1. Fiksinski AM, Breetvelt EJ, Duijff SN, Bassett AS, Kahn RS, Vorstman JA. {{Autism Spectrum and psychosis risk in the 22q11.2 deletion syndrome. Findings from a prospective longitudinal study}}. {Schizophr Res};2017 (Jan 21)
BACKGROUND: Individuals with 22q11.2 deletion syndrome (22q11DS) have a 25% risk for schizophrenia and related psychotic disorders. Some have hypothesized that Autism Spectrum Disorders (ASDs) diagnosed in children with 22q11DS may actually represent the social-communicative defects often observed during the early developmental stages of schizophrenia. METHODS: We prospectively studied 89 children with 22q11DS to test this hypothesis. At baseline, the Autism Diagnostic Interview was used to assess ASD, evaluating both current and early childhood behaviors. At follow-up, the Schedule for Affective Disorders and Schizophrenia for School-Age Children (K-SADS) was used to determine development of a psychotic disorder or psychotic symptoms. RESULTS: The average age (+/-SD) at first and last assessments was 14.3+/-1.9 and 19.0+/-3.0years, respectively. Nineteen (21.3%) children developed a psychotic disorder. Contrary to our hypothesis, there was no significant difference in the proportion that developed a psychotic disorder, comparing those with (n=9, 17.3%) and those without ASD at baseline (n=10, 27%; OR=0.500, 95% CI=0.160-1.569, p=0.235). Similar results were obtained using autistic symptom severity as quantitative predicting variable, psychotic symptoms as the outcome, and when correcting for age, gender and full scale IQ. CONCLUSION: Results indicate that in children with 22q11DS, early childhood autistic features are not associated with an increased risk for subsequent development of psychotic disorders or symptoms, replicating previous retrospective findings in adults with 22q11DS. These results indicate that ASD and psychotic disorders can emerge independently, as pleiotropic phenotypes in the context of 22q11DS.
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2. Gesundheit B, Rosenzweig JP. {{Editorial: Autism Spectrum Disorders (ASD)-Searching for the Biological Basis for Behavioral Symptoms and New Therapeutic Targets}}. {Front Neurosci};2016;10:607.
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3. Mansilla A, Chaves-Sanjuan A, Campillo NE, Semelidou O, Martinez-Gonzalez L, Infantes L, Gonzalez-Rubio JM, Gil C, Conde S, Skoulakis EM, Ferrus A, Martinez A, Sanchez-Barrena MJ. {{Interference of the complex between NCS-1 and Ric8a with phenothiazines regulates synaptic function and is an approach for fragile X syndrome}}. {Proc Natl Acad Sci U S A};2017 (Jan 24)
The protein complex formed by the Ca2+ sensor neuronal calcium sensor 1 (NCS-1) and the guanine exchange factor protein Ric8a coregulates synapse number and probability of neurotransmitter release, emerging as a potential therapeutic target for diseases affecting synapses, such as fragile X syndrome (FXS), the most common heritable autism disorder. Using crystallographic data and the virtual screening of a chemical library, we identified a set of heterocyclic small molecules as potential inhibitors of the NCS-1/Ric8a interaction. The aminophenothiazine FD44 interferes with NCS-1/Ric8a binding, and it restores normal synapse number and associative learning in a Drosophila FXS model. The synaptic effects elicited by FD44 feeding are consistent with the genetic manipulation of NCS-1. The crystal structure of NCS-1 bound to FD44 and the structure-function studies performed with structurally close analogs explain the FD44 specificity and the mechanism of inhibition, in which the small molecule stabilizes a mobile C-terminal helix inside a hydrophobic crevice of NCS-1 to impede Ric8a interaction. Our study shows the drugability of the NCS-1/Ric8a interface and uncovers a suitable region in NCS-1 for development of additional drugs of potential use on FXS and related synaptic disorders.
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4. Manwaring SS, Mead DL, Swineford L, Thurm A. {{Modelling gesture use and early language development in autism spectrum disorder}}. {Int J Lang Commun Disord};2017 (Jan 24)
BACKGROUND: Nonverbal communication abilities, including gesture use, are impaired in autism spectrum disorder (ASD). However, little is known about how common gestures may influence or be influenced by other areas of development. AIMS: To examine the relationships between gesture, fine motor and language in young children with ASD compared with a comparison group using multiple measures and methods in a structural equation modelling framework. METHODS & PROCEDURES: Participants included 110 children with ASD and a non-ASD comparison group of 87 children (that included children with developmental delays (DD) or typical development (TD)), from 12 to 48 months of age. A construct of gesture use as measured by the Communication and Symbolic Behavior Scales-Developmental Profile Caregiver Questionnaire (CQ) and the Autism Diagnostic Observation Schedule (ADOS), as well as fine motor from the Mullen Scales of Early Learning and Vineland Adaptive Behavior Scales-II (VABS-II) was examined using second-order confirmatory factor analysis (CFA). A series of structural equation models then examined concurrent relationships between the aforementioned latent gesture construct and expressive and receptive language. A series of hierarchical regression analyses was run in a subsample of 36 children with ASD with longitudinal data to determine how gesture factor scores predicted later language outcomes. OUTCOMES & RESULTS: Across study groups, the gesture CFA model with indicators of gesture use from both the CQ (parent-reported) and ADOS (direct observation), and measures of fine motor provided good fit with all indicators significantly and strongly loading onto one gesture factor. This model of gesture use, controlling for age, was found to correlate strongly with concurrent expressive and receptive language. The correlations between gestures and concurrent language were similar in magnitude in both the ASD and non-ASD groups. In the longitudinal subsample of children with ASD, gestures at time 1 predicted later receptive (but not expressive) language outcomes on the VABS-II, after controlling for nonverbal cognition, ASD severity, age and time 1 language. CONCLUSIONS & IMPLICATIONS: This study extends research on the relationship between nonverbal communication and language by supporting the idea of an underlying construct of gesture use that includes fine motor ability and relates to language in young children with ASD. This further supports theories espousing developmental influences of motor and nonverbal communication strategies as important in early language learning.
