1. Adamson J, Leppanen J, Murin M, Tchanturia K. {{Effectiveness of emotional skills training for patients with anorexia nervosa with autistic symptoms in group and individual format}}. {European eating disorders review : the journal of the Eating Disorders Association}. 2018.
OBJECTIVE: The aim of this study was to examine the effectiveness of CREST interventions in individual and group formats for adult anorexia nervosa. Furthermore, this study also aims to analyse whether patients with high levels of autistic symptoms respond differently. METHODS: Participants’ self-report measures were taken before and after individual and group interventions (N = 66 and N = 62, respectively). Mixed effects analysis was used to analyse overall response to both formats and assess interaction with autism symptoms. RESULTS: Significant improvements were observed for patients’ alexithymia in individual format, and motivation increased for participants in both interventions. Significant interactions were observed between alexithymia, social anhedonia, and autism symptoms in individual format and alexithymia in group format. No interactions between autism and time were observed for either format. CONCLUSIONS: CREST in both formats offers participants improvements in social-emotional and motivational domains. Patients with high levels of autism symptoms also score high on both social anhedonia and alexithymia measures, but this does not affect their response to treatment.
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2. Clarke AJ, Abdala Sheikh AP. {{A perspective on « cure » for Rett syndrome}}. {Orphanet journal of rare diseases}. 2018; 13(1): 44.
The reversal of the Rett syndrome disease process in the Mecp2 mouse model of Guy et al. (2007) has motivated families and researchers to work on this condition. The reversibility in adult mice suggests that there is potentially much to be gained from rational treatments applied to patients of any age. However, it may be difficult to strike the right balance between enthusiasm on the one hand and realism on the other. One effect of this has been a fragmentation of the « Rett syndrome community » with some groups giving priority to work aimed at a cure while fewer resources are devoted to medical or therapy-based interventions to enhance the quality of life of affected patients or provide support for their families.Several possible therapeutic approaches are under development that, it is claimed and hoped, may lead to a « cure » for patients with Rett syndrome. While all have a rationale, there are potential obstacles to each being both safe and effective. Furthermore, any strategy that succeeded in restoring normal levels of MECP2 gene expression throughout the brain carries potential pitfalls, so that it will be of crucial importance to introduce any clinical trials of such therapies with great care.Expectations of families for a radical, rational treatment should not be inflated beyond a cautious optimism. This is particularly because affected patients with us now may not be able to reap the full benefits of a « cure ». Thus, interventions aimed at enhancing the quality of life of affected patients should not be forgone and their importance should not be minimised.
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3. Finke EH, Hickerson BD, Kremkow JMD. {{« To Be Quite Honest, If It Wasn’t for Videogames I Wouldn’t Have a Social Life at All »: Motivations of Young Adults With Autism Spectrum Disorder for Playing Videogames as Leisure}}. {American journal of speech-language pathology}. 2018: 1-18.
Purpose: Leisure activities are underutilized as a context for intervention in the field of speech-language pathology despite the fact that leisure can be an important context for skill development. The current study investigated the perceptions of individuals with autism spectrum disorder (ASD) who play videogames as their primary leisure activity regarding the role of videogames in their lives and their motivations for playing videogames. Method: Qualitative interview methodology was used to investigate the experiences of 10 18-24-year-olds with ASD. Information was collected about the role of videogames in the lives of adolescents and young adults with ASD and the perceived benefits of playing videogames. Results: Results indicated the participants perceived playing videogames to have a positive impact on their lives and their development. The motivations for playing videogames described are similar to those reported by typically developing populations. Conclusions: Videogaming is a popular leisure pursuit for adolescents and young adults with and without ASD. Speech-language pathologists should consider how videogame play may be a useful context for teaching new communication, social, and language.
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4. Holloway JM, Long T, Biasini F. {{Concurrent Validity of Two Standardized Measures of Gross Motor Function in Young Children with Autism Spectrum Disorder}}. {Phys Occup Ther Pediatr}. 2018: 1-11.
AIMS: This study provides information on how two standardized measures based on different theoretical frameworks can be used in collecting information on motor development and performance in 4- and 5-year-olds with autism spectrum disorder (ASD). The purpose of the study was to determine the concurrent validity of the Miller Function and Participation Scales (M-FUN) with the Peabody Developmental Motor Scales, Second Edition (PDMS-2) in young children with ASD. METHODS: The gross motor sections of the PDMS-2 and the M-FUN were administered to 22 children with ASD between the ages of 48 and 71 months. Concurrent validity between overall motor scores and agreement in identification of motor delay were assessed. RESULTS: A very strong correlation (Pearson’s r =.851) was found between the M-FUN scale scores and the PDMS-2 gross motor quotients (GMQs). Strong agreement in identification of children with average motor skills and delayed motor skills at 1.5 standard deviations below the mean was also found. CONCLUSIONS: This study supports the concurrent validity of the M-FUN with the PDMS-2 for young children with ASD. While both tests provide information regarding motor delay, the M-FUN may provide additional information regarding the neurological profile of the child.
