1. Ansari S, Hosseinkhanzadeh AA, AdibSaber F, Shojaei M, Daneshfar A. {{The Effects of Aquatic Versus Kata Techniques Training on Static and Dynamic Balance in Children with Autism Spectrum Disorder}}. {J Autism Dev Disord}. 2020.
The present study aimed to compare the effect of a land-based and a swimming-based exercise program on balance abilities in children with autism. Thirty children were voluntarily selected and randomly assigned to karate exercise, aquatic training and control groups. Participants practiced for 10 weeks, 2 sessions of 60 min per week. Before and after the 10-week intervention, static and dynamic balance tests were administered. The results showed that both interventions had a significant effect on balance abilities (p < 0.001); interestingly, we found the greater improvement in balance performance in kata techniques group. Due to the importance of balance performance on daily functions, communication and interaction skills, karate and swimming exercises can be the valuable interventions added to autism's daily programs. Iranian Registry of Clinical Trials number: IRCT20180626040242N1. Lien vers le texte intégral (Open Access ou abonnement)
2. Cavallo F, Troglio F, Fagà G, Fancelli D, Shyti R, Trattaro S, Zanella M, D’Agostino G, Hughes JM, Cera MR, Pasi M, Gabriele M, Lazzarin M, Mihailovich M, Kooy F, Rosa A, Mercurio C, Varasi M, Testa G. {{High-throughput screening identifies histone deacetylase inhibitors that modulate GTF2I expression in 7q11.23 microduplication autism spectrum disorder patient-derived cortical neurons}}. {Mol Autism}. 2020; 11(1): 88.
BACKGROUND: Autism spectrum disorder (ASD) is a highly prevalent neurodevelopmental condition affecting almost 1% of children, and represents a major unmet medical need with no effective drug treatment available. Duplication at 7q11.23 (7Dup), encompassing 26-28 genes, is one of the best characterized ASD-causing copy number variations and offers unique translational opportunities, because the hemideletion of the same interval causes Williams-Beuren syndrome (WBS), a condition defined by hypersociability and language strengths, thereby providing a unique reference to validate treatments for the ASD symptoms. In the above-indicated interval at 7q11.23, defined as WBS critical region, several genes, such as GTF2I, BAZ1B, CLIP2 and EIF4H, emerged as critical for their role in the pathogenesis of WBS and 7Dup both from mouse models and human studies. METHODS: We performed a high-throughput screening of 1478 compounds, including central nervous system agents, epigenetic modulators and experimental substances, on patient-derived cortical glutamatergic neurons differentiated from our cohort of induced pluripotent stem cell lines (iPSCs), monitoring the transcriptional modulation of WBS interval genes, with a special focus on GTF2I, in light of its overriding pathogenic role. The hits identified were validated by measuring gene expression by qRT-PCR and the results were confirmed by western blotting. RESULTS: We identified and selected three histone deacetylase inhibitors (HDACi) that decreased the abnormal expression level of GTF2I in 7Dup cortical glutamatergic neurons differentiated from four genetically different iPSC lines. We confirmed this effect also at the protein level. LIMITATIONS: In this study, we did not address the molecular mechanisms whereby HDAC inhibitors act on GTF2I. The lead compounds identified will now need to be advanced to further testing in additional models, including patient-derived brain organoids and mouse models recapitulating the gene imbalances of the 7q11.23 microduplication, in order to validate their efficacy in rescuing phenotypes across multiple functional layers within a translational pipeline towards clinical use. CONCLUSIONS: These results represent a unique opportunity for the development of a specific class of compounds for treating 7Dup and other forms of intellectual disability and autism.
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3. Chen H, Long J, Yang S, He B. {{Atypical Functional Covariance Connectivity Between Gray and White Matter in Children With Autism Spectrum Disorder}}. {Autism Res}. 2020.
