Classification,prevalence and integrated care for neurodevelopmental and child mental health disorders: A brief overview for paediatricians

‘Neurodevelopmental disorders’ comprise a group of congenital or acquired long-term conditions that are attributed to disturbance of the brain and or neuromuscular system and create functional limitations, including autism spectrum disorder, attention deficit/ hyperactivity disorder, tic disorder/ Tourette’s syndrome, developmental language disorders and intellectual disability. Cerebral palsy and epilepsy are often associated with these conditions within the broader framework of paediatric neurodisability. Co-occurrence with each other and with other mental health disorders including anxiety and mood disorders and behavioural disturbance is often the norm. Together these are referred to as neurodevelopmental, emotional, behavioural, and intellectual disorders (NDEBIDs) in this paper. Varying prevalence rates for NDEBID have been reported in developed countries, up to 15%, based on varying methodologies and definitions. NDEBIDs are commonly managed by either child health paediatricians or child/ adolescent mental health (CAMH) professionals, working within multidisciplinary teams alongside social care, education, allied healthcare practitioners and voluntary sector. Fragmented services are common problems for children and young people with multi-morbidity, and often complicated by sub-threshold diagnoses. Despite repeated reviews, limited consensus among clinicians about classification of the various NDEBIDs may hamper service improvement based upon research. The recently developed “Mental, Behavioural and Neurodevelopmental disorder” chapter of the International Classification of Diseases-11 offers a way forward. In this narrative review we search the extant literature and discussed a brief overview of the aetiology and prevalence of NDEBID, enumerate common problems associated with current classification systems and provide recommendations for a more integrated approach to the nosology and clinical care of these related conditions.     

Behavioural and cognitive phenotypes in idiopathic autism versus autism associated with fragile X syndrome

Background:  In order to better understand the underlying biological mechanism/s involved in autism, it is important to investigate the cognitive and behavioural phenotypes associated with idiopathic autism (autism without a known cause) and comorbid autism (autism associated with known genetic/biological disorders such as fragile X syndrome). Parental effects associated with each type of autism also serve to cast light on the biological underpinnings of autism.
Method:  Forty-nine participants with idiopathic autism (AD; Mean age: 11.16; SD: 6.08) and their parents (45 mothers; 34 fathers), and 48 participants with fragile X syndrome and co-morbid autism (FXS/AD; Mean age: 17.30; SD: 10.22) and their parents (32 mothers; 30 fathers) were administered the ADOS-G and the age-appropriate Wechsler test to ascertain autism and cognitive profiles respectively.
Results:  The AD and FXS/AD groups showed a similar profile on the ADOS domains, with slightly higher scores on the Communication domain in the FXS/AD group, after adjusting for full-scale IQ. Marked differences between the groups in their cognitive abilities were apparent, with the FXS/AD group showing significantly lower scores on all subtests except Comprehension. While no parental effects were found for the FXS/AD group, a paternal effect was apparent on the combined ADOS score for the AD group. Moreover, midparental effects were found in this group for full-scale IQ (FSIQ) and verbal IQ (VIQ). Analyses also revealed parental effects for the subtests of Similarities, Vocabulary, and Information with predominantly maternal effect, and Digit Span with predominantly paternal effect. Both parents contributed to the midparental effect for Processing Speed.
Conclusions:  The results, together with our previous findings, suggest that the postulated combination of susceptibility genes for autism may primarily involve cognitive rather than behavioural processes.     

Feeding difficulties in children with autism spectrum disorder: Aetiology,health impacts and psychotherapeutic interventions

Feeding difficulties are common and significant issues for children with autism spectrum disorder and their families. Key features of autism are intrinsically linked with factors contributing to these children's feeding difficulties. Following a multidisciplinary assessment to exclude non‐behavioural reasons for the feeding difficulty, there are two mainstay modalities of treatment: operant conditioning and systematic desensitisation. Currently, evidence points towards operant conditioning as the most efficacious psychotherapy. However, recent research into cognitive behavioural therapy for older children with feeding difficulties has shown promising results and will be an area to monitor in the coming years. This review outlines the causes and health impacts and evaluates current evidence supporting the available psychotherapeutic interventions for children with autism spectrum disorder experiencing feeding difficulties.     

