Loss-of-function of neuroplasticity-related genes confers risk for human neurodevelopmental disorders.

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Smith, Milo R; Glicksberg, Benjamin S; Li, Li; Chen, Rong; Morishita, Hirofumi; Dudley, Joel T

2018-01-01

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.

Predictors of Co-occurring Neurodevelopmental Disabilities in Children With Autism Spectrum Disorders.

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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.

Reducing neurodevelopmental disorders and disability through research and interventions.

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Boivin, Michael J; Kakooza, Angelina M; Warf, Benjamin C; Davidson, Leslie L; Grigorenko, Elena L

2015-11-19

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

Neurodevelopmental disorders are highly over-represented in children with obesity: A cross-sectional study.

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Wentz, Elisabet; Björk, Anna; Dahlgren, Jovanna

2017-01-01

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.

Epigenetics as a basis for diagnosis of neurodevelopmental disorders: challenges and opportunities.

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Kubota, Takeo; Miyake, Kunio; Hariya, Natsuyo; Mochizuki, Kazuki

2014-07-01

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.

Language cannot be reduced to biology: perspectives from neuro-developmental disorders affecting language learning.

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Vasanta, D

2005-02-01

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

Prevalence of neurodevelopmental disorders among low-income African Americans at a clinic on Chicago's south side.

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Bell, Carl C; Chimata, Radhika

2015-05-01

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.

Increased nuchal translucency thickness and the risk of neurodevelopmental disorders

DEFF Research Database (Denmark)

Hellmuth, Signe G; Pedersen, L H; Miltoft, Caroline B

2016-01-01

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...

Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings.

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Dichter, Gabriel S; Damiano, Cara A; Allen, John A

2012-07-06

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.

"Too Withdrawn" or "Too Friendly": Considering Social Vulnerability in Two Neuro-Developmental Disorders

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Jawaid, A.; Riby, D. M.; Owens, J.; White, S. W.; Tarar, T.; Schulz, P. E.

2012-01-01

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…

Management of sleep disorders in neurodevelopmental disorders and genetic syndromes.

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Heussler, Helen S

2016-03-01

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.

A compensatory role for declarative memory in neurodevelopmental disorders

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Ullman, Michael T.; Pullman, Mariel Y.

2015-01-01

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

Histone Lysine Methylation and Neurodevelopmental Disorders

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Jeong-Hoon Kim

2017-06-01

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.

School Neuropsychology Consultation in Neurodevelopmental Disorders

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Decker, Scott L.

2008-01-01

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…

Advanced paternal age effects in neurodevelopmental disorders-review of potential underlying mechanisms.

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Janecka, M; Mill, J; Basson, M A; Goriely, A; Spiers, H; Reichenberg, A; Schalkwyk, L; Fernandes, C

2017-01-31

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.

7,8-Dihydroxyflavone as a pro-neurotrophic treatment for neurodevelopmental disorders.

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Du, X; Hill, R A

2015-10-01

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.

Male-specific deficits in natural reward learning in a mouse model of neurodevelopmental disorders

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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

Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings

Directory of Open Access Journals (Sweden)

Dichter Gabriel S

2012-07-01

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.

Maternal obesity and neurodevelopmental and psychiatric disorders in offspring

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Edlow, Andrea G.

2017-01-01

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

Adaptive Profiles in Autism and Other Neurodevelopmental Disorders

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Mouga, Susana; Almeida, Joana; Café, Cátia; Duque, Frederico; Oliveira, Guiomar

2015-01-01

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…

Children with optic nerve hypoplasia face a high risk of neurodevelopmental disorders.

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Dahl, Sara; Wickström, Ronny; Ek, Ulla; Teär Fahnehjelm, Kristina

2018-03-01

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.

Neurodevelopmental Disorders (ASD and ADHD): DSM-5, ICD-10, and ICD-11.

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Doernberg, Ellen; Hollander, Eric

2016-08-01

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.

Practitioner Review: Multilingualism and neurodevelopmental disorders - an overview of recent research and discussion of clinical implications.

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Uljarević, Mirko; Katsos, Napoleon; Hudry, Kristelle; Gibson, Jenny L

2016-11-01

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

The Endosome Localized Arf-GAP AGAP1 Modulates Dendritic Spine Morphology Downstream of the Neurodevelopmental Disorder Factor Dysbindin

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Miranda Arnold

2016-09-01

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.

Altered social behaviours in neurexin 1α knockout mice resemble core symptoms in neurodevelopmental disorders.

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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.

Altered Social Behaviours in Neurexin 1α Knockout Mice Resemble Core Symptoms in Neurodevelopmental Disorders

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Grayton, Hannah Mary; Missler, Markus

2013-01-01

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

An Open Conversation on Using Eye-Gaze Methods in Studies of Neurodevelopmental Disorders

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Venker, Courtney E.; Kover, Sara T.

2015-01-01

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…

Human GRIN2B variants in neurodevelopmental disorders

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Chun Hu

2016-10-01

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.

Assessing the Influence of Researcher-Partner Involvement on the Process and Outcomes of Participatory Research in Autism Spectrum Disorder and Neurodevelopmental Disorders: A Scoping Review

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Jivraj, Jamil; Sacrey, Lori-Ann; Newton, Amanda; Nicholas, David; Zwaigenbaum, Lonnie

2014-01-01

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…

Neurobiological circuits regulating attention, cognitive control, motivation, and emotion: disruptions in neurodevelopmental psychiatric disorders.

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Arnsten, Amy F T; Rubia, Katya

2012-04-01

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

Clinical Performance of an Ultrahigh Resolution Chromosomal Microarray Optimized for Neurodevelopmental Disorders.

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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

2016-01-01

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.

Immunization Safety Review: Thimerosal - Containing Vaccines and Neurodevelopmental Disorders

National Research Council Canada - National Science Library

Stratton, Kathleen; Gable, Alicia; McCormick, Marie C

2001-01-01

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...

Molecular underpinnings of prefrontal cortex development in rodents provide insights into the etiology of neurodevelopmental disorders.

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Schubert, D; Martens, G J M; Kolk, S M

2015-07-01

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.

Using Sibling Designs to Understand Neurodevelopmental Disorders: From Genes and Environments to Prevention Programming

OpenAIRE

Wade, Mark; Prime, Heather; Madigan, Sheri

2015-01-01

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...

Therapeutic Targets for Neurodevelopmental Disorders Emerging from Animal Models with Perinatal Immune Activation

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Daisuke Ibi

2015-11-01

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.

Hypospadias and increased risk for neurodevelopmental disorders

OpenAIRE

Butwicka, Agnieszka; Lichtenstein, Paul; Landén, Mikael; Nordenvall, Anna; Nordenström, Anna; Nordenskjöld, Agneta; Frisén, Louise

2014-01-01

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 ...

Intellectual Profiles in the Autism Spectrum and Other Neurodevelopmental Disorders

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Mouga, Susana; Café, Cátia; Almeida, Joana; Marques, Carla; Duque, Frederico; Oliveira, Guiomar

2016-01-01

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…

Hypospadias and increased risk for neurodevelopmental disorders.

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Butwicka, Agnieszka; Lichtenstein, Paul; Landén, Mikael; Nordenvall, Anna S; Nordenström, Anna; Nordenskjöld, Agneta; Frisén, Louise

2015-02-01

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

Conceptualizing neurodevelopmental disorders through a mechanistic understanding of fragile X syndrome and Williams syndrome.

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Fung, Lawrence K; Quintin, Eve-Marie; Haas, Brian W; Reiss, Allan L

2012-04-01

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.

Epigenetic Mechanisms and Therapeutic Perspectives for Neurodevelopmental Disorders

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Kunio Miyake

2012-04-01

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.

Boys with Asperger Syndrome Grow Up: Psychiatric and Neurodevelopmental Disorders 20 Years After Initial Diagnosis.

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Gillberg, I Carina; Helles, Adam; Billstedt, Eva; Gillberg, Christopher

2016-01-01

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.

Neurodevelopmental profile of Fetal Alcohol Spectrum Disorder: A systematic review.

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Lange, Shannon; Rovet, Joanne; Rehm, Jürgen; Popova, Svetlana

2017-06-23

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.

Treatments for Neurodevelopmental Disorders: Evidence, Advocacy, and the Internet

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Di Pietro, Nina C.; Whiteley, Louise; Mizgalewicz, Ania; Illes, Judy

2013-01-01

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…

Neurodevelopmental disorders: cluster 2 of the proposed meta-structure for DSM-V and ICD-11.

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Andrews, G; Pine, D S; Hobbs, M J; Anderson, T M; Sunderland, M

2009-12-01

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.

Improving treatment of neurodevelopmental disorders: recommendations based on preclinical studies

NARCIS (Netherlands)

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.

2016-01-01

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

Role of nucleosome remodeling in neurodevelopmental and intellectual disability disorders

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Alberto J Lopez

2015-04-01

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.

Role of nucleosome remodeling in neurodevelopmental and intellectual disability disorders.

Science.gov (United States)

López, Alberto J; Wood, Marcelo A

2015-01-01

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.

Using Sibling Designs to Understand Neurodevelopmental Disorders: From Genes and Environments to Prevention Programming.

Science.gov (United States)

Wade, Mark; Prime, Heather; Madigan, Sheri

2015-01-01

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.

New insights into the role of motion and form vision in neurodevelopmental disorders.

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Johnston, Richard; Pitchford, Nicola J; Roach, Neil W; Ledgeway, Timothy

2017-12-01

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.

Seroprevalence of Toxoplasma gondii infection among patients with non-schizophrenic neurodevelopmental disorders in Alexandria, Egypt.

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Shehata, Amany I; Hassanein, Faika I; Abdul-Ghani, Rashad

2016-02-01

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.

Neurodevelopmental disorders: theoretical approaches and its implications for education and rehabilitation

Directory of Open Access Journals (Sweden)

Maria Luísa Bissoto

2011-06-01

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.

Using Sibling Designs to Understand Neurodevelopmental Disorders: From Genes and Environments to Prevention Programming

Directory of Open Access Journals (Sweden)

Mark Wade

2015-01-01

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.

Neurodevelopmental Disorders in Low- and Middle-Income Countries

Science.gov (United States)

Newton, Charles R.

2012-01-01

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…

Genetic controls balancing excitatory and inhibitory synaptogenesis in neurodevelopmental disorder models

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Cheryl L Gatto

2010-06-01

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.

Childhood neurodevelopmental disorders and violent criminality: a sibling control study.

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Lundström, Sebastian; Forsman, Mats; Larsson, Henrik; Kerekes, Nora; Serlachius, Eva; Långström, Niklas; Lichtenstein, Paul

2014-11-01

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.

Which neurodevelopmental disorders get researched and why?

Directory of Open Access Journals (Sweden)

Dorothy V M Bishop

2010-11-01

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.

Schizophrenia and the neurodevelopmental continuum:evidence from genomics.

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Owen, Michael J; O'Donovan, Michael C

2017-10-01

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

Development and analysis of the factor structure of parents' internalized stigma of neurodevelopmental disorder in child scale

Directory of Open Access Journals (Sweden)

Ananya Mahapatra

2017-01-01

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

De Novo and Inherited Loss-of-Function Variants in TLK2: Clinical and Genotype-Phenotype Evaluation of a Distinct Neurodevelopmental Disorder.

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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

2018-06-07

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.

Sleep, Plasticity and the Pathophysiology of Neurodevelopmental Disorders: The Potential Roles of Protein Synthesis and Other Cellular Processes

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Dante Picchioni

2014-03-01

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.

Offspring neuroimmune consequences of maternal malnutrition: Potential mechanism for behavioral impairments that underlie metabolic and neurodevelopmental disorders.

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Smith, B L; Reyes, T M

2017-10-01

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.

Neurodevelopmental marker for limbic maldevelopment in antisocial personality disorder and psychopathy.

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Raine, Adrian; Lee, Lydia; Yang, Yaling; Colletti, Patrick

2010-09-01

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.

Boys with Asperger Syndrome Grow Up: Psychiatric and Neurodevelopmental Disorders 20 Years after Initial Diagnosis

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Gillberg, I. Carina; Helles, Adam; Billstedt, Eva; Gillberg, Christopher

2016-01-01

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…

Neurobiological Circuits Regulating Attention, Cognitive Control, Motivation, and Emotion: Disruptions in Neurodevelopmental Psychiatric Disorders

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Arnsten, Amy F. T.; Rubia, Katya

2012-01-01

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,…

Neurodevelopmental marker for limbic maldevelopment in antisocial personality disorder and psychopathy

Science.gov (United States)

Raine, Adrian; Lee, Lydia; Yang, Yaling; Colletti, Patrick

2010-01-01

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

The Influence of Maternal Prenatal and Early Childhood Nutrition and Maternal Prenatal Stress on Offspring Immune System Development and Neurodevelopmental Disorders

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Andrea Horvath Marques

2013-07-01

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

Adaptation of the "Ten Questions" to Screen for Autism and other Neurodevelopmental Disorders in Uganda

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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.

2014-01-01

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…

EPG5-related Vici syndrome: a paradigm of neurodevelopmental disorders with defective autophagy

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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

2016-01-01

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

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.

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Durukan, İbrahim; Kara, Koray; Almbaideen, Mahmoud; Karaman, Dursun; Gül, Hesna

2018-03-01

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.

Neurodevelopmental delay in children exposed in utero to hyperemesis gravidarum.

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Fejzo, Marlena S; Magtira, Aromalyn; Schoenberg, Frederic Paik; Macgibbon, Kimber; Mullin, Patrick M

2015-06-01

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.

Parenting stress among parents of children with Neurodevelopmental Disorders.

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Craig, Francesco; Operto, Francesca Felicia; De Giacomo, Andrea; Margari, Lucia; Frolli, Alessandro; Conson, Massimiliano; Ivagnes, Sara; Monaco, Marianna; Margari, Francesco

2016-08-30

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.

Postnatal testosterone may be an important mediator of the association between prematurity and male neurodevelopmental disorders: a hypothesis.

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Rice, Timothy R

2017-04-01

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.

Vitamin D deficiency: infertility and neurodevelopmental diseases (attention deficit hyperactivity disorder, autism, and schizophrenia).

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Berridge, Michael J

2018-02-01

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.

Relationship between motor coordination, cognitive abilities, and academic achievement in Japanese children with neurodevelopmental disorders

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Takuya Higashionna

2017-12-01

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.

Autism spectrum disorder in a community-based sample with neurodevelopmental problems in Lagos, Nigeria

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Yewande O. Oshodi

2017-01-01

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

Neurodevelopmental attributes of joint hypermobility syndrome/Ehlers-Danlos syndrome, hypermobility type: Update and perspectives.

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Ghibellini, Giulia; Brancati, Francesco; Castori, Marco

2015-03-01

In the last decade, increasing attention has been devoted to the extra-articular and extra-cutaneous manifestations of joint hypermobility syndrome, also termed Ehlers-Danlos syndrome, hypermobility type (i.e., JHS/EDS-HT). Despite the fact that the current diagnostic criteria for both disorders remain focused on joint hypermobility, musculoskeletal pain and skin changes, medical practice and research have started investigating a wide spectrum of visceral, neurological and developmental complications, which represent major burdens for affected individuals. In particular, children with generalized joint hypermobility often present with various neurodevelopmental issues and can be referred for neurological consultation. It is common that investigations in these patients yield negative or inconsistent results, eventually leading to the exclusion of any structural neurological or muscle disorder. In the context of specialized clinics for connective tissue disorders, a clear relationship between generalized joint hypermobility and a characteristic neurodevelopmental profile affecting coordination is emerging. The clinical features of these patients tend to overlap with those of developmental coordination disorder and can be associated with learning and other disabilities. Physical and psychological consequences of these additional difficulties add to the chief manifestations of the pre-existing connective tissue disorder, affecting the well-being and development of children and their families. In this review, particular attention is devoted to the nature of the link between joint hypermobility, coordination difficulties and neurodevelopmental issues in children. Presumed pathogenesis and management issues are explored in order to attract more attention on this association and nurture future clinical research. © 2015 Wiley Periodicals, Inc.

Insulin-Like Growth Factor 1 and Related Compounds in the Treatment of Childhood-Onset Neurodevelopmental Disorders

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Cyrus Vahdatpour

2016-09-01

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.

GABAergic circuit dysfunctions in neurodevelopmental disorders

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Bidisha eChattopadhyaya

2012-05-01

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.

Can ω-3 fatty acids and tocotrienol-rich vitamin E reduce symptoms of neurodevelopmental disorders?

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Gumpricht, Eric; Rockway, Susie

2014-01-01

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.

Associations of caesarean delivery and the occurrence of neurodevelopmental disorders, asthma or obesity in childhood based on Taiwan birth cohort study.

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Chen, Ginden; Chiang, Wan-Lin; Shu, Bih-Ching; Guo, Yue Leon; Chiou, Shu-Ti; Chiang, Tung-Liang

2017-09-27

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.

EPG5-related Vici syndrome: a paradigm of neurodevelopmental disorders with defective autophagy

Science.gov (United States)

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

2016-01-01

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

Neurodevelopmental disease-associated de novo mutations and rare sequence variants affect TRIO GDP/GTP exchange factor activity.

Science.gov (United States)

Katrancha, Sara M; Wu, Yi; Zhu, Minsheng; Eipper, Betty A; Koleske, Anthony J; Mains, Richard E

2017-12-01

Bipolar disorder, schizophrenia, autism and intellectual disability are complex neurodevelopmental disorders, debilitating millions of people. Therapeutic progress is limited by poor understanding of underlying molecular pathways. Using a targeted search, we identified an enrichment of de novo mutations in the gene encoding the 330-kDa triple functional domain (TRIO) protein associated with neurodevelopmental disorders. By generating multiple TRIO antibodies, we show that the smaller TRIO9 isoform is the major brain protein product, and its levels decrease after birth. TRIO9 contains two guanine nucleotide exchange factor (GEF) domains with distinct specificities: GEF1 activates both Rac1 and RhoG; GEF2 activates RhoA. To understand the impact of disease-associated de novo mutations and other rare sequence variants on TRIO function, we utilized two FRET-based biosensors: a Rac1 biosensor to study mutations in TRIO (T)GEF1, and a RhoA biosensor to study mutations in TGEF2. We discovered that one autism-associated de novo mutation in TGEF1 (K1431M), at the TGEF1/Rac1 interface, markedly decreased its overall activity toward Rac1. A schizophrenia-associated rare sequence variant in TGEF1 (F1538Intron) was substantially less active, normalized to protein level and expressed poorly. Overall, mutations in TGEF1 decreased GEF1 activity toward Rac1. One bipolar disorder-associated rare variant (M2145T) in TGEF2 impaired inhibition by the TGEF2 pleckstrin-homology domain, resulting in dramatically increased TGEF2 activity. Overall, genetic damage to both TGEF domains altered TRIO catalytic activity, decreasing TGEF1 activity and increasing TGEF2 activity. Importantly, both GEF changes are expected to decrease neurite outgrowth, perhaps consistent with their association with neurodevelopmental disorders. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Treatments and services for neurodevelopmental disorders on advocacy websites: Information or evaluation?

DEFF Research Database (Denmark)

Di Pietro, Nina C; Whiteley, Louise Emma; Illes, Judy

2011-01-01

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...

Autism as early neurodevelopmental disorder: evidence for an sAPPα-mediated anabolic pathway

OpenAIRE

Lahiri, Debomoy K.; Sokol, Deborah K.; Erickson, Craig; Ray, Balmiki; Ho, Chang Y.; Maloney, Bryan

2013-01-01

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...

Neurodevelopmental Disorders in Children with Severe to Profound Sensorineural Hearing Loss: A Clinical Study

Science.gov (United States)

Chilosi, Anna M.; Comparini, Alessandro; Scusa, Maria F.; Berrettini, Stefano; Forli, Francesca; Battini, Roberta; Cipriani, Paola; Cioni, Giovanni

2010-01-01

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…

Neural systems supporting cognitive-affective interactions in adolescence: The role of puberty and implications for affective disorders

Directory of Open Access Journals (Sweden)

Cecile D. Ladouceur

2012-08-01

Full Text Available Evidence from longitudinal studies suggests that adolescence may represent a period of vulnerability that, in the context of adverse events, could contribute to developmental trajectories toward behavioral and emotional health problems, including affective disorders. Adolescence is also a sensitive period for the development of neural systems supporting cognitive-affective processes, which have been implicated in the pathophysiology of affective disorders such as anxiety and mood disorders. In particular, the onset of puberty brings about a cascade of physical, hormonal, psychological, and social changes that contribute in complex ways to the development of these systems. This article provides a brief overview of neuroimaging research pertaining to the development of cognitive-affective processes in adolescence. It also includes a brief review of evidence from animal and human neuroimaging studies suggesting that sex steroids influence the connectivity between prefrontal cortical and subcortical limbic regions in ways that contribute to increased reactivity to emotionally salient stimuli. We integrate these findings in the context of a developmental affective neuroscience framework suggesting that the impact of rising levels of sex steroids during puberty on fronto-limbic connectivity may be even greater in the context of protracted development of prefrontal cortical regions in adolescence. We conclude by discussing the implications of these findings for future research aimed at identifying neurodevelopmental markers of risk for future onset of affective disorders.

EPG5-related Vici syndrome: a paradigm of neurodevelopmental disorders with defective autophagy.

Science.gov (United States)

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

2016-03-01

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

Heterogeneity of executive functions among comorbid neurodevelopmental disorders

Science.gov (United States)

Dajani, Dina R.; Llabre, Maria M.; Nebel, Mary Beth; Mostofsky, Stewart H.; Uddin, Lucina Q.

2016-01-01

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

An evaluation of speech production in two boys with neurodevelopmental disorders who received communication intervention with a speech-generating device.

Science.gov (United States)

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

2014-11-01

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.

Disruption of the ASTN2 / TRIM32 locus at 9q33.1 is a risk factor in males for Autism Spectrum Disorders, ADHD and other neurodevelopmental phenotypes

DEFF Research Database (Denmark)

Lionel, Anath C; Tammimies, Kristiina; Vaags, Andrea K

2014-01-01

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...

Neurodevelopmental Reflex Testing in Neonatal Rat Pups.

Science.gov (United States)

Nguyen, Antoinette T; Armstrong, Edward A; Yager, Jerome Y

2017-04-24

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.

Creatine Transporter Deficiency: Screening of Males with Neurodevelopmental Disorders and Neurocognitive Characterization of a Case.

Science.gov (United States)

Thurm, Audrey; Himelstein, Daniel; DʼSouza, Precilla; Rennert, Owen; Jiang, Susanqi; Olatunji, Damilola; Longo, Nicola; Pasquali, Marzia; Swedo, Susan; Salomons, Gajja S; Carrillo, Nuria

2016-05-01

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.

Inter-rater Reliability on the Individual Music-Centered Assessment Profile for Neurodevelopmental Disorders (IMCAP-ND) for autism spectrum disorder. Nordic Journal of Music Therapy

DEFF Research Database (Denmark)

Carpente, John; Gattino, Gustavo

2018-01-01

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...

Temporal changes in the incidence of treated psychiatric and neurodevelopmental disorders during adolescence: an analysis of two national Finnish birth cohorts.

Science.gov (United States)

Gyllenberg, David; Marttila, Mikko; Sund, Reijo; Jokiranta-Olkoniemi, Elina; Sourander, André; Gissler, Mika; Ristikari, Tiina

2018-03-01

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

Same or different: Common pathways of behavioral biomarkers in infants and children with neurodevelopmental disorders?

Science.gov (United States)

Marschik, Peter B; Zhang, Dajie; Esposito, Gianluca; Bölte, Sven; Einspieler, Christa; Sigafoos, Jeff

2017-01-01

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.

A Population-based Longitudinal Study of Childhood Neurodevelopmental Disorders, IQ and Subsequent Risk of Psychotic Experiences in Adolescence

Science.gov (United States)

Khandaker, Golam M.; Stochl, Jan; Zammit, Stanley; Lewis, Glyn; Jones, Peter B

2014-01-01

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

Social cognition and neural substrates of face perception: implications for neurodevelopmental and neuropsychiatric disorders.

Science.gov (United States)

Lazar, Steven M; Evans, David W; Myers, Scott M; Moreno-De Luca, Andres; Moore, Gregory J

2014-04-15

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.

Novel roles for immune molecules in neural development: Implications for neurodevelopmental disoders

Directory of Open Access Journals (Sweden)

Paula A Garay

2010-09-01

Full Text Available Although the brain has classically been considered "immune-privileged," current research suggests extensive communication between the nervous and the immune systems in both health and disease. Recent studies demonstrate that immune molecules are present at the right place and time to modulate the development and function of the healthy and diseased CNS. Indeed, immune molecules play integral roles in the CNS throughout neural development, including affecting neurogenesis, neuronal migration, axon guidance, synapse formation, activity-dependent refinement of circuits, and synaptic plasticity. Moreover, the roles of individual immune molecules in the nervous system may change over development. This review focuses on the effects of immune molecules on neuronal connections in the mammalian central nervous system—specifically the roles for MHCI and its receptors, complement, and cytokines on the function, refinement, and plasticity of cortical and hippocampal synapses and their relationship to neurodevelopmental disorders. These functions for immune molecules during neural development suggest that they could also mediate pathological responses to chronic elevations of cytokines in neurodevelopmental disorders, including autism spectrum disorders (ASD and schizophrenia.

Needs of Adolescents and Young Adults with Neurodevelopmental Disorders: Comparisons of Young People and Parent Perspectives

Science.gov (United States)

Eklund, Hanna; Findon, James; Cadman, Tim; Hayward, Hannah; Murphy, Declan; Asherson, Philip; Glaser, Karen; Xenitidis, Kiriakos

2018-01-01

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…

Neurodevelopmental risk factors in schizophrenia

Directory of Open Access Journals (Sweden)

Lobato M.I.

2001-01-01

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.

Targeting Glia with N-Acetylcysteine Modulates Brain Glutamate and Behaviors Relevant to Neurodevelopmental Disorders in C57BL/6J Mice

Science.gov (United States)

Durieux, Alice M. S.; Fernandes, Cathy; Murphy, Declan; Labouesse, Marie Anais; Giovanoli, Sandra; Meyer, Urs; Li, Qi; So, Po-Wah; McAlonan, Grainne

2015-01-01

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

Targeting glia with N-Acetylcysteine modulates brain glutamate and behaviours relevant to neurodevelopmental disorders in C57BL/6J mice

Directory of Open Access Journals (Sweden)

Alice Marie Sybille Durieux

2015-12-01

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.

MECHANISMS IN ENDOCRINOLOGY: Neurodevelopmental disorders in children born to mothers with thyroid dysfunction: evidence of fetal programming?

Science.gov (United States)

Andersen, Stine Linding; Carlé, Allan; Karmisholt, Jesper; Pedersen, Inge Bülow; Andersen, Stig

2017-07-01

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.

Neurodevelopmental functioning in children with FAS, pFAS, and ARND.

Science.gov (United States)

Chasnoff, Ira J; Wells, Anne M; Telford, Erin; Schmidt, Christine; Messer, Gwendolyn

2010-04-01

The purpose of this article is to compare the neurodevelopmental profiles of 78 foster and adopted children with fetal alcohol syndrome (FAS), partial FAS (pFAS), or alcohol-related neurodevelopmental disorder (ARND). Seventy-eight foster and adopted children underwent a comprehensive diagnostic evaluation. By using criteria more stringent than those required by current guidelines, the children were placed in 1 of 3 diagnostic categories: FAS, pFAS, or ARND. Each child was evaluated across the domains of neuropsychological functioning most frequently affected by prenatal exposure to alcohol. Multivariate analyses of variance were conducted to examine differences in neuropsychological functioning between the 3 diagnostic groups. Descriptive discriminant analyses were performed in follow-up to the multivariate analyses of variance. The children in the 3 diagnostic categories were similar for descriptive and child welfare variables. Children with FAS had significantly decreased mean weight, height, and head circumference. Children with FAS exhibited the most impaired level of general intelligence, significantly worse language-based memory compared with children with ARND, and significantly poorer functional communication skills than children with pFAS. On executive functioning, the FAS group of children performed significantly worse on sequencing and shift than either the pFAS or ARND groups. Children with pFAS and ARND were similar in all neurodevelopmental domains that were tested. The children who met tightly defined physical criteria for a diagnosis of FAS demonstrated significantly poorer neurodevelopmental functioning than children with pFAS and ARND. Children in these latter 2 groups were similar in all neurodevelopmental domains that were tested.

Oxytocin as a Modulator of Synaptic Plasticity: Implications for Neurodevelopmental Disorders

Directory of Open Access Journals (Sweden)

Keerthi Thirtamara Rajamani

2018-06-01

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.

Development and disease in a dish: the epigenetics of neurodevelopmental disorders.

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Lewis, Emily Ma; Kroll, Kristen L

2018-02-01

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.

International telemedicine consultations for neurodevelopmental disabilities.

Science.gov (United States)

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

2014-06-01

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

Effect of Neuroinflammation on Synaptic Organization and Function in the Developing Brain: Implications for Neurodevelopmental and Neurodegenerative Disorders

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Amin Mottahedin

2017-07-01

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.

Psychosocial functioning in children with neurodevelopmental disorders and externalizing behavior problems.

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Arim, Rubab G; Kohen, Dafna E; Garner, Rochelle E; Lach, Lucyna M; Brehaut, Jamie C; MacKenzie, Michael J; Rosenbaum, Peter L

2015-01-01

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

Mutation of Semaphorin-6A disrupts limbic and cortical connectivity and models neurodevelopmental psychopathology.

LENUS (Irish Health Repository)

2011-01-01

Psychiatric disorders such as schizophrenia and autism are characterised by cellular disorganisation and dysconnectivity across the brain and can be caused by mutations in genes that control neurodevelopmental processes. To examine how neurodevelopmental defects can affect brain function and behaviour, we have comprehensively investigated the consequences of mutation of one such gene, Semaphorin-6A, on cellular organisation, axonal projection patterns, behaviour and physiology in mice. These analyses reveal a spectrum of widespread but subtle anatomical defects in Sema6A mutants, notably in limbic and cortical cellular organisation, lamination and connectivity. These mutants display concomitant alterations in the electroencephalogram and hyper-exploratory behaviour, which are characteristic of models of psychosis and reversible by the antipsychotic clozapine. They also show altered social interaction and deficits in object recognition and working memory. Mice with mutations in Sema6A or the interacting genes may thus represent a highly informative model for how neurodevelopmental defects can lead to anatomical dysconnectivity, resulting, either directly or through reactive mechanisms, in dysfunction at the level of neuronal networks with associated behavioural phenotypes of relevance to psychiatric disorders. The biological data presented here also make these genes plausible candidates to explain human linkage findings for schizophrenia and autism.

Oppositional defiant- and conduct disorder-like problems: neurodevelopmental predictors and genetic background in boys and girls, in a nationwide twin study.

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Kerekes, Nóra; Lundström, Sebastian; Chang, Zheng; Tajnia, Armin; Jern, Patrick; Lichtenstein, Paul; Nilsson, Thomas; Anckarsäter, Henrik

2014-01-01

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.

The Effects of Live Music as the Discriminative Stimulus and Reinforcer on the Skill Acquisition of Learners with Neurodevelopmental Disorders

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Harms, Melanie D.

2013-01-01

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…

Neurodevelopmental Disorders and Prenatal Residential Proximity to Agricultural Pesticides: The CHARGE Study

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Geraghty, Estella M.; Tancredi, Daniel J.; Delwiche, Lora D.; Schmidt, Rebecca J.; Ritz, Beate; Hansen, Robin L.; Hertz-Picciotto, Irva

2014-01-01

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

Responding to Requests of Families for Unproven Interventions in Neurodevelopmental Disorders: Hyperbaric Oxygen "Treatment" and Stem Cell "Therapy" in Cerebral Palsy

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Bell, Emily; Wallace, Tessa; Chouinard, Isabelle; Shevell, Michael; Racine, Eric

2011-01-01

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…

Different Neurodevelopmental Symptoms Have a Common Genetic Etiology

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Pettersson, Erik; Anckarsäter, Henrik; Gillberg, Christopher; Lichtenstein, Paul

2013-01-01

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…

Genetic contribution to neurodevelopmental outcomes in congenital heart disease: are some patients predetermined to have developmental delay?

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Rollins, Caitlin K; Newburger, Jane W; Roberts, Amy E

2017-10-01

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.

Neurodevelopmental delay among children under the age of three years at immunization clinics in Lagos State, Nigeria - Preliminary report.

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Bakare, Muideen O; Bello-Mojeed, Mashudat A; Munir, Kerim M; Ogun, Oluwayemi C; Eaton, Julian

2016-04-29

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.

Neurodevelopmental Effects of Antiepileptic Drugs.

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Kellogg, Marissa; Meador, Kimford J

2017-07-01

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.

Are the components of social reciprocity transdiagnostic across pediatric neurodevelopmental disorders? Evidence for common and disorder-specific social impairments.

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Sturm, Alexandra; Rozenman, Michelle; Chang, Susanna; McGough, James J; McCracken, James T; Piacentini, John C

2018-06-01

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.

The neurobiology of psychopathy: a neurodevelopmental perspective.

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Gao, Yu; Glenn, Andrea L; Schug, Robert A; Yang, Yaling; Raine, Adrian

2009-12-01

We provide an overview of the neurobiological underpinnings of psychopathy. Cognitive and affective-emotional processing deficits are associated with abnormal brain structure and function, particularly the amygdala and orbitofrontal cortex. There is limited evidence of lower cortisol levels being associated with psychopathic personality. Initial developmental research is beginning to suggest that these neurobiological processes may have their origins early in life. Findings suggest that psychopathic personality may, in part, have a neurodevelopmental basis. Future longitudinal studies delineating neurobiological correlates of the analogues of interpersonal-affective and antisocial features of psychopathy in children are needed to further substantiate a neurodevelopmental hypothesis of psychopathy.

The European Prader-Willi Syndrome Clinical Research Database: An Aid in the Investigation of a Rare Genetically Determined Neurodevelopmental Disorder

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Holland, A.; Whittington, J.; Cohen, O.; Curfs, L.; Delahaye, F.; Dudley, O.; Horsthemke, B.; Lindgren, A. -C.; Nourissier, C.; Sharma, N.; Vogels, A.

2009-01-01

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…

The Cerebellum and Neurodevelopmental Disorders.

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Stoodley, Catherine J

2016-02-01

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.

Autistic disorder : Current psychopharmacological treatments and areas of interest for future developments

NARCIS (Netherlands)

Nikolov, R; Jonker, Jacob Jan; Scahill, L

Autistic disorder and the group of related conditions defined as pervasive developmental disorders are chronic neurodevelopmental disorders starting in early childhood and affecting a significant number of children and families. Although the causes and much of the pathophysiology of the disorder

Mutations of CDKL5 Cause a Severe Neurodevelopmental Disorder with Infantile Spasms and Mental Retardation

Science.gov (United States)

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

2004-01-01

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

Male-biased autosomal effect of 16p13.11 copy number variation in neurodevelopmental disorders.

Directory of Open Access Journals (Sweden)

Maria Tropeano

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

Integrating care for neurodevelopmental disorders by unpacking control: A grounded theory study

Directory of Open Access Journals (Sweden)

Gustaf Waxegård

2016-09-01

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.

Integrating care for neurodevelopmental disorders by unpacking control: A grounded theory study

Science.gov (United States)

Waxegård, Gustaf; Thulesius, Hans

2016-01-01

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

Oppositional defiant- and conduct disorder-like problems: neurodevelopmental predictors and genetic background in boys and girls, in a nationwide twin study

Directory of Open Access Journals (Sweden)

Nóra Kerekes

2014-04-01

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.