Autism spectrum disorder (ASD) is a type of neurodevelopmental disorder with atypical gray matter (GM) and white matter (WM) functional developmental course. However, the functional co-developmental pattern between GM and WM in ASD is unclear. Here, we utilized a functional covariance connectivity method to explore the concordance pattern between GM and WM function in individuals with ASD. A multi-center resting-state fMRI dataset composed of 105 male children with ASD and 102 well-matched healthy controls (HCs) from six sites of the ABIDE dataset was utilized. GM and WM ALFF maps were calculated for each subject. Voxel by voxel functional covariance connectivity of the ALFF values across subjects was calculated between GM and WM for children with ASD and HCs. A Z-test combining FDR multi-comparison correction was then employed to determine whether the functional covariance is significantly different between the two groups. A « bundling » strategy was utilized to ensure that the GM/WM clusters showing atypical functional covariance were larger than 5 voxels. Finally, canonical correlation analysis was conducted to explore whether the atypical GM/WM functional covariance is related to ASD symptoms. Results showed atypical functional covariance connections between specific GM and WM regions, whereas the ALFF values of these regions indicated no significant difference between the two groups. Canonical correlation analysis revealed a significant relationship between the atypical functional covariance and stereotyped behaviors of ASD. The results indicated an altered functional co-developmental pattern between WM and GM in ASD. LAY SUMMARY: White matter (WM) and gray matter (GM) are two major human brain organs supporting brain function. WM and GM functions show a specific co-developmental pattern in typical developed individuals. This study showed that this GM/WM co-developmental pattern was altered in children with ASD, while this altered GM/WM co-developmental pattern was related to stereotyped behaviors. These findings may help understand the GM/WM functional development of ASD.
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4. Dahan A, Dubnov YA, Popkov AY, Gutman I, Probolovski HG. {{Brief Report: Classification of Autistic Traits According to Brain Activity Recoded by fNIRS Using ε-Complexity Coefficients}}. {J Autism Dev Disord}. 2020.
Individuals with ASD have been shown to have different pattern of functional connectivity. In this study, brain activity of participants with many and few autistic traits, was recorded using an fNIRS device, as participants preformed an interpersonal synchronization task. This type of task involves synchronization and functional connectivity of different brain regions. A novel method for assessing signal complexity, using ε-complexity coefficients, applied for the first i.e. on fNIRS recording, was used to classify brain recording of participants with many/few autistic traits. Successful classification was achieved implying that this method may be useful for classification of fNIRS recordings and that there is a difference in brain activity between participants with low and high autistic traits as they perform an interpersonal synchronization task.
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5. Efe A, Neşelioğlu S, Soykan A. {{An Investigation of the Dynamic Thiol/Disulfide Homeostasis, As a Novel Oxidative Stress Plasma Biomarker, in Children With Autism Spectrum Disorders}}. {Autism Res}. 2020.
We aimed to investigate the role of impaired oxidant-antioxidant homeostasis on the etiopathogenesis of autism with a novel oxidative stress (OS) marker, dynamic thiol/disulfide homeostasis (DTDH), and relationship between the symptom severity and markers. A total of 60 children with ASD aged 3-10 years and 54 unaffected children were investigated for the plasma DTDH parameters. A sociodemographic-data form, K-SADS-PL, Childhood Autism Rating Scale, Abnormal Behavior Checklist, Autism Behavior Checklist, and a developmentally appropriate IQ test were administered to all participants. Distortion of DTDH to the OS-side in the autism group was determined with lower plasma levels of native and total thiol, in contrast to a higher disulfide and thiol oxidation-reduction ratio. However, biomarkers had no correlation with the symptom severity of autism. Cutoff values for each parameter on the ROC curve might be useful to predict ASD and each DTDH biomarker was detected as an independent predictor of ASD. The present study demonstrated a disturbed redox status and absence of an expected compensatory increase in antioxidant response in a pediatric sample of ASD by measuring dynamic oxidation/reduction shifts with a novel, practical and reproducible analytical technique, and contributes to data regarding oxidative hypothesis on autism and raises the question of the place of antioxidants in autism treatment. Our results may suggest predictive usefulness of the plasma DTDH biomarkers in ASD, despite the study being conducted with a modestly small sample size that makes further research with a larger replication sample necessary to substantiate the findings. LAY SUMMARY: Dynamic thiol/disulfide homeostasis is a novel plasma marker used to determine the oxidative stress which is a natural result of disequilibrium between the oxidants and antioxidants in the human body. There is increasing interest regarding a central biological linking role of oxidative stress among the other etiological factors of autism. Our findings on the disturbed plasma dynamic thiol/disulfide homeostasis in children with autism and the absence of an expected antioxidant response against increased oxidative stress supports the data concerning the role of oxidative stress on the etiology of autism and the need of further research on the place of antioxidants in autism treatment.
