Information about children reported to have ever been diagnosed with four different neurodevelopmental disorders: attention-deficit/hyperactivity disorder (ADHD), learning disabilities, autism, and intellectual disability.
Almogbel, Yasser S; Goyal, Rohit; Sansgiry, Sujit S
The objective of this study was to examine the association between parenting stress and functional impairment among children with Neurodevelopmental Disorder (NDD). A sample of 150 parents of children diagnosed with NDD were recruited from schools that offer special education services. Parents completed a self-administered survey containing the parenting stress index-short form (PSI-SF) scale and the Columbia Impairment Scale. The multiple logistic regression conducted to compare those with clinically significant PSI-SF scores indicated that the risk of parents with clinically significant scores of parenting stress increased 5.5 times with functionally impaired children with NDD. Further the risk of stress increased 4.6 times when these parents reported having their own disorder/disease. The risk of stress was reduced by 57% for those who had higher than a college level education compared to those with a college level education or below. These findings might help health care providers to initiate early intervention strategies such as peer support and education that can prevent parenting stress and reduce the risk of potential incidence of depression.
Di Pietro, Nina C; Whiteley, Louise Emma; Mizgalewicz, Ania
The Internet is a major source of health-related information for parents of sick children despite concerns surrounding quality. For neurodevelopmental disorders, the websites of advocacy groups are a largely unexamined source of information. We evaluated treatment information posted on nine highly...
Robinson-Shelton, Althea; Malow, Beth A
Sleep disturbances are extremely prevalent in children with neurodevelopmental disorders compared to typically developing children. The diagnostic criteria for many neurodevelopmental disorders include sleep disturbances. Sleep disturbance in this population is often multifactorial and caused by the interplay of genetic, neurobiological and environmental overlap. These disturbances often present either as insomnia or hypersomnia. Different sleep disorders present with these complaints and based on the clinical history and findings from diagnostic tests, an appropriate diagnosis can be made. This review aims to provide an overview of causes, diagnosis, and treatment of sleep disturbances in neurodevelopmental disorders that present primarily with symptoms of hypersomnia and/or insomnia.
Berry-Kravis, Elizabeth M; Lindemann, Lothar; Jønch, Aia E
Neurodevelopmental disorders such as fragile X syndrome (FXS) result in lifelong cognitive and behavioural deficits and represent a major public health burden. FXS is the most frequent monogenic form of intellectual disability and autism, and the underlying pathophysiology linked to its causal ge......, FMR1, has been the focus of intense research. Key alterations in synaptic function thought to underlie this neurodevelopmental disorder have been characterized and rescued in animal models of FXS using genetic and pharmacological approaches. These robust preclinical findings have led...... to the implementation of the most comprehensive drug development programme undertaken thus far for a genetically defined neurodevelopmental disorder, including phase IIb trials of metabotropic glutamate receptor 5 (mGluR5) antagonists and a phase III trial of a GABAB receptor agonist. However, none of the trials has...... been able to unambiguously demonstrate efficacy, and they have also highlighted the extent of the knowledge gaps in drug development for FXS and other neurodevelopmental disorders. In this Review, we examine potential issues in the previous studies and future directions for preclinical and clinical...
Chen, Jianping; Sørensen, Henrik Toft; Miao, Maohua; Liang, Hong; Ehrenstein, Vera; Wang, Ziliang; Yuan, Wei; Li, Jiong
Male congenital malformations as cryptorchidism may contribute to the development of neurodevelopmental disorders directly or via shared familial genetic and/or environmental factors, but the evidence is sparse. Using population-based health registries, we conducted a cohort study of all liveborn singleton boys in Denmark during 1979-2008. Boys with a diagnosis of cryptorchidism were categorized into the exposed cohort and the other boys into the unexposed comparison cohort. The outcomes were diagnoses of any neurodevelopmental disorders and their subtypes. We used Cox proportional hazards regression to compute hazard ratios (HRs), taking into consideration several potential confounders. Among 884,083 male infants, 27,505 received a diagnosis of cryptorchidism during follow-up. Boys with cryptorchidism were more likely to be diagnosed with intellectual disability (HR = 1.77; 95%confidence interval [CI]:1.59,1.97), autism spectrum disorders (ASD) (HR = 1.24; 95% CI:1.13,1.35), attention-deficit hyperactivity disorder (ADHD) (HR = 1.17; 95% CI: 1.08,1.26), anxiety (HR = 1.09; 95% CI: 1.01,1.17), and other behavioral/emotional disorders (HR = 1.16; 95% CI: 1.08,1.26) compared to boys without cryptorchidism. The observed risks of intellectual disability, ASD, and ADHD were increased further in boys with bilateral cryptorchidism. Except for anxiety, cryptorchid boys had higher risks of neurodevelopmental disorders than their non-cryptorchid full brothers. The observed increased risks were similar among boys who underwent orchiopexy, as well as among those with shorter waiting times for this surgery. Cryptorchidism may be associated with increased risks of intellectual disability, ASD, ADHD, and other behavioral/emotional disorders. Cryptorchidism and neurodevelopmental disorders may have shared genetic or in-utero/early postnatal risk factors, which need to be further investigated. Copyright © 2017. Published by Elsevier Ltd.
With approximately 67 million individuals affected worldwide, autism spectrum disorder (ASD) is the fastest growing neurodevelopmental disorder (United Nations, 2011), with a prevalence estimated to be 1/100. In France ASD affects approximately 600,000 individuals (from childhood to adulthood, half of whom are also mentally retarded), who thus have a major handicap in communication and in adapting to daily life, which leads autism to be recognized as a national public health priority. ASD is a neurodevelopmental disorder that affects several domains (i.e., socio-emotional, language, sensori-motor, executive functioning). These disorders are expressed early in life with an age of onset around 18 months. Despite evidence suggesting a strong genetic link with ASD, the genetic determinant remains unclear. The clinical picture is characterized by impairments in social interaction and communication and the presence of restrictive and repetitive behaviors (DSM-5, ICD-10). However, in addition to these two main dimensions there is significant comorbidity between ASD and other neurodevelopmental disorders such as attention deficit hyperactivity disorder or with genetic and medical conditions. One of the diagnostic features of ASD is its early emergence: symptoms must begin in early childhood for a diagnosis to be given. Due to brain plasticity, early interventions are essential to facilitate clinical improvement. Therefore, general practitioners and pediatricians are on the front line to detect early signs of ASD and to guide both medical explorations and early rehabilitation. Copyright © 2017 Elsevier Masson SAS. All rights reserved.
Zinkstok, J.; Buitelaar, J.K.
BACKGROUND: The 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM) was published in May, 2013. AIM: To review the changes in the diagnostic criteria for autism spectrum disorder (ASD) and ADHD in DSM-5, compared to DSM-IV. METHOD: The diagnostic criteria for ASD and ADHD
Although antisocial personality disorder (APD) is one of the most researched personality disorders, it is still surprisingly resistant to treatment. This lack of clinical progress may be partly due to the failure to view APD as a neurodevelopmental disorder and to consider early interventions. After first defining what constitutes a neurodevelopmental disorder, this review evaluates the extent to which APD meets neurodevelopmental criteria, covering structural and functional brain imaging, neurocognition, genetics and epigenetics, neurochemistry, and early health risk factors. Prevention and intervention strategies for APD are then outlined, focusing on addressing early biological and health systems, followed by forensic and clinical implications. It is argued both that APD meets criteria for consideration as a neurodevelopmental disorder and that consideration should be given both to the possibility that early onset conduct disorder is neurodevelopmental in nature, and also to the inclusion of psychopathy as a specifier in future Diagnostic and Statistical Manual revisions of APD.
Butwicka, Agnieszka; Lichtenstein, Paul; Landén, Mikael; Nordenvall, Anna S; Nordenström, Anna; Nordenskjöld, Agneta; Frisén, Louise
Hypospadias (aberrant opening of the urethra on the underside of the penis) occurs in 1 per 300 newborn boys. It has been previously unknown whether this common malformation is associated with increased psychiatric morbidity later in life. Studies of individuals with hypospadias also provide an opportunity to examine whether difference in androgen signaling is related to neurodevelopmental disorders. To elucidate the mechanisms behind a possible association, we also studied psychiatric outcomes among brothers of the hypospadias patients. Registry study within a national cohort of all 9,262 males with hypospadias and their 4,936 healthy brothers born in Sweden between 1973 and 2009. Patients with hypospadias and their brothers were matched with controls by year of birth and county. The following outcomes were evaluated (1) any psychiatric (2) psychotic, (3) mood, (4) anxiety, (5) eating, and (6) personality disorders, (7) substance misuse, (8) attention-deficit hyperactivity disorder (ADHD), (9) autism spectrum disorders (ASD), (10) intellectual disability, and (11) other behavioral/emotional disorders with onset in childhood. Patients with hypospadias were more likely to be diagnosed with intellectual disability (OR 3.2; 95% CI 2.8-3.8), ASD (1.4; 1.2-1.7), ADHD (1.5; 1.3-1.9), and behavioral/emotional disorders (1.4; 1.2-1.6) compared with the controls. Brothers of patients with hypospadias had an increased risk of ASD (1.6; 1.3-2.1) and other behavioral/emotional disorders with onset in childhood (1.2; 0.9-1.5) in comparison to siblings of healthy individuals. A slightly higher, although not statistically significant, risk was found for intellectual disability (1.3; 1.0-1.9). No relation between other psychiatric diagnosis and hypospadias was found. This is the first study to identify an increased risk for neurodevelopmental disorders in patients with hypospadias, as well as an increased risk for ASD in their brothers, suggesting a common familial (genetic and
Zoenen, D; Delvenne, V
The processing of information coming from the elementary sensory systems conditions the development and fulfilment of a child's abilities. A dysfunction in the sensory stimuli processing may generate behavioural patterns that might affect a child's learning capacities as well as his relational sphere. The DSM-5 recognizes the sensory abnormalities as part of the symptomatology of Autism Spectrum Disorders. However, similar features are observed in other neurodevelopmental disorders. Over the years, these conditions have been the subject of numerous controversies. Nowadays, they are all grouped together under the term of Neurodevelopmental Disorders in DSM-5. The semiology of these disorders is rich and complex due to the frequent presence of comorbidities and their impact on cognitive, behavioural, and sensorimotor organization but also on a child's personality, as well as his family, his school, or his social relationships. We carried out a review of the literature on the alterations in the treatment of sensory information in ASD but also on the different neurodevelopmental clinical panels in order to show their impact on child development. Atypical sensory profiles have been demonstrated in several neurodevelopmental clinical populations such as Autism Spectrum Disorder, Attention Deficit/Hyperactivity Disorders, Dysphasia and Intellectual Disability. Abnomalies in the processing of sensory information should be systematically evaluated in child developmental disorders.
. Amongst DSM's most vocal 'insider' critics has been Thomas Insel, Director of the US National Institute of Mental Health. Insel has publicly criticised DSM's adherence to a symptom-based classification of mental disorder, and used the weight ...
Butwicka, Agnieszka; Lichtenstein, Paul; Landén, Mikael; Nordenvall, Anna; Nordenström, Anna; Nordenskjöld, Agneta; Frisén, Louise
BACKGROUND: Hypospadias (aberrant opening of the urethra on the underside of the penis) occurs in 1 per 300 newborn boys. It has been previously unknown whether this common malformation is associated with increased psychiatric morbidity later in life. Studies of individuals with hypospadias also provide an opportunity to examine whether difference in androgen signaling is related to neurodevelopmental disorders. To elucidate the mechanisms behind ...
Decker, Scott L.
The role of school psychologists with training in neuropsychology is examined within the context of multitiered models of service delivery and educational reform policies. An expanded role is suggested that builds on expertise in the assessment of neurodevelopmental disorders and extends to broader tiers through consultation practice. Changes in…
Rangasamy, Sampathkumar; D'Mello, Santosh R; Narayanan, Vinodh
Epigenetic marks are modifications of DNA and histones. They are considered to be permanent within a single cell during development, and are heritable across cell division. Programming of neurons through epigenetic mechanisms is believed to be critical in neural development. Disruption or alteration in this process causes an array of neurodevelopmental disorders, including autism spectrum disorders (ASDs). Recent studies have provided evidence for an altered epigenetic landscape in ASDs and demonstrated the central role of epigenetic mechanisms in their pathogenesis. Many of the genes linked to the ASDs encode proteins that are involved in transcriptional regulation and chromatin remodeling. In this review we highlight selected neurodevelopmental disorders in which epigenetic dysregulation plays an important role. These include Rett syndrome, fragile X syndrome, Prader-Willi syndrome, Angelman syndrome, and Kabuki syndrome. For each of these disorders, we discuss how advances in our understanding of epigenetic mechanisms may lead to novel therapeutic approaches.
... Submit" /> Information For… Media Policy Makers Diagnosing Tic Disorders Language: English (US) Español (Spanish) Recommend on ... or postviral encephalitis). Persistent (Chronic) Motor or Vocal Tic Disorder To be diagnosed with a persistent tic ...
Full Text Available Methylation of several lysine residues of histones is a crucial mechanism for relatively long-term regulation of genomic activity. Recent molecular biological studies have demonstrated that the function of histone methylation is more diverse and complex than previously thought. Moreover, studies using newly available genomics techniques, such as exome sequencing, have identified an increasing number of histone lysine methylation-related genes as intellectual disability-associated genes, which highlights the importance of accurate control of histone methylation during neurogenesis. However, given the functional diversity and complexity of histone methylation within the cell, the study of the molecular basis of histone methylation-related neurodevelopmental disorders is currently still in its infancy. Here, we review the latest studies that revealed the pathological implications of alterations in histone methylation status in the context of various neurodevelopmental disorders and propose possible therapeutic application of epigenetic compounds regulating histone methylation status for the treatment of these diseases.
Stoodley, Catherine J
Cerebellar dysfunction is evident in several developmental disorders, including autism, attention deficit-hyperactivity disorder (ADHD), and developmental dyslexia, and damage to the cerebellum early in development can have long-term effects on movement, cognition, and affective regulation. Early cerebellar damage is often associated with poorer outcomes than cerebellar damage in adulthood, suggesting that the cerebellum is particularly important during development. Differences in cerebellar development and/or early cerebellar damage could impact a wide range of behaviors via the closed-loop circuits connecting the cerebellum with multiple cerebral cortical regions. Based on these anatomical circuits, behavioral outcomes should depend on which cerebro-cerebellar circuits are affected. Here, we briefly review cerebellar structural and functional differences in autism, ADHD, and developmental dyslexia, and discuss clinical outcomes following pediatric cerebellar damage. These data confirm the prediction that abnormalities in different cerebellar subregions produce behavioral symptoms related to the functional disruption of specific cerebro-cerebellar circuits. These circuits might also be crucial to structural brain development, as peri-natal cerebellar lesions have been associated with impaired growth of the contralateral cerebral cortex. The specific contribution of the cerebellum to typical development may therefore involve the optimization of both the structure and function of cerebro-cerebellar circuits underlying skill acquisition in multiple domains; when this process is disrupted, particularly in early development, there could be long-term alterations of these neural circuits, with significant impacts on behavior.
Stratton, Kathleen; Gable, Alicia; McCormick, Marie C
In this report, the Immunization Safety Review committee examines the hypothesis of whether or not the use of vaccines containing the preservative thimerosal can cause neurodevelopmental disorders (NDDs...
Wentz, Elisabet; Björk, Anna; Dahlgren, Jovanna
To investigate prevalence of neurodevelopmental disorders in children with obesity and to compare body mass index (BMI) and metabolic profile in the children. Seventy-six children (37 girls, 39 boys) were consecutively recruited from a university outpatient clinic specialized in severe obesity. Neurodevelopmental disorders including attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and developmental coordination disorder (DCD) were assessed using interviews and questionnaires. Neurodevelopmental diagnoses were collected retrospectively in medical records. BMI ranged between 1.9 and 5.9 SDS and age between 5.1 and 16.5 years. In 13.2% and 18.4% ASD and ADHD was assigned, respectively. In addition, 25% screened positive for DCD, 31.6% had at least one neurodevelopmental disorder, and 18.4% had a parent who screened positive for adult ADHD. Girls with ASD/ADHD had higher BMI SDS than girls without neurodevelopmental disorder (P = 0.006). One third of children with obesity referred to specialist centers have a neurodevelopmental disorder including deviant motor skills, and these problems may deteriorate weight status. One fifth of the parents exhibit ADHD symptomatology which could partly explain the poor adherence by some families in obesity units. Future obesity therapy could benefit from incorporating a neurodevelopmental treatment approach. © 2016 The Obesity Society.
Dorothy V M Bishop
Full Text Available There are substantial differences in the amount of research concerned with different disorders. This paper considers why.Bibliographic searches were conducted to identify publications (1985-2009 concerned with 35 neurodevelopmental disorders: Developmental dyslexia, Developmental dyscalculia, Developmental coordination disorder, Speech sound disorder, Specific language impairment, Attention deficit hyperactivity disorder, Autistic spectrum disorder, Tourette syndrome, Intellectual disability, Angelman syndrome, Cerebral palsy, Cornelia de Lange syndrome, Cri du chat syndrome, Down syndrome, Duchenne muscular dystrophy, Fetal alcohol syndrome, Fragile X syndrome, Galactosaemia, Klinefelter syndrome, Lesch-Nyhan syndrome, Lowe syndrome, Marfan syndrome, Neurofibromatosis type 1, Noonan syndrome, Phenylketonuria, Prader-Willi syndrome, Rett syndrome, Rubinstein-Taybi syndrome, Trisomy 18, Tuberous sclerosis, Turner syndrome, Velocardiofacial syndrome, Williams syndrome, XXX and XYY. A publication index reflecting N publications relative to prevalence was derived.The publication index was higher for rare than common conditions. However, this was partly explained by the tendency for rare disorders to be more severe.Although research activity is predictable from severity and prevalence, there are exceptions. Low rates of research, and relatively low levels of NIH funding, characterise conditions that are the domain of a single discipline with limited research resources. Growth in research is not explained by severity, and was exceptionally steep for autism and ADHD.
Dirani, Leyla Akoury; Salamoun, Mariana
Children with neurodevelopmental disorders who receive early therapeutic interventions present a better developmental pathway than children who do not. Early assessment of neurodevelopmental disorders is the first step in this process. This study aims at describing the variables that are in play in the first assessment of children with autism…
Andersen, Stine Linding; Andersen, Stig; Vestergaard, Peter
of abnormal maternal thyroid function was 12.5% in the sub-cohort and significantly higher among cases of ASD (17.9%; aHR = 1.5 [CI 1.1-2.1]), but not among other types of neurodevelopmental disorders (febrile seizures: 12.7%; epilepsy: 13.1%; SDD: 12.6%; and ADHD: 14.0%). However, evaluation of subtypes......: The design was a case-cohort study within the Danish National Birth Cohort (1997-2003). From the eligible cohort of 71,706 women, a random 12% sub-cohort (n = 7624) was selected, and all women (n = 2276) whose child was diagnosed with seizures, specific developmental disorder (SDD), autism spectrum disorder......BACKGROUND: Maternal thyroid dysfunction may adversely affect fetal brain development, but more evidence is needed to refine this hypothesis. The aim of this study was to evaluate potential fetal programming by abnormal maternal thyroid function on child neurodevelopmental disorders. METHODS...
Folliot-Le Doussal, Lise; Chadie, Alexandra; Brasseur-Daudruy, Marie; Verspyck, Eric; Saugier-Veber, Pascale; Marret, Stéphane
Neurodevelopmental outcome in children with agenesis of the corpus callosum (ACC) is correlated with the presence or absence of associated brain abnormalities. Indeed, neurodevelopmental outcome shows severe disabilities when the ACC is not isolated whereas in isolated forms, the neurologic development is mainly normal. Contrary to data in several published studies, the prognosis remains uncertain even in isolated forms, which may lead in France to medical termination of pregnancy. To evaluate long-term neurodevelopmental outcome in children with prenatally diagnosed isolated ACC. This is a follow-up study conducted in Normandy (France). It included a cohort of 25 children born between January 1991 and June 2016, with a prenatal diagnosis of isolated ACC and who were followed for at least two years. The average follow-up was 8±5years. ACC was complete in 17 patients (68%), partial in 5 (20%) and hypoplastic in 3 (12%). Whereas global motor development was normal in each case, normal neurodevelopmental outcome or mild disabilities occurred in 88% children and moderate/severe neuro-disabilities were present in 12% of children. Wechsler Intelligence Scale for Children-IV evaluations and Intellectual Total Quotients were within normal range, but we observed lower scores in verbal comprehension, social judgment, executive functions. A lower score in morphosyntax was observed among 52% of children with oral language disorders. Neurodevelopmental outcome was favorable in most of our patients with isolated ACC, but mild learning disabilities emerged in older children. Long-term follow-up until school age is essential to provide early diagnosis and appropriate care support. Copyright © 2017 Elsevier B.V. All rights reserved.
Gillberg, I. Carina; Helles, Adam; Billstedt, Eva; Gillberg, Christopher
We examined comorbid psychiatric and neurodevelopmental disorders in fifty adult males (mean age 30 years) with Asperger syndrome (AS) diagnosed in childhood and followed up prospectively for almost two decades (13-26 years). Only three of the 50 men had "never" met criteria for an additional psychiatric/neurodevelopmental diagnosis and…
Gillberg, I Carina; Helles, Adam; Billstedt, Eva; Gillberg, Christopher
We examined comorbid psychiatric and neurodevelopmental disorders in fifty adult males (mean age 30 years) with Asperger syndrome (AS) diagnosed in childhood and followed up prospectively for almost two decades (13-26 years). Only three of the 50 men had never met criteria for an additional psychiatric/neurodevelopmental diagnosis and more than half had ongoing comorbidity (most commonly either ADHD or depression or both). Any psychiatric comorbidity increased the risk of poorer outcome. The minority of the AS group who no longer met criteria for a full diagnosis of an autism spectrum disorder were usually free of current psychiatric comorbidity. The high rate of psychiatric/neurodevelopmental comorbidities underscores the need for a full psychiatric/neurodevelopmental assessment at follow-up of males with AS.
Homberg, J.R.; Kyzar, E.J.; Stewart, A.M.; Nguyen, M; Poudel, M.K.; Echevarria, D.J.; Collier, A.D.; Gaikwad, S.; Klimenko, V.M.; Norton, W.; Pittman, J.; Nakamura, S.; Koshiba, M.; Yamanouchi, H.; Apryatin, S.A.; Scattoni, M.L.; Diamond, D.M.; Ullmann, J.F.; Parker, M.O.; Brown, R.E.; Song, C.; Kalueff, A.V.
INTRODUCTION: Neurodevelopmental disorders (NDDs) are common and severely debilitating. Their chronic nature and reliance on both genetic and environmental factors makes studying NDDs and their treatment a challenging task. AREAS COVERED: Herein, the authors discuss the neurobiological mechanisms of
Gross, G; Huber, G
In the last two decades schizophrenia is viewed increasingly as a neurodevelopmental (ND) disorder; as indicators are discussed f.e. premorbid personality, behaviour anomalies, premorbid somatic signs, deviations shown by brain imaging methods, neuropathological findings or neuropsychological deficits. Premorbid personality and behaviour anomalies have to be distinguished from precursor syndromes (prodromes and outpost syndromes), preceding the first psychotic episode many years. Moreover, only a minority of patients, later developing schizophrenia, reveal abnormal premorbid personality traits. Explanations why clinical expression of the disorder is delayed until adult life or at least adolescence, remain speculative. Findings of neocortical and limbic maldevelopment, e.g. in parahippocampal cortex, are hitherto not yet conclusive. As an argument for the ND hypothesis is claimed that ventricular enlargement already is present at the onset of positive symptoms and does not progress on follow-ups. But, if a ND disorder would have caused the ventricular enlargement, cranial volume and head size must be decreased, what is not the case in schizophrenia. Furtheron, there are findings of progressive increase in ventricular size and also of gliosis, especially in subcortical and periventricular areas. Anomalies of cerebral asymmetry; also distinct ND brain anomalies such as cavum septi pellucidi or dysgenesis of corpus callosum do not occur more frequently than expected in schizophrenia. As to the rate of obstetric complications (OCs) and viral infections sufficiently reliable data are missing; the great majority of schizophrenics have no OCs. Altogether, attempts to correlate brain findings, regarded as expression of an aberrant brain development with clinical subgroups of schizophrenia, were not very successful. This is also valid for ND concepts confined to male, early onset or sporadic schizophrenias. Only a distinct psychopathological remission type with the component
Heussler, Helen S
Sleep disorders in individuals with developmental difficulties continue to be a significant challenge for families, carers, and therapists with a major impact on individuals and carers alike. This review is designed to update the reader on recent developments in this area. A systematic search identified a variety of studies illustrating advances in the regulation of circadian rhythm and sleep disturbance in neurodevelopmental disorders. Specific advances are likely to lead in some disorders to targeted therapies. There is strong evidence that behavioural and sleep hygiene measures should be first line therapy; however, studies are still limited in this area. Nonpharmacological measures such as exercise, sensory interventions, and behavioural are reported. Behavioural regulation and sleep hygiene demonstrate the best evidence for improved sleep parameters in individuals with neurodisability. Although the mainstay of management of children with sleep problems and neurodevelopmental disability is similar to that of typically developing children, there is emerging evidence of behavioural strategies being successful in large-scale trials and the promise of more targeted therapies for more specific resistant disorders.
Nguyen Quoc Vuong Tran
Full Text Available The increasing prevalence of neurodevelopmental disorders, especially autism spectrum disorders (ASD and attention deficit hyperactivity disorder (ADHD, calls for more research into the identification of etiologic and risk factors. The Developmental Origin of Health and Disease (DOHaD hypothesizes that the environment during fetal and childhood development affects the risk for many chronic diseases in later stages of life, including neurodevelopmental disorders. Epigenetics, a term describing mechanisms that cause changes in the chromosome state without affecting DNA sequences, is suggested to be the underlying mechanism, according to the DOHaD hypothesis. Moreover, many neurodevelopmental disorders are also related to epigenetic abnormalities. Experimental and epidemiological studies suggest that exposure to prenatal environmental toxicants is associated with neurodevelopmental disorders. In addition, there is also evidence that environmental toxicants can result in epigenetic alterations, notably DNA methylation. In this review, we first focus on the relationship between neurodevelopmental disorders and environmental toxicants, in particular maternal smoking, plastic-derived chemicals (bisphenol A and phthalates, persistent organic pollutants, and heavy metals. We then review studies showing the epigenetic effects of those environmental factors in humans that may affect normal neurodevelopment.
The increasing prevalence of neurodevelopmental disorders, especially autism spectrum disorders (ASD) and attention deficit hyperactivity disorder (ADHD), calls for more research into the identification of etiologic and risk factors. The Developmental Origin of Health and Disease (DOHaD) hypothesizes that the environment during fetal and childhood development affects the risk for many chronic diseases in later stages of life, including neurodevelopmental disorders. Epigenetics, a term describing mechanisms that cause changes in the chromosome state without affecting DNA sequences, is suggested to be the underlying mechanism, according to the DOHaD hypothesis. Moreover, many neurodevelopmental disorders are also related to epigenetic abnormalities. Experimental and epidemiological studies suggest that exposure to prenatal environmental toxicants is associated with neurodevelopmental disorders. In addition, there is also evidence that environmental toxicants can result in epigenetic alterations, notably DNA methylation. In this review, we first focus on the relationship between neurodevelopmental disorders and environmental toxicants, in particular maternal smoking, plastic-derived chemicals (bisphenol A and phthalates), persistent organic pollutants, and heavy metals. We then review studies showing the epigenetic effects of those environmental factors in humans that may affect normal neurodevelopment. PMID:28567415
Full Text Available GABAergic interneurons control neuronal excitability, integration, and plasticity. Further, they regulate the generation of temporal synchrony and oscillatory behavior among networks of pyramidal neurons. Such oscillations within and across neural systems are believed to serve various complex functions, such as perception, movement initiation, and memory. Alterations in the development of GABAergic circuits have been implicated in various brain diseases with neurodevelopmental origin. Here, we highlight recent studies suggesting a role for alterations of GABA transmission in the pathophysiology of two neurodevelopmental diseases, schizophrenia and autism. We further discuss how manipulations of GABA signaling may be used for novel therapeutic interventions.
Hellmuth, Signe G; Pedersen, L H; Miltoft, Caroline B
spectrum disorders (ASD), cerebral palsy, epilepsy and febrile seizures was obtained from national patient registries. RESULTS: There was no excess risk of neurodevelopmental disorders among euploid children with first-trimester NT 95(th) -99(th) percentile. For children with NT > 99(th) percentile...... in the risk of cerebral palsy (OR, 1.91 (95% CI, 0.61-5.95), 0.47%), epilepsy (OR, 1.51 (95% CI, 0.63-3.66), 0.78%) or febrile seizures (OR, 0.72 (95% CI, 0.44-1.16), 2.65%). CONCLUSIONS: In a large unselected cohort of euploid children, there was no increased risk of neurodevelopmental disorders among those......OBJECTIVE: To investigate the association between fetal nuchal translucency (NT) thickness and neurodevelopmental disorders in euploid children. METHODS: This study included 222 505 euploid children who had undergone routine first-trimester screening during fetal life. Children were divided...
Grissom, N M; McKee, S E; Schoch, H; Bowman, N; Havekes, R; O'Brien, W T; Mahrt, E; Siegel, S; Commons, K; Portfors, C; Nickl-Jockschat, T; Reyes, T M; Abel, T
Neurodevelopmental disorders, including autism spectrum disorders, are highly male biased, but the underpinnings of this are unknown. Striatal dysfunction has been strongly implicated in the pathophysiology of neurodevelopmental disorders, raising the question of whether there are sex differences in
Jokiranta-Olkoniemi, Elina; Cheslack-Postava, Keely; Sucksdorff, Dan; Suominen, Auli; Gyllenberg, David; Chudal, Roshan; Leivonen, Susanna; Gissler, Mika; Brown, Alan S; Sourander, Andre
Previous research has focused on examining the familial clustering of schizophrenia, bipolar disorder, and autism spectrum disorders (ASD). Little is known about the clustering of other psychiatric and neurodevelopmental disorders among siblings of persons with ASD. To examine the risk for psychiatric and neurodevelopmental disorders among full siblings of probands with ASD. The Finnish Prenatal Study of Autism and Autism Spectrum Disorders used a population-based cohort that included children born from January 1, 1987, to December 31, 2005, who received a diagnosis of ASD by December 31, 2007. Each case was individually matched to 4 control participants by sex and date and place of birth. The siblings of the cases and controls were born from January 1, 1977, to December 31, 2005, and received a diagnosis from January 1, 1987, to December 31, 2009. This nested case-control study included 3578 cases with ASD with 6022 full siblings and 11 775 controls with 22 127 siblings from Finnish national registers. Data were analyzed from March 6, 2014, to February 12, 2016. The adjusted risk ratio (RR) for psychiatric and neurodevelopmental disorders among siblings of probands with ASD vs siblings of matched controls. Additional analyses were conducted separately for ASD subgroups, including childhood autism, Asperger syndrome, and pervasive developmental disorders not otherwise specified. Analyses were further stratified by sex and intellectual disability among the probands. Among the 3578 cases with ASD (2841 boys [79.4%]) and 11 775 controls (9345 boys [79.4%]), 1319 cases (36.9%) and 2052 controls (17.4%) had at least 1 sibling diagnosed with any psychiatric or neurodevelopmental disorder (adjusted RR, 2.5; 95% CI, 2.3-2.6). The largest associations were observed for childhood-onset disorders (1061 cases [29.7%] vs 1362 controls [11.6%]; adjusted RR, 3.0; 95% CI, 2.8-3.3), including ASD (374 cases [10.5%] vs 125 controls [1.1%]; adjusted RR, 11.8; 95% CI, 9
Mouga, Susana; Almeida, Joana; Café, Cátia; Duque, Frederico; Oliveira, Guiomar
We investigated the influence of specific autism spectrum disorder (ASD) deficits in learning adaptive behaviour, besides intelligence quotient (IQ). Participated 217 school-aged: ASD (N = 115), and other neurodevelopmental disorders (OND) groups (N = 102) matched by Full-Scale IQ. We compared standard scores of Vineland Adaptive Behaviour Scale…
Mouga, Susana; Café, Cátia; Almeida, Joana; Marques, Carla; Duque, Frederico; Oliveira, Guiomar
The influence of specific autism spectrum disorder (ASD) deficits in Intelligence Quotients (IQ), Indexes and subtests from the Wechsler Intelligence Scale for Children-III was investigated in 445 school-aged children: ASD (N = 224) and other neurodevelopmental disorders (N = 221), matched by Full-Scale IQ and chronological age. ASD have lower…
Lange, Shannon; Rovet, Joanne; Rehm, Jürgen; Popova, Svetlana
In an effort to improve the screening and diagnosis of individuals with Fetal Alcohol Spectrum Disorder (FASD), research has focused on the identification of a unique neurodevelopmental profile characteristic of this population. The objective of this review was to identify any existing neurodevelopmental profiles of FASD and review their classification function in order to identify gaps and limitations of the current literature. A systematic search for studies published up to the end of December 2016 reporting an identified neurodevelopmental profile of FASD was conducted using multiple electronic bibliographic databases. The search was not limited geographically or by language of publication. Original research published in a peer-reviewed journal that involved the evaluation of the classification function of an identified neurodevelopmental profile of FASD was included. Two approaches have been taken to determine the pathognomonic neurodevelopmental features of FASD, namely the utilization of i) behavioral observations/ratings by parents/caregivers and ii) subtest scores from standardized test batteries assessing a variety of neurodevelopmental domains. Both approaches show some promise, with the former approach (which is dominated by research on the Neurobehavioral Screening Tool) having good sensitivity (63% to 98%), but varying specificity (42% to 100%), and the latter approach having good specificity (72% to 96%), but varying sensitivity (60% to 88%). The current review revealed that research in this area remains limited and a definitive neurodevelopmental profile of FASD has not been established. However, the identification of a neurodevelopmental profile will aid in the accurate identification of individuals with FASD, by adding to the armamentarium of clinicians. The full review protocol is available in PROSPERO ( http://www.crd.york.ac.uk/PROSPERO/ ); registration number CRD42016039326; registered 20 May 2016.
Ullman, Michael T.; Pullman, Mariel Y.
Most research on neurodevelopmental disorders has focused on their abnormalities. However, what remains intact may also be important. Increasing evidence suggests that declarative memory, a critical learning and memory system in the brain, remains largely functional in a number of neurodevelopmental disorders. Because declarative memory remains functional, and because this system can learn and retain numerous types of information, functions, and tasks, it should be able to play compensatory roles for multiple types of impairments across the disorders. Here, we examine this hypothesis for specific language impairment, dyslexia, autism spectrum disorder, Tourette syndrome, and obsessive-compulsive disorder. We lay out specific predictions for the hypothesis and review existing behavioral, electrophysiological, and neuroimaging evidence. Overall, the evidence suggests that declarative memory indeed plays compensatory roles for a range of impairments across all five disorders. Finally, we discuss diagnostic, therapeutic and other implications. PMID:25597655
Dahl, Sara; Wickström, Ronny; Ek, Ulla; Teär Fahnehjelm, Kristina
Optic nerve hypoplasia (ONH) is a congenital ocular malformation that has been associated with neurodevelopmental disorders, but the prevalence in unilateral disease and less severe visual impairment is unknown. We studied intellectual disability and autism spectrum disorders (ASDs) in patients with ONH. This was a population-based cross-sectional cohort study of 65 patients (33 female) with ONH below 20 years of age, living in Stockholm in December 2009, with data analysed in January 2016. Of these 35 were bilateral and 30 were unilateral. Neurodevelopmental disorders were diagnosed or confirmed by neurological assessments, the Five to Fifteen parent questionnaire and reviewing previous neuropsychological investigations or conducting neuropsychological tests. Bilateral ONH patients had lower mean full scale intelligence quotient scores than unilateral patients (84.4 and 99.4, respectively, p = 0.049). We assessed intellectual disability in 55 eligible patients, and it was more common in patients with bilateral ONH (18 of 32, 56%) than unilateral ONH (two of 23, 9%, p neurodevelopmental disorders, especially intellectual disability. The risk was lower in unilateral ONH, but the levels of neurodevelopmental disorders warrant screening of both groups. ©2017 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.
Zauche, Lauren Head; Darcy Mahoney, Ashley E; Higgins, Melinda K
Co-occurring neurodevelopmental disabilities (including cognitive and language delays and attention deficit hyperactivity disorder) affect over half of children with ASD and may affect later behavioral, language, and cognitive outcomes beyond the ASD diagnosis. However, no studies have examined predictors of co-occurring neurodevelopmental disabilities in children with ASD. This study investigated whether maternal sociodemographic, perinatal and neonatal factors are associated with co-occurring disabilities. This study involved a retrospective analysis of medical records for children diagnosed with ASD between 2009 and 2010 at an Autism Center in the southeast United States. Logistic regression was used to identify predictors of co-occurring neurodevelopmental disabilities. Of the 385 children in the sample, 61% had a co-occurring neurodevelopmental disability. Children whose mothers had less education (OR: 0.905), had never been married (OR: 1.803), or had bleeding during pregnancy (OR: 2.233) were more likely to have a co-occurring neurodevelopmental disability. Both preterm birth and African American race were associated with bleeding during pregnancy. Several maternal and perinatal risk factors for ASD were found to put children at risk for further diagnoses of co-occurring neurodevelopmental disabilities. While prematurity, a well-established risk factor for ASD, as well as maternal ethnicity was not found to increase the risk of a co-occurring disability, this study suggests that bleeding during pregnancy may moderate these relationships. Understanding maternal, perinatal, and neonatal risk factors may inform healthcare provider screening for ASD and co-occurring neurodevelopmental disabilities by helping providers recognize infants who present with multiple risk factors. Copyright © 2017 Elsevier Inc. All rights reserved.
Edlow, Andrea G.
There is a growing body of evidence from both human epidemiologic and animal studies that prenatal and lactational exposure to maternal obesity and high-fat diet are associated with neurodevelopmental and psychiatric disorders in offspring. These disorders include cognitive impairment, autism spectrum disorders, attention deficit hyperactivity disorder, cerebral palsy, anxiety and depression, schizophrenia, and eating disorders. This review synthesizes human and animal data linking maternal obesity and high-fat diet consumption to abnormal fetal brain development and neurodevelopmental and psychiatric morbidity in offspring. In addition, it highlights key mechanisms by which maternal obesity and maternal diet might impact fetal and offspring neurodevelopment, including neuroinflammation; increased oxidative stress, dysregulated insulin, glucose, and leptin signaling; dysregulated serotonergic and dopaminergic signaling; and perturbations in synaptic plasticity. Finally, the review summarizes available evidence regarding investigational therapeutic approaches to mitigate the harmful effects of maternal obesity on fetal and offspring neurodevelopment. PMID:27684946
Di Pietro, Nina C.; Whiteley, Louise; Mizgalewicz, Ania; Illes, Judy
The Internet is a major source of health-related information for parents of sick children despite concerns surrounding quality. For neurodevelopmental disorders, the websites of advocacy groups are a largely unexamined source of information. We evaluated treatment information posted on nine highly-trafficked advocacy websites for autism, cerebral…
Boivin, Michael J; Kakooza, Angelina M; Warf, Benjamin C; Davidson, Leslie L; Grigorenko, Elena L
We define neurodevelopment as the dynamic inter-relationship between genetic, brain, cognitive, emotional and behavioural processes across the developmental lifespan. Significant and persistent disruption to this dynamic process through environmental and genetic risk can lead to neurodevelopmental disorders and disability. Research designed to ameliorate neurodevelopmental disorders in low- and middle-income countries, as well as globally, will benefit enormously from the ongoing advances in understanding their genetic and epigenetic causes, as modified by environment and culture. We provide examples of advances in the prevention and treatment of, and the rehabilitation of those with, neurodevelopment disorders in low- and middle-income countries, along with opportunities for further strategic research initiatives. Our examples are not the only possibilities for strategic research, but they illustrate problems that, when solved, could have a considerable impact in low-resource settings. In each instance, research in low- and middle-income countries led to innovations in identification, surveillance and treatment of a neurodevelopmental disorder. These innovations have also been integrated with genotypic mapping of neurodevelopmental disorders, forming important preventative and rehabilitative interventions with the potential for high impact. These advances will ultimately allow us to understand how epigenetic influences shape neurodevelopmental risk and resilience over time and across populations. Clearly, the most strategic areas of research opportunity involve cross-disciplinary integration at the intersection between the environment, brain or behaviour neurodevelopment, and genetic and epigenetic science. At these junctions a robust integrative cross-disciplinary scientific approach is catalysing the creation of technologies and interventions for old problems. Such approaches will enable us to achieve and sustain the United Nations moral and legal mandate for
Preliminary evidence suggests that sensory processing may be affected in autism spectrum disorders (ASD). The purpose of this letter is to highlight a few recent studies on the topic and tie the findings to a recently identified epidemiological risk factor for ASD, principally environmental exposure to the air pollutant, nitrous oxide (N[subscript…
Full Text Available The development of whole exome/genome sequencing technologies has given rise to an unprecedented volume of data linking patient genomic variability to brain disorder phenotypes. A surprising number of variants have been found in the N-methyl-d-aspartate receptor (NMDAR gene family, with the GRIN2B gene encoding the GluN2B subunit being implicated in many cases of neurodevelopmental disorders, which are psychiatric conditions originating in childhood and include language, motor, and learning disorders, autism spectrum disorder (ASD, attention deficit hyperactivity disorder (ADHD, developmental delay, epilepsy, and schizophrenia. The GRIN2B gene plays a crucial role in normal neuronal development and is important for learning and memory. Mutations in human GRIN2B were distributed throughout the entire gene in a number of patients with various neuropsychiatric and developmental disorders. Studies that provide functional analysis of variants are still lacking, however current analysis of de novo variants that segregate with disease cases such as intellectual disability, developmental delay, ASD or epileptic encephalopathies reveal altered NMDAR function. Here, we summarize the current reports of disease-associated variants in GRIN2B from patients with multiple neurodevelopmental disorders, and discuss implications, highlighting the importance of functional analysis and precision medicine therapies.
Andrews, G; Pine, D S; Hobbs, M J; Anderson, T M; Sunderland, M
DSM-IV and ICD-10 are atheoretical and largely descriptive. Although this achieves good reliability, the validity of diagnoses can be increased by an understanding of risk factors and other clinical features. In an effort to group mental disorders on this basis, five clusters have been proposed. We now consider the second cluster, namely neurodevelopmental disorders. We reviewed the literature in relation to 11 validating criteria proposed by a DSM-V Task Force Study Group. This cluster reflects disorders of neurodevelopment rather than a 'childhood' disorders cluster. It comprises disorders subcategorized in DSM-IV and ICD-10 as Mental Retardation; Learning, Motor, and Communication Disorders; and Pervasive Developmental Disorders. Although these disorders seem to be heterogeneous, they share similarities on some risk and clinical factors. There is evidence of a neurodevelopmental genetic phenotype, the disorders have an early emerging and continuing course, and all have salient cognitive symptoms. Within-cluster co-morbidity also supports grouping these disorders together. Other childhood disorders currently listed in DSM-IV share similarities with the Externalizing and Emotional clusters. These include Conduct Disorder, Attention Deficit Hyperactivity Disorder and Separation Anxiety Disorder. The Tic, Eating/Feeding and Elimination disorders, and Selective Mutisms were allocated to the 'Not Yet Assigned' group. Neurodevelopmental disorders meet some of the salient criteria proposed by the American Psychiatric Association (APA) to suggest a classification cluster.
Lundström, Sebastian; Forsman, Mats; Larsson, Henrik; Kerekes, Nora; Serlachius, Eva; Långström, Niklas; Lichtenstein, Paul
The longitudinal relationship between attention deficit hyperactivity disorder (ADHD) and violent criminality has been extensively documented, while long-term effects of autism spectrum disorders (ASDs), tic disorders (TDs), and obsessive compulsive disorder (OCD) on criminality have been scarcely studied. Using population-based registers of all child and adolescent mental health services in Stockholm, we identified 3,391 children, born 1984-1994, with neurodevelopmental disorders, and compared their risk for subsequent violent criminality with matched controls. Individuals with ADHD or TDs were at elevated risk of committing violent crimes, no such association could be seen for ASDs or OCD. ADHD and TDs are risk factors for subsequent violent criminality, while ASDs and OCD are not associated with violent criminality.
Baysal, Bahar Toklu; Baysal, Bora; Genel, Ferah; Erdur, Baris; Ozbek, Erhan; Demir, Korcan; Ozkan, Behzat
To study the factors affecting a neurodevelopmental status of children with congenital hypothyroidism, diagnosed on national screening program. The study was performed in the Pediatric Endocrinology Department of Dr. Behcet Uz Children's Hospital between May 2012 and May 2013. Children with congenital hypothyroidism, aged between 24 and 36 months, diagnosed by national screening program were included in the study group. Healthy subjects at the same age group consisted of the control group. For the neurodevelopmental evaluation, Bayley Scale of Infant Development- II (BSID-II) was used. Factors possibly effective on neurodevelopment were evaluated. 42 patients and 40 healthy children (mean (SD) age, 29.4 (3.7) and 29.2 (3.5), respectively were included in the study. The mean MDI score [92.6 (7.07) vs 97.1 (9.69), P=0.14)] and the mean PDI score [97.8 (15.68) vs 99.1 (10.57), P=0.66)] in the study group and control group were not significantly different. Among the patient, 4.6% and 4.7% children were moderately retarded as per the MDI scores and PPI scores, respectively. The sex, socioeconomic status, birth weight, screening levels of TSH, severity of the congenital hypothyroidism, initiation time and the dosage of thyroid hormone replacement, length of the normalization period of TSH, and adherence to treatment were not found to affect the MDI and PDI scores of the patients. Some children with congenital hypothyrodism may have mild to moderate neurodevelopmental retardation, despite the early diagnosis and treatment, and thus need to be under regular follow-up for neurodevelopmental status.
Jawaid, A.; Riby, D. M.; Owens, J.; White, S. W.; Tarar, T.; Schulz, P. E.
In some neuro-developmental disorders, the combined effect of intellectual disability and atypicalities of social cognition may put individuals at increased vulnerability in their social environment. The neuro-developmental disorders Williams syndrome, characterised by "hypersociability", and autism spectrum disorders, characterised by "social…
Full Text Available The number of children with mild neurodevelopmental disorders, such as autism, has been recently increasing in advanced countries. This increase is probably caused by environmental factors rather than genetic factors, because it is unlikely that genetic mutation rates suddenly increased within a short period. Epigenetics is a mechanism that regulates gene expression, depending not on the underlying DNA sequence but on the chemical modifications of DNA and histone proteins. Because mental stress can alter the epigenetic status in neuronal cells, environmental factors may alter brain function through epigenetic changes. However, one advantage of epigenetic changes is their reversibility. Therefore, diseases due to abnormal epigenetic regulation are theoretically treatable. In fact, several drugs for treating mental diseases are known to have restoring effects on aberrant epigenetic statuses, and a novel therapeutic strategy targeting gene has been developed. In this review, we discuss epigenetic mechanisms of congenital and acquired neurodevelopmental disorders, drugs with epigenetic effects, novel therapeutic strategies for epigenetic diseases, and future perspectives in epigenetic medicine.
Craig, Francesco; Operto, Francesca Felicia; De Giacomo, Andrea; Margari, Lucia; Frolli, Alessandro; Conson, Massimiliano; Ivagnes, Sara; Monaco, Marianna; Margari, Francesco
In recent years, studies have shown that parents of children with Neurodevelopmental Disorders (NDDs) experience more parenting stress than parents of typically developing children, but the relation between the type of disorders and parenting stress is far from clear. The purpose of this study was to compare the parenting stress experienced by parents of 239 children with Specific Learning Disorders (SpLD), Language Disorders (LD), Autism Spectrum Disorder (ASD), Attention Deficit Hyperactivity Disorder (ADHD), and typical development (TD). Parents of children with NDDs experience more parenting stress than those of children who have TD. Although, parents of children with ASD or ADHD report the most high scores of parenting stress, also the parents of children with SpLD or LD report higher parental stress compared with parent of children without NDDs. Another interesting finding was that IQ level or emotional and behavioral problems are associated with the higher levels of parenting stress. This study suggest that parent, both mothers and fathers, of children with different type of NDDs should be provided with interventions and resources to empower them with the knowledge and skills to reduce their stress and to enhance their quality of life. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Venker, Courtney E.; Kover, Sara T.
Purpose: Eye-gaze methods have the potential to advance the study of neurodevelopmental disorders. Despite their increasing use, challenges arise in using these methods with individuals with neurodevelopmental disorders and in reporting sufficient methodological detail such that the resulting research is replicable and interpretable. Method: This…
Alberto J Lopez
Full Text Available It is becoming increasingly important to understand how epigenetic mechanisms control gene expression during neurodevelopment. Two epigenetic mechanisms that have received considerable attention are DNA methylation and histone acetylation. Human exome sequencing and genome-wide association studies have linked several neurobiological disorders to genes whose products actively regulate DNA methylation and histone acetylation. More recently, a third major epigenetic mechanism, nucleosome remodeling, has been implicated in human developmental and intellectual disability disorders. Nucleosome remodeling is driven primarily through nucleosome remodeling complexes with specialized ATP-dependent enzymes. These enzymes directly interact with DNA or chromatin structure, as well as histone subunits, to restructure the shape and organization of nucleosome positioning to ultimately regulate gene expression. Of particular interest is the neuron-specific Brg1/hBrm Associated Factor (nBAF complex. Mutations in nBAF subunit genes have so far been linked to Coffin-Siris syndrome, Nicolaides-Baraitser syndrome, schizophrenia, and Autism Spectrum Disorder. Together, these human developmental and intellectual disability disorders are powerful examples of the impact of epigenetic modulation on gene expression. This review focuses on the new and emerging role of nucleosome remodeling in neurodevelopmental and intellectual disability disorders and whether nucleosome remodeling affects gene expression required for cognition independently of its role in regulating gene expression required for development.
López, Alberto J; Wood, Marcelo A
It is becoming increasingly important to understand how epigenetic mechanisms control gene expression during neurodevelopment. Two epigenetic mechanisms that have received considerable attention are DNA methylation and histone acetylation. Human exome sequencing and genome-wide association studies have linked several neurobiological disorders to genes whose products actively regulate DNA methylation and histone acetylation. More recently, a third major epigenetic mechanism, nucleosome remodeling, has been implicated in human developmental and intellectual disability (ID) disorders. Nucleosome remodeling is driven primarily through nucleosome remodeling complexes with specialized ATP-dependent enzymes. These enzymes directly interact with DNA or chromatin structure, as well as histone subunits, to restructure the shape and organization of nucleosome positioning to ultimately regulate gene expression. Of particular interest is the neuron-specific Brg1/hBrm Associated Factor (nBAF) complex. Mutations in nBAF subunit genes have so far been linked to Coffin-Siris syndrome (CSS), Nicolaides-Baraitser syndrome (NBS), schizophrenia, and Autism Spectrum Disorder (ASD). Together, these human developmental and ID disorders are powerful examples of the impact of epigenetic modulation on gene expression. This review focuses on the new and emerging role of nucleosome remodeling in neurodevelopmental and ID disorders and whether nucleosome remodeling affects gene expression required for cognition independently of its role in regulating gene expression required for development.
Norbury, Courtenay Frazier; Sparks, Alison
Developmental disorders, such as autism spectrum disorder and specific language impairment, are biologically based disorders that currently rely on behaviorally defined criteria for diagnosis and treatment. Specific behaviors that are included in diagnostic frameworks and the point at which individual differences in behavior constitute abnormality…
Dajani, Dina R.; Llabre, Maria M.; Nebel, Mary Beth; Mostofsky, Stewart H.; Uddin, Lucina Q.
Executive functions (EFs) are used to set goals, plan for the future, inhibit maladaptive responses, and change behavior flexibly. Although some studies point to specific EF profiles in autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) — prevalent and often highly comorbid neurodevelopmental disorders — others have not differentiated them. The objective of the current study was to identify distinct profiles of EF across typically developing (TD) children and children with ASD and ADHD. We employed a latent profile analysis using indicators of EF (e.g., working memory, inhibition, and flexibility) in a mixed group of 8–13 year-olds including TD children (n = 128), children with ASD without ADHD (n = 30), children with ADHD (n = 93), and children with comorbid ASD and ADHD (n = 66). Three EF classes emerged: “above average,” “average,” and “impaired.” EF classes did not reproduce diagnostic categories, suggesting that differences in EF abilities are present within the ASD and ADHD groups. Further, greater EF dysfunction predicted more severe socioemotional problems, such as anxiety/depression. These results highlight the heterogeneity of current diagnostic groups and identify an “impaired” EF group, consisting of children with both ASD and ADHD, which could specifically be targeted for EF intervention. PMID:27827406
Maher, Gillian M
Hypertensive disorders of pregnancy (HDPs), that is chronic hypertension, gestational hypertension, pre-eclampsia (de novo or superimposed on chronic hypertension) and white coat hypertension, affect approximately 5%-15% of pregnancies. HDP exposure has been linked to an increased risk of autism spectrum disorder, attention deficit\\/hyperactivity disorder and other neurodevelopmental disorders in children. However, findings are inconsistent, and a clear consensus on the impact of HDPs on the risk of neurodevelopmental disorders is needed. Therefore, we aim to synthesise the published literature on the relationship between HDPs and the risk of neurodevelopmental disorders in the form of a systematic review and meta-analysis.
Smith, Milo R; Glicksberg, Benjamin S; Li, Li; Chen, Rong; Morishita, Hirofumi; Dudley, Joel T
High and increasing prevalence of neurodevelopmental disorders place enormous personal and economic burdens on society. Given the growing realization that the roots of neurodevelopmental disorders often lie in early childhood, there is an urgent need to identify childhood risk factors. Neurodevelopment is marked by periods of heightened experience-dependent neuroplasticity wherein neural circuitry is optimized by the environment. If these critical periods are disrupted, development of normal brain function can be permanently altered, leading to neurodevelopmental disorders. Here, we aim to systematically identify human variants in neuroplasticity-related genes that confer risk for neurodevelopmental disorders. Historically, this knowledge has been limited by a lack of techniques to identify genes related to neurodevelopmental plasticity in a high-throughput manner and a lack of methods to systematically identify mutations in these genes that confer risk for neurodevelopmental disorders. Using an integrative genomics approach, we determined loss-of-function (LOF) variants in putative plasticity genes, identified from transcriptional profiles of brain from mice with elevated plasticity, that were associated with neurodevelopmental disorders. From five shared differentially expressed genes found in two mouse models of juvenile-like elevated plasticity (juvenile wild-type or adult Lynx1-/- relative to adult wild-type) that were also genotyped in the Mount Sinai BioMe Biobank we identified multiple associations between LOF genes and increased risk for neurodevelopmental disorders across 10,510 patients linked to the Mount Sinai Electronic Medical Records (EMR), including epilepsy and schizophrenia. This work demonstrates a novel approach to identify neurodevelopmental risk genes and points toward a promising avenue to discover new drug targets to address the unmet therapeutic needs of neurodevelopmental disease.
Norbury, Courtenay Frazier; Sparks, Alison
Developmental disorders, such as autism spectrum disorder and specific language impairment, are biologically based disorders that currently rely on behaviorally defined criteria for diagnosis and treatment. Specific behaviors that are included in diagnostic frameworks and the point at which individual differences in behavior constitute abnormality are largely arbitrary decisions. Such decisions are therefore likely to be strongly influenced by cultural values and expectations. This is evident in the dramatically different prevalence rates of autism spectrum disorder across countries and across different ethnic groups within the same country. In this article, we critically evaluate the understanding of developmental disorders from a cultural perspective. We specifically consider the challenges of applying diagnostic methods across cultural contexts, the influence of cultural values and expectations on the identification and treatment of children with suspected disorders, and how cross-cultural studies can help to refine cognitive theories of disorder that have been derived exclusively from Western North American and European investigations. Our review synthesizes clinical, cultural, and theoretical work in this area, highlighting potential universals of disorder and concluding with recommendations for future research and practice.
Wade, Mark; Prime, Heather; Madigan, Sheri
Neurodevelopmental disorders represent a broad class of childhood neurological conditions that have a significant bearing on the wellbeing of children, families, and communities. In this review, we draw on evidence from two common and widely studied neurodevelopmental disorders—autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD)—to demonstrate the utility of genetically informed sibling designs in uncovering the nature and pathogenesis of these conditions. Speci...
Bell, Carl C; Chimata, Radhika
This study examined the point prevalence of neurodevelopmental disorders among predominantly low-income, African-American psychiatric patients at Jackson Park Hospital's Family Medicine Clinic on Chicago's South Side. Using active case ascertainment methodology, the authors assessed the records of 611 psychiatric patients visiting the clinic between May 23, 2013, and January 14, 2014, to identify those with DSM-5 neurodevelopmental disorders. A total of 297 patients (49%) met criteria for a neurodevelopmental disorder during childhood. Moreover, 237 (39%) had clinical profiles consistent with neurobehavioral disorder associated with prenatal alcohol exposure, and 53 (9%) had other neurodevelopmental disorders. The authors disagreed on the specific type of neurodevelopmental disorder of seven (1% of 611) of the 297 patients with neurodevelopmental disorders. A high prevalence of neurodevelopmental disorders was found among low-income predominantly African-American psychiatric patients on Chicago's South Side. If replicated, these findings should bring about substantial changes in medical practice with African-American patients.
Homberg, Judith R; Kyzar, Evan J; Stewart, Adam Michael; Nguyen, Michael; Poudel, Manoj K; Echevarria, David J; Collier, Adam D; Gaikwad, Siddharth; Klimenko, Viktor M; Norton, William; Pittman, Julian; Nakamura, Shun; Koshiba, Mamiko; Yamanouchi, Hideo; Apryatin, Sergey A; Scattoni, Maria Luisa; Diamond, David M; Ullmann, Jeremy F P; Parker, Matthew O; Brown, Richard E; Song, Cai; Kalueff, Allan V
Neurodevelopmental disorders (NDDs) are common and severely debilitating. Their chronic nature and reliance on both genetic and environmental factors makes studying NDDs and their treatment a challenging task. Herein, the authors discuss the neurobiological mechanisms of NDDs, and present recommendations on their translational research and therapy, outlined by the International Stress and Behavior Society. Various drugs currently prescribed to treat NDDs also represent a highly diverse group. Acting on various neurotransmitter and physiological systems, these drugs often lack specificity of action, and are commonly used to treat multiple other psychiatric conditions. There has also been relatively little progress in the development of novel medications to treat NDDs. Based on clinical, preclinical and translational models of NDDs, our recommendations cover a wide range of methodological approaches and conceptual strategies. To improve pharmacotherapy and drug discovery for NDDs, we need a stronger emphasis on targeting multiple endophenotypes, a better dissection of genetic/epigenetic factors or "hidden heritability," and a careful consideration of potential developmental/trophic roles of brain neurotransmitters. The validity of animal NDD models can be improved through discovery of novel (behavioral, physiological and neuroimaging) biomarkers, applying proper environmental enrichment, widening the spectrum of model organisms, targeting developmental trajectories of NDD-related behaviors and comorbid conditions beyond traditional NDDs. While these recommendations cannot be addressed all in once, our increased understanding of NDD pathobiology may trigger innovative cross-disciplinary research expanding beyond traditional methods and concepts.
Kubota, Takeo; Miyake, Kunio; Hariya, Natsuyo; Mochizuki, Kazuki
Neurodevelopmental disorders, such as autism, are complex entities that can be caused by biological and social factors. In a subset of patients with congenital neurodevelopmental disorders, clear diagnosis can be achieved using DNA sequence-based analysis to identify changes in the DNA sequence (genetic variation). However, it has recently become clear that changes to the secondary modifications of DNA and histone structures (epigenetic variation) can also cause neurodevelopmental disorders via alteration of neural gene function. Moreover, it has recently been demonstrated that epigenetic modifications are more susceptible to alterations induced by environmental factors than are DNA sequences, and that some drugs commonly used reverse mental-stress induced alterations to histone modifications in neural genes. Therefore, application of diagnostic assays to detect epigenetic alterations will provide new insight into the characterization and treatment of neurodevelopmental disorders.
Conclusion: These findings stress that it is essential to accurately identify motor coordination impairments and the interventions that would consider motor coordination problems related to cognitive abilities and academic achievement in Japanese children with neurodevelopmental disorders.
Schubert, D; Martens, G J M; Kolk, S M
The prefrontal cortex (PFC), seat of the highest-order cognitive functions, constitutes a conglomerate of highly specialized brain areas and has been implicated to have a role in the onset and installation of various neurodevelopmental disorders. The development of a properly functioning PFC is directed by transcription factors, guidance cues and other regulatory molecules and requires the intricate and temporal orchestration of a number of developmental processes. Disturbance or failure of any of these processes causing neurodevelopmental abnormalities within the PFC may contribute to several of the cognitive deficits seen in patients with neurodevelopmental disorders. In this review, we elaborate on the specific processes underlying prefrontal development, such as induction and patterning of the prefrontal area, proliferation, migration and axonal guidance of medial prefrontal progenitors, and their eventual efferent and afferent connections. We furthermore integrate for the first time the available knowledge from genome-wide studies that have revealed genes linked to neurodevelopmental disorders with experimental molecular evidence in rodents. The integrated data suggest that the pathogenic variants in the neurodevelopmental disorder-associated genes induce prefrontal cytoarchitectonical impairments. This enhances our understanding of the molecular mechanisms of prefrontal (mis)development underlying the four major neurodevelopmental disorders in humans, that is, intellectual disability, autism spectrum disorders, attention deficit hyperactivity disorder and schizophrenia, and may thus provide clues for the development of novel therapies.
Full Text Available Bioinformatics tools are recently used in various sectors of biology. Many questions regarding Neurodevelopmental disorder which arises as a major health issue recently can be solved by using various bioinformatics databases. Schizophrenia is such a mental disorder which is now arises as a major threat in young age people because it is mostly seen in case of people during their late adolescence or early adulthood period. Databases like DISGENET, GWAS, PHARMGKB, and DRUGBANK have huge repository of genes associated with schizophrenia. We found a lot of genes are being associated with schizophrenia, but approximately 200 genes are found to be present in any of these databases. After further screening out process 20 genes are found to be highly associated with each other and are also a common genes in many other diseases also. It is also found that they all are serves as a common targeting gene in many antipsychotic drugs. After analysis of various biological properties, molecular function it is found that these 20 genes are mostly involved in biological regulation process and are having receptor activity. They are belonging mainly to receptor protein class. Among these 20 genes CYP2C9, CYP3A4, DRD2, HTR1A, HTR2A are shown to be a main targeting genes of most of the antipsychotic drugs and are associated with more than 40% diseases. The basic findings of the present study enumerated that a suitable combined drug can be design by targeting these genes which can be used for the better treatment of schizophrenia.
Thurm, Audrey; Himelstein, Daniel; DʼSouza, Precilla; Rennert, Owen; Jiang, Susanqi; Olatunji, Damilola; Longo, Nicola; Pasquali, Marzia; Swedo, Susan; Salomons, Gajja S; Carrillo, Nuria
Creatine transporter deficiency (CTD) is an X-linked, neurometabolic disorder associated with intellectual disability that is characterized by brain creatine (Cr) deficiency and caused by mutations in SLC6A8, the Cr transporter 1 protein gene. CTD is identified by elevated urine creatine/creatinine (Cr/Crn) ratio or reduced Cr peak on brain magnetic resonance spectroscopy; the diagnosis is confirmed by decreased Cr uptake in cultured fibroblasts, and/or identification of a mutation in the SLC6A8 gene. Prevalence studies suggest this disorder may be underdiagnosed. We sought to identify cases from a well-characterized cohort of children diagnosed with neurodevelopmental disorders. Urine screening for CTD was performed on a cohort of 46 males with autism spectrum disorder (ASD) and 9 males with a history of non-ASD developmental delay (DD) classified with intellectual disability. We identified 1 patient with CTD in the cohort based on abnormal urine Cr/Crn, and confirmed the diagnosis by the identification of a novel frameshift mutation in the SLC6A8 gene. This patient presented without ASD but with intellectual disability, and was characterized by a nonspecific phenotype of early language delay and DD that persisted into moderate-to-severe intellectual disability, consistent with previous descriptions of CTD. Identification of patients with CTD is possible by measuring urine Cr and Crn levels and the current case adds to the growing literature of neurocognitive deficits associated with the disorder that affect cognition, language and behavior in childhood.
