Distinct genetic patterns of shared and unique genes across four neurodevelopmental disorders.

Neurodevelopmental disorders, including autism spectrum disorder (ASD), intellectual disability (ID), developmental disorders (DD) and epileptic encephalopathy (EE), have a strong clinical comorbidity, which indicates a common genetic etiology across various disorders. However, the underlying genetic mechanisms of comorbidity and specificity remain unknown across neurodevelopmental disorders. Based on de novo mutations, we compared systematically the functional characteristics between shared and unique genes under these disorders, as well as the spatiotemporal trajectory of development in brain and common molecular pathways of all shared genes. We observed that shared genes present more constrained against functional rare genetic variation, and harbor more pathogenic rare variants than do unique genes in each disorder. Furthermore, 71 shared genes formed two clusters related to synaptic transmission, transcription regulation and chromatin regulator. Particularly, we also found that two core genes STXBP1 and SCN2A, that were shared by the four neurodevelopmental disorders showed prominent pleiotropy. Our findings shed light on the shared and specific patterns across neurodevelopmental disorders and will enable us to further comprehend the etiology and provide valuable information for the diagnosis of neurodevelopmental disorders.

Mental, behavioral and neurodevelopmental disorders in the ICD-11: an international perspective on key changes and controversies.

An update of the chapter on Mental, Behavioral and Neurodevelopmental Disorders in the International Classification of Diseases and Related Health Problems (ICD) is of great interest around the world. The recent approval of the 11th Revision of the ICD (ICD-11) by the World Health Organization (WHO) raises broad questions about the status of nosology of mental disorders as a whole as well as more focused questions regarding changes to the diagnostic guidelines for specific conditions and the implications of these changes for practice and research. This Forum brings together a broad range of experts to reflect on key changes and controversies in the ICD-11 classification of mental disorders. Taken together, there is consensus that the WHO's focus on global applicability and clinical utility in developing the diagnostic guidelines for this chapter will maximize the likelihood that it will be adopted by mental health professionals and administrators. This focus is also expected to enhance the application of the guidelines in non-specialist settings and their usefulness for scaling up evidence-based interventions. The new mental disorders classification in ICD-11 and its accompanying diagnostic guidelines therefore represent an important, albeit iterative, advance for the field.

What are neurodevelopmental disorders?

PURPOSE OF REVIEW: The purpose of this review is to highlight the origin and evolution of the field of neurodevelopmental disabilities and describe the main construct(s) upon which the current classification of neurodevelopmental disorders is based. RECENT FINDINGS: We address the following questions: Are neurodevelopmental disorders independent entities? Why is it desirable to understand the neurobiological substrate for these disorders? What new knowledge have we generated by leveraging advances in neuroscience, genetics, and neuroimaging? And finally, is the current construct, that is based on functional classification, still useful? SUMMARY: As our biological understanding of brain-behavior disorders evolves, we ought to re-evaluate the current classification system and expand it into a multidimensional classification that takes into account behavioral profiles and underlying mechanisms.

Sleep Disturbances in Neurodevelopmental Disorders.

Sleep disturbances are extremely prevalent in children with neurodevelopmental disorders compared to typically developing children. The diagnostic criteria for many neurodevelopmental disorders include sleep disturbances. Sleep disturbance in this population is often multifactorial and caused by the interplay of genetic, neurobiological and environmental overlap. These disturbances often present either as insomnia or hypersomnia. Different sleep disorders present with these complaints and based on the clinical history and findings from diagnostic tests, an appropriate diagnosis can be made. This review aims to provide an overview of causes, diagnosis, and treatment of sleep disturbances in neurodevelopmental disorders that present primarily with symptoms of hypersomnia and/or insomnia.

Meaningful health outcomes for paediatric neurodisability: Stakeholder prioritisation and appropriateness of patient reported outcome measures.

