1. Abu Diab M, Eiges R. {{The Contribution of Pluripotent Stem Cell (PSC)-Based Models to the Study of Fragile X Syndrome (FXS)}}. {Brain Sci}. 2019; 9(2).
Fragile X syndrome (FXS) is the most common heritable form of cognitive impairment. It results from a deficiency in the fragile X mental retardation protein (FMRP) due to a CGG repeat expansion in the 5′-UTR of the X-linked FMR1 gene. When CGGs expand beyond 200 copies, they lead to epigenetic gene silencing of the gene. In addition, the greater the allele size, the more likely it will become unstable and exhibit mosaicism for expansion size between and within tissues in affected individuals. The timing and mechanisms of FMR1 epigenetic gene silencing and repeat instability are far from being understood given the lack of appropriate cellular and animal models that can fully recapitulate the molecular features characteristic of the disease pathogenesis in humans. This review summarizes the data collected to date from mutant human embryonic stem cells, induced pluripotent stem cells, and hybrid fusions, and discusses their contribution to the investigation of FXS, their key limitations, and future prospects.
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2. Alexander L, Farrelly N. {{A case of mistaken diagnoses: diagnostic and management challenges in a case of adult autism spectrum disorder}}. {Irish journal of psychological medicine}. 2019: 1-4.
Autism spectrum disorder (ASD) is frequently identified in children but is often unrecognised in adults. ASD is characterised by difficulties in social interaction, communication and restricted interests, but other presentations are common, especially in adults. This report describes a 34-year-old man with a history of multiple psychiatric diagnoses including generalised anxiety disorder, major depressive disorder and panic disorder. He was diagnosed with ASD in his early 30s and engaged in a targeted treatment plan, including rationalisation of medications, supportive therapy and occupational therapy, which successfully facilitated discharge from mental health services. This case illustrates the atypical presentation of ASD in adults, which is diagnostically challenging. Such cases often present to community mental health services and may be misdiagnosed as treatment resistant cases of depressive, anxiety or personality disorders. Accurate diagnosis and targeted management is more likely to yield a successful outcome.
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3. Aljehany MS, Bennett KD. {{A Comparison of Video Prompting to Least-to-Most Prompting among Children with Autism and Intellectual Disability}}. {J Autism Dev Disord}. 2019.
Students with autism spectrum disorder (ASD) and intellectual disability (ID) may experience challenges when learning tasks that are complex and require numerous steps. This difficulty can lead to employment issues for this population of learners. Therefore, researchers have explored methods to teach employment-related tasks to students with ASD and ID. Two such procedures are video prompting (VP) and least-to-most prompting. These procedures are frequently combined as an intervention package to boost student responding. The purpose of this study was to explore which of these interventions was more effective and efficient when used to teach office tasks to individuals with ASD and ID. Three adolescent students participated in this study. Using the adapted alternating treatments design, we found that VP was more effective and efficient for two participants, whereas least-to-most prompting was more effective but less efficient for the remaining participant. Implications for research and practice are discussed.
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4. Barfi S, Poortahmasebi V, Ofoghi H, Farahmand M, Ghorbani S, Norouzi M, Ghalichi L, Jazayeri SM. {{Measurement of serum hepatitis B surface antibody (HBs-Ab) levels in Iranian autistic children and evaluation of immunological memory after booster dose injection in comparison with controls}}. {Journal of medical virology}. 2019.
BACKGROUND: Responsiveness to hepatitis B vaccine among Autism Spectrum Disorders (ASD) patients has not been evaluated worldwide. We aimed to determine the anti-HBs antibody duration in autistic and healthy children few years after primary vaccination and evaluate their immunological memory against Hepatitis B virus (HBV( vaccine with booster dose administration. METHODS: 107 and 147 HBsAg-negative children from ASD and normal population were recruited, respectively. HBV seromarkers (HBc-Ab & HBs-Ag & HBs-Ab) were assessed and subsequently, molecular tests were employed on all subjects. A booster dose of vaccine was injected for those who showed low levels (<10 mIU/mL) of anti-HBs and their antibody levels was measured 4 weeks afterwards. RESULTS: The mean ages of ASD and control groups were 7.14+/- 2.42 and 8.68+/-1.96 respectively. Seven (6.5%) of ASD group were positive for anti-HBc and one child was positive for occult hepatitis B infection (HBsAg negative, HBV DNA positive). In ASD, 54 (50.4%) and 53 (49.6%) had adequate (>10 mIU/mL) and low anti-HBs levels, respectively. Among control group, 74 (50.4%) and 73 (49.6%) had sufficient and low antibody levels, respectively. After injection of a booster dose for all children with low antibody, 100% of ASD and 92% (59 of 64) of control pupils contained >10 mIU/mL of antibody, respectively. In both groups, the HBs-Ab titer increased similarly in response to the booster injection (P<0.05). CONCLUSION: Despite previous investigations regarding immune impairment in individuals with autism, the immune system of these individuals was able to manage the hepatitis B vaccine challenge. This article is protected by copyright. All rights reserved. Lien vers le texte intégral (Open Access ou abonnement)
5. Bitsika V, Arnold WA, Sharpley CF. {{The Role of Sensory Features in Mediating Associations Between Autism Symptoms and Anxiety in Boys with Autism Spectrum Disorder}}. {J Autism Dev Disord}. 2019.
