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Background\ud Children with intellectual disability frequently have multiple co-morbid neuropsychiatric conditions and poor physical health. Genomic testing is increasingly recommended as a first-line investigation for these children. We aim to determine the effect of genomics, inheritance, and socioeconomic deprivation on neuropsychiatric risk in children with intellectual disability of genetic origin as compared with the general population.\ud Methods\ud IMAGINE is a prospective cohort study using online mental health and medical assessments in a cohort of 3407 UK participants with intellectual disability and pathogenic genomic variants as identified by the UK's National Health Service (NHS). Our study is on a subset of these participants, including all children aged 4–19 years. We collected diagnostic genomic reports from NHS records and asked primary caregivers to provide an assessment of their child using the Development and Well-Being Assessment (DAWBA), the Strengths and Difficulties Questionnaire (SDQ), the Adaptive Behaviour Assessment System 3 (ABAS-3), and a medical history questionnaire. Each child was assigned a rank based on their postcode using the index of multiple deprivation (IMD). We compared the IMAGINE cohort with the 2017 National Survey of Children's Mental Health in England. The main outcomes of interest were mental health and neurodevelopment according to the DAWBA and SDQ.\ud Findings\ud We recruited 2770 children from the IMAGINE study between Oct 1, 2014 and June 30, 2019, of whom 2397 (86·5%) had a basic assessment of their mental health completed by their families and 1277 (46·1%) completed a medical history questionnaire. The mean age of participants was 9·2 years (SD 3·9); 1339 (55·9%) were boys and 1058 (44·1%) were girls. 355 (27·8%) of 1277 reported a seizure disorder and 814 (63·7%) reported movement or co-ordination problems. 1771 (73·9%) of 2397 participants had a pathogenic copy number variant (CNV) and 626 (26·1%) had a pathogenic single nucleotide variant (SNV). Participants were representative of the socioeconomic spectrum of the UK general population. The relative risk (RR) of co-occurring neuropsychiatric diagnoses, compared with the English national population, was high: autism spectrum disorder RR 29·2 (95% CI 23·9–36·5), ADHD RR 13·5 (95% CI 11·1–16·3). In children with a CNV, those with a familial variant tended to live in more socioeconomically deprived areas than those with a de novo variant. Both inheritance and socioeconomic deprivation contributed to neuropsychiatric risk in those with a CNV.\ud Interpretation\ud Children with genomic variants and intellectual disability are at an increased risk of neuropsychiatric difficulties. CNV variant inheritance and socioeconomic deprivation also contribute to the risk. Early genomic investigations of children with intellectual disability could facilitate the identification of the most vulnerable children. Additionally, harnessing parental expertise using online DAWBA assessments could rapidly identify children with exceptional needs to child mental health services.

Background This article aims to explain and elaborate upon the recently released ICD-11 criteria for Autism Spectrum Disorder (ASD, World Health Organization), which endorse a medical model. Method We integrate insights from several disciplines (e.g., psychology, linguistics, sociology and lived experiences) to reflect the scientific and ethical insights derived from the biopsychosocial, neurodiversity perspective on autism. Results First, we describe the core domains of ASD’s behavioural characteristics and then the lifetime, developmental perspective on the manifestations of these behaviours. Subsequently, we discuss potential underlying neuropsychology, related behaviours (i.e. associated features/conditions) and we consider some similarities and differences with the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM 5, American Psychological Association). Conclusions Recommendations for clinical application are provided. For instance, diagnostic classification in clinical practise should be a means to provide proper, suitable care, and therefore all diagnostic assessments should be used to tailor interventions and/or care to the capacities and genuine needs of the people that ask for professional help.