Home-based, early intervention with mechatronic toys for preterm infants at risk of neurodevelopmental disorders (CARETOY)

DEFF Research Database (Denmark)

Sgandurra, Giuseppina; Bartalena, Laura; Cioni, Giovanni

2014-01-01

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...

Association Between Parenting Stress and Functional Impairment Among Children Diagnosed with Neurodevelopmental Disorders.

Science.gov (United States)

Almogbel, Yasser S; Goyal, Rohit; Sansgiry, Sujit S

2017-05-01

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.

Neurodevelopmental variability in three young girls with a rare chromosomal disorder, 48, XXXX.

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Samango-Sprouse, Carole; Keen, Colleen; Mitchell, Francie; Sadeghin, Teresa; Gropman, Andrea

2015-10-01

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.

Touchscreen learning deficits in Ube3a, Ts65Dn and Mecp2 mouse models of neurodevelopmental disorders with intellectual disabilities.

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Leach, P T; Crawley, J N

2017-12-20

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.

Targeting brain serotonin synthesis: insights into neurodevelopmental disorders with long-term outcomes related to negative emotionality, aggression and antisocial behaviour.

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Lesch, Klaus-Peter; Araragi, Naozumi; Waider, Jonas; van den Hove, Daniel; Gutknecht, Lise

2012-09-05

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.

Pterins and affective disorders

NARCIS (Netherlands)

R. Hoekstra (Rocco)

2007-01-01

textabstractThe pathophysiology of affective disorders is largely unknown. In patients with various affective disorders the activity of pterins and related amino acids were investigated before and after clinical treatment. In particular the bipolar affective disorder could be

[Dissociative disorders and affective disorders].

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Montant, J; Adida, M; Belzeaux, R; Cermolacce, M; Pringuey, D; Da Fonseca, D; Azorin, J-M

2014-12-01

The phenomenology of dissociative disorders may be complex and sometimes confusing. We describe here two cases who were initially misdiagnosed. The first case concerned a 61 year-old woman, who was initially diagnosed as an isolated dissociative fugue and was actually suffering from severe major depressive episode. The second case concerned a 55 year-old man, who was suffering from type I bipolar disorder and polyvascular disease, and was initially diagnosed as dissociative fugue in a mooddestabilization context, while it was finally a stroke. Yet dissociative disorders as affective disorder comorbidity are relatively unknown. We made a review on this topic. Dissociative disorders are often studied through psycho-trauma issues. Litterature is rare on affective illness comorbid with dissociative disorders, but highlight the link between bipolar and dissociative disorders. The later comorbidity often refers to an early onset subtype with also comorbid panic and depersonalization-derealization disorder. Besides, unipolar patients suffering from dissociative symptoms have more often cyclothymic affective temperament. Despite the limits of such studies dissociative symptoms-BD association seems to correspond to a clinical reality and further works on this topic may be warranted. Copyright © 2014 L’Encéphale. Published by Elsevier Masson SAS.. All rights reserved.

[Schizophrenia: neurodevelopmental disorder or degenerative brain process?].

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Gross, G; Huber, G

2008-05-01

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

Abnormal Sensory Experiences, Synaesthesia, and Neurodevelopmental Disorders

Science.gov (United States)

Fluegge, Keith

2017-01-01

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…

Neurodevelopmental Treatment (NDT): Therapeutic Intervention and Its Efficacy.

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Stern, Francine Martin; Gorga, Delia

1988-01-01

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…

Bioinformatics Database Tools in Analysis of Genetics of Neurodevelopmental Disorders

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Dibyashree Mallik

2017-10-01

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.

Does Congenital Heart Disease Affect Neurodevelopmental Outcomes in Children with Down Syndrome?

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Alsaied, Tarek; Marino, Bradley S; Esbensen, Anna J; Anixt, Julia S; Epstein, Jeffery N; Cnota, James F

2016-01-01

The impact that congenital heart disease (CHD) has on the neurodevelopment of children with Down syndrome (DS) is unknown and potentially has implications for targeted early intervention. This study assessed the relationship between CHD that required surgery in the first year of life and neurodevelopmental, behavioral and emotional functioning outcomes in children with DS. A retrospective chart review of 1092 children (0-18 years) with DS who visited a single institution from 8/08-8/13 was performed. Children who underwent at least one of nine neurodevelopmental (cognitive, language, developmental) or academic tests were included in the analysis (N = 178). Cohort was age-divided into infants/toddlers (0-2 years), preschoolers (3-5 years), and school age/adolescent (6-18 years). Test scores of children with DS who underwent cardiac surgery in the first year of life were compared to children with DS without CHD. T test, chi-square and Mann Whitney U tests were used where appropriate. Infants/toddlers with cardiac surgery had lower scores for receptive (P = .01), expressive (P = .021) and composite language (P children with cardiac surgery there were no differences in IQ scores, language scores, or academic achievement scores compared to those without CHD. Also at school-age there was no difference in the incidence of ADHD, executive function or on internalizing and externalizing behavior scores. Children with DS undergoing cardiac surgery during the first year demonstrated poorer neurodevelopmental outcomes as infants/toddler but had no difference at school age compared to children with DS without CHD. These results will guide early interventions to optimize neurodevelopmental outcomes in children with DS and will help with family counseling after CHD repair. © 2016 Wiley Periodicals, Inc.

The Neurodevelopmental Basis of Early Childhood Disruptive Behavior: Irritable and Callous Phenotypes as Exemplars.

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Wakschlag, Lauren S; Perlman, Susan B; Blair, R James; Leibenluft, Ellen; Briggs-Gowan, Margaret J; Pine, Daniel S

2018-02-01

The arrival of the Journal's 175th anniversary occurs at a time of recent advances in research, providing an ideal opportunity to present a neurodevelopmental roadmap for understanding, preventing, and treating psychiatric disorders. Such a roadmap is particularly relevant for early-childhood-onset neurodevelopmental conditions, which emerge when experience-dependent neuroplasticity is at its peak. Employing a novel developmental specification approach, this review places recent neurodevelopmental research on early childhood disruptive behavior within the historical context of the Journal. The authors highlight irritability and callous behavior as two core exemplars of early disruptive behavior. Both phenotypes can be reliably differentiated from normative variation as early as the first years of life. Both link to discrete pathophysiology: irritability with disruptions in prefrontal regulation of emotion, and callous behavior with abnormal fear processing. Each phenotype also possesses clinical and predictive utility. Based on a nomologic net of evidence, the authors conclude that early disruptive behavior is neurodevelopmental in nature and should be reclassified as an early-childhood-onset neurodevelopmental condition in DSM-5. Rapid translation from neurodevelopmental discovery to clinical application has transformative potential for psychiatric approaches of the millennium. [AJP at 175: Remembering Our Past As We Envision Our Future November 1938: Electroencephalographic Analyses of Behavior Problem Children Herbert Jasper and colleagues found that brain abnormalities revealed by EEG are a potential causal factor in childhood behavioral disorders. (Am J Psychiatry 1938; 95:641-658 )].

Hotspots of missense mutation identify novel neurodevelopmental disorder genes and functional domains

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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.

2017-01-01

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

Monitoring Maternal Beta Carotene and Retinol Consumption May Decrease the Incidence of Neurodevelopmental Disorders in Offspring

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Joel S. Goldberg

2012-01-01

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.

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

OpenAIRE

Wise, Alexandra; Tenezaca, Luis; Fernandez, Robert W.; Schatoff, Emma; Flores, Julian; Ueda, Atsushi; Zhong, Xiaotian; Wu, Chun-Fang; Simon, Anne F.; Venkatesh, Tadmiri

2015-01-01

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 ...

Affective disorders among patients with borderline personality disorder.

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Sjåstad, Hege Nordem; Gråwe, Rolf W; Egeland, Jens

2012-01-01

The high co-occurrence between borderline personality disorder and affective disorders has led many to believe that borderline personality disorder should be considered as part of an affective spectrum. The aim of the present study was to examine whether the prevalence of affective disorders are higher for patients with borderline personality disorder than for patients with other personality disorders. In a national cross-sectional study of patients receiving mental health treatment in Norway (N = 36 773), we determined whether psychiatric outpatients with borderline personality disorder (N = 1 043) had a higher prevalence of affective disorder in general, and whether they had an increased prevalence of depression, bipolar disorder or dysthymia specifically. They were compared to patients with paranoid, schizoid, dissocial, histrionic, obsessive-compulsive, avoidant, dependent, or unspecified personality disorder, as well as an aggregated group of patients with personality disorders other than the borderline type (N = 2 636). Odds ratios were computed for the borderline personality disorder group comparing it to the mixed sample of other personality disorders. Diagnostic assessments were conducted in routine clinical practice. More subjects with borderline personality disorder suffered from unipolar than bipolar disorders. Nevertheless, borderline personality disorder had a lower rate of depression and dysthymia than several other personality disorder groups, whereas the rate of bipolar disorder tended to be higher. Odds ratios showed 34% lower risk for unipolar depression, 70% lower risk for dysthymia and 66% higher risk for bipolar disorder in patients with borderline personality disorder compared to the aggregated group of other personality disorders. The results suggest that borderline personality disorder has a stronger association with affective disorders in the bipolar spectrum than disorders in the unipolar spectrum. This association may reflect

Affective disorders among patients with borderline personality disorder.

Directory of Open Access Journals (Sweden)

Hege Nordem Sjåstad

Full Text Available BACKGROUND: The high co-occurrence between borderline personality disorder and affective disorders has led many to believe that borderline personality disorder should be considered as part of an affective spectrum. The aim of the present study was to examine whether the prevalence of affective disorders are higher for patients with borderline personality disorder than for patients with other personality disorders. METHODS: In a national cross-sectional study of patients receiving mental health treatment in Norway (N = 36 773, we determined whether psychiatric outpatients with borderline personality disorder (N = 1 043 had a higher prevalence of affective disorder in general, and whether they had an increased prevalence of depression, bipolar disorder or dysthymia specifically. They were compared to patients with paranoid, schizoid, dissocial, histrionic, obsessive-compulsive, avoidant, dependent, or unspecified personality disorder, as well as an aggregated group of patients with personality disorders other than the borderline type (N = 2 636. Odds ratios were computed for the borderline personality disorder group comparing it to the mixed sample of other personality disorders. Diagnostic assessments were conducted in routine clinical practice. RESULTS: More subjects with borderline personality disorder suffered from unipolar than bipolar disorders. Nevertheless, borderline personality disorder had a lower rate of depression and dysthymia than several other personality disorder groups, whereas the rate of bipolar disorder tended to be higher. Odds ratios showed 34% lower risk for unipolar depression, 70% lower risk for dysthymia and 66% higher risk for bipolar disorder in patients with borderline personality disorder compared to the aggregated group of other personality disorders. CONCLUSIONS: The results suggest that borderline personality disorder has a stronger association with affective disorders in the bipolar spectrum than

Affective Disorders among Patients with Borderline Personality Disorder

Science.gov (United States)

Sjåstad, Hege Nordem; Gråwe, Rolf W.; Egeland, Jens

2012-01-01

Background The high co-occurrence between borderline personality disorder and affective disorders has led many to believe that borderline personality disorder should be considered as part of an affective spectrum. The aim of the present study was to examine whether the prevalence of affective disorders are higher for patients with borderline personality disorder than for patients with other personality disorders. Methods In a national cross-sectional study of patients receiving mental health treatment in Norway (N = 36 773), we determined whether psychiatric outpatients with borderline personality disorder (N = 1 043) had a higher prevalence of affective disorder in general, and whether they had an increased prevalence of depression, bipolar disorder or dysthymia specifically. They were compared to patients with paranoid, schizoid, dissocial, histrionic, obsessive-compulsive, avoidant, dependent, or unspecified personality disorder, as well as an aggregated group of patients with personality disorders other than the borderline type (N = 2 636). Odds ratios were computed for the borderline personality disorder group comparing it to the mixed sample of other personality disorders. Diagnostic assessments were conducted in routine clinical practice. Results More subjects with borderline personality disorder suffered from unipolar than bipolar disorders. Nevertheless, borderline personality disorder had a lower rate of depression and dysthymia than several other personality disorder groups, whereas the rate of bipolar disorder tended to be higher. Odds ratios showed 34% lower risk for unipolar depression, 70% lower risk for dysthymia and 66% higher risk for bipolar disorder in patients with borderline personality disorder compared to the aggregated group of other personality disorders. Conclusions The results suggest that borderline personality disorder has a stronger association with affective disorders in the bipolar spectrum than disorders in the unipolar

Neurodevelopmental Versus Neurodegenerative Model of Schizophrenia and Bipolar Disorder: Comparison with Physiological Brain Development and Aging.

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Buoli, Massimiliano; Serati, Marta; Caldiroli, Alice; Cremaschi, Laura; Altamura, Alfredo Carlo

2017-03-01

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.

Neurobehavioral and neurodevelopmental effects of pesticide exposures

DEFF Research Database (Denmark)

London, Leslie; Beseler, Cheryl; Bouchard, Maryse F

2012-01-01

The association between pesticide exposure and neurobehavioral and neurodevelopmental effects is an area of increasing concern. This symposium brought together participants to explore the neurotoxic effects of pesticides across the lifespan. Endpoints examined included neurobehavioral, affective ...

Assisted reproduction and child neurodevelopmental outcomes: a systematic review.

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Bay, Bjørn; Mortensen, Erik Lykke; Kesmodel, Ulrik Schiøler

2013-09-01

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.

A Dose-Response Relationship between Organic Mercury Exposure from Thimerosal-Containing Vaccines and Neurodevelopmental Disorders

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David A. Geier

2014-09-01

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.

Seasonal affective disorder and non-seasonal affective disorders : Results from the NESDA study

NARCIS (Netherlands)

Winthorst, Wim H; Roest, Annelieke M; Bos, Elisabeth H; Meesters, Ybe; Penninx, Brenda W J H; Nolen, Willem A; de Jonge, Peter

BACKGROUND: Seasonal affective disorder (SAD) is considered to be a subtype of depression. AIMS: To compare the clinical picture of SAD to non-seasonal affective disorders (non-SADs). METHOD: Diagnoses according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) were established

Dendrite and spine modifications in autism and related neurodevelopmental disorders in patients and animal models.

Science.gov (United States)

Martínez-Cerdeño, Verónica

2017-04-01

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.

Phentermine, sibutramine and affective disorders.

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An, Hoyoung; Sohn, Hyunjoo; Chung, Seockhoon

2013-04-01

A safe and effective way to control weight in patients with affective disorders is needed, and phentermine is a possible candidate. We performed a PubMed search of articles pertaining to phentermine, sibutramine, and affective disorders. We compared the studies of phentermine with those of sibutramine. The search yielded a small number of reports. Reports concerning phentermine and affective disorders reported that i) its potency in the central nervous system may be comparatively low, and ii) it may induce depression in some patients. We were unable to find more studies on the subject; thus, it is unclear presently whether phentermine use is safe in affective disorder patients. Reports regarding the association of sibutramine and affective disorders were slightly more abundant. A recent study that suggested that sibutramine may have deleterious effects in patients with a psychiatric history may provide a clue for future phentermine research. Three explanations are possible concerning the association between phentermine and affective disorders: i) phentermine, like sibutramine, may have a depression-inducing effect that affects a specific subgroup of patients, ii) phentermine may have a dose-dependent depression-inducing effect, or iii) phentermine may simply not be associated with depression. Large-scale studies with affective disorder patients focusing on these questions are needed to clarify this matter before investigation of its efficacy may be carried out and it can be used in patients with affective disorders.

Liver transplantation may prevent neurodevelopmental deterioration in high-risk patients with urea cycle disorders.

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Kido, Jun; Matsumoto, Shirou; Momosaki, Ken; Sakamoto, Rieko; Mitsubuchi, Hiroshi; Endo, Fumio; Nakamura, Kimitoshi

2017-09-01

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.

Recurrence in affective disorder

DEFF Research Database (Denmark)

Kessing, L V; Olsen, E W; Andersen, P K

1999-01-01

The risk of recurrence in affective disorder is influenced by the number of prior episodes and by a person's tendency toward recurrence. Newly developed frailty models were used to estimate the effect of the number of episodes on the rate of recurrence, taking into account individual frailty toward...... recurrence. The study base was the Danish psychiatric case register of all hospital admissions for primary affective disorder in Denmark during 1971-1993. A total of 20,350 first-admission patients were discharged with a diagnosis of major affective disorder. For women with unipolar disorder and for all...... kinds of patients with bipolar disorder, the rate of recurrence was affected by the number of prior episodes even when the effect was adjusted for individual frailty toward recurrence. No effect of episodes but a large effect of the frailty parameter was found for unipolar men. The authors concluded...

Identification of amphiphysin 1 as an endogenous substrate for CDKL5, a protein kinase associated with X-linked neurodevelopmental disorder.

Science.gov (United States)

Sekiguchi, Mari; Katayama, Syouichi; Hatano, Naoya; Shigeri, Yasushi; Sueyoshi, Noriyuki; Kameshita, Isamu

2013-07-15

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.

Dementia in affective disorder

DEFF Research Database (Denmark)

Kessing, L V; Olsen, E W; Mortensen, P B

1999-01-01

OBJECTIVE: The aim of the study was to investigate whether patients with affective disorder have increased risk of developing dementia compared to other groups of psychiatric patients and compared to the general population. METHOD: In the Danish psychiatric central register, 3363 patients...... with unipolar affective disorder, 518 patients with bipolar affective disorder, 1025 schizophrenic and 8946 neurotic patients were identified according to the diagnosis at the first ever discharge from psychiatric hospital during the period from 1970 to 1974. The rate of discharge diagnosis of dementia...... on readmission was estimated during 21 years of follow-up. In addition, the rates were compared with the rates for admission to psychiatric hospitals with a discharge diagnosis of dementia for the total Danish population. RESULTS: Patients with unipolar and with bipolar affective disorder had a greater risk...

[DSM-5: neurodevelopmental disorders

NARCIS (Netherlands)

Zinkstok, J.; Buitelaar, J.K.

2014-01-01

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

Increased gender variance in autism spectrum disorders and attention deficit hyperactivity disorder.

Science.gov (United States)

Strang, John F; Kenworthy, Lauren; Dominska, Aleksandra; Sokoloff, Jennifer; Kenealy, Laura E; Berl, Madison; Walsh, Karin; Menvielle, Edgardo; Slesaransky-Poe, Graciela; Kim, Kyung-Eun; Luong-Tran, Caroline; Meagher, Haley; Wallace, Gregory L

2014-11-01

Evidence suggests over-representation of autism spectrum disorders (ASDs) and behavioral difficulties among people referred for gender issues, but rates of the wish to be the other gender (gender variance) among different neurodevelopmental disorders are unknown. This chart review study explored rates of gender variance as reported by parents on the Child Behavior Checklist (CBCL) in children with different neurodevelopmental disorders: ASD (N = 147, 24 females and 123 males), attention deficit hyperactivity disorder (ADHD; N = 126, 38 females and 88 males), or a medical neurodevelopmental disorder (N = 116, 57 females and 59 males), were compared with two non-referred groups [control sample (N = 165, 61 females and 104 males) and non-referred participants in the CBCL standardization sample (N = 1,605, 754 females and 851 males)]. Significantly greater proportions of participants with ASD (5.4%) or ADHD (4.8%) had parent reported gender variance than in the combined medical group (1.7%) or non-referred comparison groups (0-0.7%). As compared to non-referred comparisons, participants with ASD were 7.59 times more likely to express gender variance; participants with ADHD were 6.64 times more likely to express gender variance. The medical neurodevelopmental disorder group did not differ from non-referred samples in likelihood to express gender variance. Gender variance was related to elevated emotional symptoms in ADHD, but not in ASD. After accounting for sex ratio differences between the neurodevelopmental disorder and non-referred comparison groups, gender variance occurred equally in females and males.

Mental disorders, brain disorders, neurodevelopmental disorders ...

African Journals Online (AJOL)

. 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 ...

Chromosomal Microarray Analysis of Consecutive Individuals with Autism Spectrum Disorders Using an Ultra-High Resolution Chromosomal Microarray Optimized for Neurodevelopmental Disorders

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Karen S. Ho

2016-12-01

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.

Reproduction, Smell and Neurodevelopmental disorders: Genetic defects in different hypogonadotropic hypogonadal syndromes.

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Hernan G VALDES-SOCIN

2014-07-01

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.

Psychotic experiences co-occur with sleep problems, negative affect and mental disorders in preadolescence

DEFF Research Database (Denmark)

Jeppesen, Pia; Clemmensen, Lars; Munkholm, Anja

2015-01-01

or definitely present. The Development and Well-Being Assessment (DAWBA) was used independently to diagnose DSM-IV-mental disorders. Puberty development and sleep disturbance were self-reported. The associations between PE (any lifetime hallucination and/or delusion) and various mental problems and disorders......-reported mental health difficulties in absence of a diagnosis (31.4%). The risk of delusions increased with onset of puberty. The risk of PE increased with emotional and neurodevelopmental disorders, subthreshold depressive symptoms, sleep problems and lack of sleep, regardless of whether PE were expressed...

Sequencing chromosomal abnormalities reveals neurodevelopmental loci that confer risk across diagnostic boundaries

Science.gov (United States)

Talkowski, Michael E.; Rosenfeld, Jill A.; Blumenthal, Ian; Pillalamarri, Vamsee; Chiang, Colby; Heilbut, Adrian; Ernst, Carl; Hanscom, Carrie; Rossin, Elizabeth; Lindgren, Amelia; Pereira, Shahrin; Ruderfer, Douglas; Kirby, Andrew; Ripke, Stephan; Harris, David; Lee, Ji-Hyun; Ha, Kyungsoo; Kim, Hyung-Goo; Solomon, Benjamin D.; Gropman, Andrea L.; Lucente, Diane; Sims, Katherine; Ohsumi, Toshiro K.; Borowsky, Mark L.; Loranger, Stephanie; Quade, Bradley; Lage, Kasper; Miles, Judith; Wu, Bai-Lin; Shen, Yiping; Neale, Benjamin; Shaffer, Lisa G.; Daly, Mark J.; Morton, Cynthia C.; Gusella, James F.

2012-01-01

SUMMARY Balanced chromosomal abnormalities (BCAs) represent a reservoir of single gene disruptions in neurodevelopmental disorders (NDD). We sequenced BCAs in autism and related NDDs, revealing disruption of 33 loci in four general categories: 1) genes associated with abnormal neurodevelopment (e.g., AUTS2, FOXP1, CDKL5), 2) single gene contributors to microdeletion syndromes (MBD5, SATB2, EHMT1, SNURF-SNRPN), 3) novel risk loci (e.g., CHD8, KIRREL3, ZNF507), and 4) genes associated with later onset psychiatric disorders (e.g., TCF4, ZNF804A, PDE10A, GRIN2B, ANK3). We also discovered profoundly increased burden of copy number variants among 19,556 neurodevelopmental cases compared to 13,991 controls (p = 2.07×10−47) and enrichment of polygenic risk alleles from autism and schizophrenia genome-wide association studies (p = 0.0018 and 0.0009, respectively). Our findings suggest a polygenic risk model of autism incorporating loci of strong effect and indicate that some neurodevelopmental genes are sensitive to perturbation by multiple mutational mechanisms, leading to variable phenotypic outcomes that manifest at different life stages. PMID:22521361

Prader-Willi Syndrome and Schaaf-Yang Syndrome: Neurodevelopmental Diseases Intersecting at the MAGEL2 Gene

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Michael D. Fountain

2016-01-01

Full Text Available Prader-Willi syndrome (PWS is a neurodevelopmental disorder characterized by neonatal hypotonia, developmental delay/intellectual disability, and characteristic feeding behaviors with failure to thrive during infancy; followed by hyperphagia and excessive weight gain later in childhood. Individuals with PWS also manifest complex behavioral phenotypes. Approximately 25% meet criteria for autism spectrum disorder (ASD. PWS is caused by the absence of paternally expressed, maternally silenced genes at chromosome 15q11-q13. MAGEL2 is one of five protein-coding genes in the PWS-critical domain. Truncating point mutations of the paternal allele of MAGEL2 cause Schaaf-Yang syndrome, which has significant phenotypic overlap with PWS, but is also clinically distinct; based on the presence of joint contractures, and a particularly high prevalence of autism spectrum disorder (up to 75% of affected individuals. The clinical and molecular overlap between PWS and Schaaf-Yang syndrome, but also their distinguishing features provide insight into the pathogenetic mechanisms underlying both disorders.

The origins and consequences of attention deficit hyperactivity disorder

OpenAIRE

Chang, Zheng

2013-01-01

Attention deficit hyperactivity disorder (ADHD) is characterized by developmentally inappropriate levels of inattention, hyperactivity, and impulsivity, and is the most common neurodevelopmental disorder of childhood. This highly prevalent disorder is estimated to affect about 5% of school-age children worldwide, with a substantial degree of persistence over time. Although the specific cause of ADHD is still largely unknown, despite a long history of research, it is believed to involve multip...

Community survey of attention-deficit/hyperactivity disorder among ...

African Journals Online (AJOL)

Background: Attention-deficit/hyperactivity disorder (ADHD) is a common childhood neuro-developmental condition with early onset. ADHD affects children worldwide. However, there is a variation in the prevalence across different countries. In Nigeria, there is paucity of information on the prevalence. To provide the ...

GLIA AND NEURODEVELOPMENT: FOCUS ON FETAL ALCOHOL SPECTRUM DISORDERS

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Marina eGuizzetti

2014-11-01

Full Text Available During the last 20 years new and exciting roles for glial cells in brain development have been described. Moreover, several recent studies implicated glial cells in the pathogenesis of neurodevelopmental disorders including Down syndrome, Fragile X syndrome, Rett Syndrome, Autism Spectrum Disorders, and Fetal Alcohol Spectrum Disorders (FASD.Abnormalities in glial cell development and proliferation and increased glial cell apoptosis contribute to the adverse effects of ethanol on the developing brain and it is becoming apparent that the effects of fetal alcohol are due, at least in part, to effects on glial cells affecting their ability to modulate neuronal development and function. The three major classes of glial cells, astrocytes, oligodendrocytes, and microglia as well as their precursors are affected by ethanol during brain development. Alterations in glial cell functions by ethanol dramatically affect neuronal development, survival, and function and ultimately impair the development of the proper brain architecture and connectivity. For instance, ethanol inhibits astrocyte-mediated neuritogenesis and oligodendrocyte development, survival and myelination; furthermore, ethanol induces microglia activation and oxidative stress leading to the exacerbation of ethanol-induced neuronal cell death.This review article describes the most significant recent findings pertaining the effects of ethanol on glial cells and their significance in the pathophysiology of FASD and other neurodevelopmental disorders.

Eating disorder symptoms in affective disorder.

OpenAIRE

Wold, P N

1991-01-01

Patients with Major Affective Disorder (MAD), Secondary Depression, Panic Disorder, and bulimia with and without MAD, were given the Eating Disorder Inventory, the Beck Depression Inventory, and the General Behavior Inventory at presentation. It was found that patients with MAD have a triad of eating disorder symptoms: a disturbance in interoceptive awareness, the sense of ineffectiveness, and a tendency toward bulimia. The data supported the concept that the sense of ineffectiveness is secon...

Neurodevelopmental correlates in schizophrenia

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Ivković Maja

2003-01-01

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

Sequencing Chromosomal Abnormalities Reveals Neurodevelopmental Loci that Confer Risk across Diagnostic Boundaries

DEFF Research Database (Denmark)

Talkowski, Michael E.; Rosenfeld, Jill A.; Blumenthal, Ian

2012-01-01

Sequencing of balanced chromosomal abnormalities, combined with convergent genomic studies of gene expression, copy-number variation, and genome-wide association, identifies 22 new loci that contribute to autism and related neurodevelopmental disorders. These data support a polygenic risk model...

Improving treatment of neurodevelopmental disorders: recommendations based on preclinical studies.

Science.gov (United States)

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

2016-01-01

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.

Affective disorders in neurological diseases

DEFF Research Database (Denmark)

Nilsson, F M; Kessing, L V; Sørensen, T M

2003-01-01

OBJECTIVE: To investigate the temporal relationships between a range of neurological diseases and affective disorders. METHOD: Data derived from linkage of the Danish Psychiatric Central Register and the Danish National Hospital Register. Seven cohorts with neurological index diagnoses and two...... of affective disorder was lower than the incidence in the control groups. CONCLUSION: In neurological diseases there seems to be an increased incidence of affective disorders. The elevated incidence was found to be particularly high for dementia and Parkinson's disease (neurodegenerative diseases)....

[Comorbidity of eating disorders and bipolar affective disorders].

Science.gov (United States)

Kamińska, Katarzyna; Rybakowski, Filip

2006-01-01

Eating disorders--anorexia nervosa, bulimia nervosa and eating disorders not otherwise specified (EDNOS) occur usually in young females. The significant pathogenic differences between patients who only restrict food, and patients with binge eating and compensatory behaviours, such as vomiting and purging were described. The prevalence of bipolar affective disorders--especially bipolar II and bipolar spectrum disorders (BS) may reach 5% in the general population. About half of the depressive episodes are associated with a "mild" bipolar disorder, and such a diagnosis is suggested by impulsivity and mood-instability. Previously, majority of research on the comorbidity between eating and affective disorders focused on depressive symptomatology, however difficulties in the reliable assessment of hypomania may obfuscate the estimation of the co-occurrence of eating disorders with BS. Epidemiological studies suggest the association between BS and eating disorders with binge episodes (bulimia nervosa, anorexia- bulimic type and EDNOS with binge episodes). Co-occurrence of such disorders with depressive symptoms probably suggests the diagnosis of BS, not recurrent depression. Bulimic behaviours, impulsivity and affective disorders might be related to the impairment of the serotonergic neurotransmission, which may result from the genetic vulnerability and early life trauma. Currently, the first-line pharmacological treatment of co-occurring eating disorders with binge episodes and BS are selective serotonin reuptake inhibitors. However in some cases, the use of mood-stabilising agents as monotherapy or in combination with serotonergic drugs may be helpful.

Maternal thyroid hormone insufficiency during pregnancy and risk of neurodevelopmental disorders in offspring: A systematic review and meta-analysis.

Science.gov (United States)

Thompson, William; Russell, Ginny; Baragwanath, Genevieve; Matthews, Justin; Vaidya, Bijay; Thompson-Coon, Jo

2018-04-01

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

Maternal Metabolic Conditions and Risk for Autism and Other Neurodevelopmental Disorders

Science.gov (United States)

Walker, Cheryl K.; Bremer, Andrew A.; Baker, Alice S.; Ozonoff, Sally; Hansen, Robin L.; Hertz-Picciotto, Irva

2012-01-01

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

Affective disorders in childhood and adolescence

Directory of Open Access Journals (Sweden)

Marija Burgić-Radmanović

2011-05-01

Full Text Available Affective disorders in childhood have been more intensively studied in the last three decades. They can be recognized among the children of all ages, but are more frequent among the older children. The main characteristics of mood disorders are similar among children, adolescents and adults, although development factors affect their clinical features. Development factors affect the manifestation of all symptoms. Two main criteria for these disorders in childhood are mood disorders, such as reduced or elevated mood and irritability. These symptoms may result in social or academic damage. Depression among children is a wide-spread, family and recurrent condition, which continues episodically in adulthood. Depression is frequently associated with other psychiatric disorders, increasing the risk of suicidal behaviour, misuse of psychoactive substances and behavioural disorders. Depression in childhood brings about worse psychosocial, academic and family functioning. Family, social and environmental factors have a significant role in affective disorders of children and young people.

Neuropsychiatric manifestations in late-onset urea cycle disorder patients.

Science.gov (United States)

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

2010-03-01

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.

Copy Number Variation in Obsessive-Compulsive Disorder and Tourette Syndrome: A Cross-Disorder Study

Science.gov (United States)

McGrath, Lauren M.; Yu, Dongmei; Marshall, Christian; Davis, Lea K.; Thiruvahindrapuram, Bhooma; Li, Bingbin; Cappi, Carolina; Gerber, Gloria; Wolf, Aaron; Schroeder, Frederick A.; Osiecki, Lisa; O’Dushlaine, Colm; Kirby, Andrew; Illmann, Cornelia; Haddad, Stephen; Gallagher, Patience; Fagerness, Jesen A.; Barr, Cathy L.; Bellodi, Laura; Benarroch, Fortu; Bienvenu, O. Joseph; Black, Donald W.; Bloch, Michael H.; Bruun, Ruth D.; Budman, Cathy L.; Camarena, Beatriz; Cath, Danielle C.; Cavallini, Maria C.; Chouinard, Sylvain; Coric, Vladimir; Cullen, Bernadette; Delorme, Richard; Denys, Damiaan; Derks, Eske M.; Dion, Yves; Rosário, Maria C.; Eapen, Valsama; Evans, Patrick; Falkai, Peter; Fernandez, Thomas; Garrido, Helena; Geller, Daniel; Grabe, Hans J.; Grados, Marco A.; Greenberg, Benjamin D.; Gross-Tsur, Varda; Grünblatt, Edna; Heiman, Gary A.; Hemmings, Sian M.J.; Herrera, Luis D.; Hounie, Ana G.; Jankovic, Joseph; Kennedy, James L; King, Robert A.; Kurlan, Roger; Lanzagorta, Nuria; Leboyer, Marion; Leckman, James F.; Lennertz, Leonhard; Lochner, Christine; Lowe, Thomas L.; Lyon, Gholson J.; Macciardi, Fabio; Maier, Wolfgang; McCracken, James T.; McMahon, William; Murphy, Dennis L.; Naarden, Allan L; Neale, Benjamin M; Nurmi, Erika; Pakstis, Andrew J.; Pato, Michele T.; Pato, Carlos N.; Piacentini, John; Pittenger, Christopher; Pollak, Yehuda; Reus, Victor I.; Richter, Margaret A.; Riddle, Mark; Robertson, Mary M.; Rosenberg, David; Rouleau, Guy A.; Ruhrmann, Stephan; Sampaio, Aline S.; Samuels, Jack; Sandor, Paul; Sheppard, Brooke; Singer, Harvey S.; Smit, Jan H.; Stein, Dan J.; Tischfield, Jay A.; Vallada, Homero; Veenstra-VanderWeele, Jeremy; Walitza, Susanne; Wang, Ying; Wendland, Jens R.; Shugart, Yin Yao; Miguel, Euripedes C.; Nicolini, Humberto; Oostra, Ben A.; Moessner, Rainald; Wagner, Michael; Ruiz-Linares, Andres; Heutink, Peter; Nestadt, Gerald; Freimer, Nelson; Petryshen, Tracey; Posthuma, Danielle; Jenike, Michael A.; Cox, Nancy J.; Hanna, Gregory L.; Brentani, Helena; Scherer, Stephen W.; Arnold, Paul D.; Stewart, S. Evelyn; Mathews, Carol A.; Knowles, James A.; Cook, Edwin H.; Pauls, David L.; Wang, Kai; Scharf, Jeremiah M.