To investigate possible correlates of generalised anxiety disorder (GAD) in young males with ASD, a test of the mediation effects of sensory features (SF) upon the association between ASD symptoms and GAD was conducted with 150 males aged 6 to 18 years. GAD data were obtained from parents of the boys and from the boys themselves; SF and ASD data were obtained from parents. Symptoms of ASD were found to influence elevated levels of parent-rated GAD indirectly through greater levels of sensory avoiding, and auditory-specific sensory behaviours correlated with parent-rated anxiety more strongly than other sensory modalities. There were no significant effects for the boys’ self-rated GAD.
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6. Calleja S, Islam FMA, Kingsley J, McDonald R. {{The disparities of healthcare access for adults with autism spectrum disorder: Protocol for a systematic review}}. {Medicine}. 2019; 98(7): e14480.
INTRODUCTION: Adults living with autism spectrum disorder (ASD) can experience many factors that may impact their everyday lives. Striving for optimal health and enduring a healthy lifestyle comes with the ability to access appropriate healthcare services, yet adults with ASD have unmet healthcare needs. The barriers and enablers of healthcare access for adults with ASD remain unclear. We will conduct a systematic review to explore what is currently known about healthcare access for adults with ASD, this will determine the level and appropriateness of access to healthcare services to better support the lives of adults with ASD. METHOD AND ANALYSIS: The systematic review will report on all studies that include quantitative, qualitative, and mixed-methods designs that consider healthcare access for adults with ASD. We will search 5 databases: EBSCOhost, Scopus, PubMed, the Cochrane Library, and Web of Science. The Mixed Methods Appraisal Tool (MMAT) will be used to assess quality of articles and the Cochrane RoB 2.0 Tool will be used to assess for bias. Clarifying the evidence in this area will be important for future research directions when developing and piloting health interventions for researchers and healthcare clinicians in the field. ETHICS AND DISSEMINATION: There are no human participants, data, or tissue being directly studied for the purposes of the review; therefore, ethics approval and consent to participate is not applicable. REGISTRATION AND STATUS: PROSPERO 2018 CRD42018116093.
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7. Cole EJ, Enticott PG, Oberman LM, Gwynette MF, Casanova MF, Jackson SLJ, Jannati A, McPartland JC, Naples AJ, Puts NAJ. {{The Potential of Repetitive Transcranial Magnetic Stimulation for Autism Spectrum Disorder: A Consensus Statement}}. {Biol Psychiatry}. 2019; 85(4): e21-e2.
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8. Craig F, De Giacomo A, Operto FF, Margari M, Trabacca A, Margari L. {{Association between feeding/mealtime behavior problems and internalizing/externalizing problems in autism spectrum disorder (ASD), other neurodevelopmental disorders (NDDs) and typically developing children}}. {Minerva pediatrica}. 2019.
BACKGROUND: The aim of current study was to examine the nature and prevalence of feeding problems and mealtime behavior problems in children with ASD comparing to children with other neurodevelopmental disorders (NNDs) and TD children. We also investigated the impact of intelligence quotient (IQ) and/or emotional and behavioral problems on feeding and mealtime behavior problems. METHODS: Participants completed the following tests: Social Communication Questionnaire (SCQ), Child Behavior Checklist (CBCL), Brief Autism Mealtime Behavior Inventory (BAMBI) and Behavioral Pediatric Feeding Assessment Scale (BPFAS). RESULTS: Children with ASD showed more feeding and mealtime behavior problems including food refusal (p<.001, p<.001) and limited variety of foods (p=.014; p=.018) compared with NDDs and TD children. ASD group showed more problems in mealtime behavior (p=.034) and parent behaviors (p=.028) compared to TD group. Internalizing (p=.003) and externalizing (p=.008) problems were positively related to parent frustration during mealtime in ASD group. CONCLUSIONS: These results suggest that routine screening for feeding and mealtime behavior problems among children with ASD is necessary to prevent dietary inadequacies that may be associated with eating habits. Lien vers le texte intégral (Open Access ou abonnement)
9. Davis JM, Heft I, Scherer SW, Sikela JM. {{A Third Linear Association Between Olduvai (DUF1220) Copy Number and Severity of the Classic Symptoms of Inherited Autism}}. {Am J Psychiatry}. 2019: appiajp201818080993.