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6. Endres D, Decher N, Röhr I, Vowinkel K, Domschke K, Komlosi K, Tzschach A, Gläser B, Schiele MA, Runge K, Süß P, Schuchardt F, Nickel K, Stallmeyer B, Rinné S, Schulze-Bahr E, Tebartz van Elst L. {{New Cav1.2 Channelopathy with High-Functioning Autism, Affective Disorder, Severe Dental Enamel Defects, a Short QT Interval, and a Novel CACNA1C Loss-Of-Function Mutation}}. {International journal of molecular sciences}. 2020; 21(22).
Complex neuropsychiatric-cardiac syndromes can be genetically determined. For the first time, the authors present a syndromal form of short QT syndrome in a 34-year-old German male patient with extracardiac features with predominant psychiatric manifestation, namely a severe form of secondary high-functioning autism spectrum disorder (ASD), along with affective and psychotic exacerbations, and severe dental enamel defects (with rapid wearing off his teeth) due to a heterozygous loss-of-function mutation in the CACNA1C gene (NM_000719.6: c.2399A > C; p.Lys800Thr). This mutation was found only once in control databases; the mutated lysine is located in the Cav1.2 calcium channel, is highly conserved during evolution, and is predicted to affect protein function by most pathogenicity prediction algorithms. L-type Cav1.2 calcium channels are widely expressed in the brain and heart. In the case presented, electrophysiological studies revealed a prominent reduction in the current amplitude without changes in the gating behavior of the Cav1.2 channel, most likely due to a trafficking defect. Due to the demonstrated loss of function, the p.Lys800Thr variant was finally classified as pathogenic (ACMG class 4 variant) and is likely to cause a newly described Cav1.2 channelopathy.
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7. Klinger LG, Cook ML, Dudley KM. {{Predictors and Moderators of Treatment Efficacy in Children and Adolescents with Autism Spectrum Disorder}}. {J Clin Child Adolesc Psychol}. 2020: 1-8.
OBJECTIVE: The heterogeneous symptom presentation of autism spectrum disorder (ASD) requires clinicians to consider each child’s unique constellation of symptoms and tailor intervention accordingly. Treatment moderators, though necessary to guide evidence-based treatment decisions, are significantly under-studied. This brief report aims to expand on previous literature by providing an overview of characteristics which may influence treatment outcome and specifying future directions to build on this preliminary evidence base. METHOD: A subset of treatment modalities was identified from the National Clearinghouse on Autism Evidence and Practice Review Team’s most recent report including discrete trial early intensive behaviorally based treatment, social skills training, and cognitive behavioral interventions. Within these treatment modalities, individual interventions with significant support were specifically discussed. Due to the lack of research on treatment moderators, a discussion of significant predictors of treatment outcome is also included. RESULTS: Preliminary evidence suggests that overall, treatment intensity, duration, and parent involvement are the most consistently identified predictors (and in some studies, moderators) of treatment outcome; sessions which occur more frequently, continue for longer periods of time, and include parent training or coaching may yield the best outcomes. Other characteristics, including age and IQ, have been widely debated, with differing results found across treatment modalities. CONCLUSIONS: The sparsity of research demonstrates a clear need for continued research on moderators to guide clinical judgment. Future studies that recruit larger samples targeting specific ASD symptoms at specific ages may be more adequately powered to detect these moderating effects.
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8. Kotila A, Järvelä M, Korhonen V, Loukusa S, Hurtig T, Ebeling H, Kiviniemi V, Raatikainen V. {{Atypical Inter-Network Deactivation Associated With the Posterior Default-Mode Network in Autism Spectrum Disorder}}. {Autism Res}. 2020.