Uljarević, Mirko; Katsos, Napoleon; Hudry, Kristelle; Gibson, Jenny L
Language and communication skills are essential aspects of child development, which are often disrupted in children with neurodevelopmental disorders. Cutting edge research in psycholinguistics suggests that multilingualism has potential to influence social, linguistic and cognitive development. Thus, multilingualism has implications for clinical assessment, diagnostic formulation, intervention and support offered to families. We present a systematic review and synthesis of the effects of multilingualism for children with neurodevelopmental disorders and discuss clinical implications. We conducted systematic searches for studies on multilingualism in neurodevelopmental disorders. Keywords for neurodevelopmental disorders were based on Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition categories as follows; Intellectual Disabilities, Communication Disorders, Autism Spectrum Disorder (ASD), Attention-Deficit/Hyperactivity Disorder, Specific Learning Disorder, Motor Disorders, Other Neurodevelopmental Disorders. We included only studies based on empirical research and published in peer-reviewed journals. Fifty studies met inclusion criteria. Thirty-eight studies explored multilingualism in Communication Disorders, 10 in ASD and two in Intellectual Disability. No studies on multilingualism in Specific Learning Disorder or Motor Disorders were identified. Studies which found a disadvantage for multilingual children with neurodevelopmental disorders were rare, and there appears little reason to assume that multilingualism has negative effects on various aspects of functioning across a range of conditions. In fact, when considering only those studies which have compared a multilingual group with developmental disorders to a monolingual group with similar disorders, the findings consistently show no adverse effects on language development or other aspects of functioning. In the case of ASD, a positive effect on communication and social functioning has
Full Text Available Increasing epidemiological evidence indicates that perinatal infection with various viral pathogens enhances the risk for several psychiatric disorders. The pathophysiological significance of astrocyte interactions with neurons and/or gut microbiomes has been reported in neurodevelopmental disorders triggered by pre- and postnatal immune insults. Recent studies with the maternal immune activation or neonatal polyriboinosinic polyribocytidylic acid models of neurodevelopmental disorders have identified various candidate molecules that could be responsible for brain dysfunction. Here, we review the functions of several candidate molecules in neurodevelopment and brain function and discuss their potential as therapeutic targets for psychiatric disorders.
Newton, Charles R.
In "Global Perspective on Early Diagnosis and Intervention for Children with Developmental Delays and Disabilities" (p1079-1084, this issue), Scherzer et al. highlighted the potential increase in neurodevelopmental impairments and disabilities affecting an increasing number of children in low- and middle-income countries (LMIC). In this…
Brown, Amy; Crowe, Louise; Beauchamp, Miriam H; Anderson, Vicki; Boneh, Avihu
Glutaric aciduria type I (GA-I) is an inherited metabolic disorder that may lead to severe motor disorder and cognitive impairment. GA-I is now included in the newborn screening programme in many countries as early detection allows for prompt treatment and effectively reduces the risk of poor developmental outcome. Information regarding the long-term neurodevelopmental outcome of children with GA-I treated early is sparse.We recruited children with a confirmed diagnosis of GA-I diagnosed via newborn screening, treated in our centre and >3 years of age (n = 6). Children were assessed at two time points using a comprehensive neuropsychological test battery. Four of these had been the subject of a previous report. All participants were male, 3-6 years at the initial assessment and 6-12 years of age at the follow-up assessment.Fine motor skills were below average in all patients. Speech, which was affected in all four patients reported previously, improved following speech therapy. IQ scores remained generally stable within the normal range. Executive functioning was average to high average in four patients. Behaviour, as assessed through parental questionnaires, was problematic in two patients. Compounding factors included child neglect, family history of autism and multiple admissions to hospital (n = 1 in each).GA-I affects fine motor skills and speech, regardless of early treatment, but not IQ scores. Patients with GA-I should be referred for assessment and appropriate early intervention. Further research is needed to correlate specific neuropsychological deficits with neuroimaging.
Vinet, É; Pineau, C A; Clarke, A E; Fombonne, É; Platt, R W; Bernatsky, S
Children born to women with systemic lupus erythematosus seem to have a potentially increased risk of neurodevelopmental disorders compared to children born to healthy women. Recent experimental data suggest in utero exposure to maternal antibodies and cytokines as important risk factors for neurodevelopmental disorders. Interestingly, women with systemic lupus erythematosus display high levels of autoantibodies and cytokines, which have been shown, in animal models, to alter fetal brain development and induce behavioral anomalies in offspring. Furthermore, subjects with systemic lupus erythematosus and neurodevelopmental disorders share a common genetic predisposition, which could impair the fetal immune response to in utero immunologic insults. Moreover, systemic lupus erythematosus pregnancies are at increased risk of adverse obstetrical outcomes and medication exposures, which have been implicated as potential risk factors for neurodevelopmental disorders. In this article, we review the current state of knowledge on neurodevelopmental disorders and their potential determinants in systemic lupus erythematosus offspring. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.
Arnsten, Amy F. T.; Rubia, Katya
Objective: This article aims to review basic and clinical studies outlining the roles of prefrontal cortical (PFC) networks in the behavior and cognitive functions that are compromised in childhood neurodevelopmental disorders and how these map into the neuroimaging evidence of circuit abnormalities in these disorders. Method: Studies of animals,…
Kakooza-Mwesige, Angelina; Ssebyala, Keron; Karamagi, Charles; Kiguli, Sarah; Smith, Karen; Anderson, Meredith C.; Croen, Lisa A.; Trevathan, Edwin; Hansen, Robin; Smith, Daniel; Grether, Judith K.
Neurodevelopmental disorders are recognized to be relatively common in developing countries but little data exist for planning effective prevention and intervention strategies. In particular, data on autism spectrum disorders are lacking. For application in Uganda, we developed a 23-question screener (23Q) that includes the Ten Questions screener…
Fung, Lawrence K; Quintin, Eve-Marie; Haas, Brian W; Reiss, Allan L
The overarching goal of this review is to compare and contrast the cognitive-behavioral features of fragile X syndrome (FraX) and Williams syndrome and to review the putative neural and molecular underpinnings of these features. Information is presented in a framework that provides guiding principles for conceptualizing gene-brain-behavior associations in neurodevelopmental disorders. Abnormalities, in particular cognitive-behavioral domains with similarities in underlying neurodevelopmental correlates, occur in both FraX and Williams syndrome including aberrant frontostriatal pathways leading to executive function deficits, and magnocellular/dorsal visual stream, superior parietal lobe, inferior parietal lobe, and postcentral gyrus abnormalities contributing to deficits in visuospatial function. Compelling cognitive-behavioral and neurodevelopmental contrasts also exist in these two disorders, for example, aberrant amygdala and fusiform cortex structure and function occurring in the context of contrasting social behavioral phenotypes, and temporal cortical and cerebellar abnormalities potentially underlying differences in language function. Abnormal dendritic development is a shared neurodevelopmental morphologic feature between FraX and Williams syndrome. Commonalities in molecular machinery and processes across FraX and Williams syndrome occur as well - microRNAs involved in translational regulation of major synaptic proteins; scaffolding proteins in excitatory synapses; and proteins involved in axonal development. Although the genetic variations leading to FraX and Williams syndrome are different, important similarities and contrasts in the phenotype, neurocircuitry, molecular machinery, and cellular processes in these two disorders allow for a unique approach to conceptualizing gene-brain-behavior links occurring in neurodevelopmental disorders.
Doernberg, Ellen; Hollander, Eric
Neurodevelopmental disorders, specifically autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) have undergone considerable diagnostic evolution in the past decade. In the United States, the current system in place is the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), whereas worldwide, the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) serves as a general medical system. This review will examine the differences in neurodevelopmental disorders between these two systems. First, we will review the important revisions made from the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) to the DSM-5, with respect to ASD and ADHD. Next, we will cover the similarities and differences between ASD and ADHD classification in the DSM-5 and the ICD-10, and how these differences may have an effect on neurodevelopmental disorder diagnostics and classification. By examining the changes made for the DSM-5 in 2013, and critiquing the current ICD-10 system, we can help to anticipate and advise on the upcoming ICD-11, due to come online in 2017. Overall, this review serves to highlight the importance of progress towards complementary diagnostic classification systems, keeping in mind the difference in tradition and purpose of the DSM and the ICD, and that these systems are dynamic and changing as more is learned about neurodevelopmental disorders and their underlying etiology. Finally this review will discuss alternative diagnostic approaches, such as the Research Domain Criteria (RDoC) initiative, which links symptom domains to underlying biological and neurological mechanisms. The incorporation of new diagnostic directions could have a great effect on treatment development and insurance coverage for neurodevelopmental disorders worldwide.
Ho, Karen S; Twede, Hope; Vanzo, Rena; Harward, Erin; Hensel, Charles H; Martin, Megan M; Page, Stephanie; Peiffer, Andreas; Mowery-Rushton, Patricia; Serrano, Moises; Wassman, E Robert
Copy number variants (CNVs) as detected by chromosomal microarray analysis (CMA) significantly contribute to the etiology of neurodevelopmental disorders, such as developmental delay (DD), intellectual disability (ID), and autism spectrum disorder (ASD). This study summarizes the results of 3.5 years of CMA testing by a CLIA-certified clinical testing laboratory 5487 patients with neurodevelopmental conditions were clinically evaluated for rare copy number variants using a 2.8-million probe custom CMA optimized for the detection of CNVs associated with neurodevelopmental disorders. We report an overall detection rate of 29.4% in our neurodevelopmental cohort, which rises to nearly 33% when cases with DD/ID and/or MCA only are considered. The detection rate for the ASD cohort is also significant, at 25%. Additionally, we find that detection rate and pathogenic yield of CMA vary significantly depending on the primary indications for testing, the age of the individuals tested, and the specialty of the ordering doctor. We also report a significant difference between the detection rate on the ultrahigh resolution optimized array in comparison to the array from which it originated. This increase in detection can significantly contribute to the efficient and effective medical management of neurodevelopmental conditions in the clinic.
Du, X; Hill, R A
Neurodevelopmental disorders are a group of conditions that arises from impairments of the central nervous system during its development. The causes of the various disorders are heterogeneous and the symptoms likewise are multifarious. Most of these disorders currently have very little available treatment that is effective in combating the plethora of serious symptoms. Brain-derived neurotrophic factor (BDNF) is a fundamental neurotrophin with vital functions during brain development. Pre-clinical studies have shown that increasing BDNF signalling may be a potent way to prevent, arrest or even reverse abnormal neurodevelopmental events arising from a variety of genetic or environmental causes. However, many difficulties make BDNF problematic to administer in an efficient manner. The recent discovery of a small BDNF-mimetic, the naturally occurring flavonoid 7,8-dihydroxyflavone (7,8-DHF), may provide an avenue to allow efficient and safe activation of the BDNF pathway in tackling the symptoms of neurodevelopmental disorders. Here, evidence will be provided to support the potential of 7,8-DHF as a novel treatment for several neurodevelopmental disorders where the BDNF signalling pathway is implicated in the pathophysiology and where benefits are therefore most likely to be derived from its implementation. Copyright © 2015 Elsevier Ltd. All rights reserved.
Shehata, Amany I; Hassanein, Faika I; Abdul-Ghani, Rashad
Toxoplasma gondii is an opportunistic parasite with neurotropic characteristics that can mediate neurodevelopmental disorders, including mental, behavioral and personality aspects of their hosts. Therefore, the seroprevalence of anti-Toxoplasma antibodies has been studied in patients with different neurological disorders from different localities. On searching online databases, however, we could not find published studies on the seroprevalence of anti-Toxoplasma antibodies among patients with neurodevelopmental disorders in Egypt. Therefore, the present preliminary study was conducted to determine the serological profile of T. gondii infection among patients with non-schizophrenic neurodevelopmental disorders in Alexandria, Egypt. Data and blood samples were collected from 188 patients recruited for the study from four mental rehabilitation centers in the period from July 2014 to March 2015. The overall seropositivity rates of IgM and IgG among patients were 16.5% (31/188) and 50.0% (94/188), respectively. Of the studied patients' characteristics, only age was significantly associated with anti-Toxoplasma IgG seropositivity, with older patients being about twice more likely exposed to infection. However, no statistically significant association was found with IgM. In addition, seropositivity of anti-Toxoplasma IgG, but not IgM, was significantly associated with non-schizophrenic neurodevelopmental disorders; however, neither IgG nor IgM showed a significant association with cognitive impairment as indicated by the intelligence quotient scores. Copyright © 2015 Elsevier B.V. All rights reserved.
Full Text Available Many neurological disorders affect men and women differently regarding prevalence, progression, and severity. It is clear that many of these disorders may originate from defective signaling during fetal or perinatal brain development, which may affect males and females differently. Such sex-specific differences may originate from chromosomal or sex-hormone specific effects. This short review will focus on the estrogen receptor beta (ERβ signaling during perinatal brain development and put it in the context of sex-specific differences in neurodevelopmental disorders. We will discuss ERβ’s recent discovery in directing DNA de-methylation to specific sites, of which one such site may bear consequences for the susceptibility to the neurological reading disorder dyslexia. We will also discuss how dysregulations in sex-hormone signaling, like those evoked by endocrine disruptive chemicals, may affect this and other neurodevelopmental disorders in a sex-specific manner through ERβ.
Chilosi, Anna M.; Comparini, Alessandro; Scusa, Maria F.; Berrettini, Stefano; Forli, Francesca; Battini, Roberta; Cipriani, Paola; Cioni, Giovanni
Aim: The effects of sensorineural hearing loss (SNHL) are often complicated by additional disabilities, but the epidemiology of associated disorders is not clearly defined. The aim of this study was to evaluate the frequency and type of additional neurodevelopmental disabilities in a sample of children with SNHL and to investigate the relation…
Marschik, Peter B; Zhang, Dajie; Esposito, Gianluca; Bölte, Sven; Einspieler, Christa; Sigafoos, Jeff
The extent to which early motor patterns represent antecedents to later communicative functions, and the emergence of gesture and/or sign as potential communicative acts in neurodevelopmental disorders (NDDs), are research questions that have received recent attention. It is important to keep in mind that different NDDs have different neurological underpinnings, with correspondingly different implications for their conceptualization, detection, and treatment.
Eklund, Hanna; Findon, James; Cadman, Tim; Hayward, Hannah; Murphy, Declan; Asherson, Philip; Glaser, Karen; Xenitidis, Kiriakos
This study used the Camberwell Assessment of Need for adults with Developmental and Intellectual Disabilities (CANDID) to examine the social, physical health and mental health needs of 168 young people (aged 14-24 years) with neurodevelopmental disorders and compared young person and parent ratings of need. Agreement was poor in 21 out of 25…
Byrne, Susan; Jansen, Lara; U-King-Im, Jean-Marie; Siddiqui, Ata; Lidov, Hart G. W.; Bodi, Istvan; Smith, Luke; Mein, Rachael; Cullup, Thomas; Dionisi-Vici, Carlo; Al-Gazali, Lihadh; Al-Owain, Mohammed; Bruwer, Zandre; Al Thihli, Khalid; El-Garhy, Rana; Flanigan, Kevin M.; Manickam, Kandamurugu; Zmuda, Erik; Banks, Wesley; Gershoni-Baruch, Ruth; Mandel, Hanna; Dagan, Efrat; Raas-Rothschild, Annick; Barash, Hila; Filloux, Francis; Creel, Donnell; Harris, Michael; Hamosh, Ada; Kölker, Stefan; Ebrahimi-Fakhari, Darius; Hoffmann, Georg F.; Manchester, David; Boyer, Philip J.; Manzur, Adnan Y.; Lourenco, Charles Marques; Pilz, Daniela T.; Kamath, Arveen; Prabhakar, Prab; Rao, Vamshi K.; Rogers, R. Curtis; Ryan, Monique M.; Brown, Natasha J.; McLean, Catriona A.; Said, Edith; Schara, Ulrike; Stein, Anja; Sewry, Caroline; Travan, Laura; Wijburg, Frits A.; Zenker, Martin; Mohammed, Shehla; Fanto, Manolis; Gautel, Mathias; Jungbluth, Heinz
Vici syndrome is a progressive neurodevelopmental multisystem disorder due to recessive mutations in the key autophagy gene EPG5. We report genetic, clinical, neuroradiological, and neuropathological features of 50 children from 30 families, as well as the neuronal phenotype of EPG5 knock-down in
Lundström, Sebastian; Forsman, Mats; Larsson, Henrik; Kerekes, Nora; Serlachius, Eva; Långström, Niklas; Lichtenstein, Paul
The longitudinal relationship between attention deficit hyperactivity disorder (ADHD) and violent criminality has been extensively documented, while long-term effects of autism spectrum disorders (ASDs), tic disorders (TDs), and obsessive compulsive disorder (OCD) on criminality have been scarcely studied. Using population-based registers of all…
Dichter, Gabriel S; Damiano, Cara A; Allen, John A
This review summarizes evidence of dysregulated reward circuitry function in a range of neurodevelopmental and psychiatric disorders and genetic syndromes. First, the contribution of identifying a core mechanistic process across disparate disorders to disease classification is discussed, followed by a review of the neurobiology of reward circuitry. We next consider preclinical animal models and clinical evidence of reward-pathway dysfunction in a range of disorders, including psychiatric disorders (i.e., substance-use disorders, affective disorders, eating disorders, and obsessive compulsive disorders), neurodevelopmental disorders (i.e., schizophrenia, attention-deficit/hyperactivity disorder, autism spectrum disorders, Tourette's syndrome, conduct disorder/oppositional defiant disorder), and genetic syndromes (i.e., Fragile X syndrome, Prader-Willi syndrome, Williams syndrome, Angelman syndrome, and Rett syndrome). We also provide brief overviews of effective psychopharmacologic agents that have an effect on the dopamine system in these disorders. This review concludes with methodological considerations for future research designed to more clearly probe reward-circuitry dysfunction, with the ultimate goal of improved intervention strategies.
Dichter Gabriel S
Full Text Available Abstract This review summarizes evidence of dysregulated reward circuitry function in a range of neurodevelopmental and psychiatric disorders and genetic syndromes. First, the contribution of identifying a core mechanistic process across disparate disorders to disease classification is discussed, followed by a review of the neurobiology of reward circuitry. We next consider preclinical animal models and clinical evidence of reward-pathway dysfunction in a range of disorders, including psychiatric disorders (i.e., substance-use disorders, affective disorders, eating disorders, and obsessive compulsive disorders, neurodevelopmental disorders (i.e., schizophrenia, attention-deficit/hyperactivity disorder, autism spectrum disorders, Tourette’s syndrome, conduct disorder/oppositional defiant disorder, and genetic syndromes (i.e., Fragile X syndrome, Prader–Willi syndrome, Williams syndrome, Angelman syndrome, and Rett syndrome. We also provide brief overviews of effective psychopharmacologic agents that have an effect on the dopamine system in these disorders. This review concludes with methodological considerations for future research designed to more clearly probe reward-circuitry dysfunction, with the ultimate goal of improved intervention strategies.
Walker, Cheryl K.; Bremer, Andrew A.; Baker, Alice S.; Ozonoff, Sally; Hansen, Robin L.; Hertz-Picciotto, Irva
OBJECTIVE: We examined whether metabolic conditions (MCs) during pregnancy (diabetes, hypertension, and obesity) are associated with autism spectrum disorder (ASD), developmental delays (DD), or impairments in specific domains of development in the offspring. METHODS: Children aged 2 to 5 years (517 ASD, 172 DD, and 315 controls) were enrolled in the CHARGE (Childhood Autism Risks from Genetics and the Environment) study, a population-based, case-control investigation between January 2003 and June 2010. Eligible children were born in California, had parents who spoke English or Spanish, and were living with a biological parent in selected regions of California. Children’s diagnoses were confirmed by using standardized assessments. Information regarding maternal conditions was ascertained from medical records or structured interview with the mother. RESULTS: All MCs were more prevalent among case mothers compared with controls. Collectively, these conditions were associated with a higher likelihood of ASD and DD relative to controls (odds ratio: 1.61 [95% confidence interval: 1.10–2.37; odds ratio: 2.35 [95% confidence interval: 1.43–3.88], respectively). Among ASD cases, children of women with diabetes had Mullen Scales of Early Learning (MSEL) expressive language scores 0.4 SD lower than children of mothers without MCs (P neurodevelopmental problems in children. With obesity rising steadily, these results appear to raise serious public health concerns. PMID:22492772
Stamberger, H.; Nikanorova, M.; Willemsen, M.H.; Accorsi, P.; Angriman, M.; Baier, H.; Benkel-Herrenbrueck, I.; Benoit, V.; Budetta, M.; Caliebe, A.; Cantalupo, G.; Capovilla, G.; Casara, G.; Courage, C.; Deprez, M.; Destree, A.; Dilena, R.; Erasmus, C.E.; Fannemel, M.; Fjaer, R.; Giordano, L.; Helbig, K.L.; Heyne, H.O.; Klepper, J.; Kluger, G.J.; Lederer, D.; Lodi, M.; Maier, O.; Merkenschlager, A.; Michelberger, N.; Minetti, C.; Muhle, H.; Phalin, J.; Ramsey, K.; Romeo, A.; Schallner, J.; Schanze, I.; Shinawi, M.; Sleegers, K.; Sterbova, K.; Syrbe, S.; Traverso, M.; Tzschach, A.; Uldall, P.; Coster, R. van; Verhelst, H.; Viri, M.; Winter, S.; Wolff, M.; Zenker, M.; Zoccante, L.; Jonghe, P. De; Helbig, I.; Striano, P.; Lemke, J.R.; Moller, R.S.; Weckhuysen, S.
OBJECTIVE: To give a comprehensive overview of the phenotypic and genetic spectrum of STXBP1 encephalopathy (STXBP1-E) by systematically reviewing newly diagnosed and previously reported patients. METHODS: We recruited newly diagnosed patients with STXBP1 mutations through an international network
Maria Luísa Bissoto
Full Text Available The neurodevelopmental disorders, mainly those genetics ones, are argued with the aim to analyze the human development conceptions that underlie these, and its impact for understanding who is the individual that carries this disorder. Methodologically, epistemological presupposition from “classical” neuropsychology and from “neuroconstructivist” neuropsychology had been compared. As results of this parallel had been considered relevant: a. the role of the individual surrounding, b. the question concerning the plasticity and dynamical character of development and c. the formal developmental process, from prenatal to postnatal period. The concluding comments claims that the Neuroconstructivist approaches allow conceiving the developmental process within genetics neurodevelopmental disorders not as a “fault” but as a differentiated and particular one. That should be understood in the Educational and Rehabilitation settings not as a nosological category but as a specific way of an individual acting while looking for a mode of being-in-the-world.
Wade, Mark; Prime, Heather; Madigan, Sheri
Neurodevelopmental disorders represent a broad class of childhood neurological conditions that have a significant bearing on the wellbeing of children, families, and communities. In this review, we draw on evidence from two common and widely studied neurodevelopmental disorders-autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD)-to demonstrate the utility of genetically informed sibling designs in uncovering the nature and pathogenesis of these conditions. Specifically, we examine how twin, recurrence risk, and infant prospective tracking studies have contributed to our understanding of genetic and environmental liabilities towards neurodevelopmental morbidity through their impact on neurocognitive processes and structural/functional neuroanatomy. It is suggested that the siblings of children with ASD and ADHD are at risk not only of clinically elevated problems in these areas, but also of subthreshold symptoms and/or subtle impairments in various neurocognitive skills and other domains of psychosocial health. Finally, we close with a discussion on the practical relevance of sibling designs and how these might be used in the service of early screening, prevention, and intervention efforts that aim to alleviate the negative downstream consequences associated with disorders of neurodevelopment.
Wanke, Kai A; Devanna, Paolo; Vernes, Sonja C
Neurodevelopmental disorders have a strong genetic component, but despite widespread efforts, the specific genetic factors underlying these disorders remain undefined for a large proportion of affected individuals. Given the accessibility of exome sequencing, this problem has thus far been addressed from a protein-centric standpoint; however, protein-coding regions only make up ∼1% to 2% of the human genome. With the advent of whole genome sequencing we are in the midst of a paradigm shift as it is now possible to interrogate the entire sequence of the human genome (coding and noncoding) to fill in the missing heritability of complex disorders. These new technologies bring new challenges, as the number of noncoding variants identified per individual can be overwhelming, making it prudent to focus on noncoding regions of known function, for which the effects of variation can be predicted and directly tested to assess pathogenicity. The 3'UTRome is a region of the noncoding genome that perfectly fulfills these criteria and is of high interest when searching for pathogenic variation related to complex neurodevelopmental disorders. Herein, we review the regulatory roles of the 3'UTRome as binding sites for microRNAs or RNA binding proteins, or during alternative polyadenylation. We detail existing evidence that these regions contribute to neurodevelopmental disorders and outline strategies for identification and validation of novel putatively pathogenic variation in these regions. This evidence suggests that studying the 3'UTRome will lead to the identification of new risk factors, new candidate disease genes, and a better understanding of the molecular mechanisms contributing to neurodevelopmental disorders. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
Full Text Available Neurodevelopmental disorders represent a broad class of childhood neurological conditions that have a significant bearing on the wellbeing of children, families, and communities. In this review, we draw on evidence from two common and widely studied neurodevelopmental disorders—autism spectrum disorder (ASD and attention-deficit hyperactivity disorder (ADHD—to demonstrate the utility of genetically informed sibling designs in uncovering the nature and pathogenesis of these conditions. Specifically, we examine how twin, recurrence risk, and infant prospective tracking studies have contributed to our understanding of genetic and environmental liabilities towards neurodevelopmental morbidity through their impact on neurocognitive processes and structural/functional neuroanatomy. It is suggested that the siblings of children with ASD and ADHD are at risk not only of clinically elevated problems in these areas, but also of subthreshold symptoms and/or subtle impairments in various neurocognitive skills and other domains of psychosocial health. Finally, we close with a discussion on the practical relevance of sibling designs and how these might be used in the service of early screening, prevention, and intervention efforts that aim to alleviate the negative downstream consequences associated with disorders of neurodevelopment.
Arnsten, Amy F T; Rubia, Katya
This article aims to review basic and clinical studies outlining the roles of prefrontal cortical (PFC) networks in the behavior and cognitive functions that are compromised in childhood neurodevelopmental disorders and how these map into the neuroimaging evidence of circuit abnormalities in these disorders. Studies of animals, normally developing children, and patients with neurodevelopmental disorders were reviewed, with focus on neuroimaging studies. The PFC provides "top-down" regulation of attention, inhibition/cognitive control, motivation, and emotion through connections with posterior cortical and subcortical structures. Dorsolateral and inferior PFC regulate attention and cognitive/inhibitory control, whereas orbital and ventromedial structures regulate motivation and affect. PFC circuitries are very sensitive to their neurochemical environment, and small changes in the underlying neurotransmitter systems, e.g. by medications, can produce large effects on mediated function. Neuroimaging studies of children with neurodevelopmental disorders show altered brain structure and function in distinctive circuits respecting this organization. Children with attention-deficit/hyperactivity disorder show prominent abnormalities in the inferior PFC and its connections to striatal, cerebellar, and parietal regions, whereas children with conduct disorder show alterations in the paralimbic system, comprising ventromedial, lateral orbitofrontal, and superior temporal cortices together with specific underlying limbic regions, regulating motivation and emotion control. Children with major depressive disorder show alterations in ventral orbital and limbic activity, particularly in the left hemisphere, mediating emotions. Finally, children with obsessive-compulsive disorder appear to have a dysregulation in orbito-fronto-striatal inhibitory control pathways, but also deficits in dorsolateral fronto-parietal systems of attention. Altogether, there is a good correspondence
Janecka, M; Mill, J; Basson, M A; Goriely, A; Spiers, H; Reichenberg, A; Schalkwyk, L; Fernandes, C
Multiple epidemiological studies suggest a relationship between advanced paternal age (APA) at conception and adverse neurodevelopmental outcomes in offspring, particularly with regard to increased risk for autism and schizophrenia. Conclusive evidence about how age-related changes in paternal gametes, or age-independent behavioral traits affect neural development is still lacking. Recent evidence suggests that the origins of APA effects are likely to be multidimensional, involving both inherited predisposition and de novo events. Here we provide a review of the epidemiological and molecular findings to date. Focusing on the latter, we present the evidence for genetic and epigenetic mechanisms underpinning the association between late fatherhood and disorder in offspring. We also discuss the limitations of the APA literature. We propose that different hypotheses relating to the origins of the APA effects are not mutually exclusive. Instead, multiple mechanisms likely contribute, reflecting the etiological complexity of neurodevelopmental disorders.
Berridge, Michael J
The process of development depends on a number of signaling systems that regulates the progressive sequence of developmental events. Infertility and neurodevelopmental diseases, such as attention deficit hyperactivity disorder, autism spectrum disorders, and schizophrenia, are caused by specific alterations in these signaling processes. Calcium signaling plays a prominent role throughout development beginning at fertilization and continuing through early development, implantation, and organ differentiation such as heart and brain development. Vitamin D plays a major role in regulating these signaling processes that control development. There is an increase in infertility and an onset of neurodevelopmental diseases when vitamin D is deficient. The way in which vitamin D deficiency acts to alter development is a major feature of this review. One of the primary functions of vitamin D is to maintain the phenotypic stability of both the Ca 2+ and redox signaling pathways that play such a key role throughout development.
Merikangas, Alison K
Copy-number variation (CNV) is the most prevalent type of structural variation in the human genome. There is emerging evidence that copy-number variants (CNVs) provide a new vista on understanding susceptibility to neuropsychiatric disorders. Some challenges in the interpretation of current CNV studies include the use of overlapping samples, differing phenotypic definitions, an absence of population norms for CNVs and a lack of consensus in methods for CNV detection and analysis. Here, we review current CNV association study methods and results in autism spectrum disorders (ASD) and schizophrenia, and provide suggestions for design approaches to future studies that might maximize the translation of this work to etiological understanding.
Autism spectrum disorders (ASD), a group of neurodevelopmental disorders characterized by marked deficits in social interaction and communication with unusually restricted interests, have a tremendous impact on society and are increasingly being diagnosed. Increased developmental screening, use of standardized diagnostic tests, and a broadening of Diagnostic and Statistical Manual of Mental Disorders (American Psychiatric Association, 2000) criteria might account for the increased incidence. Evidence-based treatments for children with ASD, reviewed by the National Standards Project, are primarily behavioral interventions with foundations in the sciences of applied behavior analysis and developmental psychology and emphasize improved functional communication and social reciprocity.
Lahiri, Debomoy K.; Sokol, Deborah K.; Erickson, Craig; Ray, Balmiki; Ho, Chang Y.; Maloney, Bryan
Autism is a neurodevelopmental disorder marked by social skills and communication deficits and interfering repetitive behavior. Intellectual disability often accompanies autism. In addition to behavioral deficits, autism is characterized by neuropathology and brain overgrowth. Increased intracranial volume often accompanies this brain growth. We have found that the Alzheimer’s disease (AD) associated amyloid-β precursor protein (APP), especially its neuroprotective processing product, secrete...
Johnston, Richard; Pitchford, Nicola J; Roach, Neil W; Ledgeway, Timothy
A selective deficit in processing the global (overall) motion, but not form, of spatially extensive objects in the visual scene is frequently associated with several neurodevelopmental disorders, including preterm birth. Existing theories that proposed to explain the origin of this visual impairment are, however, challenged by recent research. In this review, we explore alternative hypotheses for why deficits in the processing of global motion, relative to global form, might arise. We describe recent evidence that has utilised novel tasks of global motion and global form to elucidate the underlying nature of the visual deficit reported in different neurodevelopmental disorders. We also examine the role of IQ and how the sex of an individual can influence performance on these tasks, as these are factors that are associated with performance on global motion tasks, but have not been systematically controlled for in previous studies exploring visual processing in clinical populations. Finally, we suggest that a new theoretical framework is needed for visual processing in neurodevelopmental disorders and present recommendations for future research. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.
Reinders, A A T S; Chalavi, S; Schlumpf, Y R; Vissia, E M; Nijenhuis, E R S; Jäncke, L; Veltman, D J; Ecker, C
To examine the two constitutes of cortical volume (CV), that is, cortical thickness (CT) and surface area (SA), in individuals with dissociative identity disorder (DID) with the view of gaining important novel insights into the underlying neurobiological mechanisms mediating DID. This study included 32 female patients with DID and 43 matched healthy controls. Between-group differences in CV, thickness, and SA, the degree of spatial overlap between differences in CT and SA, and their relative contribution to differences in regional CV were assessed using a novel spatially unbiased vertex-wise approach. Whole-brain correlation analyses were performed between measures of cortical anatomy and dissociative symptoms and traumatization. Individuals with DID differed from controls in CV, CT, and SA, with significantly decreased CT in the insula, anterior cingulate, and parietal regions and reduced cortical SA in temporal and orbitofrontal cortices. Abnormalities in CT and SA shared only about 3% of all significantly different cerebral surface locations and involved distinct contributions to the abnormality of CV in DID. Significant negative associations between abnormal brain morphology (SA and CV) and dissociative symptoms and early childhood traumatization (0 and 3 years of age) were found. In DID, neuroanatomical areas with decreased CT and SA are in different locations in the brain. As CT and SA have distinct genetic and developmental origins, our findings may indicate that different neurobiological mechanisms and environmental factors impact on cortical morphology in DID, such as early childhood traumatization. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Hannah Mary Grayton
Full Text Available BACKGROUND: Copy number variants have emerged as an important genomic cause of common, complex neurodevelopmental disorders. These usually change copy number of multiple genes, but deletions at 2p16.3, which have been associated with autism, schizophrenia and mental retardation, affect only the neurexin 1 gene, usually the alpha isoform. Previous analyses of neurexin 1α (Nrxn1α knockout (KO mouse as a model of these disorders have revealed impairments in synaptic transmission but failed to reveal defects in social behaviour, one of the core symptoms of autism. METHODS: We performed a detailed investigation of the behavioural effects of Nrxn1α deletion in mice bred onto a pure genetic background (C57BL/6J to gain a better understanding of its role in neurodevelopmental disorders. Wildtype, heterozygote and homozygote Nrxn1α KO male and female mice were tested in a battery of behavioural tests (n = 9-16 per genotype, per sex. RESULTS: In homozygous Nrxn1α KO mice, we observed altered social approach, reduced social investigation, and reduced locomotor activity in novel environments. In addition, male Nrxn1α KO mice demonstrated an increase in aggressive behaviours. CONCLUSIONS: These are the first experimental data that associate a deletion of Nrxn1α with alterations of social behaviour in mice. Since this represents one of the core symptom domains affected in autism spectrum disorders and schizophrenia in humans, our findings suggest that deletions within NRXN1 found in patients may be responsible for the impairments seen in social behaviours, and that the Nrxn1α KO mice are a useful model of human neurodevelopmental disorder.
Grayton, Hannah Mary; Missler, Markus
Background Copy number variants have emerged as an important genomic cause of common, complex neurodevelopmental disorders. These usually change copy number of multiple genes, but deletions at 2p16.3, which have been associated with autism, schizophrenia and mental retardation, affect only the neurexin 1 gene, usually the alpha isoform. Previous analyses of neurexin 1α (Nrxn1α) knockout (KO) mouse as a model of these disorders have revealed impairments in synaptic transmission but failed to reveal defects in social behaviour, one of the core symptoms of autism. Methods We performed a detailed investigation of the behavioural effects of Nrxn1α deletion in mice bred onto a pure genetic background (C57BL/6J) to gain a better understanding of its role in neurodevelopmental disorders. Wildtype, heterozygote and homozygote Nrxn1α KO male and female mice were tested in a battery of behavioural tests (n = 9–16 per genotype, per sex). Results In homozygous Nrxn1α KO mice, we observed altered social approach, reduced social investigation, and reduced locomotor activity in novel environments. In addition, male Nrxn1α KO mice demonstrated an increase in aggressive behaviours. Conclusions These are the first experimental data that associate a deletion of Nrxn1α with alterations of social behaviour in mice. Since this represents one of the core symptom domains affected in autism spectrum disorders and schizophrenia in humans, our findings suggest that deletions within NRXN1 found in patients may be responsible for the impairments seen in social behaviours, and that the Nrxn1α KO mice are a useful model of human neurodevelopmental disorder. PMID:23840597
Gyllenberg, David; Marttila, Mikko; Sund, Reijo; Jokiranta-Olkoniemi, Elina; Sourander, André; Gissler, Mika; Ristikari, Tiina
Comprehensive overviews of the temporal changes in treated psychiatric and neurodevelopmental disorders during adolescence are scarce. We reviewed data from two national cohorts, 10 years apart, to establish the change in use of specialised services for psychiatric and neurodevelopmental diagnoses in Finland. We compared the nationwide register-based incidence of psychiatric and neurodevelopmental diagnoses between the 12th birthday and 18th birthday of adolescents born in Finland in 1987 and 1997. Adolescents who emigrated or died before their 12th birthday and those with missing covariate data were excluded, as were those who, when aged 11 years, had lived in a municipality belonging to a hospital district with obviously incomplete data reports during any follow-up years in our study. Our primary outcomes were time to incident specialised service use for any psychiatric or neurodevelopmental disorder and for 17 specific diagnostic classes. We also investigated whether adolescents who died by suicide had accessed specialised services before their deaths. The cumulative incidence of psychiatric or neurodevelopmental disorders increased from 9·8 in the 1987 cohort to 14·9 in the 1997 cohort (difference 5·2 percentage points [95% CI 4·8-5·5]) among girls, and from 6·2 in the 1987 cohort to 8·8 in the 1997 (2·6 percentage points [2·4-2·9]) among boys. The hazard ratio for the overall relative increase in neurodevelopment and psychiatric disorders in the 1997 cohort compared with the 1987 cohort was 1·6 (95% CI 1·5-1·8) among girls and 1·5 (1·4-1·6) among boys. Of the studied diagnostic classes, we noted significant (ie, pneurodevelopmental disorders points to the need to deliver effective treatment to a rapidly increased patient population, whereas the relative increase in specific diagnoses should inform clinical practice. Despite increasing service use, identification of adolescents at risk of suicide remains a major public health priority. Academy
Full Text Available Previous models or hypotheses of autism spectral disorder (ASD failed to take into full consideration the chronological and causal developmental trajectory, leading to the emergence of diverse phenotypes through a complex interaction between individual etiologies and environmental factors. Those phenotypes include persistent deficits in social communication and social interaction (criteria A in DSM-5, and restricted, repetitive patterns of behavior, interests, or activities (criteria B in DSM-5. In this article, we proposed a domain-general model that can explain criteria in DSM-5 based on the assumption that the same etiological mechanism would trigger the various phenotypes observed in different individuals with ASD. In the model, we assumed the following joint causes as the etiology of autism: (1 Hypoplasia of the pons in the brainstem, occurring immediately following neural tube closure; and (2 Deficiency in the GABA (γ-aminobutyric acid developmental switch during the perinatal period. Microstructural abnormalities of the pons directly affect both the structural and functional development of the brain areas strongly connected to it, especially amygdala. The impairment of GABA switch could not only lead to the deterioration of inhibitory processing in the neural network, but could also cause abnormal cytoarchitecture. We introduced a perspective that atypical development in both brain structure and function can give full explanation of diverse phenotypes and pathogenetic mechanism of ASD. Finally, we discussed about neural mechanisms underlying the phenotypic characteristics of ASD that are not described in DSM-5 but should be considered as important foundation: sleep, global precedence, categorical perception, intelligence, interoception and motor control.
David A. Geier
Full Text Available A hypothesis testing case-control study evaluated concerns about the toxic effects of organic-mercury (Hg exposure from thimerosal-containing (49.55% Hg by weight vaccines on the risk of neurodevelopmental disorders (NDs. Automated medical records were examined to identify cases and controls enrolled from their date-of-birth (1991–2000 in the Vaccine Safety Datalink (VSD project. ND cases were diagnosed with pervasive developmental disorder (PDD, specific developmental delay, tic disorder or hyperkinetic syndrome of childhood. In addition, putative non-thimerosal-related outcomes of febrile seizure, failure to thrive and cerebral degenerations were examined. The cumulative total dose of Hg exposure from thimerosal-containing hepatitis B vaccine (T-HBV administered within the first six months of life was calculated. On a per microgram of organic-Hg basis, PDD (odds ratio (OR = 1.054, specific developmental delay (OR = 1.035, tic disorder (OR = 1.034 and hyperkinetic syndrome of childhood (OR = 1.05 cases were significantly more likely than controls to receive increased organic-Hg exposure. By contrast, none of the non-thimerosal related outcomes were significantly more likely than the controls to have received increased organic-Hg exposure. Routine childhood vaccination may be an important public health tool to reduce infectious disease-associated morbidity/mortality, but the present study significantly associates organic-Hg exposure from T-HBV with an increased risk of an ND diagnosis.
Yewande O. Oshodi
Full Text Available Autism Spectrum Disorder (ASD is a globally prevalent neurodevelopmental disorder for which early diagnosis and intervention is the mainstay of management. In the African continent, limited data is available regarding the non-clinic based samples. Lack of information available to caregivers and inadequate skilled manpower often limit early detection and access to the few available though under resourced services in the community. Community based screening can be an important drive to create awareness and improve information dissemination regarding services available for those living with this disorder. This is a descriptive cross-sectional study utilizing data obtained from participants of a community-based autism screening exercise. The surveillance exercise was part of the annual Orange Ribbon initiative for autism awareness and screening held in 2014. Data was obtained from 85 participants involved in the Autism Surveillance screening exercise within the Lagos community. Community public service radio announcements state wide and word of mouth were used to invite and enroll eligible participants to the screening and consultation exercise. A second stage screening and a brief sociodemographic questionnaire followed by a third stage clinical interview and evaluation using the Diagnostic and Statistical Manual of Mental Disorders - 5 Edition (DSM 5 were used. Appropriate consultation and referrals to services in the community were given. Participants had a mean age of 7.53 years (SD 4.35. Twenty-nine (34.5% met the diagnosis of ASD. Other diagnosis included attention deficit hyperactivity disorder (ADHD, language and speech disorder, intellectual disability (8.3% and learning disorders (9.5%. Main health concerns to caregivers were poor language development in all (100%, of which 11 (40.7% were non-verbal; gaze avoidance was seen in 14 (48.3% and challenging behavior in 12 (42.9%. Comorbidities included seizure disorders (3.4% and ADHD (6
Gumpricht, Eric; Rockway, Susie
The incidence of childhood neurodevelopmental disorders, which include autism, attention-deficit hyperactivity disorders, and apraxia, are increasing worldwide and have a profound effect on the behaviors, cognitive skills, mood, and self-esteem of these children. Although the etiologies of these disorders are unclear, they often accompany genetic and biochemical abnormalities resulting in cognitive and communication difficulties. Because cognitive and neural development require essential fatty acids (particularly long-chain ω-3 fatty acids often lacking in mother's and children's diets) during critical growth periods, the potential behavior-modifying effects of these fatty acids as "brain nutrients" has attracted considerable attention. Additionally, there is compelling evidence for increased oxidative stress, altered antioxidant defenses, and neuroinflammation in these children. The purpose of this review is to provide a scientific rationale based on cellular, experimental animal model, observational, and clinical intervention studies for incorporating the combination of ω-3 fatty acids and tocotrienol-rich vitamin E as complementary nutritional therapies in children with neurodevelopmental disorders. Should this nutritional combination correct key clinical or biochemical outcomes and/or improve behavioral patterns, it would provide a safe, complementary option for these children. Copyright © 2014 Elsevier Inc. All rights reserved.
Byrne, Susan; Jansen, Lara; U-King-Im, Jean-Marie; Siddiqui, Ata; Lidov, Hart G. W.; Bodi, Istvan; Smith, Luke; Mein, Rachael; Cullup, Thomas; Dionisi-Vici, Carlo; Al-Gazali, Lihadh; Al-Owain, Mohammed; Bruwer, Zandre; Al Thihli, Khalid; El-Garhy, Rana; Flanigan, Kevin M.; Manickam, Kandamurugu; Zmuda, Erik; Banks, Wesley; Gershoni-Baruch, Ruth; Mandel, Hanna; Dagan, Efrat; Raas-Rothschild, Annick; Barash, Hila; Filloux, Francis; Creel, Donnell; Harris, Michael; Hamosh, Ada; Kölker, Stefan; Ebrahimi-Fakhari, Darius; Hoffmann, Georg F.; Manchester, David; Boyer, Philip J.; Manzur, Adnan Y.; Lourenco, Charles Marques; Pilz, Daniela T.; Kamath, Arveen; Prabhakar, Prab; Rao, Vamshi K.; Rogers, R. Curtis; Ryan, Monique M.; Brown, Natasha J.; McLean, Catriona A.; Said, Edith; Schara, Ulrike; Stein, Anja; Sewry, Caroline; Travan, Laura; Wijburg, Frits A.; Zenker, Martin; Mohammed, Shehla; Fanto, Manolis; Gautel, Mathias
Vici syndrome is a progressive neurodevelopmental multisystem disorder due to recessive mutations in the key autophagy gene EPG5. We report genetic, clinical, neuroradiological, and neuropathological features of 50 children from 30 families, as well as the neuronal phenotype of EPG5 knock-down in Drosophila melanogaster. We identified 39 different EPG5 mutations, most of them truncating and predicted to result in reduced EPG5 protein. Most mutations were private, but three recurrent mutations (p.Met2242Cysfs*5, p.Arg417*, and p.Gln336Arg) indicated possible founder effects. Presentation was mainly neonatal, with marked hypotonia and feeding difficulties. In addition to the five principal features (callosal agenesis, cataracts, hypopigmentation, cardiomyopathy, and immune dysfunction), we identified three equally consistent features (profound developmental delay, progressive microcephaly, and failure to thrive). The manifestation of all eight of these features has a specificity of 97%, and a sensitivity of 89% for the presence of an EPG5 mutation and will allow informed decisions about genetic testing. Clinical progression was relentless and many children died in infancy. Survival analysis demonstrated a median survival time of 24 months (95% confidence interval 0–49 months), with only a 10th of patients surviving to 5 years of age. Survival outcomes were significantly better in patients with compound heterozygous mutations (P = 0.046), as well as in patients with the recurrent p.Gln336Arg mutation. Acquired microcephaly and regression of skills in long-term survivors suggests a neurodegenerative component superimposed on the principal neurodevelopmental defect. Two-thirds of patients had a severe seizure disorder, placing EPG5 within the rapidly expanding group of genes associated with early-onset epileptic encephalopathies. Consistent neuroradiological features comprised structural abnormalities, in particular callosal agenesis and pontine hypoplasia, delayed
Golembo-Smith, Shana; Schiffman, Jason; Kline, Emily
of 265 Danish children in 1972, when participants were 10-13years old. Parent psychiatric diagnoses were also obtained in order to evaluate the predictive strength of neurodevelopmental factors in combination with genetic risk. Adult diagnostic information was available for 244 members of the sample....... Participants were grouped into three categories indicating level of genetic risk: children with a parent with schizophrenia (n=94); children with a parent with a non-psychotic mental health diagnosis (n=84); and children with a parent with no records of psychiatric hospitalization (n=66). Variables measured...... included minor physical anomalies (MPAs), coordination, ocular alignment, laterality, and IQ. Adult diagnoses were assessed through psychiatric interviews in 1992, as well as through a scan of the national psychiatric registry through 2007. Through a combination of multiple childhood predictors, the model...
Raine, Adrian; Lee, Lydia; Yang, Yaling; Colletti, Patrick
Antisocial personality disorder and psychopathy have been hypothesised to have a neurodevelopmental basis, but this proposition has not been formally tested. This study tests the hypothesis that individuals with cavum septum pellucidum (CSP), a marker of limbic neural maldevelopment, will show higher levels of psychopathy and antisocial personality. Cavum septum pellucidum was assessed using anatomical magnetic resonance imaging in a community sample. Those with CSP (n = 19) were compared with those lacking CSP (n = 68) on antisocial personality, psychopathy and criminal offending. Those with CSP had significantly higher levels of antisocial personality, psychopathy, arrests and convictions compared with controls. The pervasiveness of this association was indicated by the fact that those lacking a diagnosis of antisocial personality disorder, but who were charged or convicted for an offence, had a more extensive CSP than non-antisocial controls. Results could not be attributed to prior trauma exposure, head injury, demographic factors or comorbid psychiatric conditions. Our findings appear to be the first to provide evidence for a neurodevelopmental brain abnormality in those with antisocial personality disorder and psychopathy, and support the hypothesis that early maldevelopment of limbic and septal structures predisposes to the spectrum of antisocial behaviours.
Raine, Adrian; Lee, Lydia; Yang, Yaling; Colletti, Patrick
Background Antisocial personality disorder and psychopathy have been hypothesised to have a neurodevelopmental basis, but this proposition has not been formally tested. Aims This study tests the hypothesis that individuals with cavum septum pellucidum (CSP), a marker of limbic neural maldevelopment, will show higher levels of psychopathy and antisocial personality. Method Cavum septum pellucidum was assessed using anatomical magnetic resonance imaging in a community sample. Those with CSP (n = 19) were compared with those lacking CSP (n = 68) on antisocial personality, psychopathy and criminal offending. Results Those with CSP had significantly higher levels of antisocial personality, psychopathy, arrests and convictions compared with controls. The pervasiveness of this association was indicated by the fact that those lacking a diagnosis of antisocial personality disorder, but who were charged or convicted for an offence, had a more extensive CSP than non-antisocial controls. Results could not be attributed to prior trauma exposure, head injury, demographic factors or comorbid psychiatric conditions. Conclusions Our findings appear to be the first to provide evidence for a neurodevelopmental brain abnormality in those with antisocial personality disorder and psychopathy, and support the hypothesis that early maldevelopment of limbic and septal structures predisposes to the spectrum of antisocial behaviours. PMID:20807962
Full Text Available Most psychiatric disorders are considered neurodevelopmental, and the associated genes often are expressed in tissues outside of the brain. This suggests a biological relatedness with medical co-occurrences that could have broad clinical implications for diagnosis and patient management over a lifetime. A qualitative integration of public data from genetic consortia of psychiatric disorders and medical comorbidities explores the question of whether genetically associated psychiatric illnesses present with co-occurring disturbances can be used to define specific mental-physical health relations. Novel patterns of gene-disorder relations appear with approximately one-third of conservatively defined, consortia-generated candidate risk genes with multiple psychiatric diagnoses. Moreover, nearly as many genes overlap with non-psychiatric phenotypes, including cardiovascular, renal, respiratory and metabolic disturbances. While the landscape of genetic risk will change as study populations are expanded and biological confirmations accrue, the current relationships suggest that a mostly siloed perspective of gene relatedness to one categorical psychiatric diagnosis is not clinically useful. The future holds the promise that once candidates are fully validated, genome screening and mutation identification will bring more precision for predicting the risk for complex health conditions. Our view is that as genetic data is refined, continuing to decipher a shared pattern of genetic risk for brain and peripheral organ pathophysiology is not simply an academic exercise. Rather, determining relatedness will impact predictions of multifaceted health risks, patient treatment and management.
Di Pietro, Nina C; Whiteley, Louise Emma; Illes, Judy
The Internet has quickly gained popularity as a major source of health-related information, but its impact is unclear. Here, we investigate the extent to which advocacy websites for three neurodevelopmental disorders—cerebral palsy (CP), autism spectrum disorder (ASD) and fetal alcohol spectrum...... disorder (FASD)—inform stakeholders about treatment options, and discuss the ethical challenges inherent in providing such information online. We identified major advocacy websites for each disorder and assessed website accountability, the number, attributes, and accessibility of treatments described......, and the valence of treatment information. With the exception of FASD websites, we found that advocacy websites provide a plethora of information about a wide variety of readily available products and services. Treatment information is primarily targeted at families and is overwhelmingly encouraging, regardless...
The study of language knowledge guided by a purely biological perspective prioritizes the study of syntax. The essential process of syntax is recursion--the ability to generate an infinite array of expressions from a limited set of elements. Researchers working within the biological perspective argue that this ability is possible only because of an innately specified genetic makeup that is specific to human beings. Such a view of language knowledge may be fully justified in discussions on biolinguistics, and in evolutionary biology. However, it is grossly inadequate in understanding language-learning problems, particularly those experienced by children with neurodevelopmental disorders such as developmental dyslexia, Williams syndrome, specific language impairment and autism spectrum disorders. Specifically, syntax-centered definitions of language knowledge completely ignore certain crucial aspects of language learning and use, namely, that language is embedded in a social context; that the role of envrironmental triggering as a learning mechanism is grossly underestimated; that a considerable extent of visuo-spatial information accompanies speech in day-to-day communication; that the developmental process itself lies at the heart of knowledge acquisition; and that there is a tremendous variation in the orthographic systems associated with different languages. All these (socio-cultural) factors can influence the rate and quality of spoken and written language acquisition resulting in much variation in phenotypes associated with disorders known to have a genetic component. Delineation of such phenotypic variability requires inputs from varied disciplines such as neurobiology, neuropsychology, linguistics and communication disorders. In this paper, I discuss published research that questions cognitive modularity and emphasises the role of the environment for understanding linguistic capabilities of children with neuro-developmental disorders. The discussion pertains
Lazar, Steven M; Evans, David W; Myers, Scott M; Moreno-De Luca, Andres; Moore, Gregory J
Social cognition is an important aspect of social behavior in humans. Social cognitive deficits are associated with neurodevelopmental and neuropsychiatric disorders. In this study we examine the neural substrates of social cognition and face processing in a group of healthy young adults to examine the neural substrates of social cognition. Fifty-seven undergraduates completed a battery of social cognition tasks and were assessed with electroencephalography (EEG) during a face-perception task. A subset (N=22) were administered a face-perception task during functional magnetic resonance imaging. Variance in the N170 EEG was predicted by social attribution performance and by a quantitative measure of empathy. Neurally, face processing was more bilateral in females than in males. Variance in fMRI voxel count in the face-sensitive fusiform gyrus was predicted by quantitative measures of social behavior, including the Social Responsiveness Scale (SRS) and the Empathizing Quotient. When measured as a quantitative trait, social behaviors in typical and pathological populations share common neural pathways. The results highlight the importance of viewing neurodevelopmental and neuropsychiatric disorders as spectrum phenomena that may be informed by studies of the normal distribution of relevant traits in the general population. Copyright © 2014 Elsevier B.V. All rights reserved.
Smith, B L; Reyes, T M
Maternal malnutrition significantly increases offspring risk for both metabolic and neurodevelopmental disorders. Animal models of maternal malnutrition have identified behavioral changes in the adult offspring related to executive function and reward processing. Together, these changes in executive and reward-based behaviors likely contribute to the etiology of both metabolic and neurodevelopmental disorders associated with maternal malnutrition. Concomitant with the behavioral effects, maternal malnutrition alters offspring expression of reward-related molecules and inflammatory signals in brain pathways that control executive function and reward. Neuroimmune pathways and microglial interactions in these specific brain circuits, either in early development or later in adulthood, could directly contribute to the maternal malnutrition-induced behavioral phenotypes. Understanding these mechanisms will help advance treatment strategies for metabolic and neurodevelopmental disorders, especially noninvasive dietary supplementation interventions. Copyright © 2017 Elsevier Inc. All rights reserved.
Allan, Steven; Goss, Ken
To test for differences between diagnostic groups on the severity of eating disorder beliefs and behaviours, evaluate the clinical significance of such differences, and assess the extent to which these beliefs and behaviours may be present at clinically significant levels across eating disorder diagnoses. 136 adult women outpatients (aged 18-65, with a BMI over 15) were diagnosed with an eating disorder and completed the Stirling Eating Disorder Scale. The expected pattern of statistically significant differences was found between diagnostic groups on anorexic dietary beliefs and behaviours and bulimic dietary beliefs and behaviours. A high percentage of participants in each diagnostic group scored above the clinical cut-off on the eating disorder belief and behaviour measures and a very high percentage of participants in each group reported clinically significant levels of restricting beliefs. Transdiagnostic or functional analytic approaches to treatment planning may lead to more effective interventions than current, diagnostically-based, care pathways. The high prevalence of restricting beliefs reported suggested that this may need to be a key focus for intervention for the majority of individuals presenting with an eating disorder. © 2013.
Alexithymia, depression and anxiety in parents of children with neurodevelopmental disorder: Comparative study of autistic disorder, pervasive developmental disorder not otherwise specified and attention deficit-hyperactivity disorder.
Durukan, İbrahim; Kara, Koray; Almbaideen, Mahmoud; Karaman, Dursun; Gül, Hesna
Recent studies have shown that individuals with neurodevelopmental disorders and their relatives have problems expressing and recognizing emotions, but there is a lack of studies on alexithymia, and the relationship between parental alexithymia and depression-anxiety symptoms in these groups. The aim of this study was therefore to measure alexithymia, depression, and anxiety levels in parents of children with pervasive developmental disorders and attention deficit-hyperactivity disorder (ADHD), and determine whether there is a positive correlation between the child's neurodevelopmental problem severity and parent scores. Parents of 29 autistic disorder (AD), 28 pervasive developmental disorder not otherwise specified (PDD-NOS) and 29 ADHD children were recruited into the study, and completed a demographic information form, as well as the Toronto Alexithymia Scale (TAS-20), Beck Depression Inventory, and State-Trait Anxiety Inventory. Alexithymia symptoms were higher in parents of children with AD than in others but unexpectedly, also these symptoms were higher in ADHD parents than in PDD-NOS groups. In addition, there were unexpected differences according to alexithymia subtype, while only the difference in maternal TAS-1 scores (difficulty in describing feelings) were statistically significant. Parental depression and state anxiety scores were increased as the child's symptom severity increased, but trait anxiety symptoms were higher in the AD and ADHD group than in the PDD-NOS group. In all groups, maternal depression and anxiety scores were higher than paternal scores, and differences were significant for depression and anxiety types in AD, and for only anxiety types in ADHD parents. The AD group had the strongest correlation between parental depression-anxiety and alexithymia. The possibility of alexithymia, depression and anxiety should be kept in mind when working with parents of children with neurodevelopmental disorders. © 2017 Japan Pediatric Society.
Buoli, Massimiliano; Serati, Marta; Caldiroli, Alice; Cremaschi, Laura; Altamura, Alfredo Carlo
Available data support a contribution of both neurodevelopmental and neurodegenerative factors in the etiology of schizophrenia (SCH) and bipolar disorder (BD). Of note, one of the most important issue of the current psychiatric research is to identify the specific factors that contribute to impaired brain development and neurodegeneration in SCH and BD, and especially how these factors alter normal brain development and physiological aging process. Our hypothesis is that only specific damages, taking place in precise brain development stages, are associated with future SCH /BD onset and that neurodegeneration consists of an acceleration of brain aging after SCH /BD onset. In support of our hypothesis, the results of the present narrative mini-review shows as neurodevelopmental damages generally contribute to neuropsychiatric syndromes (e.g. hypothyroidism or treponema pallidum), but only some of them are specifically associated with adult SCH and BD (e.g. toxoplasma or substance abuse), particularly if they happen in specific stages of brain development. On the other hand, cognitive impairment and brain changes, associated with long duration of SCH /BD, look like what happens during aging: memory, executive domains and prefrontal cortex are implicated both in aging and in SCH /BD progression. Future research will explore possible validity of this etiological model for SCH and BD.
Samango-Sprouse, Carole; Keen, Colleen; Mitchell, Francie; Sadeghin, Teresa; Gropman, Andrea
Fourty eight, XXXX is a rare chromosomal aneuploidy associated with neurocognitive deficits, speech and language disorders and executive dysfunction but the scarcity and variability of reported cases limit our understanding of the 48, XXXX phenotype. To our knowledge, this is the first study to report on the neurodevelopmental profile of three young females with 48, XXXX. Patient 1 (age = 11.0), Patient 2 (age = 10.9), and Patient 3 (age = 6.4) were evaluated using comprehensive neurodevelopmental assessments. Parent questionnaires were completed to assess behavioral and psychosocial domains including executive function, ADHD and anxiety. Nonverbal intelligence quotients were 56, 80, and 91 for Patients 1, 2, and 3, respectively. There were significantly impaired visual motor capacities in graphomotor and perceptual domains below the 5th centile in Patients 1 and 2, and mildly impaired visual perception skills in Patient 3. All three patients had Childhood Apraxia of Speech (CAS) but of varying severity and similar executive dysfunction, externalizing problems and social difficulties. Familial learning disabilities (FLD) in Patient 1 and the co-occurrence of ADHD in Patient's 1 and 2 may contribute to their more impaired cognitive performances relative to Patient 3 who is the second reported case of 48, XXXX to have normal intellect. These distinct and overlapping characteristics expand the phenotypic profile of 48, XXXX and may be used in the counseling of families and treatment of children with 48, XXXX. © 2015 Wiley Periodicals, Inc.
Full Text Available Sleep is important for neural plasticity, and plasticity underlies sleep-dependent memory consolidation. It is widely appreciated that protein synthesis plays an essential role in neural plasticity. Studies of sleep-dependent memory and sleep-dependent plasticity have begun to examine alterations in these functions in populations with neurological and psychiatric disorders. Such an approach acknowledges that disordered sleep may have functional consequences during wakefulness. Although neurodevelopmental disorders are not considered to be sleep disorders per se, recent data has revealed that sleep abnormalities are among the most prevalent and common symptoms and may contribute to the progression of these disorders. The main goal of this review is to highlight the role of disordered sleep in the pathology of neurodevelopmental disorders and to examine some potential mechanisms by which sleep-dependent plasticity may be altered. We will also briefly attempt to extend the same logic to the other end of the developmental spectrum and describe a potential role of disordered sleep in the pathology of neurodegenerative diseases. We conclude by discussing ongoing studies that might provide a more integrative approach to the study of sleep, plasticity, and neurodevelopmental disorders.
Lewis, Emily Ma; Kroll, Kristen L
Human neurodevelopmental disorders (NDDs) involve mutations in hundreds of individual genes, with over-representation in genes encoding proteins that alter chromatin structure to modulate gene expression. Here, we highlight efforts to model these NDDs through in vitro differentiation of patient-specific induced pluripotent stem cells into neurons. We discuss how epigenetic regulation controls normal cortical development, how mutations in several classes of epigenetic regulators contribute to NDDs, and approaches for modeling cortical development and function using both directed differentiation and formation of cerebral organoids. We explore successful applications of these models to study both syndromic and nonsyndromic NDDs and to define convergent mechanisms, addressing both the potential and challenges of using this approach to define cellular and molecular mechanisms that underlie NDDs.
Byrne, Susan; Jansen, Lara; U-King-Im, Jean-Marie; Siddiqui, Ata; Lidov, Hart G W; Bodi, Istvan; Smith, Luke; Mein, Rachael; Cullup, Thomas; Dionisi-Vici, Carlo; Al-Gazali, Lihadh; Al-Owain, Mohammed; Bruwer, Zandre; Al Thihli, Khalid; El-Garhy, Rana; Flanigan, Kevin M; Manickam, Kandamurugu; Zmuda, Erik; Banks, Wesley; Gershoni-Baruch, Ruth; Mandel, Hanna; Dagan, Efrat; Raas-Rothschild, Annick; Barash, Hila; Filloux, Francis; Creel, Donnell; Harris, Michael; Hamosh, Ada; Kölker, Stefan; Ebrahimi-Fakhari, Darius; Hoffmann, Georg F; Manchester, David; Boyer, Philip J; Manzur, Adnan Y; Lourenco, Charles Marques; Pilz, Daniela T; Kamath, Arveen; Prabhakar, Prab; Rao, Vamshi K; Rogers, R Curtis; Ryan, Monique M; Brown, Natasha J; McLean, Catriona A; Said, Edith; Schara, Ulrike; Stein, Anja; Sewry, Caroline; Travan, Laura; Wijburg, Frits A; Zenker, Martin; Mohammed, Shehla; Fanto, Manolis; Gautel, Mathias; Jungbluth, Heinz
Vici syndrome is a progressive neurodevelopmental multisystem disorder due to recessive mutations in the key autophagy gene EPG5. We report genetic, clinical, neuroradiological, and neuropathological features of 50 children from 30 families, as well as the neuronal phenotype of EPG5 knock-down in Drosophila melanogaster. We identified 39 different EPG5 mutations, most of them truncating and predicted to result in reduced EPG5 protein. Most mutations were private, but three recurrent mutations (p.Met2242Cysfs*5, p.Arg417*, and p.Gln336Arg) indicated possible founder effects. Presentation was mainly neonatal, with marked hypotonia and feeding difficulties. In addition to the five principal features (callosal agenesis, cataracts, hypopigmentation, cardiomyopathy, and immune dysfunction), we identified three equally consistent features (profound developmental delay, progressive microcephaly, and failure to thrive). The manifestation of all eight of these features has a specificity of 97%, and a sensitivity of 89% for the presence of an EPG5 mutation and will allow informed decisions about genetic testing. Clinical progression was relentless and many children died in infancy. Survival analysis demonstrated a median survival time of 24 months (95% confidence interval 0-49 months), with only a 10th of patients surviving to 5 years of age. Survival outcomes were significantly better in patients with compound heterozygous mutations (P = 0.046), as well as in patients with the recurrent p.Gln336Arg mutation. Acquired microcephaly and regression of skills in long-term survivors suggests a neurodegenerative component superimposed on the principal neurodevelopmental defect. Two-thirds of patients had a severe seizure disorder, placing EPG5 within the rapidly expanding group of genes associated with early-onset epileptic encephalopathies. Consistent neuroradiological features comprised structural abnormalities, in particular callosal agenesis and pontine hypoplasia, delayed
Geisheker, Madeleine R.; Heymann, Gabriel; Wang, Tianyun; Coe, Bradley P.; Turner, Tychele N.; Stessman, Holly A.F.; Hoekzema, Kendra; Kvarnung, Malin; Shaw, Marie; Friend, Kathryn; Liebelt, Jan; Barnett, Christopher; Thompson, Elizabeth M.; Haan, Eric; Guo, Hui; Anderlid, Britt-Marie; Nordgren, Ann; Lindstrand, Anna; Vandeweyer, Geert; Alberti, Antonino; Avola, Emanuela; Vinci, Mirella; Giusto, Stefania; Pramparo, Tiziano; Pierce, Karen; Nalabolu, Srinivasa; Michaelson, Jacob J.; Sedlacek, Zdenek; Santen, Gijs W.E.; Peeters, Hilde; Hakonarson, Hakon; Courchesne, Eric; Romano, Corrado; Kooy, R. Frank; Bernier, Raphael A.; Nordenskjöld, Magnus; Gecz, Jozef; Xia, Kun; Zweifel, Larry S.; Eichler, Evan E.