Management of sleep disorders among children and adolescents with neurodevelopmental disorders: A practical guide for clinicians

There is a complex relationship between sleep disorders and childhood neurodevelopmental, emotional, behavioral and intellectual disorders (NDEBID). NDEBID include several conditions such as attention deficit/hyperactivity disorder, autism spectrum disorder, cerebral palsy, epilepsy and learning (intellectual) disorders. Up to 75% of children and young people (CYP) with NDEBID are known to experience different types of insomnia, compared to 3% to 36% in normally developing population. Sleep disorders affect 15% to 19% of adolescents with no disability, in comparison with 26% to 36% among CYP with moderate learning disability (LD) and 44% among those with severe LD. Chronic sleep deprivation is associated with significant risks of behavioural problems, impaired cognitive development and learning abilities, poor memory, mood disorders and school problems. It also increases the risk of other health outcomes, such as obesity and metabolic consequences, significantly impacting on the wellbeing of other family members. This narrative review of the extant literature provides a brief overview of sleep physiology, aetiology, classification and prevalence of sleep disorders among CYP with NDEBIDs. It outlines various strategies for the management, including parenting training/psychoeducation, use of cognitive-behavioral strategies and pharmacotherapy. Practical management including assessment, investigations, care plan formulation and follow-up are outlined in a flow chart.     

An Exploratory Study of Self-reported Quality of Life in Children with Autism Spectrum Disorder and Intellectual Disability

We examined the content validity of the Pediatric Quality of Life Inventory? Young Child Self-report (PedsQL?-YC) in children with autism spectrum disorder (ASD) and intellectual disability and made recommendations for the development of a quality of life (QOL) measure. Ten children, 14 parents, and three teachers were recruited for focus groups and interviews. Focus groups and interviews were conducted to obtain their perceptions about the appropriateness of the PedsQL^TM-YC (Phase 1). Based on the results from Phase 1, recommendations for a QOL measure for children with ASD and intellectual disability were made (Phase 2). After piloting a QOL measure by children and subsequent interviews, further refinement was undertaken (Phase 3). Data from Phases 1 and 3 were analysed using thematic and content analyses. Findings suggest that a QOL measure for children with ASD and intellectual disability should be related specifically to the children’s daily life and contexts. Due to the specific cognitive and behavioural characteristics of this population, the wording, response options and presentation style of the existing PedsQL?-YC would need refinement. Questions about social interactions with friends appeared less relevant to children with ASD. These recommendations address the wording and formatting issues needed for a QOL measure for use in children with ASD and intellectual disability identified through qualitative research methods. Further research is needed to include additional or modified questions in the social domain.     

Cognitive and behavioural characteristics in blind children with bilateral optic nerve hypoplasia

Aim: To describe cognitive and behavioural characteristics in a group of blind children with bilateral optic nerve hypoplasia (ONH). Methods: Data from records, parents, teachers, and repeated developmental assessments of 13 blind children with ONH born in 1988-1998 were analysed. All children had neuroimaging and/or hormonal evidence of midline malformations. They were all blind and able to communicate with speech. Results: Severe mood swings and temper tantrums were common, especially during the first years of life. Later in life, sluggish tempo, low frustration tolerance and a narrow range of interests were common. Autism had been diagnosed in 6/13 children, autistic-like condition (ALC) was found in another three. The behaviour of the remaining four children was not within the autism spectrum. Eight children had cognitive capacities within the normal or near-normal range; five had mental retardation. Autism/ALC was found in all cognitive subgroups. All children exhibited fluent speech and, of these, 12 had started to talk at the expected age, but had clear deficiencies in communicative ability.

Conclusion: These children had a common pattern of behavioural characteristics including autism spectrum disorders independent of intellectual capacities.     

Precision or narrative medicine? Child neurology needs both!

