrendo constantes questionamentos no que se refere a sua validade diagnóstica. Caracterizado basicamente pela tríade sintomatológica desatençãohiperatividade-impulsividade, propusemos na pesquisa que o TDAH vem ocupando posição central na discussão sobre as leituras contemporâneas a respeito do fracasso escolar. Para compreender a associação entre TDAH e educação, mais especificamente a hipóteses sobre o fracasso escolar, realizamos um breve levantamento das definições dos sintomas, causas, tratamentos e história do transtorno conforme as edições do DSM. A exposição destes dados permitiu uma reflexão do TDAH como uma entidade complexa e multifatorial que apresenta uma diversidade de manifestações sintomáticas e variadas formas de tratamento. Procuramos demonstrar que essa diversidade de características não só permite que um número cada vez maior de indivíduos seja diagnosticado portador do transtorno como também abre caminho para intensos debates que questionam suas fronteiras flexíveis. Para dar visibilidade às discussões brasileiras, analisamos os materiais divulgados pela Associação Brasileira de Déficit de Atenção (ABDA) e pelo Fórum Sobre a Medicalização da Educação e da Sociedade, duas entidades que apresentam leituras opostas a respeito do conceito nosológico em questão. Demonstramos ainda como TDAH vem compondo discursos sobre os problemas de aprendizagem e indisciplina de crianças em idade escolar de uma escola estadual do município de Niterói, no Rio de Janeiro. Localizar o problema do fracasso escolar na biologia do indivíduo torna possível obliterar outros conflitos que se desencadeiam no ambiente escolar, mantendo como foco o objetivo disciplinador da escola. Os sintomas do TDAH se apresentam, portanto, fundamentalmente relacionados a problemas de desajuste escolar, o que promove um grande desafio aos professores. Esses profissionais recorrem cada vez mais às especialidades médicas relacionadas ao transtorno infantil a fim de buscar soluções para situações que enfrentam em sala de aula. Nesse contexto, a pesquisa de base empírica buscou verificar os sentidos que as professoras atribuem ao TDAH a partir das relações com os alunos em sala de aula. Através da coleta de dados composta por observação participante e entrevistas semiestruturadas aos professores e profissionais de saúde que ocupam o ambiente escolar pesquisado, visamos destacar a forma como se compõe os discursos acerca do TDAH neste ambiente, os quais apresentam diferenças em relação a intensidade da influência exercida pelo discurso médico formal.

Evaluation of Restorative Dentistry Specialty Registrars’ Clinical Experience of Developmental Disorders: A Survey

Background

Specialty Registrars in Restorative Dentistry (StRs) should be competent in the independent restorative management of patients with developmental disorders including hypodontia and cleft lip/palate upon completion of their specialist training.1 Knowledge and management may be assessed via the Intercollegiate Specialty Fellowship Examination (ISFE) in Restorative Dentistry.2

Objective

The aim of this study was to collate and compare data on the training and experience of StRs in the management of patients with developmental disorders across different training units within the British Isles.

Methods

Questionnaires were distributed to all StRs attending the Annual General Meeting of the Specialty Registrars in Restorative Dentistry Group, Belfast, in October 2015. Participants were asked to rate their confidence and experience of assessing and planning treatment for patients with developmental disorders, construction of appropriate prostheses, and provision of dental implants. Respondents were also asked to record clinical supervision and didactic teaching at their unit, and to rate their confidence of passing a future ISFE station assessing knowledge of developmental disorders.

Results

Responses were obtained from 32 StRs (n=32) training within all five countries of the British Isles. The majority of respondents were based in England (72%) with three in Wales, and two in each of Scotland, Northern Ireland, and the Republic of Ireland. Approximately one third of respondents (34%) were in the final years of training (years 4-6). Almost half of the StRs reported that they were not confident of independently assessing (44%) new patients with a developmental disorder, with larger numbers (72%) indicating a lack of confidence in treatment planning. Six respondents rated their experience of treating obturator patients as ‘poor’ or ‘very poor’. The majority (56%) rated their experience of implant provision in these cases as ‘good’ or ‘excellent’ with three-quarters (75%) rating clinical supervision at their unit as ‘good’ or ‘excellent’. Less than half (41%) rated the didactic teaching at their unit as ‘good’ or ‘excellent’, and only 8 StRs indicated that they were confident of passing an ISFE station focused on developmental disorders.