BackgroundParents of individuals with intellectual disabilities (ID) are vulnerable to mental health difficulties, which vary between parents and within parents over time. The underlying cause of ID can influence parents’ mental health, via uncertain pathways and within unknown time-windows. MethodsWe analysed baseline data from the IMAGINE-ID cohort, comprising 2655 parents of children and young people with ID of known genetic origin. First, we conducted a factor analysis of the SDQ Impact scale to isolate specific pathways from genetic aetiology to parents’ mental health. Second, we tested via structural equation modelling (SEM) whether genetic diagnosis affects Impact and mental health directly, or indirectly via children’s characteristics. Third, we conducted moderation analysis to explore the influence of time elapsed since genetic diagnosis. ResultsFactor analysis suggested a two-factor structure for the SDQ Impact scale, with a “home & distress” dimension and a “participation” dimension. SEM analysis identified an indirect pathway linking genetic aetiology to parents’ mental health, serially through child characteristics (physical disabilities, emotional and behavioural difficulties) and Impact: home & distress. This serial mediation model was moderated by time since diagnosis, with strongest mediating effects among recently diagnosed cases.Conclusions There are multiple steps on the pathway from ID-associated genetic diagnoses to parents’ mental health. Pathway links are strongest within 5 years of receiving a genetic diagnosis, highlighting opportunities for better post-diagnostic support. Recognition and enhanced support for children’s physical and behavioural needs might reduce impact on family life, ameliorating parents’ vulnerabilities to mental health difficulties.

This systematic review aimed to identify factors significantly associated with the occurrence of epilepsy in autistic individuals and to consider the impact of study quality on findings. Electronic databases were systematically searched on October 2nd, 2020 and records retrieved were limited to those published from 2000 onwards. Study quality was categorised as ‘good’, ‘moderate’ or ‘weak’. Fifty-three studies were included and in studies where the prevalence of epilepsy was reported (n = 257,892), 18,254 (7%) had co-occurring epilepsy. Intellectual disability/cognitive impairment was the most commonly reported risk factor associated with occurrence of epilepsy in autistic individuals. The evidence supporting other, potentially relevant factors was weak and inconsistent and requires further evaluation. Only 9/53 studies were considered ‘good’ quality.

Social skills group interventions are increasing popular for children with social communication disorders but there is little evidence of their acceptability or effectiveness when delivered online. We report a feasibility study that adapted the Program for Education and Enrichment of Relational Skills (PEERS) to provide an intensive 8 week online delivery to female adolescents, blended with some face-to-face group meetings. A systematic multiple-case series design with case tracking was developed, comprising a 3-month baseline, a 2-month intervention and a 3-month follow-up period. Seven adolescents with Turner Syndrome and social communication difficulties (17-20 years) took part, together with their parents. Acceptability and feasibility were assessed by means of qualitative feedback and attendance rates. Changes in social adaptation were tracked using measures of social knowledge, social behaviour and autistic symptoms, plus anxiety and self-esteem. Attendance rates were consistently high and there were no dropouts. Qualitative feedback indicated the online format was acceptable to both the participants and their families. Objective outcome measures showed significant gains in social knowledge and improved social initiations from measures made during the pre-intervention baseline. This proof-of-principle pilot study demonstrated blended social skills interventions are both feasible and acceptable to adolescent females with social communication difficulties. LAY SUMMARY: Social skills groups are increasingly popular for children with social communication disorders, but there is little evidence for their use online. Psychological treatments that require weekly face-to-face sessions for both children and their parents are associated with practical difficulties, disrupting family life and school commitments. Our study, is the first to use a blended online and face-to-face social skills training program for adolescent girls with social communication difficulties. We showed that this new approach to treatment was acceptable to families and has a positive and significant impact on participant's social performance and social knowledge. This new treatment approach may increase the accessibility of treatment for adolescents and young adults, especially those with social communication difficulties. Autism Res 2021, 14: 1061-1072. © 2021 The Authors. Autism Research published by International Society for Autism Research published by Wiley Periodicals LLC.

When pulp and minerals are co-processed in suspension, the mineral acts as a grinding aid, allowing cost-effective production of mineral/microfibrillated cellulose (MFC) composite materials. This processing uses robust milling equipment and is practiced at industrial scale. The resulting products can be used in many applications, including as wet- and dry-strength aids in paper and board production. Previously, we have reported that use of these MFC composite materials in fiber-based applications allow generally improved wet and dry mechanical properties with concomitant opportunities for cost savings, property improvements, or grade developments. Mineral/MFC composites made with recycled pulp feedstocks were shown to offer at least equivalent strength aid performance to composites made using virgin fibers. Selection of mineral and fiber allows preparation of mineral/MFC composites with a range of properties. For example, the viscosity of such formulations was shown to be controlled by the shape factor of the mineral chosen, effective barrier formulations were prepared, and mineral/MFC composites with graphite as the mineral were prepared. High-solids mineral/MFC composites were prepared at 75% total solids (37% fibril solids). When resuspended and used for papermaking, these high-solids products gave equivalent performance to never-dried controls.