Although de novo missense mutations have been predicted to account for more cases of autism than gene-truncating mutations, most research has focused on the latter. We identified the properties of de novo missense mutations in patients with neurodevelopmental disorders (NDDs) and highlight 35 genes with excess missense mutations. Additionally, 40 amino acid sites were recurrently mutated in 36 genes, and targeted sequencing of 20 sites in 17,689 NDD patients identified 21 new patients with identical missense mutations. One recurrent site (p.Ala636Thr) occurs in a glutamate receptor subunit, GRIA1. This same amino acid substitution in the homologous but distinct mouse glutamate receptor subunit Grid2 is associated with Lurcher ataxia. Phenotypic follow-up in five individuals with GRIA1 mutations shows evidence of specific learning disabilities and autism. Overall, we find significant clustering of de novo mutations in 200 genes, highlighting specific functional domains and synaptic candidate genes important in NDD pathology. PMID:28628100
Stuckey, Ruth; Domingues-Montanari, Sophie
Telecommunication technologies are advancing rapidly with huge investment to improve infrastructure in rural areas. Telemedicine brings the benefits of telecommunication to healthcare, especially in resource-limited and remote communities. The recent literature on telemedicine in paediatrics will be reviewed, with particular focus on its application to help children with neurodevelopmental disorders and their families living in remote regions and/or low-income countries, and gaps identified for future research. Studies show that telemedicine can enable a family's access to appropriately qualified help that physically may only be available hundreds of miles away, helping to overcome geographic barriers. Telemedicine can also train parents and equip them with the knowledge and skills to better care for their children. Despite some technological barriers to implementation, telemedicine can help transform all stages of autism treatment. However, more studies are required in low- and middle-income countries to fully elucidate the benefits offered by telemedicine to autistic children and their families.
Harms, Melanie D.
Individuals with neurodevelopmental disorders are challenged with memory and language deficits that impact their skills acquisition (Martin, Klusek, Estigarriba, & Roberts, 2009; Turner & Alborz, 2003). The value of music when applied as an antecedent and a reinforcer has long been established to address such memory and language deficits…
Keerthi Thirtamara Rajamani
Full Text Available The neuropeptide oxytocin (OXT is a crucial mediator of parturition and milk ejection and a major modulator of various social behaviors, including social recognition, aggression and parenting. In the past decade, there has been significant excitement around the possible use of OXT to treat behavioral deficits in neurodevelopmental disorders, including autism spectrum disorder (ASD. Yet, despite the fast move to clinical trials with OXT, little attention has been paid to the possibility that the OXT system in the brain is perturbed in these disorders and to what extent such perturbations may contribute to social behavior deficits. Large-scale whole-exome sequencing studies in subjects with ASD, along with biochemical and electrophysiological studies in animal models of the disorder, indicate several risk genes that play an essential role in brain synapses, suggesting that deficits in synaptic activity and plasticity underlie the pathophysiology in a considerable portion of these cases. OXT has been repeatedly shown, both in vitro and in vivo, to modify synaptic properties and plasticity and to modulate neural activity in circuits that regulate social behavior. Together, these findings led us to hypothesize that failure of the OXT system during early development, as a direct or indirect consequence of genetic mutations, may impact social behavior by altering synaptic activity and plasticity. In this article, we review the evidence that support our hypothesis.
Cheryl L Gatto
Full Text Available Proper brain function requires stringent balance of excitatory and inhibitory synapse formation during neural circuit assembly. Mutation of genes that normally sculpt and maintain this balance results in severe dysfunction, causing neurodevelopmental disorders including autism, epilepsy and Rett syndrome. Such mutations may result in defective architectural structuring of synaptic connections, molecular assembly of synapses and/or functional synaptogenesis. The affected genes often encode synaptic components directly, but also include regulators that secondarily mediate the synthesis or assembly of synaptic proteins. The prime example is Fragile X syndrome (FXS, the leading heritable cause of both intellectual disability and autism spectrum disorders. FXS results from loss of mRNA-binding FMRP, which regulates synaptic transcript trafficking, stability and translation in activity-dependent synaptogenesis and plasticity mechanisms. Genetic models of FXS exhibit striking excitatory and inhibitory synapse imbalance, associated with impaired cognitive and social interaction behaviors. Downstream of translation control, a number of specific synaptic proteins regulate excitatory versus inhibitory synaptogenesis, independently or combinatorially, and loss of these proteins is also linked to disrupted neurodevelopment. The current effort is to define the cascade of events linking transcription, translation and the role of specific synaptic proteins in the maintenance of excitatory versus inhibitory synapses during neural circuit formation. This focus includes mechanisms that fine-tune excitation and inhibition during the refinement of functional synaptic circuits, and later modulate this balance throughout life. The use of powerful new genetic models has begun to shed light on the mechanistic bases of excitation/inhibition imbalance for a range of neurodevelopmental disease states.
Joel S. Goldberg
Full Text Available Retinoic acids (13-cis and 13-trans are known teratogens, and their precursor is retinol, a form of vitamin A. In 1995, Rothman et al demonstrated an association between excessive vitamin A, > 10,000 IU/day, during the first trimester of pregnancy and teratogenic effects, particularly in the central nervous system. However, vitamin A deficiency has long been known to be deleterious to the mother and fetus. Therefore, there may be a narrow therapeutic ratio for vitamin A during pregnancy that has not previously been fully appreciated. Neurodevelopmental disorders may not be apparent by macroscopic brain examination or imaging, and proving the existence of a behavioral teratogen is not straightforward. However, an excess of retinoic acid and some neurodevelopmental disorders are both associated with abnormalities in cerebellar morphology. Physical and chemical evidence strongly supports the notion that beta carotene crosses the placenta and is metabolized to retinol. Only very limited amounts of beta carotene are stored in fetal fat cells as evidenced by the fact that maternal fat is yellow from beta carotene, whereas non-brown neonatal fat is white. Furthermore, newborns of carotenemic mothers do not share the yellow complexion of their mothers. The excess 13-trans retinoic acid derived from metabolized beta carotene in the fetus increases the concentration of the more teratogenic 13-cis retinoic acid since the isomerization equilibrium is shifted to the left. Therefore, this paper proposes that consideration be given to monitoring all potential sources of fetal 13-cis and 13-trans retinoic acid, including nutritional supplements, dietary retinol, and beta carotene, particularly in the first trimester of pregnancy.
Rice, Timothy R
Children born premature are at risk for neurodevelopmental disorders, including autism and schizophrenia. This piece advances the hypothesis that altered androgen exposure observed in premature infants is an important mediator of the neurodevelopmental risk in males associated with prematurity. Specifically, the alterations of normative physiologic postnatal activations of the hypothalamic-pituitary-gonadal axis that occur in preterm males are hypothesized to contribute to the risk of neuropsychiatric pathology of prematurity through altered androgen-mediated organizational effects on the developing brain. The physiology of testosterone and male central nervous system development in full-term births is reviewed and compared to the developmental processes of prematurity. The effects of the altered testosterone physiology observed within prematurity outside of the central nervous system are reviewed as a segue into a discussion of the effects within the nervous system, with a special focus on autism spectrum disorders and attention deficit hyperactivity disorder. The explanatory power of this model is reviewed as a supplement to the preexisting models of prematurity and neurodevelopmental risk, including infection and other perinatal central nervous system insults. The emphasis is placed on altered androgen exposure as serving as just one among many mediators of neurodevelopmental risk that may be of interest for further research and evidence-based investigation. Implications for diagnosis, management and preventative treatments conclude the piece.
Full Text Available Background: To establish integrated healthcare pathways for patients with neurodevelopmental disorders (ND such as autism spectrum disorder and attention-deficit hyperactivity disorder is challenging. This study sets out to investigate the main concerns for healthcare professionals when integrating ND care pathways and how they resolve these concerns. Methods: Using classic grounded theory (Glaser, we analysed efforts to improve and integrate an ND care pathway for children and youth in a Swedish region over a period of 6 years. Data from 42 individual interviews with a range of ND professionals, nine group interviews with healthcare teams, participant observation, a 2-day dialogue conference, focus group meetings, regional media coverage, and reports from other Swedish regional ND projects were analysed. Results: The main concern for participants was to deal with overwhelming ND complexity by unpacking control, which is control over strategies to define patients’ status and needs. Unpacking control is key to the professionals’ strivings to expand constructive life space for patients, to squeeze health care to reach available care goals, to promote professional ideologies, and to uphold workplace integrity. Control-seeking behaviour in relation to ND unpacking is ubiquitous and complicates integration of ND care pathways. Conclusions: The Unpacking control theory expands central aspects of professions theory and may help to improve ND care development.
Waxegård, Gustaf; Thulesius, Hans
Background To establish integrated healthcare pathways for patients with neurodevelopmental disorders (ND) such as autism spectrum disorder and attention-deficit hyperactivity disorder is challenging. This study sets out to investigate the main concerns for healthcare professionals when integrating ND care pathways and how they resolve these concerns. Methods Using classic grounded theory (Glaser), we analysed efforts to improve and integrate an ND care pathway for children and youth in a Swedish region over a period of 6 years. Data from 42 individual interviews with a range of ND professionals, nine group interviews with healthcare teams, participant observation, a 2-day dialogue conference, focus group meetings, regional media coverage, and reports from other Swedish regional ND projects were analysed. Results The main concern for participants was to deal with overwhelming ND complexity by unpacking control, which is control over strategies to define patients’ status and needs. Unpacking control is key to the professionals’ strivings to expand constructive life space for patients, to squeeze health care to reach available care goals, to promote professional ideologies, and to uphold workplace integrity. Control-seeking behaviour in relation to ND unpacking is ubiquitous and complicates integration of ND care pathways. Conclusions The Unpacking control theory expands central aspects of professions theory and may help to improve ND care development. PMID:27609793
Jivraj, Jamil; Sacrey, Lori-Ann; Newton, Amanda; Nicholas, David; Zwaigenbaum, Lonnie
Participatory research aims to increase the relevance and broaden the implementation of health research by involving those affected by the outcomes of health studies. Few studies within the field of neurodevelopmental disorders, particularly autism spectrum disorders, have involved autistic individuals as partners. This study sought to identify…
Full Text Available Background: Parents of children suffering from neurodevelopmental disorders, frequently face public stigma which is often internalized and leads to psychological burden. However, there is a lack of data on the perceptions of internalized stigma among parents of children with neurodevelopmental disorders, especially from lower-middle-income countries like India. Aims: This study aims to develop an adapted version of the Internalized Stigma of Mental Illness (ISMI scale for use in parents of children suffering from neurodevelopmental disorders and to explore the factor structure of this instrument through exploratory factor analysis (EFA. Settings and Design: A cross-sectional study was conducted in an outpatient setting in a tertiary care hospital in India. Materials and Methods: A total of 105 parents of children suffering from neurodevelopmental disorders (according to the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition were recruited for the study after screening for psychiatric disorder using Mini International Neuropsychiatric Interview version 6.0. A modified 16-item scale was constructed Parents' Internalized Stigma of Neurodevelopmental Disorder in Child (PISNC scale and applied on 105 parents of children suffering from neurodevelopmental disorders, after translation to Hindi and back-translation, in keeping with the World Health Organization's translation-back-translation methodology. Statistical Analysis: EFA was carried out using principal component analysis with orthogonal (varimax rotation. Internal consistency of the Hindi version of the scale was estimated in the form of Cronbach's alpha. Spearman–Brown coefficient and Guttman split-half coefficient were calculated to evaluate the split-half reliability. Results: The initial factor analysis yielded three-factor models with an eigenvalue of >1 and the total variance explained by these factors was 62.017%. The internal consistency of the 16-item scale was 0
Burns, Thomas G; King, Tricia Z; Spencer, Katherine S
A group of 47 patients diagnosed with neurodevelopmental disorders were compared to 47 age-, gender-, and racially matched typically developing children to examine the frequency of impairment across domains of the Mullen Scales of Early Learning (MSEL). The MSEL is a comprehensive measure of cognitive functioning designed to assess infants and preschool children between the ages of birth to 68 months. In the neurodevelopmental group, the sample was composed of children 2 to 4 years of age who were diagnosed with autism spectrum disorders (ASD; n = 19), cerebral palsy (CP; n = 14), and epilepsy (EPI; n = 14). A sample of 47 matched controls, taken from the normative sample of the MSEL, was used as a comparison group. Each one of the clinical groups comprising the neurodevelopmental sample demonstrated statistically significant delays across domains relative to the respective matched control group (p Children failed to demonstrate a "signature" profile for a diagnosis of ASD, CP, or EPI. The clinical sensitivity of the MSEL and the need for obtaining specific intervention services for children diagnosed with these conditions are presented. Finally, these results are discussed within the context of the clinical sensitivity of the MSEL in working with these clinical populations.
Atladóttir, H. Ó.; Schendel, D. E.; Parner, E. T.; Henriksen, T. B.
The aim of this study was to describe the profile of specific neonatal morbidities in children later diagnosed with autism spectrum disorder (ASD), and to compare this profile with the profile of children with hyperkinetic disorder, cerebral palsy, epilepsy or intellectual disability. This is a Danish population based cohort study, including all…
Geraghty, Estella M.; Tancredi, Daniel J.; Delwiche, Lora D.; Schmidt, Rebecca J.; Ritz, Beate; Hansen, Robin L.; Hertz-Picciotto, Irva
Background: Gestational exposure to several common agricultural pesticides can induce developmental neurotoxicity in humans, and has been associated with developmental delay and autism. Objectives: We evaluated whether residential proximity to agricultural pesticides during pregnancy is associated with autism spectrum disorders (ASD) or developmental delay (DD) in the Childhood Autism Risks from Genetics and Environment (CHARGE) study. Methods: The CHARGE study is a population-based case–control study of ASD, DD, and typical development. For 970 participants, commercial pesticide application data from the California Pesticide Use Report (1997–2008) were linked to the addresses during pregnancy. Pounds of active ingredient applied for organophophates, organochlorines, pyrethroids, and carbamates were aggregated within 1.25-km, 1.5-km, and 1.75-km buffer distances from the home. Multinomial logistic regression was used to estimate the odds ratio (OR) of exposure comparing confirmed cases of ASD (n = 486) or DD (n = 168) with typically developing referents (n = 316). Results: Approximately one-third of CHARGE study mothers lived, during pregnancy, within 1.5 km (just under 1 mile) of an agricultural pesticide application. Proximity to organophosphates at some point during gestation was associated with a 60% increased risk for ASD, higher for third-trimester exposures (OR = 2.0; 95% CI: 1.1, 3.6), and second-trimester chlorpyrifos applications (OR = 3.3; 95% CI: 1.5, 7.4). Children of mothers residing near pyrethroid insecticide applications just before conception or during third trimester were at greater risk for both ASD and DD, with ORs ranging from 1.7 to 2.3. Risk for DD was increased in those near carbamate applications, but no specific vulnerable period was identified. Conclusions: This study of ASD strengthens the evidence linking neurodevelopmental disorders with gestational pesticide exposures, particularly organophosphates, and provides novel results of
Full Text Available Insulin-Like Growth Factor 1 (IGF-1 is a neurotrophic polypeptide with crucial roles to play in Central Nervous System (CNS growth, development and maturation. Following interrogation of the neurobiology underlying several neurodevelopmental disorders and Autism Spectrum Disorders (ASD, both recombinant IGF-1 (mecasermin and related derivatives, such as (1-3 IGF-1, have emerged as potential therapeutic approaches. Clinical pilot studies and early reports have supported the safety/preliminary efficacy of IGF-1 and related compounds in the treatment of Rett Syndrome, with evidence mounting for its use in Phelan McDermid Syndrome and Fragile X Syndrome. In broader ASD, clinical trials are ongoing. Here, we review the role of IGF-1 in the molecular etiologies of these conditions in addition to the accumulating evidence from early clinical studies highlighting the possibility of IGF-1 and related compounds as potential treatments for these childhood-onset neurodevelopmental disorders.
Hayashida, Kristen; Anderson, Bryan; Paparella, Tanya; Freeman, Stephanny F. N.; Forness, Steven R.
Although comorbid or co-occurring psychiatric diagnoses such as attention deficit hyperactivity disorder, anxiety disorders, depression, and oppositional defiant or conduct disorders have been well studied in children or adolescents with autism spectrum disorders (ASDs), very little research is available on preschool samples. The current study…
Sturm, Alexandra; Rozenman, Michelle; Chang, Susanna; McGough, James J; McCracken, James T; Piacentini, John C
Deficits in social communication are a core feature of autism spectrum disorder (ASD), yet significant social problems have been observed in youth with many neurodevelopmental disorders. In this preliminary investigation, we aimed to explore whether domains of social reciprocity (i.e., social communication, social cognition, social awareness, social motivation, and restricted and repetitive behaviors) represent transdiagnostic traits. These domains were compared across youth ages 7-17 with obsessive-compulsive disorder (OCD; N = 32), tic disorders (TD; N = 20), severe mood dysregulation (N = 33) and autism spectrum disorder (N = 35). While the ASD group was rated by parents as exhibiting the greatest social reciprocity deficits across domains, a high proportion of youth with severe mood dysregulation also exhibited pronounced deficits in social communication, cognition, and awareness. The ASD and severe mood dysregulation groups demonstrated comparable scores on the social awareness domain. In contrast, social motivation and restricted and repetitive behaviors did not appear to be transdiagnostic domains in severe mood dysregulation, OCD, or TD groups. The present work provides preliminary support that social awareness, and to a lesser extent social communication and cognition, may represent features of social reciprocity that are transdiagnostic across ASD and severe mood dysregulation. Copyright © 2018 Elsevier B.V. All rights reserved.
Susie Ruth Berkowicz
Full Text Available Background: Brinps 1 – 3, and Astrotactins (Astn 1 and 2, are members of the Membrane Attack Complex / Perforin (MACPF superfamily that are predominantly expressed in the mammalian brain during development. Genetic variation at the human BRINP2/ASTN1 and BRINP1/ASTN2 loci has been implicated in neurodevelopmental disorders. We, and others, have previously shown that Brinp1-/- mice exhibit behaviour reminiscent of autism spectrum disorder (ASD and attention deficit hyperactivity disorder (ADHD.Method: We created Brinp2-/- mice and Brinp3-/- mice via the Cre-mediated LoxP system to investigate the effect of gene deletion on anatomy and behaviour. Additionally, Brinp2-/-Brinp3-/- double knock-out mice were generated by interbreeding Brinp2-/- and Brinp3-/- mice. Genomic validation was carried out for each knock-out line, followed by histological, weight and behavioural examination. Brinp1-/-Brinp2-/-Brinp3-/- triple knock-out mice were also generated by crossing Brinp2/3 double knock-out mice with previously generated Brinp1-/- mice, and examined by weight and histological analysis.Results: Brinp2-/- and Brinp3-/- mice differ in their behaviour: Brinp2-/- mice are hyperactive, whereas Brinp3-/- mice exhibit marked changes in anxiety-response on the elevated plus maze. Brinp3-/- mice also show evidence of altered sociability. Both Brinp2-/- and Brinp3-/- mice have normal short-term memory, olfactory responses, pre-pulse inhibition and motor learning. The double knock-out mice show behaviours of Brinp2-/- and Brinp3-/- mice, without evidence of new or exacerbated phenotypes. Conclusion: Brinp3 is important in moderation of anxiety, with potential relevance to anxiety disorders. Brinp2 dysfunction resulting in hyperactivity may be relevant to the association of ADHD with chromosome locus 1q25.2. Brinp2-/- and Brinp3-/- genes do not compensate in the mammalian brain and likely have distinct molecular or cell-type specific functions.
Arim, Rubab G; Kohen, Dafna E; Garner, Rochelle E; Lach, Lucyna M; Brehaut, Jamie C; MacKenzie, Michael J; Rosenbaum, Peter L
This study examines psychosocial functioning in children with neurodevelopmental disorders (NDDs) and/or externalizing behavior problems (EBPs) as compared to children with neither condition. The longitudinal sample, drawn from the Canadian National Longitudinal Survey of Children and Youth, included children who were 6 to 9 years old in Cycle 1 who were followed-up biennially in Cycles 2 and 3 (N = 3476). The associations between NDDs and/or EBPs, child and family socio-demographic characteristics and parenting behaviors (consistency and ineffective parenting), were examined across several measures of child psychosocial functioning: peer relationships, general self-esteem, prosocial behavior and anxiety-emotional problems. Children with NDDs, EBPs, and both NDDs and EBPs self-reported lower scores on general self-esteem. Children with NDDs and both NDDs and EBPs reported lower scores on peer relationships and prosocial behavior. Lastly, children with both NDDs and EBPs self-reported higher scores on anxiety-emotional behaviors. After considering family socio-demographic characteristics and parenting behaviors, these differences remained statistically significant only for children with both NDDs and EBPs. Child age and gender, household income and parenting behaviors were important in explaining these associations. Psychosocial functioning differs for children with NDDs and/or EBPs. Children with both NDDs and EBPs appear to report poorer psychosocial functioning compared to their peers with neither condition. However, it is important to consider the context of socio-demographic characteristics, parenting behaviors and their interactions to understand differences in children's psychosocial functioning. Implication for Rehabilitation: Practitioners may wish to consider complexity in child health by examining a comprehensive set of determinants of psychosocial outcomes as well as comorbid conditions, such as neurodevelopmental disorders (NDDs) and externalizing
Yoshizaki, Kaichi; Furuse, Tamio; Kimura, Ryuichi; Tucci, Valter; Kaneda, Hideki; Wakana, Shigeharu; Osumi, Noriko
Neurodevelopmental disorders such as autism spectrum disorder (ASD) and attention deficit and hyperactivity disorder (ADHD) have increased over the last few decades. These neurodevelopmental disorders are characterized by a complex etiology, which involves multiple genes and gene-environmental interactions. Various genes that control specific properties of neural development exert pivotal roles in the occurrence and severity of phenotypes associated with neurodevelopmental disorders. Moreover, paternal aging has been reported as one of the factors that contribute to the risk of ASD and ADHD. Here we report, for the first time, that paternal aging has profound effects on the onset of behavioral abnormalities in mice carrying a mutation of Pax6, a gene with neurodevelopmental regulatory functions. We adopted an in vitro fertilization approach to restrict the influence of additional factors. Comprehensive behavioral analyses were performed in Sey/+ mice (i.e., Pax6 mutant heterozygotes) born from in vitro fertilization of sperm taken from young or aged Sey/+ fathers. No body weight changes were found in the four groups, i.e., Sey/+ and wild type (WT) mice born to young or aged father. However, we found important differences in maternal separation-induced ultrasonic vocalizations of Sey/+ mice born from young father and in the level of hyperactivity of Sey/+ mice born from aged fathers in the open-field test, respectively, compared to WT littermates. Phenotypes of anxiety were observed in both genotypes born from aged fathers compared with those born from young fathers. No significant difference was found in social behavior and sensorimotor gating among the four groups. These results indicate that mice with a single genetic risk factor can develop different phenotypes depending on the paternal age. Our study advocates for serious considerations on the role of paternal aging in breeding strategies for animal studies.
Full Text Available Neurodevelopmental disorders such as autism spectrum disorder (ASD and attention deficit and hyperactivity disorder (ADHD have increased over the last few decades. These neurodevelopmental disorders are characterized by a complex etiology, which involves multiple genes and gene-environmental interactions. Various genes that control specific properties of neural development exert pivotal roles in the occurrence and severity of phenotypes associated with neurodevelopmental disorders. Moreover, paternal aging has been reported as one of the factors that contribute to the risk of ASD and ADHD. Here we report, for the first time, that paternal aging has profound effects on the onset of behavioral abnormalities in mice carrying a mutation of Pax6, a gene with neurodevelopmental regulatory functions. We adopted an in vitro fertilization approach to restrict the influence of additional factors. Comprehensive behavioral analyses were performed in Sey/+ mice (i.e., Pax6 mutant heterozygotes born from in vitro fertilization of sperm taken from young or aged Sey/+ fathers. No body weight changes were found in the four groups, i.e., Sey/+ and wild type (WT mice born to young or aged father. However, we found important differences in maternal separation-induced ultrasonic vocalizations of Sey/+ mice born from young father and in the level of hyperactivity of Sey/+ mice born from aged fathers in the open-field test, respectively, compared to WT littermates. Phenotypes of anxiety were observed in both genotypes born from aged fathers compared with those born from young fathers. No significant difference was found in social behavior and sensorimotor gating among the four groups. These results indicate that mice with a single genetic risk factor can develop different phenotypes depending on the paternal age. Our study advocates for serious considerations on the role of paternal aging in breeding strategies for animal studies.
Full Text Available AGAP1 is an Arf1 GTPase activating protein that interacts with the vesicle-associated protein complexes adaptor protein 3 (AP-3 and Biogenesis of Lysosome Related Organelles Complex-1 (BLOC-1. Overexpression of AGAP1 in non-neuronal cells results in an accumulation of endosomal cargoes, which suggests a role in endosome-dependent traffic. In addition, AGAP1 is a candidate susceptibility gene for two neurodevelopmental disorders, autism spectrum disorder (ASD and schizophrenia (SZ; yet its localization and function in neurons have not been described. Here, we describe that AGAP1 localizes to axons, dendrites, dendritic spines, and synapses, colocalizing preferentially with markers of early and recycling endosomes. Functional studies reveal overexpression and down-regulation of AGAP1 affects both neuronal endosomal trafficking and dendritic spine morphology, supporting a role for AGAP1 in the recycling endosomal trafficking involved in their morphogenesis. Finally, we determined the sensitivity of AGAP1 expression to mutations in the DTNBP1 gene, which is associated with neurodevelopmental disorder, and found that AGAP1 mRNA and protein levels are selectively reduced in the null allele of the mouse orthologue of DTNBP1. We postulate that endosomal trafficking contributes to the pathogenesis of neurodevelopmental disorders affecting dendritic spine morphology, and thus excitatory synapse structure and function.
Lucas, Barbara R; Elliott, Elizabeth J; Coggan, Sarah; Pinto, Rafael Z; Jirikowic, Tracy; McCoy, Sarah Westcott; Latimer, Jane
Gross motor skills are fundamental to childhood development. The effectiveness of current physical therapy options for children with mild to moderate gross motor disorders is unknown. The aim of this study was to systematically review the literature to investigate the effectiveness of conservative interventions to improve gross motor performance in children with a range of neurodevelopmental disorders. A systematic review with meta-analysis was conducted. MEDLINE, EMBASE, AMED, CINAHL, PsycINFO, PEDro, Cochrane Collaboration, Google Scholar databases and clinical trial registries were searched. Published randomised controlled trials including children 3 to ≤18 years with (i) Developmental Coordination Disorder (DCD) or Cerebral Palsy (CP) (Gross Motor Function Classification System Level 1) or Developmental Delay or Minimal Acquired Brain Injury or Prematurity (gross motor outcomes obtained using a standardised assessment tool. Meta-analysis was performed to determine the pooled effect of intervention on gross motor function. Methodological quality and strength of meta-analysis recommendations were evaluated using PEDro and the GRADE approach respectively. Of 2513 papers, 9 met inclusion criteria including children with CP (n = 2) or DCD (n = 7) receiving 11 different interventions. Only two of 9 trials showed an effect for treatment. Using the least conservative trial outcomes a large beneficial effect of intervention was shown (SMD:-0.8; 95% CI:-1.1 to -0.5) with "very low quality" GRADE ratings. Using the most conservative trial outcomes there is no treatment effect (SMD:-0.1; 95% CI:-0.3 to 0.2) with "low quality" GRADE ratings. Study limitations included the small number and poor quality of the available trials. Although we found that some interventions with a task-orientated framework can improve gross motor outcomes in children with DCD or CP, these findings are limited by the very low quality of the available evidence. High quality intervention
Dendrites and spines are the main neuronal structures receiving input from other neurons and glial cells. Dendritic and spine number, size, and morphology are some of the crucial factors determining how signals coming from individual synapses are integrated. Much remains to be understood about the characteristics of neuronal dendrites and dendritic spines in autism and related disorders. Although there have been many studies conducted using autism mouse models, few have been carried out using postmortem human tissue from patients. Available animal models of autism include those generated through genetic modifications and those non-genetic models of the disease. Here, we review how dendrite and spine morphology and number is affected in autism and related neurodevelopmental diseases, both in human, and genetic and non-genetic animal models of autism. Overall, data obtained from human and animal models point to a generalized reduction in the size and number, as well as an alteration of the morphology of dendrites; and an increase in spine densities with immature morphology, indicating a general spine immaturity state in autism. Additional human studies on dendrite and spine number and morphology in postmortem tissue are needed to understand the properties of these structures in the cerebral cortex of patients with autism. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 419-437, 2017. © 2016 Wiley Periodicals, Inc.
Debomoy K Lahiri
Full Text Available Autism is a neurodevelopmental disorder marked by social skills and communication deficits and interfering repetitive behavior. Intellectual disability often accompanies autism. In addition to behavioral deficits, autism is characterized by neuropathology and brain overgrowth. Increased intracranial volume often accompanies this brain growth. We have found that the Alzheimer’s disease (AD associated amyloid-β precursor protein (APP, especially its neuroprotective processing product, secreted APP α (sAPPα, is elevated in persons with autism. This has led to the anabolic hypothesis of autism etiology, in which neuronal overgrowth in the brain results in interneuronal misconnections that may underlie multiple autism symptoms. We review the contribution of research in brain volume and of APP to the anabolic hypothesis, and relate APP to other proteins and pathways that have already been directly associated with autism, such as fragile X mental retardation protein (FMRP, Ras small GTPase/Extracellular Signal-Regulated Kinase (Ras/ERK, and phosphoinositide 3 kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR. We also present additional evidence of MRI intracranial measurements in favor of the anabolic hypothesis. Finally, since it appears that APP’s involvement in autism is part of a multi-partner network, we extend this concept into the inherently interactive realm of epigenetics. We speculate that the underlying molecular abnormalities that influence APP’s contribution to autism are epigenetic markers overlaid onto potentially vulnerable gene sequences due to environmental influence.
Lahiri, Debomoy K; Sokol, Deborah K; Erickson, Craig; Ray, Balmiki; Ho, Chang Y; Maloney, Bryan
Autism is a neurodevelopmental disorder marked by social skills and communication deficits and interfering repetitive behavior. Intellectual disability often accompanies autism. In addition to behavioral deficits, autism is characterized by neuropathology and brain overgrowth. Increased intracranial volume often accompanies this brain growth. We have found that the Alzheimer's disease (AD) associated amyloid-β precursor protein (APP), especially its neuroprotective processing product, secreted APP α, is elevated in persons with autism. This has led to the "anabolic hypothesis" of autism etiology, in which neuronal overgrowth in the brain results in interneuronal misconnections that may underlie multiple autism symptoms. We review the contribution of research in brain volume and of APP to the anabolic hypothesis, and relate APP to other proteins and pathways that have already been directly associated with autism, such as fragile X mental retardation protein, Ras small GTPase/extracellular signal-regulated kinase, and phosphoinositide 3 kinase/protein kinase B/mammalian target of rapamycin. We also present additional evidence of magnetic resonance imaging intracranial measurements in favor of the anabolic hypothesis. Finally, since it appears that APP's involvement in autism is part of a multi-partner network, we extend this concept into the inherently interactive realm of epigenetics. We speculate that the underlying molecular abnormalities that influence APP's contribution to autism are epigenetic markers overlaid onto potentially vulnerable gene sequences due to environmental influence.
Sugathan, Aarathi; Biagioli, Marta; Golzio, Christelle; Erdin, Serkan; Blumenthal, Ian; Manavalan, Poornima; Ragavendran, Ashok; Brand, Harrison; Lucente, Diane; Miles, Judith; Sheridan, Steven D.; Stortchevoi, Alexei; Kellis, Manolis; Haggarty, Stephen J.; Katsanis, Nicholas; Gusella, James F.; Talkowski, Michael E.
Truncating mutations of chromodomain helicase DNA-binding protein 8 (CHD8), and of many other genes with diverse functions, are strong-effect risk factors for autism spectrum disorder (ASD), suggesting multiple mechanisms of pathogenesis. We explored the transcriptional networks that CHD8 regulates in neural progenitor cells (NPCs) by reducing its expression and then integrating transcriptome sequencing (RNA sequencing) with genome-wide CHD8 binding (ChIP sequencing). Suppressing CHD8 to levels comparable with the loss of a single allele caused altered expression of 1,756 genes, 64.9% of which were up-regulated. CHD8 showed widespread binding to chromatin, with 7,324 replicated sites that marked 5,658 genes. Integration of these data suggests that a limited array of direct regulatory effects of CHD8 produced a much larger network of secondary expression changes. Genes indirectly down-regulated (i.e., without CHD8-binding sites) reflect pathways involved in brain development, including synapse formation, neuron differentiation, cell adhesion, and axon guidance, whereas CHD8-bound genes are strongly associated with chromatin modification and transcriptional regulation. Genes associated with ASD were strongly enriched among indirectly down-regulated loci (P neurodevelopmental pathways in which many ASD-associated genes may converge on shared mechanisms of pathogenesis. PMID:25294932
William B. Grant
Full Text Available People with neurodevelopmental disorders and intellectual disabilities have much greater health care needs. Mainly staying indoors, such people generally have low 25-hydroxyvitamin D (25(OHD concentrations. The Vitamin D Task Force of the American Academy of Developmental Medicine and Dentistry (AADMD reviewed the evidence of 25(OHD concentrations that benefit the health of persons with developmental disabilities. Maintaining recommended optimal serum 25(OHD concentrations year long will benefit skeletal development in infants, children, and adolescents, and benefit musculoskeletal health and neuromuscular coordination in adult patients, and decrease risk of falls. Maintaining optimal concentrations decreases risks and severities of autoimmune diseases, cardiovascular disease, many types of cancer, dementia, types 1 and 2 diabetes mellitus, and respiratory tract infections. Other benefits include improved dental and oral health and improved physical performance. The Task Force recommends that 25(OHD concentrations for optimal health to be in the range of 75 to 125 nmol/L, which can be achieved using between 800 and 4000 IU/day vitamin D3 and sensible exposure to solar UVB radiation. The paper also discusses the potential risks of higher 25(OHD concentrations, the evidence from and limitations of randomized controlled trials, and the recommendations by various groups and agencies.
Grant, William B.; Wimalawansa, Sunil J.; Holick, Michael F.; Cannell, John J.; Pludowski, Pawel; Lappe, Joan M.; Pittaway, Mary; May, Philip
People with neurodevelopmental disorders and intellectual disabilities have much greater health care needs. Mainly staying indoors, such people generally have low 25-hydroxyvitamin D (25(OH)D) concentrations. The Vitamin D Task Force of the American Academy of Developmental Medicine and Dentistry (AADMD) reviewed the evidence of 25(OH)D concentrations that benefit the health of persons with developmental disabilities. Maintaining recommended optimal serum 25(OH)D concentrations year long will benefit skeletal development in infants, children, and adolescents, and benefit musculoskeletal health and neuromuscular coordination in adult patients, and decrease risk of falls. Maintaining optimal concentrations decreases risks and severities of autoimmune diseases, cardiovascular disease, many types of cancer, dementia, types 1 and 2 diabetes mellitus, and respiratory tract infections. Other benefits include improved dental and oral health and improved physical performance. The Task Force recommends that 25(OH)D concentrations for optimal health to be in the range of 75 to 125 nmol/L, which can be achieved using between 800 and 4000 IU/day vitamin D3 and sensible exposure to solar UVB radiation. The paper also discusses the potential risks of higher 25(OH)D concentrations, the evidence from and limitations of randomized controlled trials, and the recommendations by various groups and agencies. PMID:25734565
Wise, Merrill S.
Empirical evidence indicates that sleep spindles facilitate neuroplasticity and “off-line” processing during sleep, which supports learning, memory consolidation, and intellectual performance. Children with neurodevelopmental disorders (NDDs) exhibit characteristics that may increase both the risk for and vulnerability to abnormal spindle generation. Despite the high prevalence of sleep problems and cognitive deficits in children with NDD, only a few studies have examined the putative association between spindle characteristics and cognitive function. This paper reviews the literature regarding sleep spindle characteristics in children with NDD and their relation to cognition in light of what is known in typically developing children and based on the available evidence regarding children with NDD. We integrate available data, identify gaps in understanding, and recommend future research directions. Collectively, studies are limited by small sample sizes, heterogeneous populations with multiple comorbidities, and nonstandardized methods for collecting and analyzing findings. These limitations notwithstanding, the evidence suggests that future studies should examine associations between sleep spindle characteristics and cognitive function in children with and without NDD, and preliminary findings raise the intriguing question of whether enhancement or manipulation of sleep spindles could improve sleep-dependent memory and other aspects of cognitive function in this population. PMID:27478646
Grant, William B; Wimalawansa, Sunil J; Holick, Michael F; Cannell, John J; Pludowski, Pawel; Lappe, Joan M; Pittaway, Mary; May, Philip
People with neurodevelopmental disorders and intellectual disabilities have much greater health care needs. Mainly staying indoors, such people generally have low 25-hydroxyvitamin D (25(OH)D) concentrations. The Vitamin D Task Force of the American Academy of Developmental Medicine and Dentistry (AADMD) reviewed the evidence of 25(OH)D concentrations that benefit the health of persons with developmental disabilities. Maintaining recommended optimal serum 25(OH)D concentrations year long will benefit skeletal development in infants, children, and adolescents, and benefit musculoskeletal health and neuromuscular coordination in adult patients, and decrease risk of falls. Maintaining optimal concentrations decreases risks and severities of autoimmune diseases, cardiovascular disease, many types of cancer, dementia, types 1 and 2 diabetes mellitus, and respiratory tract infections. Other benefits include improved dental and oral health and improved physical performance. The Task Force recommends that 25(OH)D concentrations for optimal health to be in the range of 75 to 125 nmol/L, which can be achieved using between 800 and 4000 IU/day vitamin D3 and sensible exposure to solar UVB radiation. The paper also discusses the potential risks of higher 25(OH)D concentrations, the evidence from and limitations of randomized controlled trials, and the recommendations by various groups and agencies.
O'Conaill, Carrie R; Malisza, Krisztina L; Buss, Joan L; Bolster, R Bruce; Clancy, Christine; de Gervai, Patricia Dreessen; Chudley, Albert E; Longstaffe, Sally
Alcohol-related neurodevelopmental disorder (ARND) falls under the umbrella of fetal alcohol spectrum disorder (FASD). Diagnosis of ARND is difficult because individuals do not demonstrate the characteristic facial features associated with fetal alcohol syndrome (FAS). While attentional problems in ARND are similar to those found in attention-deficit/hyperactivity disorder (ADHD), the underlying impairment in attention pathways may be different. Functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) was conducted at 3 T. Sixty-three children aged 10 to 14 years diagnosed with ARND, ADHD, and typically developing (TD) controls performed a single-feature and a feature-conjunction visual search task. Dorsal and ventral attention pathways were activated during both attention tasks in all groups. Significantly greater activation was observed in ARND subjects during a single-feature search as compared to TD and ADHD groups, suggesting ARND subjects require greater neural recruitment to perform this simple task. ARND subjects appear unable to effectively use the very efficient automatic perceptual 'pop-out' mechanism employed by TD and ADHD groups during presentation of the disjunction array. By comparison, activation was lower in ARND compared to TD and ADHD subjects during the more difficult conjunction search task as compared to the single-feature search. Analysis of DTI data using tract-based spatial statistics (TBSS) showed areas of significantly lower fractional anisotropy (FA) and higher mean diffusivity (MD) in the right inferior longitudinal fasciculus (ILF) in ARND compared to TD subjects. Damage to the white matter of the ILF may compromise the ventral attention pathway and may require subjects to use the dorsal attention pathway, which is associated with effortful top-down processing, for tasks that should be automatic. Decreased functional activity in the right temporoparietal junction (TPJ) of ARND subjects may be due to a
Erdodi, Laszlo; Lajiness-O'Neill, Renee; Schmitt, Thomas A.
Visual and auditory verbal learning using a selective reminding format was studied in a mixed clinical sample of children with autism spectrum disorder (ASD) (n = 42), attention-deficit hyperactivity disorder (n = 83), velocardiofacial syndrome (n = 17) and neurotypicals (n = 38) using the Test of Memory and Learning to (1) more thoroughly…
Carpente, John; Gattino, Gustavo
Background: The Individual Music-Centered Assessment Profile for Neurodevelopmental Disorders (IMCAP-ND) is an evaluation instrument made up of three criterion-referenced rating scales designed to examine how clients perceive, interpret, and make music with the therapist while participating...
Fan, Qing; Yu, Junhan; Ross, Colin A; Keyes, Benjamin B; Dai, Yunfei; Zhang, Tianhong; Wang, Lanlan; Xiao, Zeping
The aim of the study was to assess the outcome of an educational effort by two North American experts in dissociative disorders to teach Chinese psychiatrists to make reliable dissociative disorder diagnoses. In the final phase of the educational effort, 569 patients at Shanghai Mental Health Center completed the Chinese version of the Dissociative Experiences Scale (DES). Patients were then randomly selected in different proportions according to their DES scores: 96 selected patients were then assessed with the Dissociative Disorders Interview Schedule (DDIS) and clinical diagnostic interviews based on DSM-IV criteria. According to the clinical diagnostic interviews, 28 (4.9%) patients were diagnosed as having dissociative disorders. Agreement between the American experts and Chinese psychiatrists for presence or absence of a dissociative disorder was 0.75 using Cohen's kappa. Dissociative disorders can be diagnosed in China with good inter-rater reliability. The authors describe the steps taken to achieve this outcome.
Rajkumar, Ravi Philip
Gender identity disorder (GID), recently renamed gender dysphoria (GD), is a rare condition characterized by an incongruity between gender identity and biological sex. Clinical evidence suggests that schizophrenia occurs in patients with GID at rates higher than in the general population and that patients with GID may have schizophrenia-like personality traits. Conversely, patients with schizophrenia may experience alterations in gender identity and gender role perception. Neurobiological research, including brain imaging and studies of finger length ratio and handedness, suggests that both these disorders are associated with altered cerebral sexual dimorphism and changes in cerebral lateralization. Various mechanisms, such as Toxoplasma infection, reduced levels of brain-derived neurotrophic factor (BDNF), early childhood adversity, and links with autism spectrum disorders, may account for some of this overlap. The implications of this association for further research are discussed.
Ravi Philip Rajkumar
Full Text Available Gender identity disorder (GID, recently renamed gender dysphoria (GD, is a rare condition characterized by an incongruity between gender identity and biological sex. Clinical evidence suggests that schizophrenia occurs in patients with GID at rates higher than in the general population and that patients with GID may have schizophrenia-like personality traits. Conversely, patients with schizophrenia may experience alterations in gender identity and gender role perception. Neurobiological research, including brain imaging and studies of finger length ratio and handedness, suggests that both these disorders are associated with altered cerebral sexual dimorphism and changes in cerebral lateralization. Various mechanisms, such as Toxoplasma infection, reduced levels of brain-derived neurotrophic factor (BDNF, early childhood adversity, and links with autism spectrum disorders, may account for some of this overlap. The implications of this association for further research are discussed.
Khandaker, Golam M.; Stochl, Jan; Zammit, Stanley; Lewis, Glyn; Jones, Peter B
Background Schizophrenia has a neurodevelopmental component to its origin, and may share overlapping pathogenic mechanisms with childhood neurodevelopmental disorders (ND). Yet longitudinal studies of psychotic outcomes among individuals with ND are limited. We report a population-based prospective study of six common childhood ND, subsequent neurocognitive performance and the risk of psychotic experiences (PEs) in early adolescence. Methods PEs were assessed by semi-structured interviews at age 13 years. IQ and working memory were measured between ages 9 and 11 years. The presence of six neurodevelopmental disorders (autism spectrum, dyslexia, dyspraxia, dysgraphia, dysorthographia, dyscalculia) was determined from parent-completed questionnaire at age 9 years. Linear regression calculated mean difference in cognitive scores between those with and without ND. The association between ND and PEs was expressed as odds ratio (OR); effects of cognitive deficits were examined. Potential confounders included age, gender, father’s social class, ethnicity and maternal education. Results Out of 8,220 children, 487 (5.9%) were reported to have ND at age 9 years. Children with, compared with those without ND performed worse on all cognitive measures; adjusted mean difference in total IQ 6.84 (95% CI 5.00- 8.69). The association between total IQ and ND was linear (pneurodevelopmental hypothesis of schizophrenia. PMID:25066026
Bastida Bermejo, José María; Hernández-Rivas, Jesús María; González-Porras, José Ramón
Inherited platelet disorders diagnosis is based on the clinical history and bleeding assessment tools. The laboratory functional assays as well as the molecular test to identify the pathogenic genetic variant are essential to confirm the accurate diagnosis of these disorders. Nowadays, the main challenges to developing a new diagnostic system are involved in reducing the samples' volume, and faster and more helpful analysis. Moreover, there are no widely available and standardised global tests. High throughput genetic testing such as next-generation sequencing has revolutionised DNA sequencing technologies as it allows the simultaneous and faster investigation of multiple genes at a manageable cost. This technology has improved the molecular characterisation of inherited platelet disorders and has been implemented in the research studies and the clinical routine practice. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.
Elias, Eileen; Weider, Katie; Mustafa, Ruman
This article is the ninth of a multi-part series on traumatic brain injury (TBI). It focuses on the process of diagnosing TBI and psychiatric disorders. Diagnosing traumatic brain injury can be challenging. It can be difficult differentiating TBI and psychiatric symptoms, as both have similar symptoms (e.g., memory problems, emotional outbursts,…
Hernan G VALDES-SOCIN
Full Text Available The neuroendocrine control of reproduction in mammals is governed by a neural hypothalamic network of nearly 1500 gonadotropin-releasing hormone (GnRH secreting neurons that modulate the activity of the reproductive axis across life. Congenital hypogonadotropic hypogonadism (HH is a clinical syndrome that is characterized by partial or complete pubertal failure. HH may result from inadequate hypothalamic GnRH axis activation, or a failure of pituitary gonadotropin secretion/effects. In man, several genes that participate in olfactory and GnRH neuronal migration are thought to interact during the embryonic life. A growing number of mutations in different genes are responsible for congenital HH. Based on the presence or absence of olfaction dysfunction, HH is divided in two syndromes: HH with olfactory alterations (Kallmann syndrome and idiopathic hypogonadotropic hypogonadism (IHH with normal smell (normosmic IHH. Kallmann syndrome (KS is a heterogeneous disorder affecting 1 in 5000 males, with a 3-5 fold of males over females. KS is associated with mutations in KAL1, FGFR1/FGF8, FGF17, IL17RD, PROK2/PROKR2, NELF, CHD7, HS6ST1, FLRT3, SPRY4, DUSP6, SEMA3A, NELF and WDR11 genes that are related to defects in neuronal migration. These reproductive and olfactory deficits include a variable non reproductive phenotype, including sensorineural deafness, coloboma, bimanual synkinesis, craniofacial abnormalities and/or renal agenesis. Interestingly, defects in PROKR2, FGFR1, FGF8, CHD7, DUSP6, and WDR11 genes are also associated with normosmic IHH, whereas mutations in KISS1/KISSR, TAC3/TACR3, GNRH1/GNRHR, LEP/LEPR, HESX1, FSHB and LHB are only present in patients with normosmic IHH. In this paper, we summarize the reproductive, neurodevelopmental and genetic aspects of HH in human pathology.
van Niekerk, Maarten E. H.; Groen, Wouter; Vissers, Constance Th. W. M.; van Driel-de Jong, Dorine; Kan, Cees C.; Voshaar, Richard C. Oude
Background: As autism spectrum disorders (ASD) have largely been neglected in old-age psychiatry, the objective of the present paper is to describe the diagnostic process in elderly patients. Methods: A systematic review of the literature on ASD in older age was undertaken and illustrated by a case
Ravi Philip Rajkumar
Gender identity disorder (GID), recently renamed gender dysphoria (GD), is a rare condition characterized by an incongruity between gender identity and biological sex. Clinical evidence suggests that schizophrenia occurs in patients with GID at rates higher than in the general population and that patients with GID may have schizophrenia-like personality traits. Conversely, patients with schizophrenia may experience alterations in gender identity and gender role perception. Neurobiological res...
Weaving, Linda S.; Christodoulou, John; Williamson, Sarah L.; Friend, Kathie L.; McKenzie, Olivia L. D.; Archer, Hayley; Evans, Julie; Clarke, Angus; Pelka, Gregory J.; Tam, Patrick P. L.; Watson, Catherine; Lahooti, Hooshang; Ellaway, Carolyn J.; Bennetts, Bruce; Leonard, Helen; Gécz, Jozef
Rett syndrome (RTT) is a severe neurodevelopmental disorder caused, in most classic cases, by mutations in the X-linked methyl-CpG-binding protein 2 gene (MECP2). A large degree of phenotypic variation has been observed in patients with RTT, both those with and without MECP2 mutations. We describe a family consisting of a proband with a phenotype that showed considerable overlap with that of RTT, her identical twin sister with autistic disorder and mild-to-moderate intellectual disability, and a brother with profound intellectual disability and seizures. No pathogenic MECP2 mutations were found in this family, and the Xq28 region that contains the MECP2 gene was not shared by the affected siblings. Three other candidate regions were identified by microsatellite mapping, including 10.3 Mb at Xp22.31-pter between Xpter and DXS1135, 19.7 Mb at Xp22.12-p22.11 between DXS1135 and DXS1214, and 16.4 Mb at Xq21.33 between DXS1196 and DXS1191. The ARX and CDKL5 genes, both of which are located within the Xp22 region, were sequenced in the affected family members, and a deletion of nucleotide 183 of the coding sequence (c.183delT) was identified in CDKL5 in the affected family members. In a screen of 44 RTT cases, a single splice-site mutation, IVS13-1G→A, was identified in a girl with a severe phenotype overlapping RTT. In the mouse brain, Cdkl5 expression overlaps—but is not identical to—that of Mecp2, and its expression is unaffected by the loss of Mecp2. These findings confirm CDKL5 as another locus associated with epilepsy and X-linked mental retardation. These results also suggest that mutations in CDKL5 can lead to a clinical phenotype that overlaps RTT. However, it remains to be determined whether CDKL5 mutations are more prevalent in specific clinical subgroups of RTT or in other clinical presentations. PMID:15492925
Jamieson, P W
The ability to diagnose multiple interacting disorders and explain them in a coherent causal framework has only partially been achieved in medical expert systems. This paper proposes a causal model for diagnosing and explaining multiple disorders whose key elements are: physician-directed hypotheses generation, object-oriented knowledge representation, and novel explanation heuristics. The heuristics modify and link the explanations to make the physician aware of diagnostic complexities. A computer program incorporating the model currently is in use for diagnosing peripheral nerve and muscle disorders. The program successfully diagnoses and explains interactions between diseases in terms of underlying pathophysiologic concepts. The model offers a new architecture for medical domains where reasoning from first principles is difficult but explanation of disease interactions is crucial for the system's operation.
Atmaca, Murad; Ozler, Sinan; Topuz, Mehtap; Goldstein, Sam
Objective: There is a dearth of literature on patients erroneously diagnosed and treated for bipolar disorder. Method: The authors report a case of an adult with attention deficit hyperactivity disorder erroneously diagnosed and treated for bipolar disorder for 6 years. At that point, methylphenidate was initiated. The patient was judged to be a…
Kido, Jun; Matsumoto, Shirou; Momosaki, Ken; Sakamoto, Rieko; Mitsubuchi, Hiroshi; Endo, Fumio; Nakamura, Kimitoshi
UCDs are among the most common inherited metabolic diseases in Japan. We investigated the clinical manifestations, treatment, and prognoses of 177 patients with UCDs who were evaluated and treated from January 1999 to March 2009 in Japan, using a questionnaire survey. Among these 177 patients, 42 (seven with carbamoyl phosphate synthetase 1 deficiency, 27 with ornithine transcarbamylase deficiency, seven with argininosuccinate synthetase deficiency, and one with arginase 1 deficiency) underwent living-donor LT. Although this study was retrospective and included limited neurodevelopmental information before and after LT, we evaluated whether LT could improve neurodevelopmental outcomes in patients with UCDs. The neurodevelopmental outcomes of patients with a MAC of <300 μmol/L at the time of onset were not significantly different between the LT and non-LT groups (P=.222). LT may have prevented further neurodevelopmental complications in children with MAC ≥300 μmol/L (P=.008) compared with non-transplant management. Therefore, Liver transplant should be considered in patients with UCD with a MAC of ≥300 μmol/L at the time of disease onset. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Sgandurra, Giuseppina; Bartalena, Laura; Cioni, Giovanni
BACKGROUND: Preterm infants are at risk for neurodevelopmental disorders, including motor, cognitive or behavioural problems, which may potentially be modified by early intervention. The EU CareToy Project Consortium (http://www.caretoy.eu) has developed a new modular system for intensive...... parents will sign a written informed consent for participation, will be randomized in CareToy training and control groups at baseline (T0). CareToy group will perform four weeks of personalized activities with the CareToy system, customized by the rehabilitation staff. The control group will continue...
Farmer, Cristan; Golden, Christine; Thurm, Audrey
Estimates of intelligence in young children with neurodevelopmental disorders are critical for making diagnoses, in characterizing symptoms of disorders, and in predicting future outcomes. The limitations of standardized testing for children with developmental delay or cognitive impairment are well known: Tests do not exist that provide developmentally appropriate material along with norms that extend to the lower reaches of ability. Two commonly used and interchanged instruments are the Mullen Scales of Early Learning (MSEL), a test of developmental level, and the Differential Ability Scales, second edition (DAS-II), a more traditional cognitive test. We evaluated the correspondence of contemporaneous MSEL and the DAS-II scores in a mixed sample of children aged 2-10 years with autism spectrum disorder (ASD), non-ASD developmental delays, and typically developing children across the full spectrum of cognitive ability. Consistent with published data on the original DAS and the MSEL, scores on the DAS-II and MSEL were highly correlated. However, curve estimation revealed large mean differences that varied as a function of the child's cognitive ability level. We conclude that interchanging MSEL and DAS-II scores without regard to the discrepancy in scores may produce misleading results in both cross-sectional and longitudinal studies of children with and without ASD, and, thus, this practice should be implemented with caution.
Anna Dyląg, Katarzyna; Sikora-Sporek, Aleksanda; Bańdo, Bożena; Boroń-Zyss, Joanna; Drożdż, Dorota; Dumnicka, Paulina; Przybyszewska, Katarzyna; Sporek, Mateusz; Walocha, Jerzy W; Wojciechowski, Wadim; Urbanik, Andrzej
The aim of the study was to analyze the findings in MRI (magnetic resonance imaging) of the brain amongst children diagnosed with fetal alcohol syndrome (FAS), partial fetal alcohol syndrome (pFAS) or alcohol related neurodevelopmental disorders (ARND). The issue has been studied in several researches previously but the experts agree that there is still few data on the MRI results in the group of younger children. MRI results of 121 patients with either FAS or pFAS or ARND diagnosed with Canadian criteria were analyzed regarding the presence of abnormalities. The group consisted of 71 patients diagnosed with FAS, 33 diagnosed with pFAS and 17 diagnosed with ARND. The mean age of the patients was 8.03 years (standard deviation 4.07). In the total group of FASD patients 61.98% of the patients’ MRI results were abnormal. The most common abnormality in MRI of the patients were demyelination plaques (incidence 23.1%) and corpus callosum narrowing (20.7%) as well as ventricular asymmetry (18.8%).The demyelination plaques and corpus callosum narrowing were more frequent among children ≤4 years old (41.7% vs 18.6%; p=0.016 and 50.0% vs.13.4%; ppFAS and ARND. Both age ≤4 years and FAS diagnosis were independent predictors for multiple anomalies in multiple logistic regression. In structural brain MRI of younger children, multiple anomalies were found more frequently than among older children. Demyelination plaques and corpus callosum narrowing were more common in younger FASD patients than in older ones.
Full Text Available Contemporary aetiopathogenetic considerations, based on neuro-imaging genetic and developmental neurobiology studies, suggest neurodevelopmental origin of schizophrenia. Several lines of evidence including structural abnormalities on in vivo brain imaging, the excess of prenatal and obstetric complications and the association of congenital and minor physical anomalies with schizophrenia, strongly indicate the neurodevelopmental pathogenesis of schizophrenia. On the other hand, controversial concept of psychotic continuum suggests schizophrenia and depression sharing the same genetic contribution to the pathogenesis. If this would be the case, depression could also be considered as neuro developmental disorder. The aims of the study were to investigate the association between: a pregnancy and birth complications (PBC, and b minor physical anomalies (MPA and schizophrenia or depression. Experimental groups consisted of 60 schizophrenic, 28 major depression patients and 30 healthy controls. All patients were diagnosed according to DSM-IV. Schizophrenic group was divided with regard to PANSS score into positive (n=32 and negative form (n=28 subgroups. PBC information were gathered from maternal recall while MPA were examined by using Waldrop scale for adults. The results showed that negative and positive schizophrenic subgroups had significantly more PBC than depressive group (p<0,05, as well than controls (p<0,001; p<0,05; respectively. There was no significant trend for more PBC in negative than in positive subgroup. All schizophrenic patients had higher rates of MPA than depressives (p<0,05. This trend for more MPA was not significant in comparison with healthy controls. These findings suggest that schizophrenia, especially its negative forms, could be considered as a member of the spectrum of neuro developmental disorders, which does not seem to be the case with depression. PBC and MPA could also be valuable in evaluation of risks for
Andrea Horvath Marques
Full Text Available The developing immune system and central nervous system in the fetus and child are extremely sensitive to both exogenous and endogenous signals. Early immune system programming, leading to changes that can persist over the life course, has been suggested, and other evidence suggests that immune dysregulation in the early developing brain may play a role in neurodevelopmental disorders such as autism spectrum disorder and schizophrenia. The timing of immune dysregulation with respect to gestational age and neurologic development of the fetus may shape the elicited response. This creates a possible sensitive window of programming or vulnerability. This review will explore the effects of prenatal maternal and infant nutritional status (from conception until early childhood as well as prenatal maternal stress and anxiety on early programming of immune function, and how this might influence neurodevelopment. We will describe fetal immune system development and maternal-fetal immune interactions to provide a better context for understanding the influence of nutrition and stress on the immune system. Finally, we will discuss the implications for prevention of neurodevelopmental disorders, with a focus on nutrition. Although certain micronutrient supplements have shown to both reduce the risk of neurodevelopmental disorders and enhance fetal immune development, we do not know whether their impact on immune development contributes to the preventive effect on neurodevelopmental disorders. Future studies are needed to elucidate this relationship, which may contribute to a better understanding of preventative mechanisms. Integrating studies of neurodevelopmental disorders and prenatal exposures with the simultaneous evaluation of neural and immune systems will shed light on mechanisms that underlie individual vulnerability or resilience to neurodevelopmental disorders and ultimately contribute to the development of primary preventions and early
Andersen, Stine Linding; Carlé, Allan; Karmisholt, Jesper; Pedersen, Inge Bülow; Andersen, Stig
Fetal programming is a long-standing, but still evolving, concept that links exposures during pregnancy to the later development of disease in the offspring. A fetal programming effect has been considered within different endocrine axes and in relation to different maternal endocrine diseases. In this critical review, we describe and discuss the hypothesis of fetal programming by maternal thyroid dysfunction in the context of fetal brain development and neurodevelopmental disorders in the offspring. Thyroid hormones are important regulators of early brain development, and evidence from experimental and observational human studies have demonstrated structural and functional abnormalities in the brain caused by the lack or excess of thyroid hormone during fetal brain development. The hypothesis that such abnormalities introduced during early fetal brain development increase susceptibility for the later onset of neurodevelopmental disorders in the offspring is biologically plausible. However, epidemiological studies on the association between maternal thyroid dysfunction and long-term child outcomes are observational in design, and are challenged by important methodological aspects. © 2017 European Society of Endocrinology.
Full Text Available Over the past 30 years, preterm births have drastically increased and today represent 12.5% of total births. About 1.2% of preterm births characterize very preterm births (GA<32weeks that, with very low birth weight (BW<1500grams, are constantly found as risk factors of unfavourable neurological outcomes in longitudinal follow up studies. Actually, also “late preterm” children (preterm born from 33 to 36 weeks of gestational age, normally considered at low risk for neurodevelopmental disabilities, are supposed to represent a population of children to be monitored. Previous findings of a general cognitive impairment in children born preterm have gradually addressed the assessment of more specific neuropsychological skills and pointed out the importance to follow these children up to adolescent age. The neuroanatomical prerequisite of an abnormality in frontal lobe development and the correlation with various neuropsychological dysfunctions (fine and gross motor disabilities, executive function and working memory deficits, visual-constructional and attentional dysfunctions underline the interference of preterm birth with normal brain maturational phases. Though showing more demanding neurodevelopmental pathways than term peers, a large number of preterm children tend to functionally normalize in adolescence. The review supports the hypothesis of a neurodevelopmental model that can be at risk to influence dysfunctional neuropsychological outcome.
Martin, Joanna; Hamshere, Marian L; Stergiakouli, Evangelia; O'Donovan, Michael C; Thapar, Anita
Attention-deficit/hyperactivity disorder (ADHD) can be viewed as the extreme end of traits in the general population. Epidemiological and twin studies suggest that ADHD frequently co-occurs with and shares genetic susceptibility with autism spectrum disorder (ASD) and ASD-related traits. The aims of this study were to determine whether a composite of common molecular genetic variants, previously found to be associated with clinically diagnosed ADHD, predicts ADHD and ASD-related traits in the general population. Polygenic risk scores were calculated in the Avon Longitudinal Study of Parents and Children (ALSPAC) population sample (N = 8229) based on a discovery case-control genome-wide association study of childhood ADHD. Regression analyses were used to assess whether polygenic scores predicted ADHD traits and ASD-related measures (pragmatic language abilities and social cognition) in the ALSPAC sample. Polygenic scores were also compared in boys and girls endorsing any (rating ≥ 1) ADHD item (n = 3623). Polygenic risk for ADHD showed a positive association with ADHD traits (hyperactive-impulsive, p = .0039; inattentive, p = .037). Polygenic risk for ADHD was also negatively associated with pragmatic language abilities (p = .037) but not with social cognition (p = .43). In children with a rating ≥ 1 for ADHD traits, girls had a higher polygenic score than boys (p = .003). These findings provide molecular genetic evidence that risk alleles for the categorical disorder of ADHD influence hyperactive-impulsive and attentional traits in the general population. The results further suggest that common genetic variation that contributes to ADHD diagnosis may also influence ASD-related traits, which at their extreme are a characteristic feature of ASD. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
This study investigated the specific emotional lexicons in narratives created by persons diagnosed with antisocial personality disorder (ASPD) to test the hypothesis that individuals with ASPD exhibit deficiencies in emotional language. Study participants consisted of 60 prison inmates with ASPD, 40 prison inmates without ASPD, and 60 men without…
Full Text Available Objective. Eating disorders commonly present with nonspecific findings, masquerading as other, more common etiologies of malnutrition and wasting. In low-prevalence populations, these ambiguities can complicate clinicians’ diagnostic reasoning, resulting in delayed or missed diagnoses. Method. We report the atypical case of a 51-year-old male with a five-year history of unexplained weight loss despite extensive past medical evaluation. Previous documentation of profound lymphopenia and bone marrow atrophy had not been linked to a known association with eating disorders. Results. Evaluation for medical etiologies of wasting was negative. Following psychiatric evaluation, the patient was diagnosed with an eating disorder, not otherwise specified, and admitted to a specialized nutritional rehabilitation program. Conclusion. The nonspecific clinical history, physical exam, and laboratory abnormalities of eating disorders can make these diagnoses challenging and delay appropriate treatment. Clinicians should consider eating disorders in patients with malnutrition, severe lymphopenias, and gelatinous marrow transformation early in their workup, so as to avoid potentially negative outcomes.