Previous studies have suggested that atypical deactivation of functional brain networks contributes to the complex cognitive and behavioral profile associated with autism spectrum disorder (ASD). However, these studies have not considered the temporal dynamics of deactivation mechanisms between the networks. In this study, we examined (a) mutual deactivation and (b) mutual activation-deactivation (i.e., anticorrelated) time-lag patterns between resting-state networks (RSNs) in young adults with ASD (n = 20) and controls (n = 20) by applying the recently defined dynamic lag analysis (DLA) method, which measures time-lag variations peak-by-peak between the networks. In order to achieve temporally accurate lag patterns, the brain imaging data was acquired with a fast functional magnetic resonance imaging (fMRI) sequence (TR = 100 ms). Group-level independent component analysis was used to identify 16 RSNs for the DLA. We found altered mutual deactivation timings in ASD in (a) three of the deactivated and (b) two of the transiently anticorrelated (activated-deactivated) RSN pairs, which survived the strict threshold for significance of surrogate data. Of the significant RSN pairs, 80% included the posterior default-mode network (DMN). We propose that temporally altered deactivation mechanisms, including timings and directionality, between the posterior DMN and RSNs mediating processing of socially relevant information may contribute to the ASD phenotype. LAY SUMMARY: To understand autistic traits on a neural level, we examined temporal fluctuations in information flow between brain regions in young adults with autism spectrum disorder (ASD) and controls. We used a fast neuroimaging procedure to investigate deactivation mechanisms between brain regions. We found that timings and directionality of communication between certain brain regions were temporally altered in ASD, suggesting atypical deactivation mechanisms associated with the posterior default-mode network.
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9. Liu Z, Liu J, Zhang Z, Yu H, Hu F. {{Facial Emotion Recognition and Polymorphisms of Dopaminergic Pathway Genes in Children with ASD}}. {Behavioural neurology}. 2020; 2020: 6376842.
BACKGROUND: It is inconclusive whether children with autism spectrum disorder (ASD) experience a deficit in facial emotion recognition. The dopaminergic pathway has been implicated in the pathogenesis of ASD. This study was aimed at determining facial emotion recognition and its correlation with polymorphisms in the dopaminergic pathway genes in children with ASD. METHODS: Facial emotion recognition was examined in 98 children with ASD and 60 age- and gender-matched healthy controls. The severity of ASD was evaluated using the Childhood Autism Rating Scale (CARS). DNA from blood cells was used to analyze the genotypes of single-nucleotide polymorphisms (SNPs) in dopaminergic pathway genes. SNPs of DBH rs1611115, DDC rs6592961, DRD1 rs251937, DRD2 rs4630328, and DRD3 rs167771 were analyzed. RESULTS: Children with ASD took a significantly longer time to recognize all facial emotions, and their interpretations were less accurate for anger at low intensity and fear at both low and high intensities. The severity of the disease was associated with significant delays in recognition of all facial emotions and with a decrease in accuracy in recognition of happiness and anger at low intensity. Accuracy in recognizing fear at high intensity and sadness at low intensity was associated with rs251937 and rs4630328, respectively, in children with ASD. Multivariate logistic regression analysis revealed that SNP rs167771, response time for the recognition of happiness, sadness and fear, and accuracy in recognition of anger and fear were all associated with the risk of childhood ASD. CONCLUSIONS: Children with ASD experience a deficit in facial emotion recognition. Certain SNPs in the dopaminergic pathway genes are associated with accuracy in recognizing selective facial emotions in children with ASD.
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10. Påhlman M, Gillberg C, Himmelmann K. {{Autism and attention-deficit/hyperactivity disorder in children with cerebral palsy: high prevalence rates in a population-based study}}. {Dev Med Child Neurol}. 2020.