BACKGROUND: Health services are increasingly focused on measuring and monitoring outcomes, particularly those that reflect patients' priorities. To be meaningful, outcomes measured should be valued by patients and carers, be consistent with what health professionals seek to achieve, and be robust in terms of measurement properties. The aim of this study was (i) to seek a shared vision between families and clinicians regarding key aspects of health as outcomes, beyond mortality and morbidity, for children with neurodisability, and (ii) to appraise which multidimensional patient reported outcome measures (PROMs) could be used to assess salient health domains. METHODS: Relevant outcomes were identified from (i) qualitative research with children and young people with neurodisability and parent carers, (ii) Delphi survey with health professionals, and (iii) systematic review of PROMs. The International Classification of Functioning Disability and Health provided a common language to code aspects of health. A subset of stakeholders participated in a prioritisation meeting incorporating a Q-sorting task to discuss and rank aspects of health. RESULTS: A total of 33 pertinent aspects of health were identified. Fifteen stakeholders from the qualitative and Delphi studies participated in the prioritisation meeting: 3 young people, 5 parent carers, and 7 health professionals. Aspects of health that emerged as more important for families and targets for health professionals were: communication, emotional wellbeing, pain, sleep, mobility, self-care, independence, mental health, community and social life, behaviour, toileting and safety. Whilst available PROMs measure many aspects of health in the ICF, no single PROM captures all the key domains prioritised as for children and young people with neurodisability. The paucity of scales for assessing communication was notable. CONCLUSIONS: We propose a core suite of key outcome domains for children with neurodisability that could be used in evaluative research, audit and as health service performance indicators. Future work could appraise domain-specific PROMs for these aspects of health; a single measure assessing the key aspects of health that could be applied across paediatric neurodisability remains to be developed.

Parent-child relational problem: field trial results, changes in DSM-5, and proposed changes for ICD-11.

Caregiving relationships are significant factors in the development, mediation, or moderation of childhood mental health problems. However, epidemiological and clinical research has been limited by lack of reliable, succinct, and standardized methods of assessing parent-child relationship constructs. The Relational Processes Workgroup (ad hoc to the DSM-5 process) proposed more specific criteria to define a parent-child relational problem (PCRP). These criteria were field tested in one of the DSM-5 Field trial sites, utilizing a similar research design as DSM-5. Participants included 133 symptomatic children (5-17 years) in active treatment for a mental health problem and their primary caregiver (86% mothers). Two separate clinicians, each blinded to the assessment of the other clinician as well as the DSM-5 diagnoses, interviewed the dyads within a 2-week period, utilizing the proposed PCRP criteria. Prior to each interview, parents were asked to write about their relationship with their child, and children (over the age of 10 years) filled out the Parental Bonding Instrument, Brief Current, and the Perceived Criticism Measure. Clinicians were able to read the narratives and see results of the child report measures before assessing the dyad. The weighted prevalence of a PCRP in this sample was 34%. The interclass kappa for overall agreement between clinicians was 0.58 (0.40, 0.72), which indicates good interrater reliability. Further, clinicians found the PCRP diagnostic criteria clinically useful and an improvement over the brief description of PCRP that was presented in DSM-IV. Relationships between children and their primary caregiver can be assessed in a reliable manner, based on clinical interview with the child-caregiver dyad and several self-report measures.

Changes in Neurodevelopmental Outcomes From Age 2 to 10 Years for Children Born Extremely Preterm.

OBJECTIVES: Evidence-based care of extremely preterm infants (<28 weeks' gestation) depends heavily on research in which a primary outcome is infant neurodevelopmental impairment (NDI), yet it is unclear how well NDI in infancy predicts long-term NDI. In this study, we aim to assess the relationship between 2- and 10-year neurodevelopment using a well-known 2-year definition and a 10-year definition developed by an expert panel. METHODS: Using data from the Extremely Low Gestational Age Newborn Study cohort, we classified 2-year NDI using definitions developed by the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. We classified 10-year NDI using definitions developed by an expert panel, which added epilepsy and ASD at 10 years. RESULTS: Of 1506 infants, 80% survived. Data sufficient to classify severity of NDI at both 2 and 10 years were available for 67% of survivors (n = 802). Among children classified as having moderate to severe NDI at 2 years, 63% had none to mild NDI at 10 years; among children classified as having profound NDI at 2 years, 36% had none to mild NDI at 10 years. Cohen's κ statistic indicated minimal to fair agreement between NDI at 2 and 10 years (0.34, P < .001). CONCLUSIONS: NDI in infancy, as defined in this study, only weakly predicts NDI in middle childhood. For the parents at risk for delivery of an extremely preterm infant, a hopeful message can be taken from our findings that one-third of surviving children classified as having profound NDI and nearly two-thirds of those classified as having moderate to severe NDI at 2 years had none to mild NDI at 10 years.