Archer, Trevor; Kostrzewa, Richard M; Beninger, Richard J; Palomo, Tomas
Cognitive symptoms, considered in conjunction both with their regional brain and biomarkers as well as affective, attributional and neurodevelopmental components, demonstrate ever-increasing complexity to facilitate conceptualization yet, unavoidably, bedevil diagnosis in neuropsychiatry even before considerations of the enigmatic processes in memory, such as executive function and working memory, are drawn into the myriads of equations that await remedial interpretations. Prefrontal and limbic regions of the brain are involved in a diversity of expressions of cognition, normal or dysfunctional, at synaptic, intracellular and molecular levels that mobilize a concatenation of signaling entities. Serotoninergic neurotransission at prefrontal regions directs cognitive-affective entities that mediate decision-making and goal-directed behaviour. Clinical, non-clinical and basic studies challenge attempts to consolidate the multitude of evidence in order to obtain therapeutic notions to alleviate the disordered status of the diagnosed and yet-to-be diagnosed individuals. Locus of control, a concept of some utility in health-seeking procedures, is examined in three self-report studies from the perspective of a cognitive-emotional situation through observations of ordinary, 'healthy' young and middle-aged individuals, to assess the predictors of internal and external locus of control. A notion based on high level executive functioning in the dorsolateral prefrontal cortex (DLPFC) in individuals characterised by internal locus of control is contrasted with a hypofunctional executive DLPFC, characterising individuals that express an external locus of control, is discussed.
Yu, Junhan; Ross, Colin A.; Keyes, Benjamin B.; Li, Ying; Dai, Yunfei; Zhang, Tianhong; Wang, Lanlan; Fan, Qing; Xiao, Zeping
The purpose of the study was to assess the prevalence of dissociative disorders in a sample of Chinese psychiatric inpatients. Participants in the study consisted of 569 consecutively admitted inpatients at Shanghai Mental Health Center, China, of whom 84.9% had a clinical diagnosis of schizophrenia based on the Chinese Classification and Diagnostic Criteria for Mental Disorders, Version 3 (CCMD-3). All participants completed a self-report measure of dissociation, the Dissociative Experiences Scale (DES) and none had a prior diagnosis of a dissociative disorder. Ninety-six randomly selected participants were interviewed with a structured interview, the Dissociative Disorders Interview Schedule (DDIS) and a clinical interview. These 96 patients did not differ significantly from the 473 patients who were not interviewed on any demographic measures or on the self-report measure dissociation. A total of 28 (15.3%, after weighting of the data) patients received a clinical diagnosis of a dissociative disorder based on DSM-IV-TR criteria. Dissociative identity disorder was diagnosed in 2 (0.53%, after weighting) patients. Compared to the patients without a dissociative disorder, patients with dissociative disorders were significantly more likely to report childhood abuse (57.1% versus 22.1%), but the two groups did not differ significantly on any demographic measures. Dissociative disorders were readily identified in an inpatient psychiatric population in China. PMID:20603768
Thompson, William; Russell, Ginny; Baragwanath, Genevieve; Matthews, Justin; Vaidya, Bijay; Thompson-Coon, Jo
In the last 2 decades, several studies have examined the association between maternal thyroid hormone insufficiency during pregnancy and neurodevelopmental disorders in children and shown conflicting results. This systematic review aimed to assess the evidence for an association between maternal thyroid hormone insufficiency during pregnancy and neurodevelopmental disorders in children. We also sought to assess whether levothyroxine treatment for maternal thyroid hormone insufficiency improves child neurodevelopment outcomes. We performed systematic literature searches in MEDLINE, EMBASE, PSYCinfo, CINAHL, AMED, BNI, Cochrane, Scopus, Web of Science, GreyLit, Grey Source and Open Grey (latest search: March 2017). We also conducted targeted web searching and performed forwards and backwards citation chasing. Meta-analyses of eligible studies were carried out using the random-effects model. We identified 39 eligible articles (37 observational studies and 2 randomized controlled trials [RCT]). Meta-analysis showed that maternal subclinical hypothyroidism and hypothyroxinaemia are associated with indicators of intellectual disability in offspring (odds ratio [OR] 2.14, 95% confidence interval [CI] 1.20 to 3.83, P = .01, and OR 1.63, 95% CI 1.03 to 2.56, P = .04, respectively). Maternal subclinical hypothyroidism and hypothyroxinaemia were not associated with attention deficit hyperactivity disorder, and their effect on the risk of autism in offspring was unclear. Meta-analysis of RCTs showed no evidence that levothyroxine treatment for maternal hypothyroxinaemia or subclinical hypothyroidism reduces the incidence of low intelligence quotient in offspring. Although studies were generally of good quality, there was evidence of heterogeneity between the included observational studies (I 2 72%-79%). Maternal hypothyroxinaemia and subclinical hypothyroidism may be associated with intellectual disability in offspring. Currently, there is no evidence that levothyroxine
Full Text Available The brain is a plastic organ where both the intrinsic CNS milieu and extrinsic cues play important roles in shaping and wiring neural connections. The perinatal period constitutes a critical time in central nervous system development with extensive refinement of neural connections, which are highly sensitive to fetal and neonatal compromise, such as inflammatory challenges. Emerging evidence suggests that inflammatory cells in the brain such as microglia and astrocytes are pivotal in regulating synaptic structure and function. In this article, we will review the role of glia cells in synaptic physiology and pathophysiology, including microglia-mediated elimination of synapses. We propose that activation of the immune system dynamically affects synaptic organization and function in the developing brain. We will discuss the role of neuroinflammation in altered synaptic plasticity following perinatal inflammatory challenges and potential implications for neurodevelopmental and neurodegenerative disorders.
Holland, A.; Whittington, J.; Cohen, O.; Curfs, L.; Delahaye, F.; Dudley, O.; Horsthemke, B.; Lindgren, A. -C.; Nourissier, C.; Sharma, N.; Vogels, A.
Background: Prader-Willi Syndrome (PWS) is a rare genetically determined neurodevelopmental disorder with a complex phenotype that changes with age. The rarity of the syndrome and the need to control for different variables such as genetic sub-type, age and gender limits clinical studies of sufficient size in any one country. A clinical research…
Bell, Emily; Wallace, Tessa; Chouinard, Isabelle; Shevell, Michael; Racine, Eric
Faced with the limitations of currently available mainstream medical treatments and interventions, parents of children with neurodevelopmental disorders often seek information about unproven interventions. These interventions frequently have undetermined efficacy and uncertain safety profiles. In this article, we present a general background and…
Vo, Megen; Accurso, Erin C; Goldschmidt, Andrea B; Le Grange, Daniel
Eating disorder diagnostic criteria were revised from the fourth to the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV and -5, respectively). This study examines the impact of these revisions on rates of eating disorder diagnoses in treatment-seeking youth. Participants were 651 youth, ages 7-18 years, presenting to an outpatient eating disorders program who met criteria for a DSM-IV eating disorder diagnosis on intake. Patients completed well-validated semi-structured interviews to assess eating disorder psychopathology and psychiatric comorbidity. Participants were predominantly female (n = 588; 90.3%) with an average age of 15.28 years (SD = 2.21), mean percent of median Body Mass Index (mBMI) of 101.91 (SD = 31.73), and average duration of illness of 16.74 months (SD = 17.63). Cases of DSM-IV Eating Disorder Not Otherwise Specified (EDNOS), now most consistent with DSM-5 Other Specified Feeding or Eating Disorder, decreased from 47.6% to 39.0%, Anorexia Nervosa increased from 29.6% to 33.5%, and Bulimia Nervosa increased from 22.7% to 24.7%. Consistent with previous studies, and in keeping with the aims of the DSM-5 for eating disorders, the revised diagnostic criteria reduced cases of DSM-IV EDNOS and increased cases of specified eating disorders. © 2016 Wiley Periodicals, Inc.(Int J Eat Disord 2017; 50:578-581). © 2016 Wiley Periodicals, Inc.
Full Text Available Copy number variants (CNVs at chromosome 16p13.11 have been associated with a range of neurodevelopmental disorders including autism, ADHD, intellectual disability and schizophrenia. Significant sex differences in prevalence, course and severity have been described for a number of these conditions but the biological and environmental factors underlying such sex-specific features remain unclear. We tested the burden and the possible sex-biased effect of CNVs at 16p13.11 in a sample of 10,397 individuals with a range of neurodevelopmental conditions, clinically referred for array comparative genomic hybridisation (aCGH; cases were compared with 11,277 controls. In order to identify candidate phenotype-associated genes, we performed an interval-based analysis and investigated the presence of ohnologs at 16p13.11; finally, we searched the DECIPHER database for previously identified 16p13.11 copy number variants. In the clinical referral series, we identified 46 cases with CNVs of variable size at 16p13.11, including 28 duplications and 18 deletions. Patients were referred for various phenotypes, including developmental delay, autism, speech delay, learning difficulties, behavioural problems, epilepsy, microcephaly and physical dysmorphisms. CNVs at 16p13.11 were also present in 17 controls. Association analysis revealed an excess of CNVs in cases compared with controls (OR = 2.59; p = 0.0005, and a sex-biased effect, with a significant enrichment of CNVs only in the male subgroup of cases (OR = 5.62; p = 0.0002, but not in females (OR = 1.19, p = 0.673. The same pattern of results was also observed in the DECIPHER sample. Interval-based analysis showed a significant enrichment of case CNVs containing interval II (OR = 2.59; p = 0.0005, located in the 0.83 Mb genomic region between 15.49-16.32 Mb, and encompassing the four ohnologs NDE1, MYH11, ABCC1 and ABCC6. Our data confirm that duplications and deletions at 16p13
Chen, Ginden; Chiang, Wan-Lin; Shu, Bih-Ching; Guo, Yue Leon; Chiou, Shu-Ti; Chiang, Tung-Liang
Whether birth by caesarean section (CS) increases the occurrence of neurodevelopmental disorders, asthma or obesity in childhood is controversial. We tried to demonstrate the association between children born by CS and the occurrence of the above three diseases at the age of 5.5 years. The database of the Taiwan Birth Cohort Study which was designed to assess the developmental trajectories of 24 200 children born in 2005 was used in this study. Associations between children born by CS and these three diseases were evaluated before and after controlling for gestational age (GA) at birth, children's characteristics and disease-related predisposing factors. Children born by CS had significant increases in neurodevelopmental disorders (20%), asthma (14%) and obesity (18%) compared with children born by vaginal delivery. The association between neurodevelopmental disorders and CS was attenuated after controlling for GA at birth (OR 1.15; 95% CI 0.98 to 1.34). Occurrence of neurodevelopmental disorders steadily declined with increasing GA up to ≤40-42 weeks. CS and childhood asthma were not significantly associated after controlling for parental history of asthma and GA at birth. Obesity in childhood remained significantly associated with CS (OR 1.13; 95% CI 1.04 to 1.24) after controlling for GA and disease-related factors. Our results implied that the association between CS birth and children's neurodevelopmental disorders was significantly influenced by GA. CS birth was weakly associated with childhood asthma since parental asthma and preterm births are stronger predisposing factors. The association between CS birth and childhood obesity was robust after controlling for disease-related factors. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
Nagata, Kensei; Ohashi, Teruaki; Ishibashi, Kazumasa; Hirohashi, Akiyuki; Sato, Kimiaki [Kurume Univ., Fukuoka (Japan). School of Medicine
We report the clinical course of 23 cases with intramedullary disorders diagnosed by MRI. Spinal vascular disease was the most common, and occurred in 11 cases, intramedullary tumor occurred in 6, and multiple sclerosis, myelitis, spinal edema each in 2. The characteristic MRI findings of the intramedullary disorders were spinal cord swelling on T1 weighted image and changes in the intensity on the T2 weighted image. Surgical treatment was performed in 5 of the 11 with spinal vascular disease and in 6 with an intra-medullary tumor. One patient with AV malformation underwent embolization of the spinal artery. The other 11 received conservative treatment. The period of follow-up ranged from 6 months to 9 years after onset. Complete recovery from symptoms was achieved in only 2 patients, some recovery was achieved in 8, no change in 10, and deterioration occurred in 3. In conclusion, it has become easy to diagnose intramedullary disorders by utilizing MRI. However, an accurate qualitative diagnosis is difficult except for spinal vascular disease. Complete recovery from the symptoms of intramedullary disorders remains difficult to achieve by available treatments. (author)
Nagata, Kensei; Ohashi, Teruaki; Ishibashi, Kazumasa; Hirohashi, Akiyuki; Sato, Kimiaki
We report the clinical course of 23 cases with intramedullary disorders diagnosed by MRI. Spinal vascular disease was the most common, and occurred in 11 cases, intramedullary tumor occurred in 6, and multiple sclerosis, myelitis, spinal edema each in 2. The characteristic MRI findings of the intramedullary disorders were spinal cord swelling on T1 weighted image and changes in the intensity on the T2 weighted image. Surgical treatment was performed in 5 of the 11 with spinal vascular disease and in 6 with an intra-medullary tumor. One patient with AV malformation underwent embolization of the spinal artery. The other 11 received conservative treatment. The period of follow-up ranged from 6 months to 9 years after onset. Complete recovery from symptoms was achieved in only 2 patients, some recovery was achieved in 8, no change in 10, and deterioration occurred in 3. In conclusion, it has become easy to diagnose intramedullary disorders by utilizing MRI. However, an accurate qualitative diagnosis is difficult except for spinal vascular disease. Complete recovery from the symptoms of intramedullary disorders remains difficult to achieve by available treatments. (author)
Drosophila mutants of the autism candidate gene neurobeachin (rugose) exhibit neuro-developmental disorders, aberrant synaptic properties, altered locomotion, impaired adult social behavior and activity patterns
Wise, Alexandra; Tenezaca, Luis; Fernandez, Robert W.; Schatoff, Emma; Flores, Julian; Ueda, Atsushi; Zhong, Xiaotian; Wu, Chun-Fang; Simon, Anne F.; Venkatesh, Tadmiri
Autism spectrum disorder (ASD) is a neurodevelopmental disorder in humans characterized by complex behavioral deficits, including intellectual disability, impaired social interactions and hyperactivity. ASD exhibits a strong genetic component with underlying multi-gene interactions. Candidate gene studies have shown that the neurobeachin gene is disrupted in human patients with idiopathic autism (Castermans et al., 2003). The gene for neurobeachin (NBEA) spans the common fragile site FRA 13A ...
Schultz Jennifer F
Full Text Available Abstract Background Previous research has documented that the symptoms of bipolar disorder are often mistaken for unipolar depression prior to a patient's first bipolar diagnosis. The assumption has been that once a patient receives a bipolar diagnosis they will no longer be given a misdiagnosis of depression. The objectives of this study were 1 to assess the rate of subsequent unipolar depression diagnosis in individuals with a history of bipolar disorder and 2 to assess the increased cost associated with this potential misdiagnosis. Methods This study utilized a retrospective cohort design using administrative claims data from 2002 and 2003. Patient inclusion criteria for the study were 1 at least 2 bipolar diagnoses in 2002, 2 continuous enrollment during 2002 and 2003, 3 a pharmacy benefit, and 4 age 18 to 64. Patients with at least 2 unipolar depression diagnoses in 2003 were categorized as having an incongruent diagnosis of unipolar depression. We used propensity scoring to control for selection bias. Utilization was evaluated using negative binomial models. We evaluated cost differences between patient cohorts using generalized linear models. Results Of the 7981 patients who met all inclusion criteria for the analysis, 17.5% (1400 had an incongruent depression diagnosis (IDD. After controlling for background differences, individuals who received an IDD had higher rates of inpatient and outpatient psychiatric utilization and cost, on average, an additional $1641 per year compared to individuals without an IDD. Conclusions A strikingly high proportion of bipolar patients are given the differential diagnosis of unipolar depression after being identified as having bipolar disorder. Individuals with an IDD had increased acute psychiatric care services, suggesting higher levels of relapses, and were at risk for inappropriate treatment, as antidepressant therapy without a concomitant mood-stabilizing medication is contraindicated in bipolar
Lindhiem, Oliver; Bennett, Charles B; Hipwell, Alison E; Pardini, Dustin A
Conduct Disorder (CD) and Oppositional Defiant Disorder (ODD) are among the most commonly diagnosed childhood behavioral health disorders. Although there is substantial evidence of heterogeneity of symptom presentations, DSM diagnoses of CD and ODD are formally diagnosed on the basis of symptom counts without regard to individual symptom patterns. We used unidimensional item response theory (IRT) two-parameter logistic (2PL) models to examine item parameters for the individual symptoms of CD and ODD using data on 6,491 adolescents (ages 13-17) from the National Comorbidity Study: Adolescent Supplement (NCS-A). For each disorder, the symptoms differed in terms of severity and discrimination parameters. As a result, some adolescents who were above DSM diagnostic thresholds for disruptive behavior disorders exhibited lower levels of the underlying construct than others below the thresholds, based on their unique symptom profile. In terms of incremental benefit, our results suggested an advantage of latent trait scores for CD but not ODD.
Forgeot D'Arc, Baudouin; Dubail-Sbasnik, Christelle; Legay, Vassilissa
Difficulties in scholarship in children are very frequent reasons for consultation in general practice. General practitioners' role is primordial in screening, diagnosis and management in these complex and long-lasting disorders. Learning difficulties often stem from developmental disorders, which are frequently co-occurring and may be associated with emotional and behavioural disorders. They often persist in adulthood, but may benefit from active management associating training interventions and school accommodations.
Møller Luef, Birgitte; Andersen, Louise B; Renault, Kristina Martha
INTRODUCTION: A correct diagnosis of preeclampsia and gestational hypertension is important for treatment and epidemiological studies. Changes in diagnostic criteria and underreporting in certain subsets of patients may hamper validity of the diagnoses. MATERIALS AND METHODS: We validated....... After validation, significantly more patients fulfilled criteria for diagnosis of preeclampsia (n = 163, 7.5%, p = 0.002); more had severe preeclampsia, 14 (0.6%) vs. 70 (3.2%), p hypertension, 62 (2.9%) vs. 46 (2.1%), p = 0.12. The diagnostic sensitivity for preeclampsia...... of hypertensive disorders in pregnancy for research purposes....
Yilmaz, Zeynep; Szatkiewicz, Jin P; Crowley, James J; Ancalade, NaEshia; Brandys, Marek K; van Elburg, Annemarie; de Kovel, Carolien G F; Adan, Roger A H; Hinney, Anke; Hebebrand, Johannes; Gratacos, Monica; Fernandez-Aranda, Fernando; Escaramis, Georgia; Gonzalez, Juan R; Estivill, Xavier; Zeggini, Eleftheria; Sullivan, Patrick F; Bulik, Cynthia M
Anorexia nervosa (AN) is a serious and heritable psychiatric disorder. To date, studies of copy number variants (CNVs) have been limited and inconclusive because of small sample sizes. We conducted a case-only genome-wide CNV survey in 1983 female AN cases included in the Genetic Consortium for Anorexia Nervosa. Following stringent quality control procedures, we investigated whether pathogenic CNVs in regions previously implicated in psychiatric and neurodevelopmental disorders were present in AN cases. We observed two instances of the well-established pathogenic CNVs in AN cases. In addition, one case had a deletion in the 13q12 region, overlapping with a deletion reported previously in two AN cases. As a secondary aim, we also examined our sample for CNVs over 1 Mbp in size. Out of the 40 instances of such large CNVs that were not implicated previously for AN or neuropsychiatric phenotypes, two of them contained genes with previous neuropsychiatric associations, and only five of them had no associated reports in public CNV databases. Although ours is the largest study of its kind in AN, larger datasets are needed to comprehensively assess the role of CNVs in the etiology of AN.
Bachmann, Christian J.; Gerste, Bettina; Hoffmann, Falk
For Germany, no data on trends in autism spectrum disorder diagnoses are available. The primary aim of this study was to establish the time trends in the administrative prevalence of autism spectrum disorder diagnoses. The second aim was to assess the stability of autism spectrum disorder diagnoses over time. We analysed administrative outpatient…
Montano, C Brendan; Rasgon, Natalie L; Herman, Barry K
Binge eating disorder (BED), now recognized as a distinct eating disorder in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, is the most prevalent eating disorder. Although nearly half of individuals with BED are obese, BED also occurs in nonobese individuals. Despite the relatively high percentage of weight loss treatment-seeking individuals meeting BED criteria, primary care physicians may not be familiar with or have ever diagnosed BED. Many providers may also have difficulty distinguishing BED as a contributory factor in obesity. This review differentiates BED from other causes of obesity by describing how obese individuals with BED differ from obese individuals without BED and from nonobese individuals with BED in areas including psychopathology, behavior, genetics, physiology, quality of life and productivity. The ways in which health-care providers can identify individuals who may have BED are also highlighted so the proper course of treatment is pursued. Overall, obese individuals with BED demonstrate a number of key characteristics that differentiate them from obese individuals without eating disorders, including increased impulsivity in response to food stimuli with loss of control over eating, resulting in the consumption of more calories. They also experience significant guilt and other negative emotions following a meal. In addition, individuals with BED patients have more psychiatric comorbidity, display more psychopathology, exhibit longer binge durations, consume more meals as snacks during the day and have less dietary restraint compared with individuals with BED who are not obese. However, the differences between individuals with BED who are obese versus not obese are not as prominent. Taken together, the evidence appears to support the conclusion that BED is a unique and treatable neurobehavioral disorder associated with distinct behavioral and psychological profiles and distinct medical and functional outcomes, and that
Zwas, S.T.; Rosenblum, Yossef; Boruchowsky, Sabina
The optimal utilization of the thyroid related radioimmunoassays T3, T4, and TSH-RIA is derived from analysing the clinical and laboratory data for 974 patients with functional thyroid disorders. A statistical computer analysis of the contribution of each of the three tests, and in combination, to the final diagnoses of hypothyroid, euthyroid, and hyper thyroid states was designed. The best contributing test for hypothyroidism and euthyroidism was TSH-RIA (98.5 and 93%, respectively). T4/T3+TSH-RIAs were the optimal dual combination for diagnosing euthyroidism (98.0%). For diagnosing hyperthyroidism T4-RIA was the best single test (82.5%) followed by T3 + T4 as an optimal dual combination (95%). Using all three tests was of no significant additional value over dual combinations. It is concluded that the work and cost of randomly performing three tests routinely is not justified without clinical basis. An algorithm is proposed to guide thyroid studies based on computer analyses of the above-mentioned single or dual-test combinations to establish accurate diagnosis at the lowest laboratory cost. (author)
Demjaha, Arsime; MacCabe, James H; Murray, Robin M
The debate endures as to whether schizophrenia and bipolar disorder are separate entities or different manifestations of a single underlying pathological process. Here, we argue that this sterile argument obscures the fact that the truth lies somewhere in between. Thus, recent studies support a model whereby, on a background of some shared genetic liability for both disorders, patients with schizophrenia have been subject to additional genetic and/or environmental factors that impair neurodevelopment; for example, copy number variants and obstetric complications are associated with schizophrenia but not with bipolar disorder. As a result, children destined to develop schizophrenia show an excess of neuromotor delays and cognitive difficulties while those who later develop bipolar disorder perform at least as well as the general population. In keeping with this model, cognitive impairments and brain structural abnormalities are present at first onset of schizophrenia but not in the early stages of bipolar disorder. However, with repeated episodes of illness, cognitive and brain structural abnormalities accumulate in both schizophrenia and bipolar disorder, thus clouding the picture.
Carballal Mariño, Marta; Gago Ageitos, Ana; Ares Alvarez, Josefa; Del Rio Garma, Mercedes; García Cendón, Clara; Goicoechea Castaño, Ana; Pena Nieto, Josefina
To determine the prevalence of psychiatric disorders in primary care pediatrics in Atlantic Galicia. An observational, descriptive, cross-sectional prevalence study was carried out in 9 outpatient clinics in A Coruña and Pontevedra with a population of 8293 children between September and November 2015. A total of 1286 randomly selected patients from 0 to 14 years of age were included. From the medical history was registered: age, sex, psychiatric diagnosis established by DSM-IV-TR criteria in its five axes, professionals who participated in the diagnosis and treatment of the process and what type of treatment was received. Authorization was obtained from the Research Ethics Committee of Galicia number 2015/427. 148 of 1286 patients presented psychiatric pathology (11,5% IC 95% 9.73-13,29), 68% male. Between 0 and 5years, the prevalence was 4.5%; between 6y and 10y, 18.5% and between 11y and 14y 22%. Symptoms lasted a median of 25 months. The most frequent pathologies in 1286 patients were ADHD (5.36%), language disorders (3.42%), learning disorders (3.26%), anxiety-depressive disorders (2.4%) and behavior disorders (1.87%). Of the 148 cases, 47% had comorbidity with another mental disorder. Most of them required attention by multiple social, health and educational professionals; 33% received psychopharmacological treatment. The prevalence of psychiatric disorders in pediatric primary care is frequent, chronic and complex, increases with age and requires many health, educational and social resources. Copyright © 2017. Publicado por Elsevier España, S.L.U.
Johnels, Jakob Åsberg; Hagberg, Bibbi; Gillberg, Christopher; Miniscalco, Carmela
Oral narrative retelling is often problematic for children with communicative and neurodevelopmental disorders. However, beyond a suggested role of language level, little is known about the basis of narrative performance. In this study we examine whether oral narrative retelling might be associated not just with language level but also with skills related to nonverbal narrative temporal sequencing. A diagnostically heterogeneous sample of Swedish-speaking children with a full scale IQ >70 was included in the study (N = 55; age 6-9 years). Narrative retelling skills were measured using the three subscores from the bus story test (BST). Independent predictors included (1) temporal sequencing skills according to a picture arrangement test and (2) a language skills factor consisting of definitional vocabulary and receptive grammar. Regression analyses show that language skills predicted BST Sentence Length and Subordinate Clauses subscores, while both temporal sequencing and language were independently linked with the BST Information subscore. When subdividing the sample based on nonverbal temporal sequencing level, a significant subgroup difference was found only for BST Information. Finally, a principal component analysis shows that temporal sequencing and BST Information loaded on a common factor, separately from the language measures. It is concluded that language level is an important correlate of narrative performance more generally in this diagnostically heterogeneous sample, and that nonverbal temporal sequencing functions are important especially for conveying story information. Theoretical and clinical implications are discussed. © 2013 The Scandinavian Psychological Associations.
Stoodley, Catherine J.; Limperopoulos, Catherine
SUMMARY The increasing appreciation of the role of the cerebellum in motor and non-motor functions is crucial to understanding the outcomes of acquired cerebellar injury and developmental lesions in high-risk fetal and neonatal populations, children with cerebellar damage (e.g. posterior fossa tumors), and neurodevelopmental disorders (e.g. autism). We review available data regarding the relationship between the topography of cerebellar injury or abnormality and functional outcomes. We report emerging structure–function relationships with specific symptoms: cerebellar regions that interconnect with sensorimotor cortices are associated with motor impairments when damaged; disruption to posterolateral cerebellar regions that form circuits with association cortices impact long-term cognitive outcomes; and midline posterior vermal damage is associated with behavioral dysregulation and an autism-like phenotype. We also explore the impact of age and the potential role for critical periods on cerebellar structure and child function. These findings suggest that the cerebellum plays a critical role in motor, cognitive, and social–behavioral development, possibly via modulatory effects on the developing cerebral cortex. PMID:27184461
Full Text Available During mammalian ontogenesis, the neurotransmitter GABA is a fundamental regulator of neuronal networks. In neuronal development, GABAergic signaling regulates neural proliferation, migration, differentiation, and neuronal-network wiring. In the adult, GABA orchestrates the activity of different neuronal cell-types largely interconnected, by powerfully modulating synaptic activity. GABA exerts these functions by binding to chloride-permeable ionotropic GABAA receptors and metabotropic GABAB receptors. According to its functional importance during development, GABA is implicated in a number of neurodevelopmental disorders such as autism, Fragile X, Rett syndrome, Down syndrome, schizophrenia, Tourette's syndrome and neurofibromatosis.The strength and polarity of GABAergic transmission is continuously modulated during physiological, but also pathological conditions. For GABAergic transmission through GABAA receptors, strength regulation is achieved by different mechanisms such as modulation of GABAA receptors themselves, variation of intracellular chloride concentration, and alteration in GABA metabolism. In the never-ending effort to find possible treatments for GABA-related neurological diseases, of great importance would be modulating GABAergic transmission in a safe and possibly physiological way, without the dangers of either silencing network activity or causing epileptic seizures. In this review, we will discuss the different ways to modulate GABAergic transmission normally at work both during physiological and pathological conditions. Our aim is to highlight new research perspectives for therapeutic treatments that reinstate natural and physiological brain functions in neuro-pathological conditions.
Muideen O. Bakare
Full Text Available Sub-Saharan African (SSA population consists of about 45% children, while in Europe and North America children population is 10- 15%. Lately, attention has been directed at mitigating childhood infectious and communicable diseases to reduce under-five mortality. As the under-five mortality index in Sub-Saharan Africa has relatively improved over the last two decades, more Sub-Saharan African children are surviving beyond the age of five and, apparently, a sizeable percentage of this population would be living with one or more childhood neurodevelopmental disorders (NDD. The distribution of child mental health service resources across the world is unequal. This manifests in the treatment gap of major childhood onset mental health problems in SSA, with the gap being more pronounced for childhood NDD. It is important to balance the public health focus and research funding priorities in Sub-Saharan Africa. We urgently need to define the burden of childhood NDD in the region for healthcare planning and policy formulation.
Schizophrenia and bipolar disorders share not only clinical features but also some risk factors such as genetic markers and childhood adversity, while other risk factors such as urbanicity and obstetric complications seem to be specific to schizophrenia. An intriguing question is whether the well-established abnormal neurodevelopment present in many children and adolescents who eventually develop schizophrenia is also present in bipolar patients. The literature on adult bipolar patients is controversial. We report data on a subgroup of patients with pediatric-onset psychotic bipolar disorder who seem to share some developmental trajectories with patients with early-onset schizophrenia. These early-onset psychotic bipolar patients have low intelligence quotient, more neurological signs, reduced frontal gray matter at the time of their first psychotic episode, and greater brain changes than healthy controls in a pattern similar to early-onset schizophrenia cases. However, patients with early-onset schizophrenia seem to have more social impairment, developmental abnormalities (eg, language problems), and lower academic achievement in childhood than early-onset bipolar patients. We suggest that some of these abnormal developmental trajectories are more related to the phenotypic features (eg, early-onset psychotic symptoms) of these 2 syndromes than to categorically defined Diagnostic and Statistical Manual of Mental Disorders disorders. PMID:24371326
Perra, Oliver; Williams, Justin H. G.; Whiten, Andrew; Fraser, Lesley; Benzie, Helen; Perrett, David I.
Several studies have reported imitative deficits in autism spectrum disorder (ASD). However, it is still debated if imitative deficits are specific to ASD or shared with clinical groups with similar mental impairment and motor difficulties. We investigated whether imitative tasks can be used to discriminate ASD children from typically developing…
Iqbal, Z.; Vandeweyer, G.; Voet, M. van der; Waryah, A.M.; Zahoor, M.Y.; Besseling, J.A.; Roca, L.T.; Silfhout, A.T. van; Nijhof, B.; Kramer, J.M.; Aa, N. van der; Ansar, M.; Peeters, H.; Helsmoortel, C.; Gilissen, C.F.H.A.; Vissers, L.E.L.M.; Veltman, J.A.; Brouwer, A.P.M. de; Kooy, R. van; Riazuddin, S.; Schenck, A.; Bokhoven, H. van; Rooms, L.
AnkyrinG, encoded by the ANK3 gene, is involved in neuronal development and signaling. It has previously been implicated in bipolar disorder and schizophrenia by association studies. Most recently, de novo missense mutations in this gene were identified in autistic patients. However, the causative
Oguro-Ando, Asami; Zuko, Amila; Kleijer, Kristel T.E.; Burbach, J. Peter H.
Contactins (Cntns) are a six-member subgroup of the immunoglobulin cell adhesion molecule superfamily (IgCAMs) with pronounced brain expression and function. Recent genetic studies of neuropsychiatric disorders have pinpointed contactin-4 (CNTN4), contactin-5 (CNTN5) and contactin-6 (CNTN6) as
Sgandurra, Giuseppina; Bartalena, Laura; Cioni, Giovanni; Greisen, Gorm; Herskind, Anna; Inguaggiato, Emanuela; Lorentzen, Jakob; Nielsen, Jens Bo; Sicola, Elisa
Preterm infants are at risk for neurodevelopmental disorders, including motor, cognitive or behavioural problems, which may potentially be modified by early intervention. The EU CareToy Project Consortium (http://www.caretoy.eu) has developed a new modular system for intensive, individualized, home-based and family-centred early intervention, managed remotely by rehabilitation staff. A randomised controlled trial (RCT) has been designed to evaluate the efficacy of CareToy training in a first sample of low-risk preterm infants. The trial, randomised, multi-center, evaluator-blinded, parallel group controlled, is designed according to CONSORT Statement. Eligible subjects are infants born preterm without major complications, aged 3-9 months of corrected age with specific gross-motor abilities defined by Ages & Stages Questionnaire scores. Recruited infants, whose parents will sign a written informed consent for participation, will be randomized in CareToy training and control groups at baseline (T0). CareToy group will perform four weeks of personalized activities with the CareToy system, customized by the rehabilitation staff. The control group will continue standard care. Infant Motor Profile Scale is the primary outcome measure and a total sample size of 40 infants has been established. Bayley-Cognitive subscale, Alberta Infants Motor Scale and Teller Acuity Cards are secondary outcome measures. All measurements will be performed at T0 and at the end of training/control period (T1). For ethical reasons, after this first phase infants enrolled in the control group will perform the CareToy training, while the training group will continue standard care. At the end of open phase (T2) all infants will be assessed as at T1. Further assessment will be performed at 18 months corrected age (T3) to evaluate the long-term effects on neurodevelopmental outcome. Caregivers and rehabilitation staff will not be blinded whereas all the clinical assessments will be performed
Durieux, Alice M. S.; Fernandes, Cathy; Murphy, Declan; Labouesse, Marie Anais; Giovanoli, Sandra; Meyer, Urs; Li, Qi; So, Po-Wah; McAlonan, Grainne
An imbalance between excitatory (E) glutamate and inhibitory (I) GABA transmission may underlie neurodevelopmental conditions such as autism spectrum disorder (ASD) and schizophrenia. This may be direct, through alterations in synaptic genes, but there is increasing evidence for the importance of indirect modulation of E/I balance through glial mechanisms. Here, we used C57BL/6J mice to test the hypothesis that striatal glutamate levels can be shifted by N-acetylcysteine (NAC), which acts at the cystine-glutamate antiporter of glial cells. Striatal glutamate was quantified in vivo using proton magnetic resonance spectroscopy. The effect of NAC on behaviors relevant to ASD was examined in a separate cohort. NAC induced a time-dependent decrease in striatal glutamate, which recapitulated findings of lower striatal glutamate reported in ASD. NAC-treated animals were significantly less active and more anxious in the open field test; and NAC-treated females had significantly impaired prepulse inhibition of startle response. This at least partly mimics greater anxiety and impaired sensorimotor gating reported in neurodevelopmental disorders. Thus glial mechanisms regulate glutamate acutely and have functional consequences even in adulthood. Glial cells may be a potential drug target for the development of new therapies for neurodevelopmental disorders across the life-span. PMID:26696857
Roche, Laura; Sigafoos, Jeff; Lancioni, Giulio E; O'Reilly, Mark F; Schlosser, Ralf W; Stevens, Michelle; van der Meer, Larah; Achmadi, Donna; Kagohara, Debora; James, Ruth; Carnett, Amarie; Hodis, Flaviu; Green, Vanessa A; Sutherland, Dean; Lang, Russell; Rispoli, Mandy; Machalicek, Wendy; Marschik, Peter B
Children with neurodevelopmental disorders often present with little or no speech. Augmentative and alternative communication (AAC) aims to promote functional communication using non-speech modes, but it might also influence natural speech production. To investigate this possibility, we provided AAC intervention to two boys with neurodevelopmental disorders and severe communication impairment. Intervention focused on teaching the boys to use a tablet computer-based speech-generating device (SGD) to request preferred stimuli. During SGD intervention, both boys began to utter relevant single words. In an effort to induce more speech, and investigate the relation between SGD availability and natural speech production, the SGD was removed during some requesting opportunities. With intervention, both participants learned to use the SGD to request preferred stimuli. After learning to use the SGD, both participants began to respond more frequently with natural speech when the SGD was removed. The results suggest that a rehabilitation program involving initial SGD intervention, followed by subsequent withdrawal of the SGD, might increase the frequency of natural speech production in some children with neurodevelopmental disorders. This effect could be an example of response generalization. Copyright © 2014 ISDN. Published by Elsevier Ltd. All rights reserved.
Alice Marie Sybille Durieux
Full Text Available An imbalance between excitatory (E glutamate and inhibitory (I GABA transmission may underlie neurodevelopmental conditions such as Autism Spectrum Disorder (ASD and schizophrenia. This may be direct, through alterations in synaptic genes, but there is increasing evidence for the importance of indirect modulation of E/I balance through glial mechanisms. Here we used C57BL/6J mice to test the hypothesis that striatal glutamate levels can be shifted by N-acetylcysteine (NAC, which acts at the cystine-glutamate antiporter of glial cells. Striatal glutamate was quantified in-vivo using proton magnetic resonance spectroscopy. The effect of NAC on behaviours relevant to ASD was examined in a separate cohort. NAC induced a time-dependent decrease in striatal glutamate, which recapitulated findings of lower striatal glutamate reported in ASD. NAC-treated animals were significantly less active and more anxious in the open field test; and NAC-treated females had significantly impaired prepulse inhibition of startle response. This at least partly mimics greater anxiety and impaired sensorimotor gating reported in neurodevelopmental disorders. Thus glial mechanisms regulate glutamate acutely and have functional consequences even in adulthood. Glial cells may be a potential drug target for the development of new therapies for neurodevelopmental disorders across the life-span.
Ye, Xin Cynthia; Ng, Isaiah; Seid-Karbasi, Puya; Imam, Tuhina; Lee, Cheryl E; Chen, Shirley Yu; Herman, Adam; Sharma, Balraj; Johal, Gurinder; Gu, Bobby; Wasserman, Wyeth W
The Portal for Families Overcoming Neurodevelopmental Disorders (PFOND) provides a structured Internet interface for the sharing of information with individuals struggling with the consequences of rare developmental disorders. Large disease-impacted communities can support fundraising organizations that disseminate Web-based information through elegant websites run by professional staff. Such quality resources for families challenged by rare disorders are infrequently produced and, when available, are often dependent upon the continued efforts of a single individual. The project endeavors to create an intuitive Web-based software system that allows a volunteer with limited technical computer skills to produce a useful rare disease website in a short time period. Such a system should provide access to emerging news and research findings, facilitate community participation, present summary information about the disorder, and allow for transient management by volunteers who are likely to change periodically. The prototype portal was implemented using the WordPress software system with both existing and customized supplementary plug-in software modules. Gamification scoring features were implemented in a module, allowing editors to measure progress. The system was installed on a Linux-based computer server, accessible across the Internet through standard Web browsers. A prototype PFOND system was implemented and tested. The prototype system features a structured organization with distinct partitions for background information, recent publications, and community discussions. The software design allows volunteer editors to create a themed website, implement a limited set of topic pages, and connect the software to dynamic RSS feeds providing information about recent news or advances. The prototype was assessed by a fraction of the disease sites developed (8 out of 27), including Aarskog-Scott syndrome, Aniridia, Adams-Oliver syndrome, Cat Eye syndrome, Kabuki syndrome
Medline Patterson PH (2002) Maternal infection: window on neuroimmune inter- actions in fetal brain development and mental illness . Curr Opin Neuro- biol...early stages of pre- and postnatal development has long-term consequences on adult brain function and behavior. Thus, 5-HT is a good candidate for...mediating the fetal programming of mental disorders such as ASD that appear later in life. In early pregnancy the placenta converts maternal TRP to 5-HT
Khokhar, Jibran Y; Todd, Travis P
Alcohol use disorder commonly occurs in patients with schizophrenia and contributes greatly to its morbidity. Unfortunately, the neural and behavioral underpinnings of alcohol drinking in these patients are not well understood. In order to begin to understand the cognitive and reward-related changes that may contribute to alcohol drinking, this study was designed to address: 1) latent inhibition; 2) conditioning; and 3) extinction of autoshaping in a neurodevelopmental rat model with relevance to co-occurring schizophrenia and alcohol use disorders, the neonatal ventral hippocampal lesioned (NVHL) rat. NVHL lesions (or sham surgeries) were performed on post-natal day 7 (PND7) and animals were given brief exposure to alcohol during adolescent (PND 28-42). Latent inhibition of autoshaping, conditioning and extinction were assessed between PND 72-90. On PND90 animals were given alcohol again and allowed to establish stable drinking. Latent inhibition of autoshaping was found to be prolonged in the NVHL rats; the NVHL rats pre-exposed to the lever stimulus were slower to acquire autoshaping than sham pre-exposed rats. NVHL rats that were not pre-exposed to the lever stimulus did not differ during conditioning, but were slower to extinguish conditioned responding compared to sham controls. Finally, the NVHL rats from both groups drank significantly more alcohol than sham rats, and the extent of latent inhibition predicted future alcohol intake in the pre-exposed animals. These findings suggest that the latent inhibition of autoshaping procedure can be used to model cognitive- and reward-related dysfunctions in schizophrenia, and these dysfunctions may contribute to the development of co-occurring alcohol use. Copyright © 2017 Elsevier B.V. All rights reserved.
Kerns, Kimberly A; Macoun, Sarah; MacSween, Jenny; Pei, Jacqueline; Hutchison, Marnie
The current study investigated the efficacy of a game-based process specific intervention for improving attention and working memory in children with Fetal Alcohol Spectrum Disorders (FASD) and Autism Spectrum Disorders (ASD). The Caribbean Quest (CQ) is a 'serious game' that consists of five hierarchically structured tasks, delivered in an adaptive format, targeting different aspects of attention and/or working memory. In addition to game play, the intervention incorporates metacognitive strategies provided by trained educational assistants (EAs), to facilitate generalization and far transfer to academic and daily skills. EAs delivered the intervention to children (ages 6-13) during their regular school day, providing children with instruction in metacognitive strategies to improve game play, with participants completing approximately 12 hours of training over an 8 to 12 school week period. Pre- and post-test analyses revealed significant improvement on measures of working memory and attention, including reduced distractibility and improved divided attention skills. Additionally, children showed significant gains in performance on an academic measure of reading fluency, suggesting that training-related gains in attention and working memory transferred to classroom performance. Exit interviews with EAs revealed that the intervention was easily delivered within the school day, that children enjoyed the intervention, and that children transferred metacognitive strategies learned in game play into the classroom. Preliminary results support this game-based process specific intervention as a potentially effective treatment and useful tool for supporting cognitive improvements in children with FASD or ASD, when delivered as part of an overall treatment plan.
Full Text Available The mediodorsal nucleus of the thalamus (MD has been implicated in executive functions (such as planning, cognitive control, working memory, and decision-making because of its significant interconnectivity with the prefrontal cortex (PFC. Yet, whilst the roles of the PFC have been extensively studied, how the MD contributes to these cognitive functions remains relatively unclear. Recently, causal evidence in monkeys has demonstrated that in everyday tasks involving rapid updating (e.g., while learning something new, making decisions, or planning the next move, the MD and frontal cortex are working in close partnership. Furthermore, researchers studying the MD in rodents have been able to probe the underlying mechanisms of this relationship to give greater insights into how the frontal cortex and MD might interact during the performance of these essential tasks. This review summarizes the circuitry and known neuromodulators of the MD, and considers the most recent behavioral, cognitive, and neurophysiological studies conducted in monkeys and rodents; in total, this evidence demonstrates that MD makes a critical contribution to cognitive functions. We propose that communication occurs between the MD and the frontal cortex in an ongoing, fluid manner during rapid cognitive operations, via the means of efference copies of messages passed through transthalamic routes; the conductance of these messages may be modulated by other brain structures interconnected to the MD. This is similar to the way in which other thalamic structures have been suggested to carry out forward modeling associated with rapid motor responding and visual processing. Given this, and the marked thalamic pathophysiology now identified in many neuropsychiatric disorders, we suggest that changes in the different subdivisions of the MD and their interconnections with the cortex could plausibly give rise to a number of the otherwise disparate symptoms (including changes to olfaction
Shiner, Brian; Leonard Westgate, Christine; Bernardy, Nancy C; Schnurr, Paula P; Watts, Bradley V
Despite long-standing interest in posttraumatic stress disorder (PTSD) and opioid use disorder comorbidity, there is a paucity of data on the prevalence of opioid use disorder in patients with PTSD. Therefore, there is limited understanding of the use of medications for opioid use disorder in this population. We determined the prevalence of diagnosed opioid use disorder and use of medications for opioid use disorder in a large cohort of patients with PTSD. We obtained administrative and pharmacy data for veterans who initiated PTSD treatment in the Department of Veterans Affairs (VA) between 2004 and 2013 (N = 731,520). We identified those with a comorbid opioid use disorder diagnosis (2.7%; n = 19,998) and determined whether they received a medication for opioid use disorder in the year following their initial clinical PTSD diagnosis (29.6%; n = 5,913). Using logistic regression, we determined the predictors of receipt of opioid use disorder medications. Comorbid opioid use disorder diagnoses increased from 2.5% in 2004 to 3.4% in 2013. Patients with comorbid opioid use disorder used more health services and had more comorbidities than other patients with PTSD. Among patients with PTSD and comorbid opioid use disorder, use of medications for opioid use disorder increased from 22.6% to 35.1% during the same time period. Growth in the use of buprenorphine (2.0% to 22.7%) was accompanied by relative decline in use of methadone (19.3% to 12.7%). Patients who received buprenorphine were younger and more likely to be rural, White, and married. Patients who received methadone were older, urban, unmarried, from racial and ethnic minorities, and more likely to see substance abuse specialists. While use of naltrexone increased (2.8% to 8.6%), most (87%) patients who received naltrexone also had an alcohol use disorder. Controlling for patient factors, there was a substantial increase in the use of buprenorphine, a substantial decrease in the use of methadone, and no change
Karen S. Ho
Full Text Available Copy number variants (CNVs detected by chromosomal microarray analysis (CMA significantly contribute to understanding the etiology of autism spectrum disorder (ASD and other related conditions. In recognition of the value of CMA testing and its impact on medical management, CMA is in medical guidelines as a first-tier test in the evaluation of children with these disorders. As CMA becomes adopted into routine care for these patients, it becomes increasingly important to report these clinical findings. This study summarizes the results of over 4 years of CMA testing by a CLIA-certified clinical testing laboratory. Using a 2.8 million probe microarray optimized for the detection of CNVs associated with neurodevelopmental disorders, we report an overall CNV detection rate of 28.1% in 10,351 consecutive patients, which rises to nearly 33% in cases without ASD, with only developmental delay/intellectual disability (DD/ID and/or multiple congenital anomalies (MCA. The overall detection rate for individuals with ASD is also significant at 24.4%. The detection rate and pathogenic yield of CMA vary significantly with the indications for testing, age, and gender, as well as the specialty of the ordering doctor. We note discrete differences in the most common recurrent CNVs found in individuals with or without a diagnosis of ASD.
Bakare, Muideen O; Bello-Mojeed, Mashudat A; Munir, Kerim M; Ogun, Oluwayemi C; Eaton, Julian
Late diagnosis and interventions characterize childhood neurodevelopmental disorders in Sub-Saharan Africa. This has negatively impacted on the prognosis of the children with neurodevelopmental disorders. This study examined the prevalence and pattern of neurodevelopmental delays among children under the age of 3 years attending immunization clinics in Lagos State, Nigeria and also affords opportunity of early follow-up and interventions, which had been documented to improve prognosis. The study involved two stage assessments; which consisted of first phase screening of the children for neurodevelopmental delays in immunization clinics at primary healthcare centers Lagos State, Nigeria and second phase which consists of definitive clinical evaluation and follow-up interventions for children screened positive for neurodevelopmental delays. Twenty seven (0.9%) of a total of 3,011 children under the age of 3 years were screened positive for neurodevelopmental delays and subsequently undergoing clinical evaluation and follow-up interventions. Preliminary working diagnoses among these children include cerebral palsy, autism spectrum disorder trait, nutritional deficiency, Down syndrome and Non-specific neurodevelopmental delay with co-morbid seizure disorder accounting for 33.3%, 14.8%, 18.5%, 7.4% and 25.9% respectively. This is a preliminary report that would be followed up with information on medium and long term intervention phase.
Kerekes, Nóra; Lundström, Sebastian; Chang, Zheng; Tajnia, Armin; Jern, Patrick; Lichtenstein, Paul; Nilsson, Thomas; Anckarsäter, Henrik
Background. Previous research has supported gender-specific aetiological factors in oppositional defiant disorder (ODD) and conduct disorder (CD). The aims of this study were to identify gender-specific associations between the behavioural problems-ODD/CD-like problems-and the neurodevelopmental disorders-attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD)-and to investigate underlying genetic effects. Methods. 17,220 twins aged 9 or 12 were screened using the Autism-Tics, AD/HD and other Comorbidities inventory. The main covariates of ODD- and CD-like problems were investigated, and the relative importance of unique versus shared hereditary and environmental effects was estimated using twin model fitting. Results. Social interaction problems (one of the ASD subdomains) was the strongest neurodevelopmental covariate of the behavioural problems in both genders, while ADHD-related hyperactivity/impulsiveness in boys and inattention in girls stood out as important covariates of CD-like problems. Genetic effects accounted for 50%-62% of the variance in behavioural problems, except in CD-like problems in girls (26%). Genetic and environmental effects linked to ADHD and ASD also influenced ODD-like problems in both genders and, to a lesser extent, CD-like problems in boys, but not in girls. Conclusions. The gender-specific patterns should be considered in the assessment and treatment, especially of CD.
Full Text Available Recent studies of the hippocampus have suggested that a network of genes is associated with the regulation of the GAD₆₇ (GAD1 expression and may play a role in γ-amino butyric acid (GABA dysfunction in schizophrenia (SZ and bipolar disorder (BD. To obtain a more detailed understanding of how GAD₆₇ regulation may result in GABAergic dysfunction, we have developed an in vitro model in which GABA cells are differentiated from the hippocampal precursor cell line, HiB5. Growth factors, such as PDGF, and BDNF, regulate the GABA phenotype by inducing the expression of GAD₆₇ and stimulating the growth of cellular processes, many with growth cones that form appositions with the cell bodies and processes of other GAD₆₇-positive cells. These changes are associated with increased expression of acetylated tubulin, microtubule-associated protein 2 (MAP2 and the post-synaptic density protein 95 (PSD95. The addition of BDNF, together with PDGF, increases the levels of mRNA and protein for GAD₆₇, as well as the high affinity GABA uptake protein, GAT1. These changes are associated with increased concentrations of GABA in the cytoplasm of "differentiated" HiB5 neurons. In the presence of Ca²⁺ and K⁺, newly synthesized GABA is released extracellularly. When the HiB5 cells appear to be fully differentiated, they also express GAD₆₅, parvalbumin and calbindin, and GluR subtypes as well as HDAC1, DAXX, PAX5, Runx2, associated with GAD₆₇ regulation. Overall, these results suggest that the HiB5 cells can differentiate into functionally mature GABA neurons in the presence of gene products that are associated with GAD₆₇ regulation in the adult hippocampus.
Pagel, Tobias; Baldessarini, Ross J; Franklin, Jeremy; Baethge, Christopher
Information on basic demographic and clinical characteristics of schizoaffective disorder is sparse and subject to sampling bias and low diagnostic reliability. In the present study we aimed to: (i) estimate the demographic and clinical descriptors in schizoaffective disorder patients and (ii) compare the findings with those with schizophrenia and bipolar disorder. To minimize sampling bias and low reliability, we systematically reviewed studies that simultaneously compared schizoaffective, schizophrenia, and bipolar disorder patients. We estimated demographic, clinical, and psychometric characteristics based on weighted pooling, and compared disorders by meta-analysis. We also estimated whether schizoaffective disorder is closer to schizophrenia or to bipolar disorder. We identified 50 studies that included 18312 patients. Most characteristics of the 2684 schizoaffective disorder patients fell between those of 4814 diagnosed with bipolar disorder and 10814 with schizophrenia. However, the schizoaffective group had the highest proportion of women (52%), had the youngest age at illness onset (23.3 ± 3.8 years), and had the highest standardized ratings of psychosis and depression. Differences in pooled parameters between schizoaffective versus schizophrenia and versus bipolar disorder subjects were similar. Values for patients with schizoaffective disorders mostly were intermediate between schizophrenia and bipolar disorder. However, the majority of studies showed schizoaffective patients to be more like schizophrenia than bipolar disorder patients in seven out of nine demographic and clinical categories as well as in five out of eight psychometric measures. These results remained similar when we restricted the analyses to studies with psychotic bipolar disorder patients only or to studies using the Diagnostic and Statistical Manual of Mental Disorders (DSM)-IIIR and DSM-IV only. The present study provided estimates of important characteristics of schizoaffective
Pearl, Phillip L; Sable, Craig; Evans, Sarah; Knight, Joseph; Cunningham, Parker; Lotrecchiano, Gaetano R; Gropman, Andrea; Stuart, Sheela; Glass, Penny; Conway, Anne; Ramadan, Issam; Paiva, Tania; Batshaw, Mark L; Packer, Roger J
A telemedicine program was developed between the Children's National Medical Center (CNMC) in Washington, DC, and the Sheikh Khalifa Bin Zayed Foundation in the United Arab Emirates (UAE). A needs assessment and a curriculum of on-site training conferences were devised preparatory to an ongoing telemedicine consultation program for children with neurodevelopmental disabilities in the underserved eastern region of the UAE. Weekly telemedicine consultations are provided by a multidisciplinary faculty. Patients are presented in the UAE with their therapists and families. Real-time (video over Internet protocol; average connection, 768 kilobits/s) telemedicine conferences are held weekly following previews of medical records. A full consultation report follows each telemedicine session. Between February 29, 2012 and June 26, 2013, 48 weekly 1-h live interactive telemedicine consultations were conducted on 48 patients (28 males, 20 females; age range, 8 months-22 years; median age, 5.4 years). The primary diagnoses were cerebral palsy, neurogenetic disorders, autism, neuromuscular disorders, congenital anomalies, global developmental delay, systemic disease, and epilepsy. Common comorbidities were cognitive impairment, communication disorders, and behavioral disorders. Specific recommendations included imaging and DNA studies, antiseizure management, spasticity management including botulinum toxin protocols, and specific therapy modalities including taping techniques, customized body vests, and speech/language and behavioral therapy. Improved outcomes reported were in clinician satisfaction, achievement of therapy goals for patients, and requests for ongoing sessions. Weekly telemedicine sessions coupled with triannual training conferences were successfully implemented in a clinical program dedicated to patients with neurodevelopmental disabilities by the Center for Neuroscience at CNMC and the UAE government. International consultations in neurodevelopmental
Mariën, Peter; Vidts, Annelies; Van Hecke, Wim; De Surgeloose, Didier; De Belder, Frank; Parizel, Paul M; Engelborghs, Sebastiaan; De Deyn, Peter P; Verhoeven, Jo
This paper reports the longitudinal clinical, neurocognitive, and neuroradiological findings in an adolescent patient with nonprogressive motor and cognitive disturbances consistent with a diagnosis of developmental coordination disorder (DCD). In addition to prototypical DCD, the development of mastication was severely impaired, while no evidence of swallowing apraxia, dysphagia, sensorimotor disturbances, abnormal tone, or impaired general cognition was found. He suffered from bronchopulmonary dysplasia and was ventilated as a newborn for 1.5 months. At the age of 3 months, a ventriculoperitoneal shunt was surgically installed because of obstructive hydrocephalus secondary to perinatal intraventricular bleeding. At the age of 5 years, the patient's attempts to masticate were characterized by rough, effortful, and laborious biting movements confined to the vertical plane. Solid food particles had a tendency to get struck in his mouth and there was constant spillage. As a substitute for mastication, he moved the unground food with his fingers in a lateral direction to the mandibular and maxillary vestibule to externally manipulate and squeeze the food between cheek and teeth with the palm of his hand. Once the food was sufficiently soft, the bolus was correctly transported by the tongue in posterior direction and normal deglutition took place. Repeat magnetic resonance imaging (MRI) during follow-up disclosed mild structural abnormalities as the sequelae of the perinatal intraventricular bleeding, but this could not explain impaired mastication behavior. Quantified Tc-99m-ethylcysteinate dimer single-photon emission computed tomography (Tc-99m-ECD SPECT), however, revealed decreased perfusion in the left cerebellar hemisphere, as well as in both inferior lateral frontal regions, both motor cortices, and the right anterior and lateral temporal areas. Anatomoclinical findings in this patient with DCD not only indicate that the functional integrity of the
Full Text Available Abstract Background A previous study showed that a high percentage of children diagnosed with Hyperkinetic Disorder (HKD displayed a consistent pattern of motor function problems. The purpose of this study was to investigate the effect of methylphenidate (MPH on such motor performance in children with HKD Methods 25 drug-naïve boys, aged 8–12 yr with a HKD-F90.0 diagnosis, were randomly assigned into two groups within a double blind cross-over design, and tested with a motor assessment instrument, during MPH and placebo conditions. Results The percentage of MFNU scores in the sample indicating 'severe motor problems' ranged from 44–84%, typically over 60%. Highly significant improvements in motor performance were observed with MPH compared to baseline ratings on all the 17 subtests of the MFNU 1–2 hr after administration of MPH. There were no significant placebo effects. The motor improvement was consistent with improvement of clinical symptoms. Conclusion The study confirmed our prior clinical observations showing that children with ADHD typically demonstrate marked improvements of motor functions after a single dose of 10 mg MPH. The most pronounced positive MPH response was seen in subtests measuring either neuromotor inhibition, or heightened muscular tone in the gross movement muscles involved in maintaining the alignment and balance of the body. Introduction of MPH generally led to improved balance and a generally more coordinated and controlled body movement.
Gavriel-Fried, Belle; Peled, Einat; Ajzenstadt, Mimi
Women with a gambling problem bear a negative social stigma. Based on the theory of symbolic interactionism, this study examined the construction of social identities by 17 Israeli women diagnosed with a gambling disorder. Interpretive interactionist analysis revealed how they construct their identity through correspondence with patterns of behavior that are perceived as normative, and identified 3 major themes: "I'm not actually a gambler" (the presentation of a multidimensional identity comprising other identities besides that of a gambler); "Staying normative during gambling"; and "I have changed" (reformed gamblers' presentation of themselves as having changed for the better). The findings underscore the complex dialogue behind the identity construction put forward by women with a gambling problem, their yearning to be perceived by society as normative women and to fit in despite their stigmatized behavior, and the tension they feel in society's relationship toward them. The findings also suggest that practitioners who work with women gamblers may want to pay attention to the power relations shaping identity construction in an interview setting, and look more closely at the women's awareness of the stigma they bear and the complex processes that make up their multidimensional identity. (c) 2015 APA, all rights reserved).
Full Text Available Background. Previous research has supported gender-specific aetiological factors in oppositional defiant disorder (ODD and conduct disorder (CD. The aims of this study were to identify gender-specific associations between the behavioural problems–ODD/CD-like problems–and the neurodevelopmental disorders–attention deficit hyperactivity disorder (ADHD, autism spectrum disorder (ASD–and to investigate underlying genetic effects.Methods. 17,220 twins aged 9 or 12 were screened using the Autism–Tics, AD/HD and other Comorbidities inventory. The main covariates of ODD- and CD-like problems were investigated, and the relative importance of unique versus shared hereditary and environmental effects was estimated using twin model fitting.Results. Social interaction problems (one of the ASD subdomains was the strongest neurodevelopmental covariate of the behavioural problems in both genders, while ADHD-related hyperactivity/impulsiveness in boys and inattention in girls stood out as important covariates of CD-like problems. Genetic effects accounted for 50%–62% of the variance in behavioural problems, except in CD-like problems in girls (26%. Genetic and environmental effects linked to ADHD and ASD also influenced ODD-like problems in both genders and, to a lesser extent, CD-like problems in boys, but not in girls.Conclusions. The gender-specific patterns should be considered in the assessment and treatment, especially of CD.
Tiskaoglu, Nesime Setge; Yazıcı, Alper; Karlıdere, Tunay; Sari, Esin; Oguz, Elif Yilmaz; Musaoglu, Musa; Aslan, Seyda; Samet Ermiş, Sıtkı
Psychiatric conditions and not just the treatments themselves might be involved in the pathophysiology of dry eye disease (DED). The aim of our study was to evaluate the association between depression and DED using objective and subjective tests in patients with newly diagnosed depressive disorder who were not using any medication which may help us to determine the sole effect of depression on dry eye. Thirty-six patients from the psychiatry clinic with a new diagnosis of depressive disorder and 32 controls were included in the study. All met the Diagnostic and Statistical Manual IV criteria for depression. Beck Depression Inventory (BDI) was used to measure depression severity and the State-Trait Anxiety Inventory (Stai1, Stai2) for concomitant anxiety symptoms. The Ocular Surface Disease Index (OSDI) and Visual Functioning Questionnaires (VFQ25) were completed and used to confirm diagnosis of DED in conjunction with the tear break up time (TBUT), ocular surface vital dye staining, and Schirmer's test. The comparison of depressive and control groups revealed significantly lower Schirmer (20.3 ± 9.9 vs. 25.7 ± 9.3 mm) and TBUT (7.8 ± 5.7 vs. 12.5 ± 7.8 s) scores with a consistently higher Oxford score (1.8 ± 3.2 vs. 0.2 ± 0.4) in the depressive group. Although the parameters were affected in the depressive group, this did not influence OSDI (86.1 ± 13.6 vs. 86.6 ± 13.3) and VFQ25 (30.8 ± 21.6 vs. 38.5 ± 29.1) scores. In both groups, the three psychological test scores (Stai1-2 and BDI) were correlated to each other but none of these tests were correlated to OSDI, VRQL, Schirmer, TBUT, and Oxford staining scores. Our study shows a definite association between depression and DED. We feel that it is important that psychiatrists take this into account especially while prescribing antidepressants which may aggravate dry eye signs.
Lesch, Klaus-Peter; Araragi, Naozumi; Waider, Jonas; van den Hove, Daniel; Gutknecht, Lise
Aggression, which comprises multi-faceted traits ranging from negative emotionality to antisocial behaviour, is influenced by an interaction of biological, psychological and social variables. Failure in social adjustment, aggressiveness and violence represent the most detrimental long-term outcome of neurodevelopmental disorders. With the exception of brain-specific tryptophan hydroxylase-2 (Tph2), which generates serotonin (5-HT) in raphe neurons, the contribution of gene variation to aggression-related behaviour in genetically modified mouse models has been previously appraised (Lesch 2005 Novartis Found Symp. 268, 111-140; Lesch & Merschdorf 2000 Behav. Sci. Law 18, 581-604). Genetic inactivation of Tph2 function in mice led to the identification of phenotypic changes, ranging from growth retardation and late-onset obesity, to enhanced conditioned fear response, increased aggression and depression-like behaviour. This spectrum of consequences, which are amplified by stress-related epigenetic interactions, are attributable to deficient brain 5-HT synthesis during development and adulthood. Human data relating altered TPH2 function to personality traits of negative emotionality and neurodevelopmental disorders characterized by deficits in cognitive control and emotion regulation are based on genetic association and are therefore not as robust as the experimental mouse results. Mouse models in conjunction with approaches focusing on TPH2 variants in humans provide unexpected views of 5-HT's role in brain development and in disorders related to negative emotionality, aggression and antisocial behaviour.
Worley, Julie A.; Matson, Johnny L.