OBJECTIVE:: The authors previously reported that the copy number of sequences encoding an Olduvai protein domain subtype (CON1) shows a linear association with the severity of social deficits and communication impairment in individuals with autism. In this study, using an improved measurement method, the authors replicated this association in an independent population. METHOD:: The authors obtained whole genome sequence (WGS) data and phenotype data on 215 individuals from the Autism Speaks MSSNG project. They derived copy number from WGS data using a modified sequence read-depth technique. A linear mixed-effects model was used to test the association between Olduvai CON1 copy number and symptom severity as measured by the Autism Diagnostic Interview-Revised. The authors then combined data from previous studies (N=524) for final analyses. RESULTS:: A significant linear association was observed between CON1 copy number and social diagnostic score (SDS) (beta=0.24) and communicative diagnostic score (CDS) (beta=0.23). Using the combined data, the authors present strong significant associations of CON1 dosage with SDS (beta=0.18) and CDS (beta=0.13). The authors also implicate Olduvai subtypes found in two genes, NBPF1 and NBPF14 (R(2)=6.2%). Associations were preferentially found in multiplex versus simplex families. CONCLUSIONS:: The finding of a third dose-dependent association between Olduvai sequences and autism severity, preferentially in multiplex families, provides strong evidence that this highly duplicated and underexamined protein domain family plays an important role in inherited autism.
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10. Dreaver J, Thompson C, Girdler S, Adolfsson M, Black MH, Falkmer M. {{Success Factors Enabling Employment for Adults on the Autism Spectrum from Employers’ Perspective}}. {J Autism Dev Disord}. 2019.
Employment outcomes for individuals with autism spectrum disorder (ASD) are poor and there is limited understanding on how best to support individuals with ASD in the workplace. Stakeholders involved in the employment of adults with ASD, including employers and employment service providers have unique insights into the factors influencing employment for this population. Organisational and individual factors facilitating successful employment for adults with ASD across Australia and Sweden were explored, including the supports and strategies underpinning employment success from an employers’ perspective. Three themes including Knowledge and Understanding of ASD, Work Environment and Job Match emerged, suggesting that a holistic approach was key to supporting success, with employer knowledge and understanding of ASD underpinning their ability to facilitate employment.
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11. Faber S, Fahrenholz T, Wolle MM, Kern JC, 2nd, Pamuku M, Miller L, Jamrom J, Skip Kingston HM. {{Chronic exposure to xenobiotic pollution leads to significantly higher total glutathione and lower reduced to oxidized glutathione ratio in red blood cells of children with autism}}. {Free radical biology & medicine}. 2019.
Analyses of reduced glutathione (GSH), oxidized glutathione (GSSG), and total glutathione (tGSH) in red blood cell samples from 30 children diagnosed with autism and 30 age, gender, and socioeconomic status matched controls were undertaken. The children’s ages ranged from 2-9. Samples were obtained from subjects residing in Western Pennsylvania, an area of the United States greatly affected by high levels of mercury deposition and airborne PM 2.5 particulates. Liquid chromatography – mass spectrometry was utilized by following EPA Method 6800 for sample analyses. The children with autism had a significantly lower mean red blood cell (RBC) reduced to oxidized glutathione ratio (GSH/GSSG) compared to the control children (p=0.025). In addition, compared to the controls, the children with autism had significantly higher RBC tGSH values (p=0.0076) and GSH values (p=0.022). These results suggest that exposure to toxic elements may prompt compensatory increases in production of GSH in children with autism in environments higher in toxins. The compensation did not fully correct the anti-oxidant properties of exposure to xenobiotics as demonstrated by the significantly lower GSH/GSSG in children with autism compared to controls. Out of a set of glutathione biomarkers, GSH/GSSG may best determine the degree of compensation for oxidative stress in children with autism.