Neurodevelopmental outcome of patients with congenital gastrointestinal malformations: a systematic review and meta-analysis.

AIM: Children with congenital gastrointestinal malformations may be at risk of neurodevelopmental impairment due to challenges to the developing brain, including perioperative haemodynamic changes, exposure to anaesthetics and postoperative inflammatory influences. This study aggregates existing evidence on neurodevelopmental outcome in these patients using meta-analysis. METHOD: PubMed, Embase and Web of Science were searched for peer-reviewed articles published until October 2019. Out of the 5316 unique articles that were identified, 47 studies met the inclusion criteria and were included. Standardised mean differences (Cohen's d) between cognitive, motor and language outcome of patients with congenital gastrointestinal malformations and normative data (39 studies) or the studies' control group (8 studies) were aggregated across studies using random-effects meta-analysis. The value of (clinical) moderators was studied using meta-regression and diagnostic subgroups were compared. RESULTS: The 47 included studies encompassed 62 cohorts, representing 2312 patients. Children with congenital gastrointestinal malformations had small-sized cognitive impairment (d=-0.435, p<0.001; 95% CI -0.567 to -0.302), medium-sized motor impairment (d=-0.610, p<0.001; 95% CI -0.769 to -0.451) and medium-sized language impairment (d=-0.670, p<0.001; 95% CI -0.914 to -0.425). Patients with short bowel syndrome had worse motor outcome. Neurodevelopmental outcome was related to the number of surgeries and length of total hospital stay, while no relations were observed with gestational age, birth weight, age and sex. INTERPRETATION: This study shows that children with congenital gastrointestinal malformations exhibit impairments in neurodevelopmental outcome, highlighting the need for routine screening of neurodevelopment during follow-up.

Changes from ICD-10 to ICD-11 and future directions in psychiatric classification
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This article provides a brief overview of the changes from ICD-10 to ICD-11 regarding the classification of mental, behavioral, or neurodevelopmental disorders. These changes include a new chapter structure, new diagnostic categories, changes in diagnostic criteria, and steps towards dimensionality. Additionally, we review evaluative field studies of ICD-11, which provide preliminary evidence for higher reliability and clinical utility of ICD-11 compared with ICD-10. Despite the extensive revision process, changes from ICD-10 to ICD-11 were relatively modest in that both systems are categorical, classifying mental phenomena based on self-reported or clinically observable symptoms. Other recent approaches to psychiatric nosology and classification (eg, neurobiology-based or hierarchical) are discussed. To meet the needs of different user groups, we propose expanding the stepwise approach to diagnosis introduced for some diagnostic categories in ICD-11, which includes categorical and dimensional elements.
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Este artículo entrega una breve descripción de los cambios de la CIE-10 a la CIE-11 con respecto a la clasificación de los trastornos mentales, conductuales o trastornos del neurodesarrollo. Estos cambios incluyen una nueva estructura del capítulo, nuevas categorías diagnósticas, cambios en los criterios diagnósticos y pasos hacia un enfoque dimensional. Además, se revisan los estudios de campo de evaluación para la CIE-11, que proporcionan evidencia preliminar de una mayor confiabilidad y utilidad clínica de la CIE-11 en comparación con la CIE-10. A pesar del extenso proceso de revisión, los cambios de la CIE-10 a la CIE-11 fueron relativamente pocos en el sentido de que ambos sistemas son categoriales y clasifican los fenómenos mentales en base a síntomas auto-reportados o que sean clínicamente observables. Se discuten otros enfoques recientes de la nosología y de la clasificación psiquiátrica (por ejemplo, basados en la neurobiología o de acuerdo a jerarquías). Para satisfacer las necesidades de diferentes grupos de usuarios, se propone expandir el enfoque gradual del diagnóstico introducido para algunas categorías diagnósticas de la CIE-11, que incluye elementos categoriales y dimensionales.