2014-01-01

Objective Obsessive-compulsive disorder (OCD) and Tourette syndrome (TS) are heritable, neurodevelopmental disorders with a partially shared genetic etiology. This study represents the first genome-wide investigation of large (>500kb), rare (<1%) copy number variants (CNVs) in OCD and the largest genome-wide CNV analysis in TS to date. Method The primary analyses utilized a cross-disorder design for 2,699 patients (1,613 ascertained for OCD, 1,086 ascertained for TS) and 1,789 controls. Parental data facilitated a de novo analysis in 348 OCD trios. Results Although no global CNV burden was detected in the cross-disorder analysis or in secondary, disease-specific analyses, there was a 3.3-fold increased burden of large deletions previously associated with other neurodevelopmental disorders (p=.09). Half of these neurodevelopmental deletions were located in a single locus, 16p13.11 (5 patient deletions: 0 control deletions, p=0.08 in current study, p=0.025 compared to published controls). Three 16p13.11 deletions were confirmed de novo, providing further support to the etiological significance of this region. The overall OCD de novo rate was 1.4%, which is intermediate between published rates in controls (0.7%) and in autism or schizophrenia (2–4%). Conclusion Several converging lines of evidence implicate 16p13.11 deletions in OCD, with weaker evidence for a role in TS. The trend toward increased overall neurodevelopmental CNV burden in TS and OCD suggests that deletions previously associated with other neurodevelopmental disorders may also contribute to these phenotypes. PMID:25062598

Perspectives from neuro-developmental disorders affecting

Indian Academy of Sciences (India)

Unknown

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Cannabinoid Receptor Type 2, but Not Type 1, Is Up-Regulated in Peripheral Blood Mononuclear Cells of Children Affected by Autistic Disorders

Science.gov (United States)

Siniscalco, Dario; Sapone, Anna; Giordano, Catia; Cirillo, Alessandra; de Magistris, Laura; Rossi, Francesco; Fasano, Alessio; Bradstreet, James Jeffrey; Maione, Sabatino; Antonucci, Nicola

2013-01-01

Autistic disorders (ADs) are heterogeneous neurodevelopmental disorders arised by the interaction of genes and environmental factors. Dysfunctions in social interaction and communication skills, repetitive and stereotypic verbal and non-verbal behaviours are common features of ADs. There are no defined mechanisms of pathogenesis, rendering…

Family psychoeducation for affective disorders

DEFF Research Database (Denmark)

Timmerby, Nina; Austin, Stephen; Bech, Per

2017-01-01

The aim of this article was to examine the evidence of family psychoeducation (FPE) for affective disorders. Evidence indicates that FPE can be an effective supplement to the standard treatment of patients with affective disorders. FPE can effectively reduce the patients' risk of relapse and redu...

An agenda for 21st century neurodevelopmental medicine: lessons from autism.

Science.gov (United States)

Klin, A; Jones, W

2018-03-01

The future of neurodevelopmental medicine has the potential of situating child neurology at the forefront of a broad-based public health effort to optimize neurodevelopmental outcomes of children born with high-prevalence and diverse genetic, pre- and peri-natal, and environmental burdens compromising early brain development and leading to lifetime disabilities. Building on advancements in developmental social neuroscience and in implementation science, this shift is already occurring in the case of emblematic neurodevelopmental disorders such as autism. Capitalizing on early neuroplasticity and on quantification of trajectories of social-communicative development, new technologies are emerging for high-throughput and cost-effective diagnosis and for community-viable delivery of powerful treatments, in seamless integration across previously fragmented systems of healthcare delivery. These solutions could be deployed in the case of other groups of children at greater risk for autism and communication delays, such as those born extremely premature or with congenital heart disease. The galvanizing concept in this aspirational future is a public health focus on promoting optimal conditions for early brain development, not unlike current campaigns promoting pre-natal care, nutrition or vaccination.

Infant Motor Delay and Early Symptomatic Syndromes Eliciting Neurodevelopmental Clinical Examinations in Japan.

Science.gov (United States)

Hatakenaka, Yuhei; Kotani, Haruko; Yasumitsu-Lovell, Kahoko; Suzuki, Keita; Fernell, Elisabeth; Gillberg, Christopher

2016-01-01

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.

Pediatric epilepsy and comorbid reading disorders, math disorders, or autism spectrum disorders: Impact of epilepsy on cognitive patterns

NARCIS (Netherlands)

van Iterson, L.; de Jong, P.F.; Zijlstra, B.J.H.

2015-01-01

Introduction: In pediatric epilepsy, comorbidities are reported to be frequent. The present study focusedon the cognitive patterns of children with isolated epilepsy, children with isolated neurodevelopmental disorders (reading disorders, math disorders, autism spectrum disorders), and children with

Epigenetics in autism and other neurodevelopmental diseases.

Science.gov (United States)

Miyake, Kunio; Hirasawa, Takae; Koide, Tsuyoshi; Kubota, Takeo

2012-01-01

Autism was previously thought to be caused by environmental factors. However, genetic factors are now considered to be more contributory to the pathogenesis of autism, based on the recent findings of mutations in the genes which encode synaptic molecules associated with the communication between neurons. Epigenetic is a mechanism that controls gene expression without changing DNA sequence but by changing chromosomal histone modifications and its abnormality is associated with several neurodevelopmental diseases. Since epigenetic modifications are known to be affected by environmental factors such as nutrition, drugs and mental stress, autistic diseases are not only caused by congenital genetic defects, but may also be caused by environmental factors via epigenetic mechanism. In this chapter, we introduce autistic diseases caused by epigenetic failures and discuss epigenetic changes by environmental factors and discuss new treatments for neurodevelopmental diseases based on the recent epigenetic findings.

Difference or disorder? Cultural issues in understanding neurodevelopmental disorders.

Science.gov (United States)

Norbury, Courtenay Frazier; Sparks, Alison

2013-01-01

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.

Ventricular enlargement in patients with affective disorders

International Nuclear Information System (INIS)

Murashita, Jun; Kato, Tadafumi; Shioiri, Toshiki; Hamakawa, Inubushi, Toshiro; Hiroshi; Takahashi, Saburo

1994-01-01

Ventricular enlargement was determined using linear measurement on MR images in a total of 71 patients with affective disorders, including bipolar affective disorder (41) and depression (30). Fourty-one healthy persons served as controls. Evans ratio, Huckman number and minimum distance of caudate nuclei (MDCN) were used as indices for ventricular enlargment. No significant difference in Evans ratio was observed between both the group of bipolar affective disorder and the group of depression and the control group. Nor did it correlate with age in any of the groups. Huckman number was significantly higher in the group of bipolar affective disorder than the other two groups. It positively correlated with age in the group of depression. MDCN was significantly increased in the group of bipolar affective disorder, as compared with the control group; and there was a positive correlation between MDCN and age in both the group of dipolar affective disorder and the group of depression. In conclusion, ventricular enlargement was dependent upon aging in affetive disorder patients. This tendency was more noticeable in the group of depression. In addition, atrophy of the caudate nuclei was likely to be severer in the group of dipolar affective disorder than the group of depression. (N.K.)

Neurodevelopmental outcomes of triplets or higher-order extremely low birth weight infants.

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Wadhawan, Rajan; Oh, William; Vohr, Betty R; Wrage, Lisa; Das, Abhik; Bell, Edward F; Laptook, Abbot R; Shankaran, Seetha; Stoll, Barbara J; Walsh, Michele C; Higgins, Rosemary D

2011-03-01

Extremely low birth weight twins have a higher rate of death or neurodevelopmental impairment than singletons. Higher-order extremely low birth weight multiple births may have an even higher rate of death or neurodevelopmental impairment. Extremely low birth weight (birth weight 401-1000 g) multiple births born in participating centers of the Neonatal Research Network between 1996 and 2005 were assessed for death or neurodevelopmental impairment at 18 to 22 months' corrected age. Neurodevelopmental impairment was defined by the presence of 1 or more of the following: moderate to severe cerebral palsy; mental developmental index score or psychomotor developmental index score less than 70; severe bilateral deafness; or blindness. Infants who died within 12 hours of birth were excluded. Maternal and infant demographic and clinical variables were compared among singleton, twin, and triplet or higher-order infants. Logistic regression analysis was performed to establish the association between singletons, twins, and triplet or higher-order multiples and death or neurodevelopmental impairment, controlling for confounding variables that may affect death or neurodevelopmental impairment. Our cohort consisted of 8296 singleton, 2164 twin, and 521 triplet or higher-order infants. The risk of death or neurodevelopmental impairment was increased in triplets or higher-order multiples when compared with singletons (adjusted odds ratio: 1.7 [95% confidence interval: 1.29-2.24]), and there was a trend toward an increased risk when compared with twins (adjusted odds ratio: 1.27 [95% confidence: 0.95-1.71]). Triplet or higher-order births are associated with an increased risk of death or neurodevelopmental impairment at 18 to 22 months' corrected age when compared with extremely low birth weight singleton infants, and there was a trend toward an increased risk when compared with twins.

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.

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Muneoka, Katsumasa; Kuwagata, Makiko; Ogawa, Tetsuo; Shioda, Seiji

2015-04-01

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.

Neurodevelopmental disruption of cortico-striatal function caused by degeneration of habenula neurons.

Directory of Open Access Journals (Sweden)

Young-A Lee

2011-04-01

Full Text Available The habenula plays an important role on cognitive and affective functions by regulating monoamines transmission such as the dopamine and serotonin, such that its dysfunction is thought to underlie a number of psychiatric conditions. Given that the monoamine systems are highly vulnerable to neurodevelopmental insults, damages in the habenula during early neurodevelopment may cause devastating effects on the wide-spread brain areas targeted by monoamine innervations.Using a battery of behavioral, anatomical, and biochemical assays, we examined the impacts of neonatal damage in the habenula on neurodevelopmental sequelae of the prefrontal cortex (PFC and nucleus accumbens (NAcc and associated behavioral deficits in rodents. Neonatal lesion of the medial and lateral habenula by ibotenic acid produced an assortment of behavioral manifestations consisting of hyper-locomotion, impulsivity, and attention deficit, with hyper-locomotion and impulsivity being observed only in the juvenile period, whereas attention deficit was sustained up until adulthood. Moreover, these behavioral alterations were also improved by amphetamine. Our study further revealed that impulsivity and attention deficit were associated with disruption of PFC volume and dopamine (DA receptor expression, respectively. In contrast, hyper-locomotion was associated with decreased DA transporter expression in the NAcc. We also found that neonatal administration of nicotine into the habenula of neonatal brains produced selective lesion of the medial habenula. Behavioral deficits with neonatal nicotine administration were similar to those caused by ibotenic acid lesion of both medial and lateral habenula during the juvenile period, whereas they were different in adulthood.Because of similarity between behavioral and brain alterations caused by neonatal insults in the habenula and the symptoms and suggested neuropathology in attention deficit/hyperactivity disorder (ADHD, these results

Neurodevelopmental outcome in prenatally diagnosed isolated agenesis of the corpus callosum.

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Folliot-Le Doussal, Lise; Chadie, Alexandra; Brasseur-Daudruy, Marie; Verspyck, Eric; Saugier-Veber, Pascale; Marret, Stéphane

2018-01-01

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.

Identification of an age-dependent biomarker signature in children and adolescents with autism spectrum disorders

NARCIS (Netherlands)

Ramsey, J.M.; Guest, P.C.; Broek, J.A.C.; Glennon, J.C.; Rommelse, N.N.J.; Franke, B.; Rahmoune, H.; Buitelaar, J.K.; Bahn, S.

2013-01-01

BACKGROUND: Autism spectrum disorders (ASDs) are neurodevelopmental conditions with symptoms manifesting before the age of 3, generally persisting throughout life and affecting social development and communication. Here, we have investigated changes in protein biomarkers in blood during childhood

Identification of an age-dependent biomarker signature in children and adolescents with autism spectrum disorders

NARCIS (Netherlands)

J.M. Ramsey (Jordan); P.C. Guest (Paul); J.A.C. Broek (Jantine A.); J.C. Glennon (Jeffrey C); N. Rommelse (Nanda); B. Franke (Barbara); H. Rahmoune (Hassan); J.K. Buitelaar (Jan); S. Bahn (Sabine)

2013-01-01

textabstractBackground: Autism spectrum disorders (ASDs) are neurodevelopmental conditions with symptoms manifesting before the age of 3, generally persisting throughout life and affecting social development and communication. Here, we have investigated changes in protein biomarkers in blood during

Interventions to improve gross motor performance in children with neurodevelopmental disorders: a meta-analysis.

Science.gov (United States)

Lucas, Barbara R; Elliott, Elizabeth J; Coggan, Sarah; Pinto, Rafael Z; Jirikowic, Tracy; McCoy, Sarah Westcott; Latimer, Jane

2016-11-29

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

Difference or Disorder? Cultural Issues in Understanding Neurodevelopmental Disorders

Science.gov (United States)

Norbury, Courtenay Frazier; Sparks, Alison

2013-01-01

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…

Shank synaptic scaffold proteins: keys to understanding the pathogenesis of autism and other synaptic disorders.

Science.gov (United States)

Sala, Carlo; Vicidomini, Cinzia; Bigi, Ilaria; Mossa, Adele; Verpelli, Chiara

2015-12-01

Shank/ProSAP proteins are essential to synaptic formation, development, and function. Mutations in the family of SHANK genes are strongly associated with autism spectrum disorders (ASD) and other neurodevelopmental and neuropsychiatric disorders, such as intellectual disability (ID), and schizophrenia. Thus, the term 'Shankopathies' identifies a number of neuronal diseases caused by alteration of Shank protein expression leading to abnormal synaptic development. With this review we want to summarize the major genetic, molecular, behavior and electrophysiological studies that provide new clues into the function of Shanks and pave the way for the discovery of new therapeutic drugs targeted to treat patients with SHANK mutations and also patients affected by other neurodevelopmental and neuropsychiatric disorders. Shank/ProSAP proteins are essential to synaptic formation, development, and function. Mutations in the family of SHANK genes are strongly associated with autism spectrum disorders (ASD) and other neurodevelopmental and neuropsychiatric disorders, such as intellectual disability (ID), and schizophrenia (SCZ). With this review we want to summarize the major genetic, molecular, behavior and electrophysiological studies that provide new clues into the function of Shanks and pave the way for the discovery of new therapeutic drugs targeted to treat patients with SHANK mutations. © 2015 International Society for Neurochemistry.

Co-morbidity in Attention-Deficit Hyperactivity Disorder: A Clinical Study from India.

Science.gov (United States)

Jacob, P; Srinath, S; Girimaji, S; Seshadri, S; Sagar, J V

2016-12-01

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.

Development and Psychometric Properties of A Screening Tool for Assessing Developmental Coordination Disorder in Adults

OpenAIRE

Clark, Carol J.

2013-01-01

Background: Developmental Coordination Disorder (DCD) is a neurodevelopmental disorder affecting motor coordination. Evidence suggests this disorder persists into adulthood and may be associated with biomechanical dysfunction and pain. We report on the development and initial validation of a questionnaire to assess for DCD in adults. Methods: An initial item pool (13 items) was derived from the American Psychiatric Association criteria and World Health Organisation definition for DCD. An expe...

Abstracts of the 11th International Conference on Developmental Coordination Disorder (DCD11

Directory of Open Access Journals (Sweden)

DCD11 Congress Delegates

2015-06-01

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.

Telemedicine is helping the parents of children with neurodevelopmental disorders living in remote and deprived areas.

Science.gov (United States)

Stuckey, Ruth; Domingues-Montanari, Sophie

2017-08-01

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.

Sleep Spindle Characteristics in Children with Neurodevelopmental Disorders and Their Relation to Cognition

Science.gov (United States)

Wise, Merrill S.

2016-01-01

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

CHD8 regulates neurodevelopmental pathways associated with autism spectrum disorder in neural progenitors

Science.gov (United States)

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.

2014-01-01

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

A Clinician's Guide to Co-Occurring ADHD among Adolescent Substance Users: Comorbidity, Neurodevelopmental Risk, and Evidence-Based Treatment Options

Science.gov (United States)

Hogue, Aaron; Evans, Steven W.; Levin, Frances R.

2017-01-01

This article introduces neurodevelopmental and clinical considerations for treating adolescents with co-occurring attention deficit hyperactivity disorder (ADHD) and adolescent substance use (ASU) in outpatient settings. We first describe neurobiological impairments common to ADHD and ASU, including comorbidity with conduct disorder, that evoke a…

Shared heritability of attention-deficit/hyperactivity disorder and autism spectrum disorder

NARCIS (Netherlands)

Rommelse, N.N.J.; Franke, B.; Geurts, H.M.; Hartman, C.A.; Buitelaar, J.K.

2010-01-01

Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are both highly heritable neurodevelopmental disorders. Evidence indicates both disorders co-occur with a high frequency, in 20-50% of children with ADHD meeting criteria for ASD and in 30-80% of ASD children meeting

Shared heritability of attention-deficit/hyperactivity disorder and autism spectrum disorder.

NARCIS (Netherlands)

Rommelse, N.N.J.; Franke, B.; Geurts, H.M.; Hartman, C.A.; Buitelaar, J.K.

2010-01-01

Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are both highly heritable neurodevelopmental disorders. Evidence indicates both disorders co-occur with a high frequency, in 20-50% of children with ADHD meeting criteria for ASD and in 30-80% of ASD children meeting

Shared heritability of attention-deficit/hyperactivity disorder and autism spectrum disorder

NARCIS (Netherlands)

Rommelse, Nanda N. J.; Franke, Barbara; Geurts, Hilde M.; Hartman, Catharina A.; Buitelaar, Jan K.

Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are both highly heritable neurodevelopmental disorders. Evidence indicates both disorders co-occur with a high frequency, in 20-50% of children with ADHD meeting criteria for ASD and in 30-80% of ASD children meeting

Affective dysfunction in a mouse model of Rett syndrome: Therapeutic effects of environmental stimulation and physical activity.

Science.gov (United States)

Kondo, Mari A; Gray, Laura J; Pelka, Gregory J; Leang, Sook-Kwan; Christodoulou, John; Tam, Patrick P L; Hannan, Anthony J

2016-02-01

Rett syndrome (RTT) is a neurodevelopmental disorder associated with mutations in the X-linked gene encoding methyl-CpG-binding protein 2 (MeCP2) and consequent dysregulation of brain maturation. Patients suffer from a range of debilitating physical symptoms, however, behavioral and emotional symptoms also severely affect their quality of life. Here, we present previously unreported and clinically relevant affective dysfunction in the female heterozygous Mecp2(tm1Tam) mouse model of RTT (129sv and C57BL6 mixed background). The affective dysfunction and aberrant anxiety-related behavior of the Mecp2(+/-) mice were found to be reversible with environmental enrichment (EE) from 4 weeks of age. The effect of exercise alone (via wheel running) was also explored, providing the first evidence that increased voluntary physical activity in an animal model of RTT is beneficial for some phenotypes. Mecp2(+/-) mutants displayed elevated corticosterone despite decreased Crh expression, demonstrating hypothalamic-pituitary-adrenal axis dysregulation. EE of Mecp2(+/-) mice normalized basal serum corticosterone and hippocampal BDNF protein levels. The enrichment-induced rescue appears independent of the transcriptional regulation of the MeCP2 targets Bdnf exon 4 and Crh. These findings provide new insight into the neurodevelopmental role of MeCP2 and pathogenesis of RTT, in particular the affective dysfunction. The positive outcomes of environmental stimulation and physical exercise have implications for the development of therapies targeting the affective symptoms, as well as behavioral and cognitive dimensions, of this devastating neurodevelopmental disorder. © 2015 Wiley Periodicals, Inc.

Increased risk of neuropsychological disorders in children born preterm without major disabilities: a neurodevelopmental model

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Dipasquale Filippo

2009-06-01

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.

Circadian polymorphisms associated with affective disorders

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Shekhtman Tatyana

2009-01-01

Full Text Available Abstract Background Clinical symptoms of affective disorders, their response to light treatment, and sensitivity to other circadian interventions indicate that the circadian system has a role in mood disorders. Possibly the mechanisms involve circadian seasonal and photoperiodic mechanisms. Since genetic susceptibilities contribute a strong component to affective disorders, we explored whether circadian gene polymorphisms were associated with affective disorders in four complementary studies. Methods Four groups of subjects were recruited from several sources: 1 bipolar proband-parent trios or sib-pair-parent nuclear families, 2 unrelated bipolar participants who had completed the BALM morningness-eveningness questionnaire, 3 sib pairs from the GenRed Project having at least one sib with early-onset recurrent unipolar depression, and 4 a sleep clinic patient group who frequently suffered from depression. Working mainly with the SNPlex assay system, from 2 to 198 polymorphisms in genes related to circadian function were genotyped in the participant groups. Associations with affective disorders were examined with TDT statistics for within-family comparisons. Quantitative trait associations were examined within the unrelated samples. Results In NR1D1, rs2314339 was associated with bipolar disorder (P = 0.0005. Among the unrelated bipolar participants, 3 SNPs in PER3 and CSNK1E were associated with the BALM score. A PPARGC1B coding SNP, rs7732671, was associated with affective disorder with nominal significance in bipolar family groups and independently in unipolar sib pairs. In TEF, rs738499 was associated with unipolar depression; in a replication study, rs738499 was also associated with the QIDS-SR depression scale in the sleep clinic patient sample. Conclusion Along with anti-manic effects of lithium and the antidepressant effects of bright light, these findings suggest that perturbations of the circadian gene network at several levels may

Exploration of large, rare copy number variants associated with psychiatric and neurodevelopmental disorders in individuals with anorexia nervosa.

Science.gov (United States)

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

2017-08-01

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.

Neurodevelopmental and neurobehavioral characteristics in males and females with CDKL5 duplications.

Science.gov (United States)

Szafranski, Przemyslaw; Golla, Sailaja; Jin, Weihong; Fang, Ping; Hixson, Patricia; Matalon, Reuben; Kinney, Daniel; Bock, Hans-Georg; Craigen, William; Smith, Janice L; Bi, Weimin; Patel, Ankita; Wai Cheung, Sau; Bacino, Carlos A; Stankiewicz, Paweł

2015-07-01

Point mutations and genomic deletions of the CDKL5 (STK9) gene on chromosome Xp22 have been reported in patients with severe neurodevelopmental abnormalities, including Rett-like disorders. To date, only larger-sized (8-21 Mb) duplications harboring CDKL5 have been described. We report seven females and four males from seven unrelated families with CDKL5 duplications 540-935 kb in size. Three families of different ethnicities had identical 667kb duplications containing only the shorter CDKL5 isoform. Four affected boys, 8-14 years of age, and three affected girls, 6-8 years of age, manifested autistic behavior, developmental delay, language impairment, and hyperactivity. Of note, two boys and one girl had macrocephaly. Two carrier mothers of the affected boys reported a history of problems with learning and mathematics while at school. None of the patients had epilepsy. Similarly to CDKL5 mutations and deletions, the X-inactivation pattern in all six studied females was random. We hypothesize that the increased dosage of CDKL5 might have affected interactions of this kinase with its substrates, leading to perturbation of synaptic plasticity and learning, and resulting in autistic behavior, developmental and speech delay, hyperactivity, and macrocephaly.

Survival and Neurodevelopmental Outcomes among Periviable Infants.

Science.gov (United States)

Younge, Noelle; Goldstein, Ricki F; Bann, Carla M; Hintz, Susan R; Patel, Ravi M; Smith, P Brian; Bell, Edward F; Rysavy, Matthew A; Duncan, Andrea F; Vohr, Betty R; Das, Abhik; Goldberg, Ronald N; Higgins, Rosemary D; Cotten, C Michael

2017-02-16

Data reported during the past 5 years indicate that rates of survival have increased among infants born at the borderline of viability, but less is known about how increased rates of survival among these infants relate to early childhood neurodevelopmental outcomes. We compared survival and neurodevelopmental outcomes among infants born at 22 to 24 weeks of gestation, as assessed at 18 to 22 months of corrected age, across three consecutive birth-year epochs (2000-2003 [epoch 1], 2004-2007 [epoch 2], and 2008-2011 [epoch 3]). The infants were born at 11 centers that participated in the National Institute of Child Health and Human Development Neonatal Research Network. The primary outcome measure was a three-level outcome - survival without neurodevelopmental impairment, survival with neurodevelopmental impairment, or death. After accounting for differences in infant characteristics, including birth center, we used multinomial generalized logit models to compare the relative risk of survival without neurodevelopmental impairment, survival with neurodevelopmental impairment, and death. Data on the primary outcome were available for 4274 of 4458 infants (96%) born at the 11 centers. The percentage of infants who survived increased from 30% (424 of 1391 infants) in epoch 1 to 36% (487 of 1348 infants) in epoch 3 (Pneurodevelopmental impairment increased from 16% (217 of 1391) in epoch 1 to 20% (276 of 1348) in epoch 3 (P=0.001), whereas the percentage of infants who survived with neurodevelopmental impairment did not change significantly (15% [207 of 1391] in epoch 1 and 16% [211 of 1348] in epoch 3, P=0.29). After adjustment for changes in the baseline characteristics of the infants over time, both the rate of survival with neurodevelopmental impairment (as compared with death) and the rate of survival without neurodevelopmental impairment (as compared with death) increased over time (adjusted relative risks, 1.27 [95% confidence interval {CI}, 1.01 to 1.59] and 1

Mice lacking Brinp2 or Brinp3, or both, exhibit behaviours consistent with neurodevelopmental disorders

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Susie Ruth Berkowicz

2016-10-01

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.

Light Therapy Boxes for Seasonal Affective Disorder

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Seasonal affective disorder treatment: Choosing a light therapy box Light therapy boxes can offer an effective treatment for seasonal affective disorder. Features such as light intensity, safety, cost and ...

Neuropsychiatric manifestations in late-onset urea cycle disorder patients

OpenAIRE

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

2010-01-01

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...

Rare CNVs in Suicide Attempt include Schizophrenia-Associated Loci and Neurodevelopmental Genes: A Pilot Genome-Wide and Family-Based Study.

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Marcus Sokolowski

Full Text Available Suicidal behavior (SB has a complex etiology involving genes and environment. One of the genetic components in SB could be copy number variations (CNVs, as CNVs are implicated in neurodevelopmental disorders. However, a recently published genome-wide and case-control study did not observe any significant role of CNVs in SB. Here we complemented these initial observations by instead using a family-based trio-sample that is robust to control biases, having severe suicide attempt (SA in offspring as main outcome (n = 660 trios. We first tested for CNV associations on the genome-wide Illumina 1M SNP-array by using FBAT-CNV methodology, which allows for evaluating CNVs without reliance on CNV calling algorithms, analogous to a common SNP-based GWAS. We observed association of certain T-cell receptor markers, but this likely reflected inter-individual variation in somatic rearrangements rather than association with SA outcome. Next, we used the PennCNV software to call 385 putative rare (100 kb CNVs, observed in n = 225 SA offspring. Nine SA offspring had rare CNV calls in a set of previously schizophrenia-associated loci, indicating the importance of such CNVs in certain SA subjects. Several additional, very large (>1MB sized CNV calls in 15 other SA offspring also spanned pathogenic regions or other neural genes of interest. Overall, 45 SA had CNVs enriched for 65 medically relevant genes previously shown to be affected by CNVs, which were characterized by a neurodevelopmental biology. A neurodevelopmental implication was partly congruent with our previous SNP-based GWAS, but follow-up analysis here indicated that carriers of rare CNVs had a decreased burden of common SNP risk-alleles compared to non-carriers. In conclusion, while CNVs did not show genome-wide association by the FBAT-CNV methodology, our preliminary observations indicate rare pathogenic CNVs affecting neurodevelopmental functions in a subset of SA, who were distinct from SA having

Apolipoprotein E-epsilon 4 frequency in affective disorder

DEFF Research Database (Denmark)

Kessing, L V; Jørgensen, O S

1999-01-01

-Bråne-Steen Dementia Rating Scale, and the Global Deterioration Scale. RESULTS: The frequency of APOE-epsilon 4 allele was approximately the same in unipolar patients (.189) and in bipolar patients (.167). Although patients showed more cognitive impairment than controls, no significant overall difference was found...... was found with gender, age at onset, the number of affective episodes, the presence of psychotic features, or the prevalence of familial affective disorder. CONCLUSIONS: It seems that cognitive impairment in affective disorder can be attributed to pathways other than the APOE genotype.......BACKGROUND: The epsilon 4 allele of apolipoprotein E (APOE) as well as affective disorder have been found to be associated with Alzheimer's disease, but it is unclear whether cognitive impairment in affective disorder or subtypes of affective disorder is mediated by the epsilon 4 allele of APOE...

General characteristics affective disorders in arterial hypertension

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A. A. Tolmachov

2016-11-01

Full Text Available The author analyzes researches on the study of affective disorders in arterial hypertension (AH. It is noted that AH at the present stage is considered as one of the factors of cognitive dysfunction. The article emphasizes that the analysis of comorbid relations of depression and hypertension is hardly possible without the study of affective and cardiovascular disorders at the clinical level, taking into account their dynamic characteristics and key features of the course of depressive states in general. The author considers the features of the current: post-stroke depressions, nosogenic depressions of anxious and anxious-hypochondriacally types, anxiety-phobic disorders, comorbid panic disorders, protracted depression with traits of endoreactive dysthymia, hypochondriacal disorders, panic attacks, and the like in patients with arterial hypertension. Some features of affective disorders are revealed in patients with cardiovascular disorders. It is emphasized that the increase in the effectiveness of treatment of mental disorders in patients with hypertensive encephalopathy can be solved by improving the methods of early diagnosis, developing additional screening and monitoring diagnostic tools using it in an interdisciplinary approach.

Heterozygous CDKL5 Knockout Female Mice Are a Valuable Animal Model for CDKL5 Disorder

OpenAIRE

Fuchs, Claudia; Gennaccaro, Laura; Trazzi, Stefania; Bastianini, Stefano; Bettini, Simone; Martire, Viviana Lo; Ren, Elisa; Medici, Giorgio; Zoccoli, Giovanna; Rimondini, Roberto; Ciani, Elisabetta

2018-01-01

CDKL5 disorder is a severe neurodevelopmental disorder caused by mutations in the X-linked CDKL5 (cyclin-dependent kinase-like five) gene. CDKL5 disorder primarily affects girls and is characterized by early-onset epileptic seizures, gross motor impairment, intellectual disability, and autistic features. Although all CDKL5 female patients are heterozygous, the most valid disease-related model, the heterozygous female Cdkl5 knockout (Cdkl5 +/−) mouse, has been little characterized. The lack of...

Autism as early neurodevelopmental disorder: evidence for an sAPPα-mediated anabolic pathway.

Science.gov (United States)

Lahiri, Debomoy K; Sokol, Deborah K; Erickson, Craig; Ray, Balmiki; Ho, Chang Y; Maloney, Bryan

2013-01-01

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.

Structure–function relationships in the developing cerebellum: evidence from early-life cerebellar injury and neurodevelopmental disorders

Science.gov (United States)

Stoodley, Catherine J.; Limperopoulos, Catherine

2016-01-01

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

The Genetic Intersection of Neurodevelopmental Disorders and Shared Medical Comorbidities – Relations that Translate from Bench to Bedside

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Jamsine Plummer

2016-08-01

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.

Clinical definitions of sensitisation in affective disorder

DEFF Research Database (Denmark)

Kessing, L V; Mortensen, P B; Bolwig, T G

1998-01-01

The observation of a progressive recurrence in affective disorder has been interpreted as a process of sensitisation. The clinical applicability of such a theoretical model was investigated using the Danish case register, which includes all hospital admissions with primary affective disorder...

Genetic and Environmental Control of Neurodevelopmental Robustness in Drosophila.

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David J Mellert

Full Text Available Interindividual differences in neuronal wiring may contribute to behavioral individuality and affect susceptibility to neurological disorders. To investigate the causes and potential consequences of wiring variation in Drosophila melanogaster, we focused on a hemilineage of ventral nerve cord interneurons that exhibits morphological variability. We find that late-born subclasses of the 12A hemilineage are highly sensitive to genetic and environmental variation. Neurons in the second thoracic segment are particularly variable with regard to two developmental decisions, whereas its segmental homologs are more robust. This variability "hotspot" depends on Ultrabithorax expression in the 12A neurons, indicating variability is cell-intrinsic and under genetic control. 12A development is more variable and sensitive to temperature in long-established laboratory strains than in strains recently derived from the wild. Strains with a high frequency of one of the 12A variants also showed a high frequency of animals with delayed spontaneous flight initiation, whereas other wing-related behaviors did not show such a correlation and were thus not overtly affected by 12A variation. These results show that neurodevelopmental robustness is variable and under genetic control in Drosophila and suggest that the fly may serve as a model for identifying conserved gene pathways that stabilize wiring in stressful developmental environments. Moreover, some neuronal lineages are variation hotspots and thus may be more amenable to evolutionary change.

Dysfunctional Affect Regulation : in borderline personality disorder and somatoform disorder

OpenAIRE

van Dijke, A.

2011-01-01

The aim of this dissertation was to provide a systematic exploration of the nature and distribution of dysfunctional affect regulation, its associated phenomena, and retrospectively reported potentially traumatizing events in 475 patients diagnosed with borderline personality disorder (BPD), somatoform disorder (SoD), comorbid BPD+SoD, and a psychiatric comparison group (PC) to provide a baseline against which to compare the hypothesized elevations in dysfunctional self and affect regulation....

Progress in Understanding and Treating SCN2A-Mediated Disorders

DEFF Research Database (Denmark)

Sanders, Stephan J.; Campbell, Arthur J.; Cottrell, Jeffrey R.

2018-01-01

Advances in gene discovery for neurodevelopmental disorders have identified SCN2A dysfunction as a leading cause of infantile seizures, autism spectrum disorder, and intellectual disability. SCN2A encodes the neuronal sodium channel NaV1.2. Functional assays demonstrate strong correlation between...... of neurodevelopmental disorders more generally. Here, we discuss the progress made, through the concerted efforts of a diverse group of academic and industry scientists as well as policy advocates, in understanding and treating SCN2A-related disorders....

Recurrence in affective disorder. I. Case register study

DEFF Research Database (Denmark)

Kessing, L V; Andersen, P K; Mortensen, P B

1998-01-01

hospital admissions with primary affective disorder in Denmark during 1971-1993. A total of 20,350 first-admission patients were discharged with a diagnosis of affective disorder, depressive or manic/cyclic type. RESULTS: The rate of recurrence increased with the number of previous episodes in both...... unipolar and bipolar disorder. Initially, the two types of disorders followed markedly different courses, but later in the course of the illness the rate of recurrence was the same for the two disorders. CONCLUSIONS: The course of severe unipolar and bipolar disorder seems to be progressive in nature...

Early neurodevelopmental outcomes of extremely preterm infants.

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Rogers, Elizabeth E; Hintz, Susan R

2016-12-01

Infants born at extreme preterm gestation are at risk for both death and disability. Although rates of survival have improved for this population, and some evidence suggests a trend toward decreased neuromotor impairment over the past decades, a significant improvement in overall early neurodevelopmental outcome has not yet been realized. This review will examine the rates and types of neurodevelopmental impairment seen after extremely preterm birth, including neurosensory, motor, cognitive, and behavioral outcomes. We focus on early outcomes in the first 18-36 months of life, as the majority of large neonatal studies examining neurodevelopmental outcomes stop at this age. However, this early age is clearly just a first glimpse into lifetime outcomes; the neurodevelopmental effects of extreme prematurity may last through school age, adolescence, and beyond. Importantly, prematurity appears to be an independent risk factor for adverse development, but this population demonstrates considerable variability in the types and severity of impairments. Understanding both the nature and prevalence of neurodevelopmental impairment among extremely preterm infants is important because it can lead to targeted interventions that in turn may lead to improved outcomes. Copyright © 2016 Elsevier Inc. All rights reserved.

Public health and research funding for childhood neurodevelopmental disorders in Sub-Saharan Africa: a time to balance priorities

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Muideen O. Bakare

2014-01-01

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.