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5. Morrissey C, Geach N, Alexander R, Chester V, Devapriam J, Duggan C, Langdon PE, Lindsay B, McCarthy J, Walker DM. Health Services and Delivery Research. Researching outcomes from forensic services for people with intellectual or developmental disabilities: a systematic review, evidence synthesis and expert and patient/carer consultation. Southampton (UK): NIHR Journals Library
Copyright (c) Queen’s Printer and Controller of HMSO 2017. This work was produced by Morrissey et al. under the terms of a commissioning contract issued by the Secretary of State for Health. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK., 2017.
Inpatient services for people with intellectual and other types of developmental disabilities (IDD) who also have forensic or risk issues are largely provided in secure hospitals. Although this is a health service sector with high levels of expenditure, there is limited empirical information on patient outcomes from such services. In order for a future substantive longitudinal outcomes study in forensic IDD services to be informed and feasible, more needs to be understood about the outcome domains that are of relevance and importance and how they should be measured. A preliminary series of studies was therefore undertaken. To synthesise evidence in relation to the outcome domains that have been researched in the existing literature from hospital and community forensic services for people with IDD, within the broad domains of service effectiveness, patient safety and patient experience. To identify a definitive framework of outcome domains (and associated measures and indicators) based both on this research evidence and on the views of patients, carers and clinicians. To synthesise the information gathered in order to inform design of future multisite longitudinal research in the sector. Three linked studies were conducted. Stage 1 was a systematic review and evidence synthesis of outcome domains and measures as found within the forensic IDD literature. Stage 2 was a consultation exercise with 15 patients with IDD and six carers. Stage 3 was a modified Delphi consensus exercise with 15 clinicians and experts using the information gathered at stages 1 and 2. At stage 1, 60 studies that researched a range of outcomes in forensic IDD services were identified from the literature. This resulted in the construction of an initial framework of outcome domains. The consultation with patients and carers at stage 2 added to these framework domains that related particularly to carer experience and the level of support post discharge in the community. The Delphi process at stage 3 confirmed the validity of the resulting framework for clinician. This survey also identified the outcome measures preferred by clinicians and those that are currently utilised in services. Thus, indicators of appropriate measures in some important domains were identified, although there was a paucity of measures in other domains. Together, these three linked studies led to the development of an evidence-based framework of key outcome domains and subdomains. A provisional list of associated measures and indicators was developed, although with the paucity of measures in some domains development of specific indicators may be required. With further refinement this could eventually be utilised by services and commissioners for comparative purposes, and in future empirical research on outcomes in forensic IDD services. An outline research proposal closely linked to recent policy initiatives was proposed. Limitations of the study include the relatively small number of carers and patients and range of experts consulted. This would comprise a national longitudinal study tracking IDD in patients through hospitalisation and discharge. This study is registered as PROSPERO CRD42015016941. The National Institute for Health Research Health Services and Delivery Research programme.
6. Postorino V, Scahill L, De Peppo L, Fatta LM, Zanna V, Castiglioni MC, Gillespie S, Vicari S, Mazzone L. {{Investigation of Autism Spectrum Disorder and Autistic Traits in an Adolescent Sample with Anorexia Nervosa}}. {J Autism Dev Disord};2017 (Jan 24)
This study aimed to examine the presence of Autism Spectrum Disorder (ASD) in a sample of female adolescents with Anorexia Nervosa (AN) during the acute phase of illness. We also compare the level of autistic traits, social perception skills and obsessive-compulsive symptoms in four groups: AN, ASD, and two gender- and age-matched control groups. Of the 30 AN participants, only three scored above the conventional ADOS-2 threshold for ASD. The AN participants were similar to their controls on autistic trait measures, and to the ASD group on obsessive-compulsive measures, and on theory of mind ability and affect recognition measures. Further longitudinal studies are needed in order to determine the association between these conditions.
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7. Tomeny TS, Ellis BM, Rankin JA, Barry TD. {{Sibling relationship quality and psychosocial outcomes among adult siblings of individuals with autism spectrum disorder and individuals with intellectual disability without autism}}. {Res Dev Disabil};2017 (Jan 22);62:104-114.
Research on adult typically-developing (TD) siblings of individuals with developmental disabilities remains limited, and outcomes for TD siblings appear to vary widely. For the current study, 82 adult TD siblings of individuals with autism spectrum disorder (ASD) or intellectual disability (ID) completed questionnaires about themselves and their affected sibling. Results of this study suggest that the attitudes possessed by adult TD siblings are important to consider when understanding adult TD sibling outcomes. Specifically, data indicate that higher levels of positive sibling relationship attitudes are related to TD siblings providing more aid/support to their sibling with a disability, along with having higher levels of general life satisfaction, and negatively related to levels of stress and depressive symptoms among TD siblings. Consistent with previous child research, siblings of individuals with ASD reported fewer positive sibling relationship attitudes compared to siblings of individuals with ID. Finally, group membership related to aid provided, depressive symptoms, and stress of TD siblings indirectly through sibling relationship attitudes. Overall, results indicate that sibling relationship attitudes may be particularly important to consider when conceptualizing sibling relationships when one sibling has an intellectual or developmental disability.