Cet article propose un aperçu des évolutions entre la CIM-10 et la CIM-11 concernant la classification des troubles mentaux, comportementaux ou neurodéveloppementaux. Un nouveau chapitre, de nouvelles catégories diagnostiques, des critères diagnostiques modifiés et des étapes dimensionnelles ont été ajoutés. De plus, nous examinons les données préliminaires issues d'études de terrain d'évaluation de la CIM-11, en faveur d'une plus grande fiabilité et utilité de cette dernière comparée à la CIM-10. Les modifications de la CIM-10 vers la CIM-11 sont relativement modestes malgré une révision étendue, les deux systèmes restant catégoriels et les troubles mentaux étant classés d'après des symptômes auto-rapportés ou cliniquement observables. Nous analysons d'autres approches récentes de la nosologie et de la classification psychiatriques (selon la neurobiologie ou hiérarchiquement par exemple). Certaines catégories diagnostiques de la CIM-11 pourraient bénéficier selon nous de cette méthode progressive en incluant des éléments catégoriels et dimensionnels.

Ensuring the rights of children with neurodevelopmental disabilities within child justice systems.

A recent UN general comment on criminal justice systems includes guidance to state parties regarding the implementation of the Convention on the Rights of the Child for children with developmental delays or neurodevelopmental disorders or disabilities. This guidance asserts that these children "should not be in the child justice system at all", but when present "should be individually assessed" to enable appropriate safeguards and accommodations to ensure the protection of their rights without discrimination. In this Viewpoint, we examine the significant barriers faced by children who are affected by neurodevelopmental disabilities to the realisation of their rights under international law and standards. These barriers include systemic and cultural barriers created by a lack of awareness among justice professionals about how to identify and work with children who have neurodevelopmental disabilities, as well as procedural barriers, which arise from the complexity and rigidity of many criminal justice processes. The effect of these barriers is that the child is denied their rights on an equal basis with other children without such disabilities.

ADHD, CD, and ODD: Systematic review of genetic and environmental risk factors.

This review aims to analyze the relationships between Attention-Deficit Hyperactivity Disorder (ADHD), Oppositional Defiant Disorder (ODD), and Conduct Disorder (CD), particularly regarding the relative importance of genetic and environmental factors in the development of these disorders. Studies that examined at least two of these disorders were obtained from multiple databases, following the procedures of the Cochrane Collaboration initiative. Of the 279 documents obtained, nine were retained for in-depth analysis and were considered eligible for inclusion. In addition, eight studies from the manual search were included. The objectives, methodological aspects (sample and instruments), and the main conclusions were extracted from each study. Overall, the results suggest that (a) the causes for the onset and maintenance of these disorders are more associated with genetic factors than environmental factors, although the importance of the latter is recognized, and (b) children with ADHD have a predisposition to manifest behaviors that are common to ODD and CD, including the antisocial behavior that these children often display.

Closing the medical mortality gap in patients with major psychiatric conditions.

This article discusses options for closing the mortality gap between the general population and people with major psychiatric conditions such as psychosis, autism, learning disability and dementia. Most of the mortality (85%) involves physical disease, with most deaths occurring in general hospitals or care homes, so is relevant to all doctors. The main focus of psychiatric treatments has been to reduce suicide, although there is no evidence that they achieve this. This article calls for psychiatrists to collaborate with medical colleagues to help reduce excess deaths from physical causes. The practicalities of combined physical and mental health monitoring and prescribing clinics are discussed, based on experience in Whitby. Potential national solutions are summarized including options for smoking cessation, sugar restriction, nutritional supplementation and flu vaccination.