Autism as early neurodevelopmental disorder: evidence for an sAPPα-mediated anabolic pathway

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Debomoy K Lahiri

2013-06-01

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.

Attention-deficit/hyperactivity disorder during adulthood.

Science.gov (United States)

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.

Cognitive computer training in children with attention deficit hyperactivity disorder (ADHD) versus no intervention

DEFF Research Database (Denmark)

Bikic, Aida; Leckman, J. F.; Lindschou, Jane

2015-01-01

BACKGROUND: Attention Deficit Hyperactivity Disorder (ADHD) is a common neurodevelopmental disorder characterized by symptoms of inattention and impulsivity and/or hyperactivity and a range of cognitive dysfunctions. Pharmacological treatment may be beneficial; however, many affected individuals...... of cognition, mostly on the working memory or attention but with poor generalization of training on other cognitive functions and functional outcome. Children with ADHD have a variety of cognitive dysfunctions, and it is important that cognitive training target multiple cognitive functions. METHODS...

Oxytocin and Social Cognition in Affective and Psychotic Disorders

Science.gov (United States)

Perez-Rodriguez, M. Mercedes; Mahon, Katie; Russo, Manuela; Ungar, Allison K.; Burdick, Katherine E.

2014-01-01

Impairments in social cognition are now recognized as core illness features in psychotic and affective disorders. Despite the significant disability caused by social cognitive abnormalities, treatments for this symptom dimension are lacking. Here, we describe the evidence demonstrating abnormalities in social cognition in schizophrenia, major depressive disorder, and bipolar disorder, as well as the neurobiology of social cognition including the role of oxytocin. We then review clinical trials of oxytocin administration in psychotic and affective disorders and the impact of this agent on social cognition. To date, several studies have demonstrated that oxytocin may improve social cognition in schizophrenia; too few studies have been conducted in affective disorders to determine the effect of oxytocin on social cognition in these disorders. Future work is needed to clarify which aspects of social cognition may be improved with oxytocin treatment in psychotic and affective disorders. PMID:25153535

Emphasizing the Health Benefits of Vitamin D for Those with Neurodevelopmental Disorders and Intellectual Disabilities

Directory of Open Access Journals (Sweden)

William B. Grant

2015-02-01

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.

Emphasizing the Health Benefits of Vitamin D for Those with Neurodevelopmental Disorders and Intellectual Disabilities

Science.gov (United States)

Grant, William B.; Wimalawansa, Sunil J.; Holick, Michael F.; Cannell, John J.; Pludowski, Pawel; Lappe, Joan M.; Pittaway, Mary; May, Philip

2015-01-01

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

Emphasizing the health benefits of vitamin D for those with neurodevelopmental disorders and intellectual disabilities.

Science.gov (United States)

Grant, William B; Wimalawansa, Sunil J; Holick, Michael F; Cannell, John J; Pludowski, Pawel; Lappe, Joan M; Pittaway, Mary; May, Philip

2015-02-27

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.

Disorders of visual perception

NARCIS (Netherlands)

Ffytche, Dominic H.; Blom, J. D.; Catani, M.

Visual perceptual disorders are often presented as a disparate group of neurological deficits with little consideration given to the wide range of visual symptoms found in psychiatric and neurodevelopmental disease. Here, the authors attempt a functional anatomical classification of all disorders

Disorders of visual perception

NARCIS (Netherlands)

Ffytche, Dominic H.; Blom, J. D.; Catani, M.

2010-01-01

Visual perceptual disorders are often presented as a disparate group of neurological deficits with little consideration given to the wide range of visual symptoms found in psychiatric and neurodevelopmental disease. Here, the authors attempt a functional anatomical classification of all disorders

Neurodevelopmental and Cognitive Outcomes in Children With Intestinal Failure.

Science.gov (United States)

Chesley, Patrick M; Sanchez, Sabrina E; Melzer, Lilah; Oron, Assaf P; Horslen, Simon P; Bennett, F Curt; Javid, Patrick J

2016-07-01

Recent advances in medical and surgical management have led to improved long-term survival in children with intestinal failure. Yet, limited data exist on their neurodevelopmental and cognitive outcomes. The aim of the present study was to measure neurodevelopmental outcomes in children with intestinal failure. Children enrolled in a regional intestinal failure program underwent prospective neurodevelopmental and psychometric evaluation using a validated scoring tool. Cognitive impairment was defined as a mental developmental index Neurodevelopmental impairment was defined as cerebral palsy, visual or hearing impairment, or cognitive impairment. Univariate analyses were performed using the Wilcoxon rank-sum test. Data are presented as median (range). Fifteen children with a remnant bowel length of 18 (5-85) cm were studied at age 17 (12-67) months. Thirteen patients remained dependent on parenteral nutrition. Twelve (80%) subjects scored within the normal range on cognitive testing. Each child with cognitive impairment was noted to have additional risk factors independent of intestinal failure including cardiac arrest and extreme prematurity. On univariate analysis, cognitive impairment was associated with longer inpatient hospital stays, increased number of surgical procedures, and prematurity (P neurodevelopmental impairment. A majority of children with intestinal failure demonstrated normal neurodevelopmental and cognitive outcomes on psychometric testing. These data suggest that children with intestinal failure without significant comorbidity may be at low risk for long-term neurodevelopmental impairment.

Dysfunctional affect regulation in borderline personality disorder and in somatoform disorder

Directory of Open Access Journals (Sweden)

Annemiek van Dijke

2012-09-01

Full Text Available Background: Although affect dysregulation is considered a core component of borderline personality disorder (BPD and somatoform disorders (SoD, remarkably little research has focused on the prevalence and nature of affect dysregulation in these disorders. Also, despite apparent similarities, little is known about how dysfunctional under- and overregulation of affect and positive and negative somatoform and psychoform dissociative experiences inter-relate. Prior studies suggest a clear relationship between early childhood psychological trauma and affect dysregulation, especially when the caretaker is emotionally, sexually, or physically abusing the child, but how these relate to under- and overregulation while differentiating for developmental epochs is not clear. Although an elevated risk of childhood trauma exposure or complex posttraumatic stress disorder (CPTSD symptoms has been reported in BPD and SoD, trauma histories, dysfunctional affect regulation, dissociation, PTSD, and CPTSD were never assessed in unison in BPD and/or SoD. Method: BPD and/or SoD diagnoses were confirmed or ruled out in 472 psychiatric inpatients using clinical interviews. Dysfunctional under- and overregulation of affect and somatoform and psychoform dissociation, childhood trauma-by-primary-caretaker (TPC, PTSD, and CPTSD were all measured using self reports. Results: No disorder-specific form of dysfunctional affect regulation was found. Although both BPD and SoD can involve affect dysregulation and dissociation, there is a wide range of intensity of dysfunctional regulation phenomena in patients with these diagnoses. Evidence was found for the existence of three qualitatively different forms of experiencing states: inhibitory experiencing states (overregulation of affect and negative psychoform dissociation most commonly found in SoD, excitatory experiencing states (underregulation of affect and positive psychoform dissociation most commonly found in BPD, and

Bipolar Affective Disorder and Migraine

Directory of Open Access Journals (Sweden)

Birk Engmann

2012-01-01

Full Text Available This paper consists of a case history and an overview of the relationship, aetiology, and treatment of comorbid bipolar disorder migraine patients. A MEDLINE literature search was used. Terms for the search were bipolar disorder bipolar depression, mania, migraine, mood stabilizer. Bipolar disorder and migraine cooccur at a relatively high rate. Bipolar II patients seem to have a higher risk of comorbid migraine than bipolar I patients have. The literature on the common roots of migraine and bipolar disorder, including both genetic and neuropathological approaches, is broadly discussed. Moreover, bipolar disorder and migraine are often combined with a variety of other affective disorders, and, furthermore, behavioural factors also play a role in the origin and course of the diseases. Approach to treatment options is also difficult. Several papers point out possible remedies, for example, valproate, topiramate, which acts on both diseases, but no first-choice treatments have been agreed upon yet.

Copy number variation in obsessive-compulsive disorder and tourette syndrome: A cross-disorder study

NARCIS (Netherlands)

L.M. McGrath; D. Yu (D.); C.R. Marshall (Christian); L.K. Davis (Lea); B. Thiruvahindrapuram (Bhooma); B. Li (Bingbin); C. Cappi (Carolina); G. Gerber (Gloria); A. de Wolf (Anneke); F.A. Schroeder (Frederick); L. Osiecki (Lisa); C. O'Dushlaine (Colm); A. Kirby (Andrew); C. Illmann (Cornelia); S. Haddad (Stephen); P. Gallagher (Patience); J. Fagerness (Jesen); C.L. Barr (Cathy); L. Bellodi (Laura); F. Benarroch (Fortu); O.J. Bienvenu (Oscar); D.W. Black (Donald); J. Bloch (Jocelyne); R.D. Bruun (Ruth); C.L. Budman (Cathy); B. Camarena (Beatriz); D. Cath (Daniëlle); M.C. Cavallini (Maria); S. Chouinard; V. Coric (Vladimir); C. Cullen; R. Delorme (Richard); D.A.J.P. Denys (Damiaan); E.M. Derks (Eske); Y. Dion (Yves); M.C. Rosário (Maria); C.E. Eapen (Chundamannil Eapen); P. Evans; P. Falkai (Peter); T.V. Fernandez (Thomas); H. Garrido (Helena); D. Geller (Daniel); H.J. Grabe (Hans Jörgen); M. Grados (Marco); B.D. Greenberg (Benjamin); V. Gross-Tsur (Varda); E. Grünblatt (Edna); M.L. Heiman (Mark); S.M.J. Hemmings (Sian); L.D. Herrera (Luis); A.G. Hounie (Ana); J. Jankovic (Joseph); J.L. Kennedy; R.A. King; R. Kurlan; N. Lanzagorta (Nuria); M. Leboyer (Marion); J.F. Leckman; L. Lennertz (Leonhard); C. Lochner (Christine); T.L. Lowe (Thomas); H.N. Lyon (Helen); F. MacCiardi (Fabio); W. Maier (Wolfgang); J.T. McCracken (James); W.M. McMahon (William); D.L. Murphy (Dennis); A.L. Naarden (Allan); E. Nurmi (Erika); A.J. Pakstis; C. Pato (Carlos); C. Pato (Carlos); J. Piacentini (John); C. Pittenger (Christopher); M.N. Pollak (Michael); V.I. Reus (Victor); M.A. Richter (Margaret); M. Riddle (Mark); M.M. Robertson; D. Rosenberg (David); G.A. Rouleau; S. Ruhrmann (Stephan); A.S. Sampaio (Aline); J. Samuels (Jonathan); P. Sandor (Paul); B. Sheppard (Brooke); H.S. Singer (Harvey); J.H. Smit (Jan); D.J. Stein (Dan); J.A. Tischfield (Jay); H. Vallada (Homero); J. Veenstra-Vanderweele (Jeremy); S. Walitza (Susanne); Y. Wang (Ying); A. Wendland (Annika); Y.Y. Shugart; E.C. Miguel (Euripedes); H. Nicolini (Humberto); B.A. Oostra (Ben); R. Moessner (Rainald); M. Wagner (Michael); A. Ruiz-Linares (Andres); P. Heutink (Peter); G. Nestadt (Gerald); N.B. Freimer (Nelson); T.L. Petryshen (Tracey); D. Posthuma (Danielle); M.A. Jenike (Michael); N.J. Cox (Nancy); G.L. Hanna (Gregory); H. Brentani (Helena); S.W. Scherer (Stephen); P.D. Arnold (Paul); S.E. Stewart; C. Mathews; J.A. Knowles (James A); E.H. Cook (Edwin); D.L. Pauls (David); K. Wang (Kai); J.M. Scharf; B.M. Neale (Benjamin)

2014-01-01

textabstractObjective Obsessive-compulsive disorder (OCD) and Tourette syndrome (TS) are heritable neurodevelopmental disorders with a partially shared genetic etiology. This study represents the first genome-wide investigation of large (>500 kb), rare (<1%) copy number variants (CNVs) in OCD and

Elimination diets' efficacy and mechanisms in attention deficit hyperactivity disorder and autism spectrum disorder

NARCIS (Netherlands)

Ly, Verena; Bottelier, Marco; Hoekstra, Pieter J.; Vasquez, Alejandro Arias; Buitelaar, Jan K.; Rommelse, Nanda N.

Nutrition plays an important role in neurodevelopment. This insight has led to increasing research into the efficacy of nutrition-related interventions for treating neurodevelopmental disorders. This review discusses an elimination diet as a treatment for attention deficit hyperactivity disorder and

The Neuroanatomy of Autism Spectrum Disorder: An Overview of Structural Neuroimaging Findings and Their Translatability to the Clinical Setting

Science.gov (United States)

Ecker, Christine

2017-01-01

Autism spectrum disorder is a complex neurodevelopmental disorder, which is accompanied by differences in brain anatomy, functioning and brain connectivity. Due to its neurodevelopmental character, and the large phenotypic heterogeneity among individuals on the autism spectrum, the neurobiology of autism spectrum disorder is inherently difficult…

Neurodevelopmental Outcome of Children with Congenital Hypothyroidism Diagnosed in a National Screening Program in Turkey.

Science.gov (United States)

Baysal, Bahar Toklu; Baysal, Bora; Genel, Ferah; Erdur, Baris; Ozbek, Erhan; Demir, Korcan; Ozkan, Behzat

2017-05-15

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.

Disruption of the ASTN2/TRIM32 locus at 9q33.1 is a risk factor in males for autism spectrum disorders, ADHD and other neurodevelopmental phenotypes

Science.gov (United States)

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.

2014-01-01

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

Tourette and tic disorders in ICD-11: standing at the diagnostic crossroads.

Science.gov (United States)

Woods, Douglas W; Thomsen, Per H

2014-01-01

This article reflects discussion by the WHO ICD-11 Working Group on the Classification of Obsessive-Compulsive and Related Disorders. After reviewing the historical classification of tic disorders, this article discusses their placement in ICD-11. Existing problems with diagnostic labels and criteria, appropriate placement of the tic disorders category within the ICD-11 system, and pragmatic factors affecting classification are reviewed. The article ends with recommendations to (a) maintain consistency with the DSM-5 diagnostic labels for tic disorders, (b) add a minimum duration guideline for a provisional tic disorder diagnosis, (c) remove the multiple motor tic guideline for the diagnosis of Tourette disorder, and (d) co-parent the tic disorder diagnoses in the disorders of the nervous system and the mental and behavioral disorders categories, with secondary co-parenting in the obsessive-compulsive and related disorders and neurodevelopmental disorders sections.

Long-term neurodevelopmental outcomes of congenital diaphragmatic hernia survivors not treated with extracorporeal membrane oxygenation.

Science.gov (United States)

Frisk, Virginia; Jakobson, Lorna S; Unger, Sharon; Trachsel, Daniel; O'Brien, Karel

2011-07-01

Although there has been a marked improvement in the survival of children with congenital diaphragmatic hernia (CDH) in the past 2 decades, there are few reports of long-term neurodevelopmental outcome in this population. The present study examined neurodevelopmental outcomes in 10- to 16-year-old CDH survivors not treated with extracorporeal membrane oxygenation (ECMO). Parents of 27 CDH survivors completed questionnaires assessing medical problems, daily living skills, educational outcomes, behavioral problems, and executive functioning. Fifteen CDH survivors and matched full-term controls completed standardized intelligence, academic achievement, phonological processing, and working memory tests. Non-ECMO-treated CDH survivors demonstrated high rates of clinically significant difficulties on standardized academic achievement measures, and 14 of the 27 survivors had a formal diagnosis of specific learning disability, attention deficit hyperactivity disorder, or developmental disability. Specific problems with executive function, cognitive and attentional weaknesses, and social difficulties were more common in CDH patients than controls. Perioperative hypocapnia was linked to executive dysfunction, behavioral problems, lowered intelligence, and poor achievement in mathematics. Non-ECMO-treated CDH survivors are at substantial risk for neurodevelopmental problems in late childhood and adolescence. Copyright © 2011 Elsevier Inc. All rights reserved.

Neurodevelopmental comorbidities and seizure control 24 months after a first unprovoked seizure in children.

Science.gov (United States)

Jason, Eva Åndell; Tomson, Torbjörn; Carlsson, Sofia; Tedroff, Kristina; Åmark, Per

2018-07-01

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.

Copy number variation in obsessive-compulsive disorder and tourette syndrome: a cross-disorder study.

NARCIS (Netherlands)

McGrath, L.M.; Yu, D.; Marshall, C.; Davis, L.K.; Thiruvahindrapuram, B.; Li, B.; Cappi, C.; Gerber, G.; Wolf, A.; Schroeder, F.A.; Osiecki, L.; O'Dushlaine, C.; Kirby, A.; Illmann, C.; Haddad, S.; Gallagher, P.; Fagerness, J.A.; Barr, C.L.; Bellodi, L.; Benarroch, F.; Bienvenu, O.J.; Black, D. W.; Bloch, M.H.; Bruun, R.D.; Budman, C.L.; Camarena, B.; Cath, D.C.; Cavallini, M.C.; Chouinard, S.; Coric, V.; Cullen, B.; Delorme, R.; Denys, D.; Derks, E.M.; Dion, Y.; Rosário, M.C.; Eapen, V.; Evans, P.; Falkai, P.; Fernandez, T.V.; Garrido, H.; Geller, D.; Grabe, H.J.; Grados, M.A.; Greenberg, B.D.; Gross-Tsur, V.; Grünblatt, E.; Heiman, G.A.; Hemmings, S.M.; Herrera, L.D.; Hounie, A.G.; Jankovic, J.; Kennedy, J.L.; King, R.A.; Kurlan, R.; Lanzagorta, N.; Leboyer, M.; Leckman, J.F.; Lennertz, L.; Lochner, C.; Lowe, T.L.; Lyon, G.J.; Macciardi, F.; Maier, W.; McCracken, J.T.; McMahon, W.; Murphy, D.L.; Naarden, A.L.; Neale, B. M.; Nurmi, E.; Pakstis, A.J.; Pato, M. T.; Piacentini, J.; Pittenger, C.; Pollak, Y.; Reus, V.I.; Richter, M.A.; Riddle, M.; Robertson, M.M.; Rosenberg, D.; Rouleau, G.A.; Ruhrmann, S.; Sampaio, A.S.; Samuels, J.; Sandor, P.; Sheppard, B.; Singer, H.S.; Smit, J.H.; Stein, D.J.; Tischfield, J.A.; Vallada, H.; Veenstra-Vanderweele, J.; Walitza, S.; Wang, Y.; Wendland, J.R.; Shugart, Y.Y.; Miguel, E.C.; Nicolini, H.; Oostra, B.A.; Moessner, R.; Wagner, M.; Ruiz-Linares, A.; Heutink, P.; Nestadt, G.; Freimer, N.; Petryshen, T.; Posthuma, D.; Jenike, M.A.; Cox, N.J.; Hanna, G.L.; Brentani, H.; Scherer, S.W.; Arnold, P.D.; Stewart, S.E.; Mathews, C.A.; Knowles, J.A.; Cook, E.H.; Pauls, D.L.; Wang, K.; Scharf, J.M.

2014-01-01

Objective Obsessive-compulsive disorder (OCD) and Tourette syndrome (TS) are heritable neurodevelopmental disorders with a partially shared genetic etiology. This study represents the first genome-wide investigation of large (>500 kb), rare (<1%) copy number variants (CNVs) in OCD and the largest

Copy number variation in obsessive-compulsive disorder and tourette syndrome : a cross-disorder study

NARCIS (Netherlands)

McGrath, Lauren M; Yu, Dongmei; Marshall, Christian; Davis, Lea K; Thiruvahindrapuram, Bhooma; Li, Bingbin; Cappi, Carolina; Gerber, Gloria; Wolf, Aaron; Schroeder, Frederick A; Osiecki, Lisa; O'Dushlaine, Colm; Kirby, Andrew; Illmann, Cornelia; Haddad, Stephen; Gallagher, Patience; Fagerness, Jesen A; Barr, Cathy L; Bellodi, Laura; Benarroch, Fortu; Bienvenu, O Joseph; Black, Donald W; Bloch, Michael H; Bruun, Ruth D; Budman, Cathy L; Camarena, Beatriz; Cath, Danielle C; Cavallini, Maria C; Chouinard, Sylvain; Coric, Vladimir; Cullen, Bernadette; Delorme, Richard; Denys, D.; Derks, Eske M; Dion, Yves; Rosário, Maria C; Eapen, Valsama; Evans, Patrick; Falkai, Peter; Fernandez, Thomas V; Garrido, Helena; Geller, Daniel; Grabe, Hans J; Grados, Marco A; Greenberg, Benjamin D; Gross-Tsur, Varda; Grünblatt, Edna; Heiman, Gary A; Hemmings, Sian M J; Herrera, Luis D; Hounie, Ana G; Jankovic, Joseph; Kennedy, James L; King, Robert A; Kurlan, Roger; Lanzagorta, Nuria; Leboyer, Marion; Leckman, James F; Lennertz, Leonhard; Lochner, Christine; Lowe, Thomas L; Lyon, Gholson J; Macciardi, Fabio; Maier, Wolfgang; McCracken, James T; McMahon, William; Murphy, Dennis L; Naarden, Allan L; Neale, Benjamin M; Nurmi, Erika; Pakstis, Andrew J; Pato, Michele T; Pato, Carlos N; Piacentini, John; Pittenger, Christopher; Pollak, Yehuda; Reus, Victor I; Richter, Margaret A; Riddle, Mark; Robertson, Mary M; Rosenberg, David; Rouleau, Guy A; Ruhrmann, Stephan; Sampaio, Aline S; Samuels, Jack; Sandor, Paul; Sheppard, Brooke; Singer, Harvey S; Smit, Jan H; Stein, Dan J; Tischfield, Jay A; Vallada, Homero; Veenstra-VanderWeele, Jeremy; Walitza, Susanne; Wang, Ying; Wendland, Jens R; Shugart, Yin Yao; Miguel, Euripedes C; Nicolini, Humberto; Oostra, Ben A; Moessner, Rainald; Wagner, Michael; Ruiz-Linares, Andres; Heutink, Peter; Nestadt, Gerald; Freimer, Nelson; Petryshen, Tracey; Posthuma, Danielle; Jenike, Michael A; Cox, Nancy J; Hanna, Gregory L; Brentani, Helena; Scherer, Stephen W; Arnold, Paul D; Stewart, S Evelyn; Mathews, Carol A; Knowles, James A; Cook, Edwin H; Pauls, David L; Wang, Kai; Scharf, Jeremiah M

OBJECTIVE: Obsessive-compulsive disorder (OCD) and Tourette syndrome (TS) are heritable neurodevelopmental disorders with a partially shared genetic etiology. This study represents the first genome-wide investigation of large (>500 kb), rare (<1%) copy number variants (CNVs) in OCD and the largest

Copy number variation in obsessive-compulsive disorder and tourette syndrome: a cross-disorder study

NARCIS (Netherlands)

McGrath, Lauren M.; Yu, Dongmei; Marshall, Christian; Davis, Lea K.; Thiruvahindrapuram, Bhooma; Li, Bingbin; Cappi, Carolina; Gerber, Gloria; Wolf, Aaron; Schroeder, Frederick A.; Osiecki, Lisa; O'Dushlaine, Colm; Kirby, Andrew; Illmann, Cornelia; Haddad, Stephen; Gallagher, Patience; Fagerness, Jesen A.; Barr, Cathy L.; Bellodi, Laura; Benarroch, Fortu; Bienvenu, O. Joseph; Black, Donald W.; Bloch, Michael H.; Bruun, Ruth D.; Budman, Cathy L.; Camarena, Beatriz; Cath, Danielle C.; Cavallini, Maria C.; Chouinard, Sylvain; Coric, Vladimir; Cullen, Bernadette; Delorme, Richard; Denys, Damiaan; Derks, Eske M.; Dion, Yves; Rosário, Maria C.; Eapen, Valsama; Evans, Patrick; Falkai, Peter; Fernandez, Thomas V.; Garrido, Helena; Geller, Daniel; Grabe, Hans J.; Grados, Marco A.; Greenberg, Benjamin D.; Gross-Tsur, Varda; Grünblatt, Edna; Heiman, Gary A.; Hemmings, Sian M. J.; Herrera, Luis D.; Hounie, Ana G.; Jankovic, Joseph; Kennedy, James L.; King, Robert A.; Kurlan, Roger; Lanzagorta, Nuria; Leboyer, Marion; Leckman, James F.; Lennertz, Leonhard; Lochner, Christine; Lowe, Thomas L.; Lyon, Gholson J.; Macciardi, Fabio; Maier, Wolfgang; McCracken, James T.; McMahon, William; Murphy, Dennis L.; Naarden, Allan L.; Neale, Benjamin M.; Nurmi, Erika; Pakstis, Andrew J.; Pato, Michele T.; Pato, Carlos N.; Piacentini, John; Pittenger, Christopher; Pollak, Yehuda; Reus, Victor I.; Richter, Margaret A.; Riddle, Mark; Robertson, Mary M.; Rosenberg, David; Rouleau, Guy A.; Ruhrmann, Stephan; Sampaio, Aline S.; Samuels, Jack; Sandor, Paul; Sheppard, Brooke; Singer, Harvey S.; Smit, Jan H.; Stein, Dan J.; Tischfield, Jay A.; Vallada, Homero; Veenstra-Vanderweele, Jeremy; Walitza, Susanne; Wang, Ying; Wendland, Jens R.; Shugart, Yin Yao; Miguel, Euripedes C.; Nicolini, Humberto; Oostra, Ben A.; Moessner, Rainald; Wagner, Michael; Ruiz-Linares, Andres; Heutink, Peter; Nestadt, Gerald; Freimer, Nelson; Petryshen, Tracey; Posthuma, Danielle; Jenike, Michael A.; Cox, Nancy J.; Hanna, Gregory L.; Brentani, Helena; Scherer, Stephen W.; Arnold, Paul D.; Stewart, S. Evelyn; Mathews, Carol A.; Knowles, James A.; Cook, Edwin H.; Pauls, David L.; Wang, Kai; Scharf, Jeremiah M.

2014-01-01

Obsessive-compulsive disorder (OCD) and Tourette syndrome (TS) are heritable neurodevelopmental disorders with a partially shared genetic etiology. This study represents the first genome-wide investigation of large (>500 kb), rare ( <1%) copy number variants (CNVs) in OCD and the largest genome-wide

Overlapping and disease specific trait, response, and reflection impulsivity in adolescents with first-episode schizophrenia spectrum disorders or attention-deficit/hyperactivity disorder

DEFF Research Database (Denmark)

Jepsen, J. R.M.; Rydkjaer, J.; Fagerlund, B.

2018-01-01

and Schizophrenia for School-aged Children – Present and Lifetime Version. Subjects with early-onset, first-episode schizophrenia spectrum disorders (EOS) (N = 29) or ADHD (N = 29) and healthy controls (N = 45) were compared on two performance measures (Information Sampling Task, Stop Signal Task) and a subjective......Background: Schizophrenia and attention-deficit/hyperactivity disorder (ADHD) are developmental disorders with shared clinical characteristics such as cognitive impairments and impulsivity. Impulsivity is a core feature of ADHD and an important factor in aggression, violence, and substance use...... in schizophrenia. Based on the hypothesis that schizophrenia and ADHD represent a continuum of neurodevelopmental impairments, the aim was to identify overlapping and disease specific forms of impulsivity. Methods: Adolescents between 12 and 17 years of age were assessed with the Schedule for Affective Disorders...

Testing Brain Overgrowth and Synaptic Models of Autism Using NPCs and Neurons From Patient Derived iPS Cells

Science.gov (United States)

2015-12-01

are complex neurodevelopmental diseases that affect about 1% of children in the United States. Such disorders are characterized by deficits in...neurodevelopmental diseases that affect about 1% of children in the United States. Such disorders are characterized by deficits in verbal communication...have been generated for several neurological disorders and diseases, including Rett syndrome, a syndromic ASD (Marchetto et al. 2010). The objective

Structural Brain Abnormalities in Adolescents with Autism Spectrum Disorder and Patients with Attention Deficit/Hyperactivity Disorder

Science.gov (United States)

Brieber, Sarah; Neufang, Susanne; Bruning, Nicole; Kamp-Becker, Inge; Remschmidt, Helmut; Herpertz-Dahlmann, Beate; Fink, Gereon R.; Konrad, Kerstin

2007-01-01

Background: Although autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD) are two distinct neurodevelopmental diseases, they share behavioural, neuropsychological and neurobiological characteristics. For the identification of endophenotypes across diagnostic categories, further investigations of phenotypic overlap…

Association between Severity of Behavioral Phenotype and Comorbid Attention Deficit Hyperactivity Disorder Symptoms in Children with Autism Spectrum Disorders

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Rao, Patricia A.; Landa, Rebecca J.

2014-01-01

Autism spectrum disorder and attention deficit hyperactivity disorder are neurodevelopmental disorders that cannot be codiagnosed under existing diagnostic guidelines ("Diagnostic and Statistical Manual of the American Psychiatric Association," 4th ed., text rev.). However, reports are emerging that attention deficit hyperactivity…

Effect of co-twin gender on neurodevelopmental symptoms: a twin register study.

Science.gov (United States)

Eriksson, Jonna Maria; Lundström, Sebastian; Lichtenstein, Paul; Bejerot, Susanne; Eriksson, Elias

2016-01-01

Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are neurodevelopmental disorders thought to have both genetic and environmental causes. It has been hypothesized that exposure to elevated levels of prenatal testosterone is associated with elevated traits of ASD and ADHD. Assuming that testosterone levels from a dizygotic male twin fetus may lead to enhanced testosterone exposure of its co-twins, we aimed to test the prenatal testosterone hypothesis by comparing same-sex with opposite-sex dizygotic twins with respect to neurodevelopmental symptoms. Neuropsychiatric traits were assessed in a population-based twin cohort from the Child and Adolescent Twin Study in Sweden (CATSS). Parental interviews were conducted for 16,312 dizygotic twins, 9 and 12 years old, with the Autism-Tics, ADHD, and other Comorbidities inventory (A-TAC). Girls with a female co-twin had an increased risk of reaching the cut-off score for ADHD compared with girls with a male co-twin. Both boys and girls with a female co-twin displayed a larger number of traits related to attention deficit and repetitive and stereotyped behaviors than those with a male twin. In girls, this also extended to social interaction and the combined measures for ASD and ADHD, however, with small effect sizes. Our results are reverse to what would have been expected from the prenatal testosterone hypothesis but consistent with a previous study of ASD and ADHD traits in dizygotic twins. The seemingly protective effect for girls of having a twin brother may be an effect of parent report bias, but may also be an unexpected effect of sharing the intrauterine environment with a male co-twin.

STRENGTHENING THE REFLECTIVE FUNCTIONING CAPACITIES OF PARENTS WHO HAVE A CHILD WITH A NEURODEVELOPMENTAL DISABILITY THROUGH A BRIEF, RELATIONSHIP-FOCUSED INTERVENTION.

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Sealy, Julie; Glovinsky, Ira P

2016-01-01

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.

Attention deficit hyperactivity disorder and autism spectrum disorder symptoms in school-age children born very preterm

NARCIS (Netherlands)

Bröring, Tinka; Oostrom, Kim J.; van Dijk-Lokkart, Elisabeth M.; Lafeber, Harrie N.; Brugman, Anniek; Oosterlaan, Jaap

Background: Very preterm (VP) children face a broad range of neurodevelopmental sequelae, including behavioral problems. Aim: To investigate prevalence, pervasiveness and co-occurrence of symptoms of attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) in school-age

Attention deficit hyperactivity disorder and autism spectrum disorder symptoms in school-age children born very preterm

NARCIS (Netherlands)

Bröring, Tinka; Oostrom, Kim J.; van Dijk-Lokkart, Elisabeth M.; Lafeber, Harrie N.; Brugman, Anniek; Oosterlaan, Jaap

2018-01-01

Very preterm (VP) children face a broad range of neurodevelopmental sequelae, including behavioral problems. To investigate prevalence, pervasiveness and co-occurrence of symptoms of attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) in school-age children born very

Individuals with Smith-Magenis syndrome display profound neurodevelopmental behavioral deficiencies and exhibit food-related behaviors equivalent to Prader-Willi syndrome.

Science.gov (United States)

Alaimo, Joseph T; Barton, Laura V; Mullegama, Sureni V; Wills, Rachel D; Foster, Rebecca H; Elsea, Sarah H

2015-12-01

Smith-Magenis syndrome (SMS) is a neurodevelopmental disorder associated with intellectual disability, sleep disturbances, early onset obesity and vast behavioral deficits. We used the Behavior Problems Inventory-01 to categorize the frequency and severity of behavioral abnormalities in a SMS cohort relative to individuals with intellectual disability of heterogeneous etiology. Self-injurious, stereotyped, and aggressive/destructive behavioral scores indicated that both frequency and severity were significantly higher among individuals with SMS relative to those with intellectual disability. Next, we categorized food behaviors in our SMS cohort across age using the Food Related Problems Questionnaire (FRPQ) and found that problems began to occur in SMS children as early as 5-11 years old, but children 12-18 years old and adults manifested the most severe problems. Furthermore, we evaluated the similarities of SMS adult food-related behaviors to those with intellectual disability and found that SMS adults had more severe behavioral problems. Many neurodevelopmental disorders exhibit syndromic obesity including SMS. Prader-Willi syndrome (PWS) is the most frequent neurodevelopmental disorder with syndromic obesity and has a well-established management and treatment plan. Using the FRPQ we found that SMS adults had similar scores relative to PWS adults. Both syndromes manifest weight gain early in development, and the FRPQ scores highlight specific areas in which behavioral similarities exist, including preoccupation with food, impaired satiety, and negative behavioral responses. SMS food-related behavior treatment paradigms are not as refined as PWS, suggesting that current PWS treatments for prevention of obesity may be beneficial for individuals with SMS. Copyright © 2015 Elsevier Ltd. All rights reserved.

Course and cognitive outcome in major affective disorder

DEFF Research Database (Denmark)

Kessing, Lars Vedel

2015-01-01

analyses conducted without survival models and without paying attention to diagnostic instability or the individual heterogeneity of the course of episodes. Totally, these drawbacks and pitfalls affect the results of previous studies in unpredictable ways and make it hazardous to draw conclusions about...... as an expression of an affective episode. On average, a progressive course with increasing risk of recurrence with every new episode was found for unipolar and bipolar affective disorders. Initially, the two types of disorders followed markedly different courses, but later in the course of the illness the risk...... a progressive course of episodes. Initially in the course of affective disorders, socio-demographic variables such as gender, age at onset, and marital status and co-morbidity with alcoholism acted as risk factors for further recurrence. Later, however, particularly variables related to the previous course...

Analysis of affective disorders in patients with vascular dementia

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D. V. Zakharchenko

2012-01-01

Full Text Available The outpatient records of 147 patients followed up for diagnosed vascular dementia were analyzed to assess the relationship between affective disorders and severe cognitive impairments. It was found that 7% of the examinees had a history of depressive states. Estimating the development time for vascular dementia could divide the patients into 2 groups: 1 60% of the patients in whom cognitive impairments began to determine its clinical picture just within the first 2 years after identification of affective disorders and 2 40%, in whom cognitive impairments occurred 10—20 years later. In both groups, mental disorders occurred at an equal age in the presence of depressive disorders; in Group 1, vascular dementia developed nearly twice as often as that in Group 2. At the same time, the occurrence of cognitive impairments in Group 1 patients just in the early disease stages is indicative of the organic genesis of affective disorders, as confirmed by the moderately rapid progression of psychopathological symptoms, such as sharpening of personality traits, increased rigidity of psychic processes, emotional lability, variations in affective symptomatology, inadequate remissions, and the presence of neurological symptoms. Another type of a ratio of depressive to severe cognitive disorders was found in the elderly persons in Group 2. The long existence of affective disorders without signs of cognitive diminution leads one to say that they have recurrent depressive disorder with further addition of a comorbid vascular process. These patients showed a fairly high severity of affective pathology that was responsible for more frequent admissions, as well as a phase course with relatively pure remissions without any clear intellectual-mnestic reduction and a predominance of hysterical character traits.