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12. Guerini FR, Bolognesi E, Sotgiu S, Carta A, Clerici C, Chiappedi M, Ghezzo A, Zanette M, Martina Mensi M, Paola Canevini M, Zanzottera M, Agliardi C, Saul Costa A, Balottin U, Clerici M. {{HLA-G allelic distribution in Sardinian children with Autism Spectrum Disorders: a replication study}}. {Brain, behavior, and immunity}. 2019.
Recent results show that in mainland Italian children with Autism spectrum disorder (ASD), HLA-G coding alleles distribution is skewed and an association between HLA-G*01:05N and ASD is present. Herein, in an independent cohort of Sardinian ASD (sASD) children and their relatives, we verify whether HLA-G allele association with ASD could be confirmed in this genetically peculiar insular population. One hundred children with a diagnosis of ASD, born in Sardinia and of Sardinian descent, 91 of their mothers, and 40 of their healthy siblings were enrolled. DNA sequencing analysis of HLA-G exon 2, 3 and 4 was used to obtain HLA-G allelic frequencies. Alleles distribution was compared with that of continental ASD children and with a control group of Caucasoid couples of multiparous women and their partners from Brazil and Denmark. Skewing of HLA-G allele distribution was replicated in sASD children; in particular, the HLA-G*01:03 allele, associated with reduced fetal tolerogenicity and development of myeloid leukemia, was more common in both ASD groups compared to controls (pc=1×10(-3); OR:3.5, 95%CI: 1.8-6.8). However, given the lack of data on HLA-G*01:03 allelic distribution among Sardinian healthy subjects, we cannot exclude a population effect. These data confirm an association of HLA-G locus with ASD development, particularly with those alleles linked to a lower expression of tolerogenic HLA-G protein, thus warranting further studies on HLA-G polymorphism distribution in different ASD populations.
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13. Huang H, Liu X, Jin Y, Lee SW, Wee CY, Shen D. {{Enhancing the representation of functional connectivity networks by fusing multi-view information for autism spectrum disorder diagnosis}}. {Hum Brain Mapp}. 2019; 40(3): 833-54.
Functional connectivity network provides novel insights on how distributed brain regions are functionally integrated, and its deviations from healthy brain have recently been employed to identify biomarkers for neuropsychiatric disorders. However, most of brain network analysis methods utilized features extracted only from one functional connectivity network for brain disease detection and cannot provide a comprehensive representation on the subtle disruptions of brain functional organization induced by neuropsychiatric disorders. Inspired by the principles of multi-view learning which utilizes information from multiple views to enhance object representation, we propose a novel multiple network based framework to enhance the representation of functional connectivity networks by fusing the common and complementary information conveyed in multiple networks. Specifically, four functional connectivity networks corresponding to the four adjacent values of regularization parameter are generated via a sparse regression model with group constraint ( l2,1 -norm), to enhance the common intrinsic topological structure and limit the error rate caused by different views. To obtain a set of more meaningful and discriminative features, we propose using a modified version of weighted clustering coefficients to quantify the subtle differences of each group-sparse network at local level. We then linearly fuse the selected features from each individual network via a multi-kernel support vector machine for autism spectrum disorder (ASD) diagnosis. The proposed framework achieves an accuracy of 79.35%, outperforming all the compared single network methods for at least 7% improvement. Moreover, compared with other multiple network methods, our method also achieves the best performance, that is, with at least 11% improvement in accuracy.
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14. Kikkawa T, Casingal CR, Chun SH, Shinohara H, Hiraoka K, Osumi N. {{The role of Pax6 in brain development and its impact on pathogenesis of autism spectrum disorder}}. {Brain Res}. 2019; 1705: 95-103.
Pax6 transcription factor is a key player in several aspects of brain development and function. Autism spectrum disorder (ASD) is a neurodevelopmental disorder in which several loci and/or genes have been suggested as causative candidate factors. Based on data obtained from meta-analyses of the transcriptome and ChIP analyses, we hypothesized that the neurodevelopmental gene PAX6 regulates and/or binds to a large number of genes (including many ASD-related ones) that modulate the fate of neural stem/progenitor cells and functions of neuronal cells, subsequently affecting animal behavior. Network analyses of PAX6/ASD-related molecules revealed significant clusters of molecular interactions involving regulation of cell-cell adhesion, ion transport, and transcriptional regulation. We discuss a novel function of Pax6 as a chromatin modulator that alters the chromatin status of ASD genes, thereby inducing diverse phenotypes of ASD and related neurodevelopmental diseases.