In addition to the triad of impairments experienced by children and adolescents diagnosed with Autism Spectrum Disorders (ASD), they often present with symptoms of psychiatric disorders. To date, very few studies have examined gender differences in regards to psychiatric symptoms in children and adolescents diagnosed with an ASD. Thus, the current…
Holland, Lauren A; Brown, Tiffany A; Keel, Pamela K
The current study sought to compare different features of unhealthy exercise on associations with disordered eating and their ability to identify individuals with eating disorders. A secondary aim of the study was to compare prevalence and overlap of different aspects of unhealthy exercise and potential differences in their gender distribution. Cross-sectional epidemiological study. A community-based sample of men (n=592) and women (n=1468) completed surveys of health and eating patterns, including questions regarding exercise habits and eating disorder symptoms. Compulsive and compensatory features of exercise were the best predictors of disordered eating and eating disorder diagnoses compared to exercise that was excessive in quantity. Further, compulsive and compensatory aspects of unhealthy exercise represented overlapping, yet distinct qualities in both men and women. Including the compulsive quality among the defining features of unhealthy exercise may improve identification of eating disorders, particularly in men. Results suggest that the compensatory aspect of unhealthy exercise is not adequately captured by the compulsive aspect of unhealthy exercise. Thus, interventions that target unhealthy exercise behaviors among high-risk individuals, such as athletes, may benefit from addressing both the compulsive and compensatory aspects of unhealthy exercise. Future prospective longitudinal studies will aid in determining the direction of the association between these features of unhealthy exercise and the onset of eating pathology.
Nguyen, Antoinette T; Armstrong, Edward A; Yager, Jerome Y
Neurodevelopmental reflex testing is commonly used in clinical practice to assess the maturation of the nervous system. Neurodevelopmental reflexes are also referred to as primitive reflexes. They are sensitive and consistent with later outcomes. Abnormal reflexes are described as an absence, persistence, reappearance, or latency of reflexes, which are predictive indices of infants that are at high risk for neurodevelopmental disorders. Animal models of neurodevelopmental disabilities, such as cerebral palsy, often display aberrant developmental reflexes, as would be observed in human infants. The techniques described assess a variety of neurodevelopmental reflexes in neonatal rats. Neurodevelopmental reflex testing offers the investigator a testing method that is not otherwise available in such young animals. The methodology presented here aims to assist investigators in examining developmental milestones in neonatal rats as a method of detecting early-onset brain injury and/or determining the effectiveness of therapeutic interventions. The methodology presented here aims to provide a general guideline for investigators.
Gillberg, Christopher; Lundström, Sebastian; Fernell, Elisabeth; Nilsson, Gill; Neville, Brian
There is a recently well-documented association between childhood epilepsy and earlysymptomaticsyndromeselicitingneurodevelopmentalclinicalexaminations (ESSENCE) including autism spectrum disorder, but the relationship between febrile seizures and ESSENCE is less clear. The Child and Adolescent Twin Study in Sweden (CATSS) is an ongoing population-based study targeting twins born in Sweden since July 1, 1992. Parents of 27,092 twins were interviewed using a validated DSM-IV-based interview for ESSENCE, in connection with the twins' ninth or twelfth birthday. Diagnoses of febrile seizures (n = 492) and epilepsy (n = 282) were based on data from the Swedish National Patient Register. Prevalence of ESSENCE in individuals with febrile seizures and epilepsy was compared with prevalence in the twin population without seizures. The association between febrile seizures and ESSENCE was considered before and after adjustment for epilepsy. Age of diagnosis of febrile seizures and epilepsy was considered as a possible correlate of ESSENCE in febrile seizures and epilepsy. The rate of ESSENCE in febrile seizures and epilepsy was significantly higher than in the total population without seizures (all P epilepsy, a significant association between febrile seizures and autism spectrum disorder, developmental coordination disorder, and intellectual disability remained. Earlier age of onset was associated with all ESSENCE except attention-deficit/hyperactivity disorder in epilepsy but not with ESSENCE in febrile seizures. In a nationally representative sample of twins, there was an increased rate of ESSENCE in childhood epilepsy and in febrile seizures. Febrile seizures alone could occur as a marker for a broader ESSENCE phenotype. Copyright © 2017 Elsevier Inc. All rights reserved.
Reijnders, Margot R F; Miller, Kerry A; Alvi, Mohsan; Goos, Jacqueline A C; Lees, Melissa M; de Burca, Anna; Henderson, Alex; Kraus, Alison; Mikat, Barbara; de Vries, Bert B A; Isidor, Bertrand; Kerr, Bronwyn; Marcelis, Carlo; Schluth-Bolard, Caroline; Deshpande, Charu; Ruivenkamp, Claudia A L; Wieczorek, Dagmar; Baralle, Diana; Blair, Edward M; Engels, Hartmut; Lüdecke, Hermann-Josef; Eason, Jacqueline; Santen, Gijs W E; Clayton-Smith, Jill; Chandler, Kate; Tatton-Brown, Katrina; Payne, Katelyn; Helbig, Katherine; Radtke, Kelly; Nugent, Kimberly M; Cremer, Kirsten; Strom, Tim M; Bird, Lynne M; Sinnema, Margje; Bitner-Glindzicz, Maria; van Dooren, Marieke F; Alders, Marielle; Koopmans, Marije; Brick, Lauren; Kozenko, Mariya; Harline, Megan L; Klaassens, Merel; Steinraths, Michelle; Cooper, Nicola S; Edery, Patrick; Yap, Patrick; Terhal, Paulien A; van der Spek, Peter J; Lakeman, Phillis; Taylor, Rachel L; Littlejohn, Rebecca O; Pfundt, Rolph; Mercimek-Andrews, Saadet; Stegmann, Alexander P A; Kant, Sarina G; McLean, Scott; Joss, Shelagh; Swagemakers, Sigrid M A; Douzgou, Sofia; Wall, Steven A; Küry, Sébastien; Calpena, Eduardo; Koelling, Nils; McGowan, Simon J; Twigg, Stephen R F; Mathijssen, Irene M J; Nellaker, Christoffer; Brunner, Han G; Wilkie, Andrew O M
Next-generation sequencing is a powerful tool for the discovery of genes related to neurodevelopmental disorders (NDDs). Here, we report the identification of a distinct syndrome due to de novo or inherited heterozygous mutations in Tousled-like kinase 2 (TLK2) in 38 unrelated individuals and two affected mothers, using whole-exome and whole-genome sequencing technologies, matchmaker databases, and international collaborations. Affected individuals had a consistent phenotype, characterized by mild-borderline neurodevelopmental delay (86%), behavioral disorders (68%), severe gastro-intestinal problems (63%), and facial dysmorphism including blepharophimosis (82%), telecanthus (74%), prominent nasal bridge (68%), broad nasal tip (66%), thin vermilion of the upper lip (62%), and upslanting palpebral fissures (55%). Analysis of cell lines from three affected individuals showed that mutations act through a loss-of-function mechanism in at least two case subjects. Genotype-phenotype analysis and comparison of computationally modeled faces showed that phenotypes of these and other individuals with loss-of-function variants significantly overlapped with phenotypes of individuals with other variant types (missense and C-terminal truncating). This suggests that haploinsufficiency of TLK2 is the most likely underlying disease mechanism, leading to a consistent neurodevelopmental phenotype. This work illustrates the power of international data sharing, by the identification of 40 individuals from 26 different centers in 7 different countries, allowing the identification, clinical delineation, and genotype-phenotype evaluation of a distinct NDD caused by mutations in TLK2. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.
Bay, Bjørn; Mortensen, Erik Lykke; Kesmodel, Ulrik Schiøler
To systematically review the existing literature on neurodevelopmental outcomes in children born after medically assisted reproduction compared with those of children born after spontaneous conception. Systematic review. Not applicable. Children born after medically assisted reproduction vs. reference groups of spontaneously conceived children. Data were reviewed from worldwide published articles, without restrictions as to publication year or language. A total of 80 studies included between 31 and 2,446,044 children. Child neurodevelopmental outcomes categorized as cognitive, behavioral, emotional or psychomotor development, or diagnoses of mental disorders. For infants, studies on psychomotor development showed no deficits, but few investigated cognitive or behavioral development. Studies on toddlers generally reported normal cognitive, behavioral, socio-emotional, and psychomotor development. For children in middle childhood, development seems comparable in children born after assisted reproduction and controls, although fewer studies have been conducted with follow-up to this age. Very few studies have assessed neurodevelopmental outcomes among teens, and the results are inconclusive. Studies investigating the risk of diagnoses of mental disorders are generally large, with long follow-up, but the results are inconsistent. It may tentatively be concluded that the neurodevelopment of children born after fertility treatment is overall comparable to that in children born after spontaneous conception. Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
Sekiguchi, Mari; Katayama, Syouichi; Hatano, Naoya; Shigeri, Yasushi; Sueyoshi, Noriyuki; Kameshita, Isamu
Cyclin-dependent kinase-like 5 (CDKL5) is a Ser/Thr protein kinase predominantly expressed in brain and mutations of its gene are known to be associated with neurodevelopmental disorders such as X-linked West syndrome and Rett syndrome. However, the physiological substrates of CDKL5 that are directly linked to these neurodevelopmental disorders are currently unknown. In this study, we explored endogenous substrates for CDKL5 in mouse brain extracts fractionated by a liquid-phase isoelectric focusing. In conjunction with CDKL5 phosphorylation assay, this approach detected a protein band with an apparent molecular mass of 120kDa that is remarkably phosphorylated by CDKL5. This 120-kDa protein was identified as amphiphysin 1 (Amph1) by LC-MS/MS analysis, and the site of phosphorylation by CDKL5 was determined to be Ser-293. The phosphorylation mimic mutants, Amph1(S293E) and Amph1(S293D), showed significantly reduced affinity for endophilin, a protein involved in synaptic vesicle endocytosis. Introduction of point mutations in the catalytic domain of CDKL5, which are disease-causing missense mutations found in Rett patients, resulted in the impairment of kinase activity toward Amph1. These results suggest that Amph1 is the cytoplasmic substrate for CDKL5 and that its phosphorylation may play crucial roles in the neuronal development. Copyright © 2013 Elsevier Inc. All rights reserved.
... NICHD Research Information Find a Study More Information Pharmacology Condition Information NICHD Research Information Find a Study ... computed tomography (CT or CAT) scan or a magnetic resonance imaging (MRI) scan may be useful in diagnosing an ...
Olfson, Mark; Crystal, Stephen; Gerhard, Tobias; Huang, Cecilia; Walkup, James T.; Scahill, Lawrence; Walkup, John T.
Objective: This study examined the prevalence and demographic and clinical correlates of children diagnosed with Tourette disorder, chronic motor or vocal tic disorder, and other tic disorders in public and private insurance plans over the course of a 1-year period. Method: Claims were reviewed of Medicaid (n = 10,247,827) and privately (n =…
Kroeger, Rhiannon A
This study used data from the National Longitudinal Study of Adolescent to Adult Health (Add Health) to examine whether young adult parents diagnosed with Attention Deficit Hyperactivity Disorder experience less parental happiness and/or more parental strain than their counterparts not diagnosed with Attention Deficit Hyperactivity Disorder. Results from logistic regression models indicated that young adult parents ever diagnosed with Attention Deficit Hyperactivity Disorder have significantly greater odds of feeling overwhelmed as parents and significantly lower odds of feeling close to their children or happy in their role as parents compared to those never diagnosed with Attention Deficit Hyperactivity Disorder. Potential implications of these results for scholars as well as health professionals treating adult Attention Deficit Hyperactivity Disorder patients with children are discussed.
Nesvåg, Ragnar; Hartz, Ingeborg; Bramness, Jørgen G; Hjellvik, Vidar; Handal, Marte; Skurtveit, Svetlana
Antipsychotic drugs are used increasingly by children and adolescents and there is concern about off-label use. We aimed to study which substances, and for which mental disorder diagnoses, antipsychotic drugs were prescribed to 0-18-year-old boys and girls in Norway. Linked data from the national health registry for prescription drugs in 2010 and mental disorder diagnoses in 2008-2012 were used to study the prevalence of antipsychotic drug use, the type of antipsychotic drug substances used, mental disorder diagnoses in users and distribution of drugs per diagnostic category across gender. In total, 0.18% of Norwegian children and adolescents were prescribed antipsychotic drugs during 2010, of which there were more boys (0.23%) than girls (0.13%). Risperidone was the most frequently used substance among boys (57.4%) and girls (32.3%), followed by aripiprazole (19.4%) in boys and quetiapine (27.4%) in girls. The most common mental disorder diagnoses among male users were hyperkinetic (49.9%) and autism spectrum disorder (27.1%), while anxiety disorders (41.5%) and depressive illness (33.6%) were most common among female users. A schizophrenia-like psychosis diagnosis was given to 11.1% of the male and 18.2% of the female users. A hyperkinetic disorder was diagnosed among 56.9% and 52.4% of the male risperidone and aripiprazole users, respectively. Among female quetiapine users, 57.1% were diagnosed with anxiety disorders and 52.4% with depressive illness. These results demonstrate that children and adolescents who use antipsychotic drugs are predominantly diagnosed with non-psychotic mental disorders such as hyperkinetic disorder among boys and anxiety disorder or depressive illness among girls. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.
psychiatric disorder who live outside rather than inside the psychiatric ..... behaviours, signs and symptoms (Frances & Egger,. 1999). .... and a student at university. He was ..... This experience of being misinterpreted, of being perceived as a ...
Whitaker, Ashley M; Bell, Terece S; Houskamp, Beth M; O'Callaghan, Erin T
Intellectual giftedness is associated with strong strategic verbal memory while attention-deficit hyperactivity disorder (ADHD) is associated with strategic verbal memory deficits; however, no previous research has explored how this contradiction manifests in gifted populations with diagnoses of ADHD. The purpose of this study was to explore strategic verbal memory processes among intellectually gifted youth with and without ADHD to provide clarification regarding this specific aspect of neuropsychological functioning within this population. One hundred twenty-five youth completed neuropsychological evaluations including the Wechsler Intelligence Scale for Children-Fourth Edition and California Verbal Learning Test-Children's Version (CVLT-C). Results revealed significant differences between groups, with intellectually gifted youth with ADHD achieving lower T scores on CVLT-C Trials 1 through 5 compared with intellectually gifted youth without ADHD, and intellectually gifted youth with ADHD achieving higher T scores than youth of average intellectual abilities with ADHD. Additionally, repeated-measures analysis of variance revealed a main effect improvement among gifted youth with ADHD in short-delay recall when provided with organizational cues. Findings revealed new evidence about the role of twice exceptionality (specifically intellectual giftedness and ADHD) in strategic verbal memory and have important implications for parents, educators, psychologists and neuropsychologists, and other mental health professionals working with this population.
Dietz, C.; Swinkels, S.H.N.; Buitelaar, J.K.; Daalen, E. van; Engeland, H.M. van
AIM: To investigate cognitive development in preschool-age children diagnosed with Autistic Spectrum Disorder (ASD; N = 39) compared with that of children diagnosed with mental retardation (MR; N = 14) and normally developing children (NC; N = 36). METHOD: In a prospective longitudinal study,
Clark, Megan Louise Erin; Vinen, Zoe; Barbaro, Josephine; Dissanayake, Cheryl
Early diagnosis of Autism Spectrum Disorder is considered best practice, increasing access to early intervention. Yet, many children are diagnosed after 3-years. The current study investigated the school age outcomes of children who received an early and later diagnosis of ASD. The cognitive and behavioural outcomes of children diagnosed early (n…
Sansone, Randy A; Sansone, Lori A
Borderline personality disorder is a personality dysfunction that is characterized by disinhibition and impulsivity, which oftentimes manifest as self-regulation difficulties. Patients with this disorder have always been present in medical settings, but have been described as "difficult patients" rather than patients with borderline personality disorder. According to empirical findings, a number of behaviors and medical syndromes/diagnoses are suggestive of borderline personality disorder. Suggestive behaviors in the medical setting may include aggressive or disruptive behaviors, the intentional sabotage of medical care, and excessive healthcare utilization. Suggestive medical syndromes and diagnoses in the medical setting may include alcohol and substance misuse (including the abuse of prescription medications), multiple somatic complaints, chronic pain, obesity, sexual impulsivity, and hair pulling. While not all-inclusive or diagnostic, these behaviors and syndromes/diagnoses may invite further clinical evaluation of the patient for borderline personality disorder.
Buhmann, Cæcilie Böck; Andersen, Henrik Steen
The post-traumatic stress disorder (PTSD) diagnosis has undergone large developments. With the changes in DSM-5 and the proposed changes in ICD-11, the two systems move in different directions. Treatment for PTSD is developing, but the evidence for the effect is lacking behind. Trauma...
A. A. Kulesh
Full Text Available The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5 replaces the term «dementia» with «major neurocognitive disorder» (MNCD, which can reduce the stigmatization of patients and focus the attention of specialists on the preserved abilities of patients rather than deficit symptoms. In the next 35 years, the number of patients with MNCD in the world is predicted to almost triple. The article considers the concept, epidemiology, and etiological pattern of this syndrome. It characterizes in detail Alzheimer's disease (AD that is a cause of MNCD in 50–70% of cases. The current diagnostic criteria and clinical presentations of the disease are given. The presence of early and significant episodic memory disorders as both alone or concurrent with other cognitive and behavioral changes reflects the main clinical phenotype of AD. Magnetic resonance morphometry, amyloid positron emission tomography, and estimation of cerebrospinal fluid β-amyloid and tau protein levels find increasing applications in research and routine practice. Drug and non-drug treatments for MNCD are considered. The use of akatinol memantine to treat this disorder and the issues related to the comprehensive management of patients with severe cognitive impairment are analyzed.
Leach, P T; Crawley, J N
Mutant mouse models of neurodevelopmental disorders with intellectual disabilities provide useful translational research tools, especially in cases where robust cognitive deficits are reproducibly detected. However, motor, sensory and/or health issues consequent to the mutation may introduce artifacts that preclude testing in some standard cognitive assays. Touchscreen learning and memory tasks in small operant chambers have the potential to circumvent these confounds. Here we use touchscreen visual discrimination learning to evaluate performance in the maternally derived Ube3a mouse model of Angelman syndrome, the Ts65Dn trisomy mouse model of Down syndrome, and the Mecp2 Bird mouse model of Rett syndrome. Significant deficits in acquisition of a 2-choice visual discrimination task were detected in both Ube3a and Ts65Dn mice. Procedural control measures showed no genotype differences during pretraining phases or during acquisition. Mecp2 males did not survive long enough for touchscreen training, consistent with previous reports. Most Mecp2 females failed on pretraining criteria. Significant impairments on Morris water maze spatial learning were detected in both Ube3a and Ts65Dn, replicating previous findings. Abnormalities on rotarod in Ube3a, and on open field in Ts65Dn, replicating previous findings, may have contributed to the observed acquisition deficits and swim speed abnormalities during water maze performance. In contrast, these motor phenotypes do not appear to have affected touchscreen procedural abilities during pretraining or visual discrimination training. Our findings of slower touchscreen learning in 2 mouse models of neurodevelopmental disorders with intellectual disabilities indicate that operant tasks offer promising outcome measures for the preclinical discovery of effective pharmacological therapeutics. © 2017 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.
Korenev, Sergei; Morris, Andrew A M
Disorders of the mitochondrial respiratory chain are an exceedingly diverse group. The clinical features can affect any tissue or organ and occur at any age, with any mode of inheritance. The diagnosis of mitochondrial disorders requires knowledge of the clinical phenotypes and access to a wide range of laboratory techniques. A few syndromes are associated with a specific genetic defect and in these cases it is appropriate to proceed directly to an appropriate test of blood or urine. In most cases, however, the best strategy starts with biochemical and histochemical studies on a muscle biopsy. Appropriate molecular genetic studies can then be chosen, based on these results and the clinical picture. Unfortunately, there is currently limited availability of respiratory chain studies in India. Exome sequencing is undertaken increasingly often; without preceding mitochondrial studies, this can lead to misleading results.
Buhmann, Cæcilie Böck; Andersen, Henrik Steen
The post-traumatic stress disorder (PTSD) diagnosis has undergone large developments. With the changes in DSM-5 and the proposed changes in ICD-11, the two systems move in different directions. Treatment for PTSD is developing, but the evidence for the effect is lacking behind. Trauma-focused cog......-focused cognitive behavioural therapy and eye movement desensitization and reprocessing remain first choice. Pharmacotherapy is secondary. There is evidence for the effect of paroxetine, venlafaxine and fluoxetine and less so for sertraline....
Coolidge, Frederick L; Estey, Alisa J; Segal, Daniel L; Marle, Peter D
Relationships among alexithymia, personality disorders, and higher-order psychopathological and interpersonal dimensions were examined in 199 college students and a close relative of each. Alexithymia, the difficulty to express and identify emotions, was measured by the Observer Alexithymia Scale (OAS; [Haviland, M. G., Warren, W. L., & Riggs, M. L. (2000). An observer scale to measure alexithymia. Psychosomatics, 41, 385-392]), which was completed by each student's relative. Each student completed three self-report measures: the Coolidge Axis II Inventory (CATI; [Coolidge, F. L. (2000). Coolidge Axis II Inventory: Manual. Colorado Springs, CO: Author.), the Five Dimensional Personality Test (5DPT; [van Kampen, D. (2009). Personality and psychopathology: A theory-based revision of Eysenck's PEN model. Clinical Practice and Epidemiology in Mental Health, 5, 9-21]), and the Horney-Coolidge Tridimensional Inventory (HCTI; [Coolidge, F. L. (1998). Horney-Coolidge Tridimensional Inventory: Manual. Colorado Springs, CO: Author]). Results indicated that higher levels of alexithymia are associated with personality disorders and their traits, such as schizoid, avoidant, and paranoid. With regard to the issue of the similarity and difference between alexithymia and schizoid personality disorder, there was sufficient evidence across all of the measures to suggest that they are not synonymous entities. Finally, alexithymic traits were associated with concurrent depressive traits even in a non-clinical sample. Copyright © 2013 Elsevier Inc. All rights reserved.
Mouridsen, S.E.; Rich, B.; Isager, T.
The objective of this study was to compare the prevalence and types of psychiatric disorders in a clinical sample of 118 individuals diagnosed as children with infantile autism (IA) with psychiatric disorders in 336 matched controls from the general population using data from the nationwide Danish...
Hiller, Rachel M.; Young, Robyn L.; Weber, Nathan
In the absence of intellectual impairment, girls are diagnosed with autism spectrum disorder significantly less and later than boys. This study explored potential reasons for why autism spectrum disorder may be more difficult to identify in girls, based on carer concerns during the pre-diagnosis period. Carers of 92 boys and 60 girls diagnosed…
Rogers, Claire L.; Goddard, Lorna; Hill, Elisabeth L.; Henry, Lucy A.; Crane, Laura
To date, research exploring experiences of diagnosing autism spectrum disorder has largely focused on parental perspectives. In order to obtain a more complete account of the autism spectrum disorder diagnostic process, it is essential that the views and experiences of professionals are heard. In this study, 116 multidisciplinary professionals…
Nesvåg, Ragnar; Jönsson, Erik G; Bakken, Inger Johanne; Knudsen, Gun Peggy; Bjella, Thomas D; Reichborn-Kjennerud, Ted; Melle, Ingrid; Andreassen, Ole A
Utilization of diagnostic information from national patient registries rests on the quality of the registered diagnoses. We aimed to investigate the agreement and consistency of diagnoses of psychotic and bipolar disorders in the Norwegian Patient Registry (NPR) compared to structured interview-based diagnoses given as part of a clinical research project. Diagnostic data from NPR were obtained for the period 01.01.2008-31.12.2013 for all patients who had been included in the Thematically Organized Psychosis (TOP) study between 18.10.2002 and 01.09.2014 with a Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) diagnosis of schizophrenia (n = 537), delusional disorder (n = 48), schizoaffective disorder (n = 118) or bipolar disorder (n = 408). Diagnostic agreement between the primary DSM-IV diagnosis in TOP and the International Classification of Diseases, 10th revision (ICD-10) diagnoses in NPR was evaluated using Cohen's unweighted nominal kappa (κ). Diagnostic consistency was calculated as the proportion of all registered severe mental disorder diagnoses in NPR that were equivalent to the primary diagnosis given in the TOP study. The proportion of patients registered with the equivalent ICD-10 diagnosis as the primary DSM-IV diagnosis given in TOP was 84.2% for the schizophrenia group, 68.8% for the delusional disorder group, 76.3% for the schizoaffective disorder group, and 78.4% for the bipolar disorder group. Diagnostic agreement was good for schizophrenia (κ = 0.74) and bipolar disorder (κ = 0.72), fair for schizoaffective disorder (κ = 0.63), and poor for delusional disorder (κ = 0.39). Among patients with DSM-IV schizophrenia, 4.7% were diagnosed with ICD-10 bipolar disorder, and among patients with DSM-IV bipolar disorder, 2.5% were diagnosed with ICD-10 schizophrenia. Diagnostic consistency was 84.9% for schizophrenia, 59.1% for delusional disorder, 65.9% for schizoaffective disorder, and 91
Serrano Mercedes L.; Martins Cecilia E.; Pérez-Dueñas Belén; Gómez-López Lilian; Murgui Empar; Fons Carmen; García-Cazorla Ángels; Artuch Rafael M D; Jara Fernando; Arranz José Antonio; Häberle Johannes; Briones Paz; Campistol Jaume M D; Pineda Mercè; Vilaseca María Antònia Antonia
Inherited urea cycle disorders represent one of the most common groups of inborn errors of metabolism. Late onset urea cycle disorders caused by partial enzyme deficiencies may present with unexpected clinical phenotypes. We report 9 patients followed up in our hospital presenting late onset urea cycle disorders who initially manifested neuropsychiatric/neurodevelopmental symptoms (the most prevalent neuropsychiatric/neurodevelopmental diagnoses were mental retardation attention deficit hyper...
Full Text Available The authors review environmental and neurodevelopmental risk factors for schizophrenic disorders, with emphasis on minor physical anomalies, particularly craniofacial anomalies and dermatoglyphic variations. The high prevalence of these anomalies among schizophrenic subjects supports the neurodevelopmental theory of the etiology of schizophrenia, since they suggest either genetically or epigenetically controlled faulty embryonic development of structures of ectodermal origin like brain and skin. This may disturb neurodevelopment that in turn may cause these subjects to be at increased risk for the development of schizophrenia and related disorders. The precise confirmation of this theory, at least in some cases, will provide further understanding of these illnesses, allowing easy and inexpensive identification of subjects at risk and providing guidelines for the development of new pharmacological interventions for early treatment and even for primary prevention of the illness.
Aggarwal, Shilpa; Angus, Beth
The diagnosis of children with autism spectrum disorders (ASDs) is sometimes delayed until adolescence. This study tries to identify the symptoms in clients that initiated a referral to an autism team of an early intervention service providing psychiatric care for young people between the ages of 15 and 25 and who subsequently receive a new diagnosis of autism. Thirty-one ASD assessments were carried out during a period of 3 years in an early intervention service in Australia. An attempt to identify the common presenting symptoms and trends in the referrals for ASD assessment within the service was made. Most common presentation of adolescents getting referred for ASD assessment was with depressive symptoms followed by mixed anxiety and depression and primary psychotic symptoms. There was a significant gender difference, with a higher number of males getting referred for ASD assessment. ASDs can go undetected during childhood and these clients can sometimes present during adolescence to mental health services for a psychiatric comorbidity. Regular training opportunities for clinicians dealing with them could improve the chances of ASDs being picked up during their episode of care at an early intervention service, thus optimizing their management. © The Royal Australian and New Zealand College of Psychiatrists 2015.
van Santvoort, Floor; Hosman, Clemens M H; Janssens, Jan M A M; van Doesum, Karin T M; Reupert, Andrea; van Loon, Linda M A
Children of mentally ill parents are at high risk of developing problems themselves. They are often identified and approached as a homogeneous group, despite diversity in parental diagnoses. Some studies demonstrate evidence for transgenerational equifinality (children of parents with various disorders are at risk of similar problems) and multifinality (children are at risk of a broad spectrum of problems). At the same time, other studies indicate transgenerational specificity (child problems are specifically related to the parent's diagnosis) and concordance (children are mainly at risk of the same disorder as their parent). Better insight into the similarities and differences between children of parents with various mental disorders is needed and may inform the development and evaluation of future preventive interventions for children and their families. Accordingly, we systematically compared 76 studies on diagnoses in children of parents with the most prevalent axis I disorders: unipolar depression, bipolar disorder, and anxiety disorders. Methodological characteristics of the studies were compared, and outcomes were analyzed for the presence of transgenerational equifinality, multifinality, specificity, and concordance. Also, the strengths of the relationships between child and parent diagnoses were investigated. This review showed that multifinality and equifinality appear to be more of a characteristic of children of unipolar and bipolar parents than of children of anxious parents, whose risk is mainly restricted to developing anxiety disorders. For all children, risk transmission is assumed to be partly specific since the studies indicate a strong tendency for children to develop the same disorder as their parent.
Full Text Available Background: Childhood mortality from infectious diseases has declined steadily in many low and middle-income (LAMIC countries, with increased recognition of non-communicable diseases such as neurodevelopmental disorders (NDD. There is lack of data on the burden of NDD in LAMIC. Current global burden of these disorders are largely extrapolated from high-income countries. The main objective of the study was therefore to estimate the burden of NDD in LAMIC using meta-analytic techniques. Methods: We systematically searched online databases including Medline/PubMed, PsychoInfo, and Embase for studies that reported prevalence or incidence of NDD. Pooled prevalence, heterogeneity and risk factors for prevalence were determined using meta-analytic techniques. Results: We identified 4,802 records, but only 51 studies met the eligibility criteria. Most studies were from Asia-Pacific (52.2% and most were on neurological disorders (63.1%. The median pooled prevalence per 1,000 for any NDD was 7.6 (95%CI 7.5-7.7, being 11.3 (11.7-12.0 for neurological disorders and 3.2 (95%CI 3.1-3.3 for mental conditions such as attention-deficit hyperactivity disorder (ADHD. The type of NDD was significantly associated with the greatest prevalence ratio in the multivariable model (PR=2.6(95%CI 0.6-11.6 (P>0.05. Incidence was only reported for epilepsy (mean of 447.7 (95%CI 415.3-481.9 per 100,000. Perinatal complications were the commonest risk factor for NDD. Conclusion: The burden of NDD in LAMIC is considerable. Epidemiological surveys on NDD should screen all types of NDD to provide reliable estimates.
Kronenberg, Linda M.; Verkerk-Tamminga, Roeliene; Goossens, Peter J. J.; van den Brink, Wim; van Achterberg, Theo
The process of personal recovery in people diagnosed with substance use disorder and comorbid attention deficit/hyperactivity disorder (ADHD) or autism spectrum disorder (ASD) was mapped. Four general themes representing four consecutive stages in the recovery process were identified in both client
Sanders, Avihay; Szymanski, Kate
This study examines the potential for posttraumatic growth (PTG) for siblings of persons diagnosed with a mental disorder. Using the posttraumatic growth Inventory we compared siblings (N = 33) with a comparison group of participants who did not experience trauma (N = 30). Our group of participants who had a sibling diagnosed with a mental disorder by a mental health professional (N = 33) reported higher PTG scores with mostly large effect sizes on most of the inventory subscales. Participants who took an active role in care giving experienced less PTG than participants who did not. Having a sibling diagnosed with a mental disorder presents an opportunity to experience PTG. Implications for the therapeutic milieus are discussed.
Dillenburger, Karola; Keenan, Mickey; Dogherty, Alvyn; Byrne, Tony; Gallagher, Stephen
The number of children diagnosed with an autistic spectrum disorder (ASD) is rising and is now thought to be as high as 1:100. While the debate about best treatment continues, the effects of having a child diagnosed with ASD on family life remain relatively unexplored. This article, by Karola Dillenburger of Queens University Belfast, Mickey Keenan of the University of Ulster, Alvin Doherty from the Health Service Executive Western Region, Tony Byrne of Parents’ Education as Autism Therapists...
Drosophila mutants of the autism candidate gene neurobeachin (rugose) exhibit neuro-developmental disorders, aberrant synaptic properties, altered locomotion, and impaired adult social behavior and activity patterns.
Wise, Alexandria; Tenezaca, Luis; Fernandez, Robert W; Schatoff, Emma; Flores, Julian; Ueda, Atsushi; Zhong, Xiaotian; Wu, Chun-Fang; Simon, Anne F; Venkatesh, Tadmiri
Autism spectrum disorder (ASD) is a neurodevelopmental disorder in humans characterized by complex behavioral deficits, including intellectual disability, impaired social interactions, and hyperactivity. ASD exhibits a strong genetic component with underlying multigene interactions. Candidate gene studies have shown that the neurobeachin (NBEA) gene is disrupted in human patients with idiopathic autism ( Castermans et al., 2003 ). The NBEA gene spans the common fragile site FRA 13A and encodes a signal scaffold protein ( Savelyeva et al., 2006 ). In mice, NBEA has been shown to be involved in the trafficking and function of a specific subset of synaptic vesicles. ( Medrihan et al., 2009 ; Savelyeva et al., 2006 ). Rugose (rg) is the Drosophila homolog of the mammalian and human NBEA. Our previous genetic and molecular analyses have shown that rg encodes an A kinase anchor protein (DAKAP 550), which interacts with components of the epidermal growth factor receptor or EGFR and Notch-mediated signaling pathways, facilitating cross talk between these and other pathways ( Shamloula et al., 2002 ). We now present functional data from studies on the larval neuromuscular junction that reveal abnormal synaptic architecture and physiology. In addition, adult rg loss-of-function mutants exhibit defective social interactions, impaired habituation, aberrant locomotion, and hyperactivity. These results demonstrate that Drosophila NBEA (rg) mutants exhibit phenotypic characteristics reminiscent of human ASD and thus could serve as a genetic model for studying ASDs.
Hempel, Annmarie; Pagnamenta, Alistair T; Blyth, Moira; Mansour, Sahar; McConnell, Vivienne; Kou, Ikuyo; Ikegawa, Shiro; Tsurusaki, Yoshinori; Matsumoto, Naomichi; Lo-Castro, Adriana; Plessis, Ghislaine; Albrecht, Beate; Battaglia, Agatino; Taylor, Jenny C; Howard, Malcolm F; Keays, David; Sohal, Aman Singh; Kühl, Susanne J; Kini, Usha; McNeill, Alisdair
Background SOX11 is a transcription factor proposed to play a role in brain development. The relevance of SOX11 to human developmental disorders was suggested by a recent report of SOX11 mutations in two patients with Coffin–Siris syndrome. Here we further investigate the role of SOX11 variants in neurodevelopmental disorders. Methods We used array based comparative genomic hybridisation and trio exome sequencing to identify children with intellectual disability who have deletions or de novo point mutations disrupting SOX11. The pathogenicity of the SOX11 mutations was assessed using an in vitro gene expression reporter system. Loss-of-function experiments were performed in xenopus by knockdown of Sox11 expression. Results We identified seven individuals with chromosome 2p25 deletions involving SOX11. Trio exome sequencing identified three de novo SOX11 variants, two missense (p.K50N; p.P120H) and one nonsense (p.C29*). The biological consequences of the missense mutations were assessed using an in vitro gene expression system. These individuals had microcephaly, developmental delay and shared dysmorphic features compatible with mild Coffin–Siris syndrome. To further investigate the function of SOX11, we knocked down the orthologous gene in xenopus. Morphants had significant reduction in head size compared with controls. This suggests that SOX11 loss of function can be associated with microcephaly. Conclusions We thus propose that SOX11 deletion or mutation can present with a Coffin–Siris phenotype. PMID:26543203
Carnahan, Ryan M; Letuchy, Elena M
Nursing home quality measures include the proportion of residents who receive antipsychotics. Residents with bipolar disorder are included even though antipsychotics are FDA-approved for this indication. We evaluated how including residents with bipolar disorder impacted the antipsychotic use quality measure for long-stay residents. We evaluated the agreement of minimum data set (MDS) bipolar disorder diagnoses with Medicare data, whether dementia was diagnosed before bipolar disorder, and how less-specific bipolar disorder diagnoses impacted findings. Cross-sectional study. Nursing homes in Iowa. 21,955 long-stay nursing home residents in the first quarter of 2014. We identified antipsychotic use and bipolar disorder using MDS data. We compared MDS bipolar disorder diagnoses with Chronic Conditions Warehouse (CCW) "ever" bipolar disorder indicators, and prior year claims. We compared CCW condition onset dates to identify bipolar disorder diagnosed after dementia. The mean (SD) proportion receiving antipsychotics was 19.6% (11.1%) with bipolar disorder and 18.3% (10.8%) without. The positive predictive value (PPV) of MDS bipolar disorder diagnoses was 80.2% versus CCW lifetime indicators, and 74.6% versus claims. PPV decreased by 27.1% when "bipolar disorder, unspecified" and "other bipolar disorders" diagnoses were excluded. Nearly three-quarters of residents with bipolar disorder had dementia. Over half of those with dementia had dementia first per CCW records. This proportion was lower among those with more specific bipolar disorder diagnoses or MDS bipolar disorder indicators. Bipolar disorder in nursing home residents is often first diagnosed after dementia using nonspecific diagnoses. This practice deserves further evaluation. Copyright © 2017 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.
Background The aim of this comparative study was to investigate the type and frequency of diagnoses preceding adult bipolar disorder (BD) and schizophrenia (SZ). Methods A follow-back study of all preceding diagnoses in all patients aged 21–34 years with a primary, first time diagnosis of BD (N = 784) or SZ (N = 1667) in 2008 to 2010. Data were taken from the Danish Psychiatric Central Research Register (DPCRR) including ICD-10 and ICD-8 diagnoses. Results The numbers of patients with any preceding diagnoses amounted to 69.3% in BD and 76.6% in SZ with affective disorders (excluding BD) being the most frequent preceding diagnosis (46.6 vs. 28.0%), followed by psychoses (PSY) other than SZ (14.2 vs. 41.5%, p adolescence. Overall patients with SZ had a minor but statistically significant earlier onset of any psychiatric disorder compared to BD (mean age: 23.3 vs. 22.5, p < .001). Regression analyses indicated that BD was associated with an increased risk of having experienced preceding affective disorders and ADHD, while SZ was associated with an increased risk of preceding substance use disorders, psychosis, anxiety disorders, and personality disorders. Conclusions Specific developmental trajectories of preceding disorders were delineated for BD and SZ with affective disorders being more specific for BD and both SUD and PSY more specific to SZ. There are different patterns of vulnerability in terms of preceding diagnosis in young adults with BD and SZ. PMID:24359146
Caroline A. Bonham
Full Text Available Background. Anxiety disorders are associated with considerable disability in the domains of (1 work, (2 social, and (3 family and home interactions. Psychiatric comorbidity is also known to be associated with disability. Methods. Data from the Cross-National Collaborative Panic Study was used to identify rates of comorbid diagnoses, anxiety and depression symptom ratings, and Sheehan disability scale ratings from a clinical sample of 1165 adults with panic disorder. Results. Comorbid diagnoses of agoraphobia, major depression, and social phobia were associated with disability across the three domains of work, social, and family and home interactions. The symptom of agoraphobic avoidance makes the largest contribution to disability but there is no single symptom cluster that entirely predicts impairment and disability. Limitations. The findings about the relative contributions that comorbid diagnoses make to disability only apply to a population with panic disorder. Conclusions. Although panic disorder is not generally considered to be among the serious and persistent mental illnesses, when it is comorbid with other diagnoses, it is associated with considerable impairment. In particular, the presence of agoraphobic avoidance should alert the clinician to the likelihood of important functional impairment. When measuring the functional impact of comorbid anxiety disorders, both the categorical and the dimensional approaches to diagnosis make valuable contributions.
Serrano, Mercedes; Martins, Cecilia; Pérez-Dueñas, Belén; Gómez-López, Lilian; Murgui, Empar; Fons, Carmen; García-Cazorla, Angels; Artuch, Rafael; Jara, Fernando; Arranz, José A; Häberle, Johannes; Briones, Paz; Campistol, Jaume; Pineda, Mercedes; Vilaseca, Maria A
Inherited urea cycle disorders represent one of the most common groups of inborn errors of metabolism. Late-onset urea cycle disorders caused by partial enzyme deficiencies may present with unexpected clinical phenotypes. We report 9 patients followed up in our hospital presenting late-onset urea cycle disorders who initially manifested neuropsychiatric/neurodevelopmental symptoms (the most prevalent neuropsychiatric/neurodevelopmental diagnoses were mental retardation, attention-deficit hyperactivity disorder [ADHD], language disorder, and delirium). Generally, these clinical pictures did not benefit from pharmacological treatment. Conversely, dietary treatment improved the symptoms. Regarding biochemical data, 2 patients showed normal ammonium but high glutamine levels. This study highlights the fact that neuropsychiatric/neurodevelopmental findings are common among the initial symptomatology of late-onset urea cycle disorders. The authors recommend that unexplained or nonresponsive neuropsychiatric/neurodevelopmental symptoms appearing during childhood or adolescence be followed by a study of ammonia and amino acid plasmatic levels to rule out a urea cycle disorder.
Rosello-Miranda, B; Berenguer-Forner, C; Miranda-Casas, A
Autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) present difficulties in adaptive functioning and learning, possibly associated with failures in executive functioning characteristic of both disorders. To analyze the impact of executive functioning in the adaptive behaviors of socialization and daily life and in learning behaviors in children with ASD and children with ADHD. The participants were 124 children matched in age and intellectual quotient: 37 children with typical development, 52 children with ASD and 35 children with ADHD. Parents reported on their children's adaptive behaviors, while teachers provided information on learning behaviors and executive functioning in daily life. There are significant differences between the groups with ASD and ADHD with the typical development group in all domains evaluated. In addition, the group with ASD had worse socialization skills while persistence in learning was more affected in children with ADHD. Finally, the metacognitive index of executive functioning predicted the socialization and persistence of children with ASD. On the other hand, the index of behavioral regulation and the educational level of the parents predicted the socialization skills in children with ADHD. The results highlight the need to include differentiated executive strategies in the intervention of children with ASD and children with ADHD.
Benedict, Susan L.
Diffusion-weighted imaging (DWI) has provided a way to measure early changes in cellular function in the central nervous system. It has permitted rapid, less invasive diagnosis and treatment of neurological disorders that were once thought to be untreatable. DWI has also created new avenues of research and alternative ways to measure study outcomes. Seven clinical cases illustrate how DWI enhances the ability of the pediatric neurologist to rapidly diagnose acute neurological disorders in infants and children. (orig.)
Vannucci, Anna; Nelson, Eric E.; Bongiorno, Diana M.; Pine, Daniel S.; Yanovski, Jack A.; Tanofsky-Kraff, Marian
Background Pediatric loss-of-control eating is a robust behavioral precursor to binge-type eating disorders. Elucidating precursors to loss-of-control eating and binge-type eating disorders may refine developmental risk models of eating disorders and inform interventions. Method We review evidence within constructs of the Negative Valence Systems (NVS)-domain, as specified by the Research Domain Criteria framework. Based on published studies, we propose an integrated NVS model of binge-type eating disorder risk. Results Data implicate altered corticolimbic functioning, neuroendocrine dysregulation, and self-reported negative affect as possible risk-factors. However, neuroimaging and physiological data in children and adolescents are sparse, and most prospective studies are limited to self-report measures. Conclusions We discuss a broad NVS framework for conceptualizing early risk for binge-type eating disorders. Future neural and behavioral research on the developmental trajectory of loss-of-control and binge-type eating disorders is required. PMID:26040923
Graystone, H J; Garner, M J; Baldwin, D S
Social phobia is a common, persistent and disabling anxiety disorder in which co-existing depressive symptoms are common. However the prevalence of social anxiety symptoms in patients with other mood and anxiety disorders is uncertain. In consecutive patients attending a tertiary referral mood and anxiety disorders service, depressive symptoms were assessed by the Montgomery-Asberg Depression Rating Scale (MADRS) and social anxiety symptoms by the Liebowitz Social Anxiety Scale (LSAS). The Clinical Global Impression of Severity (CGI-S) was completed following the appointment. 75 patients (48 women, 27 men; mean age 45.9 years) completed the study. 38 had a single diagnosis and 37 co-morbid diagnoses: 15 patients had bipolar disorder, 35 unipolar depressive disorder, 19 an anxiety disorder, and 6 other disorders. Independent samples t-tests and one-way between-subjects ANOVA revealed that the severity of social anxiety symptoms but not depressive symptoms was significantly greater in patients with co-morbid diagnoses (LSAS 73.7 vs 54.2, t(72)=2.44, pdepression or bipolar disorder (respectively; LSAS 78.8 vs 59.4 vs 50.0, F(2, 65)=3.13, p=.05; MADRS 22.2 vs 19.8 vs 17.5, F(2, 66)depression (R(2)=0.376, pdepressive and social anxiety symptoms across a range of diagnoses. Depressive and social anxiety symptoms were most severe but least well correlated among tertiary care outpatients with anxiety disorders, emphasising the need for comprehensive evaluation and treatment.
Ziv, Yair; Hadad, Bat Sheva; Khateeb, Yasmine
The social cognitive deficiencies of children diagnosed with autism spectrum disorders (ASDs) are well documented. However, the mechanisms underlying these deficiencies are unclear. Therefore, we examined the social information processing (SIP) patterns and social behaviors of 25 preschool children with ASDs in comparison to a matched group of 25…
Leaf, Justin B.; Leaf, Ronald; Alcalay, Aditt; Leaf, Jeremy A.; Ravid, Daniel; Dale, Stephanie; Kassardjian, Alyne; Tsuji, Kathleen; Taubman, Mitchell; McEachin, John; Oppenheim-Leaf, Misty
The systematic use of reinforcers is an essential component of behavioral intervention for individuals diagnosed with Autism Spectrum Disorder. Today, the use of rigorous formal preference assessments, including paired-preference assessments, are widely conducted to help determine which items to use as reinforcers during intervention. Although…
Schwitzer, Alan M.
This article presents research and evidence-based practices for identifying, understanding, diagnosing, conceptualizing, and providing a continuum of treatment for the most commonly experienced types of eating-related counseling concerns--namely, eating disorders not otherwise specified--among the population most likely to present these types of…
Ngazimbi, Evadne E.; Lambie, Glenn W.; Shillingford, M. Ann
Clients diagnosed with bipolar disorder often suffer from mood instability, and research suggests that these clients need both counseling services and pharmacotherapy. Narrative therapy is a social constructionist approach grounded on the premise that there is no single "truth"; individuals may create new meanings and retell their stories to…
Ben-Porath, Denise D.
Therapists often struggle with managing intersession contact with clients diagnosed with borderline personality disorder, particularly when dangerous and life-threatening symptoms are communicated (Gunderson, 1996). Difficulties have arisen, in part, because previous phone contacts with this population have failed to recognize the importance of…
Leaf, Justin B.; Leaf, Jeremy A.; Milne, Christine; Taubman, Mitchell; Oppenheim-Leaf, Misty; Torres, Norma; Townley-Cochran, Donna; Leaf, Ronald; McEachin, John; Yoder, Paul
In this study we evaluated a social skills group which employed a progressive applied behavior analysis model for individuals diagnosed with autism spectrum disorder. A randomized control trial was utilized; eight participants were randomly assigned to a treatment group and seven participants were randomly assigned to a waitlist control group. The…
Fernandes, Lucrecia Cabral; Gillberg, Carina I.; Cederlund, Mats; Hagberg, Bibbi; Gillberg, Christopher; Billstedt, Eva
The literature concerning sexuality in autism spectrum disorders (ASDs) is limited regarding inappropriate sexual behaviours and paraphilias and its relation to age, verbal ability, symptom severity, intellectual ability, or adaptive functioning. A cohort of 184 adolescents and young adults (ages 15-39 years) with ASD diagnosed in childhood,…
Carbonell, Claudia L.
This literature review of attention deficit hyperactivity disorder (ADHD) reviews the diagnosis and treatment options for children diagnosed with ADHD. It describes the complexity of ADHD, its symptoms, treatments, and implications on a child's social and academic development as well as strategies for assisting such children. Individual sections…
Jakobsen, Klaus Damgaard; Hansen, Thomas Folkmann; Dam, Henrik
investigated. A standardized schema for basic anamnesis and the Operational Criteria Checklist for Psychotic and Affective Illness (OPCRIT) were used. The sensitivity, specificity, positive and negative predictive values of clinical affective disorder ICD-10 diagnoses and the formal agreement between clinical...
This study used exploratory data analysis (EDA) to examine the use of a biofeedback intervention in the treatment of anxiety for college students diagnosed with an Autism Spectrum Disorder (ASD) (n = 10) and in a typical college population (n = 37). The use of EDA allowed for trends to emerge from the data and provided a foundation for future…
Lionel, Anath C; Tammimies, Kristiina; Vaags, Andrea K
Rare copy number variants (CNVs) disrupting ASTN2 or both ASTN2 and TRIM32 have been reported at 9q33.1 by genome-wide studies in a few individuals with neurodevelopmental disorders. The vertebrate-specific astrotactins, ASTN2 and its paralog ASTN1, have key roles in glial-guided neuronal migration...... during brain development. To determine the prevalence of astrotactin mutations and delineate their associated phenotypic spectrum, we screened ASTN2/TRIM32 and ASTN1 (1q25.2) for exonic CNVs in clinical microarray data from 89,985 individuals across 10 sites, including 64,114 neurodevelopmental disorder...... subjects. In this clinical dataset, we identified 46 deletions and 12 duplications affecting ASTN2. Deletions of ASTN1 were much rarer. Deletions near the 3' terminus of ASTN2, which would disrupt all transcript isoforms (a subset of these deletions also included TRIM32), were significantly enriched...
Whitehouse, Andrew J O; Cooper, Matthew N; Bebbington, Keely; Alvares, Gail; Lin, Ashleigh; Wray, John; Glasson, Emma J
The increasing prevalence of Autism Spectrum Disorders (ASD) may in part be due to a shift in the diagnostic threshold that has led to individuals with a less severe behavioral phenotype receiving a clinical diagnosis. This study examined whether there were changes over time in the qualitative and quantitative phenotype of individuals who received the diagnosis of Autistic Disorder. Data were from a prospective register of new diagnoses in Western Australia (n = 1252). From 2000 to 2006, we examined differences in both the percentage of newly diagnosed cases that met each criterion as well as severity ratings of the behaviors observed (not met, partially met, mild/moderate and extreme). Linear regression determined there was a statistically significant reduction from 2000 to 2006 in the percentage of new diagnoses meeting two of 12 criteria. There was also a reduction across the study period in the proportion of new cases rated as having extreme severity on six criteria. There was a reduction in the proportion of individuals with three or more criteria rated as extreme from 2000 (16.0%) to 2006 (1.6%), while percentage of new cases with no "extreme" rating on any criteria increased from 58.5% to 86.6% across the same period. This study provides the first clear evidence of a reduction over time in the behavioral severity of individuals diagnosed with Autistic Disorder during a period of stability in diagnostic criteria. A shift toward diagnosing individuals with less severe behavioral symptoms may have contributed to the increasing prevalence of Autistic Disorder diagnoses. Autism Res 2017, 10: 179-187. © 2016 International Society for Autism Research, Wiley Periodicals, Inc. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.
Bojović, Katarina; Stanković, Biljana; Kotur, Nikola; Krstić-Milošević, Dijana; Gašić, Vladimir; Pavlović, Sonja; Zukić, Branka; Ignjatović, Đurđica
Gastrointestinal disturbances, nutritional deficiencies, and food intolerances are frequently observed in children with neurodevelopmental disorders (NDD). To reveal possible association of celiac disease risk variants (HLA-DQ), lactose intolerance associated variant (LCT-13910C>T) as well as variant associated with vitamin D function (VDR FokI) with NDD, polymerase chain reaction-based methodology was used. Additionally, intestinal peptide permeability was estimated in NDD patients and healthy children by measuring the level of peptides in urine using high-performance liquid chromatography. Levels of opioid peptides, casomorphin 8, and gluten exorphin C were significantly elevated in urine samples of NDD patients (P = 0.004 and P = 0.005, respectively), but no association of genetic risk variants for celiac disease and lactose intolerance with NDD was found. Our results indicate that increased intestinal peptide permeability observed in analyzed NDD patients is not associated with genetic predictors of celiac disease or lactose intolerance. We have also found that FF genotype of VDR FokI and lower serum levels of vitamin D (25-OH) showed association with childhood autism (CHA), a subgroup of NDD. We hypothesize that vitamin D might be important for the development of CHA.
Yilmaz, Zeynep; Szatkiewicz, Jin P; Crowley, James J; Ancalade, NaEshia; Brandys, Marek K; van Elburg, Annemarie; de Kovel, Carolien G F; Adan, Roger A H; Hinney, Anke; Hebebrand, Johannes; Gratacos, Monica; Fernandez-Aranda, Fernando; Escaramis, Georgia; Gonzalez, Juan R; Estivill, Xavier; Zeggini, Eleftheria; Sullivan, Patrick F; Bulik, Cynthia M; Genetic Consortium for Anorexia Nervosa, Wellcome Trust Case Control Consortium 3
Anorexia nervosa (AN) is a serious and heritable psychiatric disorder. To date, studies of copy number variants (CNVs) have been limited and inconclusive because of small sample sizes. We conducted a case-only genome-wide CNV survey in 1983 female AN cases included in the Genetic Consortium for
Isles, Anthony R; Ingason, Andrés; Lowther, Chelsea
Duplications at 15q11.2-q13.3 overlapping the Prader-Willi/Angelman syndrome (PWS/AS) region have been associated with developmental delay (DD), autism spectrum disorder (ASD) and schizophrenia (SZ). Due to presence of imprinted genes within the region, the parental origin of these duplications m...
Durkin, Nora E; Swanson, Sonja A; Crow, Scott J; Mitchell, James; Peterson, Carol B; Crosby, Ross
Chewing and spitting (CS) out food is a relatively understudied eating disorder behavior. The aim of this study was to examine lifetime and current frequencies of CS across eating disorder diagnostic groups and to compare the severity of eating disorder symptomatology between participants who did and did not endorse CS. A total of 972 individuals presenting for outpatient eating disorder treatment between 1985 and 1996 completed a questionnaire that included items regarding current and lifetime eating disorder behaviors, including CS. Results indicated that both lifetime and current prevalence estimates of CS varied cross-diagnostically, with CS being more common among those with anorexia nervosa and bulimia nervosa compared to those with eating disorder not otherwise specified. CS was significantly associated with several eating disorder symptoms, including compensatory behaviors, meal restriction, and lower BMI. Those who reported CS were also younger in age compared to those who did not report CS. These findings indicate that CS is associated with more severe eating and weight pathology and is not equally prevalent across eating disorder diagnoses. These results also support the relatively high occurrence of CS and the importance of targeting this behavior in eating disorder treatment. Future research should clarify the correlates, mechanisms, and function of CS in eating disorders.
Schulz, Kurt P; Li, Xiaobo; Clerkin, Suzanne M; Fan, Jin; Berwid, Olga G; Newcorn, Jeffrey H; Halperin, Jeffrey M
The protracted and highly variable development of prefrontal cortex regions that support cognitive control has been purported to shape the adult outcome of attention-deficit/hyperactivity disorder (ADHD). This neurodevelopmental model was tested in a prospectively followed sample of 27 adult probands who were diagnosed with ADHD in childhood and 28 carefully matched comparison subjects aged 21-28 years. Probands were classified with persistent ADHD or remitted ADHD. Behavioral and neural responses to the Stimulus and Response Conflict Task (SRCT) performed during functional magnetic resonance imaging (fMRI) were compared in probands and comparison subjects and in probands with persistent and remitted ADHD. Response speed and accuracy for stimulus, response, and combined conflicts did not differ across groups. Orbitofrontal, inferior frontal and parietal activation was lower in probands than comparison subjects, but only for combined conflicts, when demand for cognitive control was highest. Reduced activation for combined conflicts in probands was almost wholly attributable to the persistence of ADHD; orbitofrontal, inferior frontal, anterior cingulate and parietal activation was lower in probands with persistent ADHD than both probands with remitted ADHD and comparison subjects, but did not differ between probands with remitted ADHD and comparison subjects. These data provide the first evidence that prefrontal and parietal activation during cognitive control parallels the adult outcome of ADHD diagnosed in childhood, with persistence of symptoms linked to reduced activation and symptom recovery associated with activation indistinguishable from adults with no history of ADHD. Copyright © 2017 Elsevier Ltd. All rights reserved.
Ronca, April E.
Intrauterine complications have been implicated in the etiology of neuripsychiatric disorders including schizophrenia, autism and ADHD. This presentation will describe new translational studies derived from in vivo magnetic resonance imaging of developing and adult brain following perinatal asphyxia (PA). Our findings reveal significant effects of PA on neurometabolic profiles at one week of age, and significant relationships between early metabolites and later life phenotypes including behavior and brain morphometry
Mekori-Domachevsky, Ehud; Guri, Yael; Yi, James; Weisman, Omri; Calkins, Monica E; Tang, Sunny X; Gross, Raz; McDonald-McGinn, Donna M; Emanuel, Beverly S; Zackai, Elaine H; Zalsman, Gil; Weizman, Abraham; Gur, Ruben C; Gur, Raquel E; Gothelf, Doron
About one third of individuals with 22q11.2 deletion syndrome (22q11.2DS) develop schizophrenia. Notably, a full-blown psychotic disorder is usually preceded by subthreshold symptoms. Therefore, it is important to identify early signs of psychosis in this population, a task that is complicated by the intellectual disabilities typically seen in 22q11.2DS. We aimed to identify subthreshold psychotic symptoms that distinguish 22q11.2DS from other neurodevelopmental disorders. The study included two independent cohorts from Tel Aviv and Philadelphia. 22q11.2DS (N=171) and typically developing (TD; N=832) individuals were enrolled at both sites and further compared to two groups with intellectual disabilities: Williams syndrome (WS; N=21) in the Tel Aviv cohort and idiopathic developmental disabilities (IDD; N=129) in the Philadelphia cohort. Participants and their primary caregivers were interviewed with the Structured Interview for Prodromal Symptoms (SIPS) and psychopathologies were assessed using standardized tools; general cognitive abilities were assessed with the Computerized Neurocognitive Battery. Negative/disorganized subthreshold syndrome was significantly more common in the 22q11.2DS group than in the WS (OR=3.90, 95% CI=1.34-11.34) or IDD (OR=5.05, 95% CI=3.01-10.08) groups. The 22q11.2DS group had higher scores than the two intellectual disabilities groups on several SIPS negative items, including avolition and decreased expression of emotion. Overall, there were few significant correlations between level of cognitive deficits and severity of negative symptoms in 22q11.2DS and only in the Tel Aviv cohort. Our findings suggest that 22q11.2DS individuals at the age of risk for developing psychosis should be closely monitored for negative symptoms. Copyright © 2016 Elsevier B.V. All rights reserved.
Hempel, Annmarie; Pagnamenta, Alistair T; Blyth, Moira; Mansour, Sahar; McConnell, Vivienne; Kou, Ikuyo; Ikegawa, Shiro; Tsurusaki, Yoshinori; Matsumoto, Naomichi; Lo-Castro, Adriana; Plessis, Ghislaine; Albrecht, Beate; Battaglia, Agatino; Taylor, Jenny C; Howard, Malcolm F; Keays, David; Sohal, Aman Singh; Kühl, Susanne J; Kini, Usha; McNeill, Alisdair
SOX11 is a transcription factor proposed to play a role in brain development. The relevance of SOX11 to human developmental disorders was suggested by a recent report of SOX11 mutations in two patients with Coffin-Siris syndrome. Here we further investigate the role of SOX11 variants in neurodevelopmental disorders. We used array based comparative genomic hybridisation and trio exome sequencing to identify children with intellectual disability who have deletions or de novo point mutations disrupting SOX11. The pathogenicity of the SOX11 mutations was assessed using an in vitro gene expression reporter system. Loss-of-function experiments were performed in xenopus by knockdown of Sox11 expression. We identified seven individuals with chromosome 2p25 deletions involving SOX11. Trio exome sequencing identified three de novo SOX11 variants, two missense (p.K50N; p.P120H) and one nonsense (p.C29*). The biological consequences of the missense mutations were assessed using an in vitro gene expression system. These individuals had microcephaly, developmental delay and shared dysmorphic features compatible with mild Coffin-Siris syndrome. To further investigate the function of SOX11, we knocked down the orthologous gene in xenopus. Morphants had significant reduction in head size compared with controls. This suggests that SOX11 loss of function can be associated with microcephaly. We thus propose that SOX11 deletion or mutation can present with a Coffin-Siris phenotype. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
Full Text Available Richard BarnumPrivate practice, Child and adolescent psychiatry, MA, USAAbstract: Conversion Disorder (CD is a diagnosis offered to explain signs and symptoms that do not correspond to recognized medical conditions. Pediatric patients with variable, vague, and multisystem complaints are at increased risk for being diagnosed with CD. Little is known about the impact of such a diagnosis. In making such diagnoses, it is likely that pediatric providers hope to encourage patients to access mental health care, but no basis exists to show that these diagnoses result in such access in any useful way. This article presents the case of a child with Ehlers-Danlos Syndrome, who had been previously (incorrectly diagnosed with CD and referred for mental health care. It offers commentary based on interviews with other pediatric patients with similar experiences – conducted in collaboration with the Ehlers-Danlos National Foundation. These cases indicate that CD diagnoses can seriously undermine patients’ trust in doctors, and can create such defensiveness that it may interfere with (especially patients’ abilities to engage with mental health services. Such interference is an important problem, if the diagnosis is accurate. But, in the (more likely event that it is not accurate, this defensiveness can interfere with both important mental health care and further ongoing necessary medical care.Keywords: somatoform disorders, dysautonomias, pain, collagen diseases, mitochondrial diseases, complex regional pain syndromes
Chailangkarn, Thanathom; Trujillo, Cleber A; Freitas, Beatriz C; Hrvoj-Mihic, Branka; Herai, Roberto H; Yu, Diana X; Brown, Timothy T; Marchetto, Maria C; Bardy, Cedric; McHenry, Lauren; Stefanacci, Lisa; Järvinen, Anna; Searcy, Yvonne M; DeWitt, Michelle; Wong, Wenny; Lai, Philip; Ard, M Colin; Hanson, Kari L; Romero, Sarah; Jacobs, Bob; Dale, Anders M; Dai, Li; Korenberg, Julie R; Gage, Fred H; Bellugi, Ursula; Halgren, Eric; Semendeferi, Katerina; Muotri, Alysson R
Williams syndrome is a genetic neurodevelopmental disorder characterized by an uncommon hypersociability and a mosaic of retained and compromised linguistic and cognitive abilities. Nearly all clinically diagnosed individuals with Williams syndrome lack precisely the same set of genes, with breakpoints in chromosome band 7q11.23 (refs 1-5). The contribution of specific genes to the neuroanatomical and functional alterations, leading to behavioural pathologies in humans, remains largely unexplored. Here we investigate neural progenitor cells and cortical neurons derived from Williams syndrome and typically developing induced pluripotent stem cells. Neural progenitor cells in Williams syndrome have an increased doubling time and apoptosis compared with typically developing neural progenitor cells. Using an individual with atypical Williams syndrome, we narrowed this cellular phenotype to a single gene candidate, frizzled 9 (FZD9). At the neuronal stage, layer V/VI cortical neurons derived from Williams syndrome were characterized by longer total dendrites, increased numbers of spines and synapses, aberrant calcium oscillation and altered network connectivity. Morphometric alterations observed in neurons from Williams syndrome were validated after Golgi staining of post-mortem layer V/VI cortical neurons. This model of human induced pluripotent stem cells fills the current knowledge gap in the cellular biology of Williams syndrome and could lead to further insights into the molecular mechanism underlying the disorder and the human social brain.
Meier, Sandra M; Bulik, Cynthia M; Thornton, Laura M; Mattheisen, Manuel; Mortensen, Preben B; Petersen, Liselotte
Anxiety disorders and anorexia nervosa are frequently acknowledged to be highly comorbid conditions, but still, little is known about the clinical and aetiological cohesion of specific anxiety diagnoses and anorexia nervosa. Using the comprehensive Danish population registers, we aimed to determine the risk of anorexia nervosa in patients with register-detected severe anxiety disorders. We also explored whether parental psychopathology was associated with offspring's anorexia nervosa. Anxiety disorders increased the risk of subsequent anorexia nervosa, with the highest risk observed in obsessive-compulsive disorder. Especially, male anxiety patients were at an increased risk for anorexia nervosa. Furthermore, an increased risk was observed in offspring of fathers with panic disorder. A diagnosis of an anxiety disorder, specifically obsessive-compulsive disorder, constitutes a risk factor for subsequent diagnosis of anorexia nervosa. These observations support the notion that anxiety disorders and anorexia nervosa share etiological mechanisms and/or that anxiety represents one developmental pathway to anorexia nervosa. Copyright © 2015 John Wiley & Sons, Ltd and Eating Disorders Association.