ObjectiveTo identify clinical features that could distinguish children presenting with autistic-like features and a history of severe early maltreatment from children with idiopathic autism spectrum disorders (ASDs).DesignMatched-comparison study.SettingGreat Ormond Street Hospital, UK.Participants46 children with a history of early maltreatment, mean (SD) age 10.6 (3.3) years and 47 children with an ASD, mean (SD) age 10.4 (2.9) years.Main outcome measuresA range of standardised interview and observational measures that are designed to quantify autistic traits. Caregiver and teacher reports were obtained on broader aspects of behavioural and emotional adjustment.ResultsBoth groups had normal range IQ and were predominantly male. On the basis of autistic traits alone, caregiver interview and structured observation concurred that over 60% of the formerly maltreated children met criteria for an ASD. Autistic symptom profiles were very similar in both groups, although children with idiopathic ASD had significantly more marked repetitive and stereotyped behaviours. Teacher and caregiver reports indicated that children from both groups had an increased and broadly similar prevalence of emotional and behavioural disorders.ConclusionChildren presenting with a history of early maltreatment, who show autistic traits of behaviour, have a high risk of meeting diagnostic criteria for ASD. Their symptom profiles are virtually indistinguishable from children with idiopathic autism.

Stirred media mills are used by the mining industry for ultrafine grinding to enhance liberation, and to decrease particle sizes of industrial minerals to tailor functional properties. This review describes stirred media mill technologies and operating principles, and summarises stress intensity theory which can be used for selecting efficient operating conditions. For fine and ultrafine grinding, the Bond work index is an inappropriate measure of grindability, so alternatives are discussed. Using literature data, the variation in the appropriate energy-size models between examples is assessed, and rationalised with stress intensity theory. A Rittinger operating index was found to be the best choice for assessing operation efficiency. Finally, a modification of stress intensity theory that tunes operating conditions based upon material properties, and the fmat mastercurve theory are discussed, with the conclusions that, although promising, laboratory-scale milling tests remain the most practical method of assessing material grindability and predicting industrial energy requirements.

A wide variety of wood and non-wood cellulosic fibre sources were used as a feed to produce microfibrillated cellulose (MFC) using a grinding process. Nanopaper was formed using this product, and the tensile index was measured. The hemicellulose content of the feed fibres was measured, and was found to correlate with the production of finer microfibrils and a higher MFC tensile strength. The correlation with tensile strength was improved by the inclusion of a measurement of the MFC particle lengths as measured by a fibre image analyser, with the resulting relation fitting a modified Page Equation. It was hypothesised that the frequency of flaws in the feed fibre cross-section influences the length of the MFC particles produced, and so the zero-span tensile index of the fibres was measured as a proxy for this since it forces cross-sectional fibre breakage. The fibre zero-span tensile index was found to correlate with MFC particle length and so was used in its place in the equation. The resultant equation can predict MFC tensile strength from zero-span tensile index and hemicellulose content measurements of cellulosic fibres and can aid in optimising feedstock selection for mechanical MFC production processes.

Light-adapted (LA) electroretinograms (ERGs) from 90 individuals with autism spectrum disorder (ASD), mean age (13.0 ± 4.2), were compared to 87 control subjects, mean age (13.8 ± 4.8). LA-ERGs were produced by a random series of nine different Troland based, full-field flash strengths and the ISCEV standard flash at 2/s on a 30 cd m−2 white background. A random effects mixed model analysis showed the ASD group had smaller b- and a-wave amplitudes at high flash strengths (p