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15. Kozhemiako N, Vakorin V, Nunes AS, Iarocci G, Ribary U, Doesburg SM. {{Extreme male developmental trajectories of homotopic brain connectivity in autism}}. {Hum Brain Mapp}. 2019; 40(3): 987-1000.
It has been proposed that autism spectrum disorder (ASD) may be characterized by an extreme male brain (EMB) pattern of brain development. Here, we performed the first investigation of how age-related changes in functional brain connectivity may be expressed differently in females and males with ASD. We analyzed resting-state functional magnetic resonance imaging data of 107 typically developing (TD) females, 114 TD males, 104 females, and 115 males with ASD (6-26 years) from the autism brain imaging data exchange repository. We explored how interhemispheric homotopic connectivity and its maturational curvatures change across groups. Differences between ASD and TD and between females and males with ASD were observed for the rate of changes in connectivity in the absence of overall differences in connectivity. The largest portion of variance in age-related changes in connectivity was described through similarities between TD males, ASD males, and ASD females, in contrast to TD females. We found that shape of developmental curvature is associated with symptomatology in both males and females with ASD. We demonstrated that females and males with ASD tended to follow the male pattern of developmental changes in interhemispheric connectivity, supporting the EMB theory of ASD.
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16. Kumari D, Gazy I, Usdin K. {{Pharmacological Reactivation of the Silenced FMR1 Gene as a Targeted Therapeutic Approach for Fragile X Syndrome}}. {Brain Sci}. 2019; 9(2).
More than ~200 CGG repeats in the 5′ untranslated region of the FMR1 gene results in transcriptional silencing and the absence of the FMR1 encoded protein, FMRP. FMRP is an RNA-binding protein that regulates the transport and translation of a variety of brain mRNAs in an activity-dependent manner. The loss of FMRP causes dysregulation of many neuronal pathways and results in an intellectual disability disorder, fragile X syndrome (FXS). Currently, there is no effective treatment for FXS. In this review, we discuss reactivation of the FMR1 gene as a potential approach for FXS treatment with an emphasis on the use of small molecules to inhibit the pathways important for gene silencing.
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17. Maskey M, Rodgers J, Grahame V, Glod M, Honey E, Kinnear J, Labus M, Milne J, Minos D, McConachie H, Parr JR. {{A Randomised Controlled Feasibility Trial of Immersive Virtual Reality Treatment with Cognitive Behaviour Therapy for Specific Phobias in Young People with Autism Spectrum Disorder}}. {J Autism Dev Disord}. 2019.
We examined the feasibility and acceptability of using an immersive virtual reality environment (VRE) alongside cognitive behaviour therapy (CBT) for young people with autism experiencing specific phobia. Thirty-two participants were randomised to treatment or control. Treatment involved one session introducing CBT techniques and four VRE sessions, delivered by local clinical therapists. Change in target behaviour was independently rated. Two weeks after treatment, four treatment participants (25%) and no control participants were responders; at 6 months after treatment, six (38%) treatment and no control participants were responders. At 6 months post-treatment, symptoms had worsened for one treatment and five control (untreated) participants. Brief VRE exposure with CBT is feasible and acceptable to deliver through child clinical services and is effective for some participants.
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18. Morrison KE, Pinkham AE, Kelsven S, Ludwig K, Penn DL, Sasson NJ. {{Psychometric evaluation of social cognitive measures for adults with autism}}. {Autism Res}. 2019.
Although social cognition is frequently identified as a target in clinical trials and psychosocial interventions for adults with autism spectrum disorder (ASD), these efforts are hampered by a lack of consensus and validation of social cognitive measures. The current study provides psychometric evaluation of 11 frequently used measures encompassing different subdomains of social cognition. Adults with autism (N = 103) and typically developing controls (N = 95) completed 11 commonly used social cognitive tasks spanning the domains of emotion processing, social perception, and mentalizing/theory of mind. We examined each measure’s internal reliability and sensitivity to group differences, how performance related to general intellectual ability, and alignment of measures with a proposed two-factor structure of social cognition in ASD. Controls outperformed the ASD group on 8 of the 11 social cognitive tasks, with the largest group differences occurring on two mentalizing measures, The awareness of social inference task (TASIT) and hinting task. In ASD, all tasks demonstrated strong internal consistency and avoided ceiling and floor effects. Social cognitive performance was also related to, but not redundant with, intellectual functioning. We also found support for a two-factor structure of social cognition, with basic social perception and emotional processing aligning into a lower-order social perception factor, while mentalizing tasks aligned into a higher-order social appraisal factor. In sum, eight tasks showed adequate to strong psychometric properties. The psychometric data, effect size estimates, and correlations between measures reported here can be used for study planning for social cognitive interventions in autism. Autism Res 2019, 999: 1-13. (c) 2019 The Authors. Autism Research published by International Society for Autism Research published by Wiley Periodicals, Inc. LAY SUMMARY: We examined 11 tasks that measure how adults with autism perceive and interpret social information. Eight of the tasks were reliable and showed lower performance in adults with autism compared to typically-developing controls. Task performance was related to but distinguishable from IQ. These measures evaluated here may be useful in assessing the effectiveness of interventions and treatments to improve social abilities in adults with autism.