Conclusion

Experience and training regarding patients with developmental disorders is inconsistent for StRs across the British Isles with a number of trainees reporting a lack of clinical exposure.

Oxidative pathways as a drug target for the treatment of autism

Importance of the field: Autism is a severe, pervasive developmental disorder, the aetiology of which is poorly understood. Current pharmacological treatment options for autism are often focused on addressing comorbid behavioural problems, rather than core features of the disorder. Investigation of a new treatment approach is needed.

Areas covered in this review: Recent research has indicated a possible role of abnormalities in oxidative homeostasis in the pathophysiology of autism, based on reports that a range of oxidative biomarkers are significantly altered in people with autism. This article reviews the current findings on oxidative stress in autism, including genetic links to oxidative pathways, changes in antioxidant levels and other oxidative stress markers. We conducted a search of the literature up to June 2010, using Medline, Pubmed, PsycINFO, CINAHL PLUS and BIOSIS Previews.

What the reader will gain: This review provides an overview of the current understanding of the role of oxidative stress in autism. This will assist in highlighting areas of future therapeutic targets and potential underlying pathophysiology of this disorder.

Take home message: Abnormalities in oxidative homeostasis may play a role in the pathophysiology of autism. Antioxidant treatment may form a potential therapeutic pathway for this complex disorder.

Cognitive behavioral treatment of obsessive compulsive disorder : a broader framework

Obsessive Compulsive Disorder (OCD) is rated as a leading cause of disability by the World Health Organization (1996). OCD is a heterogeneous and complex anxiety disorder characterized by the occurrence of repeated and distressing intrusive thoughts, and compulsive actions that are performed in order to lessen distress or prevent the negative outcome associated with the intrusions. Over the last several decades, cognitive behavioral treatments (CBT) of OCD have dramatically improved the prognosis for the disorder. However, a significant proportion of individuals presenting with OCD may still fail to benefit from treatment. In this paper, we present current CBT treatment models of OCD. We then propose several ways of enhancing CBT for OCD by targeting clients' attachment anxiety and dysfunctional self perceptions.

Molecular and Cytogenetic Analyses on Brazilian Youths with Pervasive Developmental Disorders

The Pervasive Developmental Disorders (PDDs) constitute a group of behavioral and neurobiological impairment conditions whose main features are delayed communicative and cognitive development. Genetic factors are reportedly associated with PDDs and particular genetic abnormalities are frequently found in specific diagnostic subgroups such as the autism spectrum disorders. This study evaluated cytogenetic and molecular parameters in 30 youths with autism or other PDDs. The fragile X syndrome was the most common genetic abnormality detected, presented by 1 patient with autism and 1 patient with PPD not-otherwise specified (PPD-NOS). One girl with PDD-NOS was found to have tetrasomy for the 15q11-q13 region, and one patient with autism exhibited in 2/100 metaphases an inv(7)(p15q36), thus suggesting a mosaicism 46,XX/46,XX,inv(7)(p15q36) or representing a coincidental finding. The high frequency of chromosomopathies support the hypothesis that PDDs may develop as a consequence to chromosomal abnormalities and justify the cytogenetic and molecular assessment in all patients with PDDs for establishment of diagnosis.

Growth and developmental outcomes of the extremely preterm infant

Objetive: To provide information for pediatricians and neonatologists to create realistic outcome expectations and thus help plan their actions. Sources of data: Searches were made of the Cochrane Library, MEDLINE, and Lilacs databases. Summary of the findings: The assessment of growth and development over the first 2-3 years must adjust chronological age with respect of the degree of prematurity. There is special concern regarding the prognoses of small for gestational age preterm infants, and for those with bronchopulmonary dysplasia. Attention must be directed towards improving the nutrition of extremely low birth weight infants during their first years of life; these infants have high prevalence levels of failure to catch-up on growth, diseases and rehospitalizations during their first 2 years. They are frequently underweight and shorter than expected during early childhood, but delayed catch-up growth may occur between 8 and 14 years. Extremely low birth weight infants are at increased risk of neurological abnormalities and developmental delays during their first years of life. Educational, psychological, and behavioral problems are frequent during school years. Teenage and adult outcomes show that although some performance differences persist, social integration is not impaired. Conclusions: The growth and neurodevelopment of all ELBW infants must be carefully monitored after discharge, to ensure that children and their families receive adequate support and intervention to optimize prognoses. Copyright © 2005 by Sociedade Brasileira de Pediatria.