AIM: To assess a total population of school-age children with cerebral palsy (CP) for autism and attention-deficit/hyperactivity disorder (ADHD) with a view to determining their prevalence and to relate findings to motor function, intellectual disability, and other associated impairments. METHOD: Of 264 children, born between 1999 and 2006, from the CP register of western Sweden, 200 children (109 males, 91 females, median age at assessment 14y, range 7-18y) completed comprehensive screening and further neuropsychiatric clinical assessments. RESULTS: Ninety children (45%) were diagnosed with autism, ADHD, or both, 59 (30%) were diagnosed with autism, and 60 (30%) were diagnosed with ADHD. Intellectual disability was present in 51%. Two-thirds had autism, ADHD, and/or intellectual disability. In regression models, autism was mainly predicted by intellectual disability (odds ratio [OR]=4.1) and ADHD (OR=3.2), and ADHD was predicted by intellectual disability (OR=2.3) and autism (OR=3.0). Autism was more common in children born preterm (OR=2.0). Gross motor function was not associated with autism. ADHD prevalence was low in children with severe motor impairment, possibly due to diagnostic limitations. INTERPRETATION: Autism and ADHD were common in this population of children with CP and were mainlyindependent of motor severity and CP type. The strongest predictor of autism/ADHD was intellectual disability. Assessment for autism and ADHD is warranted as part of the evaluation in CP.
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11. Pereira ET, Montenegro ACA, Rosal AGC, Walter CCF. {{Augmentative and Alternative Communication on Autism Spectrum Disorder: Impacts on Communication}}. {CoDAS}. 2020; 32(6): e20190167.
PURPOSE: To verify the effects of the Speech-Language Intervention with Augmentative and Alternative Communication (AAC) in communicative acts in children with Autism Spectrum Disorder (ASD). METHOD: This is a longitudinal case-study design involving three subjects attended in a Speech-Language Pathology (SLP) Clinic School. Primary data were obtained from the observation of recorded videos of pre and post-intervention therapist assessment sessions with each child in play activities, while secondary data come from interviews with parents. The analysis was performed based on the Pragmatic Test of the Infant Language Test – ABFW, through observational recordings, aiming to identify and quantify the communicative acts. RESULTS: It was possible to observe a 51.47% increase in the production of communicative acts in the three research subjects. In addition, it was found that there was higher quality in the acts produced, using more present verbal components and decreased acts that had non-interpersonal functions, such as gestures and vocal acts. Thus, there was an evolution in the functional language of the subjects. CONCLUSION: The use of Augmentative and Alternative Communication in the SLP therapy clinic is promising and effective in promoting the development of communication skills of individuals with ASD.
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12. Pinto C, Pinto S. {{Care workers of people with intellectual and developmental disabilities feel the need for soft skills training to accomplish better palliative care deliverance}}. {Evidence-based nursing}. 2020.
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13. Rahi S, Mehan S. {{Understanding Abnormal SMO-SHH Signaling in Autism Spectrum Disorder: Potential Drug Target and Therapeutic Goals}}. {Cellular and molecular neurobiology}. 2020.
Autism is a multifactorial neurodevelopmental condition; it demonstrates some main characteristics, such as impaired social relationships and increased repetitive behavior. The initiation of autism spectrum disorder is mostly triggered during brain development by the deregulation of signaling pathways. Sonic hedgehog (SHH) signaling is one such mechanism that influences neurogenesis and neural processes during the development of the central nervous system. SMO-SHH signaling is also an important part of a broad variety of neurological processes, including neuronal cell differentiation, proliferation, and survival. Dysregulation of SMO-SHH signaling leads to many physiological changes that lead to neurological disorders such as ASD and contribute to cognitive decline. The aberrant downregulation of SMO-SHH signals contributes to the proteolytic cleavage of GLI (glioma-associated homolog) into GLI3 (repressor), which increases oxidative stress, neuronal excitotoxicity, neuroinflammation, and apoptosis by suppressing target gene expression. We outlined in this review that SMO-SHH deregulation plays a crucial role in the pathogenesis of autism and addresses the current status of SMO-SHH pathway modulators. Additionally, a greater understanding of the SHH signaling pathway is an effort to improve successful treatment for autism and other neurological disorders.
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14. Rawsthorne H, Calahorro F, Feist E, Holden-Dye L, O’Connor V, Dillon J. {{Neuroligin dependence of social behaviour in C. elegans provides a model to investigate an autism associated gene}}. {Hum Mol Genet}. 2020.