Long-Term Neurodevelopmental Outcomes of Premature Infants in Singapore.

Science.gov (United States)

Teo, Charmaine M; Poon, Woei Bing; Ho, Selina Ky

2018-02-01

Neonatal care advances have resulted in improved survival but have raised concerns of increase in neurodevelopmental impairment. This study looked at long-term neurodevelopmental outcomes at ages 5 and 8 years of very low birthweight infants born in the 2000s as compared to the 1990s. Neurodevelopmental assessment at 2 years old was compared to that at 5 and 8 years to determine if assessment at 2 years was predictive of later outcomes. A retrospective cohort study of consecutive infants with birthweight less than 1250 grams admitted to a tertiary centre in Singapore between January 1994 to December 1995 (Epoch I) and January 2004 to December 2005 (Epoch II) were included. Neurodevelopmental impairment was defined as having intelligence quotient (IQ) of less than 70, cerebral palsy, legal blindness, or hearing impairment requiring hearing aids. Mean gestational age was lower for Epoch II compared to Epoch I (28.1 ± 2.5 vs 29.4 ± 2.7 weeks, P = 0.004). Death or neurodevelopmental impairment rates did not differ (24.3% and 17.1% at 5 years old, P = 0.398; 29.1% and 25.0% at 8 years old, P = 0.709). There was improvement in visual impairment rate at 8 years in Epoch II (10.7% vs 34.0%, P = 0.024). Mean IQ was better in Epoch II (109 and 107 vs 97 and 99 at 5 [ P = 0.001] and 8 years [ P = 0.047], respectively). All infants with no neurodevelopmental impairment at 2 years remained without impairment later on. Over a decade, neurodevelopmental outcomes did not worsen despite lower mean gestational age. Long- term improvement in IQ scores and a reduction in visual impairment rates were seen. Our data suggests that children without neurodevelopmental impairment at 2 years are without impairment later on; therefore, they may need only developmental monitoring with targeted assessments instead of routine formal IQ assessments.

Quality of life in unaffected twins discordant for affective disorder

DEFF Research Database (Denmark)

Vinberg, Maj; Bech, Per; Kyvik, Kirsten Ohm

2006-01-01

BACKGROUND: The disability and hardship associated with affective disorder is shared by the family members of affective patients and might affect the family member's quality of life. METHOD: In a cross-sectional, high-risk, case-control study, monozygotic (MZ) and dizygotic (DZ) twins with (High......-Risk twins) and without (the control group/Low-Risk twins) a co-twin history of affective disorder were identified through nationwide registers. The aim of the present study was to investigate the hypothesis that a genetic liability to affective disorder is associated with a lower perception of quality...

Pediatric Neurodevelopmental Treatment

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Camacho, Ricardo; McCauley, Brandon; Szczech Moser, Christy

2016-01-01

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.

Testing Brain Overgrowth and Synaptic Models of Autism Using NPCs and Neurons from Patient-Derived IPS Cells

Science.gov (United States)

2015-12-01

neurodevelopmental diseases that affect about 1% of children in the United States. Such disorders are characterized by deficits in verbal communication...18 4 1. INTRODUCTION: Autism and autism spectrum disorders (ASD) are complex neurodevelopmental diseases that affect about 1% of children in the...cellular model of complex human neurogenetic diseases (Marchetto et al. 2011). Now, iPSCs have been generated for several neurological disorders and

Insight in seasonal affective disorder.

Science.gov (United States)

Ghaemi, S N; Sachs, G S; Baldassano, C F; Truman, C J

1997-01-01

Lack of insight complicates the evaluation and treatment of patients with psychotic and affective disorders. No studies of insight in seasonal affective disorder (SAD) have been reported. Thirty patients with SAD diagnosed by the Structured Clinical Interview for DSM-III-R but no other axis I conditions were treated short-term with light-therapy. Insight was measured with the Scale to Assess Unawareness of Mental Disorder (SUMD) as modified by the authors to assess the self-report of insight into depressive symptoms. Increasing scores (1 to 5) indicated increasing unawareness of illness (i.e., less insight). SAD patients displayed a moderate amount of insight when depressed (mean SUMD score, 2.5). When recovered, they showed no significant change in insight into past depressive symptoms (mean SUMD score, 2.8). Greater insight into current depressive symptoms correlated with more depressive symptoms on the Hamilton Rating Scale for Depression score ([HRSD] r = .35, P depressive symptoms that does not change after recovery, a result in agreement with studies of insight in psychosis and mania. Further, in SAD, increased severity of illness may be associated with increased insight into depressive symptoms, consistent with the hypothesis of depressive realism.

[Hereditary factors in attention deficit hyperactivity disorder

NARCIS (Netherlands)

Fliers, E.A.; Franke, B.

2005-01-01

Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by concentration problems, hyperactivity and impulsivity. Disturbances in dopamine and/or noradrenalin neurotransmission are probably the underlying pathophysiological mechanisms of ADHD. Around 80% of

Salivary cortisol in unaffected twins discordant for affective disorder

DEFF Research Database (Denmark)

Vinberg, Maj; Bennike, Bente; Kyvik, Kirsten Ohm

2008-01-01

. In conclusion, a high genetic liability to affective disorder was associated with a higher evening cortisol level, but not with awakening cortisol level. Future prospective family, high-risk and twin studies are needed to decide whether abnormalities in the HPA axis can be identified as an endophenotype......Dysfunction in the hypothalamic-pituitary-adrenal (HPA) axis has been proposed as a biological endophenotype for affective disorders. In the present study the hypothesis that a high genetic liability to affective disorder is associated with higher cortisol levels was tested in a cross......-sectional high-risk study. Healthy monozygotic (MZ) and dizygotic (DZ) twins with (High-Risk twins) and without (Low-Risk twins) a co-twin history of affective disorder were identified through nationwide registers. Awakening and evening salivary cortisol levels were compared between the 190 High- and Low...

Neuropeptide Y in Alcohol Addiction and Affective Disorders

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Annika Thorsell

2017-07-01

Full Text Available Neuropeptide Y (NPY, a neuropeptide highly conserved throughout evolution, is present at high levels in the central nervous system (CNS, as well as in peripheral tissues such as the gut and cardiovascular system. The peptide exerts its effects via multiple receptor subtypes, all belonging to the G-protein-coupled receptor superfamily. Of these subtypes, the Y1 and the Y2 are the most thoroughly characterized, followed by the Y5 subtype. NPY and its receptors have been shown to be of importance in central regulation of events underlying, for example, affective disorders, drug/alcohol use disorders, and energy homeostasis. Furthermore, within the CNS, NPY also affects sleep regulation and circadian rhythm, memory function, tissue growth, and plasticity. The potential roles of NPY in the etiology and pathophysiology of mood and anxiety disorders, as well as alcohol use disorders, have been extensively studied. This focus was prompted by early indications for an involvement of NPY in acute responses to stress, and, later, also data pointing to a role in alterations within the CNS during chronic, or repeated, exposure to adverse events. These functions of NPY, in addition to the peptide’s regulation of disease states, suggest that modulation of the activity of the NPY system via receptor agonists/antagonists may be a putative treatment mechanism in affective disorders as well as alcohol use disorders. In this review, we present an overview of findings with regard to the NPY system in relation to anxiety and stress, acute as well as chronic; furthermore we discuss post-traumatic stress disorder and, in part depression. In addition, we summarize findings on alcohol use disorders and related behaviors. Finally, we briefly touch upon genetic as well as epigenetic mechanisms that may be of importance for NPY function and regulation. In conclusion, we suggest that modulation of NPY-ergic activity within the CNS, via ligands aimed at different receptor

BRF1 mutations alter RNA polymerase III–dependent transcription and cause neurodevelopmental anomalies

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Hög, Friederike; Dentici, Maria Lisa; Tan, Perciliz L.; Sowada, Nadine; Medeira, Ana; Gueneau, Lucie; Thiele, Holger; Kousi, Maria; Lepri, Francesca; Wenzeck, Larissa; Blumenthal, Ian; Radicioni, Antonio; Schwarzenberg, Tito Livio; Mandriani, Barbara; Fischetto, Rita; Morris-Rosendahl, Deborah J.; Altmüller, Janine; Reymond, Alexandre; Nürnberg, Peter; Merla, Giuseppe; Dallapiccola, Bruno; Katsanis, Nicholas; Cramer, Patrick; Kubisch, Christian

2015-01-01

RNA polymerase III (Pol III) synthesizes tRNAs and other small noncoding RNAs to regulate protein synthesis. Dysregulation of Pol III transcription has been linked to cancer, and germline mutations in genes encoding Pol III subunits or tRNA processing factors cause neurogenetic disorders in humans, such as hypomyelinating leukodystrophies and pontocerebellar hypoplasia. Here we describe an autosomal recessive disorder characterized by cerebellar hypoplasia and intellectual disability, as well as facial dysmorphic features, short stature, microcephaly, and dental anomalies. Whole-exome sequencing revealed biallelic missense alterations of BRF1 in three families. In support of the pathogenic potential of the discovered alleles, suppression or CRISPR-mediated deletion of brf1 in zebrafish embryos recapitulated key neurodevelopmental phenotypes; in vivo complementation showed all four candidate mutations to be pathogenic in an apparent isoform-specific context. BRF1 associates with BDP1 and TBP to form the transcription factor IIIB (TFIIIB), which recruits Pol III to target genes. We show that disease-causing mutations reduce Brf1 occupancy at tRNA target genes in Saccharomyces cerevisiae and impair cell growth. Moreover, BRF1 mutations reduce Pol III–related transcription activity in vitro. Taken together, our data show that BRF1 mutations that reduce protein activity cause neurodevelopmental anomalies, suggesting that BRF1-mediated Pol III transcription is required for normal cerebellar and cognitive development. PMID:25561519

Tourette and tic disorders in ICD-11: standing at the diagnostic crossroads

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Douglas W. Woods

2014-01-01

Full Text Available This article reflects discussion by the WHO ICD-11 Working Group on the Classification of Obsessive-Compulsive and Related Disorders. After reviewing the historical classification of tic disorders, this article discusses their placement in ICD-11. Existing problems with diagnostic labels and criteria, appropriate placement of the tic disorders category within the ICD-11 system, and pragmatic factors affecting classification are reviewed. The article ends with recommendations to (a maintain consistency with the DSM-5 diagnostic labels for tic disorders, (b add a minimum duration guideline for a provisional tic disorder diagnosis, (c remove the multiple motor tic guideline for the diagnosis of Tourette disorder, and (d co-parent the tic disorder diagnoses in the disorders of the nervous system and the mental and behavioral disorders categories, with secondary co-parenting in the obsessive-compulsive and related disorders and neurodevelopmental disorders sections.

Structural brain abnormalities in a single gene disorder associated with epilepsy, language impairment and intellectual disability

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Joe Bathelt

2016-01-01

Full Text Available Childhood speech and language deficits are highly prevalent and are a common feature of neurodevelopmental disorders. However, it is difficult to investigate the underlying causal pathways because many diagnostic groups have a heterogeneous aetiology. Studying disorders with a shared genetic cause and shared cognitive deficits can provide crucial insight into the cellular mechanisms and neural systems that give rise to those impairments. The current study investigated structural brain differences of individuals with mutations in ZDHHC9, which is associated with a specific neurodevelopmental phenotype including prominent speech and language impairments and intellectual disability. We used multiple structural neuroimaging methods to characterise neuroanatomy in this group, and observed bilateral reductions in cortical thickness in areas surrounding the temporo-parietal junction, parietal lobule, and inferior frontal lobe, and decreased microstructural integrity of cortical, subcortical-cortical, and interhemispheric white matter projections. These findings are compared to reports for other genetic groups and genetically heterogeneous disorders with a similar presentation. Overlap in the neuroanatomical phenotype suggests a common pathway that particularly affects the development of temporo-parietal and inferior frontal areas, and their connections.

Visual search for feature conjunctions: an fMRI study comparing alcohol-related neurodevelopmental disorder (ARND) to ADHD.

Science.gov (United States)

O'Conaill, Carrie R; Malisza, Krisztina L; Buss, Joan L; Bolster, R Bruce; Clancy, Christine; de Gervai, Patricia Dreessen; Chudley, Albert E; Longstaffe, Sally

2015-01-01

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

Preschool Neurodevelopmental Outcomes in Children with Congenital Heart Disease.

Science.gov (United States)

Brosig, Cheryl L; Bear, Laurel; Allen, Sydney; Hoffmann, Raymond G; Pan, Amy; Frommelt, Michele; Mussatto, Kathleen A

2017-04-01

To describe preschool neurodevelopmental outcomes of children with complex congenital heart disease (CHD), who were evaluated as part of a longitudinal cardiac neurodevelopmental follow-up program, as recommended by the American Heart Association and the American Academy of Pediatrics, and identify predictors of neurodevelopmental outcomes in these children. Children with CHD meeting the American Heart Association/American Academy of Pediatrics high-risk criteria for neurodevelopmental delay were evaluated at 4-5 years of age. Testing included standardized neuropsychological measures. Parents completed measures of child functioning. Scores were compared by group (single ventricle [1V]; 2 ventricles [2V]; CHD plus known genetic condition) to test norms and classified as: normal (within 1 SD of mean); at risk (1-2 SD from mean); and impaired (>2 SD from mean). Data on 102 patients were analyzed. Neurodevelopmental scores did not differ based on cardiac anatomy (1V vs 2V); both groups scored lower than norms on fine motor and adaptive behavior skills, but were within 1 SD of norms. Patients with genetic conditions scored significantly worse than 1V and 2V groups and test norms on most measures. Children with CHD and genetic conditions are at greatest neurodevelopmental risk. Deficits in children with CHD without genetic conditions were mild and may not be detected without formal longitudinal testing. Parents and providers need additional education regarding the importance of developmental follow-up for children with CHD. Copyright © 2016 Elsevier Inc. All rights reserved.

Autism and Related Disorders

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McPartland, James; Volkmar, Fred R.

2012-01-01

The Pervasive Developmental Disorders are a group of neurodevelopmental disorders that include Autistic Disorder, Asperger’s Disorder, Pervasive Developmental Disorder - Not Otherwise Specified (PDD-NOS), Childhood Disintegrative Disorder (CDD), and Rett’s Disorder. All feature childhood onset with a constellation of symptoms spanning social interaction and communication and including atypical behavior patterns. The first three disorders (Autistic Disorder, Asperger’s Disorder, and PDD-NOS) are currently referred to as Autism Spectrum Disorders, reflecting divergent phenotypic and etiologic characteristics compared to Rett’s Disorder and CDD. This chapter reviews relevant research and clinical information relevant to appropriate medical diagnosis and treatment. PMID:22608634

Subjective Experience of Episodic Memory and Metacognition: A Neurodevelopmental Approach

Science.gov (United States)

Souchay, Céline; Guillery-Girard, Bérengère; Pauly-Takacs, Katalin; Wojcik, Dominika Zofia; Eustache, Francis

2013-01-01

Episodic retrieval is characterized by the subjective experience of remembering. This experience enables the co-ordination of memory retrieval processes and can be acted on metacognitively. In successful retrieval, the feeling of remembering may be accompanied by recall of important contextual information. On the other hand, when people fail (or struggle) to retrieve information, other feelings, thoughts, and information may come to mind. In this review, we examine the subjective and metacognitive basis of episodic memory function from a neurodevelopmental perspective, looking at recollection paradigms (such as source memory, and the report of recollective experience) and metacognitive paradigms such as the feeling of knowing). We start by considering healthy development, and provide a brief review of the development of episodic memory, with a particular focus on the ability of children to report first-person experiences of remembering. We then consider neurodevelopmental disorders (NDDs) such as amnesia acquired in infancy, autism, Williams syndrome, Down syndrome, or 22q11.2 deletion syndrome. This review shows that different episodic processes develop at different rates, and that across a broad set of different NDDs there are various types of episodic memory impairment, each with possibly a different character. This literature is in agreement with the idea that episodic memory is a multifaceted process. PMID:24399944

ESSENCE-Q – a first clinical validation study of a new screening questionnaire for young children with suspected neurodevelopmental problems in south Japan

Directory of Open Access Journals (Sweden)

Hatakenaka Y

2016-07-01

Full Text Available Yuhei Hatakenaka,1,2 Elisabeth Fernell,2 Masahiko Sakaguchi,3 Hitoshi Ninomiya,3 Ichiro Fukunaga,1 Christopher Gillberg2 1Kochi Gillberg Neuropsychiatry Centre, Kochi Prefectural Medical and Welfare Centre, Kochi, Japan; 2Gillberg Neuropsychiatry Centre, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; 3Integrated Centre for Advanced Medical Technologies, Kochi University Medical School, Kochi, Japan Background: Early identification of autism spectrum disorder, intellectual developmental disorder, attention-deficit/hyperactivity disorder, and other neurodevelopmental disorders/problems is crucial, yet diagnosis is often delayed for years under the often misguided “wait-and-see” paradigm. The early symptomatic syndromes eliciting neurodevelopmental clinical examinations-questionnaire (ESSENCE-Q is a brief (12-item screening questionnaire developed specifically for the purpose of speeding up the identification process of a wide variety of neurodevelopmental problems. The aims were to 1 estimate the reliability of the ESSENCE-Q, 2 evaluate the clinical cutoff levels suggested by the author of the ESSENCE-Q, and 3 propose optimal cutoff levels based on receiver operating characteristic analysis.Methods: The ESSENCE-Q was used for 1 year by a psychiatrist in Kochi, Japan, assessing children under the age of 6 years referred for developmental problems. The children were also clinically assessed with regard to whether or not they met criteria for a developmental disorder (diagnosis positive and diagnosis negative groups. We contrasted the results of the ESSENCE-Q and those of clinical diagnostic assessments in 130 cases.Results: Cronbach’s alpha was 0.82, sensitivity was 0.94 (95% confidence interval [CI]: [0.88, 0.98], and specificity 0.53 (95% CI: [0.28, 0.77], which are reasonable psychometrics for a first-step screening tool. Based on receiver operating characteristic analysis, we recommended an optimal cutoff level of yes �

Neurodevelopmental outcome of infantile spasms: A systematic review and meta-analysis.

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Widjaja, Elysa; Go, Cristina; McCoy, Blathnaid; Snead, O Carter

2015-01-01

The aims of this systematic review and meta-analysis were to assess (i) estimates of good neurodevelopmental outcome in infantile spasms (IS), (ii) if neurodevelopmental outcome has changed since the publication of the first guideline on medical treatment of IS in 2004 and (iii) effect of lead time to treatment (LTTT). The Medline, Embase, Cochrane, PsycINFO, Web of Science and Scopus databases, and reference lists of retrieved articles were searched. Studies inclusion criteria were: (i) >5 patients with IS, (ii) mean/median follow-up of >6 months, (iii) neurodevelopmental outcome, and (iv) randomized and observational studies. The data extracted included proportion of good neurodevelopmental outcome, year of publication, cryptogenic or symptomatic IS and LTTT. Of the 1436 citations screened, 55 articles were included in final analysis, with a total of 2967 patients. The pooled estimate for good neurodevelopmental outcome was 0.236 (95% CI: 0.193-0.286). There was no difference between the proportions of good neurodevelopmental outcome for the 21 studies published after 2004 [0.264 (95% CI: 0.197-0.344)] compared to the 34 studies published before 2004 [0.220 (95% CI: 0.168-0.283)] (Q value=0.862, p=0.353). The pooled estimate of good neurodevelopmental outcome for cryptogenic IS [0.543 (95% CI: 0.458-0.625)] was higher than symptomatic IS [0.125 (95% CI: 0.09-0.171)] (Q value=69.724, p4weeks for good neurodevelopmental outcome of 8 studies was 1.519 (95% CI: 1.064-2.169). Neurodevelopmental outcome was overall poor in patients with IS and has not changed since the publication of first guideline on IS. Although cryptogenic IS has better prognosis than symptomatic IS, the outcome for cryptogenic IS remained poor. There was heterogeneity in neurodevelopmental outcome ascertainment methods, highlighting the need for a more standardized and comprehensive assessment of cognitive, behavioural, emotional and functional outcomes. Copyright © 2014 Elsevier B.V. All rights

Macrophage migration inhibitory factor and autism spectrum disorders

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Grigorenko, Elena L.; Han, Summer S.; Yrigollen, Carolyn M.; Leng, Lin; Mizue, Yuka; Anderson, George M.; Mulder, Erik J.; de Bildt, Annelies; Minderaa, Ruud B.; Volkmar, Fred R.; Chang, Joseph T.; Bucala, Richard

OBJECTIVE. Autistic spectrum disorders are childhood neurodevelopmental disorders characterized by social and communicative impairment and repetitive and stereotypical behavior. Macrophage migration inhibitory factor (MIF) is an upstream regulator of innate immunity that promotes

Studies of brain and cognitive maturation through childhood and adolescence: a strategy for testing neurodevelopmental hypotheses.

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Luna, B; Sweeney, J A

2001-01-01

Although neurodevelopmental models of schizophrenia are now widely accepted, there is minimal direct human evidence of dysmaturation in schizophrenia to support this theory. This is especially the case regarding maturational changes during late childhood and adolescence, which immediately precede the typical age of onset of the disorder. By integrating new noninvasive methods of functional magnetic resonance imaging with techniques of developmental cognitive neuroscience, it is now possible to begin systematic research programs to directly test hypotheses of neurodevelopmental abnormalities in schizophrenia. In this article, we describe strategies for characterizing developmental changes taking place during the critical period of adolescence that can elucidate dysmaturation processes in schizophrenia. We emphasize the need for studies characterizing normal development before examining at-risk or clinical populations, and the potential value of using neurobehavioral and neuroimaging approaches to directly characterize the dysmaturation associated with schizophrenia.

Executive Functioning Differences between Adults with Attention Deficit Hyperactivity Disorder and Autistic Spectrum Disorder in Initiation, Planning and Strategy Formation

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Bramham, Jessica; Ambery, Fiona; Young, Susan; Morris, Robin; Russell, Ailsa; Xenitidis, Kiriakos; Asherson, Philip; Murphy, Declan

2009-01-01

Executive functioning deficits characterize the neuropsychological profiles of the childhood neurodevelopmental disorders of attention deficit hyperactivity disorder (ADHD) and autistic spectrum disorder (ASD). This study sought to determine whether similar impairments exist in adults with ADHD (N = 53) and ASD (N = 45) in comparison with a…

Pediatric AIDS. Neuroradiologic and neurodevelopmental findings

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Price, D.B.; Haller, J.O.; Kramer, J.; Hotson, G.C.; Loh, J.P.; Schlusselberg, D.; Inglese, C.M.; Jacobs, J.; Rose, A.L.; Menez-Bautista, R.

1988-09-01

A group of 23 pediatric patients seropositive for HIV antibody were studied by computed tomography and evaluated neurodevelopmentally. Significant neurodevelopmental delays were found in over 95% of the patients studied. CT findings in six patients were normal and thirteen of 23 (57%) had prominence of the CSF spaces. Less frequent findings included calcifications in the basal ganglia and white matter. Cerebral mass lesions included one case of lymphoma and one case of hemorrhage. The CT findings in the pediatric age group differs from the adult population in that that contrast enhancing inflammatory mass lesions are uncommon.

Newly postulated neurodevelopmental risks of pediatric anesthesia.

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Hays, Stephen R; Deshpande, Jayant K

2011-04-01

Recent animal and human studies have raised concern that exposure to anesthetic agents in children may cause neuronal damage and be associated with adverse neurodevelopmental outcomes. Exposure of young animals to anesthetic agents above threshold doses and durations during a critical neurodevelopmental window in the absence of concomitant painful stimuli causes widespread neuronal apoptosis and subsequent abnormal behaviors. The relevance of such animal data to humans is unknown. Untreated neonatal pain and stress also are associated with enhanced neuronal death and subsequent maladaptive behaviors, which can be prevented by exposure to these same anesthetic agents. Retrospective observational human studies have suggested a dose-dependent association between multiple anesthetic exposures in early childhood and subsequent learning disability, the causality of which is unknown. Ongoing prospective investigations are underway, the results of which may clarify if and what neurodevelopmental risks are associated with pediatric anesthesia. No change in current practice is yet indicated.

The hypothalamo-pituitary-adrenal axis in major affective disorder

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Christensen, M V; Kessing, L V

2001-01-01

disorder. The HPA axis is a complex neuroendocrine network with multiple integrated levels of control, and it is likely that the dysregulation involves abnormalities at several sites within the axis. At present, it is not clear whether the abnormalities are related to the affective episodes only......This paper reviews studies of the hypothalamo-pituitary-adrenal (HPA)-axis activity in patients with affective disorders. It is concluded that, despite methodological drawbacks in most studies, dysregulation of the HPA axis seems to be a consistent finding in a proportion of patients with affective...... or to the disorder itself. There is a need for prospective studies of larger samples of patients to be followed during successive affective episodes with a combination of measurements of the HPA-axis activity and brain imaging....

Bipolar Disorder and Cognitive Dysfunction: A Complex Link.

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Cipriani, Gabriele; Danti, Sabrina; Carlesi, Cecilia; Cammisuli, Davide Maria; Di Fiorino, Mario

2017-10-01

The aim of this article was to describe the current evidence regarding phenomenon of cognitive functioning and dementia in bipolar disorder (BD). Cochrane Library and PubMed searches were conducted for relevant articles, chapters, and books published before 2016. Search terms used included "bipolar disorder," "cognitive dysfunction," and "dementia." At the end of the selection process, 159 studies were included in our qualitative synthesis. As result, cognitive impairments in BD have been previously considered as infrequent and limited to the affective episodes. Nowadays, there is evidence of stable and lasting cognitive dysfunctions in all phases of BD, including remission phase, particularly in the following domains: attention, memory, and executive functions. The cause of cognitive impairment in BD raises the question if it subtends a neurodevelopmental or a neurodegenerative process. Impaired cognitive functioning associated with BD may contribute significantly to functional disability, in addition to the distorted affective component usually emphasized.

Long-term neurodevelopmental outcome after selective feticide in monochorionic pregnancies.

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van Klink, Jmm; Koopman, H M; Middeldorp, J M; Klumper, F J; Rijken, M; Oepkes, D; Lopriore, E

2015-10-01

To assess the incidence of and risk factors for adverse long-term neurodevelopmental outcome in complicated monochorionic pregnancies treated with selective feticide at our centre between 2000 and 2011. Observational cohort study. National referral centre for fetal therapy (Leiden University Medical Centre, the Netherlands). Neurodevelopmental outcome was assessed in 74 long-term survivors. Children, at least 2 years of age, underwent an assessment of neurologic, motor and cognitive development using standardised psychometric tests and the parents completed a behavioural questionnaire. A composite outcome termed neurodevelopmental impairment including cerebral palsy (GMFCS II-V), cognitive and/or motor test score of Neurodevelopmental impairment was detected in 5/74 [6.8%, 95% confidence interval (CI), 1.1-12.5] of survivors. Overall adverse outcome, including perinatal mortality or neurodevelopmental impairment was 48/131 (36.6%). In multivariate analysis, parental educational level was associated with cognitive test scores (regression coefficient B 3.9, 95% CI 1.8-6.0). Behavioural problems were reported in 10/69 (14.5%). Adverse long-term outcome in survivor twins of complicated monochorionic pregnancies treated with selective feticide appears to be more prevalent than in the general population. Cognitive test scores were associated with parental educational level. Neurodevelopmental impairment after selective feticide was detected in 5/74 (6.8%, 95% CI 1.1-12.5) of survivors. © 2015 Royal College of Obstetricians and Gynaecologists.

Risk. Impact of having a first-degree relative with affective disorder

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Vinberg, Maj

2016-01-01

-risk twins and 5 low-risk twins) developed a psychiatric disorder during the 7-year follow-up period: 24 developed mood disorder (67%), 7 anxiety disorder (19%) and 5 (14%) substance abuse, schizophrenia or personality disorder. The results showed that familial risk, impaired stress tolerance and discrete......: the high-risk group comprised twins at risk of developing affective disorder (DZ or MZ twin; index co-twin affected); the low risk group (control group) comprised twins at low risk of developing affective disorder (DZ or MZ twin; index co-twin not affected). At baseline 234 participants were divided...... boundaries in order to have an impact on prevention. Furthermore, there is a need to move beyond the notion of ''magic bullets'', instead developing an integrated paradigm encompassing clusters of biomarkers related to behavioural measures of developmental psychopathology. Finally, as most psychiatric...

Gender identity disorder and schizophrenia: neurodevelopmental disorders with common causal mechanisms?

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Rajkumar, Ravi Philip

2014-01-01

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.

Gender Identity Disorder and Schizophrenia: Neurodevelopmental Disorders with Common Causal Mechanisms?

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Ravi Philip Rajkumar

2014-01-01

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.

Increased mortality among patients admitted with major psychiatric disorders: a register-based study comparing mortality in unipolar depressive disorder, bipolar affective disorder, schizoaffective disorder, and schizophrenia

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Laursen, Thomas Munk; Munk-Olsen, Trine; Nordentoft, Merete

2007-01-01

disorder has never been examined in a population-based study. OBJECTIVE: Our objective was to examine and compare mortality rates after admission with schizophrenia, schizoaffective disorder, unipolar depressive disorder, or bipolar affective disorder and to examine the impact of family history......: Unipolar depressive disorder, bipolar affective disorder, and schizoaffective disorder were associated with the same pattern of excess mortality. Schizophrenia had a lower mortality from unnatural causes of death and a higher mortality from natural causes compared to the 3 other disorders. Family history...

Gestational Age and Autism Spectrum Disorder

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Atladóttir, H Ó; Schendel, D.E.; Henriksen, T B

2016-01-01

Autism Spectrum Disorder (ASD) is a serious neurodevelopmental disorder. Several previous studies have identified pre-term birth as a risk factor for ASD but none has studied whether the association between gestational age and ASD has changed over time. This is a Danish population-based follow...

Association between severity of behavioral phenotype and comorbid attention deficit hyperactivity disorder symptoms in children with autism spectrum disorders

OpenAIRE

Rao, Patricia A; Landa, Rebecca J

2013-01-01

Autism spectrum disorder and attention deficit hyperactivity disorder are neurodevelopmental disorders that cannot be codiagnosed under existing diagnostic guidelines (Diagnostic and Statistical Manual of the American Psychiatric Association, 4th ed., text rev.). However, reports are emerging that attention deficit hyperactivity disorder is sometimes comorbid with autism spectrum disorder. In the current study, we examined rates of parent-reported clinically significant symptoms of attention ...

Urbanicity during upbringing and bipolar affective disorders in Denmark

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Pedersen, Carsten Bøcker; Mortensen, Preben Bo

2006-01-01

It has been suggested that known or suspected risk factors for schizophrenia may also be of importance for other psychoses, but the empirical evidence regarding this is limited. Urbanicity of place of birth and during upbringing has been shown to be related to the risk of schizophrenia. Few studies...... of urbanicity in relation to bipolar affective disorder exist. Objective: To investigate the potential association between urbanicity at birth and during upbringing and the risk of bipolar affective disorder. Method: Using data from the Danish Civil Registration System, we established a population-based cohort...... of 2.04 million people born in Denmark during 1956-1986, which included information on place of residence during upbringing. Bipolar affective disorder in cohort members was identified by linkage with the Danish Psychiatric Central Register. Results: Overall, 2232 people developed bipolar affective...

Automatic processing of facial affects in patients with borderline personality disorder: associations with symptomatology and comorbid disorders.

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Donges, Uta-Susan; Dukalski, Bibiana; Kersting, Anette; Suslow, Thomas

2015-01-01

Instability of affects and interpersonal relations are important features of borderline personality disorder (BPD). Interpersonal problems of individuals suffering from BPD might develop based on abnormalities in the processing of facial affects and high sensitivity to negative affective expressions. The aims of the present study were to examine automatic evaluative shifts and latencies as a function of masked facial affects in patients with BPD compared to healthy individuals. As BPD comorbidity rates for mental and personality disorders are high, we investigated also the relationships of affective processing characteristics with specific borderline symptoms and comorbidity. Twenty-nine women with BPD and 38 healthy women participated in the study. The majority of patients suffered from additional Axis I disorders and/or additional personality disorders. In the priming experiment, angry, happy, neutral, or no facial expression was briefly presented (for 33 ms) and masked by neutral faces that had to be evaluated. Evaluative decisions and response latencies were registered. Borderline-typical symptomatology was assessed with the Borderline Symptom List. In the total sample, valence-congruent evaluative shifts and delays of evaluative decision due to facial affect were observed. No between-group differences were obtained for evaluative decisions and latencies. The presence of comorbid anxiety disorders was found to be positively correlated with evaluative shifting owing to masked happy primes, regardless of baseline-neutral or no facial expression condition. The presence of comorbid depressive disorder, paranoid personality disorder, and symptoms of social isolation and self-aggression were significantly correlated with response delay due to masked angry faces, regardless of baseline. In the present affective priming study, no abnormalities in the automatic recognition and processing of facial affects were observed in BPD patients compared to healthy individuals

Heterozygous CDKL5 Knockout Female Mice Are a Valuable Animal Model for CDKL5 Disorder

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Claudia Fuchs

2018-01-01

Full Text Available CDKL5 disorder is a severe neurodevelopmental disorder caused by mutations in the X-linked CDKL5 (cyclin-dependent kinase-like five gene. CDKL5 disorder primarily affects girls and is characterized by early-onset epileptic seizures, gross motor impairment, intellectual disability, and autistic features. Although all CDKL5 female patients are heterozygous, the most valid disease-related model, the heterozygous female Cdkl5 knockout (Cdkl5 +/− mouse, has been little characterized. The lack of detailed behavioral profiling of this model remains a crucial gap that must be addressed in order to advance preclinical studies. Here, we provide a behavioral and molecular characterization of heterozygous Cdkl5 +/− mice. We found that Cdkl5 +/− mice reliably recapitulate several aspects of CDKL5 disorder, including autistic-like behaviors, defects in motor coordination and memory performance, and breathing abnormalities. These defects are associated with neuroanatomical alterations, such as reduced dendritic arborization and spine density of hippocampal neurons. Interestingly, Cdkl5 +/− mice show age-related alterations in protein kinase B (AKT and extracellular signal-regulated kinase (ERK signaling, two crucial signaling pathways involved in many neurodevelopmental processes. In conclusion, our study provides a comprehensive overview of neurobehavioral phenotypes of heterozygous female Cdkl5 +/− mice and demonstrates that the heterozygous female might be a valuable animal model in preclinical studies on CDKL5 disorder.

Amygdala response to emotional faces in seasonal affective disorder

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Borgsted, Camilla; Ozenne, Brice; Mc Mahon, Brenda

2018-01-01

BACKGROUND: Seasonal affective disorder (SAD) is characterized by seasonally recurring depression. Heightened amygdala activation to aversive stimuli is associated with major depressive disorder but its relation to SAD is unclear. We evaluated seasonal variation in amygdala activation in SAD......, we correlated change in symptom severity, assessed with The Hamilton Rating Scale for Depression - Seasonal Affective Disorder version (SIGH-SAD), with change in amygdala activation. RESULTS: We found no season-by-group, season or group effect on our aversive contrast. Independent of season, SAD...... of the presence of depressive symptoms....