Precision medicine aims to understand the mechanisms of diseases and to find treatments adapted to each individual or group of patients, on the basis of biological characteristics and environment. It uses new tools based on digital technologies. Narrative medicine was theorized, in the 2000s, as a reaction to the increasing technicality and the notion of a lack of human relations in care: It focuses on recognizing the essential place of the patient's experience of illness and life history in the diagnosis and management of diseases as well as in the training of caregivers.These two opposite currents are rarely considered together. In fact, they have in common the basic principle that each patient is unique, and both are often more closely intertwined than we think, especially in the field of child neurology. Five case histories and discussions presented here aim to demonstrate that combining the precision approach with the narrative approach can improve the diagnosis, treatment, classification, and understanding of neurological conditions, as well as enhance the dialog with families and make teaching more meaningful. Not only rare diseases but common problems, such as paroxysmal events, pain, epilepsy, intellectual disability, and autism spectrum disorder, are addressed from both perspectives.     

Integrated care for autism assessment,diagnosis and intervention

Autism spectrum disorder is one of a group of conditions considered to be a neurodevelopmental disorder. These conditions, including ADHD, language disorders and intellectual disability frequently co-occur. Diagnostic pathways often focus on assessment of a named condition (e.g. autism spectrum disorder) in isolation, resulting in inefficiencies in service delivery; other services look holistically at the child's strengths and needs, and provide a neurodevelopmental diagnostic formulation. However, there is growing support for a change to this neurodevelopmental approach that informs recommendations for ongoing multiagency support and intervention for the child and their family. Whilst there may be different ways to deliver a successful neurodevelopmental pathway, the move to integrated commissioning offers an opportunity to redesign services to bring together teams; for example, CAMHS and child development services could deliver an integrated neurodevelopmental pathway, instead of separate single condition pathways. This paper presents the research and reasoning, as well as potential pitfalls, for services to deliver a neurodevelopmental approach, and what this means for clinical practice.     

The behaviour and wellbeing of children and adults with severe intellectual disability and complex needs: the Be-Well checklist for carers and professionals

Children and adults with severe intellectual disability and complex needs often show behaviours and distress that carers and professionals find difficult to identify causes for, manage and decrease. The prevailing view is that these behaviours and distress are learned and consequently interventions focus on behavioural techniques. In this article we summarise the findings of research that indicate that behaviour and distress in this population are influenced by transient and stable characteristics or conditions that can interact with aspects of learning, be independent of learning, and interact with each other. These transient and stable characteristics or conditions are: pain and discomfort, sensory sensitivity, anxiety and low mood, sleep problems, atypical emotional regulation, specific cognitive difference, and differences in social behaviour. To aid carers and professionals, we present a checklist of the elements of an assessment process that covers these transient and stable characteristics or conditions and other relevant influences on behaviour and distress such as seizures, medication, learning and communication. We also draw attention to the benefit of identifying the cause of intellectual disability to inform the assessment process.     

Sensory abnormalities in children with autism spectrum disorder

Objective

The clinical picture of children with autism spectrum disorder is characterized by deficits of social interaction and communication, as well as by repetitive interests and activities. Sensory abnormalities are a very frequent feature that often go unnoticed due to the communication difficulties of these patients. This narrative review summarizes the main features of sensory abnormalities and the respective implications for the interpretation of several signs and symptoms of autism spectrum disorder, and therefore for its management.

Attention across modalities as a longitudinal predictor of early outcomes: the case of fragile X syndrome

Background: Fragile X syndrome (FXS) is an early diagnosed monogenic disorder, associated with a striking pattern of cognitive/attentional difficulties and a high risk of poor behavioural outcomes. FXS therefore represents an ideal model disorder to study prospectively the impact of early attention deficits on behaviour. Methods: Thirty‐seven boys with FXS aged 4–10 years and 74 typically developing (TD) boys took part. Study 1 was designed to assess visual and auditory attention at two time‐points, 1 year apart. Study 2 investigated attention to multimodal information. Both tested attention markers as longitudinal predictors of risk for poor behaviour in FXS. Results: Children with FXS attended less well than mental‐age matched TD boys and experienced greater difficulties with auditory compared to visual stimuli. In addition, unlike TD children, they did not benefit from multimodal information. Attention markers were significant predictors of later behavioural difficulties in boys with FXS. Conclusions: Findings demonstrate, for the first time, greater difficulties with auditory attention and atypical processing of multimodal information, in addition to pervasive global attentional difficulties in boys with FXS. Attention predicted outcomes longitudinally, underscoring the need to dissect what drives differing developmental trajectories for individual children within a seemingly homogeneous group.     