Duchenne muscular dystrophy (DMD) is characterised by loss of dystrophin in muscle. Patients affected by DMD also have variable degree of intellectual disability and neurobehavioural co-morbidities. In contrast to muscle, in which a single full-length isoform (Dp427) is produced, multiple dystrophin isoforms are produced in the brain, and their deficiency accounts for the variability of CNS manifestations, with increased risk of comorbidities in patients carrying mutations affecting the 3’ end of gene, disrupting the shorter Dp140 and Dp71 isoforms. The mdx mouse model of DMD lacks Dp427 in muscle and CNS and exhibits exaggerated startle responses to threat, linked to the deficiency of dystrophin in limbic structures such as the amygdala, which normalise with postnatal brain dystrophin-restoration therapies. A pathological startle response is not a recognised feature of DMD, and its characterisation has implications for improved clinical management and translational research.To investigate startle responses in DMD, we used a novel fear-conditioning task in an observational study of 56 males aged 7-12 years (31 DMD, mean age 9.7±1.8 years; 25 Controls, mean age 9.6±1.4 years). Trials of two neutral visual stimuli were presented to participants: one ‘safe’ cue presented alone; one ‘threat’ cue paired with an aversive noise to enable conditioning of physiological startle responses (skin conductance response, SCR; heart rate, HR). Retention of conditioned physiological responses was subsequently tested with presentation of both cues without the aversive noise in an ‘extinction’ phase. Primary outcomes were the magnitude of the initial unconditioned SCR and HR change responses to the aversive ‘threat’ and acquisition and retention of conditioned responses after conditioning. Secondary outcomes were neuropsychological measures and genotype associations.The initial (unconditioned) mean SCR to threat was greater in DMD than Controls (Mean difference 3.0 µS (95% CI 1.0, 5.1), P=.004), associated with a significant threat-induced bradycardia only in the DMD group (mean difference -5.6 bpm (95% CI 0.51, 16.9); P=.04). DMD participants found the task more aversive than Controls, consequently early termination during the extinction phase occurred in 26% of the DMD group (vs. 0% Controls; P=.007).This study provides the first evidence that boys with DMD show increased unconditioned startle responses to threat, similar to the mdx mouse phenotype that also responds to brain dystrophin restoration. Our study provides new insights into the neurobiology underlying the complex neuropsychiatric co-morbidities in DMD and defines an objective measure of this CNS phenotype, which will be valuable for future CNS-targeted dystrophin-restoration studies.

Duchenne muscular dystrophy (DMD), an X-linked childhood-onset muscular dystrophy caused by loss of the protein dystrophin, can be associated with neurodevelopmental, emotional and behavioural problems. A DMD mouse model also displays a neuropsychiatric phenotype, including increased startle responses to threat which normalise when dystrophin is restored in the brain.We hypothesised that startle responses may also be increased in humans with DMD, which would have potential translational therapeutic implications. To investigate this, we first designed a novel discrimination fear-conditioning task and tested it in six healthy volunteers, followed by male DMD (n=11) and Control (n=9) participants aged 7-12 years. The aims of this methodological task development study were to: i) confirm the task efficacy; ii) optimise data processing procedures; iii) determine the most appropriate outcome measures.In the task, two neutral visual stimuli were presented: one ‘safe’ cue presented alone; one ‘threat’ cue paired with a threat stimulus (aversive noise) to enable conditioning of physiological startle responses (skin conductance response, SCR, and heart rate). Outcomes were the unconditioned physiological startle responses to the initial threat, and retention of conditioned responses in the absence of the threat stimulus.We present the protocol development and optimisation of data processing methods based on empirical data. We found that the task was effective in producing significantly higher physiological startle SCR in reinforced ‘threat’ trials compared to ‘safe’ trials (PP=.01) and reliability assessment in test-retest analysis (rho=.86). The definition of this novel outcome will allow us to study this response in a DMD population.