Autism spectrum disorder (ASD) is characterised by a triad of behavioural impairments including social behaviour. Neuroligin, a trans-synaptic adhesion molecule, has emerged as a penetrant genetic determinant of behavioural traits that signature the neuroatypical behaviours of autism. However, the function of neuroligin in social circuitry and the impact of genetic variation to this gene is not fully understood. Indeed, in animal studies designed to model autism there remains controversy regarding the role of neuroligin dysfunction in the expression of disrupted social behaviours. The model organism, C. elegans, offers an informative experimental platform to investigate the impact of genetic variants on social behaviour. In a number of paradigms it has been shown that inter-organismal communication by chemical cues regulates C. elegans social behaviour. We utilise this social behaviour to investigate the effect of autism associated genetic variants within the social domain of the research domain criteria. We have identified neuroligin as an important regulator of social behaviour and segregate the importance of this gene to the recognition and/or processing of social cues. We also use CRISPR/Cas9 to edit an R-C mutation that mimics a highly penetrant human mutation associated with autism. C. elegans carrying this mutation phenocopy the behavioural dysfunction of a C. elegans neuroligin null mutant, thus confirming its significance in the regulation of animal social biology. This highlights that quantitative behaviour and precision genetic intervention can be used to manipulate discrete social circuits of the worm to provide further insight to complex social behaviour.
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15. Salcedo-Arellano MJ, Cabal-Herrera AM, Punatar RH, Clark CJ, Romney CA, Hagerman RJ. {{Overlapping Molecular Pathways Leading to Autism Spectrum Disorders, Fragile X Syndrome, and Targeted Treatments}}. {Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics}. 2020.
Autism spectrum disorders (ASD) are subdivided into idiopathic (unknown) etiology and secondary, based on known etiology. There are hundreds of causes of ASD and most of them are genetic in origin or related to the interplay of genetic etiology and environmental toxicology. Approximately 30 to 50% of the etiologies can be identified when using a combination of available genetic testing. Many of these gene mutations are either core components of the Wnt signaling pathway or their modulators. The full mutation of the fragile X mental retardation 1 (FMR1) gene leads to fragile X syndrome (FXS), the most common cause of monogenic origin of ASD, accounting for ~ 2% of the cases. There is an overlap of molecular mechanisms in those with idiopathic ASD and those with FXS, an interaction between various signaling pathways is suggested during the development of the autistic brain. This review summarizes the cross talk between neurobiological pathways found in ASD and FXS. These signaling pathways are currently under evaluation to target specific treatments in search of the reversal of the molecular abnormalities found in both idiopathic ASD and FXS.
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16. Suliman-Lavie R, Title B, Cohen Y, Hamada N, Tal M, Tal N, Monderer-Rothkoff G, Gudmundsdottir B, Gudmundsson KO, Keller JR, Huang GJ, Nagata KI, Yarom Y, Shifman S. {{Pogz deficiency leads to transcription dysregulation and impaired cerebellar activity underlying autism-like behavior in mice}}. {Nat Commun}. 2020; 11(1): 5836.
Several genes implicated in autism spectrum disorder (ASD) are chromatin regulators, including POGZ. The cellular and molecular mechanisms leading to ASD impaired social and cognitive behavior are unclear. Animal models are crucial for studying the effects of mutations on brain function and behavior as well as unveiling the underlying mechanisms. Here, we generate a brain specific conditional knockout mouse model deficient for Pogz, an ASD risk gene. We demonstrate that Pogz deficient mice show microcephaly, growth impairment, increased sociability, learning and motor deficits, mimicking several of the human symptoms. At the molecular level, luciferase reporter assay indicates that POGZ is a negative regulator of transcription. In accordance, in Pogz deficient mice we find a significant upregulation of gene expression, most notably in the cerebellum. Gene set enrichment analysis revealed that the transcriptional changes encompass genes and pathways disrupted in ASD, including neurogenesis and synaptic processes, underlying the observed behavioral phenotype in mice. Physiologically, Pogz deficiency is associated with a reduction in the firing frequency of simple and complex spikes and an increase in amplitude of the inhibitory synaptic input in cerebellar Purkinje cells. Our findings support a mechanism linking heterochromatin dysregulation to cerebellar circuit dysfunction and behavioral abnormalities in ASD.