The Role of the Immune System in Autism Spectrum Disorder.

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Meltzer, Amory; Van de Water, Judy

2017-01-01

Autism is a neurodevelopmental disorder characterized by deficits in communication and social skills as well as repetitive and stereotypical behaviors. While much effort has focused on the identification of genes associated with autism, research emerging within the past two decades suggests that immune dysfunction is a viable risk factor contributing to the neurodevelopmental deficits observed in autism spectrum disorders (ASD). Further, it is the heterogeneity within this disorder that has brought to light much of the current thinking regarding the subphenotypes within ASD and how the immune system is associated with these distinctions. This review will focus on the two main axes of immune involvement in ASD, namely dysfunction in the prenatal and postnatal periods. During gestation, prenatal insults including maternal infection and subsequent immunological activation may increase the risk of autism in the child. Similarly, the presence of maternally derived anti-brain autoantibodies found in ~20% of mothers whose children are at risk for developing autism has defined an additional subphenotype of ASD. The postnatal environment, on the other hand, is characterized by related but distinct profiles of immune dysregulation, inflammation, and endogenous autoantibodies that all persist within the affected individual. Further definition of the role of immune dysregulation in ASD thus necessitates a deeper understanding of the interaction between both maternal and child immune systems, and the role they have in diagnosis and treatment.

NEURODEVELOPMENTAL EFFECTS OF ENVIRONMENTAL EXPOSURES

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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...

Coping styles in healthy individuals at risk of affective disorder

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Vinberg, Maj; Froekjaer, Vibe Gedsoe; Kessing, Lars Vedel

2010-01-01

Coping styles may influence the perceived life stress experienced by an individual and, therefore, also be critical in the development of affective disorders. This study examined whether familial risk of affective disorder is associated with the use of maladaptive coping styles, in healthy...

Behavioral predictors of alcohol drinking in a neurodevelopmental rat model of schizophrenia and co-occurring alcohol use disorder.

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Khokhar, Jibran Y; Todd, Travis P

2018-04-01

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.

Concurrent validity of the differential ability scales, second edition with the Mullen Scales of Early Learning in young children with and without neurodevelopmental disorders.

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Farmer, Cristan; Golden, Christine; Thurm, Audrey

2016-01-01

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.

Inattention and hyperactivity/impulsivity among children with attention-deficit/hyperactivity-disorder, autism spectrum disorder, and intellectual disability.

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McClain, Maryellen Brunson; Hasty Mills, Amber M; Murphy, Laura E

2017-11-01

Attention-Deficit/Hyperactivity Disorder (ADHD), Autism Spectrum Disorder (ASD), and Intellectual Disability (ID) are common co-occurring neurodevelopmental disorders; however, limited research exists regarding the presentation and severity of overlapping symptomology, particularly inattention and hyperactivity/impulsivity, when a child is diagnosed with one of more of these neurodevelopmental disorders. As difficulties with inattention and hyperactivity/impulsivity are symptoms frequently associated with these disorders, the current study aims to determine the differences in the severity of inattention and hyperactivity/impulsivity in children diagnosed with ADHD, ASD, ID, and co-occurring diagnosis of ADHD/ID, ASD/ADHD, and ASD/ID. Participants in the current study included 113 children between the ages of 6 and 11 who were diagnosed with ADHD, ASD, ID, ADHD/ID, ASD/ADHD, or ASD/ID. Two MANOVA analyses were used to compare these groups witih respsect to symptom (i.e., inattention, hyperactivity/impulsivity) severity. Results indicated that the majority of diagnostic groups experienced elevated levels of both inattention and hyperactivity/impulsivity. However, results yielded differences in inattention and hyperactivity/impulsivity severity. In addition, differences in measure sensitivity across behavioral instruments was found. Children with neurodevelopmental disorders often exhibit inattention and hyperactivity/impulsivity, particularly those with ADHD, ASD, ASD/ADHD, and ADHD/ID; therefore, differential diagnosis may be complicated due to similarities in ADHD symptom severity. However, intellectual abilities may be an important consideration for practitioners in the differential diagnosis process as children with ID and ASD/ID exhibited significantly less inattention and hyperactive/impulsive behaviors. Additionally, the use of multiple behavior rating measures in conjunction with other assessment procedures may help practitioners determine the most

Overlapping and disease specific trait, response, and reflection impulsivity in adolescents with first-episode schizophrenia spectrum disorders or attention-deficit/hyperactivity disorder.

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Jepsen, J R M; Rydkjaer, J; Fagerlund, B; Pagsberg, A K; Jespersen, R Av F; Glenthøj, B Y; Oranje, B

2018-03-01

Schizophrenia and attention-deficit/hyperactivity disorder (ADHD) are developmental disorders with shared clinical characteristics such as cognitive impairments and impulsivity. Impulsivity is a core feature of ADHD and an important factor in aggression, violence, and substance use in schizophrenia. Based on the hypothesis that schizophrenia and ADHD represent a continuum of neurodevelopmental impairments, the aim was to identify overlapping and disease specific forms of impulsivity. Adolescents between 12 and 17 years of age were assessed with the Schedule for Affective Disorders and Schizophrenia for School-aged Children - Present and Lifetime Version. Subjects with early-onset, first-episode schizophrenia spectrum disorders (EOS) (N = 29) or ADHD (N = 29) and healthy controls (N = 45) were compared on two performance measures (Information Sampling Task, Stop Signal Task) and a subjective personality trait measure of impulsivity (Barratt Impulsiveness Scale, Version 11 (BIS-11)). Significantly increased reflection impulsivity was observed in ADHD but not in the EOS group. No significant response inhibition deficits (stop signal reaction time) were found in the two clinical groups. The ADHD and the EOS group showed significantly increased motor, attentional, and non-planning subtraits of impulsivity. Impaired pre-decisional information gathering appeared to be specific for ADHD while the information gathering was not significantly reduced in subjects with EOS. Neither the ADHD nor EOS group showed impaired response inhibition but shared increased personality subtraits of attentional, non-planning, and motor impulsivity although the latter was significantly more pronounced in ADHD. These increased subtraits of impulsivity may reflect diagnostic non-specific neurodevelopmental impairments in ADHD and EOS in adolescence.

Dysfunctional Affect Regulation : in borderline personality disorder and somatoform disorder

NARCIS (Netherlands)

van Dijke, A.

2011-01-01

The aim of this dissertation was to provide a systematic exploration of the nature and distribution of dysfunctional affect regulation, its associated phenomena, and retrospectively reported potentially traumatizing events in 475 patients diagnosed with borderline personality disorder (BPD),

Deletions and de novo mutations of SOX11 are associated with a neurodevelopmental disorder with features of Coffin–Siris syndrome

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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

2016-01-01

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

An adolescent with 48,xxyy syndrome with hypergonadotrophic hypogonadism, attention deficit hyperactive disorder and renal malformations

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Prasad Katulanda; J. Rasika D. K. Rajapakse; Jayani Kariyawasam; Rohan Jayasekara; Vajira H. W. Dissanayake

2012-01-01

48,XXYY is a rare sex chromosome aneuploidy affecting 1 in 18,000 to 50,000 male births. They present with developmental delay, hypogonadism, gynecomastia, intention tremors, and a spectrum of neurodevelopmental and psychiatric disorders. At one time this condition was considered a variant of Klinefelter syndrome. In clinically suspected cases, 48,XXYY syndrome can be diagnosed by chromosome culture and karyotyping. This patient presented with hypergonadotrophic hypogonadism, attention defici...

Affective instability as a clinical feature of avoidant personality disorder.

Science.gov (United States)

Snir, Avigal; Bar-Kalifa, Eran; Berenson, Kathy R; Downey, Geraldine; Rafaeli, Eshkol

2017-10-01

The current study's main goal was to examine whether affective instability is elevated among individuals suffering from avoidant personality disorder (APD) by comparing it to the affective instability found among individuals suffering from borderline personality disorder (BPD) as well that found among healthy controls. Adults (N = 152, aged 18-65 years) with BPD, APD, or no psychopathology participated in a 3-week computerized diary study. We examined temporal instability in negative affect using experience-sampling methods. Both within and between days, individuals with APD showed greater affective instability compared to the healthy control individuals, although less affective instability compared to individuals with BPD. The findings are in line with affective instability (or emotional lability) as a key dimension relevant across personality disorders. Additionally, they emphasize the need for research and clinical attention to affective characteristics (alongside the more readily recognized interpersonal characteristics) of APD. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Assisted reproduction and child neurodevelopmental outcomes

DEFF Research Database (Denmark)

Bay, Bjørn; Mortensen, Erik Lykke; Kesmodel, Ulrik Schiøler

2013-01-01

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....

Negative Affect Instability among Individuals with Comorbid Borderline Personality Disorder and Posttraumatic Stress Disorder

Science.gov (United States)

Scheiderer, Emily M.; Wang, Ting; Tomko, Rachel L.; Wood, Phillip K.; Trull, Timothy J.

2015-01-01

Ecological momentary assessment (EMA; Stone & Shiffman, 1994) was utilized to examine affective instability (AI) in the daily lives of outpatients with borderline personality disorder (BPD; n=78) with and without posttraumatic stress disorder (PTSD). A psychiatric control group (n=50) composed of outpatients with major depressive disorder/dysthymia (MDD/DYS) was employed to compare across subgroups: BPD-only, BPD+PTSD, MDD/DYS-only, and MDD/DYS+PTSD. Compared to the BPD-only group, the BPD+PTSD group had significantly greater instability of fear and sadness, but did not significantly differ in instability of hostility or aggregate negative affect. This pattern of elevated instability of fear and sadness was not present—and, in fact, was reversed—in the MDD/DYS group. Results emphasize the importance of examining AI within the context of specific comorbidities and affect types. Treatment and research addressing AI in the context of BPD-PTSD comorbidity may benefit from a focus on fear and sadness as separate from hostility or general negative affect. PMID:26904388

Marital adjustment of patients with substance dependence, schizophrenia and bipolar affective disorder

Directory of Open Access Journals (Sweden)

Shital S Muke

2014-01-01

Full Text Available Background: Marital adjustment is considered as a part of social well-being. Disturbed marital relationship can directly affect the disease adjustment and the way they face disease outcomes and complications. It may adversely affect physical health, mental health, the quality-of-life and even economic status of individuals. Aim: The aim of this study was to compare the marital adjustment among patients with substance dependence, schizophrenia and bipolar affective disorder. Materials and Methods: The sample consisted of each 30 patients with substance dependence, bipolar affective disorder and schizophrenia, diagnosed as per international classification of diseases-10 diagnostic criteria for research with a minimum duration of illness of 1 year were evaluated using marital adjustment questionnaire. The data was analyzed using parametric and non-parametric statistics. Results: Prevalence of poor marital adjustment in patients with schizophrenia, bipolar affective disorder and substance dependence was 60%, 70% and 50% respectively. There was a significant difference on overall marital adjustment among substance dependence and bipolar affective disorder patients. There was no significant difference on overall marital adjustment among patients with substance dependence and schizophrenia as well as among patients with schizophrenia and bipolar affective disorder. On marital adjustment domains, schizophrenia patients had significantly poor sexual adjustment than substance dependence patients while bipolar affective disorder patients had significantly poor sexual and social adjustment compared with substance dependence patients. Conclusion: Patients with substance dependence have significant better overall marital adjustment compared with bipolar affective disorder patients. Patients with substance dependence have significantly better social and sexual adjustment than patients with bipolar affective disorder as well as significantly better sexual

Theoretical and clinical overview of affective temperaments in mood disorders

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Xenia Gonda

2015-07-01

Full Text Available Temperaments are imperturbable variations of personality, traits and ways of reacting to the environment that characterize individuals and remain constant throughout several different situations. Temperaments usually play a central role in determining emotional reactions, therefore several temperamental models have attempted to establish the potential relationship between temperaments and affective disorders. According to Hagop Akiskal, affective temperaments are subclinical and subaffective trait-like manifestations of affective disorders. Unlike several models of temperament which were exclusively developed theoretically in order to describe healthy human functioning, later extrapolated to capture the pathological domains of mental and behavioral features, the current model of affective temperaments was developed on classical traditions and mainly based on the observation of subjects with mood disorders and their healthy first degree relatives. There is accumulating evidence concerning the development of affective temperaments based on their adaptive evolutionary characteristics and genetic background, and normative data from large national studies on general and healthy samples indicate their universal characteristics. Studies in affective patient populations indicate that the relationship between affective temperaments and affective illness is more complex than a simple extrapolation from psychopathology and mental health, and affective temperaments may represent a latent state of the staging model, playing a pathoplastic role in mood disorders determining their evolution, clinical features, main characteristics and outcome. A large body of data on affective temperaments has been published during the last decade, deserving a critical analysis presented in this overview.

Childhood Neurodevelopmental Disorders and Violent Criminality: A Sibling Control Study

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Lundström, Sebastian; Forsman, Mats; Larsson, Henrik; Kerekes, Nora; Serlachius, Eva; Långström, Niklas; Lichtenstein, Paul

2014-01-01

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…

Narrative retelling in children with neurodevelopmental disorders: is there a role for nonverbal temporal-sequencing skills?

Science.gov (United States)

Johnels, Jakob Åsberg; Hagberg, Bibbi; Gillberg, Christopher; Miniscalco, Carmela

2013-10-01

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.

Quality of life in unaffected twins discordant for affective disorder

DEFF Research Database (Denmark)

Vinberg, Maj; Bech, Per; Kyvik, Kirsten Ohm

2007-01-01

-Risk twins) and without (the control group/Low-Risk twins) a co-twin history of affective disorder were identified through nationwide registers. The aim of the present study was to investigate the hypothesis that a genetic liability to affective disorder is associated with a lower perception of quality......BACKGROUND: The disability and hardship associated with affective disorder is shared by the family members of affective patients and might affect the family member's quality of life. METHOD: In a cross-sectional, high-risk, case-control study, monozygotic (MZ) and dizygotic (DZ) twins with (High...... of life. RESULTS: Univariate analyses showed that quality of life in all domains was impaired for the 121 High-Risk twins compared to the 84 Low-Risk twins. In multiple regression analyses, the differences remained significant after adjustment for sex, age, marital status and years of education. Adjusted...

Modulation of GABAergic Transmission in Development and Neurodevelopmental Disorders: Investigating Physiology and Pathology to Gain Therapeutic Perspectives

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Gabriele eDeidda

2014-05-01

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.

Adult attention-deficit hyperactivity disorder: Why should we pay ...

African Journals Online (AJOL)

Background: Attention-deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder, with a chronic, costly and debilitating course if untreated. Limited access to diagnosis and treatment for adults with ADHD contributes to the cost of the disorder and the burden of disease. Aim: This study aims to identify ...

Assessing neurodevelopmental effects of arsenolipids in pre-differentiated human neurons.

Science.gov (United States)

Witt, Barbara; Ebert, Franziska; Meyer, Sören; Francesconi, Kevin A; Schwerdtle, Tanja

2017-11-01

In the general population exposure to arsenic occurs mainly via diet. Highest arsenic concentrations are found in seafood, where arsenic is present predominantly in its organic forms including arsenolipids. Since recent studies have provided evidence that arsenolipids could reach the brain of an organism and exert toxicity in fully differentiated human neurons, this work aims to assess the neurodevelopmental toxicity of arsenolipids. Neurodevelopmental effects of three arsenic-containing hydrocarbons (AsHC), two arsenic-containing fatty acids (AsFA), arsenite and dimethylarsinic acid (DMA V ) were characterized in pre-differentiated human neurons. AsHCs and arsenite caused substantial cytotoxicity in a similar, low concentration range, whereas AsFAs and DMA V were less toxic. AsHCs were highly accessible for cells and exerted pronounced neurodevelopmental effects, with neurite outgrowth and the mitochondrial membrane potential being sensitive endpoints; arsenite did not substantially decrease those two endpoints. In fully differentiated neurons, arsenite and AsHCs caused neurite toxicity. These results indicate for a neurodevelopmental potential of AsHCs. Taken into account the possibility that AsHCs might easily reach the developing brain when exposed during early life, neurotoxicity and neurodevelopmental toxicity cannot be excluded. Further studies are needed in order to progress the urgently needed risk assessment. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Affective spectrum disorders and role of serotonergic system of the brain

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Timotijević Ivana P.

2014-01-01

Full Text Available Affective spectrum disorders include mood and anxiety disorders, whereas the term functional somatic syndromes describes disorders in which the main symptom is chronic pain, with no pathognomonic tissue damage, such as fibromyalgia, irritable colon, tension headache. Pain as a symptom is often present in patients with depression and anxiety, and similarly, depressed mood, anxiety and other psychiatric symptoms are common in patients with functional somatic syndromes. This explains attitudes that affective disorders and functional somatic syndromes should be found along the same spectrum, due to a similar neurobiochemicalmehanism and dysfunction of these CNS structures and neurotransmitter systems, which lead to similar symptoms in both groups. The symptoms of affective disorders, including somatic are associated with serotonin and serotonergic transmission in the CNS. The existence of depressive and anxiety disorders, such as fatigue, sleep disorders, cognitive disorders, depressed mood, anxiety, and functional somatic syndromes code indicate a similar mechanism of origin. Hypothesis of central neuropathic pain explains the possibility of the descending inhibitory pain mechanisms, including serotonergic and noradrenergic projections and their receptors. Central suprasegmental senzitization in nociceptive pathways, also at the level of the thalamus and the sensory cortex, trigered by an emotional stressors can cause painful symptoms in both groups of disorders. Serotonergic and noradrenergic pathways and voltage sensitive channels of their receptors are included in the mechanism. Modern psychopharmacology can no longer ignore the existence of painful symptoms in affective disorder or depressive and anxiety symptoms in functional somatic syndromes and their treatment can improve. Therapeutic effects of SSRI and SNRI antidepressants and alpha 2 delta ligands for all kinds of painful symptoms in affective disorders - serotonergic spectrum is

Portal for Families Overcoming Neurodevelopmental Disorders (PFOND): Implementation of a Software Framework for Facilitated Community Website Creation by Nontechnical Volunteers.

Science.gov (United States)

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

2013-08-06

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

Clinical use of coping in affective disorder, a critical review of the literature

DEFF Research Database (Denmark)

Christensen, Maj Vinberg; Kessing, Lars Vedel

2005-01-01

/or avoidance coping styles are associated with a higher risk of developing affective disorder, so this hypothesis remains unclear. Most studies shows that emotion-oriented and avoidance coping strategies are associated with relapse of depressive episodes. Conversely, problem-focused and task-oriented coping......BACKGROUND: The relationship between life stressors, coping and affective disorder is interesting when predicting onset of a affective disorder and relapse of mood episodes. METHODS: A literature review of cross-sectional and longitudinal studies concerning coping and affective disorder in adults...... including a Medline and Embase search was conducted. RESULTS: 11 cross-sectional studies and 17 longitudinal studies concerning affective disorder and coping were found, among these, two studies include patients with bipolar disorder exclusively. Only four studies elucidate whether emotion-oriented and...

Early Childhood Neurodevelopmental Outcomes in Infants Exposed to Infectious Syphilis In Utero.

Science.gov (United States)

Verghese, Valsan P; Hendson, Leonora; Singh, Ameeta; Guenette, Tamara; Gratrix, Jennifer; Robinson, Joan L

2018-06-01

There are minimal neurodevelopmental follow-up data for infants exposed to syphilis in utero. This is an inception cohort study of infants exposed to syphilis in utero. We reviewed women with reactive syphilis serology in pregnancy or at delivery in Edmonton (Canada), 2002 through 2010 and describe the neurodevelopmental outcomes of children with and without congenital syphilis. There were 39 births to women with reactive syphilis serology, 9 of whom had late latent syphilis (n = 4), stillbirths (n = 2) or early neonatal deaths (n = 3), leaving 30 survivors of which 11 with and 7 without congenital syphilis had neurodevelopmental assessment. Those with congenital syphilis were all born to women with inadequate syphilis treatment before delivery. Neurodevelopmental impairment was documented in 3 of 11 (27%) infants with congenital syphilis and one of 7 (14%) without congenital syphilis with speech language delays in 4 of 11 (36%) with congenital syphilis and 3 of 7 (42%) without congenital syphilis. Infants born to mothers with reactive syphilis serology during pregnancy are at high risk for neurodevelopmental impairment, whether or not they have congenital syphilis, so should all be offered neurodevelopmental assessments and early referral for services as required.

The Comprehensive Assessment List for Affective Disorders (COALA): a polydiagnostic, comprehensive, and serial semistructured interview system for affective and related disorders.

Science.gov (United States)

Furukawa, T; Takahashi, K; Kitamura, T; Okawa, M; Miyaoka, H; Hirai, T; Ueda, H; Sakamoto, K; Miki, K; Fujita, K

1995-01-01

This supplement describes the development and structure of the Comprehensive Assessment List of Affective Disorders (COALA) system, which was recently developed for a collaborative follow-up study of a broad spectrum of affective disorders in Japan and which consists of a series of semistructured interviews for affective and related disorders. The COALA distinguishes itself from the extant semistructured interviews by being able to provide polydiagnostic, comprehensive and serial assessments. It is polydiagnostic because it derives diagnoses according to 29 historical and modern diagnostic systems through computer algorithms. It is comprehensive because it not only depicts the symptoms profile and rates their severity according to various endogenicity indices and severity rating scales but also measures, in the psychosocial domain, the life events and their characteristics. In addition, it has sections for past illnesses and family history. It is serial because the system includes follow-up semistructured interviews that can be administered monthly and that monitor changes in the psychopathological and psychosocial features. The theoretical underpinnings of the COALA system, especially its polydiagnostic approach to a broad spectrum of affective disorders and its treatment of psychosocial factors, are discussed in view of recent proposals for the future nosological research. The findings of the interrater reliability study (n = 107) are also presented, with satisfactory to excellent results for almost all of the psychopathological and psychosocial variables, all of the composite severity ratings and most of the polydiagnostic evaluations.

[Adaptive behaviour and learning in children with neurodevelopmental disorders (autism spectrum disorders and attention deficit hyperactivity disorder). Effects of executive functioning].

Science.gov (United States)

Rosello-Miranda, B; Berenguer-Forner, C; Miranda-Casas, A

2018-03-01

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.

Cognitive impairment in the euthymic phase of affective disorder

DEFF Research Database (Denmark)

Kessing, L V

1998-01-01

BACKGROUND: A review of studies of cognition in the euthymic phase of unipolar and bipolar affective disorder reveals diverging results. METHODS: The study was designed as a controlled cohort study, with the Danish psychiatric case register of admissions used to identify patients and the Danish...... civil register to identify controls. Patients who were hospitalized between 19 and 25 years ago with an affective diagnosis and who at interviews fulfilled criteria for a primary affective unipolar or bipolar disorder, according to ICD-10, were compared with age- and gender-matched controls. Interviews...... and assessment of the cognitive function were made in the euthymic phase of the disorder. In all, 118 unipolar patients, 28 bipolar patients and 58 controls were included. Analyses were adjusted for differences in the level of education and for subclinical depressive and anxiety symptoms. RESULTS: Patients...

A human neurodevelopmental model for Williams syndrome.

Science.gov (United States)

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

2016-08-18

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.

Postnatal Phencyclidine (PCP) as a Neurodevelopmental Animal Model of Schizophrenia Pathophysiology and Symptomatology: A Review.

Science.gov (United States)

Grayson, B; Barnes, S A; Markou, A; Piercy, C; Podda, G; Neill, J C

that it will provide a useful neurodevelopmental model to complement other models such as maternal immune activation, particularly when combined with other manipulations to produce dual or triple hit models. However, the developmental trajectory of behavioural and neuropathological changes induced by postnatal PCP and their relevance to schizophrenia must be carefully mapped out. Overall, we support further development of dual (or triple) hit models incorporating genetic, neurodevelopmental and appropriate environmental elements in the search for more aetiologically valid animal models of schizophrenia and neurodevelopmental disorders (NDDs).

Childhood traumatization by primary caretaker and affect dysregulation in patients with borderline personality disorder and somatoform disorder

Directory of Open Access Journals (Sweden)

Annemiek van Dijke

2011-03-01

Full Text Available Affect regulation is often compromised as a result of early life interpersonal traumatization and disruption in caregiving relationships like in situations where the caretaker is emotionally, sexually or physically abusing the child. Prior studies suggest a clear relationship between early childhood attachment-related psychological trauma and affect dysregulation. We evaluated the relationship of retrospectively recalled childhood traumatization by primary caretaker(s (TPC and affect dysregulation in 472 adult psychiatric patients diagnosed with borderline personality disorder (BPD, somatoform disorder (SoD, both BPD and SoD, or disorders other than BPD or SoD, using the Bermond-Vorst Alexithymia Questionnaire, the self-report version of the Structured Interview for Disorders of Extreme Stress, the Self-rating Inventory for Posttraumatic Stress Disorder (SRIP and the Traumatic Experiences Checklist. Almost two-thirds of participants reported having experienced childhood TPC, ranging from approximately 50% of patients with SoD or other psychiatric disorders to more than 75% of patients with comorbid BPD + SoD. Underregulation of affect was associated with emotional TPC and TPC occurring in developmental epoch 0–6 years. Over-regulation of affect was associated with physical TPC. Childhood trauma by a primary caretaker is prevalent among psychiatric patients, particularly those with BPD, and differentially associated with underand over-regulation of affect depending on the type of traumatic exposure.For the abstract or full text in other languages, please see Supplementary files under Reading Tools online

Affective disorders and functional (non-epileptic) seizures in persons with epilepsy.

Science.gov (United States)

Johnson, Keith A; Macfarlane, Matthew D; Looi, Jeffrey Cl

2016-12-01

This paper aims to describe the prevalence, assessment and management of affective disorders as well as functional (non-epileptic) seizures in people with epilepsy. This paper comprises a selective review of the literature of the common affective manifestations of epilepsy. Affective disorders are the most common psychiatric comorbidity seen in people with epilepsy and assessment and management parallels that of the general population. Additionally, people with epilepsy may experience higher rates of mood instability, irritability and euphoria, classified together as a group, interictal dysphoric disorder and resembling an unstable bipolar Type II disorder. Functional seizures present unique challenges in terms of identification of the disorder and a lack of specific management. Given their high prevalence, it is important to be able to recognise affective disorders in people with epilepsy. Management principles parallel those in the general population with specific caution exercised regarding the potential interactions between antidepressant medications and antiepileptic drugs. Functional seizures are more complex and require a coordinated approach involving neurologists, psychiatrists, general practitioners, nursing and allied health. There is very limited evidence to guide psychological and behavioural interventions for neurotic disorders in epilepsy and much more research is needed. © The Royal Australian and New Zealand College of Psychiatrists 2016.

[Formula: see text]Selecting measures for the neurodevelopmental assessment of children in low- and middle-income countries.

Science.gov (United States)

Semrud-Clikeman, Margaret; Romero, Regilda Anne A; Prado, Elizabeth L; Shapiro, Elsa G; Bangirana, Paul; John, Chandy C

2017-10-01

Diseases affecting millions of children in low- and middle-income countries (LMICs), such as malnutrition, micronutrient deficiency, malaria, and HIV, can lead to adverse neurodevelopmental outcomes. Thus, a key health outcome in children is neurodevelopmental status. In this paper, the neurodevelopmental screening and testing measures most commonly utilized in LMICs are reviewed, and a matrix is presented to help researchers and clinicians determine which measures may be most useful for various LMIC inquiries. The matrix is based on an Internet literature review of 114 publications for the period January 1998 to February 2016, reporting the psychometric properties of instruments tested in LMIC children. The measures are classified as screening tests or more detailed tests that include both comprehensive batteries of general development and tests of specific domains. For completeness, two experts have reviewed this paper, as well as the authors. An overview of the tests used to date is presented, including the benefits and drawbacks of each test, in order to provide researchers and developmental clinicians with a way to decide which tests may be best suited to their developmental assessment goals. Remarkable progress has been made in neurodevelopmental testing in children in LMICs over the past two decades but there remains a need for additional research in this area to develop new tests, better evaluate and adapt current tests, and assess test validity and reliability across cultures.

A study of hippocampal shape anomaly in schizophrenia and in families multiply affected by schizophrenia or bipolar disorder

Energy Technology Data Exchange (ETDEWEB)

Connor, S.E.J. [Department of Neuroradiology, Kings Healthcare NHS Trust, King' s College Hospital, Denmark Hill, SE5 9RS, London (United Kingdom); Ng, V. [Department of Neuroimaging, Maudsley Hospital, London (United Kingdom); McDonald, C.; Schulze, K.; Morgan, K.; Dazzan, P.; Murray, R.M. [Division of Psychological Medicine, Institute of Psychiatry, London (United Kingdom)

2004-07-01

Hippocampal shape anomaly (HSA), characterised by a rounded hippocampus, has been documented in congenital malformations and epileptic patients. Subtle structural hippocampal abnormalities have been demonstrated in patients with schizophrenia. We tested the hypothesis that HSA is more frequent in schizophrenia, particularly in patients from families multiply affected by schizophrenia, and that HSA is transmitted within these families. We also aimed to define the anatomical features of the hippocampus and other cerebral structures in the HSA spectrum and to determine the prevalence of HSA in a control group. We reviewed the magnetic resonance imaging of a large number of subjects with schizophrenia and bipolar disorder, many of who came from multiply affected families, relatives of the affected probands, and controls. Quantitative measures of hippocampal shape and position and other qualitative anatomical measures were performed (including depth of dominant sulcus cortical cap, angle of dominant sulcus and hippocampal fissure, bulk of collateral white matter, prominence of temporal horn lateral recess and blurring of internal hippocampal architecture) on subjects with HSA. A spectrum of mild, moderate and severe HSA was defined. The prevalence of HSA was, 7.8% for the controls (n=218), 9.3% for all schizophrenic subjects (n=151) and 12.3% for familial schizophrenic subjects (n=57). There was a greater prevalence of moderate or severe forms of HSA in familial schizophrenics than controls. However, there was no increase in the prevalence of HSA in the unaffected first-degree relatives of schizophrenic patients or in patients with familial bipolar disorder. HSA was rarely transmitted in families. HSA was frequently associated with a deep, vertical collateral/occipito-temporal sulcus and a steep hippocampal fissure. Our data raise the possibility that HSA is linked to disturbances of certain neurodevelopmental genes associated with schizophrenia. However, the lack of

A study of hippocampal shape anomaly in schizophrenia and in families multiply affected by schizophrenia or bipolar disorder

International Nuclear Information System (INIS)

Connor, S.E.J.; Ng, V.; McDonald, C.; Schulze, K.; Morgan, K.; Dazzan, P.; Murray, R.M.

2004-01-01

Hippocampal shape anomaly (HSA), characterised by a rounded hippocampus, has been documented in congenital malformations and epileptic patients. Subtle structural hippocampal abnormalities have been demonstrated in patients with schizophrenia. We tested the hypothesis that HSA is more frequent in schizophrenia, particularly in patients from families multiply affected by schizophrenia, and that HSA is transmitted within these families. We also aimed to define the anatomical features of the hippocampus and other cerebral structures in the HSA spectrum and to determine the prevalence of HSA in a control group. We reviewed the magnetic resonance imaging of a large number of subjects with schizophrenia and bipolar disorder, many of who came from multiply affected families, relatives of the affected probands, and controls. Quantitative measures of hippocampal shape and position and other qualitative anatomical measures were performed (including depth of dominant sulcus cortical cap, angle of dominant sulcus and hippocampal fissure, bulk of collateral white matter, prominence of temporal horn lateral recess and blurring of internal hippocampal architecture) on subjects with HSA. A spectrum of mild, moderate and severe HSA was defined. The prevalence of HSA was, 7.8% for the controls (n=218), 9.3% for all schizophrenic subjects (n=151) and 12.3% for familial schizophrenic subjects (n=57). There was a greater prevalence of moderate or severe forms of HSA in familial schizophrenics than controls. However, there was no increase in the prevalence of HSA in the unaffected first-degree relatives of schizophrenic patients or in patients with familial bipolar disorder. HSA was rarely transmitted in families. HSA was frequently associated with a deep, vertical collateral/occipito-temporal sulcus and a steep hippocampal fissure. Our data raise the possibility that HSA is linked to disturbances of certain neurodevelopmental genes associated with schizophrenia. However, the lack of

Intragenic deletions affecting two alternative transcripts of the IMMP2L gene in patients with Tourette syndrome

DEFF Research Database (Denmark)

Bertelsen, Birgitte; Melchior, Linea; Jensen, Lars R

2014-01-01

Tourette syndrome is a neurodevelopmental disorder characterized by multiple motor and vocal tics, and the disorder is often accompanied by comorbidities such as attention-deficit hyperactivity-disorder and obsessive compulsive disorder. Tourette syndrome has a complex etiology, but the underlying...

Burden of neurodevelopmental disorders in low and middle-income countries: A systematic review and meta-analysis [version 3; referees: 1 approved, 2 approved with reservations

Directory of Open Access Journals (Sweden)

Mary Bitta

2018-03-01

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.

QUANTITATIVE EEG COMPARATIVE ANALYSIS BETWEEN AUTISM SPECTRUM DISORDER (ASD AND ATTENTION DEFICIT HYPERACTIVITY DISORDER (ADHD

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Plamen D. Dimitrov

2017-01-01

Full Text Available Background: Autism is a mental developmental disorder, manifested in the early childhood. Attention deficit hyperactivity disorder is another psychiatric condition of the neurodevelopmental type. Both disorders affect information processing in the nervous system, altering the mechanisms which control how neurons and their synapses are connected and organized. Purpose: To examine if quantitative EEG assessment is sensitive and simple enough to differentiate autism from attention deficit hyperactivity disorder and neurologically typical children. Material and methods: Quantitative EEG is a type of electrophysiological assessment that uses computerized mathematical analysis to convert the raw waveform data into different frequency ranges. Each frequency range is averaged across a sample of data and quantified into mean amplitude (voltage in microvolts mV. We performed quantitative EEG analysis and compared 4 cohorts of children (aged from 3 to 7 years: with autism (high [n=27] and low [n=52] functioning, with attention deficit hyperactivity disorder [n=34], and with typical behavior [n75]. Results: Our preliminary results show that there are significant qEEG differences between the groups of patients and the control cohort. The changes affect the potential levels of delta-, theta-, alpha-, and beta- frequency spectrums. Conclusion: The present study shows some significant quantitative EEG findings in autistic patients. This is a step forward in our efforts, aimed at defining specific neurophysiologic changes, in order to develop and refine strategies for early diagnosis of autism spectrum disorders, differentiation from other development conditions in childhood, detection of specific biomarkers and early initiation of treatment.

Exposure to Alumina Nanoparticles in Female Mice During Pregnancy Induces Neurodevelopmental Toxicity in the Offspring.