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19. Okamoto N, Takata A, Miyake N, Matsumoto N. {{RALA mutation in a patient with autism spectrum disorder and Noonan syndrome like phenotype}}. {Congenital anomalies}. 2019.
RASopathies including Noonan syndrome (NS), Costello syndrome, and Cardiofaciocutaneous syndrome are caused by heterozygous germline mutations in genes of the RAS/MAPK pathway that plays a role in cellular proliferation, differentiation, and survival. Novel genes associated with RASopathies are increasing in number (Aoki et al. 2016). This article is protected by copyright. All rights reserved.
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20. Percy AK. {{Rett syndrome: from recognition to diagnosis to intervention}}. {Expert review of endocrinology & metabolism}. 2008; 3(3): 327-36.
Rett syndrome is a relatively rare neurodevelopmental disorder (incidence: approximately one out of 10,000 female births) that reached worldwide prominence in the early 1980s. Owing to its overwhelming predominance in females, Rett syndrome was regarded as a genetic disorder. However, its occurrence is sporadic, with a recurrence risk well below 0.5%. In 1999, confirmation was provided by the demonstration of mutations in the MECP2 gene. At present, more than 95% of females who fulfill consensus criteria for Rett syndrome have a mutation in this gene. Over the past 25 years, understanding of the clinical features and natural history of this unique neurodevelopmental disorder has evolved dramatically. However, large segments of healthcare professionals and the general public still remain relatively uninformed. This review details the clinical picture of Rett syndrome and the diagnostic strategies required, explores the critical medical issues and recent advances in molecular neurobiology, provides an overview of intervention strategies that have been developed to date and sets the stage for future treatment trials as novel, and potentially effective, pharmacologic or molecular interventions become available.
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21. Poisson A, Chatron N, Labalme A, Till M, Broussolle E, Sanlaville D, Demily C, Lesca G. {{Regressive Autism Spectrum Disorder Expands the Phenotype of BSCL2/Seipin-Associated Neurodegeneration}}. {Biol Psychiatry}. 2019; 85(4): e17-e9.
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22. Ruane A, Carr A, Moffat V, Finn T, Murphy A, O’Brien O, Groarke H, O’Dwyer R. {{A randomised controlled trial of the Group Stepping Stones Triple P training programme for parents of children with developmental disabilities}}. {Clinical child psychology and psychiatry}. 2019: 1359104519827622.
The central aim of this study was to examine the effectiveness of Group Stepping Stones Triple P (GSSTP) in an Irish context for families of children with both developmental disabilities and internalising and externalising behavioural problems. Parents of 84 children (mean age = 5.73; SD = 2.06) with developmental disabilities and co-occurring behaviour problems attending Irish public health services were randomly assigned to a 9-week GSSTP group or a waiting list control (WLC) group. All parents completed self-report measures before (Time 1) and after (Time 2) the programme and parents in the GSSTP group were assessed at 3- to 5-month follow-up (Time 3). At Time 2, clinical improvement and reliable change rates on the primary dependent variables (summary scales of the Developmental Behaviour Checklist and Strengths and Difficulties Questionnaire) were significantly higher in the GSSTP group than in the WLC group. At Time 2, mean scores of the GSSTP group showed significant, small to medium improvements relative to the WLC group on parent-reported child behaviour problems, parenting skills and confidence, and parental adjustment. Most of these improvements were maintained at 3- to 5-month follow-up. These results indicate that GSSTP is a promising intervention for improving child behaviour and parenting outcomes in a mixed-disability group in an Irish context.