Full Text Available Richard A Kanaan,1,2 David Armstrong,3 Simon Wessely2 1Department of Psychiatry, University of Melbourne, Austin Health, Heidelberg, VIC, Australia; 2Department of Psychological Medicine, King’s College London, Institute of Psychiatry, Weston Education Centre, Denmark Hill, 3Department of General Practice, King’s College London, Capital House, London, UK Objective: Since DSM-5 removed the requirement for a psychosocial formulation, neurologists have been able to make the diagnosis of conversion disorder without psychiatric input. We sought to examine whether neurologists and specialist psychiatrists concurred with this approach.Design: We used mixed methods, first surveying all the neurologists in the UK and then interviewing the neuropsychiatrists in a large UK region on the role of psychiatrists in diagnosing conversion disorder.Results: Of the surveyed neurologists, 76% did not think that psychiatrists were essential for the diagnosis and 71% thought that psychiatrists did not even consider conversion disorder when referred a case. The neuropsychiatrists who were interviewed held complex models of conversion disorder. They believed all cases could be explained psychosocially in theory, but the nature of the diagnostic encounter often prevented it in practice; all felt that psychosocial formulation could be very helpful and some felt that it was essential to diagnosis.Conclusion: Although neurologists do not think psychiatrists are required for diagnosing conversion disorder, specialist psychiatrists disagree, at least in some cases. Keywords: functional neurological disorders, classification, qualitative research, survey, psychiatric formulation
Wiksten-Almströmer, Marianne; Hirschberg, Angelica Lindën; Hagenfeldt, Kerstin
To evaluate the long-term effects on bone mineral density (BMD) in women diagnosed with menstrual disorders in their adolescence. Prospective follow-up study six years after the initial investigation. A youth clinic that is part of the school health system in Stockholm. Eighty-seven women diagnosed with secondary amenorrhea or oligomenorrhea in adolescence. Subjects underwent gynecological examination, evaluation of eating behavior and physical activity. Whole body Dual Energy X-ray Absorptiometry was used for measurement of BMD. BMD. The overall frequency of osteopenia/osteoporosis was 52%, and three girls had osteoporosis. Women with previous secondary amenorrhea had significantly lower BMD in the pelvis and lumbar spine than those with previous oligomenorrhea. The strongest predictor of low BMD was a restrictive eating disorder in adolescence and the most important counteraction was high physical activity at follow-up and a body mass index (BMI) > or = 22. Persistent menstrual dysfunction at follow-up was associated with polycystic ovary syndrome and lower frequency of osteopenia. This clinical follow-up study has demonstrated a high frequency of osteopenia in women diagnosed with menstrual disorders in adolescence. Previous anorectic behavior was the strongest negative predictor of BMD. It is important to pay attention to an underlying eating disorder in young women with menstrual dysfunction in order to promote bone health.
Morey, L C; Benson, K T; Skodol, A E
The DSM-5 Personality and Personality Disorders Work Group formulated a hybrid dimensional/categorical model that represented personality disorders as combinations of core impairments in personality functioning with specific configurations of problematic personality traits. Specific clusters of traits were selected to serve as indicators for six DSM categorical diagnoses to be retained in this system - antisocial, avoidant, borderline, narcissistic, obsessive-compulsive and schizotypal personality disorders. The goal of the current study was to describe the empirical relationships between the DSM-5 section III pathological traits and DSM-IV/DSM-5 section II personality disorder diagnoses. Data were obtained from a sample of 337 clinicians, each of whom rated one of his or her patients on all aspects of the DSM-IV and DSM-5 proposed alternative model. Regression models were constructed to examine trait-disorder relationships, and the incremental validity of core personality dysfunctions (i.e. criterion A features for each disorder) was examined in combination with the specified trait clusters. Findings suggested that the trait assignments specified by the Work Group tended to be substantially associated with corresponding DSM-IV concepts, and the criterion A features provided additional diagnostic information in all but one instance. Although the DSM-5 section III alternative model provided a substantially different taxonomic structure for personality disorders, the associations between this new approach and the traditional personality disorder concepts in DSM-5 section II make it possible to render traditional personality disorder concepts using alternative model traits in combination with core impairments in personality functioning.
Rück, Christian; Larsson, K Johan; Lind, Kristina; Perez-Vigil, Ana; Isomura, Kayoko; Sariaslan, Amir; Lichtenstein, Paul; Mataix-Cols, David
The usefulness of cases diagnosed in administrative registers for research purposes is dependent on diagnostic validity. This study aimed to investigate the validity and inter-rater reliability of recorded diagnoses of tic disorders and obsessive-compulsive disorder (OCD) in the Swedish National Patient Register (NPR). Chart review of randomly selected register cases and controls. 100 tic disorder cases and 100 OCD cases were randomly selected from the NPR based on codes from the International Classification of Diseases (ICD) 8th, 9th and 10th editions, together with 50 epilepsy and 50 depression control cases. The obtained psychiatric records were blindly assessed by 2 senior psychiatrists according to the criteria of the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) and ICD-10. Positive predictive value (PPV; cases diagnosed correctly divided by the sum of true positives and false positives). Between 1969 and 2009, the NPR included 7286 tic disorder and 24,757 OCD cases. The vast majority (91.3% of tic cases and 80.1% of OCD cases) are coded with the most recent ICD version (ICD-10). For tic disorders, the PPV was high across all ICD versions (PPV=89% in ICD-8, 86% in ICD-9 and 97% in ICD-10). For OCD, only ICD-10 codes had high validity (PPV=91-96%). None of the epilepsy or depression control cases were wrongly diagnosed as having tic disorders or OCD, respectively. Inter-rater reliability was outstanding for both tic disorders (κ=1) and OCD (κ=0.98). The validity and reliability of ICD codes for tic disorders and OCD in the Swedish NPR is generally high. We propose simple algorithms to further increase the confidence in the validity of these codes for epidemiological research. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
Thompson-Hollands, Johanna; Farchione, Todd J; Barlow, David H
Thought-action fusion (TAF) is a cognitive error that has been frequently investigated within the context of obsessive-compulsive disorder (OCD). However, evidence suggests that this error may also be present in disorders other than OCD, indicating that TAF is related to higher order factors rather than a specific diagnosis. We explored TAF in a sample of patients with mixed diagnoses undergoing treatment with a transdiagnostic CBT protocol. Elevated TAF levels at baseline were not specific to patients with OCD. However, the presence of any generalized anxiety disorder (GAD) diagnosis was unexpectedly the strongest predictor of likelihood TAF. Likelihood TAF, a particular component of TAF, was reduced after transdiagnostic treatment, and this reduction was not affected by the presence of a GAD diagnosis. Results indicate that TAF is responsive to treatment and should be assessed and, perhaps, treated in disorders beyond OCD.
Mazlum, Betül; Anlar, Banu; Kalkanoğlu-Sivri, H Serap; Karlı-Oğuz, Kader; Özusta, Şeniz; Ünal, Fatih
Phenylketonuria is one of the most prevalent autosomal recessive hereditary disorders in Turkey. If untreated, it results in severe brain damage and can also be associated with autism in certain patients. We present a three-year old boy who exhibited the symptoms of autism and was subsequently diagnosed with phenylketonuria. This case illustrates that because the majority of autism cases are idiopathic, an occasional patient with a metabolic disorder might be overlooked especially in the era of newborn screening. We also discuss the possible pathogenetic processes leading to autistic symptoms in phenylketonuria, and wish to draw attention to the possibility of cases missed in the screening program because of less than 100% coverage or insufficient food intake before blood sampling. Clinicians should keep in mind the possibility of treatable disorders in children with autism even when such disorders appear unlikely.
Pan, Chien-Yu; Tsai, Chia-Liang; Chu, Chia-Hua
The purpose of this study was to compare the movement skills of children with autism spectrum disorders (ASD), attention deficit hyperactivity disorder (ADHD), and those without disabilities. Ninety-one children (ASD, n = 28; ADHD, n = 29; control, n = 34), ages 6-10 years, were of average IQ participated. After controlling for age, both ASD and…
Kanaan, Richard A; Armstrong, David; Wessely, Simon
Since DSM-5 removed the requirement for a psychosocial formulation, neurologists have been able to make the diagnosis of conversion disorder without psychiatric input. We sought to examine whether neurologists and specialist psychiatrists concurred with this approach. We used mixed methods, first surveying all the neurologists in the UK and then interviewing the neuropsychiatrists in a large UK region on the role of psychiatrists in diagnosing conversion disorder. Of the surveyed neurologists, 76% did not think that psychiatrists were essential for the diagnosis and 71% thought that psychiatrists did not even consider conversion disorder when referred a case. The neuropsychiatrists who were interviewed held complex models of conversion disorder. They believed all cases could be explained psychosocially in theory, but the nature of the diagnostic encounter often prevented it in practice; all felt that psychosocial formulation could be very helpful and some felt that it was essential to diagnosis. Although neurologists do not think psychiatrists are required for diagnosing conversion disorder, specialist psychiatrists disagree, at least in some cases.
Moriwaki, Hiroto; Uchida, Akira; Chiba, Sachiko; Moriyama, Hiroshi; Tokunaga, Masakazu
Polysomnography is useful for assessing the severity of sleep breathing disorder, including obstructive sleep apnea hypopnea syndrome. The clinical condition is difficult to understand completely, however, based on the apnea hypopnea index (AHI) alone, however, and longitudinal change of shape in the upper airway must be clarified. Most diagnoses of obstructive sites in the upper airway were diagnosed statically, so we attempted to assess changes in upper airway shape using dynamic magnetic resonance imaging (MRI), emphasizing the movement of tongue and lower chin, to analyze the relationship between AHI. Subjects were 62 patients with sleep breathing disorder examined by nocturnal polysomnography and dynamic MRI, assessing the change of shape in the upper airway. We concluded that: the group whose rotation angle of the tongue exceeded 6 deg and that the group whose distance of lower chin movement was longer during sleep than while awake were severe cases. (author)
Moriwaki, Hiroto; Uchida, Akira; Chiba, Sachiko; Moriyama, Hiroshi [Jikei Univ., Tokyo (Japan). School of Medicine; Chiba, Shintarou; Yagi, Asako; Ohta, Masaji [Ohta General Hospital, Kawasaki, Kanagawa (Japan); Tokunaga, Masakazu [Kanagawa Prefecture Midwives and Nurses Training School (Japan). Hospital
Polysomnography is useful for assessing the severity of sleep breathing disorder, including obstructive sleep apnea hypopnea syndrome. The clinical condition is difficult to understand completely, however, based on the apnea hypopnea index (AHI) alone, however, and longitudinal change of shape in the upper airway must be clarified. Most diagnoses of obstructive sites in the upper airway were diagnosed statically, so we attempted to assess changes in upper airway shape using dynamic magnetic resonance imaging (MRI), emphasizing the movement of tongue and lower chin, to analyze the relationship between AHI. Subjects were 62 patients with sleep breathing disorder examined by nocturnal polysomnography and dynamic MRI, assessing the change of shape in the upper airway. We concluded that: the group whose rotation angle of the tongue exceeded 6 deg and that the group whose distance of lower chin movement was longer during sleep than while awake were severe cases. (author)
Lemcke, Sanne; Parner, Erik T; Bjerrum, Merete
Studies have shown that children later diagnosed with autism spectrum disorders (ASD) in their first years of life might show symptoms in main developmental areas and that these signs might be sensed by the parents. The present study investigated in a large birth cohort if children later diagnosed...... with ASD had deviations at 6 and 18 months in areas such as the ability to self-regulate emotions, feeding, and sleeping. The study was based on prospective information collected from 76,322 mothers who participated in the Danish National Birth Cohort. When the children reached an average age of 11 years......, 973 children with ASD and a control group of 300 children with intellectual disability (IDnoASD) were identified via Danish health registries. Associations were found between short periods of breast-feeding and the children later diagnosed with ASD and IDnoASD as well as associations at 18 months...
The study investigates the process of recovery for people diagnosed with personality disorder. This is related to the application of the new meaning of recovery from mental illness as explored by members of The Haven which, as the service setting for the study, addresses the problems of a client group that suffers significant social exclusion, known to impact on demand for health and other public services. It aims to examine efforts which attempt to reverse this social exclusion as an aspect ...
Traylor, Jessica; Chandrasekaran, Suchitra; Limaye, Meghana; Srinivas, Sindhu; Durnwald, Celeste P
The objective of this study is to evaluate a woman's risk perception for future cardiovascular disease (CVD) after being diagnosed with a hypertensive disorder of pregnancy. A prospective cohort of women diagnosed with a hypertensive disorder of pregnancy (HDP) was studied. Each woman completed two surveys, one prior to hospital discharge and one 2 weeks later, designed to assess knowledge of and risk perception for future CVD based on their recent diagnosis of a HDP. Rates of postpartum depression were also assessed. Of the 146 subjects included, 28% were diagnosed with preeclampsia with severe features, 52.1% with preeclampsia with mild features, and 19.9% had chronic hypertension. Women with severe features and those delivering preterm were more likely to report a perception of increased risk of both recurrent HDP in a future pregnancy (p = 0.004 and 0.005, respectively) and hypertension later in life (p = 0.01 and 0.03, respectively). Women delivering preterm were more likely to report an accurate perception of increased risk of myocardial infarction and stroke compared to those delivering at term (p = 0.006 and 0.002, respectively). Disease severity and preterm delivery were associated with a higher likelihood of the perception of an increased risk for both recurrent HDP and hypertension in the future. Only preterm delivery was associated with a higher risk perception for stroke and myocardial infarction. Interventions targeted at improved health awareness in women diagnosed with HDP are warranted.
Henry, Charles A; Nowinski, Lisa; Koesterer, Karmen; Ferrone, Christine; Spybrook, Jessaca; Bauman, Margaret
The purpose of this study was to investigate the prevalence of depression diagnoses and related clinical data in an outpatient sample of youth with autistic disorder. Records of 123 psychiatrically referred children and adolescents with a Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision (DSM-IV-TR) diagnosis of autistic disorder were examined. Mood disorder diagnoses and chief complaints along with family mood disorder history were the primary variables analyzed. Four subjects (3%) presented with depressed mood. Irritability complaints were frequent (n=78, 63%). Six subjects (5%) received a mood disorder diagnosis; all with mood disorder, not otherwise specified. No subjects received a depressive disorder diagnosis. Family history of mood disorders was common. Findings raise questions about the appropriate characterization and potential misdiagnoses of depression in youth with autistic disorder.
Jacob, P; Srinath, S; Girimaji, S; Seshadri, S; Sagar, J V
To assess the prevalence of neurodevelopmental and psychiatric co-morbidities in children and adolescents diagnosed with attention-deficit hyperactivity disorder at a tertiary care child and adolescent psychiatry centre. A total of 63 children and adolescents who were diagnosed with attention-deficit hyperactivity disorder and fulfilled the inclusion criteria were comprehensively assessed for neurodevelopmental and psychiatric co-morbidities. The tools used included the Mini-International Neuropsychiatric Interview for Children and Adolescents, Attention Deficit Hyperactivity Disorder Rating Scale IV (ADHD-RS), Children's Global Assessment Scale, Clinical Global Impression Scale, Vineland Social Maturity Scale, and Childhood Autism Rating Scale. All except 1 subject had neurodevelopmental and / or psychiatric disorder co-morbid with attention-deficit hyperactivity disorder; 66.7% had both neurodevelopmental and psychiatric disorders. Specific learning disability was the most common co-existing neurodevelopmental disorder and oppositional defiant disorder was the most common psychiatric co-morbidity. The mean baseline ADHD-RS scores were significantly higher in the group with psychiatric co-morbidities, especially in the group with oppositional defiant disorder. Co-morbidity is present at a very high frequency in clinic-referred children diagnosed with attention-deficit hyperactivity disorder. Psychiatric co-morbidity, specifically oppositional defiant disorder, has an impact on the severity of attention-deficit hyperactivity disorder. Co-morbidity needs to be explicitly looked for during evaluation and managed appropriately.
Multilingualism poses unique psychiatric problems, especially in the field of child psychiatry. The author discusses several linguistic and transcultural issues in relation to Language Disorder, Specific Learning Disorder and Selective Mutism. Linguistic characteristics of multiple language development, including so-called profile effects and code-switching, need to be understood for differential diagnosis. It is also emphasized that Language Disorder in a bilingual person is not different or worse than that in a monolingual person. Second language proficiency, cultural background and transfer from the first language all need to be considered in an evaluation for Specific Learning Disorder. Selective Mutism has to be differentiated from the silent period observed in the normal successive bilingual development. The author concludes the review by remarking on some caveats around methods of language evaluation in a multilingual person.
Owen, Michael J; O'Donovan, Michael C
The idea that disturbances occurring early in brain development contribute to the pathogenesis of schizophrenia, often referred to as the neurodevelopmental hypothesis, has become widely accepted. Despite this, the disorder is viewed as being distinct nosologically, and by implication pathophysiologically and clinically, from syndromes such as autism spectrum disorders, attention-deficit/hyperactivity disorder (ADHD) and intellectual disability, which typically present in childhood and are grouped together as "neurodevelopmental disorders". An alternative view is that neurodevelopmental disorders, including schizophrenia, rather than being etiologically discrete entities, are better conceptualized as lying on an etiological and neurodevelopmental continuum, with the major clinical syndromes reflecting the severity, timing and predominant pattern of abnormal brain development and resulting functional abnormalities. It has also been suggested that, within the neurodevelopmental continuum, severe mental illnesses occupy a gradient of decreasing neurodevelopmental impairment as follows: intellectual disability, autism spectrum disorders, ADHD, schizophrenia and bipolar disorder. Recent genomic studies have identified large numbers of specific risk DNA changes and offer a direct and robust test of the predictions of the neurodevelopmental continuum model and gradient hypothesis. These findings are reviewed in detail. They not only support the view that schizophrenia is a disorder whose origins lie in disturbances of brain development, but also that it shares genetic risk and pathogenic mechanisms with the early onset neurodevelopmental disorders (intellectual disability, autism spectrum disorders and ADHD). They also support the idea that these disorders lie on a gradient of severity, implying that they differ to some extent quantitatively as well as qualitatively. These findings have important implications for nosology, clinical practice and research. © 2017 World
Isles, Anthony R.; Ingason, Andrés; Lowther, Chelsea; Gawlick, Micha; Stöber, Gerald; Potter, Harry; Georgieva, Lyudmila; Pizzo, Lucilla; Ozaki, Norio; Kushima, Itaru; Ikeda, Masashi; Iwata, Nakao; Levinson, Douglas F.; Gejman, Pablo V.; Shi, Jianxin; Sanders, Alan R.; Duan, Jubao; Sisodiya, Sanjay; Costain, Gregory; Degenhardt, Franziska; Giegling, Ina; Rujescu, Dan; Hreidarsson, Stefan J.; Saemundsen, Evald; Ahn, Joo Wook; Ogilvie, Caroline; Stefansson, Hreinn; Stefansson, Kari; O’Donovan, Michael C.; Owen, Michael J.; Bassett, Anne; Kirov, George
Duplications at 15q11.2-q13.3 overlapping the Prader-Willi/Angelman syndrome (PWS/AS) region have been associated with developmental delay (DD), autism spectrum disorder (ASD) and schizophrenia (SZ). Due to presence of imprinted genes within the region, the parental origin of these duplications may be key to the pathogenicity. Duplications of maternal origin are associated with disease, whereas the pathogenicity of paternal ones is unclear. To clarify the role of maternal and paternal duplications, we conducted the largest and most detailed study to date of parental origin of 15q11.2-q13.3 interstitial duplications in DD, ASD and SZ cohorts. We show, for the first time, that paternal duplications lead to an increased risk of developing DD/ASD/multiple congenital anomalies (MCA), but do not appear to increase risk for SZ. The importance of the epigenetic status of 15q11.2-q13.3 duplications was further underlined by analysis of a number of families, in which the duplication was paternally derived in the mother, who was unaffected, whereas her offspring, who inherited a maternally derived duplication, suffered from psychotic illness. Interestingly, the most consistent clinical characteristics of SZ patients with 15q11.2-q13.3 duplications were learning or developmental problems, found in 76% of carriers. Despite their lower pathogenicity, paternal duplications are less frequent in the general population with a general population prevalence of 0.0033% compared to 0.0069% for maternal duplications. This may be due to lower fecundity of male carriers and differential survival of embryos, something echoed in the findings that both types of duplications are de novo in just over 50% of cases. Isodicentric chromosome 15 (idic15) or interstitial triplications were not observed in SZ patients or in controls. Overall, this study refines the distinct roles of maternal and paternal interstitial duplications at 15q11.2-q13.3, underlining the critical importance of maternally
Anthony R Isles
Full Text Available Duplications at 15q11.2-q13.3 overlapping the Prader-Willi/Angelman syndrome (PWS/AS region have been associated with developmental delay (DD, autism spectrum disorder (ASD and schizophrenia (SZ. Due to presence of imprinted genes within the region, the parental origin of these duplications may be key to the pathogenicity. Duplications of maternal origin are associated with disease, whereas the pathogenicity of paternal ones is unclear. To clarify the role of maternal and paternal duplications, we conducted the largest and most detailed study to date of parental origin of 15q11.2-q13.3 interstitial duplications in DD, ASD and SZ cohorts. We show, for the first time, that paternal duplications lead to an increased risk of developing DD/ASD/multiple congenital anomalies (MCA, but do not appear to increase risk for SZ. The importance of the epigenetic status of 15q11.2-q13.3 duplications was further underlined by analysis of a number of families, in which the duplication was paternally derived in the mother, who was unaffected, whereas her offspring, who inherited a maternally derived duplication, suffered from psychotic illness. Interestingly, the most consistent clinical characteristics of SZ patients with 15q11.2-q13.3 duplications were learning or developmental problems, found in 76% of carriers. Despite their lower pathogenicity, paternal duplications are less frequent in the general population with a general population prevalence of 0.0033% compared to 0.0069% for maternal duplications. This may be due to lower fecundity of male carriers and differential survival of embryos, something echoed in the findings that both types of duplications are de novo in just over 50% of cases. Isodicentric chromosome 15 (idic15 or interstitial triplications were not observed in SZ patients or in controls. Overall, this study refines the distinct roles of maternal and paternal interstitial duplications at 15q11.2-q13.3, underlining the critical importance of
Treloar, Amanda Jane Commons; Lewis, Andrew J.
This paper reviews the history of the recognition of borderline personality disorder as a clinical disorder, followed by a review of the contemporary practice of diagnosing borderline personality disorder in psychiatric settings. Many researchers have cautioned against the conflation of difficult patients with the diagnostic category of borderline…
Gradus, Jaimie L; Qin, Ping; Lincoln, Alisa K
Adjustment disorder is a diagnosis given following a significant psychosocial stressor from which an individual has difficulty recovering. The individual's reaction to this event must exceed what would be observed among similar people experiencing the same stressor. Adjustment disorder is associa...... regression analyses revealed that those diagnosed with adjustment disorder had 12 times the rate of suicide as those without an adjustment disorder diagnosis, after controlling for history of depression diagnosis, marital status, income, and the matched factors....... is associated with suicidal ideation and suicide attempt. However the association between adjustment disorder and completed suicide has yet to be examined. The current study is a population-based case control study examining this association in the population of Denmark aged 15 to 90 years. All suicides...... in Denmark from 1994 to 2006 were included, resulting in 9,612 cases. For each case, up to 30 controls were matched on gender, exact date of birth, and calendar time, yielding 199,306 controls. Adjustment disorder diagnosis was found in 7.6% of suicide cases and 0.52% of controls. Conditional logistic...
Bonnington, Oliver; Rose, Diana
This study explores experiences of stigma and discrimination amongst people diagnosed with bipolar disorder (BD) or borderline personality disorder (BPD). Inspired by Margaret Archer's morphogenetic sequence and the ontological depth of critical realism, a temporal framework for stigmatisation, incorporating structure and agency, is developed and used to situate these experiences. A literature review found very little existing research on the subjective experience of stigma amongst these diagnostic groups. Indeed, most mental illness stigma research is quantitative and focussed on schizophrenia and depression. In-depth interviews were conducted with twenty-nine people diagnosed with BD or BPD, along with five 'friendship' mini-focus groups within the UK. Participants were recruited via charities and participant networking. Using thematic analysis, along with abductive and retroductive inference, experiences and anticipation of stigma and discrimination for participants with one of the two diagnoses in various contexts of social interaction were found to coincide with 'four faces' of oppression: cultural imperialism (pathologisation, normalisation and stereotyping), powerlessness, marginalisation and violence. Such experiences implied a range of antecedent social and cultural structures. Implications for the stigma concept are discussed. Copyright © 2014. Published by Elsevier Ltd.
The association of anxiety disorders and obsessive compulsive personality disorder with anorexia nervosa: evidence from a family study with discussion of nosological and neurodevelopmental implications.
Strober, Michael; Freeman, Roberta; Lampert, Carlyn; Diamond, Jane
To investigate the association of anorexia nervosa with anxiety disorders through use of a case-control family study design. Lifetime prevalence of anxiety disorders and obsessive compulsive personality disorder was determined among 574 first-degree relatives of 152 probands with anorexia nervosa and compared to rates observed among 647 first-degree relatives of 181 never-ill control probands. Adjusting for comorbidity of the same illness in the proband, relatives of probands with anorexia nervosa, had a significantly higher prevalence of generalized anxiety, obsessive compulsive disorder, separation anxiety disorder, social phobia, panic disorder, and obsessive compulsive personality disorder compared to relatives of never-ill control probands. Anorexia nervosa may share familial liability factors in common with various anxiety phenotypes. In suggesting that a transmitted propensity for anxiety is a key aspect of vulnerability in anorexia nervosa, the findings point to research developments in the affective neurosciences, specifically the neurocircuitry of fear and anxiety, as a heuristic framework in which to interpret aspects of premorbid temperamental anxieties and clinical symptoms. (c) 2007 by Wiley Periodicals, Inc.
Schaefert, Rainer; Laux, Gunter; Kaufmann, Claudia; Schellberg, Dieter; Bölter, Regine; Szecsenyi, Joachim; Sauer, Nina; Herzog, Wolfgang; Kuehlein, Thomas
(i) To analyze general practitioners' diagnosis of somatisation disorder (P75) using the International Classification of Primary Care (ICPC)-2-E in routine general practice. (ii) To validate the distinctiveness of the ICD-10 to ICPC-2 conversion rule which maps ICD-10 dissociative/conversion disorder (F44) as well as half of the somatoform categories (F45.0-2) to P75 and codes the other half of these disorders (F45.3-9), including autonomic organ dysfunctions and pain syndromes, as symptom diagnoses plus a psychosocial code in a multiaxial manner. Cross-sectional analysis of routine data from a German research database comprising the electronic patient records of 32 general practitioners from 22 practices. For each P75 patient, control subjects matched for age, gender, and practice were selected from the 2007 yearly contact group (YCG) without a P75 diagnosis using a propensity-score algorithm that resulted in eight controls per P75 patient. Of the 49,423 patients in the YCG, P75 was diagnosed in 0.6% (302) and F45.3-9 in 1.8% (883) of cases; overall, somatisation syndromes were diagnosed in 2.4% of patients. The P75 coding pattern coincided with typical characteristics of severe, persistent medically unexplained symptoms (MUS). F45.3-9 was found to indicate moderate MUS that otherwise showed little clinical difference from P75. Pain syndromes exhibited an unspecific coding pattern. Mild and moderate MUS were predominantly recorded as symptom diagnoses. Psychosocial codes were rarely documented. ICPC-2 P75 was mainly diagnosed in cases of severe MUS. Multiaxial coding appears to be too complicated for routine primary care. Instead of splitting P75 and F45.3-9 diagnoses, it is proposed that the whole MUS spectrum should be conceptualized as a continuum model comprising categorizations of uncomplicated (mild) and complicated (moderate and severe) courses. Psychosocial factors require more attention. Copyright (c) 2010 Elsevier Inc. All rights reserved.
Full Text Available Katrina Wilcox Hagberg, Susan S Jick Boston Collaborative Drug Surveillance Program, Boston University School of Public Health, Lexington, MA, USA Background: Prior studies have reported that the validity of autism spectrum disorder (ASD diagnoses recorded in the Clinical Practice Research Datalink (CPRD was high; however, diagnostic criteria and screening practices have changed since the last study was published in 2004.Objectives: 1 To calculate the positive predictive value (PPV of ASD diagnoses recorded in the CPRD compared to original medical records and 2 to describe characteristics of cases and use of clinical codes that support the ASD diagnosis as recorded in the electronic data by general practitioners over time.Methods: We identified children with a code for ASD (autism spectrum disorder, autism, Asperger’s, or pervasive developmental disorder in the CPRD from 1990 to 2014. We evaluated presence of codes in the electronic medical record indicating the presence of developmental delay, speech delay, behavioral problems, and other supporting clinical codes (e.g., therapy, referrals, etc.. We also evaluated changes in recording of these clinical codes over time. We compared the information present in the electronic medical record to original medical records for a sample of cases and calculated PPVs of ASD diagnoses recorded in the CPRD.Results: We identified 2154 children with a code for ASD. The mean age at diagnosis was 5.8 years, and 84% of cases were male. The majority (78.4% had 1 ASD diagnosis code in their electronic medical record. Approximately half of the cases had a code indicating behavioral problem, developmental delay, or speech delay, and 24.7% had a code indicating specialist referral or visit. After review of original medical records, the PPV of ASD diagnoses recorded in the CPRD was 91.9%. Conclusion: The results of this study suggest that ASD diagnoses recorded in the CPRD are reliable and can be used with confidence
Simms, Mark D; Jin, Xing Ming
• Based on strong research evidence (1), the prevalence of autism spectrum disorders (ASDs) has increased over the past decade, with a 2010 prevalence of 1:68 (1.5%) in children age 8 years. • Based on some research evidence as well as consensus (3), the most recent revision of the American Psychiatric Association's Diagnostic and Statistical Manual (DSM-V) identifies two core dimensions for the diagnosis of ASD: social (social communication and social interaction) and nonsocial (restricted, repetitive patterns of behaviors, interests, or activities). • Based on some research evidence as well as consensus (3) (31) (32) (33) (34), DSM-V identifies social pragmatic communication disorder (SPCD) as a dissociable dimension of language and communication ability that affects how individuals use language for social exchanges. SPCD is often found in children with language impairments and children with attention-deficit/hyperactivity disorder and other genetic/neurologic conditions. • Based on strong research evidence (2) (26) (27) (28), childhood language disorders affect 7.4% of kindergarteners, and 50% to 80% of these children experience persistent language, academic, and social-emotional difficulties into their adult years, despite having normal nonverbal cognitive abilities. • Based primarily on consensus due to lack of relevant clinical studies, differential diagnosis of autism and language disorders may require a multidisciplinary evaluation that takes into account a child’s overall development, including cognitive, communication, and social abilities. Monitoring the response to appropriate interventions and trajectory of development over time may improve the accuracy of diagnosis, especially in very young children.
Brukner-Wertman, Yael; Laor, Nathaniel; Golan, Ofer
DSM-5 introduced two diagnoses describing neurodevelopmental deficits in social communication (SC); Autism Spectrum Disorder (ASD) and Social (Pragmatic) Communication Disorder (SPCD). These diagnoses are differentiated by Repetitive and Restricted Behaviors (RRB), required for an ASD diagnosis and absent in SPCD. We highlight the gaps between the…
Al-Khotani, Amal; Naimi-Akbar, Aron; Albadawi, Emad; Ernberg, Malin; Hedenberg-Magnusson, Britt; Christidis, Nikolaos
Studies have indicated that the prevalence of symptoms and signs of temporomandibular disorders (TMD) are rare early in childhood, but become more prevalent in adolescents and adulthood. To our knowledge, no study has investigated the prevalence of TMD-diagnoses in children in the general population. The aim was thus to investigate the prevalence of TMD-diagnoses among children and adolescents in the general population using the Research Diagnostic Criteria for TMD (RDC/TMD). The current cross-sectional study consisted of 456 children and adolescents, aged between 10 and 18, randomly enrolled from 10 boy's- and 10 girl's- schools in Jeddah. The participants first answered two validated questions about TMD-pain, followed by a clinical examination according to RDC/TMD. One hundred twenty-four participants (27.2 %) were diagnosed with at least one TMD-diagnosis. Myofascial pain was the most common diagnosis (15 %) followed by disc displacement with reduction, arthralgia, myofascial pain with limited mouth opening and osteoarthrosis. Children diagnosed with myofascial pain more often reported orofacial pain, headache and tooth clenching (p headache as well as bruxism were associated with a TMD-pain diagnosis and disc displacement. A surprisingly low percentage of children and adolescents sought treatment by a dentist or physician for their pains.
Leivonen, Susanna; Voutilainen, Arja; Hinkka-Yli-Salomäki, Susanna; Timonen-Soivio, Laura; Chudal, Roshan; Gissler, Mika; Huttunen, Jukka; Sourander, Andre
The aim of this study was to describe the characteristics and incidence rates of diagnosed tic disorders in the Finnish Hospital Discharge Register, including changing incidence rates between 1991 and 2010. We also aimed to validate the diagnoses of Tourette's syndrome recorded in the register. Children born between January 1, 1991 and December 31, 2010, who were diagnosed with tic disorders, were identified from the Finnish Hospital Discharge Register (n = 3003). We studied the validity of the Tourette's syndrome diagnoses by reviewing the medical charts of 88 children born since 1997 and carrying out telephone interviews with 55 of their guardians. The incidence rates of all diagnosed tic disorders increased during the study period. A comorbid diagnosis of hyperkinetic disorder diagnosis was recorded in 28.2% of the children with Tourette's syndrome, and the validity of the register-based Tourette's syndrome diagnosis was approximately 95%. This is the first nationwide study to demonstrate the increasing incidence of all register-based tic disorder diagnoses. The validity of the Tourette's syndrome diagnoses in the Finnish Hospital Discharge Register was good, and the data provided are suitable for use in further register-based studies of tic disorders. ©2014 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.
Hatakenaka, Yuhei; Kotani, Haruko; Yasumitsu-Lovell, Kahoko; Suzuki, Keita; Fernell, Elisabeth; Gillberg, Christopher
Abnormalities of early motor development have been reported in autism spectrum disorder, attention-deficit/hyperactivity disorder, intellectual developmental disorder, developmental coordination disorder, and other Early Symptomatic Syndromes Eliciting Neurodevelopmental Clinical Examinations (ESSENCE). However, few studies have been conducted with a view to following up a clinically representative cohort of children coming for assessment of motor delay before age two years. We performed a prospective clinical cohort study to examine whether or not early motor delay is often an indication of ESSENCE. The sample comprised a one-year cohort of all children who came to a Japanese neurodevelopmental center before their second birthday because of delayed or abnormal gross motor development. The children were followed up from the ESSENCE viewpoint. Of the 30 children, 28 (18 boys and 10 girls) (93%) were given diagnoses subsumed under the ESSENCE umbrella. Of the 15 children with an identified or strongly suspected etiology, 13 (8 boys and 5 girls) (87%) had ESSENCE disorders or symptoms. Of the 15 children without a known etiology, all had ESSENCE disorders or symptoms. This study indicated that the vast majority of children with motor delay or abnormality in the first two years of life meet criteria for a disorder within the group of ESSENCE at follow-up; this means that young children, presenting with motor problems always need a broad clinical assessment, not just related to motor function, and systematic follow-up. Copyright © 2016 Elsevier Inc. All rights reserved.
U. A. Tsoy
Full Text Available Background: Obstructive sleep disordered breathing or obstructive sleep apnea (OSA is the most common respiratory impairment in acromegaly. OSA is bound up with heightened cardiovascular mortality. Aim: Тo study frequency, features, and structure of sleep disordered breathing in patients with newly diagnosed acromegaly and to elucidate the factors influencing their development. Materials and methods: 38 patients (10 men, 28 women, median age 53 (28-76 years, median body mass index (BMI 29 (19.9-44.3 kg/m² with newly diagnosed acromegaly were recruited into the study. All subjects underwent full polysomnography (Embla N7000, Natus, USA and Remlogica software (USA. Results: Sleep disordered breathing was found in 28 (73.7% patients. OSA was revealed in all cases, in 11 (39.3% subjects it was mixed. In 10 (35.7% patients OSA was mild, in 8 (28.6% moderate, and in 10 (35.7% severe. BMI (р<0.01, disease duration (р=0.003, and insulin-like growth factor-1 (IGF-1 level (р=0.04 were different in patients without OSA and patients with moderate-to-severe OSA. No difference was found in sex (р=0.4, age (р=0.064, and growth hormone level (р=0.6. Frequency of arterial hypertension, diabetes mellitus, and other glucose metabolism impairments was the same in subjects without OSA and with severe-to-moderate OSA. Conclusion: All patients with newly diagnosed acromegaly should undergo polysomnography. BMI, disease duration, and IGF-1 level are significant risk factors for OSA development. Correlation OSA with arterial hypertension and glucose metabolism impairments needs to be further investigated.
Mouridsen, Svend Erik; Rich, Bente; Isager, Torben
AIM: To study the sex ratio (proportion of males) in siblings of individuals diagnosed with autism spectrum disorders (ASDs) as children. METHOD: In the current study, we extended previous studies dealing with the androgen theory of autism and examined sex ratios in the siblings of 326 individuals...... the Danish live-birth sex ratio over the same period (0.514, p=0.001). The sibling sex ratio was not associated with the IQ in the autistic probands. INTERPRETATION: Our findings suggest a potential indirect confirmation of the androgen theory of autism....
Boysen, Guy A; VanBergen, Alexandra
Dissociative Identity Disorder (DID) has long been surrounded by controversy due to disagreement about its etiology and the validity of its associated phenomena. Researchers have conducted studies comparing people diagnosed with DID and people simulating DID in order to better understand the disorder. The current research presents a systematic review of this DID simulation research. The literature consists of 20 studies and contains several replicated findings. Replicated differences between the groups include symptom presentation, identity presentation, and cognitive processing deficits. Replicated similarities between the groups include interidentity transfer of information as shown by measures of recall, recognition, and priming. Despite some consistent findings, this research literature is hindered by methodological flaws that reduce experimental validity. Copyright © 2013 Elsevier Ltd. All rights reserved.
Can, Ganime; Tanrıverdi, Derya
The aim of this descriptive study was to determine social functioning and internalized stigma in individuals with substance use disorder. The study sample consisted of 105 patients diagnosed with substance use disorder according to the DSM-IV-TR diagnostic criteria. A Descriptive Information Form, Internalized Stigma of Mental Illness Scale (ISMI) and Social Functioning Scale (SFS) were used for data collection. Average total SFS score of the patients was 103.25±25.09 points, indicating an intermediate level of social functioning. Average total ISMI score of patients was 2.92±0.48 points, reflecting a high level of internalized stigma. A negative significant association was observed between the internalized stigma levels and social functioning of patients. These results suggest that rehabilitation of substance users should include counseling services in order to reduce internal perception of stigma and improve their social functioning. Copyright © 2015 Elsevier Inc. All rights reserved.
Jóźwik, Jagoda; Kałużna-Czaplińska, Joanna
Currently, analysis of various human body fluids is one of the most essential and promising approaches to enable the discovery of biomarkers or pathophysiological mechanisms for disorders and diseases. Analysis of these fluids is challenging due to their complex composition and unique characteristics. Development of new analytical methods in this field has made it possible to analyze body fluids with higher selectivity, sensitivity, and precision. The composition and concentration of analytes in body fluids are most often determined by chromatography-based techniques. There is no doubt that proper use of knowledge that comes from a better understanding of the role of body fluids requires the cooperation of scientists of diverse specializations, including analytical chemists, biologists, and physicians. This article summarizes current knowledge about the application of different chromatographic methods in analyses of a wide range of compounds in human body fluids in order to diagnose certain diseases and disorders.
Smith, Isaac C.; Reichow, Brian; Volkmar, Fred R.
A growing body of research has raised concerns about the number of individuals diagnosed with autism spectrum disorder (ASD) according to DSM-IV-TR who may no longer qualify for diagnoses under the new DSM-5 criteria, published in May 2013. The current study systematically reviews 25 articles evaluating samples according to both DSM-IV-TR and…
Olley, B O; Zeier, M D; Seedat, S; Stein, D J
This study examined the prevalence of and factors associated with post-traumatic stress disorder in recently diagnosed HIV/AIDS patients in South Africa. One hundred and forty-nine (44 male, 105 female) recently diagnosed HIV/AIDS patients (mean duration since diagnosis = 5.8 months, SD = 4.1) were evaluated. Subjects were assessed using the MINI International Neuropsychiatric Interview (MINI), the Carver Brief COPE coping scale and the Sheehan Disability Scale. In addition, previous exposures to trauma and past risk behaviours were assessed. Twenty-two patients (14.8%) met criteria for PTSD. Current psychiatric conditions more likely to be associated with PTSD included major depressive disorder (29% in PTSD patients versus 7% in non-PTSD patients, p = 0.004), suicidality (54% versus 11%, p = 0.001) and social anxiety disorder (40% versus 13%, p = 0.04). Further patients with PTSD reported significantly more work impairment and demonstrated a trend towards higher usage of alcohol as a means of coping. Discriminant function analysis indicated that female gender and a history of sexual violation in the past year were significantly associated with a diagnosis of PTSD. Patients whose PTSD was a direct result of an HIV/AIDS diagnosis (8/22) did not differ from other patients with PTSD on demographic or clinical features. In the South African context, PTSD is not an uncommon disorder in patients with HIV/AIDS. In some cases, PTSD is secondary to the diagnosis of HIV/AIDS but in most cases it is seen after other traumas, with sexual violation and intimate partner violence in women being particularly important.
Camacho, Ricardo; McCauley, Brandon; Szczech Moser, Christy
Over 70 years ago Dr. Karel Bobath and his wife Bertha Bobath began to craft the therapeutic intervention now known as neurodevelopmental treatment (NDT). This edition of Reviews, Tools, and Resources will highlight a historical review of research studies that have been completed, current websites, books, and blogs focusing on NDT.
Full Text Available Background: Gastroesophageal reflux disease (GERD is associated with a number of comorbidities in pediatrics. However, its association with attention deficit hyperactivity disorder (ADHD has not been reported. The aim of the present study was to investigate the prevalence of ADHD in pediatric patients newly diagnosed with GERD. Materials and Methods: Sixty newly-diagnosed treatment naive GERD patients and sixty healthy controls aging between 5 to 12 years referring to the Children and Adolescent’s medical center, Tehran, Iran were recruited in a case-control study during the year 2015. Then patients were evaluated for ADHD by a psychiatrist according to the DSM-IV criteria. The revised Conners' Parent Rating Scale (CPRS-R was used for assessment of the symptoms of ADHD. To screen for psychiatry disorders other than ADHD, the Kiddie-Sads-Present and Lifetime Version (K-SADS-PL questionnaire was used. Logistic regression analysis was used for modeling the association between GERD and ADHD in the study sample. Results: The mean age of GERD patients was 5.77±2.27 and for non-GERD controls was 6.03±2.52 (P= 0.543. Thirty-three out of 60 (55% GERD patients and 37 out of 60(61.66% non-GERD controls were male (P: 0.579. Prevalence of ADHD was 33.60 (55% in GERD patients and 10.60 (16.66% in non-GERD (P
Pasterski, Vickie; Mastroyannopoulou, Kiki; Wright, Deborah; Zucker, Kenneth J; Hughes, Ieuan A
The aims of the current study were twofold: (1) to assess the prevalence/severity of posttraumatic stress symptoms (PTSS) as well as cognitive and emotional responses in parents whose children were diagnosed with a disorder of sex development (DSD); and (2) to assess factors which contributed to PTSS. We hypothesized that parents would show elevated levels of PTSS and that negative cognitive and/or emotional responses would be predictive. Participants were parents of children diagnosed with a DSD. Thirty-six mothers and 11 fathers completed a measure of posttraumatic stress and reported difficulties in the domains of cognition (e.g., confusion) and emotion (e.g., grief). Using multiple regression, we determined factors contributing to parental PTSS. Reported PTSS was high: 31 % of mothers and 18 % of fathers met the threshold for caseness for Posttraumatic Stress Disorder. Regression included: child sex, parent sex, child age at diagnosis, years since diagnosis, genital ambiguity, father occupation, cognitive confusion, and emotional distress. Only cognitive confusion contributed significantly to variance in PTSS. Parents of children with DSD may experience the diagnosis as traumatic, evidenced by high rates of PTSS in the current report. Assessment of reactions to their children's diagnoses revealed that cognitive confusion, and not emotional distress, predicted PTSS. In this case, direct cognitive interventions may be applicable. Though psychological support is widely recommended, no detailed intervention has been offered. Our findings suggest that we may directly apply models successful in other areas of pediatrics, such as pediatric oncology. Future studies may assess the usefulness of such an intervention.
Fejzo, Marlena S; Magtira, Aromalyn; Schoenberg, Frederic Paik; Macgibbon, Kimber; Mullin, Patrick M
The purpose of this study is to determine the frequency of emotional, behavioral, and learning disorders in children exposed in utero to hyperemesis gravidarum (HG) and to identify prognostic factors for these disorders. Neurodevelopmental outcomes of 312 children from 203 mothers with HG were compared to neurodevelopmental outcomes from 169 children from 89 unaffected mothers. Then the clinical profiles of patients with HG and a normal child outcome were compared to the clinical profiles of patients with HG and a child with neurodevelopmental delay to identify prognostic factors. Binary responses were analyzed using either a Chi-square or Fisher Exact test and continuous responses were analyzed using a t-test. Children exposed in utero to HG have a 3.28-fold increase in odds of a neurodevelopmental diagnosis including attention disorders, learning delay, sensory disorders, and speech and language delay (Pneurodevelopmental delay. We found no evidence for increased risk of 13 emotional, behavioral, and learning disorders, including autism, intellectual impairment, and obsessive-compulsive disorder. However, the study was not sufficiently powered to detect rare conditions. Medications, treatments, and preterm birth were not associated with an increased risk for neurodevelopmental delay. Women with HG are at a significantly increased risk of having a child with neurodevelopmental delay. Common antiemetic treatments were not linked to neurodevelopmental delay, but early symptoms may play a role. There is an urgent need to address whether aggressive treatment that includes vitamin and nutrient supplementation in women with early symptoms of severe nausea of pregnancy decreases the risk of neurodevelopmental delay. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
Brossard-Racine, Marie; Shevell, Michael; Snider, Laurie; Belanger, Stacey Ageranioti; Majnemer, Annette
Motor difficulties are common in children with Attention Deficit Hyperactivity Disorder (ADHD). Although preliminary evidence has suggested that methylphenidate can improve the motor skills in children with ADHD and Developmental Coordination Disorder (DCD), the effect of stimulant medication on motor performance in children newly diagnosed with…
Matson, Johnny L.; Hess, Julie A.; Mahan, Sara
One-hundred nine children 3-16 years of age diagnosed with Autistic Disorder, Pervasive Developmental Disorder Not Otherwise Specified, or Asperger's Syndrome were studied. Children resided in six states in the United States. Using moderation analysis via multiple regression, verbal communication and challenging behaviors and how they interact…
Full Text Available Abstract Background Sixty percent of eating disorders do not meet criteria for anorexia- or bulimia nervosa, as defined by the Diagnostic and Statistical Manual version 4 (DSM-IV. Instead they are diagnosed as ‘eating disorders not otherwise specified’ (EDNOS. Discrepancies between criteria and clinical reality currently hampering eating disorder diagnoses in the DSM-IV will be addressed by the forthcoming DSM-V. However, future diagnoses for eating disorders will rely on current advances in the fields of neuroimaging and genetics for classification of symptoms that will ultimately improve treatment. Discussion Here we debate the classification issues, and discuss how brain imaging and genetic discoveries might be interwoven into a model of eating disorders to provide better classification and treatment. The debate concerns: a current issues in the classification of eating disorders in the DSM-IV, b changes proposed for DSM-V, c neuroimaging eating disorder research and d genetic eating disorder research. Summary We outline a novel evidence-based ‘impulse control’ spectrum model of eating disorders. A model of eating disorders is proposed that will aid future diagnosis of symptoms, coinciding with contemporary suggestions by clinicians and the proposed changes due to be published in the DSM-V.
Background Sixty percent of eating disorders do not meet criteria for anorexia- or bulimia nervosa, as defined by the Diagnostic and Statistical Manual version 4 (DSM-IV). Instead they are diagnosed as ‘eating disorders not otherwise specified’ (EDNOS). Discrepancies between criteria and clinical reality currently hampering eating disorder diagnoses in the DSM-IV will be addressed by the forthcoming DSM-V. However, future diagnoses for eating disorders will rely on current advances in the fields of neuroimaging and genetics for classification of symptoms that will ultimately improve treatment. Discussion Here we debate the classification issues, and discuss how brain imaging and genetic discoveries might be interwoven into a model of eating disorders to provide better classification and treatment. The debate concerns: a) current issues in the classification of eating disorders in the DSM-IV, b) changes proposed for DSM-V, c) neuroimaging eating disorder research and d) genetic eating disorder research. Summary We outline a novel evidence-based ‘impulse control’ spectrum model of eating disorders. A model of eating disorders is proposed that will aid future diagnosis of symptoms, coinciding with contemporary suggestions by clinicians and the proposed changes due to be published in the DSM-V. PMID:22770364
Aiach Dominitz, Valerie
The aim of the present paper is to open the discourse regarding the unmet needs of specific patients, especially those with substance use disorder and/or personality disorder where 'multimorbidities', and/or 'overdiagnosis' and/or 'diagnosis overlap' are frequent. An additional aim is to review the main therapeutic purpose and concepts of Gestalt therapy which might be appropriate in the treatment of these patients often characterized by their difficulties in being aware and in contact in the 'here and now'. I first start with an overview of Gestalt therapy concepts. Then, I illustrate Gestalt's 'here and now' and awareness concepts applied during 18 sessions with an inpatient diagnosed with substance use and bipolar disorders. In addition, the patient had to face an open criminal charge, was regarded as having an antisocial personality disorder and argued suffering from post-traumatic stress disorder. After this two-month therapy period, the patient entered for the first time a daily rehabilitation program in the community, where he was doing well (this after a few prior hospitalizations). The awareness development in the 'here and now' through which different contact styles and cycles of experiences are experienced is a process that allowed the patient to start experiencing contact with himself, his true needs and his environment. This contributed to his well-being improvement, led and supported his rehabilitation and reinsertion within the society and decrease his relapses, either with drugs or criminal activities. Copyright © 2016 John Wiley & Sons, Ltd. People with substance use disorder (where 'multimorbidities', 'overdiagnosis' or 'diagnosis overlap' are frequent), people with personality disorder(s) or people who have difficulties in defining what really disturbs them are the same people who could benefit of GT encouraging awareness and contact development in the 'here and now'. Gestalt therapy should not be regarded as a practitioner's toolbox but as a
Mother/offspring co-administration of the traditional herbal remedy yokukansan during the nursing period influences grooming and cerebellar serotonin levels in a rat model of neurodevelopmental disorders.
Muneoka, Katsumasa; Kuwagata, Makiko; Ogawa, Tetsuo; Shioda, Seiji
Neurodevelopmental impairment in the serotonergic system may be involved in autism spectrum disorder. Yokukansan is a traditional herbal remedy for restlessness and agitation in children, and mother-infant co-administration (MICA) to both the child and the nursing mother is one of the recommended treatment approaches. Recent studies have revealed the neuropharmacological properties of Yokukansan (YKS), including its 5-HT1A (serotonin) receptor agonistic effects. We investigated the influence of YKS treatment on behavior in a novel environment and on brain monoamine metabolism during the nursing period in an animal model of neurodevelopmental disorders, prenatally BrdU (5-bromo-2'-deoxyuridine)-treated rats (BrdU-rats). YKS treatment did not influence locomotor activity in BrdU-rats but reduced grooming in open-field tests. YKS treatment without MICA disrupted the correlation between locomotor behaviors and rearing and altered levels of serotonin and its metabolite in the cerebellum. These effects were not observed in the group receiving YKS treatment with MICA. These data indicate a direct pharmacological effect of YKS on the development of grooming behavior and profound effects on cerebellar serotonin metabolism, which is thought to be influenced by nursing conditions.
Fernańdez-Alcántara, Manuel; García-Caro, M Paz; Pérez-Marfil, M Nieves; Hueso-Montoro, Cesar; Laynez-Rubio, Carolina; Cruz-Quintana, Francisco
Various authors have reported feelings of loss and grief in parents of children with autism spectrum disorder. However, no previous studies have investigated the structure of these feelings. To analyze in depth the feelings of loss in parents of children diagnosed with autism spectrum disorder. A qualitative study was conducted based on grounded theory. Twenty parents participated through purposive sampling. Semi-structured interviews were conducted, asking about different emotional aspects of the upbringing of a child with autism spectrum disorder. Atlas.ti 6.2 program was used for open, axial, and selective coding. The core category that explained the feelings of these parents was unexpected child loss, associated with shock, negation, fear, guilt, anger, and/or sadness. Two processes were identified, one associated with the resolution of grief and the other with obstacles to overcoming it. Feelings of loss play an important role in explaining the complex emotions experienced by these parents. Different intervention strategies are proposed. Copyright © 2016 Elsevier Ltd. All rights reserved.
Tufan, Asli; Ilhan, Birkan; Bahat, Gulistan; Karan, Mehmet Akif
Sleep disorders are commonly under-diagnosed in the geriatric population. We aimed to determine the prevalence of sleep problems among older adults admitted to the geriatrics out-patient clinic. Two hundred and three patients (136 female) older than 75 years of age were included in the study. Patients underwent comprehensive geriatric assessment, including identification of sleep problems using the Sleep Disturbance Scale, Rapid eye movement (REM) sleep behavior disorder (RBD) Single-Question Screen questionnaire (RBD1Q) and The Johns Hopkins Restless Leg Syndrome Severity Scale. Demographic and clinical data including age, sex, medications, comorbid diseases, body mass index and functional scores was noted. The mean age of the patients was 80.92±4.3 years. 35.5% of the patients had findings of REM-SBD and 32.5% of the patients had restless legs syndrome. Ninety-seven percent of the patients answered 'yes' to at least one of the sleep disturbance scale questions. There was no significant difference between male and female groups. We observed that sleep disorders were common among older adults. For this reason, the course and quality of sleep should be examined in all patients as a routine part of comprehensive geriatric assessment.
Falcus, Craig; Johnson, Darren
This study explored the violent offence accounts of life-sentenced prisoners diagnosed with comorbid antisocial personality disorder (ASPD) and borderline personality disorder (BPD). The aim of the current study was to gain needed clinical insight into the mechanisms involved in this specific group offenders' use of violence against others. Six adult male personality-disordered offenders were interviewed via a semistructured interview schedule to collate individual offence accounts. Interview transcripts were analyzed by the lead researcher (first author) using interpretative phenomenological analysis (IPA) who compared and contrasted findings to develop superordinate themes across the group. External auditing analysis was conducted by the second researcher. Four superordinate themes resulted. These were "A victim of a hostile and rejecting world," "Self as unacceptable to others," "Unwanted emotions that cannot be tolerated or controlled," and "Violent revenge as catharsis." The results support the view that emotional dysregulation is central in driving acts of violence in those with comorbid ASPD/BPD; nevertheless, shame was particularly prevalent. Thus an argument is made for the adaptation of evidence-based treatments for this specific forensic population to ensure a particular focus on helping men tolerate feelings of shame. The limitations of the study are also discussed.
The Danish High Risk and Resilience Study--VIA 7--a cohort study of 520 7-year-old children born of parents diagnosed with either schizophrenia, bipolar disorder or neither of these two mental disorders.
Thorup, Anne A E; Jepsen, Jens Richardt; Ellersgaard, Ditte Vestbjerg; Burton, Birgitte Klee; Christiani, Camilla Jerlang; Hemager, Nicoline; Skjærbæk, Mette; Ranning, Anne; Spang, Katrine Søborg; Gantriis, Ditte Lou; Greve, Aja Neergaard; Zahle, Kate Kold; Mors, Ole; Plessen, Kerstin Jessica; Nordentoft, Merete
Severe mental illnesses like schizophrenia and bipolar disorder are known to be diseases that to some extent, but not entirely can be understood genetically. The dominating hypothesis is that these disorders should be understood in a neurodevelopmental perspective where genes and environment as well as gene-environment-interactions contribute to the risk of developing the disease. We aim to analyse the influences of genetic risk and environmental factors in a population of 520 7-year-old children with either 0, 1 or 2 parents diagnosed with schizophrenia spectrum psychosis or bipolar disorder on mental health and level of functioning. We hypothesize that a larger proportion of children growing up with an ill parent will display abnormal or delayed development, behavioural problems or psychiatric symptoms compared to the healthy controls. We are establishing a cohort of 5207 year old children and both their parents for a comprehensive investigation with main outcome measures being neurocognition, behaviour, psychopathology and neuromotor development of the child. Parents and children are examined with a comprehensive battery of instruments and are asked for genetic material (saliva or blood) for genetic analyses. The participants are recruited via Danish registers to ensure representativity. Data from registers concerning social status, birth complications, somatic illnesses and hospitalization are included in the database. Psychological and relational factors like emotional climate in the family, degree of stimulation and support in the home and attachment style are also investigated. Data collection started January 1, 2013, and is successfully ongoing. By Aug 2015 424 families are included. About 20% of the invited families decline to participate, equal for all groups.
Leaf, Justin B; Leaf, Jeremy A; Milne, Christine; Taubman, Mitchell; Oppenheim-Leaf, Misty; Torres, Norma; Townley-Cochran, Donna; Leaf, Ronald; McEachin, John; Yoder, Paul
In this study we evaluated a social skills group which employed a progressive applied behavior analysis model for individuals diagnosed with autism spectrum disorder. A randomized control trial was utilized; eight participants were randomly assigned to a treatment group and seven participants were randomly assigned to a waitlist control group. The social skills group consisted of 32, 2 h sessions. Teachers implemented a variety of behaviorally based procedures. A blind evaluator measured participants' behavior immediately prior to intervention, immediately following intervention, and during 16 and 32-week maintenance probes. Results of the study demonstrated that participants made significant improvements with their social behavior (p < .001) following intervention, and the results were maintained up to 32 weeks after intervention had concluded.
Svanborg, P; Gustavsson, P J; Mattila-Evenden, M; Asberg, M
Although an operationalized and commonly accepted definition of maladaptiveness is lacking, the delineation of personality traits as being adaptive or maladaptive is essential in diagnosing personality disorders (PDs). A way to explore the meaning of maladaptiveness is to compare how patients from all DSM-III-R PDs relate to different traits and dimensions of various dimensional models of personality. In the present study, the Karolinska Scales of Personality (KSP) were used in a sample of 94 psychiatric outpatients who were assessed according to severity of maladaption and according to type of predominant cluster type of deviant traits. Only one of four factors of the scores of the KSP subscales, "Interpersonal Aversiveness," was related to degree of maladaption, indicating high detachment, suspicion, irritability, dysphoria, and low socialization as core features of maladaptiveness. Three subscales of the KSP Socialization were all associated with maladaptiveness. However, one subscale, "Childhood Adjustment," was also related to the predominant cluster type of personality pathology.
Posluszny, Donna M; Dougall, Angela Liegey; Johnson, Jonas T; Argiris, Athanassios; Ferris, Robert L; Baum, Andrew; Bovbjerg, Dana H; Dew, Mary Amanda
Head and neck cancer is a life-threatening illness requiring aversive treatments. Despite clear potential for posttraumatic stress disorder (PTSD) symptoms in both patients and their partners, research is scant. Newly diagnosed patients and partners (number of dyads = 42) completed questionnaires to assess symptoms of PTSD, anxiety, and depression, as well as demographic, medical, and attitudinal variables. Partners had higher average levels of PTSD symptoms than patients (p = .023). More partners (28.6%) met criteria for estimated PTSD caseness than did patients (11.9%). There were no significant differences in levels of other anxiety or depression symptoms. Perceived threat of disease appeared to be a stronger correlate of PTSD symptom levels than medical variables in patients and partners. A diagnosis of head and neck cancer elicits significant levels of PTSD symptoms in patients, and even higher levels among partners. Identified correlates of distress, including perceived threat of disease, are potential intervention targets. © 2014 Wiley Periodicals, Inc.
Ramos, Vera; Canta, Guilherme; de Castro, Filipa; Leal, Isabel
Research suggests that borderline personality disorder (BPD) can be diagnosed in adolescents and is marked by considerable heterogeneity. This study aimed to identify personality features characterizing adolescents with BPD and possible meaningful patterns of heterogeneity that could lead to personality subgroups. The authors analyzed data on 60 adolescents, ages 15 to 18 years, who met DSM criteria for a BPD diagnosis. The authors used latent class analysis (LCA) to identify subgroups based on the personality pattern scales from the Millon Adolescent Clinical Inventory (MACI). LCA indicated that the best-fitting solution was a two-class model, identifying two discrete subgroups of BPD adolescents that were described as internalizing and externalizing. The subgroups were then compared on clinical and sociodemographic variables, measures of personality dimensions, DSM BPD criteria, and perception of attachment styles. Adolescents with a BPD diagnosis constitute a heterogeneous group and vary meaningfully on personality features that can have clinical implications for treatment.
Delia L. Lang
Full Text Available Objective. Despite recommendations for concurrent use of contraceptives and condoms to prevent unintended pregnancy and STIs, multimethod contraceptive use among women is poor. This study examined individual-, interpersonal-, and environmental-level factors that predict multimethod use among sexually active adolescent women diagnosed with psychological disorders. Methods. This multisite study analyzed data from 288 sexually active adolescent women who provided sociodemographic, psychosocial, and behavioral data related to birth control and condom use. Results. 34.7% of the participants reported multimethod use in the past three months. Controlling for empirically and theoretically relevant covariates, a multivariable logistic regression identified self-efficacy, multiple partners, pregnancy history, parental communication, parental norms about sex, and neighborhood cohesion as significant predictors of multimethod use. Conclusions. While continued targeted messages about multi-method contraceptive use are imperative at the individual level, an uptake in messages targeting interpersonal- and environmental-level factors such as adolescents' parents and the broader community is urgently needed.
Jason, Eva Åndell; Tomson, Torbjörn; Carlsson, Sofia; Tedroff, Kristina; Åmark, Per
To follow children with newly diagnosed unprovoked seizures to determine (1) whether the prevalence of neurodevelopmental comorbidities and cerebral palsy (CP) changed after the initial seizure, and (2) the association between studied comorbidities and seizures 13-24 months after seizure onset or initiation of treatment. Analyses were based on 750 children (28 days-18 years) with a first unprovoked seizure (index) included in a population-based Incidence Registry in Stockholm between 2001 and 2006. The children were followed for two years and their medical records were examined for a priori defined neurodevelopmental/psychiatric comorbidities and CP and seizure frequency. Baseline information was collected from medical records from before, and up to six months after, the index seizure. Odds ratios (OR) of repeated seizures 13-24 months after the first seizure or after initiation of anti-epileptic drug treatment was calculated by logistic regression and adjusted for age and sex. At baseline, 32% of the children had neurodevelopmental/psychiatric comorbidities or CP compared to 35%, 24 months later. Children with such comorbidities more often experienced seizures 13-24 months after the index seizure (OR 2.87, CI 2.07-3.99) with the highest OR in those with CP or attention deficit hyperactivity disorder (ADHD). Children diagnosed at age neurodevelopmental comorbidities and CP in children with epilepsy tend to be present already at seizure onset and that such comorbidities are strong indicators of poor outcome regarding seizure control with or without treatment. Copyright © 2018 Elsevier B.V. All rights reserved.
Niebudek-Bogusz, Ewa; Just, Marcin; Tyc, Michał; Wiktorowicz, Justyna; Morawska, Joanna; Śliwińska-Kowalska, Mariola
An objective determination of the range of vocal efficiency is rather difficult. The aim of the study was to assess the possibility of application of short-term acoustic efficiency analysis in diagnosing occupational voice disorders. The study covered 98 people (87 women and 11 men) diagnosed with occupational dysphonia throuigh videostroboscopic examination. The control group comprised 100 people (81 women and 19 men) with normal voices. The short-term acoustic analysis was carried out by means of DiagnoScope software, including classical parameters (Jitter group, Shimmer group and the assessment of noise degree NHR), as well as new short-term efficiency parameters determined in a short time period during sustained phonation of the vowel "a." The results were then compared. Results: The values of all the examined classical parameters were considerably higher in the study group of pathological voices than in the control group of normal voices (p = 0.00). The aerodynamic parameter, maximum phonation time, was significantly shorter by over 0.5 s in the study group than in the control group. The majority of the acoustic efficiency parameters were also considerably worse in the study group of subjects with occupational dysphonia than in the control group (p = 0.00). Moreover, the correlation between the efficiency parameters and most of the classical acoustic parameters in the study group implies that for the voices with occupational pathology the decreased efficiency of the vocal apparatus is reflected in the acoustic voice structure. Effliciency parameters determined during short-term acoustic analysis can be an objective indicator of the decreased phonatory function of the larnx, useful in diagnosing occupational vocal pathology.