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17. Tang Y, Liu Y, Tong L, Feng S, Du D, Chen F. {{Identification of a β-Arrestin 2 Mutation Related to Autism by Whole-Exome Sequencing}}. {BioMed research international}. 2020; 2020: 8872577.
Autism spectrum disorder (ASD) is a complex neurological disease characterized by impaired social communication and interaction skills, rigid behavior, decreased interest, and repetitive activities. The disease has a high degree of genetic heterogeneity, and the genetic cause of ASD in many autistic individuals is currently unclear. In this study, we report a patient with ASD whose clinical features included social interaction disorder, communication disorder, and repetitive behavior. We examined the patient’s genetic variation using whole-exome sequencing technology and found new de novo mutations. After analysis and evaluation, ARRB2 was identified as a candidate gene. To study the potential contribution of the ARRB2 gene to the human brain development and function, we first evaluated the expression profile of this gene in different brain regions and developmental stages. Then, we used weighted gene coexpression network analysis to analyze the associations between ARRB2 and ASD risk genes. Additionally, the spatial conformation and stability of the ARRB2 wild type and mutant proteins were examined by simulations. Then, we further established a mouse model of ASD. The results showed abnormal ARRB2 expression in the mouse ASD model. Our study showed that ARRB2 may be a risk gene for ASD, but the contribution of de novo ARRB2 mutations to ASD is unclear. This information will provide references for the etiology of ASD and aid in the mechanism-based drug development and treatment.
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18. Umesawa Y, Atsumi T, Fukatsu R, Ide M. {{Decreased utilization of allocentric coordinates during reaching movement in individuals with autism spectrum disorder}}. {PLoS One}. 2020; 15(11): e0236768.
Despite numerous reports of abnormalities in limb motor controls in spatial orientation in individuals with autism spectrum disorder (ASD), the underlying mechanisms have not been elucidated. We studied the influence of allocentric coordinates on ongoing reaching movements, which has been reported to strongly affect the reaching movements of typically developing (TD) individuals. ASD and TD participants observed a target presented randomly on one of the four corners of a frame on a screen. After it disappeared, another frame was presented slightly shifted leftward/rightward. The participants touched the memorized position of the target relatively congruent with a reference frame (allocentric condition) or ignoring it (egocentric condition). Results suggested that TD individuals were apt to touch the positions in allocentric manner rather than egocentric manner, while ASDs did not show this prioritization. Our findings demonstrate that decreased utilization of visual landmarks in ongoing movement may underlie motor disabilities in autism.
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19. van ‘t Hof M, Tisseur C, van Berckelear-Onnes I, van Nieuwenhuyzen A, Daniels AM, Deen M, Hoek HW, Ester WA. {{Age at autism spectrum disorder diagnosis: A systematic review and meta-analysis from 2012 to 2019}}. {Autism}. 2020: 1362361320971107.
We currently assume that the global mean age at diagnosis of autism spectrum disorder ranges from 38 to 120 months. However, this range is based on studies from 1991 to 2012 and measures have since been introduced to reduce the age at autism spectrum disorder diagnosis. We performed a systematic review and meta-analysis (statistical analysis that combines the results of multiple scientific studies) for studies published between 2012 and 2019 to evaluate the current age at autism spectrum disorder diagnosis. We included 56 studies that reported the age at diagnosis for 40 countries (containing 120,540 individuals with autism spectrum disorder). Results showed the current mean age at diagnosis to be 60.48 months (range: 30.90-234.57 months) and 43.18 months (range: 30.90-74.70 months) for studies that only included children aged ⩽10 years. Numerous factors that may influence age at diagnosis (e.g. type of autism spectrum disorder diagnosis, additional diagnoses and gender) were reported by 46 studies, often with conflicting or inconclusive results. Our study is the first to determine the global average age at autism spectrum disorder diagnosis from a meta-analysis. Although progress is being made in the earlier detection of autism spectrum disorder, it requires our constant attention.