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23. Smith AM, King JJ, West PR, Ludwig MA, Donley ELR, Burrier RE, Amaral DG. {{Amino Acid Dysregulation Metabotypes: Potential Biomarkers for Diagnosis and Individualized Treatment for Subtypes of Autism Spectrum Disorder}}. {Biol Psychiatry}. 2019; 85(4): 345-54.
BACKGROUND: Autism spectrum disorder (ASD) is behaviorally and biologically heterogeneous and likely represents a series of conditions arising from different underlying genetic, metabolic, and environmental factors. There are currently no reliable diagnostic biomarkers for ASD. Based on evidence that dysregulation of branched-chain amino acids (BCAAs) may contribute to the behavioral characteristics of ASD, we tested whether dysregulation of amino acids (AAs) was a pervasive phenomenon in individuals with ASD. This is the first article to report results from the Children’s Autism Metabolome Project (CAMP), a large-scale effort to define autism biomarkers based on metabolomic analyses of blood samples from young children. METHODS: Dysregulation of AA metabolism was identified by comparing plasma metabolites from 516 children with ASD with those from 164 age-matched typically developing children recruited into the CAMP. ASD subjects were stratified into subpopulations based on shared metabolic phenotypes associated with BCAA dysregulation. RESULTS: We identified groups of AAs with positive correlations that were, as a group, negatively correlated with BCAA levels in ASD. Imbalances between these two groups of AAs identified three ASD-associated amino acid dysregulation metabotypes. The combination of glutamine, glycine, and ornithine amino acid dysregulation metabotypes identified a dysregulation in AA/BCAA metabolism that is present in 16.7% of the CAMP subjects with ASD and is detectable with a specificity of 96.3% and a positive predictive value of 93.5% within the ASD subject cohort. CONCLUSIONS: Identification and utilization of metabotypes of ASD can lead to actionable metabolic tests that support early diagnosis and stratification for targeted therapeutic interventions.
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24. Top DN, Jr., Luke SG, Stephenson KG, South M. {{Psychophysiological Arousal and Auditory Sensitivity in a Cross-Clinical Sample of Autistic and Non-autistic Anxious Adults}}. {Frontiers in psychiatry}. 2018; 9: 783.
Many autistic people report overwhelming sensory experiences and also elevated levels of anxiety. Understanding how these experiences are linked to each other can contribute to improved support and intervention for reducing sensory overload and anxiety. This study included 95 young adult participants including autistic adults, non-autistic adults reporting to a psychotherapy clinic with high levels of anxiety, and neurotypical adults with no psychiatric concerns. We measured pupil size using including a baseline task with no auditory stimulus followed by two blocks of simple auditory habituation. In a subset of 80 participants we also measured self-report levels of sensory processing, anxious apprehension, and intolerance of uncertainty. The autism group showed atypical sensory processing on all four measured domains of the Adolescent and Adult Sensory Profile including sensory sensitivity, sensory seeking, sensory avoidance, and low registration subscales. Dimensional analyses across all participants showed significant positive correlations between sensory sensitivity, sensory seeking, and sensory avoidance domains with scores from the Intolerance of Uncertainty Scale-Short Form and Penn State Worry Questionnaire. The autism group showed significantly larger pupil size than other groups at baseline, before any auditory stimulation. There were no group differences in the rate of auditory habituation, nonetheless the overall, absolute larger pupil size remained in the autism group throughout the experiment. We suggest that this and other findings could indicate chronic hyperarousal in many autistic people. Treatment for anxiety in autism should be informed by knowledge of unique aspects of anxiety in autism and consider the role of sensory experience and everyday psychophysiological arousal.
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25. Topal J, Roman V, Turcsan B. {{The dog (Canis familiaris) as a translational model of autism: It is high time we move from promise to reality}}. {Wiley interdisciplinary reviews Cognitive science}. 2019: e1495.
Selecting appropriate animal models for a particular human phenomenon is a difficult but important challenge. The difficulty lies in finding animal behaviors that are not only sufficiently relevant and analog to the complex human symptoms (face validity) but also have similar underlying biological and etiological mechanisms (translational or construct validity), and have « human-like » responses to treatment (predictive validity). Over the past several years, the domestic dog (Canis familiaris) has become increasingly proposed as a model for comparative and translational neuroscience. In parallel to the recent advances in canine behavior research, dogs have also been proposed as a model of many human neuropsychiatric conditions, including autism spectrum disorder (ASD). In this opinion paper we will shortly discuss the challenging nature of autism research then summarize the different neurocognitive frameworks for ASD making the case for a canine model of autism. The translational value of a dog model stems from the recognition that (a) there is a large inter-individual variability in the manifestation of dogs’ social cognitive abilities including both high and low phenotypic extremes; (b) the phenotypic similarity between the dog and human symptoms are much higher than between the rodent and human symptoms; (c) the symptoms are functionally analogous to the human condition; and (d) more likely to have similar etiology. This article is categorized under: Psychology > Comparative Psychology Cognitive Biology > Evolutionary Roots of Cognition.