To develop a Pediatric glucocorticoid toxicity index (pGTI), a standardized, weighted clinical outcome assessment that measures change in glucocorticoid (GC) toxicity over time.Fourteen physician experts from 7 subspecialties participated. The physician experts represented multiple subspecialties in which GCs play a major role in the treatment of inflammatory disease: nephrology, rheumatology, oncology, endocrinology, genetics, psychiatry, and maternal-fetal medicine. Nine investigators were from Canada, Europe, or New Zealand, and 5 were from the United States. Group consensus methods and multi-criteria decision analysis were used. The pGTI is an aggregate assessment of GC toxicities that are common, important, and dynamic. These toxicities are organized into health domains graded as minor, moderate, or major and are weighted according to severity. The relative weights were derived by group consensus and multi-criteria decision analysis using the 1000MindsOne hundred and seven (107) toxicity items were included in the pGTI and thirty-two (32) in the Damage Checklist. To assess the degree to which the pGTI corresponds to expert clinical judgement, the investigators ranked 15 cases by clinical judgement from highest to lowest GC toxicity. Expert rankings were then compared to case ranking by the pGTI, yielding excellent agreement (weighted kappa 0.86). The pGTI was migrated to a digital environment following its development and initial validation. The digital platform is designed to ensure ease-of-use in the clinic, rigor in application, and accuracy of scoring. Clinic staff enter vital signs, laboratory results, and medication changes relevant to pGTI scoring. Clinicians record findings for GC myopathy, skin toxicity, mood dysfunction, and infection. The pGTI algorithms then apply the weights to these raw data and calculate scores. Embedded logic accounts for the impact of age- and sex-related reference ranges on several health domains: blood pressure, lipid metabolism, and bone mineral density. Other algorithms account for anticipated changes in the height Z-scores used in the growth domain, thereby addressing a concern unique to GC toxicity in children. The Damage Checklist ensures comprehensive measurement of GC toxicity but does not contribute to pGTI scoring, because the scored domains emphasize manifestations of GC toxicity that are likely to change over the course of a trial.We describe the development and initial evaluation of a weighted, composite toxicity index for the assessment of morbidity related to GC use in children and adolescents. Developing the pGTI digital platform was essential for performing the nuanced calculations necessary to ensure rigor, accuracy, and ease-of-use in both clinic and research settings.

Copy number variants are amongst the most highly penetrant risk factors for psychopathology and neurodevelopmental deficits, but little information about the detailed clinical phenotype associated with particular variants is available. We present the largest study of the microdeletion and -duplication at the distal 1q21 locus, which has been associated with schizophrenia and intellectual disability, in order to investigate the range of psychiatric phenotypes. Clinical and cognitive data from 68 deletion and 55 duplication carriers were analysed with logistic regression analysis to compare frequencies of mental disorders between carrier groups and controls, and linear mixed models to compare quantitative phenotypes. Both children and adults with copy number variants at 1q21 had high frequencies of psychopathology. In the children, neurodevelopmental disorders were most prominent (56% for deletion, 68% for duplication carriers). Adults had increased prevalence of mood (35% for deletion [OR = 6.6 (95% CI: 1.4-40.1)], 55% for duplication carriers [8.3 (1.4-55.5)]) and anxiety disorders (24% [1.8 (0.4-8.4)] and 55% [10.0 (1.9-71.2)]). The adult group, which included mainly genetically affected parents of probands, had an IQ in the normal range. These results confirm high prevalence of neurodevelopmental disorders associated with CNVs at 1q21 but also reveal high prevalence of mood and anxiety disorders in a high-functioning adult group with these CNVs. Because carriers of neurodevelopmental CNVs who show relevant psychopathology but no major cognitive impairment are not currently routinely receiving clinical genetic services widening of genetic testing in psychiatry may be considered.

Background Turner Syndrome (TS; 45,X) is a sex chromosome aneuploidy associated with deficits in social interaction, for which clinical care guidelines have recently recommended trialling a social skills training intervention. The present study aimed to gather preliminary evidence to support a training programme for young women. Methods Semi-structured interviews and psychometric questionnaires about social ability were administered to young women with TS aged 16 to 25 years old (n=17) and their parents (n=20). Interview transcripts were analysed using thematic analysis. Results Although young women with TS experienced a "wide range of social competencies," they attributed social challenges to "personal and contextual factors." The magnitude of these challenges to social integration intensified during adolescence. They felt increasingly "out of sync" with their peers. They also considered their social abilities to be better than their parents did; on a scale of autistic traits (rated by parents), half had mild to severe autistic traits. Most expressed interest in taking part in a social skills programme. Conclusion Young women with TS are aware they experience difficulties in social communication, and they express interest in improving their social skills. Accordingly, social skills training during adolescence would be welcomed by them and their families. Any intervention should take account of their feelings of social dislocation arising from hearing difficulties together with limited recognition, and slow processing, of social cues.