Editorial Perspective: Neurodiversity – a revolutionary concept for autism and psychiatry

Should we continue to refer to autism as a ‘disease’ or ‘disorder’, or is the framework of ‘neurodiversity’ a more humane and accurate lens through which to view people with autism? Evidence at the genetic, neural, behavioural and cognitive levels reveals people with autism show both differences, and signs of disability, but not disorder. Disability requires societal support, acceptance of difference and diversity, and societal “reasonable adjustment”, whilst disorder is usually taken to require cure or treatment. These are very different frameworks. It will be important to see how the concept of neurodiversity is applied to the 300 diagnoses in DSM-5, and if it revolutionizes both the science and the practice of psychiatry.     

The behavioral phenotype in fragile X: symptoms of autism in very young children with fragile X syndrome, idiopathic autism, and other developmental disorders.

This study was designed to explore the behavioral phenotype of autism in a group of young children with fragile X syndrome (FXS). Twenty-four children with FXS, ages 21 to 48 months, were compared with two well-matched groups: 27 children with autism (AD) and 23 children with other developmental delays (DD), on two standardized autism instruments, as well as on measures of development and adaptive behavior. Two FXS subgroups emerged. One subgroup (n = 16) did not meet study criteria for autism. Their profiles on the autism instruments and the developmental instruments were virtually identical to the other DD group. The other FXS subgroup (n = 8, or 33% of the total FXS group) met study criteria for autism. Their profiles on the autism instruments were virtually identical to the group with autism. The finding of two FXS subgroups raises a hypothesis of additional genetic influences in the FXS autism group, warranting further genetic studies.     

Maturing insights into the genetic architecture of neurodevelopmental disorders – from common and rare variant interplay to precision psychiatry

The categorisation of neurodevelopmental and psychiatric disorders by clinical syndromes, rather than by aetiology, continues to obstruct progress in biomarker identification as well as innovative drug development and effective treatment in general. There is a decisive move to think of neurodevelopmental disorders as a spectrum rather than discrete categorical entities. We might call them neurodevelopmental spectrum disorders (NSDs) ranging from intellectual disability (ID) to autism (ASD), and attention‐deficit/hyperactivity disorder (ADHD) (Kiser, Rivero, & Lesch, 2015 ).     

Hypothesis on supine sleep,sudden infant death syndrome reduction and association with increasing autism incidence

AIM: To identify a hypothesis on: Supine sleep, sudden infant death syndrome (SIDS) reduction and association with increasing autism incidence. METHODS: Literature was searched for autism spectrum disorder incidence time trends, with correlation of change-points matching supine sleep campaigns. A mechanistic model expanding the hypothesis was constructed based on further review of epidemiological and other literature on autism. RESULTS: In five countries (Denmark, United Kingdom, Australia, Israel, United States) with published time trends of autism, change-points coinciding with supine sleep campaigns were identified. The model proposes that supine sleep does not directly cause autism, but increases the likelihood of expression of a subset of autistic criteria in individuals with genetic susceptibility, thereby specifically increasing the incidence of autism without intellectual disability. CONCLUSION: Supine sleep is likely a physiological stressor, that does reduce SIDS, but at the cost of impact on emotional and social development in the population, a portion of which will be susceptible to, and consequently express autism. A re-evaluation of all benefits and harms of supine sleep is warranted. If the SIDS mechanism proposed and autism model presented can be verified, the research agenda may be better directed, in order to further decrease SIDS, and reduce autism incidence.     