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26. Tu Z, Zhao H, Li B, Yan S, Wang L, Tang Y, Li Z, Bai D, Li C, Lin Y, Li Y, Liu J, Xu H, Guo X, Jiang YH, Zhang YQ, Li XJ. {{CRISPR/Cas9-mediated disruption of SHANK3 in monkey leads to drug-treatable autism-like symptoms}}. {Hum Mol Genet}. 2019; 28(4): 561-71.
Monogenic mutations in the SHANK3 gene, which encodes a postsynaptic scaffold protein, play a causative role in autism spectrum disorder (ASD). Although a number of mouse models with Shank3 mutations have been valuable for investigating the pathogenesis of ASD, species-dependent differences in behaviors and brain structures post considerable challenges to use small animals to model ASD and to translate experimental therapeutics to the clinic. We have used clustered regularly interspersed short palindromic repeat/CRISPR-associated nuclease 9 to generate a cynomolgus monkey model by disrupting SHANK3 at exons 6 and 12. Analysis of the live mutant monkey revealed the core behavioral abnormalities of ASD, including impaired social interaction and repetitive behaviors, and reduced brain network activities detected by positron-emission computed tomography (PET). Importantly, these abnormal behaviors and brain activities were alleviated by the antidepressant fluoxetine treatment. Our findings provide the first demonstration that the genetically modified non-human primate can be used for translational research of therapeutics for ASD.
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27. Vaughan S, McGlone F, Poole H, Moore DJ. {{A Quantitative Sensory Testing Approach to Pain in Autism Spectrum Disorders}}. {J Autism Dev Disord}. 2019.
Sensory abnormalities in autism has been noted clinically, with pain insensitivity as a specified diagnostic criterion. However, there is limited research using psychophysically robust techniques. Thirteen adults with ASD and 13 matched controls completed an established quantitative sensory testing (QST) battery, supplemented with measures of pain tolerance and central modulation. The ASD group showed higher thresholds for light touch detection and mechanical pain. Notably, the ASD group had a greater range of extreme scores (the number of z-scores outside of the 95% CI > 2), dynamic mechanical allodynia and paradoxical heat sensation; phenomena not typically seen in neurotypical individuals. These data support the need for research examining central mechanisms for pain in ASD and greater consideration of individual difference.
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28. Zhou WZ, Zhang J, Li Z, Lin X, Li J, Wang S, Yang C, Wu Q, Ye AY, Wang M, Wang D, Pu TZ, Wu YY, Wei L. {{Targeted resequencing of 358 candidate genes for autism spectrum disorder in a Chinese cohort reveals diagnostic potential and genotype-phenotype correlations}}. {Human mutation}. 2019.
Autism spectrum disorder (ASD) is a childhood neuropsychiatric disorder with a complex genetic architecture. The diagnostic potential of a targeted panel of ASD genes has only been evaluated in small cohorts to date and is especially understudied in the Chinese population. Here, we designed a capture panel with 358 genes (111 syndromic and 247 non-syndromic) for ASD and sequenced a Chinese cohort of 539 cases evaluated with the Autism Diagnostic Interview-Revised (ADI-R) and the Autism Diagnostic Observation Schedule (ADOS) as well as 512 controls. ASD cases were found to carry significantly more ultra-rare functional variants than controls. A subset of 78 syndromic and 54 non-syndromic genes were the most significantly associated and should be given high priority in future screening of ASD patients. Pathogenic and likely pathogenic variants were detected in 9.5% of cases. Variants in SHANK3 and SHANK2 were the most frequent, especially in females, and occurred in 1.2% of cases. Duplications of 15q11-13 were detected in 0.8% of cases. Variants in CNTNAP2 and MEF2C were correlated with epilepsy/tics in cases. Our findings reveal the diagnostic potential of ASD genetic panel testing and new insights regarding the variant spectrum. Genotype-phenotype correlations may facilitate the diagnosis and management of ASD. This article is protected by copyright. All rights reserved.