Full Text Available Background: An objective determination of the range of vocal efficiency is rather difficult. The aim of the study was to assess the possibility of application of short-term acoustic efficiency analysis in diagnosing occupational voice disorders. Material and Methods: The study covered 98 people (87 women and 11 men diagnosed with occupational dysphonia through videostroboscopic examination. The control group comprised 100 people (81 women and 19 men with normal voices. The short-term acoustic analysis was carried out by means of DiagnoScope software, including classical parameters (Jitter group, Shimmer group and the assessment of noise degree NHR, as well as new short-term efficiency parameters determined in a short time period during sustained phonation of the vowel “a.” The results were then compared. Results: The values of all the examined classical parameters were considerably higher in the study group of pathological voices than in the control group of normal voices (p = 0.00. The aerodynamic parameter, maximum phonation time, was significantly shorter by over 0.5 s in the study group than in the control group. The majority of the acoustic efficiency parameters were also considerably worse in the study group of subjects with occupational dysphonia than in the control group (p = 0.00. Moreover, the correlation between the efficiency parameters and most of the classical acoustic parameters in the study group implies that for the voices with occupational pathology the decreased efficiency of the vocal apparatus is reflected in the acoustic voice structure. Conclusions: Efficiency parameters determined during short-term acoustic analysis can be an objective indicator of the decreased phonatory function of the larynx, useful in diagnosing occupational vocal pathology. Med Pr 2015;66(2:225–234
Taylor, Jeanette; Iacono, William G.
This study tested differences in personality traits measured by the Multidimensional Personality Questionnaire (MPQ) in a community sample of adolescents with definite or probable conduct disorder (CD) diagnoses that did not progress to a diagnosis of antisocial personality disorder (ASPD) by early adulthood (n=43), those with definite or probable…
McFadden, Dennis; Westhafer, J. Gregory; Pasanen, Edward G.; Tucker, David M.; Carlson, Caryn L.
Attention-deficit/hyperactivity disorder (ADHD) is generally acknowledged to be more prevalent in males than in females. Further, some precursors to ADHD appear early in life. Together these facts suggest that ADHD may be influenced by androgenic mechanisms operating early in development. This reasoning raises the question of whether the otoacoustic emissions (OAEs) of children with ADHD are masculinized. Click-evoked OAEs were measured for one click level in 8 boys and 3 girls diagnosed as ADHD/Combined, in 11 males and 5 females diagnosed as ADHD/Inattentive (IA), and in 17 male and 18 female controls. The ages of these samples ranged between 7 and 15. As in adults, the CEOAEs of the control males were weaker than those of the control females. Further, the CEOAEs of the ADHD/IA males were weaker than in the control males (a hypermasculinization) and the CEOAEs of the IA females were weaker than in the female controls (a masculinization). The CEOAEs of the Combined groups were slightly stronger (feminized) than those of the control males and females. One interpretation is that the IA subgroup of ADHD boys and girls (but not the Combined subgroup) was exposed to higher-than-normal levels of androgens sometime early in development. [Work supported by NIDCD.
McEvoy, Beth; O'Connor, John; McCarthy, Odhran
The diagnostic category of social anxiety disorder (SAD) is one that is widely drawn upon in mental health settings; SAD is primarily characterized by a marked fear of social performance situations and possible scrutiny by other people (American Psychiatric Association [APA], 1994, 2013). The current study aims to explore the experiences of people diagnosed with SAD. Psychoanalytically informed research interviews, drawing on psychoanalytic ideas around the parameters of engagement and levels of engagement and analysis, were carried out with 4 male and 2 female participants with diagnoses of SAD. Four themes emerged strongly, reflecting the content and process of interviews: "A Critical Voice," "A Passive Presence," "Failure to Launch," and "Behind the Mask." These emerging themes and the overall findings are conceptualized through a Winnicottian lens, emphasising the role of the good-enough mother and facilitating environment in the struggle of participants to achieve an experience of individuation as well as authenticity with others. Theoretical, clinical, and research implications are discussed, including the need for clinicians to consider the role of early parent-child dynamics and the overall home environment and what these have left in the here and now for people presenting in this way, particularly in the way services are used and the therapeutic relationship develops. Further research into underlying dynamic issues in the origins and maintenance of social anxiety is proposed.
Huerta, Marisela; Bishop, Somer L; Duncan, Amie; Hus, Vanessa; Lord, Catherine
Substantial revisions to the DSM-IV criteria for autism spectrum disorders (ASDs) have been proposed in efforts to increase diagnostic sensitivity and specificity. This study evaluated the proposed DSM-5 criteria for the single diagnostic category of autism spectrum disorder in children with DSM-IV diagnoses of pervasive developmental disorders (PDDs) and non-PDD diagnoses. Three data sets included 4,453 children with DSM-IV clinical PDD diagnoses and 690 with non-PDD diagnoses (e.g., language disorder). Items from a parent report measure of ASD symptoms (Autism Diagnostic Interview-Revised) and clinical observation instrument (Autism Diagnostic Observation Schedule) were matched to DSM-5 criteria and used to evaluate the sensitivity and specificity of the proposed DSM-5 criteria and current DSM-IV criteria when compared with clinical diagnoses. Based on just parent data, the proposed DSM-5 criteria identified 91% of children with clinical DSM-IV PDD diagnoses. Sensitivity remained high in specific subgroups, including girls and children under 4. The specificity of DSM-5 ASD was 0.53 overall, while the specificity of DSM-IV ranged from 0.24, for clinically diagnosed PDD not otherwise specified (PDD-NOS), to 0.53, for autistic disorder. When data were required from both parent and clinical observation, the specificity of the DSM-5 criteria increased to 0.63. These results suggest that most children with DSM-IV PDD diagnoses would remain eligible for an ASD diagnosis under the proposed DSM-5 criteria. Compared with the DSM-IV criteria for Asperger's disorder and PDD-NOS, the DSM-5 ASD criteria have greater specificity, particularly when abnormalities are evident from both parents and clinical observation.
Oh, Sechang; Kwon, Hyeokjun; Varadan, Vijay K.
Good sleep is critical for one's overall physical and mental health but more than 50 million Americans have experienced or are suffering from sleep disorders. Nevertheless, 85% of them remain undiagnosed or untreated. They can lead to chronic diseases. Sleep disorders are diagnosed through polysomnography, also known as sleep study, performed in a sleep laboratory overnight. This perturbs his/her daily sleep routine, and consequently, an accurate diagnosis cannot be made. Many companies have been developing home sleep test systems to reduce the cost of sleep studies and provide a more convenience solution to patients. The category of the system varies as type II, type III and type IV according to the type of sleep study. Current systems cannot be easily extended from one type to include a higher type. A patient who has a type III system to diagnose sleep apnea should additionally purchase a type II system which has functions that overlap with a type III system, to evaluate sleep stages. In this paper, we propose a wireless telemedicine system for easy extension of channels using the start network topology of the Zigbee protocol. The HST system consists of two wireless HST devices with a Zigbee module, a wireless HST receiver with both a Zigbee and a Wi-Fi module, and a sever which monitors/saves the physiological signals. One transmitter provides 5 channels for 2x EOG, 2x EEG and EMG to evaluate sleep stages. The other transmitter provides 5 additional channels for ECG, nasal air flow, body position, abdominal/chest efforts and oxygen saturation to diagnose sleep apnea. These two transmitters, acting as routers, and the receiver as a coordinator form a Zigbee star network. The data from each transmitter in the receiver are retransmitted to the monitoring unit through Wi-Fi. By building a star network with Zigbee, channels can be easily extended so that low level systems can be upgraded to higher level systems by simply adding the necessary channels. In addition
Gómez-Romero, M; Jiménez-Palomares, M; Rodríguez-Mansilla, J; Flores-Nieto, A; Garrido-Ardila, E M; González López-Arza, M V
Dementia is characterised by cognitive deterioration and the manifestation of psychological and behavioural symptoms, especially changes in perception, thought content, mood, and conduct. In addition to drug therapy, non-pharmacological treatments are used to manage these symptoms, and one of these latter treatments is music therapy. Since this novel technique in non-verbal, it can be used to treat patients with dementia at any stage, even when cognitive deterioration is very severe. Patients' responses to music are conserved even in the most advanced stages of the disease DEVELOPMENT: A literature research was carried out using the following databases: Academic Search Complete, PubMed, Science Direct y Dialnet. The period of publication was 2003 to 2013 and the search keywords were 'Music Therapy, Dementia, Behaviour, Behaviour Disorders y Behavioural Disturbances'. Out of the 2188 studies that were identified, 11 studies met inclusion criteria for the systematic review. Music therapy is beneficial and improves behavior disorders, anxiety and agitation in subjects diagnosed with dementia. Copyright © 2014 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.
Fernanda Mara de Paiva Bertoli
Full Text Available The prevalence of signs and symptoms of temporomandibular disorders (TMD increases during adolescence and adulthood. Few studies have examined TMD prevalence in Brazilian adolescents.To investigate the prevalence of TMD in Brazilian adolescents.A representative population-based sample of 934 adolescents (10-14-years-old was examined. TMD screening was performed using a questionnaire by the American Academy of Orofacial Pain. TMD diagnoses used research diagnostic criteria for temporomandibular disorders (RDC/TMD-Axis-I. Examinations were performed by a single calibrated examiner (kappa > 0.80.The prevalence of TMD symptoms was 34.9%; the most frequently reported symptoms were headache and neck ache (20.9%, followed by joint sounds (18.5%. Myofascial pain was the most prevalent type (10.3%, followed by disc displacement with reduction (8.0% and arthralgia (3.5%. There was a significant association between sex and TMD symptoms; prevalence was significantly higher in girls (RP = 1.37; 95% CI = 1.14-1.65; p = 0.001. Myofascial pain of TMD and displacement with reduction were more prevalent in girls (RP = 1.76; p = 0.007 and RP = 2.06; p = 0.004, respectively.TMD symptoms were present in 34.9% of adolescents, with myofascial pain being the most prevalent type (10.3%. TMD was significantly more common in girls. Routine pediatric dental care should include a TMD screening.
Janet C'de Baca
Full Text Available Personality Disorders (PDs impair the ability to function socially and occupationally. PD prevalence rates among veterans who have also been diagnosed with posttraumatic stress disorder (PTSD range from 45%–79%. This study examined ethnic differences in PDs assessed with the Millon Clinical Multiaxial Inventory-III in 260 non-Hispanic white (64%, Hispanic (27%, and African American (9%, mostly single, women veterans in treatment for PTSD. After adjusting for covariates including number and sexual-nature of trauma, findings revealed the adjusted odds ratio of having a cluster A PD was almost three times higher for African Americans (p = 0.046 then the other two ethnic groups, which may be driven by the paranoid PD scale and potentially reflects an adaptive response to racial discrimination. In cluster designation analysis, the odds were twice as high of having a cluster B PD with childhood trauma (p = 0.046, and a cluster C PD with sexual trauma (p = 0.004, demonstrating the significance of childhood and sexual trauma on long-term chronic personality patterns in women veterans. These results highlight the importance of using instruments with demonstrated diagnostic validity for minority populations.
Blázquez, Ana; Mas, Sergi; Plana, Maria Teresa; Gassó, Patricia; Méndez, Iria; Torra, Mercè; Arnaiz, Joan Albert; Lafuente, Amàlia; Lázaro, Luisa
Fluoxetine (FLX) has been one of the most widely studied selective serotonin reuptake inhibitors in adolescents. Despite its efficacy, however, 30% to 40% of patients do not respond to treatment. The aim of this study was to evaluate whether clinical improvement or adverse events are related to the corrected dose of FLX at 8 and 12 weeks after starting treatment in a sample of adolescents diagnosed with major depressive disorder, obsessive-compulsive disorder, or generalized anxiety disorder. Seventy-four subjects aged between 10 and 17 years participated in the study. Clinical improvement was measured with the Clinical Global Impression-Improvement Scale, whereas the UKU (Udvalg for Klinske Undersogelser) scale was administered to assess adverse effects of treatment. Fluoxetine per kilograms of body weight was related to serum concentration of FLX, NORFLX (norfluoxetine), FLX + NORFLX, and FLX/NORFLX. No relationship was found between dose-corrected FLX levels and therapeutic or adverse effects. No differences in serum concentrations were found between responders and nonresponders to treatment. Sex differences were observed in relation to dose and FLX serum concentration. The analysis by diagnosis revealed differences in FLX dose between obsessive-compulsive disorder patients and both generalized anxiety disorder and major depressive disorder patients. Fluoxetine response seems to be influenced by factors such as sex, diagnosis, or certain genes that might be involved in the drug's pharmacokinetics and pharmacodynamics. Clinical and pharmacogenetic studies are needed to elucidate further the differences between treatment responders and nonresponders.
Michalska-Leśniewicz, Magdalena; Gruszczyński, Wojciech
The essential element of the functioning of patients is the assessment of quality of life and its determinants. Taking into account the depression process and its specific nature this seems to be of special importance. The aim of this paper was the assessment of importance of psychological determinants of quality of life in women with depressive disorders. The tests were carried out on the basis of the analysis of medical documentation, including the psychiatric records. The following criteria were measured: depression level (Beck Hopelessness Scale), quality of life (The Life Satisfaction Questionnaire FLZ according to Fahrenberg), personality model (NEO Five-Factor Inventory), optimism (The Life Orientation Test-Revised LOT-R by M. Scheier, ChS. Carver and M. Bridges adapted by R. Poprawa and Z. Juczyński), purpose in life (The Purpose-in-Life Test developed by Crumbaugh and Maholick according to the authorised translation by Z. Płuzek), social support (The Social Support Questionnaire by Sommer G, Fydrich T, 1989 adapted by Z. Juczyński), health satisfaction (General Health Questionnaire GHQ 28 by David Goldberg). Women diagnosed with depressive disorders were qualified for testing. The tested group of women included 80 patients in the age bracket of 40 to 60 years from the Outpatient Department of Mental Health, Regional Specialised Hospital in Zgierz. The reference group consisted of 30 women showing no symptoms of depressive disorders. The statistical analysis of variables taken into account in the tests showed essential statistical differences between the compared groups with regard to almost all parameters. Significant differences were found in respect of life satisfaction, personality variables, social support, health satisfaction and purpose in life. The obtained results showed significant differences regarding the assessment of quality of life between the group of women with depressive disorders and the group of women without any symptoms of such
Black, Donald W; Shaw, Martha; Allen, Jeff
The authors assessed clinical symptoms and self-reported shopping and spending behavior in people diagnosed with compulsive shopping (CS) at a 5-year follow-up interview. All met the criteria of McElroy et al. for lifetime CS and had the disorder for >1year. Structured and semistructured instruments and self-report questionnaires were used to collect data. Of the original 26 subjects, 17 (65%) were interviewed and are the focus of this report. At follow-up, their ages ranged from 23 to 67years (mean=44years). Lifetime psychiatric comorbidity was common, but few had current psychiatric disorders at follow-up. Interest in shopping and spending decreased for eight (47%), stayed the same for five (29%), and increased for four (24%) subjects. Eleven subjects (65%) reported having attempted to quit their CS and three (18%) reported successfully doing so. Triggers for returning to CS included feelings of pressure/excitement/tension to shop; boredom; negative feelings such as sadness, depression, frustration, or anger; and the desire for positive feelings like happiness, power, or elation. Mean scores on the Compulsive Buying Scale (CBS) and the shopping version of the Yale-Brown Obsessive-Compulsive Scale showed overall improvement in CS symptoms (d=1.16 and d=-1.19, respectively); subjects were also less impulsive (d=-0.48). At baseline and follow-up, those with a lifetime mood disorder tended to have greater CS severity. While the subjects showed overall improvement, most had ongoing symptoms of CS. The implications of the findings are discussed. Copyright © 2016 Elsevier Inc. All rights reserved.
Yıldız, Yılmaz; Dursun, Ali; Tokatlı, Ayşegül; Coşkun, Turgay; Sivri, Hatice Serap
Phenylketonuria, previously a common cause of severe intellectual disability, is a metabolic disorder now promptly diagnosed and effectively treated thanks to newborn screening programs. Here, we report a male patient presenting with dyslexia and attention-deficit hyperactivity disorder, who was diagnosed with mild phenylketonuria at eight years of age. Earlier recognition and treatment before the establishment of irreversible brain damage would have resulted in better neurobehavioural outcomes. Classical phenylketonuria and milder phenotypes of phenylalanine hydroxylase deficiency need to be considered in the differential diagnosis of all cognitive and behavioural problems of unknown cause.
Full Text Available Successful automated diagnoses of attention deficit hyperactive disorder (ADHD using imaging and functional biomarkers would have fundamental consequences on the public health impact of the disease. In this work, we show results on the predictability of ADHD using imaging biomarkers and discuss the scientific and diagnostic impacts of the research. We created a prediction model using the landmark ADHD 200 data set focusing on resting state functional connectivity (rs-fc and structural brain imaging. We predicted ADHD status and subtype, obtained by behavioral examination, using imaging data, intelligence quotients and other covariates. The novel contributions of this manuscript include a thorough exploration of prediction and image feature extraction methodology on this form of data, including the use of singular value decompositions, CUR decompositions, random forest, gradient boosting, bagging, voxel-based morphometry and support vector machines as well as important insights into the value, and potentially lack thereof, of imaging biomarkers of disease. The key results include the CUR-based decomposition of the rs-fc-fMRI along with gradient boosting and the prediction algorithm based on a motor network parcellation and random forest algorithm. We conjecture that the CUR decomposition is largely diagnosing common population directions of head motion. Of note, a byproduct of this research is a potential automated method for detecting subtle in-scanner motion. The final prediction algorithm, a weighted combination of several algorithms, had an external test set specificity of 94% with sensitivity of 21%. The most promising imaging biomarker was a correlation graph from a motor network parcellation. In summary, we have undertaken a large-scale statistical exploratory prediction exercise on the unique ADHD 200 data set. The exercise produced several potential leads for future scientific exploration of the neurological basis of ADHD.
Eloyan, Ani; Muschelli, John; Nebel, Mary Beth; Liu, Han; Han, Fang; Zhao, Tuo; Barber, Anita D; Joel, Suresh; Pekar, James J; Mostofsky, Stewart H; Caffo, Brian
Successful automated diagnoses of attention deficit hyperactive disorder (ADHD) using imaging and functional biomarkers would have fundamental consequences on the public health impact of the disease. In this work, we show results on the predictability of ADHD using imaging biomarkers and discuss the scientific and diagnostic impacts of the research. We created a prediction model using the landmark ADHD 200 data set focusing on resting state functional connectivity (rs-fc) and structural brain imaging. We predicted ADHD status and subtype, obtained by behavioral examination, using imaging data, intelligence quotients and other covariates. The novel contributions of this manuscript include a thorough exploration of prediction and image feature extraction methodology on this form of data, including the use of singular value decompositions (SVDs), CUR decompositions, random forest, gradient boosting, bagging, voxel-based morphometry, and support vector machines as well as important insights into the value, and potentially lack thereof, of imaging biomarkers of disease. The key results include the CUR-based decomposition of the rs-fc-fMRI along with gradient boosting and the prediction algorithm based on a motor network parcellation and random forest algorithm. We conjecture that the CUR decomposition is largely diagnosing common population directions of head motion. Of note, a byproduct of this research is a potential automated method for detecting subtle in-scanner motion. The final prediction algorithm, a weighted combination of several algorithms, had an external test set specificity of 94% with sensitivity of 21%. The most promising imaging biomarker was a correlation graph from a motor network parcellation. In summary, we have undertaken a large-scale statistical exploratory prediction exercise on the unique ADHD 200 data set. The exercise produced several potential leads for future scientific exploration of the neurological basis of ADHD.
Kjellgren, Anette; Edebol, Hanna; Nordén, Tommy; Norlander, Torsten
The aim of this single-subject study was to report experiences from one and a half years of regular floating as described by a person with neuropsychiatric and mental health disorders. Floating, or Flotation Restricted Environmental Stimulation Technique, involves relaxation and sensory deprivation by means of resting in a tank with highly salted and body-tempered water. The subject, a 24-year-old woman diagnosed with attention deficit hyperactivity disorder, atypical autism, post-traumatic s...
Rubinsky, Anna D; Chen, Cheng; Batki, Steven L; Williams, Emily C; Harris, Alex H S
Patients with alcohol use disorder (AUD) and another co-occurring psychiatric disorder are a vulnerable population with high symptom severity. Such patients may benefit from a full arsenal of treatment options including pharmacotherapy. Receipt of AUD pharmacotherapy is generally very low despite recommendations that it be made available to every patient with AUD, including those with co-occurring disorders. Little is known about pharmacotherapy rates for AUD compared to other psychiatric disorders among patients with dual diagnoses. This study compared rates of pharmacotherapy for AUD to those for non-substance use psychiatric disorders and tobacco use disorder among patients with dual diagnoses in the U.S. Veterans Affairs (VA) healthcare system. VA data were used to identify patients with AUD and another psychiatric disorder in fiscal year 2012, and to estimate the proportion receiving pharmacotherapy for AUD and for each comorbid condition. Among subsets of patients with AUD and co-occurring schizophrenic, bipolar, posttraumatic stress or major depressive disorder, receipt of medications for AUD ranged from 7% to 11%, whereas receipt of medications for the comorbid disorder ranged from 69% to 82%. Among patients with AUD and co-occurring tobacco use disorder, 6% received medication for their AUD and 34% for their tobacco use disorder. Among patients with dual diagnoses, rates of pharmacotherapy for AUD were far lower than those for the comorbid disorders and contrary to evidence that medications for AUD are effective. Additional system-wide implementation efforts to identify and address patient- and provider-level barriers are needed to increase AUD pharmacotherapy in this high-need population. Published by Elsevier Ltd.
Background DSM-IV eating disorder (ED) diagnoses have been criticized for lack of clinical utility, diagnostic instability, and over-inclusiveness of the residual category “ED not otherwise specified” (EDNOS). Revisions made in DSM-5 attempt to generate a more scientifically valid and clinically relevant system of ED classification. The aim with the present study was to examine clinical characteristics and distinctiveness of the new DSM-5 ED diagnoses, especially concerning purging disorder (PD). Methods Using a large naturalistic Swedish ED database, 2233 adult women were diagnosed using DSM-5. Initial and 1-year follow-up psychopathology data were analyzed. Measures included the Eating Disorder Examination Questionnaire, Structural Eating Disorder Interview, Clinical Impairment Assessment, Structural Analysis of Social Behavior, Comprehensive Psychiatric Rating Scale, and Structured Clinical Interview for DSM-IV Axis I Disorders. Results Few meaningful differences emerged between anorexia nervosa binge/purge subtype (ANB/P), PD, and bulimia nervosa (BN). Unspecified Feeding and Eating Disorders (UFED) showed significantly less severity compared to other groups. Conclusions PD does not appear to constitute a distinct diagnosis, the distinction between atypical AN and PD requires clarification, and minimum inclusion criteria for UFED are needed. Further sub-classification is unlikely to improve clinical utility. Instead, better delineation of commonalities is important. PMID:24999410
Gonçalves, Daniela A G; Camparis, Cinara M; Speciali, José G; Franco, Ana L; Castanharo, Sabrina M; Bigal, Marcelo E
Temporomandibular disorders (TMDs) are considered to be comorbid with headaches. Earlier population studies have suggested that TMD may also be a risk factor for migraine progression. If that is true, TMD should be associated with specific headache syndromes (eg, migraine and chronic migraine), but not with headaches overall. Accordingly, our aim was to explore the relationship between TMD subtypes and severity with primary headaches in a controlled clinical study. The sample consisted of 300 individuals. TMDs were assessed using the Research Diagnostic Criteria for TMD, and primary headache was classified according to International Classification for Headache Disorders-2. Univariate and multivariate models assessed headache diagnoses and frequency as a function of the parameters of TMD. Relative to those without TMD, individuals with myofascial TMD were significantly more likely to have chronic daily headaches (CDHs) [relative risk (RR)=7.8; 95% confidence interval (CI), 3.1-19.6], migraine (RR=4.4; 95% CI, 1.7-11.7), and episodic tension-type headache (RR=4.4; 95% CI, 1.5-12.6). Grade of TMD pain was associated with increased odds of CDH (Pheadache (Pheadache frequency. In multivariate analyses, TMD was associated with migraine and CDH (P=0.001). Painful TMD (P=0.0034) and grade of TMD pain (Pheadache frequency. TMD, TMD subtypes, and TMD severity are independently associated with specific headache syndromes and with headache frequency. This differential association suggests that the presence of central facilitation of nociceptive inputs may be of importance, as positive association was observed only when muscular TMD pain was involved.
Factors Associated With Participation and Change Over Time in Domestic Life, Peer Relations, and School for Adolescents With and Without Self-Reported Neurodevelopmental Disorders. A Follow-Up Prospective Study
Full Text Available Even though participation in everyday events is a vital part in the fulfillment of human rights, adolescents with neurodevelopmental disorders (NDD often face participation restrictions in every-day activities. Few studies have investigated the predictors for participation in different contexts, over time and in relation to the same outcome variables.Objective: Objective of the current study was therefore to investigate predictors of change in participation operationalized as frequency of attendance and perceived importance in domestic life activities, peer related activities, and school activities as experienced by adolescents with and without self-reported neurodevelopmental disorders.Method: Associations with participation, both in terms of frequency and perceived importance, in domestic life, peer relations, and the school setting were investigated using six independent variables measuring experience of time and self, sex, age, stress, support from siblings, and atmosphere in family at two-time (with ~2 years in between. The sample consisted of adolescents with and without self-reported NDD (n = 916. Adolescents with self-reported NDD were n = 154 and adolescents without self-reported NDD was n = 762. Data was collected via self-reported questionnaires administered in schools.Results: Three key findings are presented. (1 more factors were associated with participation outcomes at time1 for adolescents without NDD than for adolescents with NDD, but this difference in the number of factors decreases with time; (2 few associations were related to time for both adolescents with and without NDD; and (3 patterns of predicting variables were different for adolescents with and without NDD.Conclusion: The findings indicate that the factors related to participation in and outside school differs between groups, when the impairment or disability is not considered as a predictor for participation. This study supports the need for using a multidimensional
Pettersson, Erik; Anckarsäter, Henrik; Gillberg, Christopher; Lichtenstein, Paul
Background: Although neurodevelopmental disorders are demarcated as discrete entities in the Diagnostic Statistical Manual of mental disorders, empirical evidence indicates that there is a high degree of overlap among them. The first aim of this investigation was to explore if a single general factor could account for the large degree of observed…
Magnin, E; Maurs, C
Attention-Deficit/Hyperactivity Disorder (ADHD), although considered a childhood-onset neurodevelopmental condition, is nevertheless a frequent and disabling condition in adults. A proportion of such patients are not diagnosed during childhood or adolescence, as diagnosis of the syndrome is rather complex, especially when other psychiatric, neurological or other neurodevelopmental conditions are also associated, yet comorbidities and consequences of ADHD are frequently observed in adults and older populations. As ADHD patients present to memory clinics with attentional and executive disorders, neuropsychological examinations of undiagnosed ADHD patients may reveal atypical cognitive profiles that can complicate the usual diagnostic procedure and increase the risk of delayed diagnosis or misdiagnosis. Thus, explorations of cognitive and/or behavioral disorders in adult populations should systematically screen for this neurodevelopmental condition. Accurate diagnosis could lead to non-pharmaceutical and/or pharmaceutical treatments to improve symptoms and quality of life for adult ADHD patients. Copyright © 2017 Elsevier Masson SAS. All rights reserved.
Welsh, Justine Wittenauer; Knight, John R; Hou, Sherry Shu-Yeu; Malowney, Monica; Schram, Patricia; Sherritt, Lon; Boyd, J Wesley
Adolescents with substance use disorders are more likely to have a current psychiatric disorder. However, when compared with the adult literature, there is relatively limited information regarding the specific co-occurrence of certain mental health diagnoses and substance use disorders in adolescents. The objectives of this study were to build on the previous literature regarding mental health diagnoses and different types of substance use disorders in adolescents, as well as explore the differences, if any, between groupings of mental health diagnosis and type of substance used. Data were extracted from the clinical records of 483 individuals aged 11-24 years referred for an evaluation at the Adolescent Substance Abuse Program at Boston Children's Hospital. According to DSM-IV-Text Revision criteria, individuals received diagnoses of substance abuse or dependence and any additional psychiatric disorders. Problematic use was included within the sample for greater power analysis. A multivariable logistic regression model estimated the association between psychiatric diagnosis and substance use while adjusting for covariates including age and gender. Multiple significant associations were found, including having any anxiety-related diagnosis and opioid use (odds ratio [OR] = 2.23, p < .001), generalized anxiety disorder and opioids (OR = 3.42, p = .008), cocaine and post-traumatic stress disorder (OR = 3.61, p = .01), and marijuana and externalizing behavior disorders (OR = 2.10, p = .024). Our study found multiple significant associations between specific substances and certain co-occurring psychiatric disorders. The use of office screening systems to efficiently identify these youths should be a part of routine medical and psychiatric care. Copyright © 2017 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.
Gilderthorp, Rosanna C.
This study aimed to critically review all studies that have set out to evaluate the use of eye movement desensitization and reprocessing (EMDR) for people diagnosed with both intellectual disability (ID) and post-traumatic stress disorder (PTSD). Searches of the online databases Psych Info, The Cochrane Database of Systematic Reviews, The Cochrane…
Meurs, Maaike; Roest, Annelieke M.; Wolffenbuttel, Bruce H. R.; Stolk, Ronald P.; de Jonge, Peter; Rosmalen, Judith G. M.
Objective To compare the odds of depressive and anxiety disorders for participants with diagnosed diabetes, participants with diabetes but unaware of this, and participants without diabetes. Such knowledge might improve etiological insight into psychopathology in diabetes. Methods Data of 90,686
Ryder, Richard R., Jr.
The intention of the this qualitative study was to explore the perceptions of military combat veteran college students (MCVCS) who self-identify as having been diagnosed with Posttraumatic Stress Disorder (PTSD). They were offered the opportunity to answer questions on the experiences they have in higher education. The study inquired on the…
Emanuel, M. H.; Wamsteker, K.; Lammes, F. B.
To determine the predictive value of dilatation and curettage (D&C) for diagnosing intrauterine disorders in patients with persistent abnormal uterine bleeding. An observational descriptive study was performed in a large university-affiliated teaching hospital. The suspicion of intrauterine
Emin Mehmet Ceylan
Full Text Available Meningiomas are mostly benign tumors of the meninges that may stay clinically silent or present first with psychiatric symptoms only. We present a case of medial cranial fossa meningioma that was first diagnosed as mixed anxiety disorder with dissociative symptoms and vertigo. In light of the intact neurological and vestibular system examination, our patient’s vertigo and depersonalization were firstly addressed as psychosomatic symptoms of the psychiatric syndrome. Despite decreased anxiety and improved mood, dissociative symptoms and vertigo were resistant to treatment which prompted further research yielding a left hemisphere localized meningioma. Resection of meningioma resulted in full remission of the patient proving it to be responsible for the etiology of the psychiatric syndrome and vertigo. We suggest that brain imaging should be performed for patients with late-onset (>50 years psychiatric symptoms and those with treatment resistance. It is important to keep in mind always that medically unexplained symptoms may become explicable with detailed assessment and regular follow-up of the patient.
Sanders, Avihay; Szymanski, Kate; Fiori, Kate
In order to cope with the diagnosis of mental illness in a family member, siblings may be forced to adjust their roles in the family. Taking into account the crucial role that some siblings play in caregiving for the mentally ill especially when the parents are no longer available, it is imperative to develop awareness of their unique needs and address them. Thirty-three adult siblings of people diagnosed with a mental disorder completed the Role Behaviour Inventory (RBI) and a general questionnaire including open-ended questions regarding the roles they played in their families of origin. Findings from the inventory and general questionnaire suggest that the well siblings score higher on two roles, the Hero and Lost Child, and lower on the Mascot and Scapegoat roles relative to a comparison group (N = 33). Being a sibling caregiver emerged as a risk factor to assume certain dysfunctional roles in the family. Implications for future research and therapy are discussed. © 2013 International Union of Psychological Science.
Kornstein, Susan G; Keck, Paul E; Herman, Barry K; Puhl, Rebecca M; Wilfley, Denise E; DiMarco, Ilyse D
Physician-patient conversations were examined to identify barriers to effective discussions about binge eating disorder (BED) arising from discrepancies in how physicians and patients communicate about BED. Conversations between suspected or diagnosed BED patients (n = 38) and psychiatrists (n = 11) were recorded and the transcripts were reviewed for BED-related lexical terms using automated conversation analysis software. Researchers disambiguated multivalent terms and combined similar terms. The results showed that psychiatrists evaluated some diagnostic criteria (e.g., the absence of compensatory behavior) but not others (e.g., eating more rapidly than normal), focused more on symptoms in relation to weight and generally discussed weight-related issues more often than did patients, and asked about the type of food consumed more often than the diagnostic criterion related to the quantity of food consumed. In contrast, patients used terminology that attempted to clarify the relationships between feelings, coping strategies, and compulsion to binge eat when discussing binge eating episodes. These findings suggest that educational materials promoting more effective physician-patient dialogues regarding eating behaviors in general, and BED specifically, may be beneficial. Conversations should highlight the BED diagnostic criteria, assessment of patients' emotions and sense of lack of control, and relationships between body weight and BED.
Zand, Debra H; Bultas, Margaret W; McMillin, Stephen Edward; Halloran, Donna; White, Taryn; McNamara, Donnamarie; Pierce, Katherine J
Disruptive behaviors can be of comparable or greater concern to parents than the core symptoms of Autism Spectrum Disorder (ASD). Provision of effective interventions to address these behaviors within the first year of initial diagnosis holds great potential for improving the child's, parents', and family's functioning. We piloted a four-session, manualized, positive parenting program on 21 parents of newly diagnosed children ages 2 through 12 years using a mixed methods design. Seventy-five percent of parents completed four sessions, with 100% reporting high levels of service satisfaction. Preliminary results indicated clinically and statistically significant reductions in child maladaptive behaviors, as well as improvements in parental and family functioning. Practitioners and parents identified several potential implementation adaptations, including additional sessions to focus on ASD education and real-time parent-child interactions. Taken as a whole, these data suggest that a brief positive parenting intervention may be a feasible way to improve child, parent, and family functioning during the first year of ASD diagnosis. Findings point to the need for additional research to determine treatment efficacy and to assist with the identification of moderators and mediators of effects. © 2017 Family Process Institute.
Huri, Meral; Şahin, Sedef; Kayıhan, Hülya
The present study was designed to compare hand function in autistic children with history of upper extremity trauma with that of autistic children those who do not have history of trauma. The study group included total of 65 children diagnosed with autism spectrum disorder (ASD) and was divided into 2 groups: children with trauma history (Group I) and control group (Group II) (Group I: n=28; Group II: n=37). Hand function was evaluated with 9-Hole Peg Test and Jebsen Hand Function Test. Somatosensory function was evaluated using somatosensory subtests of Sensory Integration and Praxis Test. Results were analyzed with Student's t-test and Mann-Whitney U test using SPSS version 20 software. Hand function and somatosensory perception test scores were statistically significantly better in children without upper extremity trauma history (pManual Form Perception and Localization of Tactile Stimuli Test results (p<0.05). Autistic children with upper extremity trauma history had poor somatosensory perception and hand function. It is important to raise awareness among emergency service staff and inform them about strong relationship between somatosensory perception, hand function, and upper extremity trauma in children with ASD in order to develop appropriate rehabilitation process and prevent further trauma.
Santelmann, Hanno; Franklin, Jeremy; Bußhoff, Jana; Baethge, Christopher
The diagnosis of schizoaffective disorder (SAD) is well established in clinical practice but is heavily disputed on theoretical grounds. We analyzed the extent and direction of diagnostic shift in SAD patients. We searched Medline, Embase, and PsycINFO systematically for all studies documenting two diagnostic assessments at different points in time (rediagnosis studies) and used meta-analytic methods to quantify diagnostic shift. Multiple prespecified and post-hoc subgroup analyses (e.g., rater blinding) and meta-regressions (e.g., year of publication) were carried out. We included 31 studies out of 4,415 articles screened: 27 studies on the shift from and 23 studies on the shift to SAD (median time span was two years). A total of 36% of patients with a diagnosis of SAD at first assessment switch, many to schizophrenia (19%), 14% to affective disorders, and 6% to other disorders. Among patients diagnosed with SAD at second assessment, 55% had received a different diagnosis at first assessment, a large portion of whom had been initially diagnosed with affective disorder (24%), schizophrenia (18%), and other disorders (12%). Diagnostic shift in SAD patients is substantial. Psychiatrists need to reassess the diagnosis during the course of the illness and to adjust treatment. Slightly more diagnoses of SAD are changed to schizophrenia than to affective disorders, and among patients rediagnosed with SAD, fewer have been diagnosed with schizophrenia than with affective disorders. Thus, at the diagnostic level, there seems to be a slight trend toward schizophrenia during the course of functional psychoses. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Blood serum concentrations of kynurenic acid in patients diagnosed with recurrent depressive disorder, depression in bipolar disorder, and schizoaffective disorder treated with electroconvulsive therapy.
Olajossy, Marcin; Olajossy, Bartosz; Wnuk, Sebastian; Potembska, Emilia; Urbańska, Ewa
The aim of the present study was to compare blood serum kynurenic acid (KYNA) concentrations measured before ECT and after 1, 6 and 12 electroconvulsive treatment (ECT) sessions in patients with diagnoses of recurrent depressive disorder (RDD), depression in bipolar disorder (DBD) and schizoaffective disorder (SAD). The study group comprised of 50 patients with ICD-10 diagnoses of RDD, DBD and SAD. Blood serum KYNA concentrations were determined and clinical assessment was performed using the MADRS and the GAF scale. Significant differences were found in blood serum KYNA levels between RDD, DBD and SAD patients treated with electroconvulsive therapy and healthy controls: 1) KYNA concentrations in DBD patients measured before ECT and after 12 ECT sessions were significantly lower than in the control group; 2) KYNA concentrations in the serum of RDD patients measured before ECT and after one and 12 ECT sessions were significantly lower than in the control group, while those measured after 6 ECT session did not differ significantly from KYNA concentrations in healthy controls; 3) higher pre-treatment blood serum concentrations of KYNA in DBD patients correlated with a higher number of illness phases and poorer general functioning before treatment; 4) significant relationships were found between higher blood serum concentrations of KYNA in RDD patients after 1 ECT session and male gender, and between higher KYNA concentrations after 6 ECT sessions and increased depression and poorer functioning before treatment in those patients. Results show that KYNA concentrations in all diagnostic groups were lower before ECT (not statistically significant for the SAD group) and that there were no significant changes in those concentrations (compared with the baseline) during ECT.
Masevicius, Fabio D; Dubin, Arnaldo
The Stewart approach-the application of basic physical-chemical principles of aqueous solutions to blood-is an appealing method for analyzing acid-base disorders. These principles mainly dictate that pH is determined by three independent variables, which change primarily and independently of one other. In blood plasma in vivo these variables are: (1) the PCO2; (2) the strong ion difference (SID)-the difference between the sums of all the strong (i.e., fully dissociated, chemically nonreacting) cations and all the strong anions; and (3) the nonvolatile weak acids (Atot). Accordingly, the pH and the bicarbonate levels (dependent variables) are only altered when one or more of the independent variables change. Moreover, the source of H(+) is the dissociation of water to maintain electroneutrality when the independent variables are modified. The basic principles of the Stewart approach in blood, however, have been challenged in different ways. First, the presumed independent variables are actually interdependent as occurs in situations such as: (1) the Hamburger effect (a chloride shift when CO2 is added to venous blood from the tissues); (2) the loss of Donnan equilibrium (a chloride shift from the interstitium to the intravascular compartment to balance the decrease of Atot secondary to capillary leak; and (3) the compensatory response to a primary disturbance in either independent variable. Second, the concept of water dissociation in response to changes in SID is controversial and lacks experimental evidence. In addition, the Stewart approach is not better than the conventional method for understanding acid-base disorders such as hyperchloremic metabolic acidosis secondary to a chloride-rich-fluid load. Finally, several attempts were performed to demonstrate the clinical superiority of the Stewart approach. These studies, however, have severe methodological drawbacks. In contrast, the largest study on this issue indicated the interchangeability of the Stewart and
Weiss, Amy L; Van Haren, Melissa S
The roles and responsibilities of speech-language pathologists and pediatricians have become greater with the changing population demographics in the United States. In some states, the majority of the population belongs to a national cultural minority, eg, New Mexico. Even a state such as Iowa, with only a 5% nonmajority population, has a school-aged population that is almost 10% nonmajority. This growth of diversity is likely to continue. Rather than viewing sensitivity to the influence of culture on language learning and other developmental areas as an "add-on" to a practice, it may be wiser to recognize that approaching all clients with as few assumptions about their behaviors as possible will guarantee nonbiased service delivery for all. Without nonbiased service delivery, incorrect diagnoses and provision of inappropriate therapy become more likely. Fortunately, many resources are available to assist pediatricians and speech-language pathologists in learning about various cultures. Institutional review boards have become more vigilant about the inclusion of a cross-section of subject populations as participants in research studies in addition to protecting the rights of all participants. Funding agencies also have expressed as a priority the inclusion of research subjects from minority populations to add to the information available about the incidence and prevalence of disorders across the range of our potential patients. In a society in which cultural differences are not just defined by race or ethnicity, but by gender, sexual orientation, age, geographic region, and religion, belief systems about disease, disability, and treatment are dynamic entities for health professionals to take into consideration. It is a challenge that speech-language pathologists and pediatricians must meet if they are to provide the best and most appropriate services for their patients.
Musliner, K L; Østergaard, S D
Conversion from unipolar depression (UD) to bipolar disorder (BD) is a clinically important event that should lead to treatment modifications. Unfortunately, recognition of this transition is often delayed. Therefore, the objective of this study was to identify predictors of diagnostic conversion from UD to BD. Historical prospective cohort study based on 91 587 individuals diagnosed with UD in Danish hospital psychiatry between 1995 and 2016. The association between a series of potential predictors and the conversion from UD to BD during follow-up (702 710 person-years) was estimated by means of Cox regression with death as competing risk. During follow-up, 3910 individuals with UD developed BD. The cumulative incidence of conversion was slightly higher in females (8.7%, 95% CI: 8.2-9.3) compared to males (7.7%, 95% CI: 7.0-8.4). The strongest predictor of conversion from UD to BD was parental history of BD (adjusted hazard ratio (aHR) = 2.60, 95% CI: 2.20-3.07)). Other predictors included psychotic depression at the index UD episode (aHR = 1.73, 95% CI: 1.48-2.02), a prior/concomitant non-affective psychosis (aHR = 1.73, 95% CI: 1.51-1.99), and in-patient treatment at the index episode (aHR = 1.76, 95% CI: 1.63-1.91). Diagnostic conversion from UD to BD is predicted by severe depression requiring in-patient treatment, psychotic symptomatology, and parental history of BD. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Mumtaz, Wajid; Ali, Syed Saad Azhar; Yasin, Mohd Azhar Mohd; Malik, Aamir Saeed
Major depressive disorder (MDD), a debilitating mental illness, could cause functional disabilities and could become a social problem. An accurate and early diagnosis for depression could become challenging. This paper proposed a machine learning framework involving EEG-derived synchronization likelihood (SL) features as input data for automatic diagnosis of MDD. It was hypothesized that EEG-based SL features could discriminate MDD patients and healthy controls with an acceptable accuracy better than measures such as interhemispheric coherence and mutual information. In this work, classification models such as support vector machine (SVM), logistic regression (LR) and Naïve Bayesian (NB) were employed to model relationship between the EEG features and the study groups (MDD patient and healthy controls) and ultimately achieved discrimination of study participants. The results indicated that the classification rates were better than chance. More specifically, the study resulted into SVM classification accuracy = 98%, sensitivity = 99.9%, specificity = 95% and f-measure = 0.97; LR classification accuracy = 91.7%, sensitivity = 86.66%, specificity = 96.6% and f-measure = 0.90; NB classification accuracy = 93.6%, sensitivity = 100%, specificity = 87.9% and f-measure = 0.95. In conclusion, SL could be a promising method for diagnosing depression. The findings could be generalized to develop a robust CAD-based tool that may help for clinical purposes.
Sealy, Julie; Glovinsky, Ira P
This randomized controlled trial examined the reflective functioning capacities of caregivers who have a child with a neurodevelopmental disorder between the ages of 2 years 0 months and 6 years 11 months. Children with a neurodevelopmental disorder receive a range of diagnoses, including sutism; however, they all exhibit social communication challenges that can derail social relationships. Forty parent-child dyads in Barbados were randomly assigned to either a developmental individual-difference, relationship-based/floortime(DIR/FT) group (n = 20), or a psychoeducational (wait-list) group (n = 20) with parental reflective functioning measured before and after a 12-week DIR/FT treatment intervention. Results revealed significant gains in parental reflective functioning in the treatment group, as compared to the psychoeducational (wait-list) group, after the 12-week relationship-focused intervention. © 2016 Michigan Association for Infant Mental Health.
Herpers, Pierre C M; Klip, Helen; Rommelse, Nanda N J; Greven, Corina U; Buitelaar, Jan K
Research regarding callous-unemotional (CU) traits in non-conduct disorder (CD) diagnoses is sparse. We investigated the presence of high CU traits and their associations with quality of life (QoL) in a clinically referred sample of youths with non-CD diagnoses. Parents of 1018 children referred to a child and adolescent psychiatric clinic and rated their child's CU traits and QoL. Experienced clinicians derived DSM-IV-TR diagnoses based on systematic clinical evaluations of these children. High CU traits compared to low CU traits were present in 38.5 % of the sample, and more often in boys than girls (69.4 vs. 30.6 %, p = .004), and were associated with more police contacts (12.2 vs. 3.5 %, p disorder (odds ratio; OR = 1.61; 95 % CI 1.24-2.09; p disorder not otherwise specified/oppositional defiant disorder (OR = 4.98; 95 % CI 2.93-8.64; p disorder (OR = 1.01; 95 % CI .79-1.31; p = .94), were more likely to have high than low CU traits. Those with anxiety/mood disorders were more likely to have low than high CU traits (OR = .59; 95 % CI .42-82; p = .002). In all diagnostic groups, high CU compared to low CU traits were associated with significantly lower QoL, while controlling for gender, age, and comorbidity. As such, high CU traits significantly modify QoL in non-CD disorders.
Rosenberg, Rebecca E.; Kaufmann, Walter E.; Law, J. Kiely; Law, Paul A.
We used a national online registry to examine variation in cumulative prevalence of community diagnosis of psychiatric comorbidity in 4343 children with autism spectrum disorders (ASD). Adjusted multivariate logistic regression models compared influence of individual, family, and geographic factors on cumulative prevalence of parent-reported anxiety disorder, depression, bipolar disorder, and attention deficit/hyperactivity disorder or attention deficit disorder. Adjusted odds of community-as...
Holtom-Viesel, Anita; Allan, Steven
The objectives of this review were to systematically identify and evaluate quantitative research comparing family functioning (a) in eating disorder families with control families, (b) in families with different eating disorder diagnoses (c) perceptions of different family members and (d) the relationship between family functioning and recovery. This adds to the findings of previous reviews of family functioning by including data from control families, the range of diagnoses, and focusing on recovery. Findings were considered in relation to models of family functioning. Using specific search criteria, 17 research papers were identified and evaluated. Findings indicated that eating disorder families reported worse family functioning than control families but there was little evidence for a typical pattern of family dysfunction. A consistent pattern of family dysfunction for different diagnoses was not suggested but patients consistently rated their family as more dysfunctional than one or both of their parents. With respect to outcome and recovery, those with more positive perceptions of family functioning generally had more positive outcomes, irrespective of severity of eating disorder. Conclusions were limited by inconsistent findings and methodological issues. Further research is needed into the relationship between family functioning and outcome and the assessment of family functioning beyond self-report. © 2013.
Rollins, Caitlin K; Newburger, Jane W; Roberts, Amy E
Neurodevelopmental impairment is common in children with moderate to severe congenital heart disease (CHD). As children live longer and healthier lives, research has focused on identifying causes of neurodevelopmental morbidity that significantly impact long-term quality of life. This review will address the role of genetic factors in predicting neurodevelopmental outcome in CHD. A robust literature suggests that among children with various forms of CHD, those with known genetic/extracardiac anomalies are at highest risk of neurodevelopmental impairment. Advances in genetic technology have identified genetic causes of CHD in an increasing percentage of patients. Further, emerging data suggest substantial overlap between mutations in children with CHD and those that have previously been associated with neurodevelopmental disorders. Innate and patient factors appear to be more important in predicting neurodevelopmental outcome than medical/surgical variables. Future research is needed to establish a broader understanding of the mutations that contribute to neurodevelopmental disorders and the variations in expressivity and penetrance.
Polderman, Florens N.; Cohen, Joeri; Blom, Nico A.; Delhaas, Tammo; Helbing, Wim A.; Lam, Jan; Sobotka-Plojhar, Marta A.; Temmerman, Arno M.; Sreeram, Narayanswani
BACKGROUND: It is known that children with previously diagnosed heart defects die suddenly. The causes of death are often unknown. OBJECTIVE: The aim of the study was to identify all infants and children within the Netherlands with previously diagnosed heart disease who had a sudden unexpected death
Polderman, F.N.; Cohen, Joeri; Blom, N.A.; Delhaas, T.; Helbing, W.A.; Lam, J.; Sobotka-Plojhar, M.A.; Temmerman, Arno M.; Sreeram, N.
Background: It is known that children with previously diagnosed heart defects die suddenly. The causes of death are often unknown. Objective: The aim of the study was to identify all infants and children within the Netherlands with previously diagnosed heart disease who had a sudden unexpected death
Mazefsky, Carla A.; Oswald, Donald P.; Day, Taylor N.; Eack, Shaun M.; Minshew, Nancy J.; Lainhart, Janet E.
Varied presentations of emotion dysregulation in autism complicate diagnostic decision making and may lead to inaccurate psychiatric diagnoses or delayed autism diagnosis for high-functioning children. This pilot study aimed to determine the concordance between prior psychiatric diagnoses and the results of an autism-specific psychiatric interview…
Reddon, Hudson; Pettes, Tyler; Wood, Evan; Nosova, Ekaterina; Milloy, Michael-John; Kerr, Thomas; Hayashi, Kanna
Limited attention has been given to the predictors of mental health diagnoses among people who inject drugs (PWID) in community settings. Therefore, we sought to longitudinally examine the prevalence, incidence and predictors of mental disorder diagnosis among a community-recruited cohort of PWID. Data were derived from two prospective cohort studies of PWID (VIDUS and ACCESS) in Vancouver, Canada between December 2005 and May 2015. We used multivariable extended Cox regression to identify factors independently associated with self-reported mental disorder diagnosis during follow-up among those without a history of such diagnoses at baseline. Among the 923 participants who did not report a mental disorder at baseline, 206 (22.3%) reported a first diagnosis of a mental disorder during follow-up for an incidence density of 4.29 [95% confidence interval (CI) 3.72-4.91] per 100 person-years. In the multivariable analysis, female sex [adjusted hazards ratio (AHR) = 1.74, 95% CI 1.29-2.33], experiencing non-fatal overdose (AHR = 2.33, 95% CI 1.38-3.94), accessing any drug or alcohol treatment (AHR = 1.68, 95% CI 1.24-2.27), accessing any community health or social services (AHR = 1.53, 95% CI 1.02-2.28) and experiencing violence (AHR = 1.60, 95% CI 1.12-2.29) were independently associated with a mental disorder diagnosis at follow-up. We observed a high prevalence and incidence of mental disorders among our community-recruited sample of PWID. The validity and implication of these diagnoses for key substance use and public health outcomes are an urgent priority. © 2017 Australasian Professional Society on Alcohol and other Drugs.
Novel de novo variant in EBF3 is likely to impact DNA binding in a patient with a neurodevelopmental disorder and expanded phenotypes: patient report, in silico functional assessment, and review of published cases.
Blackburn, Patrick R; Barnett, Sarah S; Zimmermann, Michael T; Cousin, Margot A; Kaiwar, Charu; Pinto E Vairo, Filippo; Niu, Zhiyv; Ferber, Matthew J; Urrutia, Raul A; Selcen, Duygu; Klee, Eric W; Pichurin, Pavel N
Pathogenic variants in EBF3 were recently described in three back-to-back publications in association with a novel neurodevelopmental disorder characterized by intellectual disability, speech delay, ataxia, and facial dysmorphisms. In this report, we describe an additional patient carrying a de novo missense variant in EBF3 (c.487C>T, p.(Arg163Trp)) that falls within a conserved residue in the zinc knuckle motif of the DNA binding domain. Without a solved structure of the DNA binding domain, we generated a homology-based atomic model and performed molecular dynamics simulations for EBF3, which predicted decreased DNA affinity for p.(Arg163Trp) compared with wild-type protein and control variants. These data are in agreement with previous experimental studies of EBF1 showing the paralogous residue is essential for DNA binding. The conservation and experimental evidence existing for EBF1 and in silico modeling and dynamics simulations to validate comparable behavior of multiple variants in EBF3 demonstrates strong support for the pathogenicity of p.(Arg163Trp). We show that our patient presents with phenotypes consistent with previously reported patients harboring EBF3 variants and expands the phenotypic spectrum of this newly identified disorder with the additional feature of a bicornuate uterus.
Neurodevelopmental Effects of Environmental ExposuresSherry G. Selevan, Pauline Mendola, Deborah C. Rice (US EPA, Washington,DC) The nervous system starts development early in gestation and continues to develop through adolescence. Thus, critical windows of vuln...
Lionel, Anath C.; Tammimies, Kristiina; Vaags, Andrea K.; Rosenfeld, Jill A.; Ahn, Joo Wook; Merico, Daniele; Noor, Abdul; Runke, Cassandra K.; Pillalamarri, Vamsee K.; Carter, Melissa T.; Gazzellone, Matthew J.; Thiruvahindrapuram, Bhooma; Fagerberg, Christina; Laulund, Lone W.; Pellecchia, Giovanna; Lamoureux, Sylvia; Deshpande, Charu; Clayton-Smith, Jill; White, Ann C.; Leather, Susan; Trounce, John; Melanie Bedford, H.; Hatchwell, Eli; Eis, Peggy S.; Yuen, Ryan K.C.; Walker, Susan; Uddin, Mohammed; Geraghty, Michael T.; Nikkel, Sarah M.; Tomiak, Eva M.; Fernandez, Bridget A.; Soreni, Noam; Crosbie, Jennifer; Arnold, Paul D.; Schachar, Russell J.; Roberts, Wendy; Paterson, Andrew D.; So, Joyce; Szatmari, Peter; Chrysler, Christina; Woodbury-Smith, Marc; Brian Lowry, R.; Zwaigenbaum, Lonnie; Mandyam, Divya; Wei, John; MacDonald, Jeffrey R.; Howe, Jennifer L.; Nalpathamkalam, Thomas; Wang, Zhuozhi; Tolson, Daniel; Cobb, David S.; Wilks, Timothy M.; Sorensen, Mark J.; Bader, Patricia I.; An, Yu; Wu, Bai-Lin; Musumeci, Sebastiano Antonino; Romano, Corrado; Postorivo, Diana; Nardone, Anna M.; Monica, Matteo Della; Scarano, Gioacchino; Zoccante, Leonardo; Novara, Francesca; Zuffardi, Orsetta; Ciccone, Roberto; Antona, Vincenzo; Carella, Massimo; Zelante, Leopoldo; Cavalli, Pietro; Poggiani, Carlo; Cavallari, Ugo; Argiropoulos, Bob; Chernos, Judy; Brasch-Andersen, Charlotte; Speevak, Marsha; Fichera, Marco; Ogilvie, Caroline Mackie; Shen, Yiping; Hodge, Jennelle C.; Talkowski, Michael E.; Stavropoulos, Dimitri J.; Marshall, Christian R.; Scherer, Stephen W.
Rare copy number variants (CNVs) disrupting ASTN2 or both ASTN2 and TRIM32 have been reported at 9q33.1 by genome-wide studies in a few individuals with neurodevelopmental disorders (NDDs). The vertebrate-specific astrotactins, ASTN2 and its paralog ASTN1, have key roles in glial-guided neuronal migration during brain development. To determine the prevalence of astrotactin mutations and delineate their associated phenotypic spectrum, we screened ASTN2/TRIM32 and ASTN1 (1q25.2) for exonic CNVs in clinical microarray data from 89 985 individuals across 10 sites, including 64 114 NDD subjects. In this clinical dataset, we identified 46 deletions and 12 duplications affecting ASTN2. Deletions of ASTN1 were much rarer. Deletions near the 3′ terminus of ASTN2, which would disrupt all transcript isoforms (a subset of these deletions also included TRIM32), were significantly enriched in the NDD subjects (P = 0.002) compared with 44 085 population-based controls. Frequent phenotypes observed in individuals with such deletions include autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), speech delay, anxiety and obsessive compulsive disorder (OCD). The 3′-terminal ASTN2 deletions were significantly enriched compared with controls in males with NDDs, but not in females. Upon quantifying ASTN2 human brain RNA, we observed shorter isoforms expressed from an alternative transcription start site of recent evolutionary origin near the 3′ end. Spatiotemporal expression profiling in the human brain revealed consistently high ASTN1 expression while ASTN2 expression peaked in the early embryonic neocortex and postnatal cerebellar cortex. Our findings shed new light on the role of the astrotactins in psychopathology and their interplay in human neurodevelopment. PMID:24381304
Major Depressive Disorder (MDD) and Posttraumatic Stress Disorder (PTSD) are highly prevalent illnesses that can result in profound impairment. While many patients with these disorders present in primary care, research suggests that physicians under-detect and suboptimally manage MDD and PTSD in their patients. The development of more effective…
A. V. Mordyk
Full Text Available The assessment of immunological indicators in 76 first time diagnosed infiltrative tuberculosis of lungs in socially safe patients prior to treatment and in 2 months of chemotherapy was carried out. It is revealed that immunological disorders are connected with efficiency of tuberculosis treatment . It can be criterion of quality of provided chemotherapy. The activation of cell immunity, stimulation of phagocytosis activity of neutrophils would contribute for effective treatment of tuberculosis.
Full Text Available Abstract Background Noonan syndrome (NS and Noonan syndrome with multiple lentigines (NSML are autosomal dominant developmental disorders. NS and NSML are caused by abnormalities in genes that encode proteins related to the RAS-MAPK pathway, including PTPN11, RAF1, BRAF, and MAP2K. In this study, we diagnosed ten NS or NSML patients via targeted sequencing or whole exome sequencing (TS/WES. Methods TS/WES was performed to identify mutations in ten Chinese patients who exhibited the following manifestations: potential facial dysmorphisms, short stature, congenital heart defects, and developmental delay. Sanger sequencing was used to confirm the suspected pathological variants in the patients and their family members. Results TS/WES revealed three mutations in the PTPN11 gene, three mutations in RAF1 gene, and four mutations in BRAF gene in the NS and NSML patients who were previously diagnosed based on the abovementioned clinical features. All the identified mutations were determined to be de novo mutations. However, two patients who carried the same mutation in the RAF1 gene presented different clinical features. One patient with multiple lentigines was diagnosed with NSML, while the other patient without lentigines was diagnosed with NS. In addition, a patient who carried a hotspot mutation in the BRAF gene was diagnosed with NS instead of cardiofaciocutaneous syndrome (CFCS. Conclusions TS/WES has emerged as a useful tool for definitive diagnosis and accurate genetic counseling of atypical cases. In this study, we analyzed ten Chinese patients diagnosed with NS and related disorders and identified their correspondingPTPN11, RAF1, and BRAF mutations. Among the target genes, BRAF showed the same degree of correlation with NS incidence as that of PTPN11 or RAF1.
García-Alandete, Joaquín; Ros, Montserrat Cañabate; Salvador, José Heliodoro Marco; Rodríguez, Sandra Pérez
The aim of this study was to analyze the psychometric properties of the Purpose-In-Life Test (PIL), as well as the age-related differences in meaning in life in women diagnosed with eating disorders. Participants were 250 Spanish women diagnosed with eating disorders who ranged from 12 to 60 years old. Confirmatory Factor Analysis, descriptive analyses, estimation of the internal consistency of the PIL, correlations between the PIL and the Beck Hopelessness Scale (BHS), Overweight Preoccupation Scale (OPS), and Body Investment Scale (BIS), and age differences were calculated. A 19-item model that showed a good fit and internal consistency, a negative correlation between the PIL and both the BHS and OPS, and a positive correlation with the BIS, as well as significant differences between the adolescents and the mature adults, were found. It would be advisable to increase the inclusion of meaning in life in psychotherapeutic interventions with women diagnosed with eating disorders. Copyright © 2017 Elsevier B.V. All rights reserved.
Anderson, Ariana E; Mansolf, Maxwell; Reise, Steven P; Savitz, Adam; Salvadore, Giacomo; Li, Qingqin; Bilder, Robert M
Although the Positive and Negative Syndrome Scale (PANSS) was developed for use in schizophrenia (SZ), antipsychotic drug trials use the PANSS to measure symptom change also for bipolar (BP) and schizoaffective (SA) disorder, extending beyond its original indications. If the dimensions measured by the PANSS are different across diagnoses, then the same score change for the same drug condition may have different meanings depending on which group is being studied. Here, we evaluated whether the factor structure in the PANSS was consistent across schizophrenia (n = 3647), bipolar disorder (n = 858), and schizoaffective disorder (n = 592). Along with congruency coefficients, Hancock's H, and Jaccard indices, we used target rotations and statistical tests of invariance based on confirmatory factor models. We found the five symptom dimensions measured by the 30-item PANSS did not generalize well to schizoaffective and bipolar disorders. A model based on an 18-item version of the PANSS generalized better across SZ and BP groups, but significant problems remained in generalizing some of the factors to the SA sample. Schizophrenia and bipolar disorder showed greater similarity in factor structure than did schizophrenia and schizoaffective disorder. The Anxiety/Depression factor was the most consistent across disorders, while the Positive factor was the least consistent. Copyright © 2017 Elsevier B.V. All rights reserved.
Santvoort, F. van; Hosman, C.M.H.; Janssens, J.M.A.M.; Doesum, K.T.M. van; Reupert, A.E.; Loon, L.M.A. van
Children of mentally ill parents are at high risk of developing problems themselves. They are often identified and approached as a homogeneous group, despite diversity in parental diagnoses. Some studies demonstrate evidence for transgenerational equifinality (children of parents with various
Cooney, Megan; Lieberman, Melissa; Guimond, Tim; Katzman, Debra K
Avoidant/Restrictive Food Intake Disorder (ARFID) is an eating disorder first described in the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) [American Psychiatric Association, Diagnostic and statistical manual of mental disorders, 2013]. Patients with ARFID do not fear gaining weight or have body image distortions. ARFID involves a persistent disturbance in feeding and eating that results in an inability to meet nutritional and/or energy needs with one of the following: weight loss or failure to achieve appropriate weight gain, nutritional deficiency, dependence on enteral feeding or nutritional supplements and significant interference with psychosocial functioning. To date, studies on patients with ARFID have retrospectively applied the DSM-5 diagnostic criteria for ARFID to reclassify patients diagnosed with DSM-IV eating disorders. A descriptive retrospective chart review was completed on patients less than 18-years diagnosed with ARFID after a comprehensive eating disorder assessment between May 2013 and March 2016. The data collected included demographics, anthropometrics, historical information, clinical features, co-morbid diagnoses, need for inpatient hospitalization and psychometric measures. Three hundred and sixty-nine patients were assessed for an eating disorder between May 2013 and March 2016. Of these, 31 (8.4%) received a DSM-5 diagnosis of ARFID. A full chart review was performed on 28 (90.3%) patients. Weight loss or failure to achieve appropriate weight gain was the reason for diagnosis in 96.4% (27/28). All of our patients had 2 or more physical symptoms at the time of diagnosis and 16 (57.1%) had a co-morbid psychiatric disorder. Twenty (71.4%) reported a specific trigger for their eating disturbance. Admission for inpatient hospitalization occurred in 57.1% (16/28) of patients. Thirteen (46.4%) patients had been previously assessed by another specialist for their eating disturbance. None of the patients had
Stern, Francine Martin; Gorga, Delia
Use of neurodevelopmental treatment, also known as the Bobath method, is discussed, including its history, philosophy, goals, and treatment emphasis with infants and children with movement disorders. Examples of children before and after therapeutic intervention illustrate use of the technique, and controversies in measuring therapy efficacy are…
Eric K. Cooper
Full Text Available Attention Deficit//Hyperactivity Disorder is a childhood disorder on the increase in the United States, and parents are searching for additional ways to help alleviate the symptoms associated with this disorder. One of the ways parents are looking to help with ADHD is through exercise programs, including the martial arts. As more of our students are diagnosed with ADHD, it is imperative we, as martial artists and teachers, understand the nature of this disorder. Therefore, this article is intended to educate those in the martial arts about ADHD. First, an introduction about ADHD, what it is and what it is not, is offered to demystify the disorder and to insure instructors are using appropriate language and terminology. Second, current research regarding the use of the martial arts as an intervention for ADHD will be discussed. Third, the issue of confidentiality related to psychological disorders will be discussed and suggestions offered to decrease the chances of instructors breaching confidentiality. Finally, some strategies for working with children with ADHD will be offered.