The ARX story (epilepsy, mental retardation, autism, and cerebral malformations): one gene leads to many phenotypes

PURPOSE OF REVIEW: Infantile spasms, mental retardation, autism, and dystonia represent disabling diseases for which little etiologic information is available. Mutations in the Aristaless related homeobox gene (ARX) have been found in patients with these conditions. This discovery provides important genetic information and may ultimately offer treatment options for these patients. RECENT FINDINGS: Recent work has demonstrated that mutations in ARX cause X-linked West syndrome, X-linked myoclonic epilepsy with spasticity and intellectual disability, Partington syndrome (mental retardation, ataxia, and dystonia), as well as nonsyndromic forms of mental retardation. Patients with these aforementioned diseases and ARX mutations were not reported to have brain imaging abnormalities. In contrast, mutations in ARX mutations have also been found in X-linked lissencephaly with abnormal genitalia, which typically includes severe brain malformations (lissencephaly, agenesis of the corpus callosum, and midbrain malformations), intractable seizures, and a severely shortened lifespan. ARX knockout mice manifest defects in overall neuroblast proliferation as well as selective abnormalities in gamma-aminobutyric acid-ergic interneuron migration. Consistent with these findings in mice, phenotype/genotype studies in humans suggest that truncating mutations cause X-linked lissencephaly with abnormal genitalia, and insertion/missense mutations result in epilepsy and mental retardation without cortical dysplasia. SUMMARY: Mutations in the homeobox gene, ARX, cause a diverse spectrum of disease that includes cognitive impairment, epilepsy, and in another group of patients severe cortical malformations. Although the precise prevalence of ARX mutations is unclear, ARX may rival Fragile X as a cause of mental retardation and epilepsy in males.     

可导致孤独症谱系障碍的肉碱缺乏症

孤独症谱系障碍是一组神经发育障碍性疾病, 导致社交障碍、 交流困难及行为异常, 病因复杂, 已知多种遗传和非遗传因素可导致多种类型的孤独症表现。左旋肉碱（左卡尼汀）是一种水溶性维生素亚类, 结构类似氨基酸, 参与多种物质代谢, 主要功能是将长链脂肪酸从胞浆转移到线粒体内质网进行β-氧化代谢。肉碱缺乏症可导致孤独症谱系障碍等精神行为异常, 一些患者发生心脏、 骨骼肌、 脑、 肝脏等多器官损伤, 严重者猝死。正常情况下, 机体通过饮食摄入、 内源合成、 肾脏排泄与重吸收来保证左卡尼汀的稳态。肉碱在机体的内源性合成通过线粒体内四步酶促反应完成, 三甲基赖氨酸羟化酶是肉碱合成中的一个关键酶。三甲基赖氨酸羟化酶缺乏症是一种X连锁遗传病, 引起肉碱合成障碍, 是导致孤独症谱系障碍病因之一。早期诊断, 早期补充左卡尼汀, 是改善三甲基赖氨酸羟化酶缺乏症所致孤独症患者预后的关键。     

Analysis of prevalence trends of autism spectrum disorder in Minnesota

BACKGROUND: Alarming increases in the prevalence of autism spectrum disorder have been reported recently in the United States and Europe. OBJECTIVES: To quantify and characterize prevalence trends over time in autism spectrum disorder in Minnesota. METHODS: We conducted an age-period-birth cohort analysis of special educational disability data from the Minnesota Department of Children, Families & Learning from the 1981-1982 through the 2001-2002 school years. RESULTS: Prevalence rates of autism spectrum disorder rose substantially over time within single-age groups and increased from year to year within birth cohorts. Autism spectrum disorder prevalence among children aged 6 to 11 years increased from 3 per 10 000 in 1991-1992 to 52 per 10 000 in 2001-2002. All other special educational disability categories also increased during this period, except for mild mental handicap, which decreased slightly from 24 per 10 000 to 23 per 10 000. We found that federal and state administrative changes favoring identification of autism spectrum disorders corresponded in time with the increasing rates. CONCLUSIONS: We observed dramatic increases in the prevalence of autism spectrum disorder as a primary special educational disability starting in the 1991-1992 school year, and the trends show no sign of abatement. We found no corresponding decrease in any special educational disability category to suggest diagnostic substitution as an explanation for the autism trends in Minnesota. We could not assess changes in actual disease incidence with these data, but federal and state administrative changes in policy and law favoring better identification and reporting of autism are likely contributing factors to the prevalence increases and may imply that autism spectrum disorder has been underdiagnosed in the past.