Clinical relevance: To ascertain if the photopic negative response of the electroretinogram is different in autism spectrum disorder as a potential clinical marker. Background: Visual function can be atypical in autism spectrum disorder and structural imaging of the ganglion cell layers has been reported to differ in these individuals. Therefore, we sought to investigate if the photopic negative response of the full field electroretinograms, a measure of ganglion cell function, could help explain the visual perceptual differences in autism spectrum disorder and support the structural changes observed. Methods: Participants (n = 55 autism spectrum disorder, aged 5.4–26.7 years) and control (n = 87, aged 5.4–27.3 years) were recruited for the study. Full-field light-adapted electroretinograms using a Troland protocol with 10 flash strengths from −0.367 to 1.204 log photopic cd.s.m−2 were recorded in each eye. The photopic negative response amplitudes at Tmin and at t = 72 ms were compared between groups along with the a- and b-wave values. Results: There were no significant interactions between groups for the Photopic Negative Response measures of amplitude or time (p > 0.30). There was a group interaction between groups and flash strengths for the b-wave amplitude as previously reported (p < 0.001). Conclusion: The photopic negative response results suggest that there are no significant differences in the summed retinal ganglion cell responses produced by a full-field stimulus. Refereed/Peer-reviewed

BackgroundAutism is a heterogenous collection of disorders with a complex molecular underpinning. Evidence from post-mortem brain studies using adult brains have indicated that early prenatal development may be altered in autism. Induced pluripotent stem cells (iPSCs) generated from autistic individuals with macrocephaly also indicate prenatal development as a critical period for this condition. But little is known about early altered cellular events during prenatal stages in autism.MethodsIPSCs were generated from 9 unrelated autistic individuals without macrocephaly and with heterogeneous genetic backgrounds, and 6 typically developing, control, individuals. IPSCs were differentiated towards either cortical or midbrain fates. Gene expression and high throughput cellular phenotyping was used to characterise iPSCs at different stage of differentiation.ResultsA subset of autism-iPSC cortical neurons were RNA-sequenced to reveal autism-specific signatures similar to post-mortem brain studies, indicating a potential common biological mechanism. Autism-iPSCs differentiated towards a cortical fate displayed impairments in the ability to self-form into neural rosettes. In addition, autism-iPSCs demonstrated significant differences in rate of cell type assignment of cortical precursors, and dorsal and ventral forebrain precursors. These cellular phenotypes occurred in the absence of alterations in cell proliferation during cortical differentiation, differing from previous studies. Acquisition of cell fate during midbrain differentiation was not different between control- and autism-iPSCs.ConclusionsTaken together, our data indicate that autism-iPSCs diverge from control-iPSCs at a cellular level during early stage of neurodevelopment. This suggests that unique developmental differences associated with autism may be established at early prenatal stages.

Our mission on BJPsych International is simple. First, to promote best practice in the care and treatment of people with mental health problems worldwide. Second, to educate psychiatrists and other mental health professionals about international developments in policy and the delivery of mental health services. We aim to provide a publication platform for authors globally, with a focus on those from low- and middle-income countries who have a message to send about innovations in their country's mental health services that would be of interest to our readership. Our recent success in obtaining a listing on PubMed makes all our articles accessible to a much wider audience and will enhance interest in the journal's unique content. Importantly, the journal, which has a distribution of over 20 000 copies, is entirely open access.

This month's issue of BJPsych International focuses on Bangladesh, one of the most densely populated countries in the world and geographically vulnerable to a wide range of natural disasters. Mental health has been deteriorating since the COVID-19 crisis, but few psychiatrists and clinical psychologists are available to manage the consequences.

Objectives: This study aimed to explore the experiences of parents caring for children with intellectual and developmental disability during the UK national lockdown in spring 2020, resulting from the Covid-19 pandemic. Design: Participants were identified using opportunity sampling from the IMAGINE-ID national (UK) cohort, and completed an online survey followed by a semi-structured interview. Interviews were analysed using thematic analysis. Setting: Interviews were conducted over the telephone in July 2020 as the first UK lockdown was ending. Participants: 23 mothers of children with intellectual and developmental disabilities aged 5 to 15 were recruited. Results: Themes reported by parents included: managing pre-existing challenges during a time of extreme change, having mixed emotions about the benefits and difficulties that arose during the lockdown, and the need for appropriate, individualised support. Conclusions: Observations raised by parents suggested recommendations for policy in the event of future pandemic restrictions, namely: empowering parents as experts, providing tailored digital intervention, and supporting parents’ mental health to support children.