Nguyen, Cathina T; Fairclough, Diane L; Noll, Robert B
Problem-solving skills training is an intervention designed to teach coping skills that has shown to decrease negative affectivity (depressive symptoms, negative mood, and post-traumatic stress symptoms) in mothers of children with cancer. The objective of this study was to see whether mothers of children recently diagnosed with autism spectrum disorder would be receptive to receiving problem-solving skills training (feasibility trial). Participants were recruited from a local outpatient developmental clinic that is part of a university department of pediatrics. Participants were to receive eight 1-h sessions of problem-solving skills training and were asked to complete assessments prior to beginning problem-solving skills training (T1), immediately after intervention (T2), and 3 months after T2 (T3). Outcome measures assessed problem-solving skills and negative affectivity (i.e. distress). In total, 30 mothers were approached and 24 agreed to participate (80.0%). Of them, 17 mothers completed problem-solving skills training (retention rate: 70.8%). Mothers of children with autism spectrum disorder who completed problem-solving skills training had significant decreases in negative affectivity and increases in problem-solving skills. A comparison to mothers of children with cancer shows that mothers of children with autism spectrum disorder displayed similar levels of depressive symptoms but less negative mood and fewer symptoms of post-traumatic stress. Data suggest that problem-solving skills training may be an effective way to alleviate distress in mothers of children recently diagnosed with autism spectrum disorder. Data also suggest that mothers of children with autism spectrum disorder were moderately receptive to receiving problem-solving skills training. Implications are that problem-solving skills training may be beneficial to parents of children with autism spectrum disorder; modifications to improve retention rates are suggested. © The Author(s) 2015.
Mouridsen, Svend Erik Birkebæk; Hauschild, K.M.
The prevalence and types of schizophrenia- and affective spectrum disorders were studied in 469 individuals with a developmental language disorder (DLD), assessed in the same clinic during a period of 10 years, and 2,345 controls from the general population. All participants were screened through...... the nationwide Danish Psychiatric Central Register (DPCR). The mean length of follow-up was 34.7 years, and the mean age at follow-up 35.8 years. The results show an excess of schizophrenia spectrum disorders (F20-F29) within participants with DLD when compared with controls from the overall population (6.4% vs....... 1.8%; P disorder was significantly associated with a schizophrenia spectrum disorder diagnosis in the DPCR. There was no significant increase in affective...
Rubin, P; Holm, S; Madsen, P L
Regional cerebral blood flow distribution (rCBF) in 24 first admissions with schizophrenia or schizophreniform disorder and in 17 healthy volunteers was examined. Single photon emission computed tomography with a brain-retained tracer, technetium-99m-d,l-hexamethyl-propylene amine oxime, was used...... interrelationship in schizophrenia and schizophreniform disorder....
Moree, Brittany N.; Davis, Thompson E., III
Anxiety disorders have been found to be highly comorbid with autism spectrum disorders (ASDs). Even so, the identification and dissemination of empirically supported treatments for anxiety in adults or children who have ASD has lagged behind the larger evidence-based trend. This review examines the efficacy of cognitive-behavioral therapy as a…
Boat, Barbara W.; Peterson, Gary
Describes reasons why therapists may hesitate to address the needs of children when treating parents with Dissociative Identity Disorder (DID) (formerly Multiple Personality Disorder). Summarizes the literature supporting assessment of these children, relates clinical observations on the potential impact of DID on children, and suggests…
Kent, Rachel G.; Carrington, Sarah J.; Le Couteur, Ann; Gould, Judith; Wing, Lorna; Maljaars, Jarymke; Noens, Ilse; Berckelaer-Onnes, Ina; Leekam, Susan R.
Background: Introduction of proposed criteria for DSM-5 Autism Spectrum Disorder (ASD) has raised concerns that some individuals currently meeting diagnostic criteria for Pervasive Developmental Disorder (PDD; DSM-IV-TR/ICD- 10) will not qualify for a diagnosis under the proposed changes. To date, reports of sensitivity and specificity of the new…
Mullins-Sweatt, Stephanie N; Bernstein, David P; Widiger, Thomas A
One of the official proposals for the fifth edition of the American Psychiatric Association's (APA) diagnostic manual (DSM-5) is to delete half of the existing personality disorders (i.e., dependent, histrionic, narcissistic, paranoid, and schizoid). Within the APA guidelines for DSM-5 decisions, it is stated that there should be expert consensus agreement for the deletion of a diagnostic category. Additionally, categories to be deleted should have low clinical utility and/or minimal evidence for validity. The current study surveyed members of two personality disorder associations (n = 146) with respect to the utility, validity, and status of each DSM-IV-TR personality disorder diagnosis. Findings indicated that the proposal to delete five of the personality disorders lacks consensus support within the personality disorder community.
Mandell, David S.; Ittenbach, Richard F.; Levy, Susan E.; Pinto-Martin, Jennifer A.
This study estimated differences by ethnicity in the diagnoses assigned prior to the diagnosis of autism. In this sample of 406 Medicaid-eligible children, African-Americans were 2.6 times less likely than white children to receive an autism diagnosis on their first specialty care visit. Among children who did not receive an autism diagnosis on…
Kelly, Sharon M; Gryczynski, Jan; Mitchell, Shannon Gwin; Kirk, Arethusa; O'Grady, Kevin E; Schwartz, Robert P
The recently published Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5) includes several major revisions to substance use diagnoses. Studies have evaluated the impact of these changes among adult samples but research with adolescent samples is lacking. 525 adolescents (93% African American) awaiting primary care appointments in Baltimore, Maryland were recruited for a study evaluating a substance use screening instrument. Participants were assessed for DSM-5 nicotine, alcohol, and cannabis use disorder, DSM-IV alcohol and cannabis abuse, and DSM-IV dependence for all three substances during the past year using the modified Composite International Diagnostic Interview-2, Substance Abuse Module. Contingency tables examining DSM-5 vs. DSM-IV joint frequency distributions were examined for each substance. Diagnoses were more prevalent using DSM-5 criteria compared with DSM-IV for nicotine (4.0% vs. 2.7%), alcohol (4.6% vs. 3.8%), and cannabis (10.7% vs. 8.2%). Cohen's κ, Somers' d, and Cramer's V ranged from 0.70 to 0.99 for all three substances. Of the adolescents categorized as "diagnostic orphans" under DSM-IV, 7/16 (43.8%), 9/29 (31.0%), and 13/36 (36.1%) met criteria for DSM-5 disorder for nicotine, alcohol, and cannabis, respectively. Additionally, 5/17 (29.4%) and 1/21 (4.8%) adolescents who met criteria for DSM-IV abuse did not meet criteria for a DSM-5 diagnosis for alcohol and cannabis, respectively. Categorizing adolescents using DSM-5 criteria may result in diagnostic net widening-particularly for cannabis use disorders-by capturing adolescents who were considered diagnostic orphans using DSM-IV criteria. Future research examining the validity of DSM-5 substance use disorders with larger and more diverse adolescent samples is needed. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
Palmer, Steven C.; Taggi, Alison; DeMichele, Angela; Coyne, James C.
BACKGROUND: A key purpose of routine distress screening is to ensure that cancer patients receive appropriate mental health care. Most studies validating screening instruments overestimate the effectiveness of screening by not differentiating between patients with untreated disorders and patients
Verhoeven, F. E. A.; Swaab, L. S. M. A.; Carlier, I. V. E.; van Hemert, A. M.; Zitman, F. G.; Ruhé, H. G.; Schoevers, R. A.; Giltay, E. J.
Background: Standardized Diagnostic Interviews (SDIs) such as the Mini International Neuropsychiatric Interview (MINI) are widely used to systematically screen for psychiatric disorders in research. To support generalizability of results to clinical practice, we assessed agreement between the MINI
Kellogg, Marissa; Meador, Kimford J
Increasing evidence suggests that exposure to certain antiepileptic drugs (AEDs) during critical periods of development may induce transient or long-lasting neurodevelopmental deficits across cognitive, motor and behavioral domains. The developing nervous system may endure prolonged chronic exposure to AEDs during pregnancy (in utero) or during childhood, which can lead to neurodevelopmental defects such as congenital neural tube defects, lower IQ, language deficits, autism and ADHD. To date, valproate is the most widely recognized AED to significantly negatively affect neurodevelopment, and demonstrates greater adverse effects than any other AEDs that have been assessed. Although some AEDs appear to have low risk (i.e., lamotrigine, levetiracetam), other AEDs have been implicated in a variety of studies detailed below, and many AEDs have not been adequately assessed. The purpose of this review article is to summarize our current understanding of the neurodevelopmental effects of AEDs.
Alonso, Sandra; Marco, José H; Andani, Joaquín
Sick leave in patients with a mental disorder is characterized by having a long duration. Studies suggest that the time until a patient on sick leave for a common mental health disorder initiates evaluation and treatment by a healthcare professional is an important factor in the duration of the sick leave. However, in these studies, the intervention was not performed by a mental health specialist. The aim of this study was to find out whether the length of sick leave was associated with the time before initiating psychotherapy, age, time until returning to work after psychotherapy ends, and duration of psychotherapy. In a further analysis, we examined whether the model composed of age, duration of psychotherapy, and time before initiating psychotherapy predicted the length of sick leave. The sample consisted of 2,423 participants, 64.1% (n = 1,554) women and 35.9% (n = 869) men, who were on sick leave for anxiety disorders or depressive disorder. The total duration of the sick leave of participants diagnosed with depression and anxiety was positively associated with the time before beginning psychotherapy. Time before beginning psychotherapy predicted the length of sick leave when the variables age and duration of psychotherapy were controlled. It is necessary to reduce the time until beginning psychotherapy in people on sick leave for common mental disorders. Copyright © 2017 John Wiley & Sons, Ltd.
Background The present paper reports the results of research aimed at identifying intra-group differences among females suffering from different eating disorders (anorexia nervosa, bulimia nervosa or binge eating disorder) in terms of the subjects’ psychological traits, adoption of socio-cultural norms (through media pressure, internationalization of norms, and exposure to information concerning body image standards), and the level of body dissatisfaction. The following research question...
Full Text Available Psychological disorders have been proven to be associated with poor physiological, psychological and immune outcomes in cancer patients. However, despite of many challenges of the changed self-image/body image and the altered sexual/urinary function, relatively little is known about psychological disorders of patients with newly diagnosed bladder and kidney cancer. We aimed to investigate the prevalence of depression, anxiety, post-traumatic stress disorder (PTSD and the associated psychosocial factors among bladder/kidney cancer patients.A cross-sectional study was conducted of consecutive inpatients with bladder/kidney cancer in the First Affiliated Hospital of China Medical University in Liaoning Province, northeast China. A total of 489 early-stage cancer patients eligible for this study completed questionnaires on demographic and clinical variables, depression, anxiety, PTSD, perceived social support and positive psychological variables (hope, optimism and resilience anonymously during October 2013 and August 2014. Hierarchical regression analysis was used to examine the relationships between psychosocial resources and psychological disorders, while controlling for possible covariates.The prevalence of depression, anxiety and PTSD was 77.5%, 69.3% and 25.2%, respectively, while 24.9% of patients had psychological co-morbidity. Psychosocial resources together explained more than one-third of the variance on psychological disorders. Under standardized estimate (β sequence, patient's perception of social support from family was significantly associated with depression, anxiety and PTSD (p < 0.01. Optimism and resilience showed integrated and independent effects on psychological disorders, and hope represented the significant association with PTSD only (p < 0.01.The high prevalence of psychological disorders in newly diagnosed patients with early-stage bladder/kidney cancer should receive more attention in Chinese medical settings
Wagner, Elizabeth E.; Miller, Alec L.; Greene, Lori I.; Winiarski, Mark G.
The primary aim of this article is to describe modifications made to Dialectical Behavior Therapy (DBT) for a predominantly ethnic minority population of persons living with HIV/AIDS with substance-use diagnoses and borderline personality disorder (BPD) or three features of BPD plus suicidality (i.e., the triply diagnosed). Despite the myriad…
Golubchik, Pavel; Weizman, Abraham
To assess the Empathizing Quotient (EQ) of patients diagnosed with attention-deficit/hyperactivity disorder (ADHD) only or comorbid with oppositional defiant disorder (ODD) and compare the two groups' responses to methylphenidate (MPH) treatment. Fifty-two children (8-18 years) diagnosed with ADHD, 26 of whom were also diagnosed with comorbid ODD (ADHD/ODD), were treated with MPH for 12 weeks. The level of EQ was assessed with the Children's version of the Empathizing Quotient (EQ-C) and the severity of ADHD symptoms with the ADHD Rating Scale (ADHD-RS). Assessments were done at baseline and at end point. A significant increase in EQ scores was obtained in both groups following MPH treatment (p = 0.003 for ADHD/ODD; p = 0.002 for ADHD). Significant correlation was found in the ADHD group between the changes in ADHD-RS and those in EQ, following MPH treatment (p = 0.015), but not in the ADHD/ODD group (p = 0.48). A correlation exists between MPH-related improvement in ADHD symptoms and between more empathy in children with ADHD not comorbid with ODD.
Full Text Available We report the case of a Moroccan boy with mental retardation, hyperactivity, epilepsy, developmental problems and behavioural disorders. Cytogenetic analysis showed the presence of a supernumerary marker chromosome. Molecular cytogenetics allowed us to determine the marker as an inverted duplication of chromosome 15. It is the first case of a Moroccan patient with tetrasomy 15q in which fluorescence in situ hybridization (FISH enabled us to specify the diagnosis. Interestingly, this patient has an infantile autism with cytogenetic abnormalities on chromosomal region 15q11-q13 as reported in patients with Autistic Disorder.
Huskamp, Haiden A; Samples, Hillary; Hadland, Scott E; McGinty, Emma E; Gibson, Teresa B; Goldman, Howard H; Busch, Susan H; Stuart, Elizabeth A; Barry, Colleen L
The Mental Health Parity and Addiction Equity Act (MHPAEA) was intended to eliminate differences in insurance coverage for mental health and substance use disorder services and medical-surgical care. No studies have examined mental health service use after federal parity implementation among individuals with diagnoses of eating disorders, for whom financial access to care has often been limited. This study examined whether MHPAEA implementation was associated with changes in use of mental health services and spending in this population. Using Truven Health MarketScan data from 2007 to 2012, this study examined trends in mental health spending and intensity of use of specific mental health services (inpatient days, total outpatient visits, psychotherapy visits, and medication management visits) among individuals ages 13-64 with a diagnosis of an eating disorder (N=27,594). MHPAEA implementation was associated with a small increase in total mental health spending ($1,271.92; p<.001) and no change in out-of-pocket spending ($112.99; p=.234) in the first year after enforcement of the parity law. The law's implementation was associated with an increased number of outpatient mental health visits among users, corresponding to an additional 5.8 visits on average during the first year (p<.001). This overall increase was driven by an increase in psychotherapy use of 2.9 additional visits annually among users (p<.001). MHPAEA implementation was associated with increased intensity of outpatient mental health service use among individuals with diagnoses of eating disorders but no increase in out-of-pocket expenditures, suggesting improvements in financial protection.
Van Rheenen, Tamsyn E; Bryce, Shayden; Tan, Eric J; Neill, Erica; Gurvich, Caroline; Louise, Stephanie; Rossell, Susan L
Despite known overlaps in the pattern of cognitive impairments in individuals with bipolar disorder (BD), schizophrenia (SZ) and schizoaffective disorder (SZA), few studies have examined the extent to which cognitive performance validates traditional diagnostic boundaries in these groups. Individuals with SZ (n=49), schizoaffective disorder (n=33) and BD (n=35) completed a battery of cognitive tests measuring the domains of processing speed, immediate memory, semantic memory, learning, working memory, executive function and sustained attention. A discriminant functions analysis revealed a significant function comprising semantic memory, immediate memory and processing speed that maximally separated patients with SZ from those with BD. Initial classification scores on the basis of this function showed modest diagnostic accuracy, owing in part to the misclassification of SZA patients as having SZ. When SZA patients were removed from the model, a second cross-validated classifier yielded slightly improved diagnostic accuracy and a single function solution, of which semantic memory loaded most heavily. A cluster of non-executive cognitive processes appears to have some validity in mapping onto traditional nosological boundaries. However, since semantic memory performance was the primary driver of the discrimination between BD and SZ, it is possible that performance differences between the disorders in this cognitive domain in particular, index separate underlying aetiologies. Copyright © 2015 Elsevier B.V. All rights reserved.
Kerins, Carolyn A; McWhorter, Alton G; Seale, N Sue
The purpose of this study was to conduct a survey of Texas pediatric dentists to determine: (1) the percentage of patients they treat with attention deficit disorder (ADD)/attention deficit hyperactivity disorder (ADHD); (2) the behavior management techniques that are utilized to treat their patients who suffer from ADD/ADHD; and (3) the relative success rates of these techniques in their practices. A 17-question, single-answer, multiple choice survey was mailed to 343 Texas pediatric dentists. The mailing list was obtained from American Academy of Pediatric Dentistry and Texas Academy of Pediatric Dentistry member rosters. One mailing was sent, including a self-addressed stomped envelope, for returned responses. A 54% response rate (186 surveys) revealed that nitrous oxide was the most frequently used pharmacologic behavior management technique; however, demerol/promethazine/nitrous oxide was rated as effective most often for treating ADD/ADHD patients. Practitioners believe the incidence of attention deficit disorder/attention deficit hyperactivity disorder is increasing, and they are familiar with the medications used to treat the conditions. Texas pediatric dentists are using a variety of sedation techniques and are interested in developing guidelines for sedation of these patients.
Hogg, Daniel; Kingham, Simon; Wilson, Thomas M; Griffin, Edward; Ardagh, Michael
The 22nd February 2011 Christchurch earthquake killed 185 people, injured over 8000, damaged over 100,000 buildings and on-going aftershocks maintained high anxiety levels. This paper examines the dose of exposure effect of earthquake damage assessments, earthquake intensity measures, liquefaction and lateral spreading on mood and anxiety disorders in Christchurch after this event. We hypothesise that such disorders are more likely to develop in people who have experienced greater exposure to these impacts within their neighborhood than others who have been less exposed, but also live in the city. For this purpose, almost all clinically diagnosed incident and relapsed cases in Christchurch in a 12 months period after the 2011 earthquake were analysed. Spatio-temporal cluster analysis shows that people living in the widely affected central and eastern parts after the 2010/11 earthquakes have a 23% higher risk of developing a mood or anxiety disorder than people living in other parts of the city. Generally, mood and anxiety-related disorders increase with closer proximity to damage from liquefaction and moderate to major lateral spreading, as well as areas that are more likely to suffer from damage in future earthquakes. Copyright © 2014 Elsevier Ltd. All rights reserved.
Whyatt, Caroline; Craig, Cathy M.
Growing evidence suggests that significant motor problems are associated with a diagnosis of Autism Spectrum Disorders (ASD), particularly in catching tasks. Catching is a complex, dynamic skill that involves the ability to synchronise one's own movement to that of a moving target. To successfully complete the task, the participant must pick up…
Mouridsen, S.E.; Rich, B.; Isager, T.
The prevalence and types of psychiatric disorders were studied in a clinical sample of 89 individuals with atypical autism (AA) first seen as children, and 258 matched controls from the general population using data from the nationwide Danish Psychiatric Central Register. The average observation...
Bastiaansen, Jojanneke A.; Meffert, Harma; Hein, Simone; Huizinga, Petra; Ketelaars, Cees; Pijnenborg, Marieke; Bartels, Arnold; Minderaa, Ruud; Keysers, Christian; de Bildt, Annelies
Autism Diagnostic Observation Schedule (ADOS) module 4 was investigated in an independent sample of high-functioning adult males with an autism spectrum disorder (ASD) compared to three specific diagnostic groups: schizophrenia, psychopathy, and typical development. ADOS module 4 proves to be a
Shillingford-Butler, M. Ann; Theodore, Lea
The school setting can be a difficult place for children with attention deficit hyperactivity disorder (ADHD). The core symptoms of ADHD, which include inattention, hyperactivity, and impulsivity, make meeting the curriculum demands of the classroom challenging. That ADHD negatively impacts not only academic performance but also social and…
Bastiaansen, Jojanneke A.; Meffert, Harma; Hein, Simone; Huizinga, Petra; Ketelaars, Cees; Pijnenborg, Marieke; Bartels, Arnold; Minderaa, Ruud; Keysers, Christian; de Bildt, Annelies
Autism Diagnostic Observation Schedule (ADOS) module 4 was investigated in an independent sample of high-functioning adult males with an autism spectrum disorder (ASD) compared to three specific diagnostic groups: schizophrenia, psychopathy, and typical development. ADOS module 4 proves to be a reliable instrument with good predictive value. It…
Full Text Available The paper presents a case of hypoglycemic paroxysm, manifested as epilepsy, in 53-year-old man, suffering from diabetes mellitus type 1, complicated by steatohepatosis following excretory and endocrine pancreatic insufficiency, disorders of renal excretory function, triggered by the lack of food after insulin administration.
Brossard-Racine, Marie; Majnemer, Annette; Shevell, Michael; Snider, Laurie; Belanger, Stacey Ageranioti
Preliminary evidence suggests that children with Attention Deficit Hyperactivity Disorder (ADHD) may exhibit handwriting difficulties. However, the exact nature of these difficulties and the extent to which they may relate to motor or behavioural difficulties remains unclear. The aim of this study was to describe handwriting capacity in children…
Scott, David; Burke, Karena; Williams, Susan; Happell, Brenda; Canoy, Doreen; Ronan, Kevin
To compare chronic physical health disorder prevalence amongst Australian adults with and without mental illness. Total n=1,716 participants (58% female) with a mean age of 52 ± 13 years (range: 18 to 89 years) completed an online survey of Australian adults in 2010. Outcome measures including prevalence of chronic physical conditions and self-reported body mass index (BMI) in n=387 (23%) with a self-reported mental illness diagnosis were compared to respondents without mental illness. A significantly higher proportion of participants with mental illness were obese (BMI ≥ 30; 31 vs 24%, p=0.005). Adjusted odds ratios (OR) for coronary heart disease, diabetes, chronic bronchitis or emphysema, asthma, irritable bowel syndrome, and food allergies or intolerances (OR range: 1.54-3.19) demonstrated that chronic physical disorders were significantly more common in participants with a mental illness. Australian adults with a diagnosis for mental illness have a significantly increased likelihood of demonstrating chronic physical health disorders compared to persons without mental illness. Health professionals must be alert to the increased likelihood of comorbid chronic physical disorders in persons with a mental illness and should consider the adoption of holistic approaches when treating those with either a mental or physical illness. © 2012 The Authors. ANZJPH © 2012 Public Health Association of Australia.
Mhatre, Dimpi; Bapat, Deepa; Udani, Vrajesh
We investigated long-term outcomes in children with diagnosis of autism spectrum disorders based on Childhood Autism Rating Scale (CARS score). Information about outcomes such as speech, friendships and activities of daily living (ADLs) was collected through telephone-based interviews. Gilliam Autism Rating Scale-2 and Vineland Social Maturity…
Pasiali, Varvara; LaGasse, A Blythe; Penn, Saundra L
Given the effect of musical training on the rate and accuracy of processing auditory information, therapeutic uses of music may potentially have remedial benefits for individuals with neurodevelopmental deficits. However, additional studies are needed to establish efficacy of music therapy interventions for attention skills in children/adolescents with neurodevelopmental disabilities including those with Autism Spectrum Disorders (ASD). To establish feasibility and preliminary efficacy of a group music therapy protocol to improve attention skills (sustained, selective, attentional control/switching) in adolescents diagnosed with autism and/or developmental delays. This single group pretest/posttest study took place in a private school for high functioning adolescents with neurodevelopmental delays. Nine students (4 males, 5 females), ages 13 to 20, participated in the study. Autism severity was assessed using the CARS2-HF and indicated the following distribution for study participants: severe (n = 3), mild (n = 4), or minimal/no (n = 2) symptoms. We assessed feasibility of implementing a 45-min Musical Attention Control Training (MACT) intervention delivered by a board-certified music therapist eight times over 6 weeks in a school setting. We also examined preliminary efficacy of the MACT to improve attention skills using the Test of Everyday Attention for Children (TEA-Ch). Parental consent rate was 100%. All nine participants successfully completed testing measures and 6 weeks of the intervention. Average participation rate was 97%. Data analysis showed positive trends and improvements on measures of attentional control/switching and selective attention. The results showed that the intervention and testing measures were feasible to implement and acceptable to the participants who all completed the protocol. Data analysis demonstrated positive trends indicating that more research on the use of music therapy attention training in high-functioning adolescents with
Modan-Moses, Dalit; Levy-Shraga, Yael; Pinhas-Hamiel, Orit; Kochavi, Brigitte; Enoch-Levy, Adi; Vered, Iris; Stein, Daniel
Previous studies assessing vitamin D status in adolescents with eating disorders showed inconsistent results. The aim of the current study was to assess vitamin D status in a large cohort of adolescent inpatients with eating disorders and its relation to bone mineral density (BMD) and depression. 25-Hydroxyvitamin D (25OHD), calcium, phosphorus, and alkaline phosphatase levels as well as BMD and depression were assessed on admission in 87 inpatients (aged 16 ± 2 years, females = 81) with eating disorders [anorexia nervosa (AN) = 64; bulimia nervosa (BN) = 5; eating disorders not otherwise specified-binge/purge type (EDNOS-B/P) = 18]. Mean 25OHD levels were 24.1 ± 7.5 ng/ml (25.0 ± 7.6, 25.4 ± 9.9, and 22.0 ± 9.9 ng/ml in patients with AB, BN, and EDNOS-B/P, respectively). Vitamin D deficiency (32 ng/ml, considered optimal by some experts. No associations were found between 25OHD levels and BMD or comorbid depression. 25OHD levels during winter were significantly lower than summer levels (p EDNOS-B/P type was low (-1.5 ± 1.1) and correlated with body mass index standard deviation score (p = .03). Adolescents with eating disorders show a high prevalence of vitamin D deficiency and insufficiency. Given the risk of osteoporosis in this population, 25OHD levels found in this group may not offer optimal bone protection. Vitamin D levels should be routinely checked and supplementation should be administered as required. © 2014 Wiley Periodicals, Inc.
Schaevitz, Laura R; Picker, Jonathan D; Rana, Jasmine; Kolodny, Nancy H; Shane, Barry; Berger-Sweeney, Joanne E; Coyle, Joseph T
Interactions between genetic and environmental risk factors underlie a number of neuropsychiatric disorders, including schizophrenia (SZ) and autism (AD). Due to the complexity and multitude of the genetic and environmental factors attributed to these disorders, recent research strategies focus on elucidating the common molecular pathways through which these multiple risk factors may function. In this study, we examine the combined effects of a haplo-insufficiency of glutamate carboxypeptidase II (GCPII) and dietary folic acid deficiency. In addition to serving as a neuropeptidase, GCPII catalyzes the absorption of folate. GCPII and folate depletion interact within the one-carbon metabolic pathway and/or of modulate the glutamatergic system. Four groups of mice were tested: wild-type, GCPII hypomorphs, and wild-types and GCPII hypomorphs both fed a folate deficient diet. Due to sex differences in the prevalence of SZ and AD, both male and female mice were assessed on a number of behavioral tasks including locomotor activity, rotorod, social interaction, prepulse inhibition, and spatial memory. Wild-type mice of both sexes fed a folic acid deficient diet showed motor coordination impairments and cognitive deficits, while social interactions were decreased only in males. GCPII mutant mice of both sexes also exhibited reduced social propensities. In contrast, all folate-depleted GCPII hypomorphs performed similarly to untreated wild-type mice, suggesting that reduced GCPII expression and folate deficiency are mutually protective. Analyses of folate and neurometabolite levels associated with glutamatergic function suggest several potential mechanisms through which GCPII and folate may be interacting to create this protective effect. Copyright © 2011 Wiley Periodicals, Inc.
Ferrer, Marc; Andión, Óscar; Calvo, Natalia; Ramos-Quiroga, Josep A; Prat, Mònica; Corrales, Montserrat; Casas, Miguel
Common environmental etiological factors between borderline personality disorder (BPD) and attention deficit/hyperactivity disorder (ADHD) have not been fully studied. The main aim of this study was to investigate the relationship between childhood trauma histories, assessed by the Childhood Trauma Questionnaire-Short Form (CTQ-SF), with adult BPD, ADHD or BPD-ADHD diagnoses. Comorbid BPD-ADHD patients exhibited significantly higher clinical severity and higher scores in the Total Neglect Scale, compared to BPD and ADHD patients, and only a marginal difference was observed for Sexual Abuse when BPD and ADHD patients were compared. Physical Trauma Scales were associated with ADHD diagnosis, whereas Emotional Abuse and Sexual Abuse Scales were associated with BPD or BPD-ADHD diagnoses. The study findings support the association between experiencing traumatic events in childhood and a higher clinical severity of BPD in adulthood. Furthermore, physical trauma history in childhood could be associated with the persistence of ADHD in adulthood and emotional or sexual abuse with later development of BPD or comorbid BPD-ADHD. Whereas experiencing childhood traumas is associated with later development of more general psychopathology, our study supports that a specific type of traumatic event could increase the risk for the consolidation of a concrete psychiatric disorder in the trajectory from childhood to adulthood of vulnerable subjects.
Bhaumik, Sabyasachi; Tyrer, Freya; Barrett, Mary; Tin, Nyunt; McGrother, Catherine W; Kiani, Reza
It is often difficult to determine the triad of impairments and whether autistic features are the consequence of intellectual impairment or autism spectrum disorders in people with intellectual disability (ID). The aim of the current study was to investigate the relationship between carer-reported autistic traits and independent diagnoses of autism spectrum disorders (ASD). Data were collected on carers' subjective report of autistic traits and clinical diagnoses of ASD. Of 1145 adults with ID identified, 220 (19%) individuals had a diagnosis of ASD, and 778 (68%) individuals had at least one autistic trait. Optimal sensitivity and specificity were achieved with two or more autistic traits (sensitivity 63%; specificity 79%) and the positive predictive value increased substantially as the number of autistic traits increased. However, a significant proportion of individuals with ID who did not have a diagnosis of ASD also displayed autistic traits. Our findings suggest that in the absence of other measures, the presence of autistic traits can serve as a useful proxy measure for ASD in research (and/or clinical settings). However, although information on autistic traits may help healthcare practitioners to identify people with possible ASD, it cannot be used alone to make a formal diagnosis. 2010 Elsevier Ltd. All rights reserved.
Schnell, Thomas; Koethe, Dagmar; Krasnianski, Anna; Gairing, Stefanie; Schnell, Knut; Daumann, Jörg; Gouzoulis-Mayfrank, Euphrosyne
Clozapine is considered to be particularly effective in the treatment of dually diagnosed (DD) patients with psychosis and substance use disorders. However, its use is restricted by potentially severe side effects. The aim of the present pilot study was to compare the effects of clozapine with the newer second generation antipsychotic (SGA) ziprasidone in DD-patients. Thirty (n = 30) patients with schizophrenia and cannabis abuse/dependence were randomized to ziprasidone or clozapine and were followed up for up to 12 months. Cannabis use was reduced in both groups during follow-up. Clozapine treatment was associated with less positive symptoms of schizophrenia, more side effects and poorer compliance with treatment. Results from this small pilot RCT suggest beneficial effects of both clozapine and ziprasidone in the treatment of cannabis use disorders in psychotic patients. Larger-scale RCTs are needed in order to assess advantages and disadvantages of the different SGAs in dually diagnosed populations. © American Academy of Addiction Psychiatry.
Fossati, Andrea; Somma, Antonella; Borroni, Serena; Maffei, Cesare; Markon, Kristian E; Krueger, Robert F
To evaluate the associations between Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) Alternative Model of Personality Disorder traits and domains and categorically diagnosed narcissistic personality disorder (NPD) and borderline personality disorder (BPD), respectively, 238 inpatient and outpatient participants who were consecutively admitted to the Clinical Psychology and Psychotherapy Unit of San Raffaele Hospital in Milan, Italy, were administered the Personality Inventory for DSM-5 (PID-5) and the Structured Clinical Interview for DSM-IV Axis II Personality Disorders (SCID-II). Based on SCID-II, the participants were assigned to the following groups: a) NPD (n = 49), b) BPD (n = 32), c) any other PD (n = 91), and d) no PD (n = 63). Emotional lability, separation insecurity, depressivity, impulsivity, risk taking, and hostility were significantly associated with BPD diagnosis. Attention seeking significantly discriminated participants who received an SCID-II categorical NPD diagnosis. Separation insecurity, impulsivity, distractibility, and perceptual dysregulation were the DSM-5 traits that significantly discriminated BPD participants. Domain-level analyses confirmed and extended trait-level findings.
Lebedeva, Elena R; Kobzeva, Natalia R; Gilev, Denis
BACKGROUND: The aim of our study was to estimate the one-year prevalence of primary headache disorders in three different social groups using the third edition beta of the International Classification of Headache Disorders (ICHD-3 beta). MATERIAL AND METHODS: The study population included a total...... of 3124 participants: 1042 students (719 females, 323 males, mean age 20.6, age range 17-40), 1075 workers (146 females, 929 males, mean age 40.4, age range 21-67) and 1007 blood donors (484 females, 523 males, mean age 34.1, age range 18-64). We used a semi-structured, validated face-to-face interview....... RESULTS: The age-adjusted one-year prevalence of migraine in females was significantly higher (p Age-adjusted prevalence of migraine among males did not differ among the three groups: 4.5% in students, 4.9% in workers and 4...
Niebudek-Bogusz, Ewa; Fiszer, Marta; Sliwińska-Kowalska, Mariola
Laryngovideostroboscopy is the method most frequently used in the assessment of voice disorders. However, the employment of quantitative methods, such as voice acoustic analysis, is essential for evaluating the effectiveness of prophylactic and therapeutic activities as well as for objective medical certification of larynx pathologies. The aim of this study was to examine voice acoustic parameters in female teachers with occupational voice diseases. Acoustic analysis (IRIS software) was performed in 66 female teachers, including 35 teachers with occupational voice diseases and 31 with functional dysphonia. The teachers with occupational voice diseases presented the lower average fundamental frequency (193 Hz) compared to the group with functional dysphonia (209 Hz) and to the normative value (236 Hz), whereas other acoustic parameters did not differ significantly in both groups. Voice acoustic analysis, when applied separately from vocal loading, cannot be used as a testing method to verify the diagnosis of occupational voice disorders.
Fandiño, Julia N; Benchimol, Alexander K; Fandiño, Leila N; Barroso, Fernando L; Coutinho, Walmir F; Appolinário, José C
Wernicke-Korsakoff syndrome (WKS) and disordered eating behavior have been reported separately after bariatric surgery. We report a patient who following a bariatric operation developed WKS associated with a disturbed eating behavior without vomiting. This morbidly obese man developed an intense fear of gaining weight in the postoperative period and engaged in an extreme form of "food avoidance behavior". 2 months postoperatively after severe weight loss, he was hospitalized with disorientation and an amnesic syndrome. He was discharged 2 months later with stable weight and regular eating habits. Despite this, at the last follow-up visit 2 years postoperatively, he still had a residual partial amnesic syndrome. The surgical team must be aware of peculiar forms of pathological eating that may appear after bariatric surgery; the emergence of an eating avoidance disorder may be associated with the development of WKS.
Full Text Available Background The present paper reports the results of research aimed at identifying intra-group differences among females suffering from different eating disorders (anorexia nervosa, bulimia nervosa or binge eating disorder in terms of the subjects’ psychological traits, adoption of socio-cultural norms (through media pressure, internationalization of norms, and exposure to information concerning body image standards, and the level of body dissatisfaction. The following research question was asked: is it possible to distinguish specific profiles of psychological characteristics, as well as levels of body dissatisfaction, social pressure, media exposure and internalization of common standards of body image? Participants and procedure The clinical population consisted of 121 females aged 20-26. The research was conducted in the years 2007-2012. The following research methods and procedures were applied: 1 a clinical interview, 2 the Contour Drawing Rating Scale, 3 the Eating Disorder Inventory (EDI, 4 a Polish translation of the Socio-cultural Attitudes Towards Appearance Questionnaire (SATAQ-3. Results Cluster analysis of the research data allowed four significantly different clusters to be distinguished in the group of 121 examined females suffering from eating disorders. In the next step, analysis of variance (the ANOVA test was used to compare the differences between the examined clusters in terms of the investigated variables and their indicators. Conclusions Due to significant differences between the examined females in terms of the strength levels and the configuration of psychological and socio-cultural variables investigated in the present study, the females were classified into four different psychological types referred to as neurotic, perfectionist, impulsive and adolescent-narcissistic.
Mayes, Susan D.
The smallest subset of items from the 30-item Checklist for Autism Spectrum Disorder (CASD) that differentiated 607 referred children (3-17 years) with and without autism with 100% accuracy was identified. This 6-item subset (CASD-Short Form) was cross-validated on an independent sample of 397 referred children (1-18 years) with and without autism…
As a supplement of the study on a dignosed case of MPD (Multiple Personality Disorder), the effect of the psychotherapy was discussed. The patient was a twenty-four-year-old woman suspected of an attempted murder. In this article, continued from the previous one reporting the process of a series of ten psychotherapeutic interviews with her, the general comment on that was made, and the merits and demerits of the psychotherapy were clarified.
Full Text Available Background: The principle features of Attention deficit hyperactivity disorder (ADHD are hyperactivity, inattention and impulsivity. There is little evidence that confirms that Attention deficit hyperactivity disorder (ADHD is arising purely from child rearing methods or social factors.76 % of children with ADHD has a family history, and the similar cases can be seen in the family. The symptoms of more than 50 % of ADHD children will continue in adulthood which requires treatment. Most of the causes appear for ADHD are categorizing the condition in a group of neurobiological and genetic disorders. This does not mean to say that the influence of environmental factors on the severity of disorder, impairment and suffering the child may experience is nil, but those factors do not give rise to the condition by themselves. The chances of getting associated problems like Oppositional Defiant Disorder (ODD in children with ADHD is one-third to one-half and ODD is more common in boys with ADHD. These children are often non compliant, stubborn, defiant, have outbursts of temper, or become belligerent. Case description: This is a case report of a child who diagnosed as attention deficit hyper active disordered and Oppositional Defiant Disordered (ODD child, with finger contractures of right hand, which treated with medications, behavioral therapy, physiotherapy, relaxation techniques and music therapy as the means of rehabilitation. Outcome measures: The evaluation measures used are Nine-hole peg test, behavioral rating scale and a seven items temperament evaluation scale. Discussion: A holistic rehabilitation therapy increased attention, listening to suggestions, short stories and sleeping in time. Oppositional behaviors were also reduced both at home and school. Her relationships with parent, teachers and school mates were improved. Listening skills, attention, daily activities such as wake up, brushing, bathing, going to school in time were also
Nygaard, Mette Kathrine; Sonne, Charlotte Kærgaard; Carlsson, Jessica
at Competence Centre for Transcultural Psychiatry (CTP) were examined, and all the PTSD patients were divided into two groups; one group with secondary psychotic features (PTSD-SP group) and one without (PTSD group). A categorisation and description of the secondary psychotic features was undertaken. RESULTS......-SP prevalence in a clinical refugee population with PTSD. The study points to the difficulties distinguishing psychotic features from flashbacks and the authors call for attention to psychotic features in PTSD patients in order to improve documentation and understanding of the disorder....
Panischev, Yu; Panischeva, S N; Demin, S A
Here we demonstrate a capability of method based on the Flicker-Noise Spectroscopy (FNS) in analyzing the manifestation bipolar affective disorder (BAD) in EEG. Generally EEG from BAD patient does not show the visual differences from healthy EEG. Analyzing the behavior of FNS-parameters and the structure of 3D-cross correlators allows to discover the differential characteristics of BAD. The cerebral cortex electric activity of BAD patients have a specific collective dynamics and configuration of the FNS-characteristics in comparison with healthy subjects. (paper)
Omolehinwa, Temitope T; Musbah, Thamer; Desai, Bhavik; O'Malley, Bert W; Stoopler, Eric T
Head and neck neoplasms may be difficult to detect because of wide-ranging symptoms and the presence of overlapping anatomic structures in the region. This case report describes a patient with chronic otalgia and temporomandibular disorder, who developed sudden-onset neuralgia while receiving transcutaneous electrical nerve stimulation (TENS) therapy. Further diagnostic evaluation revealed a skull base tumor consistent with adenoid cystic carcinoma. To our knowledge, this is the first report of TENS-associated neuralgia leading to a diagnosis of primary intracranial adenoid cystic carcinoma. Copyright © 2015 Elsevier Inc. All rights reserved.
Scott, James G; Giørtz Pedersen, Marianne; Erskine, Holly E
by specialist services were followed from their first birthday to 2013. Those with and without DBDs were compared using mortality rate ratios (MRRs) estimated using Poisson regression and adjusted for calendar period, age, sex, family history of psychiatric disorders, maternal age at time of birth, paternal age...... at time of birth, parental education status, and parental employment status. Over the course of follow up, which totalled 24.9 million person-years, 5580 cohort members died including 78 individuals with DBDs. The mortality rate per 10,000 person-years was 9.66 for individuals with DBDs compared to 2...
Thongseiratch, Therdpong; Worachotekamjorn, Juthamas
This study compared the number of attention deficit hyperactivity disorder (ADHD) cases defined by Diagnostic and Statistical Manual (DSM)-IV versus DSM-V criterion in children who have learning or behavioral problems with high IQ. The medical records of children ≤15 years of age who presented with learning or behavioral problems and underwent a Wechsler Intelligence Scale for Children (WISC)-III IQ test at the Pediatric Outpatient Clinic unit between 2010 and 2015 were reviewed. Information on DSM-IV and DSM-V criteria for ADHD were derived from computer-based medical records. Twenty-eight children who had learning or behavioral problems were identified to have a full-scale IQ ≥120. Sixteen of these high-IQ children met the DSM-IV criteria diagnosis for ADHD. Applying the extension of the age-of-onset criterion from 7 to 12 years in DSM-V led to an increase of three cases, all of which were the inattentive type ADHD. Including the pervasive developmental disorder criterion led to an increase of one case. The total number of ADHD cases also increased from 16 to 20 in this group. The data supported the hypothesis that applying the extension of the age-of-onset ADHD criterion and enabling the diagnosis of children with pervasive developmental disorders will increase the number of ADHD diagnoses among children with high IQ. © The Author(s) 2016.
Elizabeth B. Torres
Full Text Available Background: The approximate 5:1 male to female ratio in clinical detection of Autism Spectrum Disorder (ASD prevents research from characterizing the female phenotype. Current open access repositories [such as those in the Autism Brain Imaging Data Exchange (ABIDE I-II] contain large numbers of females to help begin providing a new characterization of females on the autistic spectrum. Here we introduce new methods to integrate data in a scale-free manner from continuous biophysical rhythms of the nervous systems and discrete (ordinal observational scores.Methods: New data-types derived from image-based involuntary head motions and personalized statistical platform were combined with a data-driven approach to unveil sub-groups within the female cohort. Further, to help refine the clinical DSM-based ASD vs. Asperger's Syndrome (AS criteria, distributional analyses of ordinal score data from Autism Diagnostic Observation Schedule (ADOS-based criteria were used on both the female and male phenotypes.Results: Separate clusters were automatically uncovered in the female cohort corresponding to differential levels of severity. Specifically, the AS-subgroup emerged as the most severely affected with an excess level of noise and randomness in the involuntary head micro-movements. Extending the methods to characterize males of ABIDE revealed ASD-males to be more affected than AS-males. A thorough study of ADOS-2 and ADOS-G scores provided confounding results regarding the ASD vs. AS male comparison, whereby the ADOS-2 rendered the AS-phenotype worse off than the ASD-phenotype, while ADOS-G flipped the results. Females with AS scored higher on severity than ASD-females in all ADOS test versions and their scores provided evidence for significantly higher severity than males. However, the statistical landscapes underlying female and male scores appeared disparate. As such, further interpretation of the ADOS data seems problematic, rather suggesting the
DCD11 Congress Delegates
Full Text Available CD11 – Developmental coordination disorder and other neurodevelopmental disorders: a focus on comorbidity; Toulouse, France, July 2-4, 2015 Comorbidity refers to the presence of two or more disorders in the same person (especially DCD, dyslexia and attention deficit hyperactivity disorder in terms of developmental disorders. There has been growing interest in the presence of comorbidity in persons with neurodevelopmental disorders. Many recent studies suggest that up to half of all individuals diagnosed with a psychiatric or neurodevelopmental disorder have more than one condition. Comorbidity not only impacts patient outcomes but can also create a significant strain on both family and school life. It can also complicate diagnosis and healthcare organization. The 11th congress on DCD aimed to address some of the important issues surrounding comorbidity in neurodevelopmental disorders. Three main topics were covered during oral and poster presentations: (1 assessment and diagnostic criteria, (2 underlying processes, causal factors, and prognostic markers, and (3 intervention and management of DCD and associated disorders.
Marin-Avellan, Luisa E; McGauley, Gillian A; Campbell, Colin D; Fonagy, Peter
Current DSM-based instruments for personality disorders (PDs) limit the investigation of the course and outcome of treatment of these disorders. This study examined the validity of the Shedler-Westen Assessment Procedure-200 (SWAP-200) and the Structured Clinical Interview for DSM-IV Axis II PD (SCID-II) in a sample of forensic PD patients. Results based on 66 participants indicated that the SWAP-200 Q-factors reduced the frequency of diagnostic comorbidity of PD categories by half compared with the SCID-II. Only the SWAP-200's Antisocial PD category showed good convergent and discriminant validity with respect to other instruments describing aspects of PD. The validity of the cutoff score for severe antisocial PD was confirmed, and this category predicted severe incidents in the hospital at 1 year of follow-up. A violence risk scale was constructed, which differentiated violent and nonviolent offenders. The results support the validity of the SWAP-200 and its potential clinical utility with forensic PD patients.
Mazzoni, Paola; Kimhy, David; Khan, Shamir; Posner, Kelly; Maayan, Lawrence; Eilenberg, Mara; Messinger, Julie; Kestenbaum, Clarice; Corcoran, Cheryl
REASONS: Schizophrenia is typically an adult neurodevelopmental disorder that has its antecedents in childhood and adolescence. Little is known about disorders "usually first diagnosed in infancy, childhood and adolescence" (e.g., childhood-onset disorders) in "prodromal" teens at heightened clinical risk for psychotic disorder. Childhood-onset disorders were prevalent in putatively prodromal teens, including anxiety and disruptive disorders, attention-deficit/hyperactivity disorder (ADHD), and, surprisingly, elimination disorders. These may reflect developmental antecedents in psychotic disorders such as schizophrenia. A case series of 9 teens (ages 13-17) identified as prodromal to psychosis were evaluated with the Kiddie Schedule for Affective Disorders and Schizophrenia-Present and Lifetime Version (K-SADS-PL). Childhood-onset diagnoses commonly endorsed (threshold or subthreshold) included ADHD (5/9), oppositional defiant disorder (5/9), enuresis or encopresis (4/9), conduct disorder (2/9), separation anxiety (3/9), and transient tic disorder (2/9). Enuresis was identified in 3 of the 4 older teens (ages 15-17). An understanding of the childhood-onset disorders that occur in teens at risk for psychotic illnesses, such as schizophrenia, can shed light on the pathophysiology of schizophrenia and potentially inform early identification and intervention.
Full Text Available We highlight the importance of exome sequencing in solving a clinical case of a child who died at 14 months after a series of respiratory crises. He was the half-brother of a girl diagnosed at 7 years with the early-onset seizure variant of Rett syndrome due to CDKL5 mutation. We performed a test for CDKL5 in the boy, which came back negative. Driven by the mother’s compelling need for a diagnosis, we moved forward performing whole exome sequencing analysis. Surprisingly, two missense mutations in compound heterozygosity were identified in the RAPSN gene encoding a receptor-associated protein with a key role in clustering and anchoring nicotinic acetylcholine receptors at synaptic sites. This gene is responsible for a congenital form of myasthenic syndrome, a disease potentially treatable with cholinesterase inhibitors. Therefore, an earlier diagnosis in this boy would have led to a better clinical management and prognosis. Our study supports the key role of exome sequencing in achieving a definite diagnosis in severe perinatal diseases, an essential step especially when a specific therapy is available.
Uzawa, Akiyuki; Mori, Masahiro; Uchida, Tomohiko; Masuda, Hiroki; Ohtani, Ryohei; Kuwabara, Satoshi
Recently, new diagnostic criteria for neuromyelitis optica spectrum disorders (NMOSD) were published. Our primary aim was to evaluate the usefulness of the new diagnostic criteria in anti-aquaporin 4 (AQP4) antibody-negative cases. Consecutive 471 patients whose anti-AQP4 antibody was measured at Chiba University were reviewed. Four anti-AQP4 antibody negative-patients, who fulfilled the new diagnostic criteria for NMOSD but not 2006 diagnostic criteria for neuromyelitis optica (NMO), were identified. They showed high cerebrospinal fluid interleukin-6 and glial fibrillary acidic protein levels, an absence of oligoclonal bands and/or cloud-like enhancement on magnetic resonance imaging, which are compatible findings for NMO. The new diagnostic criteria are clinically useful in seronegative NMOSD. © The Author(s), 2015.
Lian, Wee Bin; Ho, Selina Kah Ying
There has been a rising trend in childhood developmental and behavioural disorders (CDABD). This study reports the profile of children with autistic spectrum disorders (ASD) initially referred for evaluation of CDABD. The CDABD database prospectively collected data of all consenting children referred in 2003 to the then Child Development Unit at KK Women's and Children's Hospital. All received medical consultation, followed by further assessments and intervention. Patients were tracked for one year. Among 542 referred children, 32% (n = 170) received a diagnosis of ASD one year after the first consultation. Most were male, with a male to female ratio of 4.5:1. The median age at the first consultation was 41 (19,109) months. The main presenting concern was a delay in the development of speech and language skills in 78% of the children. A significant number had behavioural (63%) and social interaction (34%) issues. Criteria for the diagnosis of ASD according to the Diagnostic Statistical Manual IV-Revised were fulfilled in almost 90%. With the remaining refusing or deferring evaluation, only 74% received a psychological assessment. ASD was assessed to be severe or moderate in 86% of the children. Three-quarters remained on follow-up one year after the first consultation. The majority were referred for either centre- or school-based intervention programmes, with 70% assessed to have improved at the one-year mark. This is the first presentation of local data that aids programme planning and resource allocation. Children with ASD have varied outcomes. It is important to identify and intervene early in order to optimise development and functionality.
Wood, Dennis Patrick; Wiederhold, Brenda K; Spira, James
Virtual-reality (VR) therapy has been distinguished from other psychotherapy interventions through the use of computer-assisted interventions that rely on the concepts of "immersion," "presence," and "synchrony." In this work, these concepts are defined, and their uses, within the VR treatment architecture, are discussed. VR therapy's emphasis on the incorporation of biofeedback and meditation, as a component of the VR treatment architecture, is also reviewed. A growing body of research has documented VR therapy as a successful treatment for combat-related Posttraumatic Stress Disorder (PTSD). The VR treatment architecture, utilized to treat 30 warriors diagnosed with combat-related PTSD, is summarized. Lastly, case summaries of two warriors successfully treated with VR therapy are included to assist with the goal of better understanding a VR treatment architecture paradigm. Continued validation of the VR treatment model is encouraged.
Rosen, Craig S; Greenbaum, Mark A; Fitt, Julie E; Laffaye, Charlene; Norris, Virginia A; Kimerling, Rachel
Survey and medical record data from 482 Veterans Affairs (VA) patients who recently received diagnoses of posttraumatic stress disorder (PTSD) were examined to determine need and predisposing factors associated with utilization of psychotherapy and counseling. More than half (58%) of participants initiated VA psychotherapy for PTSD within a year of diagnosis. Of those, one third completed eight or more sessions. Roughly two thirds of participants initiated counseling at a Vet Center. Initiating PTSD psychotherapy was associated with greater impairment but not with stigma, concerns about fitting in, or satisfaction with care. The use of Vet Center counseling was associated with desire for help, concerns about fitting in, and satisfaction with care. Unexpectedly, veterans with greater stigma concerns completed more psychotherapy visits and Vet Center counseling. Negative attitudes about mental health treatment did not seem to be substantial barriers to engaging in psychotherapy among these VA patients. Future research should consider enabling treatment system factors in addition to predisposing patient characteristics.
Sung, Min; Goh, Tze Jui; Tan, Bei Lin Joelene; Chan, Jialei Stephanie; Liew, Hwee Sen Alvin
Our study examines the Diagnostic and Statistical Manual-Fifth Edition (DSM-5) and Diagnostic and Statistical Manual-Fourth Edition, Text Revision (DSM-IV-TR) when applied concurrently against the best estimate clinical diagnoses for 110 children (5.1-19.6 years old) referred for diagnostic assessments of Autism Spectrum Disorder (ASD) in a Singaporean outpatient speciality clinic. DSM-IV-TR performed slightly better, yielding sensitivity of 0.946 and specificity of 0.889, compared to DSM-5 (sensitivity = 0.837; specificity = 0.833). When considering the ASD sub-categories, sensitivity ranged from 0.667 to 0.933, and specificity ranged from 0.900 to 0.975. More participants with a PDD-NOS best estimate clinical diagnosis (40%) were misclassified on DSM-5. Merits and weaknesses to both classification systems, and implications for access to services and policy changes are discussed.
Chawarska, Katarzyna; Macari, Suzanne; Shic, Frederick
The ability to spontaneously attend to the social overtures and activities of others is essential for the development of social cognition and communication. This ability is critically impaired in toddlers with autism spectrum disorders (ASD); however, it is not clear if prodromal symptoms in this area are already present in the first year of life of those affected by the disorder. To examine whether 6-month-old infants later diagnosed with ASD exhibit atypical spontaneous social monitoring skills, visual responses of 67 infants at high-risk and 50 at low-risk for ASD were studied using an eye-tracking task. Based on their clinical presentation in the third year, infants were divided into those with ASD, those exhibiting atypical development, and those developing typically. Compared with the control groups, 6-month-old infants later diagnosed with ASD attended less to the social scene, and when they did look at the scene, they spent less time monitoring the actress in general and her face in particular. Limited attention to the actress and her activities was not accompanied by enhanced attention to objects. Prodromal symptoms of ASD at 6 months include a diminished ability to attend spontaneously to people and their activities. A limited attentional bias toward people early in development is likely to have a detrimental impact on the specialization of social brain networks and the emergence of social interaction patterns. Further investigation into its underlying mechanisms and role in psychopathology of ASD in the first year is warranted. Copyright © 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
Full Text Available Objectives: Given the paucity of research on adolescent ADHD, this study aimed to establish the prevalence of DSM-IV ADHD in a cohort of South African adolescents who had been diagnosed with the disorder in childhood. It also aimed to establish the prevalence of psychiatric comorbidities and adjustment difficulties in this sample. Method: Data regarding age of diagnosis, current ADHD status, current ADHD-related pharmacological management, current psychopathology and current adjustment were gathered from 64 adolescents and their guardians via self-report questionnaire. Descriptive statistics were calculated with regard to current ADHD status, comorbid psychopathology and adjustment difficulties, as well as current ADHD-related medication. Results: According to parent reports, 59.38% of the sample met DSM-IV criteria for ADHD Inattentive subtype, while 37.50% met the criteria for ADHD Hyperactive/Impulsive subtype. Approximately sixty-four percent (64.06% of the adolescents were still using stimulant medication. Based on the adolescent self-report, 43.75% of the sample reported clinically significant symptoms of psychopathology or maladjustment. Furthermore, 39.28% of the adolescents met the diagnostic criteria for at least one psychiatric comorbidity. Conclusion: ADHD did persist into adolescence in the current sample. A significant psychopathological and maladjustment load appears evident amongst adolescents previously diagnosed with ADHD despite continuous pharmacological management of the condition.
Miller, Meghan; Sheridan, Margaret; Cardoos, Stephanie L; Hinshaw, Stephen P
We examined decision-making in young adulthood in a follow-up study of females diagnosed with attention-deficit/hyperactivity disorder (ADHD) between 6 and 12 years. Participants with childhood ADHD (n = 114) and matched comparison females (n = 77), followed prospectively for 10 years, performed the Iowa Gambling Task (IGT) at ages 17-25 years. This task assesses preference for high-reward/high-risk chances that result in lower overall gains (disadvantageous decks of cards) compared to low-reward/low-risk chances that result in higher overall gains (advantageous decks of cards). Relative to comparison participants, young adult females with a history of ADHD did not increase their preference for advantageous decks across time blocks, suggesting difficulties in learning to change behavior over the course of the IGT. Overall, childhood diagnoses of ADHD were associated with disadvantageous decision-making in young adulthood. These results extend findings on decision-making in males with ADHD by demonstrating comparable levels of impairment in an all-female sample.
Palermo, Mark T; Bogaerts, Stefan
Posthumous diagnoses are not uncommonly given to notorious public and historical figures by applying retrospectively, and typically in the absence of the individual being diagnosed, contemporary diagnostic criteria. Although this may be relatively easy and free of consequences when it concerns clear-cut medical conditions, it may have unintended repercussions in the case of psychiatric disorders by creating myths and perpetuating stigma. The case of serial killer Jeffrey Dahmer is a typical example where a somewhat facile and almost syllogistic application of perhaps over-inclusive criteria may have contributed to the legend of solitary murderers as possibly suffering from an autism spectrum condition. Although there may be an understandable human need to explain abominable and heinous behaviors, the lack of the possibility to verify a diagnostic theory and the ill-advised attempt to make a diagnosis fit may de facto be the basis of prejudice and profiling that do not correspond to clinical reality. Although there is no doubt that the brain is the organ of behavior, the authors caution against a budding neo-Lombrosian approach to crime and criminality and against the all too common use of widely differing terms in the study of deviance, such as crime, delinquency, and aggression, the operational use of which, often used interchangeably even in association studies, often erroneously leads to further confusion. © The Author(s) 2014.
Dreyfus, Remi; Xu, Ye; Still, Tim; Hough, L. A.; Yodh, A. G.; Torquato, Salvatore
Hyperuniformity characterizes a state of matter for which (scaled) density fluctuations diminish towards zero at the largest length scales. However, the task of determining whether or not an image of an experimental system is hyperuniform is experimentally challenging due to finite-resolution, noise, and sample-size effects that influence characterization measurements. Here we explore these issues, employing video optical microscopy to study hyperuniformity phenomena in disordered two-dimensional jammed packings of soft spheres. Using a combination of experiment and simulation we characterize the possible adverse effects of particle polydispersity, image noise, and finite-size effects on the assignment of hyperuniformity, and we develop a methodology that permits improved diagnosis of hyperuniformity from real-space measurements. The key to this improvement is a simple packing reconstruction algorithm that incorporates particle polydispersity to minimize the free volume. In addition, simulations show that hyperuniformity in finite-sized samples can be ascertained more accurately in direct space than in reciprocal space. Finally, our experimental colloidal packings of soft polymeric spheres are shown to be effectively hyperuniform.
Bertó, Clara; Ferrin, Maite; Barberá, María; Livianos, Lorenzo; Rojo, Luis; García-Blanco, Ana
Maltreated children usually show a specific pattern of emotional and behavioral symptoms that exceed those relating to posttraumatic stress disorder (PTSD). These symptoms have been defined as Complex PTSD (CPTSD). The underlying attentional mechanisms of abnormal emotional processing and their relation to the clinical presentation of CPTSD are not well understood. A visual dot-probe paradigm involving pre-attentive (i.e., 500ms) and attentive (i.e., 1500ms) presentation rates of neutral versus emotional (i.e., angry, happy or sad) facial expressions was applied. Twenty-one maltreated CPTSD children were compared with twenty-six controls. The results are as follows: an attention bias away from threatening faces and an attentional bias towards sad faces were observed in maltreated CPTSD children during pre-attentive and attentive processing. Whereas the attentional bias away from angry faces was associated with social problems, the attentional bias towards sad faces was associated with depressive and withdrawn symptoms. Therefore, CPTSD children develop maladaptive negative cognitive styles, which may underlie not only social problems (by a cognitive avoidance of threatening stimuli) but also depressive symptoms (by a cognitive approach to sad stimuli). Attention processing abnormalities should be considered as therapeutic targets for new treatment approaches in this population. Copyright © 2017 Elsevier Ltd. All rights reserved.
Steven D. Hicks
Full Text Available A number of studies have implicated pesticides in childhood developmental delay (DD and autism spectrum disorder (ASD. The influence of the route of pesticide exposure on neurodevelopmental delay is not well defined. To study this factor, we examined ASD/DD diagnoses rates in an area near our regional medical center that employs yearly aerial pyrethroid pesticide applications to combat mosquito-borne encephalitis. The aim of this study was to determine if areas with aerial pesticide exposure had higher rates of ASD/DD diagnoses. This regional study identified higher rates of ASD/DD diagnoses in an area with aerial pesticides application. Zip codes with aerial pyrethroid exposure were 37% more likely to have higher rates of ASD/DD (adjusted RR = 1.37, 95% CI = 1.06–1.78, p = 0.02. A Poisson regression model controlling for regional characteristics (poverty, pesticide use, population density, and distance to medical center, subject characteristics (race and sex, and local birth characteristics (prematurity, low birthweight, and birth rates identified a significant relationship between aerial pesticide use and ASD/DD rates. The relationship between pesticide application and human neurodevelopment deserves additional study to develop safe and effective methods of mosquito prevention, particularly as communities develop plans for Zika virus control.
Hicks, Steven D; Wang, Ming; Fry, Katherine; Doraiswamy, Vignesh; Wohlford, Eric M
A number of studies have implicated pesticides in childhood developmental delay (DD) and autism spectrum disorder (ASD). The influence of the route of pesticide exposure on neurodevelopmental delay is not well defined. To study this factor, we examined ASD/DD diagnoses rates in an area near our regional medical center that employs yearly aerial pyrethroid pesticide applications to combat mosquito-borne encephalitis. The aim of this study was to determine if areas with aerial pesticide exposure had higher rates of ASD/DD diagnoses. This regional study identified higher rates of ASD/DD diagnoses in an area with aerial pesticides application. Zip codes with aerial pyrethroid exposure were 37% more likely to have higher rates of ASD/DD (adjusted RR = 1.37, 95% CI = 1.06-1.78, p = 0.02). A Poisson regression model controlling for regional characteristics (poverty, pesticide use, population density, and distance to medical center), subject characteristics (race and sex), and local birth characteristics (prematurity, low birthweight, and birth rates) identified a significant relationship between aerial pesticide use and ASD/DD rates. The relationship between pesticide application and human neurodevelopment deserves additional study to develop safe and effective methods of mosquito prevention, particularly as communities develop plans for Zika virus control.
Thomas, Jennifer J; Eddy, Kamryn T; Murray, Helen B; Tromp, Marilou D P; Hartmann, Andrea S; Stone, Melissa T; Levendusky, Philip G; Becker, Anne E
This study evaluated the relative distribution and inter-rater reliability of revised DSM-5 criteria for eating disorders in a residential treatment program. Consecutive adolescent and young adult females (N=150) admitted to a residential eating disorder treatment facility were assigned both DSM-IV and DSM-5 diagnoses by a clinician (n=14) via routine clinical interview and a research assessor (n=4) via structured interview. We compared the frequency of diagnostic assignments under each taxonomy and by type of assessor. We evaluated concordance between clinician and researcher assignment through inter-rater reliability kappa and percent agreement. Significantly fewer patients received either clinician or researcher diagnoses of a residual eating disorder under DSM-5 (clinician-12.0%; researcher-31.3%) versus DSM-IV (clinician-28.7%; researcher-59.3%), with the majority of reassigned DSM-IV residual cases reclassified as DSM-5 anorexia nervosa. Researcher and clinician diagnoses showed moderate inter-rater reliability under DSM-IV (κ=.48) and DSM-5 (κ=.57), though agreement for specific DSM-5 other specified feeding or eating disorder (OSFED) presentations was poor (κ=.05). DSM-5 revisions were associated with significantly less frequent residual eating disorder diagnoses, but not with reduced inter-rater reliability. Findings support specific dimensions of clinical utility for revised DSM-5 criteria for eating disorders. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
Paesani, D A; Lobbezoo, F; Gelos, C; Guarda-Nardini, L