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5. Kilburn TR, Sorensen MJ, Thastum M, Rapee RM, Rask CU, Arendt KB, Thomsen PH. {{Rationale and design for cognitive behavioral therapy for anxiety disorders in children with autism spectrum disorder: a study protocol of a randomized controlled trial}}. {Trials}. 2018; 19(1): 210.
BACKGROUND: Autism spectrum disorder (ASD) is found in approximately 1% of the population and includes core symptoms that affect general and social development. Beside these core symptoms, it is suggested that up to 60% of children with ASD suffer from comorbid anxiety disorders which may further affect educational, social and general development as well as quality of life. The main goal of this study is to examine the effectiveness of a manualized cognitive behavioral therapy (CBT) anxiety program adapted for children with ASD. METHODS: This study is a randomized controlled trial (RCT). Fifty children with ASD and anxiety, aged 7 to 13 years, will be randomly assigned to group CBT or a wait-list control (WL) condition. The design will follow a two (CBT and WL) by two (pre-post assessment) mixed between-within design. The control group will receive intervention after the waitlist period of 13 weeks. Primary outcomes are diagnostic status and severity of the anxiety disorders, measured with The Anxiety Disorder Interview Schedule for DSM-IV, Parent and Child Versions. Secondary outcomes are parent and child ratings on questionnaires on the child’s level of anxiety and impact on everyday life. Additional outcomes entail information gathered from parents, child and teachers on the child’s behavior and negative self-statements, together with social and adaptive skills. Follow-up data will be collected 3 months after intervention. DISCUSSION: This study aims to evaluate the effectiveness of a manualized CBT program in Danish children with ASD and anxiety within a mental health clinic setting. The hypothesis is that training anxiety reduction skills will decrease anxiety in children, as well as ensure better psychosocial development for the child in general. TRIAL REGISTRATION: https://ClinicalTrials.gov ( NCT02908321 ). Registered 19th of September 2016.
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6. Liu CX, Li CY, Hu CC, Wang Y, Lin J, Jiang YH, Li Q, Xu X. {{CRISPR/Cas9-induced shank3b mutant zebrafish display autism-like behaviors}}. {Mol Autism}. 2018; 9: 23.
Background: Human genetic and genomic studies have supported a strong causal role of SHANK3 deficiency in autism spectrum disorder (ASD). However, the molecular mechanism underlying SHANK3 deficiency resulting in ASD is not fully understood. Recently, the zebrafish has become an attractive organism to model ASD because of its high efficiency of genetic manipulation and robust behavioral phenotypes. The orthologous gene to human SHANK3 is duplicated in the zebrafish genome and has two homologs, shank3a and shank3b. Previous studies have reported shank3 morphants in zebrafish using the morpholino method. Here, we report the generation and characterization of shank3b mutant zebrafish in larval and adult stages using the CRISPR/Cas9 genome editing technique. Methods: CRISPR/Cas9 was applied to generate a shank3b loss-of-function mutation (shank3b(-/-) ) in zebrafish. A series of morphological measurements, behavioral tests, and molecular analyses were performed to systematically characterize the behavioral and molecular changes in shank3b mutant zebrafish. Results: shank3b(-/-) zebrafish exhibited abnormal morphology in early development. They showed reduced locomotor activity both as larvae and adults, reduced social interaction and time spent near conspecifics, and significant repetitive swimming behaviors. Additionally, the levels of both postsynaptic homer1 and presynaptic synaptophysin were significantly reduced in the adult brain of shank3b-deficient zebrafish. Conclusions: We generated the first inheritable shank3b mutant zebrafish model using CRISPR/Cas9 gene editing approach. shank3b(-/-) zebrafish displayed robust autism-like behaviors and altered levels of the synaptic proteins homer1 and synaptophysin. The versatility of zebrafish as a model for studying neurodevelopment and conducting drug screening will likely have a significant contribution to future studies of human SHANK3 function and ASD.
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7. Lovelace JW, Ethell IM, Binder DK, Razak KA. {{Translation-relevant EEG phenotypes in a mouse model of Fragile X Syndrome}}. {Neurobiology of disease}. 2018; 115: 39-48.