Discriminant validity of spatial and temporal postural index in children with neurodevelopmental disorders.

Autism, learning disabilities and attention deficit/hyperactive disorder are often comorbid disorders. In order to try and find some markers that might be transnosographic, we hypothesized that abnormal postural sway profiles may discriminate children with neurodevelopmental disorders (NDDs) from typically developing children. The aim of our study was thus to compare spatial and temporal measures of the Center of Pressure in three distinct groups of children with NDDs (high functioning autism spectrum disorders, learning disabilities (dyslexia) and attention deficit/hyperactive disorders) and in typically developing children. Postural performances were thus evaluated in 92 children (23 per group, sex-, age- and IQ-matched groups) by using the Multitest Equilibre platform (Framiral®). Two viewing conditions (eyes open and eyes closed) were tested on a stable and unstable platform. Results reported similar poor postural instability for the three groups of children with NDDs with respect to the typically developing children, and this was observed for both spatial as well as temporal analysis of displacement of the center of pressure. Such postural instability observed in children with NDDs could be due to impairment in using sensorial inputs to eliminate body sway, probably due to poor cerebellar integration.

[Sluggish cognitive tempo: an updated review]. / Tempo cognitivo lento: una revision actualizada.

INTRODUCTION: The study of sluggish cognitive tempo (SCT) arose largely from research carried out on attention deficit hyperactivity disorder (ADHD). This construct is defined by a range of behavioural symptoms such as the appearance of drowsiness, daydreaming, physical hypoactivity, little initiative, lethargy and apathy. DEVELOPMENT: The construct of SCT is reviewed by means of recently published papers on its clinical characteristics, associated symptoms, evaluation, prevalence, aetiology, comorbidity, neuropsychological profiles and treatment. The latest studies propose that SCT should be understood as a cluster of symptoms that is distinct from ADHD. Although there is no clear consensus on the matter, the evidence is becoming increasingly more consistent and endows SCT with a high degree of external validity, associating it with internalising symptoms. CONCLUSIONS: We believe the different subtypes of ADHD must be grounded in attentional conceptual models. Hence, the attentional guidance network would be related with SCT, the vigilance or sustained attention network would be linked with the inattentive subtype of ADHD, and executive attention would be involved in the combined subtype of ADHD. The evidence obtained to date, including this review, supports the idea that SCT is an attention disorder distinct from ADHD but, like any dimensional disorder, it can overlap with it in around half the cases.

TITLE: Tempo cognitivo lento: una revision actualizada.Introduccion. El estudio del tempo cognitivo lento (TCL) surgio en gran parte de las investigaciones del trastorno por deficit de atencion/hiperactividad (TDAH). Este constructo se define con una gama de sintomas conductuales, como apariencia de somnolencia, soñar despierto, hipoactividad fisica, pobre iniciativa, letargo y apatia. Desarrollo. Se revisa el constructo de TCL a traves de articulos recientemente publicados al respecto sobre caracteristicas clinicas, sintomas asociados, evaluacion, prevalencia, etiologia, comorbilidad, perfiles neuropsicologicos y tratamiento. Los trabajos mas actuales proponen entender el TCL como un cluster de sintomas distintivo del TDAH. Aunque no hay un consenso claro, los datos son cada vez mas consistentes y dotan de gran validez externa al TCL, asociandolo con sintomas internalizantes. Conclusiones. Consideramos necesario anclar los diferentes subtipos de TDAH en modelos conceptuales atencionales. Asi, la red de orientacion atencional se relacionaria con el TCL, la red de vigilancia o atencion sostenida con el TDAH subtipo inatento, y la atencion ejecutiva seria la implicada en el TDAH subtipo combinado. La evidencia hasta la fecha, incluyendo esta revision, apoya la idea de que el TCL es un trastorno de atencion diferenciado del TDAH, pero que, como cualquier trastorno dimensional, puede solaparse con el aproximadamente en la mitad de los casos.