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Zhang, Qinli; Ding, Yong; He, Kaihong; Li, Huan; Gao, Fuping; Moehling, Taylor J; Wu, Xiaohong; Duncan, Jeremy; Niu, Qiao

2018-01-01

Alumina nanoparticles (AlNP) have been shown to accumulate in organs and penetrate biological barriers which lead to toxic effects in many organ systems. However, it is not known whether AlNP exposure to female mice during pregnancy can affect the development of the central nervous system or induce neurodevelopmental toxicity in the offspring. The present study aims to examine the effect of AlNP on neurodevelopment and associated underlying mechanism. ICR strain adult female mice were randomly divided into four groups, which were treated with normal saline (control), 10 μm particle size of alumina (bulk-Al), and 50 and 13 nm AlNP during entire pregnancy period. Aluminum contents in the hippocampus of newborns were measured and neurodevelopmental behaviors were tracked in the offspring from birth to 1 month of age. Furthermore, oxidative stress and neurotransmitter levels were measured in the cerebral cortex of the adolescents. Our results showed that aluminum contents in the hippocampus of newborns in AlNP-treated groups were significantly higher than those in bulk-Al and controls. Moreover, the offspring delivered by AlNP-treated female mice displayed stunted neurodevelopmental behaviors. Finally, the offspring of AlNP-treated mice demonstrated significantly increased anxiety-like behavior with impaired learning and memory performance at 1 month of age. The underlying mechanism could be related to increased oxidative stress and decreased neurotransmitter levels in the cerebral cortex. We therefore conclude that AlNP exposure of female mice during pregnancy can induce neurodevelopmental toxicity in offspring.

Improving Neurodevelopmental Surveillance and Follow-up in Infants with Congenital Heart Disease.

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Michael, Mark; Scharf, Rebecca; Letzkus, Lisa; Vergales, Jeffrey

2016-01-01

We hypothesize that neurodevelopmental surveillance of targeted patients with congenital heart disease during the admission for their cardiac surgery would improve neurodevelopmental assessment and outpatient follow-up rates. All patients under 12 months of age who were operated on between October 2013 and October 2014 and were considered at risk for neurodevelopmental delay in accordance with the 2012 American Heart Association Scientific Statement were included. A protocol was implemented to increase surveillance of targeted patients during the hospitalization for their cardiac surgery. A historical control cohort was used from a 6-month period that preceded initiation of the program from July 2012 to December 2012. Univariate analysis assessed the effects of patient demographics, anatomy, postoperative course, and distance from clinic on inpatient screening and follow-up to evaluate areas for future improvement. Neurodevelopmental surveillance in the post-protocol period increased from 21% to 82% (P neurodevelopmental surveillance of high risk patients. Individuals that were younger and in the hospital longer were more likely to be successfully seen and comply with outpatient follow-up than those not receiving inpatient risk assessment. Patients with single ventricle anatomy may benefit from a modified follow-up schedule to improve compliance rates. Travel distance has no effect on likelihood of outpatient cardiac neurodevelopmental follow-up. © 2016 Wiley Periodicals, Inc.

Cortical complexity in bipolar disorder applying a spherical harmonics approach.

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Nenadic, Igor; Yotter, Rachel A; Dietzek, Maren; Langbein, Kerstin; Sauer, Heinrich; Gaser, Christian

2017-05-30

Recent studies using surface-based morphometry of structural magnetic resonance imaging data have suggested that some changes in bipolar disorder (BP) might be neurodevelopmental in origin. We applied a novel analysis of cortical complexity based on fractal dimensions in high-resolution structural MRI scans of 18 bipolar disorder patients and 26 healthy controls. Our region-of-interest based analysis revealed increases in fractal dimensions (in patients relative to controls) in left lateral orbitofrontal cortex and right precuneus, and decreases in right caudal middle frontal, entorhinal cortex, and right pars orbitalis, and left fusiform and posterior cingulate cortices. While our analysis is preliminary, it suggests that early neurodevelopmental pathologies might contribute to bipolar disorder, possibly through genetic mechanisms. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Behavioral and Neurodevelopmental Precursors to Binge-Type Eating Disorders: Support for the Role of Negative Valence Systems

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Vannucci, Anna; Nelson, Eric E.; Bongiorno, Diana M.; Pine, Daniel S.; Yanovski, Jack A.; Tanofsky-Kraff, Marian

2015-01-01

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

Subclinical psychopathology and socio-economic status in unaffected twins discordant for affective disorder

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Christensen, Maj Vinberg; Kyvik, Kirsten Ohm; Kessing, Lars Vedel

2006-01-01

BACKGROUND: The most potent risk factor for affective disorders is a family history of affective disorder but the specific factors that are transmitted in families are unknown. It is possible to investigate the relation between risk factors and affective disorder by using a high-risk design e.g.:...

Recovery from episodes during the course of affective disorder

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Kessing, L V; Mortensen, P B

1999-01-01

OBJECTIVE: The aim of the study was to investigate whether the duration of treated episodes changes during the course of unipolar and bipolar affective disorder. METHOD: The rate of recovery from successive hospitalized episodes was estimated with survival analyses in a case-register study...... including all hospital admissions with primary affective disorder in Denmark during the period 1971-1993. RESULTS: A total of 9174 patients with recurrent episodes were followed from their first admission. The rate of recovery from hospitalized episodes did not change with the number of episodes in unipolar...... or bipolar disorder. Furthermore, the rate of recovery was constant across episodes, regardless of the combination of age, gender and type of disorder. Initially in the course of the illness, the rate was a little faster for bipolar than for unipolar patients, but later in the course of the illness the rate...

Post-traumatic stress disorder symptoms, underlying affective vulnerabilities, and smoking for affect regulation.

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Mathew, Amanda R; Cook, Jessica W; Japuntich, Sandra J; Leventhal, Adam M

2015-01-01

Post-traumatic stress disorder (PTSD) is overrepresented among cigarette smokers. It has been hypothesized that those with PTSD smoke to alleviate negative affect and counteract deficient positive affect commonly associated with the disorder; however, limited research has examined associations between PTSD symptoms, smoking motives, and affective vulnerability factors. In the current study, we examined (1) whether PTSD symptoms were associated with positive reinforcement and negative reinforcement smoking motives; and (2) whether two affective vulnerability factors implicated in PTSD-anxiety sensitivity and anhedonia-mediated relationships between PTSD symptoms and smoking motives. Data were drawn from a community sample of non-treatment-seeking smokers recruited without regard for trauma history (N = 342; 10+ cig/day). We used the Posttraumatic Stress Disorder Checklist-Civilian Version (PCL-C) to assess overall PTSD symptom severity as well as individual PTSD subfactors. Overall, PTSD symptom severity was significantly associated with negative reinforcement, but not positive reinforcement, smoking motives. Variation in anxiety sensitivity significantly mediated the relation between PTSD symptom severity and negative reinforcement smoking motives, whereas anhedonia did not. Regarding PTSD subfactors, emotional numbing was the only PTSD subfactor associated with smoking rate, while re-experiencing symptoms were uniquely associated with both positive reinforcement and negative reinforcement smoking motives. Findings suggest that anxiety sensitivity may be an important feature associated with PTSD that enhances motivation to smoke for negative reinforcement purposes. Smoking cessation interventions that alleviate anxiety sensitivity and enhance coping with negative affect may be useful for smokers with elevated PTSD symptoms. © American Academy of Addiction Psychiatry.

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

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Frida Lygnegård

2018-04-01

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

Seizures and Epilepsy and Their Relationship to Autism Spectrum Disorders

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Matson, Johnny L.; Neal, Daniene

2009-01-01

Autism spectrum disorders (ASD) are serious neurodevelopmental disorders which often co-occur with intellectual disabilities. A disorder which is strongly correlated with both of these disabilities are seizures and epilepsy. The purpose of this review was to provide an overview of available research on seizures and epilepsy in the ASD population…

Narcissistic disorder and the failure of symbolisation: a Relational Affective Hypothesis.

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Mizen, C S

2014-09-01

The psychoanalytic concept of narcissistic disorder is broader than that of Narcissistic Personality Disorder (DSM-5 [1]), underlying a range of Personality Disorders (PD) and their co-morbidities. Existing Mentalisation, Psychoanalytic and Cognitive models, fail to account fully for the emerging evidence of biological, developmental, relational and defensive contributions to narcissistic disorder, nor do they account for the common and variant features of co-morbidities namely Anorexia Nervosa, Somatisation, Substance Misuse and Autistic Spectrum Disorder. Alexithymia and concrete modes of relating are common findings in narcissistic disorder and these co-morbid conditions. Current models do not provide a comprehensive account, on the basis of neuro-scientific and developmental evidence, of how affective feelings come to be represented in words and the association between narcissistic disorders and failures of symbolisation. In this paper I propose an empirically based Relational Affective Hypothesis that narcissistic disorder and its comorbidities represent failures at specific points on a representational function pathway through which subcortical affect and visceral feeling in a relational context become the basis for abstraction and language. The elucidation of this pathway allows investigation of the contribution of biological, social and psychogenic factors in narcissistic disorders. It also brings a new understanding of the neurological underpinning of psychodynamic defences in narcissistic disorders. Research and novel treatment implications are briefly considered. Copyright © 2014 Elsevier Ltd. All rights reserved.

Variants in TTC25 affect autistic trait in patients with autism spectrum disorder and general population.

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Vojinovic, Dina; Brison, Nathalie; Ahmad, Shahzad; Noens, Ilse; Pappa, Irene; Karssen, Lennart C; Tiemeier, Henning; van Duijn, Cornelia M; Peeters, Hilde; Amin, Najaf

2017-08-01

Autism spectrum disorder (ASD) is a highly heritable neurodevelopmental disorder with a complex genetic architecture. To identify genetic variants underlying ASD, we performed single-variant and gene-based genome-wide association studies using a dense genotyping array containing over 2.3 million single-nucleotide variants in a discovery sample of 160 families with at least one child affected with non-syndromic ASD using a binary (ASD yes/no) phenotype and a quantitative autistic trait. Replication of the top findings was performed in Psychiatric Genomics Consortium and Erasmus Rucphen Family (ERF) cohort study. Significant association of quantitative autistic trait was observed with the TTC25 gene at 17q21.2 (effect size=10.2, P-value=3.4 × 10 -7 ) in the gene-based analysis. The gene also showed nominally significant association in the cohort-based ERF study (effect=1.75, P-value=0.05). Meta-analysis of discovery and replication improved the association signal (P-value meta =1.5 × 10 -8 ). No genome-wide significant signal was observed in the single-variant analysis of either the binary ASD phenotype or the quantitative autistic trait. Our study has identified a novel gene TTC25 to be associated with quantitative autistic trait in patients with ASD. The replication of association in a cohort-based study and the effect estimate suggest that variants in TTC25 may also be relevant for broader ASD phenotype in the general population. TTC25 is overexpressed in frontal cortex and testis and is known to be involved in cilium movement and thus an interesting candidate gene for autistic trait.

Seizure disorders and developmental disorders: impact on life of affected families-a structured interview.

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Spindler, Ulrike Petra; Hotopp, Lena Charlott; Bach, Vivien Angela; Hornemann, Frauke; Syrbe, Steffen; Andreas, Anna; Merkenschlager, Andreas; Kiess, Wieland; Bernhard, Matthias Karl; Bertsche, Thilo; Neininger, Martina Patrizia; Bertsche, Astrid

2017-08-01

Seizure disorder and developmental disorder are two of the most common chronic disorders in childhood. Data on perceived parental burden and specific effects on daily life is scarce. We performed a structured interview, consecutively talking to all parents of pediatric outpatients of our university hospital diagnosed with seizure or developmental disorder. Three hundred seven parents (of 317 affected children: 53 with seizure disorder, 44 with specific developmental disorder, 35 with learning disorder, 71 with intellectual disability, 15 with seizure + specific developmental disorder, 23 with seizure + learning disorder, 76 with seizure disorder + intellectual disability) were interviewed. Parents of children with both seizure disorder and intellectual disability stated the highest constraints in daily life, regarding friends, hobbies, emotional pressure, occupation, partnership, habitation, and financial burden. Due to diagnosis of seizure or developmental disorder, 155/307 (51%) parents reduced their working hours/stopped working, 62/307 (20%) changed their habitation, and 46/307 (15%) broke up. As judged by parents, 148/317 (47%) children are being discriminated against, even own family/friends and educators are held responsible. Parents perceive changes in their daily life and discrimination of their children due to their children's seizure and developmental disorders. An intellectual disability combined with seizure disorder caused the highest constraint. What is Known: • Seizure and/or developmental disorders of children may adversely influence quality of life for affected parents. • Caring for a child with special health care needs can take complete attention and own parental needs may therefore be difficult to meet. What is New: • Two out of three parents stated changes of their daily life such as quitting work, change of habitation, or breakup of partnership due to their child's diagnosis. • As judged by the parents, one in two children with

Daily Interpersonal and Affective Dynamics in Personality Disorder

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Wright, Aidan G.C.; Hopwood, Christopher J.; Simms, Leonard J.

2015-01-01

In this naturalistic study we adopt the lens of interpersonal theory to examine between-and within-person differences in dynamic processes of daily affect and interpersonal behaviors among individuals (N = 101) previously diagnosed with personality disorders who completed daily diaries over the course of 100 days. Dispositional ratings of interpersonal problems and measures of daily stress were used as predictors of daily shifts in interpersonal behavior and affect in multilevel models. Results indicate that ~40%–50% of the variance in interpersonal behavior and affect is due to daily fluctuations, which are modestly related to dispositional measures of interpersonal problems but strongly related to daily stress. The findings support conceptions of personality disorders as a dynamic form of psychopathology involving the individuals interacting with and regulating in response to the contextual features of their environment. PMID:26200849

Piece Work: Fabric Collage as a Neurodevelopmental Approach to Trauma Treatment

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Homer, Eliza S.

2015-01-01

This article describes the use of collaborative fabric collage based on a neurodevelopmental adaptation for an adult who was being treated for trauma. The case demonstrates the value of thinking about neurodevelopmental factors when creating art therapy interventions. A biologically respectful treatment that offers relational, relevant,…

[Temperament and affective disorders--historical basis of current discussion].

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Ehrt, U; Brieger, P; Marneros, A

2003-06-01

The history of the temperament concept begins in ancient Greece. The humoral theory remained influential over the centuries. At the beginning of the 20 th century, both Wilhelm Wundt and his pupil Emil Kraepelin formulated new aspects. Wundt described two dimensions: "speed of variability of emotions" and "intensity of emotions". Kraepelin observed four fundamental states (depressive, manic, irritable and cyclothymic), which he linked to manic-depressive illness. Since then different lines of temperament research have evolved: (1) psychiatric-psychopathological theories (e. g. Ewald, Kretschmer and Sheldon), which tend to see temperament as a dilution of full-blown affective disorders; (2) neurobiological theories (e. g. Pavlov, Eysenck and Gray), which understand temperament as determined by underlying neurobiological processes - especially levels of arousal; and (3) developmental theories (e. g. Chess & Thomas, Rothbart and Kagan), which derived their temperament concept from early childhood observations. Recent theories (e. g. those of Cloninger or Akiskal) combine different aspects. After reviewing the historical temperament concepts we present underlying factors which are linked to affective disorders (such as emotional reactivity, cyclicity or trait affectivity). Finally, we illustrate the importance of temperament concepts for research in affective disorders.

De Novo Coding Variants Are Strongly Associated with Tourette Disorder

DEFF Research Database (Denmark)

Willsey, A Jeremy; Fernandez, Thomas V; Yu, Dongmei

2017-01-01

Whole-exome sequencing (WES) and de novo variant detection have proven a powerful approach to gene discovery in complex neurodevelopmental disorders. We have completed WES of 325 Tourette disorder trios from the Tourette International Collaborative Genetics cohort and a replication sample of 186 ...

Neurodevelopmental effects of chronic exposure to elevated levels of pro-inflammatory cytokines in a developing visual system

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Ruthazer Edward S

2010-01-01

Full Text Available Abstract Background Imbalances in the regulation of pro-inflammatory cytokines have been increasingly correlated with a number of severe and prevalent neurodevelopmental disorders, including autism spectrum disorder, schizophrenia and Down syndrome. Although several studies have shown that cytokines have potent effects on neural function, their role in neural development is still poorly understood. In this study, we investigated the link between abnormal cytokine levels and neural development using the Xenopus laevis tadpole visual system, a model frequently used to examine the anatomical and functional development of neural circuits. Results Using a test for a visually guided behavior that requires normal visual system development, we examined the long-term effects of prolonged developmental exposure to three pro-inflammatory cytokines with known neural functions: interleukin (IL-1β, IL-6 and tumor necrosis factor (TNF-α. We found that all cytokines affected the development of normal visually guided behavior. Neuroanatomical imaging of the visual projection showed that none of the cytokines caused any gross abnormalities in the anatomical organization of this projection, suggesting that they may be acting at the level of neuronal microcircuits. We further tested the effects of TNF-α on the electrophysiological properties of the retinotectal circuit and found that long-term developmental exposure to TNF-α resulted in enhanced spontaneous excitatory synaptic transmission in tectal neurons, increased AMPA/NMDA ratios of retinotectal synapses, and a decrease in the number of immature synapses containing only NMDA receptors, consistent with premature maturation and stabilization of these synapses. Local interconnectivity within the tectum also appeared to remain widespread, as shown by increased recurrent polysynaptic activity, and was similar to what is seen in more immature, less refined tectal circuits. TNF-α treatment also enhanced the

Lifetime Prevalence and Correlates of Schizophrenia-Spectrum, Affective, and Other Non-affective Psychotic Disorders in the Chinese Adult Population.

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Chang, Wing Chung; Wong, Corine Sau Man; Chen, Eric Yu Hai; Lam, Linda Chiu Wa; Chan, Wai Chi; Ng, Roger Man Kin; Hung, Se Fong; Cheung, Eric Fuk Chi; Sham, Pak Chung; Chiu, Helen Fung Kum; Lam, Ming; Lee, Edwin Ho Ming; Chiang, Tin Po; Chan, Lap Kei; Lau, Gary Kar Wai; Lee, Allen Ting Chun; Leung, Grace Tak Yu; Leung, Joey Shuk Yan; Lau, Joseph Tak Fai; van Os, Jim; Lewis, Glyn; Bebbington, Paul

2017-10-21

Lifetime prevalence of psychotic disorders varies widely across studies. Epidemiological surveys have rarely examined prevalences of specific psychotic disorders other than schizophrenia, and the majority used a single-phase design without employing clinical reappraisal interview for diagnostic verification. The current study investigated lifetime prevalence, correlates and service utilization of schizophrenia-spectrum, affective, and other non-affective psychotic disorders in a representative sample of community-dwelling Chinese adult population aged 16-75 years (N = 5719) based on a territory-wide, population-based household survey for mental disorders in Hong Kong. The survey adopted a 2-phase design comprising first-phase psychosis screening and second-phase diagnostic verification incorporating clinical information from psychiatrist-administered semi-structured interview and medical record review to ascertain DSM-IV lifetime diagnosis for psychotic disorders. Data on sociodemographics, psychosocial characteristics and service utilization were collected. Our results showed that lifetime prevalence was 2.47% for psychotic disorder overall, 1.25% for schizophrenia, 0.15% for delusional disorder, 0.38% for psychotic disorder not otherwise specified, 0.31% for bipolar disorder with psychosis, and 0.33% for depressive disorder with psychosis. Schizophrenia-spectrum disorder was associated with family history of psychosis, cigarette smoking and variables indicating socioeconomic disadvantage. Victimization experiences were significantly related to affective psychoses and other non-affective psychoses. Around 80% of participants with any psychotic disorder sought some kind of professional help for mental health problems in the past year. Using comprehensive diagnostic assessment involving interview and record data, our results indicate that approximately 2.5% of Chinese adult population had lifetime psychotic disorder which represents a major public health concern. �

Functional alterations of astrocytes in mental disorders: pharmacological significance as a drug target

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Yutaka eKoyama

2015-07-01

Full Text Available Astrocytes play an essential role in supporting brain functions in physiological and pathological states. Modulation of their pathophysiological responses have beneficial actions on nerve tissue injured by brain insults and neurodegenerative diseases, therefore astrocytes are recognized as promising targets for neuroprotective drugs. Recent investigations have identified several astrocytic mechanisms for modulating synaptic transmission and neural plasticity. These include altered expression of transporters for neurotransmitters, release of gliotransmitters and neurotrophic factors, and intercellular communication through gap junctions. Investigation of patients with mental disorders shows morphological and functional alterations in astrocytes. According to these observations, manipulation of astrocytic function by gene mutation and pharmacological tools reproduce mental disorder-like behavior in experimental animals. Some drugs clinically used for mental disorders affect astrocyte function. As experimental evidence shows their role in the pathogenesis of mental disorders, astrocytes have gained much attention as drug targets for mental disorders. In this article, I review functional alterations of astrocytes in several mental disorders including schizophrenia, mood disorder, drug dependence, and neurodevelopmental disorders. The pharmacological significance of astrocytes in mental disorders is also discussed.

Cross-Disorder Genome-Wide Analyses Suggest a Complex Genetic Relationship Between Tourette's Syndrome and OCD

NARCIS (Netherlands)

Yu, Dongmei; Mathews, Carol A.; Scharf, Jeremiah M.; Neale, Benjamin M.; Davis, Lea K.; Gamazon, Eric R.; Derks, Eske M.; Evans, Patrick; Edlund, Christopher K.; Crane, Jacquelyn; Osiecki, Lisa; Gallagher, Patience; Gerber, Gloria; Haddad, Stephen; Illmann, Cornelia; McGrath, Lauren M.; Mayerfeld, Catherine; Arepalli, Sampath; Barlassina, Cristina; Barr, Cathy L.; Bellodi, Laura; Benarroch, Fortu; Berrio, Gabriel Bedoya; Bienvenu, O. Joseph; Black, Donald W.; Bloch, Michael H.; Brentani, Helena; Bruun, Ruth D.; Budman, Cathy L.; Camarena, Beatriz; Campbell, Desmond D.; Cappi, Carolina; Silgado, Julio C. Cardona; Cavallini, Maria C.; Chavira, Denise A.; Chouinard, Sylvain; Cook, Edwin H.; Cookson, M. R.; Coric, Vladimir; Cullen, Bernadette; Cusi, Daniete; Delorme, Richard; Denys, Damiaan; Dion, Yves; Eapen, Valsama; Egberts, Karin; Falkai, Peter; Fernandez, Thomas; Fournier, Eduardo; Garrido, Helena; Geller, Daniel; Gilbert, Donald L.; Girard, Simon L.; Grabe, Hans J.; Grados, Marco A.; Greenberg, Benjamin D.; Gross-Tsur, Varda; Gruenblatt, Edna; Hardy, John; Heiman, Gary A.; Hemmings, Sian M. J.; Herrera, Luis D.; Hezel, Dianne M.; Hoekstra, Pieter J.; Jankovic, Joseph; Kennedy, James L.; King, Robert A.; Konkashbaev, Anuar I.; Kremeyer, Barbara; Kurlan, Roger; Lanzagorta, Nuria; Leboyer, Marion; Leckman, James F.; Lennertz, Leonhard; Liu, Chunyu; Lochner, Christine; Lowe, Thomas L.; Lupoli, Sara; Macciardi, Fabio; Maier, Wolfgang; Manunta, Paolo; Marconi, Maurizio; McCracken, James T.; Restrepo, Sandra C. Mesa; Moessner, Rainald; Moorjani, Priya; Morgan, Jubel; Muller, Heike; Murphy, Dennis L.; Naarden, Allan L.; Nurmi, Erika; Ochoa, William Cornejo; Ophoff, Roel A.; Pakstis, Andrew J.; Pato, Michele T.; Pato, Carlo N.; Piacentini, John; Pittenger, Christopher; Pollak, Yehuda; Rauch, Scott L.; Renner, Tobias; Reus, Victor I.; Richter, Margaret A.; Riddle, Mark A.; Robertson, Mary M.; Romero, Roxana; Rosario, Maria C.; Rosenberg, David; Ruhrmann, Stephan; Sabatti, Chiara; Salvi, Erika; Sampaio, Aline S.; Samuels, Jack; Sandor, Paul; Service, Susan K.; Sheppard, Brooke; Singer, Harvey S.; Smit, Jan H.; Stein, Dan J.; Strengman, Eric; Tischfield, Jay A.; Turiel, Maurizio; Duarte, Ana V. Valencia; Vallada, Homero; Veenstra-VanderWeele, Jeremy; Walitza, Susanne; Wang, Ying; Weale, Mike; Weiss, Robert; Wendland, Jens R.; Westenberg, Herman G. M.; Shugart, Yin Yao; Hounie, Ana G.; Miguel, Euripedes C.; Nicolini, Humberto; Wagner, Michael; Ruiz-Linares, Andres; Cath, Danielle C.; McMahon, William; Posthuma, Danielle; Oostra, Ben A.; Nestadt, Gerald; Routeau, Guy A.; Purcell, Shaun; Jenike, Michael A.; Heutink, Peter; Hanna, Gregory L.; Conti, David V.; Arnold, Paul D.; Freimer, Nelson B.; Stewart, Evelyn; Knowles, James A.; Cox, Nancy J.; Pauls, David L.

Objective: Obsessive-compulsive disorder (OCD) and Tourette's syndrome are highly heritable neurodevelopmental disorders that are thought to share genetic risk factors. However, the identification of definitive susceptibility genes for these etiologically complex disorders remains elusive. The

Cross-Disorder Genome-Wide Analyses Suggest a Complex Genetic Relationship Between Tourette's Syndrome and OCD

NARCIS (Netherlands)

Yu, Dongmei; Mathews, Carol A; Scharf, Jeremiah M; Neale, Benjamin M; Davis, Lea K; Gamazon, Eric R; Derks, Eske M; Evans, Patrick; Edlund, Christopher K; Crane, Jacquelyn; Fagerness, Jesen A; Osiecki, Lisa; Gallagher, Patience; Gerber, Gloria; Haddad, Stephen; Illmann, Cornelia; McGrath, Lauren M; Mayerfeld, Catherine; Arepalli, Sampath; Barlassina, Cristina; Barr, Cathy L; Bellodi, Laura; Benarroch, Fortu; Berrió, Gabriel Bedoya; Bienvenu, O Joseph; Black, Donald W; Bloch, Michael H; Brentani, Helena; Bruun, Ruth D; Budman, Cathy L; Camarena, Beatriz; Campbell, Desmond D; Cappi, Carolina; Silgado, Julio C Cardona; Cavallini, Maria C; Chavira, Denise A; Chouinard, Sylvain; Cook, Edwin H; Cookson, M R; Coric, Vladimir; Cullen, Bernadette; Cusi, Daniele; Delorme, Richard; Denys, Damiaan; Dion, Yves; Eapen, Valsama; Egberts, Karin; Falkai, Peter; Fernandez, Thomas; Fournier, Eduardo; Garrido, Helena; Geller, Daniel; Gilbert, Donald L; Girard, Simon L; Grabe, Hans J; Grados, Marco A; Greenberg, Benjamin D; Gross-Tsur, Varda; Grünblatt, Edna; Hardy, John; Heiman, Gary A; Hemmings, Sian M J; Herrera, Luis D; Hezel, Dianne M; Hoekstra, Pieter J; Jankovic, Joseph; Kennedy, James L; King, Robert A; Konkashbaev, Anuar I; Kremeyer, Barbara; Kurlan, Roger; Lanzagorta, Nuria; Leboyer, Marion; Leckman, James F; Lennertz, Leonhard; Liu, Chunyu; Lochner, Christine; Lowe, Thomas L; Lupoli, Sara; Macciardi, Fabio; Maier, Wolfgang; Manunta, Paolo; Marconi, Maurizio; McCracken, James T; Mesa Restrepo, Sandra C; Moessner, Rainald; Moorjani, Priya; Morgan, Jubel; Muller, Heike; Murphy, Dennis L; Naarden, Allan L; Nurmi, Erika; Ochoa, William Cornejo; Ophoff, Roel A; Pakstis, Andrew J; Pato, Michele T; Pato, Carlos N; Piacentini, John; Pittenger, Christopher; Pollak, Yehuda; Rauch, Scott L; Renner, Tobias; Reus, Victor I; Richter, Margaret A; Riddle, Mark A; Robertson, Mary M; Romero, Roxana; Rosário, Maria C; Rosenberg, David; Ruhrmann, Stephan; Sabatti, Chiara; Salvi, Erika; Sampaio, Aline S; Samuels, Jack; Sandor, Paul; Service, Susan K; Sheppard, Brooke; Singer, Harvey S; Smit, Jan H|info:eu-repo/dai/nl/113700644; Stein, Dan J; Strengman, Eric; Tischfield, Jay A; Turiel, Maurizio; Valencia Duarte, Ana V; Vallada, Homero; Veenstra-VanderWeele, Jeremy; Walitza, Susanne; Wang, Ying; Weale, Mike; Weiss, Robert; Wendland, Jens R; Westenberg, Herman G M; Shugart, Yin Yao; Hounie, Ana G; Miguel, Euripedes C; Nicolini, Humberto; Wagner, Michael; Ruiz-Linares, Andres; Cath, Danielle C|info:eu-repo/dai/nl/194111423; McMahon, William; Posthuma, Danielle; Oostra, Ben A; Nestadt, Gerald; Rouleau, Guy A; Purcell, Shaun; Jenike, Michael A; Heutink, Peter; Hanna, Gregory L; Conti, David V; Arnold, Paul D; Freimer, Nelson B; Stewart, S Evelyn; Knowles, James A; Cox, Nancy J; Pauls, David L

OBJECTIVE: Obsessive-compulsive disorder (OCD) and Tourette's syndrome are highly heritable neurodevelopmental disorders that are thought to share genetic risk factors. However, the identification of definitive susceptibility genes for these etiologically complex disorders remains elusive. The

Cross-disorder genome-wide analyses suggest a complex genetic relationship between Tourette's syndrome and OCD

NARCIS (Netherlands)

Yu, Dongmei; Cusi, Daniele; Delorme, Richard; Denys, D.; Dion, Yves; Eapen, Valsama; Heutink, Peter; Cox, Nancy J; Pauls, David L

OBJECTIVE: Obsessive-compulsive disorder (OCD) and Tourette's syndrome are highly heritable neurodevelopmental disorders that are thought to share genetic risk factors. However, the identification of definitive susceptibility genes for these etiologically complex disorders remains elusive. The

Glutamate synapses in human cognitive disorders.

Science.gov (United States)

Volk, Lenora; Chiu, Shu-Ling; Sharma, Kamal; Huganir, Richard L

2015-07-08

Accumulating data, including those from large genetic association studies, indicate that alterations in glutamatergic synapse structure and function represent a common underlying pathology in many symptomatically distinct cognitive disorders. In this review, we discuss evidence from human genetic studies and data from animal models supporting a role for aberrant glutamatergic synapse function in the etiology of intellectual disability (ID), autism spectrum disorder (ASD), and schizophrenia (SCZ), neurodevelopmental disorders that comprise a significant proportion of human cognitive disease and exact a substantial financial and social burden. The varied manifestations of impaired perceptual processing, executive function, social interaction, communication, and/or intellectual ability in ID, ASD, and SCZ appear to emerge from altered neural microstructure, function, and/or wiring rather than gross changes in neuron number or morphology. Here, we review evidence that these disorders may share a common underlying neuropathy: altered excitatory synapse function. We focus on the most promising candidate genes affecting glutamatergic synapse function, highlighting the likely disease-relevant functional consequences of each. We first present a brief overview of glutamatergic synapses and then explore the genetic and phenotypic evidence for altered glutamate signaling in ID, ASD, and SCZ.

An adolescent with 48,xxyy syndrome with hypergonadotrophic hypogonadism, attention deficit hyperactive disorder and renal malformations

Directory of Open Access Journals (Sweden)

Prasad Katulanda

2012-01-01

Full Text Available 48,XXYY is a rare sex chromosome aneuploidy affecting 1 in 18,000 to 50,000 male births. They present with developmental delay, hypogonadism, gynecomastia, intention tremors, and a spectrum of neurodevelopmental and psychiatric disorders. At one time this condition was considered a variant of Klinefelter syndrome. In clinically suspected cases, 48,XXYY syndrome can be diagnosed by chromosome culture and karyotyping. This patient presented with hypergonadotrophic hypogonadism, attention deficit hyperactive disorder, and renal malformatons. Klinefelter syndrome was clinically suspected. The karyotype confirmed the diagnosis of 48,XXYY syndrome. This is the first reported case of 48,XXYY syndrome from Sri Lanka.

Ophthalmic implications of seasonal affective disorder

International Nuclear Information System (INIS)

Paramore, J.E.; King, V.M.

1989-01-01

A review of seasonal affective disorder (SAD) is presented with a discussion of its standard treatment of phototherapy. A number of ophthalmic implications related to SAD are proposed. These implications relate to both the condition and the phototherapy used in its treatment, especially the use of full spectrum light which contains ultraviolet and near ultraviolet radiation. 12 references

The neuro-immune axis: Prospect for novel treatments for mental disorders

NARCIS (Netherlands)

Kraneveld, Aletta D.; de Theije, Caroline G.M.; van Heesch, Floor; Borre, Yuliya; de Kivit, Sander; Olivier, Berend; Korte, Mechiel; Garssen, Johan

2014-01-01

Disturbed bidirectional pathways between the (central) nervous system and immune system have been implicated in various mental disorders, including depressive and neurodevelopmental disorders. In this minireview, the role of the neuro-immune axis and its targetability in relation to major depression

Negative subthreshold psychotic symptoms distinguish 22q11.2 deletion syndrome from other neurodevelopmental disorders: A two-site study.

Science.gov (United States)

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

2017-10-01

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.

Cross-Disorder Genome-Wide Analyses Suggest a Complex Genetic Relationship Between Tourette's Syndrome and OCD

NARCIS (Netherlands)

Yu, D.M.; Mathews, C.A.; Scharf, J.M.; Neale, B.M.; Davis, L.K.; Gamazon, E.R.; Derks, E.M.; Evans, P.; Edlund, C.K.; Crane, J.; Osiecki, L.; Gallagher, P.; Gerber, G.; Haddad, S.; Illmann, C.; McGrath, L.M.; Mayerfeld, C.; Arepalli, S.; Barlassina, C.; Barr, C.L.; Bellodi, L.; Benarroch, F.; Berrio, G.B.; Bienvenu, O.J.; Black, D.W.; Bloch, M.H.; Brentani, H.; Bruun, R.D.; Budman, C.L.; Camarena, B.; Campbell, D.D.; Cappi, C.; Silgado, J.C.C.; Cavallini, M.C.; Chavira, D.A.; Chouinard, S.; Cook, E.H.; Cookson, M.R.; Coric, V.; Cullen, B.; Cusi, D.; Delorme, R.; Denys, D.; Dion, Y.; Eapen, V.; Egberts, K.; Falkai, P.; Fernandez, T.; Fournier, E.; Garrido, H.; Geller, D.; Gilbert, D.L.; Girard, S.L.; Grabe, H.J.; Grados, M.A.; Greenberg, B.D.; Gross-Tsur, V.; Grunblatt, E.; Hardy, J.; Heiman, G.A.; Hemmings, S.M.J.; Herrera, L.D.; Hezel, D.M.; Hoekstra, P.J.; Jankovic, J.; Kennedy, J.L.; King, R.A.; Konkashbaev, A.I.; Kremeyer, B.; Kurlan, R.; Lanzagorta, N.; Leboyer, M.; Leckman, J.F.; Lennertz, L.; Liu, C.Y.; Lochner, C.; Lowe, T.L.; Lupoli, S.; Macciardi, F.; Maier, W.; Manunta, P.; Marconi, M.; McCracken, J.T.; Restrepo, S.C.M.; Moessner, R.; Moorjani, P.; Morgan, J.; Muller, H.; Murphy, D.L.; Naarden, A.L.; Nurmi, E.; Ochoa, W.C.; Ophoff, R. A.; Pakstis, A.J.; Pato, M.T.; Pato, C.N.; Piacentini, J.; Pittenger, C.; Pollak, Y.; Smit, J.H.; Posthuma, D.; Cox, N.J.; Pauls, D.L.