Identification of comparable biomarkers in humans and validated animal models will facilitate pre-clinical to clinical therapeutic pipelines to treat neurodevelopmental disorders. Fragile X Syndrome (FXS) is a leading known genetic cause of intellectual disability with symptoms that include increased anxiety, social and sensory processing deficits. Recent EEG studies in humans with FXS have identified neural oscillation deficits that include enhanced resting state gamma power and reduced inter-trial coherence of sound evoked gamma oscillations. To determine if analogous phenotypes are present in an animal model of FXS, we recorded EEGs in awake, freely moving Fmr1 knock out (KO) mice using similar stimuli as in the human studies. We report remarkably similar neural oscillation phenotypes in the Fmr1 KO mouse including enhanced resting state gamma power and reduced evoked gamma synchronization. The gamma band inter-trial coherence of neural response was reduced in both auditory and frontal cortex of Fmr1 KO mice stimulated with a sound whose envelope was modulated from 1 to 100Hz, similar to that seen in humans with FXS. These deficits suggest a form of enhanced ‘resting state noise’ that interferes with the ability of the circuit to mount a synchronized response to sensory input, predicting specific sensory and cognitive deficits in FXS. The abnormal gamma oscillations are consistent with parvalbumin neuron and perineuronal net deficits seen in the Fmr1 KO mouse auditory cortex indicating that the EEG biomarkers are not only clinically relevant, but could also be used to probe cellular and circuit mechanisms of sensory hypersensitivity in FXS.
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8. Wadsworth HM, Maximo JO, Donnelly RJ, Kana RK. {{Action simulation and mirroring in children with autism spectrum disorders}}. {Behav Brain Res}. 2018; 341: 1-8.
Mental imitation, perhaps a precursor to motor imitation, involves visual perspective-taking and motor imagery. Research on mental imitation in autism spectrum disorders (ASD) has been rather limited compared to that on motor imitation. The main objective of this fMRI study is to determine the differences in brain responses underlying mirroring and mentalizing networks during mental imitation in children and adolescents with ASD. Thirteen high-functioning children and adolescents with ASD and 15 age-and- IQ-matched typically developing (TD) control participants took part in this fMRI study. In the MRI scanner, participants were shown cartoon pictures of people performing everyday actions (Transitive actions: e.g., ironing clothes but with the hand missing; and Intransitive actions: e.g., clapping hands with the palms missing) and were asked to identify which hand or palm orientation would best fit the gap. The main findings are: 1) both groups performed equally while processing transitive and intransitive actions; 2) both tasks yielded activation in the bilateral inferior frontal gyrus (IFG) and inferior parietal lobule (IPL) in ASD and TD groups; 3) Increased activation was seen in ASD children, relative to TD, in left ventral premotor and right middle temporal gyrus during intransitive actions; and 4) ASD symptom severity positively correlated with activation in left parietal, right middle temporal, and right premotor regions across all subjects. Overall, our findings suggest that regions mediating mirroring may be recruiting more brain resources in ASD and may have implications for understanding social movement through modeling.
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9. Wong CW, Or PMY, Wang Y, Li L, Li J, Yan M, Cao Y, Luk HM, Tong TMF, Leslie NR, Lo IF, Choy KW, Chan AML. {{Identification of a PTEN mutation with reduced protein stability, phosphatase activity, and nuclear localization in Hong Kong patients with autistic features, neurodevelopmental delays, and macrocephaly}}. {Autism Res}. 2018.
PTEN is a tumor suppressor gene inactivated in over 30% of human cancers. It encodes a lipid phosphatase that serves as a gatekeeper of the phosphoinositide 3-kinase signaling pathway. Germline mutation frequently occurs in this gene in patients diagnosed with PTEN Hamartoma Tumor Syndrome (PHTS). PHTS individuals are characterized by macrocephaly, benign growth of multiple tissues and increased tumor risk. In addition, autistic phenotypes are found in 10-20% of individuals carrying the germline PTEN mutation with macrocephaly. In this report, 13 suspected PHTS patients were screened for mutation in the PTEN gene. A missense variant (c. 302T > C) substituting the isoleucine at codon 101 to a threonine, a single nucleotide insertion (c. 327-328insC) causing a frame shift mutation and termination at codon 109, and a nonsense variant (c. 1003C > T) truncated the protein at codon 335 were identified. The I101T mutation significantly reduced PTEN protein expression levels by 2.5- to 4.0-fold. Mechanistically, I101T reduced the protein half-life of PTEN possibly due to enhanced polyubiquitination at Lysine 13. However, the I101T mutant retained almost 30% of the lipid phosphatase activity of the wild-type protein. Finally, the I101T mutant has reduced phosphorylation at a PTEN auto-dephosphorylation site at Threonine 366 and a lowered ratio of nuclear to cytosolic protein level. These partial losses of multiple PTEN biochemical functions may contribute to the tissue overgrowth and autistic features of this PHTS patient. Autism Res 2018. (c) 2018 The Authors Autism Research published by International Society for Autism Research and Wiley Periodicals, Inc. LAY SUMMARY: The genetics of autism spectrum disorders is highly complex with individual risk influenced by both genetic and environmental factors. Mutation in the human PTEN gene confers a high risk of developing autistic behavior. This report revealed that PTEN mutations occurred in 23% of a selected group of Hong Kong patients harboring autistic features with gross overgrowth symptoms. Detailed characterization of a PTEN mutation revealed reduced protein stability as one of the underlying mechanisms responsible for reduced PTEN activity.