Copy number variants are amongst the most highly penetrant risk factors for psychopathology and neurodevelopmental deficits, but little information about the detailed clinical phenotype associated with particular variants is available. We present the largest study of the microdeletion and -duplication at the distal 1q21 locus, which has been associated with schizophrenia and intellectual disability, in order to investigate the range of psychiatric phenotypes. Clinical and cognitive data from 68 deletion and 55 duplication carriers were analysed with logistic regression analysis to compare frequencies of mental disorders between carrier groups and controls, and linear mixed models to compare quantitative phenotypes. Both children and adults with copy number variants at 1q21 had high frequencies of psychopathology. In the children, neurodevelopmental disorders were most prominent (56% for deletion, 68% for duplication carriers). Adults had increased prevalence of mood (35% for deletion [OR = 6.6 (95% CI: 1.4–40.1)], 55% for duplication carriers [8.3 (1.4–55.5)]) and anxiety disorders (24% [1.8 (0.4–8.4)] and 55% [10.0 (1.9–71.2)]). The adult group, which included mainly genetically affected parents of probands, had an IQ in the normal range. These results confirm high prevalence of neurodevelopmental disorders associated with CNVs at 1q21 but also reveal high prevalence of mood and anxiety disorders in a high-functioning adult group with these CNVs. Because carriers of neurodevelopmental CNVs who show relevant psychopathology but no major cognitive impairment are not currently routinely receiving clinical genetic services widening of genetic testing in psychiatry may be considered.

In 2013, the American Psychiatric Association (APA) published the 5th edition of its Diagnostic and Statistical Manual of Mental Disorders (DSM-5). In 2019, the World Health Assembly approved the 11th revision of the International Classification of Diseases (ICD-11). It has often been suggested that the field would benefit from a single, unified classification of mental disorders, although the priorities and constituencies of the two sponsoring organizations are quite different. During the development of the ICD-11 and DSM-5, the World Health Organization (WHO) and the APA made efforts toward harmonizing the two systems, including the appointment of an ICD-DSM Harmonization Group. This paper evaluates the success of these harmonization efforts and provides a guide for practitioners, researchers and policy makers describing the differences between the two systems at both the organizational and the disorder level. The organization of the two classifications of mental disorders is substantially similar. There are nineteen ICD-11 disorder categories that do not appear in DSM-5, and seven DSM-5 disorder categories that do not appear in the ICD-11. We compared the Essential Features section of the ICD-11 Clinical Descriptions and Diagnostic Guidelines (CDDG) with the DSM-5 criteria sets for 103 diagnostic entities that appear in both systems. We rated 20 disorders (19.4%) as having major differences, 42 disorders (40.8%) as having minor definitional differences, 10 disorders (9.7%) as having minor differences due to greater degree of specification in DSM-5, and 31 disorders (30.1%) as essentially identical. Detailed descriptions of the major differences and some of the most important minor differences, with their rationale and related evidence, are provided. The ICD and DSM are now closer than at any time since the ICD-8 and DSM-II. Differences are largely based on the differing priorities and uses of the two diagnostic systems and on differing interpretations of the evidence. Substantively divergent approaches allow for empirical comparisons of validity and utility and can contribute to advances in the field.

Copy number variants (CNVs) play an important role in the genetic underpinnings of neuropsychiatric/neurodevelopmental disorders. The chromosomal region 16p11.2 (BP4-BP5) harbours both deletions and duplications that are associated in carriers with neurodevelopmental and neuropsychiatric conditions as well as several rare disorders including congenital malformation syndromes. The aim of this article is to provide a review of the current knowledge of the diverse neurodevelopmental disorders (NDD) associated with 16p11.2 deletions and duplications reported in published cohorts. A literature review was conducted using the PubMed/MEDLINE electronic database limited to papers published in English between 1 January 2010 and 31 July 2020, describing 16p11.2 deletions and duplications carriers' cohorts. Twelve articles meeting inclusion criteria were reviewed from the 75 articles identified by the search. Of these twelve papers, eight described both deletions and duplications, three described deletions only and one described duplications only. This study highlights the heterogeneity of NDD descriptions of the selected cohorts and inconsistencies concerning accuracy of data reporting. info:eu-repo/semantics/publishedVersion