2015-01-01

Objective: Obsessive-compulsive disorder (OCD) and Tourette's syndrome are highly heritable neurodevelopmental disorders that are thought to share genetic risk factors. However, the identi fication of definitive susceptibility genes for these etiologically complex disorders remains elusive. The

Annual Research Review: Infant Development, Autism, and ADHD--Early Pathways to Emerging Disorders

Science.gov (United States)

Johnson, Mark H.; Gliga, Teodora; Jones, Emily; Charman, Tony

2015-01-01

Background: Autism spectrum disorders (ASD) and attention deficit hyperactivity disorder (ADHD) are two of the most common neurodevelopmental disorders, with a high degree of co-occurrence. Methods: Prospective longitudinal studies of infants who later meet criteria for ASD or ADHD offer the opportunity to determine whether the two disorders share…

The effect of erythropoietin on cognition in affective disorders

DEFF Research Database (Denmark)

Ott, Caroline Vintergaard; Vinberg, Maj; Kessing, Lars V

2016-01-01

impairment predicted treatment-efficacy. Pearson correlations were used to assess associations between objective and subjective cognition, quality of life and socio-occupational capacity. EPO improved speed of complex cognitive processing across affective disorders at weeks 9 and 14 (p≤0.05). In EPO......-efficacy and (III) if cognitive improvement correlates with better subjective cognitive function, quality of life and socio-occupational capacity. Patients with unipolar or bipolar disorder were randomized to eight weekly EPO (N=40) or saline (N=39) infusions. Cognition, mood, quality of life and socio...... improvement correlated with reduced cognitive complaints but not with quality of life or socio-occupational function. As the analyses were performed post-hoc, findings are only hypothesis-generating. In conclusion, pro-cognitive effects of EPO occurred across affective disorders. Neuropsychological screening...

Deletions and de novo mutations of SOX11 are associated with a neurodevelopmental disorder with features of Coffin-Siris syndrome.

Science.gov (United States)

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

2016-03-01

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/

Predictors of recurrence in affective disorder. A case register study

DEFF Research Database (Denmark)

Kessing, Lars Vedel; Andersen, Per Kragh; Mortensen, P.B.

1998-01-01

BACKGROUND: The risk of recurrence in affective disorder is affected by socio-demographic variables such as gender, age at onset and marital status and by illness related factors as the length of previous episodes and the total duration of the illness. The present study investigated how the effect...... of these variables changed with the progression of the illness. METHOD: Using survival analysis, the risk of recurrence was estimated in a case register study including all hospital admissions with primary affective disorder in Denmark during 1971-1993. RESULTS: Totally, 20350 first admission patients had been...... disorder socio-demographic variables such as gender, age at onset and marital status act as risk factors for further recurrence. Later, however, the illness itself seem to follow its own rhythm regardless of prior predictors. LIMITATION: The data relate to re-admissions rather than recurrence...

Long-term neurodevelopmental outcome of monochorionic and matched dichorionic twins.

Directory of Open Access Journals (Sweden)

Karien E A Hack

Full Text Available BACKGROUND: Monochorionic (MC twins are at increased risk for perinatal mortality and serious morbidity due to the presence of placental vascular anastomoses. Cerebral injury can be secondary to haemodynamic and hematological disorders during pregnancy (especially twin-to-twin transfusion syndrome (TTTS or intrauterine co-twin death or from postnatal injury associated with prematurity and low birth weight, common complications in twin pregnancies. We investigated neurodevelopmental outcome in MC and dichorionic (DC twins at the age of two years. METHODS: This was a prospective cohort study. Cerebral palsy (CP was studied in 182 MC infants and 189 DC infants matched for weight and age at delivery, gender, ethnicity of the mother and study center. After losses to follow-up, 282 of the 366 infants without CP were available to be tested with the Griffiths Mental Developmental Scales at 22 months corrected age, all born between January 2005 and January 2006 in nine perinatal centers in The Netherlands. Due to phenotypic (unalikeness in mono-or dizygosity, the principal investigator was not blinded to chorionic status; perinatal outcome, with exception of co-twin death, was not known to the examiner. FINDINGS: Four out of 182 MC infants had CP (2.2% - two of the four CP-cases were due to complications specific to MC twin pregnancies (TTTS and co-twin death and the other two cases of CP were the result of cystic PVL after preterm birth - compared to one sibling of a DC twin (0.5%; OR 4.2, 95% CI 0.5-38.2 of unknown origin. Follow-up rate of neurodevelopmental outcome by Griffith's test was 76%. The majority of 2-year-old twins had normal developmental status. There were no significant differences between MC and DC twins. One MC infant (0.7% had a developmental delay compared to 6 DC infants (4.2%; OR 0.2, 95% 0.0-1.4. Birth weight discordancy did not influence long-term outcome, though the smaller twin had slightly lower developmental scores than its

Cross-disorder genome-wide analyses suggest a complex genetic relationship between Tourette's syndrome and OCD

NARCIS (Netherlands)

Yu, Dongmei; Mathews, Carol A.; Scharf, Jeremiah M.; Neale, Benjamin M.; Davis, Lea K.; Gamazon, Eric R.; Derks, Eske M.; Evans, Patrick; Edlund, Christopher K.; Crane, Jacquelyn; Fagerness, Jesen A.; Osiecki, Lisa; Gallagher, Patience; Gerber, Gloria; Haddad, Stephen; Illmann, Cornelia; McGrath, Lauren M.; Mayerfeld, Catherine; Arepalli, Sampath; Barlassina, Cristina; Barr, Cathy L.; Bellodi, Laura; Benarroch, Fortu; Berrió, Gabriel Bedoya; Bienvenu, O. Joseph; Black, Donald W.; Bloch, Michael H.; Brentani, Helena; Bruun, Ruth D.; Budman, Cathy L.; Camarena, Beatriz; Campbell, Desmond D.; Cappi, Carolina; Silgado, Julio C. Cardona; Cavallini, Maria C.; Chavira, Denise A.; Chouinard, Sylvain; Cook, Edwin H.; Cookson, M. R.; Coric, Vladimir; Cullen, Bernadette; Cusi, Daniele; Delorme, Richard; Denys, Damiaan; Dion, Yves; Eapen, Valsama; Egberts, Karin; Falkai, Peter; Fernandez, Thomas; Fournier, Eduardo; Garrido, Helena; Geller, Daniel; Gilbert, Donald L.; Girard, Simon L.; Grabe, Hans J.; Grados, Marco A.; Greenberg, Benjamin D.; Gross-Tsur, Varda; Grünblatt, Edna; Hardy, John; Heiman, Gary A.; Hemmings, Sian M. J.; Herrera, Luis D.; Hezel, Dianne M.; Hoekstra, Pieter J.; Jankovic, Joseph; Kennedy, James L.; King, Robert A.; Konkashbaev, Anuar I.; Kremeyer, Barbara; Kurlan, Roger; Lanzagorta, Nuria; Leboyer, Marion; Leckman, James F.; Lennertz, Leonhard; Liu, Chunyu; Lochner, Christine; Lowe, Thomas L.; Lupoli, Sara; Macciardi, Fabio; Maier, Wolfgang; Manunta, Paolo; Marconi, Maurizio; McCracken, James T.; Mesa Restrepo, Sandra C.; Moessner, Rainald; Moorjani, Priya; Morgan, Jubel; Muller, Heike; Murphy, Dennis L.; Naarden, Allan L.; Nurmi, Erika; Ochoa, William Cornejo; Ophoff, Roel A.; Pakstis, Andrew J.; Pato, Michele T.; Pato, Carlos N.; Piacentini, John; Pittenger, Christopher; Pollak, Yehuda; Rauch, Scott L.; Renner, Tobias; Reus, Victor I.; Richter, Margaret A.; Riddle, Mark A.; Robertson, Mary M.; Romero, Roxana; Rosário, Maria C.; Rosenberg, David; Ruhrmann, Stephan; Sabatti, Chiara; Salvi, Erika; Sampaio, Aline S.; Samuels, Jack; Sandor, Paul; Service, Susan K.; Sheppard, Brooke; Singer, Harvey S.; Smit, Jan H.; Stein, Dan J.; Strengman, Eric; Tischfield, Jay A.; Turiel, Maurizio; Valencia Duarte, Ana V.; Vallada, Homero; Veenstra-Vanderweele, Jeremy; Walitza, Susanne; Wang, Ying; Weale, Mike; Weiss, Robert; Wendland, Jens R.; Westenberg, Herman G. M.; Shugart, Yin Yao; Hounie, Ana G.; Miguel, Euripedes C.; Nicolini, Humberto; Wagner, Michael; Ruiz-Linares, Andres; Cath, Danielle C.; McMahon, William; Posthuma, Danielle; Oostra, Ben A.; Nestadt, Gerald; Rouleau, Guy A.; Purcell, Shaun; Jenike, Michael A.; Heutink, Peter; Hanna, Gregory L.; Conti, David V.; Arnold, Paul D.; Freimer, Nelson B.; Stewart, S. Evelyn; Knowles, James A.; Cox, Nancy J.; Pauls, David L.

2015-01-01

Obsessive-compulsive disorder (OCD) and Tourette's syndrome are highly heritable neurodevelopmental disorders that are thought to share genetic risk factors. However, the identification of definitive susceptibility genes for these etiologically complex disorders remains elusive. The authors report a

Neurodevelopmental profiles of children with glutaric aciduria type I diagnosed by newborn screening: a follow-up case series.

Science.gov (United States)

Brown, Amy; Crowe, Louise; Beauchamp, Miriam H; Anderson, Vicki; Boneh, Avihu

2015-01-01

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.

Early Conventional MRI for Prediction of Neurodevelopmental Impairment in Extremely-Low-Birth-Weight Infants.

Science.gov (United States)

Slaughter, Laurel A; Bonfante-Mejia, Eliana; Hintz, Susan R; Dvorchik, Igor; Parikh, Nehal A

2016-01-01

Extremely-low-birth-weight (ELBW; ≤1,000 g) infants are at high risk for neurodevelopmental impairments. Conventional brain MRI at term-equivalent age is increasingly used for prediction of outcomes. However, optimal prediction models remain to be determined, especially for cognitive outcomes. The aim was to evaluate the accuracy of a data-driven MRI scoring system to predict neurodevelopmental impairments. 122 ELBW infants had a brain MRI performed at term-equivalent age. Conventional MRI findings were scored with a standardized algorithm and tested using a multivariable regression model to predict neurodevelopmental impairment, defined as one or more of the following at 18-24 months' corrected age: cerebral palsy, bilateral blindness, bilateral deafness requiring amplification, and/or cognitive/language delay. Results were compared with a commonly cited scoring system. In multivariable analyses, only moderate-to-severe gyral maturational delay was a significant predictor of overall neurodevelopmental impairment (OR: 12.6, 95% CI: 2.6, 62.0; p neurodevelopmental impairment/death. Diffuse cystic abnormality was a significant predictor of cerebral palsy (OR: 33.6, 95% CI: 4.9, 229.7; p neurodevelopmental impairment. In our cohort, conventional MRI at term-equivalent age exhibited high specificity in predicting neurodevelopmental outcomes. However, sensitivity was suboptimal, suggesting additional clinical factors and biomarkers are needed to enable accurate prognostication. © 2016 S. Karger AG, Basel.

No association between serum cholesterol and death by suicide in patients with schizophrenia, bipolar affective disorder, or major depressive disorder.

Science.gov (United States)

Park, Subin; Yi, Ki Kyoung; Na, Riji; Lim, Ahyoung; Hong, Jin Pyo

2013-12-05

Previous research on serum total cholesterol and suicidality has yielded conflicting results. Several studies have reported a link between low serum total cholesterol and suicidality, whereas others have failed to replicate these findings, particularly in patients with major affective disorders. These discordant findings may reflect the fact that studies often do not distinguish between patients with bipolar and unipolar depression; moreover, definitions and classification schemes for suicide attempts in the literature vary widely. Subjects were patients with one of the three major psychiatric disorders commonly associated with suicide: schizophrenia, bipolar affective disorder, and major depressive disorder (MDD). We compared serum lipid levels in patients who died by suicide (82 schizophrenia, 23 bipolar affective disorder, and 67 MDD) and non-suicide controls (200 schizophrenia, 49 bipolar affective disorder, and 175 MDD). Serum lipid profiles did not differ between patients who died by suicide and control patients in any diagnostic group. Our results do not support the use of biological indicators such as serum total cholesterol to predict suicide risk among patients with a major psychiatric disorder.

Development of an integrated model of personality, personality disorders and severe axis I disorders, with special reference to major affective disorders.

Science.gov (United States)

von Zerssen, Detlev

2002-04-01

A unidimensional model of the relationships between normal temperament, psychopathic variants of it and the two main forms of so-called endogenous psychoses (major affective disorders and schizophrenia) was derived from Kretschmer's constitutional typology. It was, however, not confirmed by means of a biometric approach nor was Kretschmer's broad concept of cyclothymia as a correlate of physical stoutness on the one hand and major affective disorders on the other supported by empirical data. Yet the concept of the 'melancholic type' of personality of patients with severe unipolar major depression (melancholia) which resembles descriptions by psychoanalysts could be corroborated. This was also true for the 'manic type' of personality as a (premorbid) correlate of predominantly manic forms of a bipolar I disorder. As predicted from a spectrum concept of major affective disorders, the ratio of traits of either type co-varied with the ratio of the depressive and the manic components in the long-term course of such a disorder. The two types of premorbid personality and a rare variant of the 'manic type', named 'relaxed, easy-going type', were conceived as 'affective types' dominating in major affective disorders. They are opposed to three 'neurotoid types' prevailing in so-called neurotic disorders as well as in schizophrenic psychoses. The similarity among the types can be visualized as spatial relationships in a circular, i.e. a two-dimensional, model (circumplex). Personality disorders as maladapted extreme variants of personality are, by definition, located outside the circle, mainly along its 'neurotoid' side. However, due to their transitional nature, axis I disorders cannot be represented adequately within the plane which represents (adapted as well as maladapted) forms of habitual behaviour (personality types and disorders, respectively). To integrate them into the spatial model of similarity interrelations, a dimension of actual psychopathology has to be added

Genetic disorders affecting white matter in the pediatric age.

Science.gov (United States)

Di Rocco, Maja; Biancheri, Roberta; Rossi, Andrea; Filocamo, Mirella; Tortori-Donati, Paolo

2004-08-15

Pediatric white matter disorders can be distinguished into well-defined leukoencephalopathies, and undefined leukoencephalopathies. The first category may be subdivided into: (a) hypomyelinating disorders; (b) dysmyelinating disorders; (c) leukodystrophies; (d) disorders related to cystic degeneration of myelin; and (e) disorders secondary to axonal damage. The second category, representing up to 50% of leukoencephalopathies in childhood, requires a multidisciplinar approach in order to define novel homogeneous subgroups of patients, possibly representing "new genetic disorders" (such as megalencephalic leukoencepahlopathy with subcortical cysts and vanishing white matter disease that have recently been identified). In the majority of cases, pediatric white matter disorders are inherited diseases. An integrated description of the clinical, neuroimaging and pathophysiological features is crucial for categorizing myelin disorders and better understanding their genetic basis. A review of the genetic disorders affecting white matter in the pediatric age, including some novel entities, is provided. Copyright 2004 Wiley-Liss, Inc.

Neurodevelopmental consequences of being born SGA

NARCIS (Netherlands)

van Wassenaer, Aleid

2005-01-01

Fetal growth retardation is associated with postnatal growth retardation and cardio-vascular and metabolic problems later on in life. Less well described are the consequences of neurodevelopmental outcome. The term SGA is associated with mild to moderate school problems, still present in late

Home-based, early intervention with mechatronic toys for preterm infants at risk of neurodevelopmental disorders (CARETOY): a RCT protocol.

Science.gov (United States)

Sgandurra, Giuseppina; Bartalena, Laura; Cioni, Giovanni; Greisen, Gorm; Herskind, Anna; Inguaggiato, Emanuela; Lorentzen, Jakob; Nielsen, Jens Bo; Sicola, Elisa

2014-10-15

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

Chromosomal Abnormalities and Putative Susceptibility Genes in Autism Spectrum Disorders

DEFF Research Database (Denmark)

Nielsen, Mette Gilling

Autism spectrum disorders (ASDs) is a heterogeneous group of neurodevelopmental disorders with a significant genetic component as shown by family and twin studies. However, only a few genes have repeatedly been shown to be involved in the development of ASDs. The aim of this study has been...

The Relationship between Autism Spectrum Disorder and Melatonin during Fetal Development

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Yunho Jin

2018-01-01

Full Text Available The aim of this review is to clarify the interrelationship between melatonin and autism spectrum disorder (ASD during fetal development. ASD refers to a diverse range of neurodevelopmental disorders characterized by social deficits, impaired communication, and stereotyped or repetitive behaviors. Melatonin, which is secreted by the pineal gland, has well-established neuroprotective and circadian entraining effects. During pregnancy, the hormone crosses the placenta into the fetal circulation and transmits photoperiodic information to the fetus allowing the establishment of normal sleep patterns and circadian rhythms that are essential for normal neurodevelopment. Melatonin synthesis is frequently impaired in patients with ASD. The hormone reduces oxidative stress, which is harmful to the central nervous system. Therefore, the neuroprotective and circadian entraining roles of melatonin may reduce the risk of neurodevelopmental disorders such as ASD.

Daily weather variables and affective disorder admissions to psychiatric hospitals

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McWilliams, Stephen; Kinsella, Anthony; O'Callaghan, Eadbhard

2014-12-01

Numerous studies have reported that admission rates in patients with affective disorders are subject to seasonal variation. Notwithstanding, there has been limited evaluation of the degree to which changeable daily meteorological patterns influence affective disorder admission rates. A handful of small studies have alluded to a potential link between psychiatric admission rates and meteorological variables such as environmental temperature (heat waves in particular), wind direction and sunshine. We used the Kruskal-Wallis test, ARIMA and time-series regression analyses to examine whether daily meteorological variables—namely wind speed and direction, barometric pressure, rainfall, hours of sunshine, sunlight radiation and temperature—influence admission rates for mania and depression across 12 regions in Ireland over a 31-year period. Although we found some very weak but interesting trends for barometric pressure in relation to mania admissions, daily meteorological patterns did not appear to affect hospital admissions overall for mania or depression. Our results do not support the small number of papers to date that suggest a link between daily meteorological variables and affective disorder admissions. Further study is needed.

Electronic monitoring of patients with bipolar affective disorder

DEFF Research Database (Denmark)

Jacoby, Anne Sophie; Faurholt-Jepsen, Maria; Vinberg, Maj

2012-01-01

Bipolar disorder is a great challenge to patients, relatives and clinicians, and there is a need for development of new methods to identify prodromal symptoms of affective episodes in order to provide efficient preventive medical and behavioural intervention. Clinical trials prove that electronic...... monitoring is a feasible, valid and acceptable method. Hence it is recommended, that controlled trials on the effect of electronic monitoring on patients' course of illness, level of function and quality of life are conducted.......Bipolar disorder is a great challenge to patients, relatives and clinicians, and there is a need for development of new methods to identify prodromal symptoms of affective episodes in order to provide efficient preventive medical and behavioural intervention. Clinical trials prove that electronic...

Altered small-world topology of structural brain networks in infants with intrauterine growth restriction and its association with later neurodevelopmental outcome.

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Batalle, Dafnis; Eixarch, Elisenda; Figueras, Francesc; Muñoz-Moreno, Emma; Bargallo, Nuria; Illa, Miriam; Acosta-Rojas, Ruthy; Amat-Roldan, Ivan; Gratacos, Eduard

2012-04-02

Intrauterine growth restriction (IUGR) due to placental insufficiency affects 5-10% of all pregnancies and it is associated with a wide range of short- and long-term neurodevelopmental disorders. Prediction of neurodevelopmental outcomes in IUGR is among the clinical challenges of modern fetal medicine and pediatrics. In recent years several studies have used magnetic resonance imaging (MRI) to demonstrate differences in brain structure in IUGR subjects, but the ability to use MRI for individual predictive purposes in IUGR is limited. Recent research suggests that MRI in vivo access to brain connectivity might have the potential to help understanding cognitive and neurodevelopment processes. Specifically, MRI based connectomics is an emerging approach to extract information from MRI data that exhaustively maps inter-regional connectivity within the brain to build a graph model of its neural circuitry known as brain network. In the present study we used diffusion MRI based connectomics to obtain structural brain networks of a prospective cohort of one year old infants (32 controls and 24 IUGR) and analyze the existence of quantifiable brain reorganization of white matter circuitry in IUGR group by means of global and regional graph theory features of brain networks. Based on global and regional analyses of the brain network topology we demonstrated brain reorganization in IUGR infants at one year of age. Specifically, IUGR infants presented decreased global and local weighted efficiency, and a pattern of altered regional graph theory features. By means of binomial logistic regression, we also demonstrated that connectivity measures were associated with abnormal performance in later neurodevelopmental outcome as measured by Bayley Scale for Infant and Toddler Development, Third edition (BSID-III) at two years of age. These findings show the potential of diffusion MRI based connectomics and graph theory based network characteristics for estimating differences in the

Longitudinal population-based studies of affective disorders: Where to from here?

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Beard John R

2008-09-01

Full Text Available Abstract Background Longitudinal, population-based, research is important if we are to better characterize the lifetime patterns and determinants of affective disorders. While studies of this type are becoming increasingly prevalent, there has been little discussion about the limitations of the methods commonly used. Methods Discussion paper including a brief review of key prospective population-based studies as the basis for a critical appraisal of current approaches. Results We identified a number of common methodological weaknesses that restrict the potential of longitudinal research to characterize the diversity, prognosis, and determinants of affective disorders over time. Most studies using comprehensive diagnostic instruments have either been of relatively brief duration, or have suffered from long periods between waves. Most etiologic research has focused on first onset diagnoses, although these may be relatively uncommon after early adulthood and the burden of mental disorders falls more heavily on individuals with recurring disorders. Analysis has tended to be based on changes in diagnostic status rather than anges in symptom levels, limiting study power. Diagnoses have generally been treated as homogeneous entities and few studies have explored whether diagnostic subtypes such as atypical depression vary in their etiology or prognosis. Little research has considered whether there are distinct trajectories of symptoms over time and most has focused on individual disorders such as depression, rather than considering the relationship over time between symptoms of different affective disorders. There has also been limited longitudinal research on factors in the physical or social environment that may influence the onset, recurrence or chronicity of symptoms. Conclusion Many important, and in some respects quite basic, questions remain about the trajectory of depression and anxiety disorders over the life course and the factors that

Term-equivalent functional brain maturational measures predict neurodevelopmental outcomes in premature infants.

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El Ters, Nathalie M; Vesoulis, Zachary A; Liao, Steve M; Smyser, Christopher D; Mathur, Amit M

2018-04-01

Term equivalent age (TEA) brain MRI identifies preterm infants at risk for adverse neurodevelopmental outcomes. But some infants may experience neurodevelopmental impairments even in the absence of neuroimaging abnormalities. Evaluate the association of TEA amplitude-integrated EEG (aEEG) measures with neurodevelopmental outcomes at 24-36 months corrected age. We performed aEEG recordings and brain MRI at TEA (mean post-menstrual age of 39 (±2) weeks in a cohort of 60 preterm infants born at a mean gestational age of 26 (±2) weeks. Forty-four infants underwent Bayley Scales of Infant Development, 3rd Edition (BSID-III) testing at 24-36 months corrected age. Developmental delay was defined by a score greater than one standard deviation below the mean (neurodevelopmental outcomes was assessed using odds ratio, then adjusted for confounding variables using logistic regression. Infants with developmental delay in any domain had significantly lower values of SEF 90 . Absent cyclicity was more prevalent in infants with cognitive and motor delay. Both left and right SEF 90  neurodevelopmental outcomes. Therefore, a larger study is needed to validate these results in premature infants at low and high risk of brain injury. Copyright © 2018. Published by Elsevier B.V.

Allostatic load in parents of children with developmental disorders: moderating influence of positive affect.

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Song, Jieun; Mailick, Marsha R; Ryff, Carol D; Coe, Christopher L; Greenberg, Jan S; Hong, Jinkuk

2014-02-01

This study examines whether parents of children with developmental disorders are at risk of elevated allostatic load relative to control parents and whether positive affect moderates difference in risk. In all, 38 parents of children with developmental disorders and 38 matched comparison parents were analyzed. Regression analyses revealed a significant interaction between parent status and positive affect: parents of children with developmental disorders had lower allostatic load when they had higher positive affect, whereas no such association was evident for comparison parents. The findings suggest that promoting greater positive affect may lower health risks among parents of children with developmental disorders.

Developmental origins of brain disorders: roles for dopamine

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Kelli M Money

2013-12-01

Full Text Available Neurotransmitters and neuromodulators, such as dopamine, participate in a wide range of behavioral and cognitive functions in the adult brain, including movement, cognition, and reward. Dopamine-mediated signaling plays a fundamental neurodevelopmental role in forebrain differentiation and circuit formation. These developmental effects, such as modulation of neuronal migration and dendritic growth, occur before synaptogenesis and demonstrate novel roles for dopaminergic signaling beyond neuromodulation at the synapse. Pharmacologic and genetic disruptions demonstrate that these effects are brain region- and receptor subtype-specific. For example, the striatum and frontal cortex exhibit abnormal neuronal structure and function following prenatal disruption of dopamine receptor signaling. Alterations in these processes are implicated in the pathophysiology of neuropsychiatric disorders, and emerging studies of neurodevelopmental disruptions may shed light on the pathophysiology of abnormal neuronal circuitry in neuropsychiatric disorders.

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.

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Strober, Michael; Freeman, Roberta; Lampert, Carlyn; Diamond, Jane

2007-11-01

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.

Systems genetics identifies a convergent gene network for cognition and neurodevelopmental disease.

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Johnson, Michael R; Shkura, Kirill; Langley, Sarah R; Delahaye-Duriez, Andree; Srivastava, Prashant; Hill, W David; Rackham, Owen J L; Davies, Gail; Harris, Sarah E; Moreno-Moral, Aida; Rotival, Maxime; Speed, Doug; Petrovski, Slavé; Katz, Anaïs; Hayward, Caroline; Porteous, David J; Smith, Blair H; Padmanabhan, Sandosh; Hocking, Lynne J; Starr, John M; Liewald, David C; Visconti, Alessia; Falchi, Mario; Bottolo, Leonardo; Rossetti, Tiziana; Danis, Bénédicte; Mazzuferi, Manuela; Foerch, Patrik; Grote, Alexander; Helmstaedter, Christoph; Becker, Albert J; Kaminski, Rafal M; Deary, Ian J; Petretto, Enrico

2016-02-01

Genetic determinants of cognition are poorly characterized, and their relationship to genes that confer risk for neurodevelopmental disease is unclear. Here we performed a systems-level analysis of genome-wide gene expression data to infer gene-regulatory networks conserved across species and brain regions. Two of these networks, M1 and M3, showed replicable enrichment for common genetic variants underlying healthy human cognitive abilities, including memory. Using exome sequence data from 6,871 trios, we found that M3 genes were also enriched for mutations ascertained from patients with neurodevelopmental disease generally, and intellectual disability and epileptic encephalopathy in particular. M3 consists of 150 genes whose expression is tightly developmentally regulated, but which are collectively poorly annotated for known functional pathways. These results illustrate how systems-level analyses can reveal previously unappreciated relationships between neurodevelopmental disease-associated genes in the developed human brain, and provide empirical support for a convergent gene-regulatory network influencing cognition and neurodevelopmental disease.

Comparing diagnostic classification of neurobehavioral disorder associated with prenatal alcohol exposure with the Canadian fetal alcohol spectrum disorder guidelines: a cohort study.

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Sanders, James L; Breen, Rebecca E Hudson; Netelenbos, Nicole

2017-01-01

Diagnostic criteria have recently been introduced in the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5), for neurobehavioral disorder associated with prenatal alcohol exposure (ND-PAE). The purpose of this study is to assess the classification of this condition using the Canadian fetal alcohol spectrum disorder (FASD) multidisciplinary diagnostic guidelines as the standard of comparison. First, classification of ND-PAE was compared with Canadian FASD diagnoses of fetal alcohol syndrome (FAS), partial FAS and alcohol-related neurodevelopmental disorder. Second, classification of ND-PAE was compared with FAS and pFAS only, a criterion for which includes facial features highly predictive of prenatal alcohol exposure and effects. Eighty-two patients underwent multidisciplinary clinical evaluations using the Canadian FASD diagnostic guidelines between 2011 and 2015. Two clinicians independently reviewed patient files for evidence of diagnostic criteria for ND-PAE when applying an impairment cut-off level of 2 or more standard deviations below the mean, or clinically significant impairment in the absence of standardized norm-referenced measures. Good interrater reliability was established between clinicians (κ = 0.79). Classifications of ND-PAE and Canadian FASD diagnoses, including alcohol-related neurodevelopmental disorder, were moderately correlated (Cramer V [82] = 0.44, p 0.05). Although there is considerable overlap between both sets of criteria, ND-PAE was less likely to identify patients with FASD. Although the neurobehavioral domains assessed by ND-PAE are supported in research, its diagnostic structure restricts the identification of FASD at the impairment threshold of 2 or more standard deviations. A disconnect remains with regard to impairment thresholds between FASD, which relies on neurodevelopmental data, and ND-PAE, which relies on clinical judgment.

Premorbid multivariate markers of neurodevelopmental instability in the prediction of adult schizophrenia-spectrum disorder

DEFF Research Database (Denmark)

Golembo-Smith, Shana; Schiffman, Jason; Kline, Emily

2012-01-01

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...

Electroconvulsive therapy and subsequent epilepsy in patients with affective disorders

DEFF Research Database (Denmark)

Bøg, Fie Krossdal; Jørgensen, Martin Balslev; Andersen, Zorana Jovanovic

2018-01-01

and antipsychotic medication use. RESULTS: A total of 5875 patients had at least one ECT and 1873 patients developed epilepsy (Incidence rate: 213 pr. 100,000 person years) during the follow-up of mean 5 years. In patients below age 40 years, ECT was associated with a higher rate of epilepsy after adjustment...... epilepsy in patients with affective disorder. We also explored whether any association varied with number of ECTs and time since last treatment. METHODS: All 169,457 patients with first hospital contact for an affective disorder between January 2005 and December 2015 were identified in the Danish National...... for covariables (Hazard Ratio (HR) = 1.84; 95% Confidence Intervals (CI) = [1.24-2.74]). In patients aged 41-60 years ECT was not associated with epilepsy, while for those above 60 treated with ECT the rate was lower (HR = 0.57; (95% CI = [0.37-0.89]). CONCLUSION: In patients with affective disorders, we found...

Rapid cycling bipolar affective disorder and recurrent strokes secondary to high blood homocysteine.

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Awara, Mahmoud A; Zahid, Shazia; Elnenaei, Manal O

2014-10-01

The interface between psychiatric disorders and organicity has been a matter for contentious debate. To report an interesting clinical case of moderate homocystinuria presenting with significant psychiatric and neurological deficits. A case report highlighting the impact of homocystinuria on producing intractable rapid cycling bipolar affective disorder. Homocystinuria is a frequently missed cause for treatment-resistant bipolar affective disorder.

Anatomy and Cell Biology of Autism Spectrum Disorder : Lessons from Human Genetics

NARCIS (Netherlands)

Kleijer, Kristel T E; Huguet, Guillaume; Tastet, Julie; Bourgeron, Thomas; Burbach, J P H

2017-01-01

Until recently autism spectrum disorder (ASD) was regarded as a neurodevelopmental condition with unknown causes and pathogenesis. In the footsteps of the revolution of genome technologies and genetics, and with its high degree of heritability, ASD became the first neuropsychiatric disorder for

Associations between positive and negative affect and 12-month physical disorders in a national sample.

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Weiser, Eric B

2012-06-01

Associations between positive and negative affect and a range of 12-month physical disorders were investigated in the Midlife Development in the United States Survey, a nationally representative sample of 3,032 adults ages 25-74. These associations were examined, controlling for relevant sociodemographic and psychiatric covariates. High positive affect was associated with decreased risk of physical disorders, whereas high negative affect was associated with increased risk. However, associations between positive affect and physical disorders were partially attenuated following adjustment for concurrent negative affect. Additionally, high affect balance was associated with decreased risk of physical disorders before and after adjustments. These findings underscore the relevance of affective disposition in health status, suggesting that both positive and negative affect may serve as viable health risk parameters.

The effect of comorbid alcoholism on recurrence in affective disorder

DEFF Research Database (Denmark)

Kessing, L V

1999-01-01

BACKGROUND: Studies of the effect of comorbid alcoholism on the risk of recurrence in affective disorder have given contradictory results. METHOD: Using survival analysis, the rate of recurrence was calculated in a case register study including all hospital admissions with primary affective...... an auxiliary diagnosis of alcoholism. Patients with a current auxiliary diagnosis of alcoholism had increased rate of recurrence following the first three affective episodes but not following subsequent episodes compared with patients without auxiliary diagnoses. The effect of alcoholism declined...... with the number of episodes. In contrast, no effect was found of other auxiliary diagnoses on the rate of recurrence. CONCLUSION: Rehospitalisation data suggest that concurrent alcoholism increases the risk of recurrence of affective episodes during the initial course of unipolar and bipolar disorder but has...

Neurodevelopmental outcome after cardiac surgery utilizing cardiopulmonary bypass in children

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Aymen N Naguib

2015-01-01

Full Text Available Introduction: Modulating the stress response and perioperative factors can have a paramount impact on the neurodevelopmental outcome of infants who undergo cardiac surgery utilizing cardiopulmonary bypass. Materials and Methods: In this single center prospective follow-up study, we evaluated the impact of three different anesthetic techniques on the neurodevelopmental outcomes of 19 children who previously underwent congenital cardiac surgery within their 1 st year of life. Cases were done from May 2011 to December 2013. Children were assessed using the Stanford-Binet Intelligence Scales (5 th edition. Multiple regression analysis was used to test different parental and perioperative factors that could significantly predict the different neurodevelopmental outcomes in the entire cohort of patients. Results: When comparing the three groups regarding the major cognitive scores, a high-dose fentanyl (HDF patients scored significantly higher than the low-dose fentanyl (LDF + dexmedetomidine (DEX (LDF + DEX group in the quantitative reasoning scores (106 ± 22 vs. 82 ± 15 P = 0.046. The bispectral index (BIS value at the end of surgery for the -LDF group was significantly higher than that in LDF + DEX group (P = 0.011. For the entire cohort, a strong correlation was seen between the standard verbal intelligence quotient (IQ score and the baseline adrenocorticotropic hormone level, the interleukin-6 level at the end of surgery and the BIS value at the end of the procedure with an R 2 value of 0.67 and P < 0.04. There was an inverse correlation between the cardiac Intensive Care Unit length of stay and the full-scale IQ score (R = 0.4675 and P 0.027. Conclusions: Patients in the HDF group demonstrated overall higher neurodevelopmental scores, although it did not reach statistical significance except in fluid reasoning scores. Our results may point to a possible correlation between blunting the stress response and improvement of the neurodevelopmental

Lobular patterns of cerebellar resting-state connectivity in adults with Autism Spectrum Disorder.

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Olivito, Giusy; Lupo, Michela; Laghi, Fiorenzo; Clausi, Silvia; Baiocco, Roberto; Cercignani, Mara; Bozzali, Marco; Leggio, Maria

2018-03-01