1. Abraham J, Szoko N, Natowicz MR. {{Proteomic Investigations of Autism Spectrum Disorder: Past Findings, Current Challenges, and Future Prospects}}. {Advances in experimental medicine and biology}. 2019; 1118: 235-52.
Proteomics is a powerful tool to study biological systems and is potentially useful in identifying biomarkers for clinical screening and diagnosis, for monitoring treatment, and for exploring pathogenetic mechanisms in autism. Unlike numerous other experimental approaches employed in autism research, there have been few proteomic-based analyses. Herein, we discuss the findings of studies regarding autism that utilized a proteomic approach and review key considerations in sample acquisition, processing, and analysis. Most proteomic studies on autism used blood or other peripheral tissues. Few studies used brain tissue, the main site of biological difference between persons with autism and others. The findings have varied and are not yet replicated. Some showed abnormalities of synaptic proteins or proteins of mitochondrial bioenergetics. Various abnormalities of proteins relating to immune processes and lipid metabolism have also been noted. Whether any of the proteomic differences between autism and control cases are primary or secondary phenomena is currently unclear. Consequently, no definitive biomarkers for autism have been identified, and the pathophysiological insights provided by proteomic studies to date are uncertain in the absence of replication. Based on this body of work and the challenges in using proteomics to study autism, we suggest considerations for future study design. These include attention to subject and specimen inclusion/exclusion criteria, attention to the state of specimens prior to proteomic analysis, and use of a replicate set of specimens. We end by discussing especially promising applications of proteomics in the study of autism pathobiology.
Lien vers le texte intégral (Open Access ou abonnement)
2. Ailey SH, Johnson TJ, Cabrera A. {{Evaluation of Factors Related to Prolonged Lengths of Stay for Patients With Autism With or Without Intellectual Disability}}. {Journal of psychosocial nursing and mental health services}. 2019: 1-6.
Patients with autism spectrum disorder and/or intellectual disability (ASD/ID) face unique health care challenges. In addition to hospital experiences characterized by fear and insufficient staff training, these patients have 1.5-times longer lengths of stay (LOS) than patients without ASD/ID, and 3.4% of patients with ASD/ID have prolonged LOS (i.e., >/=30 days). Little research exists on factors related to prolonged LOS of patients with ASD/ID, hindering efforts to develop and implement evidence-based practices to improve care and reduce prolonged LOS. The purpose of the current study was to describe factors related to prolonged LOS of adult patients with ASD/ID in acute care settings using a retrospective chart review of 10 patients discharged from one academic medical center. Findings indicate that health care institutions should evaluate performance with this patient population and identify evidence-based strategies to provide a safe environment for care and reduce LOS that is due to non-health care needs. [Journal of Psychosocial Nursing and Mental Health Services, xx(x), xx-xx.].
Lien vers le texte intégral (Open Access ou abonnement)
3. Alessandria C, Caviglia GP, Campion D, Nalbone F, Sanna C, Musso A, Abate ML, Rizzetto M, Saracco GM, Balzola F. {{HLA-DQ Genotyping, Duodenal Histology, and Response to Exclusion Diet in Autistic Children With Gastrointestinal Symptoms}}. {Journal of pediatric gastroenterology and nutrition}. 2019.
OBJECTIVES: A correlation between autism spectrum disorders (ASDs) and gastrointestinal (GI) problems, and a possible link between gluten consumption and ASD have been increasingly reported. Gluten/casein-free diet (GCFD) is often undertaken, with conflicting results. This study aimed at evaluating the distribution of human leukocyte antigen (HLA)-DQ2/DQ8 typing among patients with ASD with GI symptoms, together with its correlation with duodenal histology and response to GCFD. METHODS: Between 2002 and 2015 all patients with ASD with GI symptoms referred to our outpatient clinic, displaying clinical, laboratory, or ultrasound findings suggestive of organic disease, underwent endoscopy, celiac disease (CD) serum antibodies testing and HLA-DQ2/DQ8 genotyping. Patients were prescribed a 6-month GCFD, and then clinically reassessed. RESULTS: Among 151 enrolled patients, 134 (89%) were negative for CD-specific antibodies; 72 (48%) were positive for HLA-DQ2/DQ8; and 56 (37%) showed duodenal microscopic inflammation. Clinical improvement was observed in non-CD patients irrespective of the rigorous or partial adherence to the diet, being the difference nonstatistically significant. Response to diet was related to the presence of histological duodenal alterations at baseline (odds ratio 11.323, 95% confidence interval 1.386-92.549 for Marsh 2 pattern), but not to HLA-DQ2/DQ8 positivity (odds ratio 1.120, 95% confidence interval 0.462-2.716). CONCLUSIONS: Our data suggest that children with ASD with GI symptoms have a high prevalence of duodenal intraepithelial lymphocytic infiltration, which seems to be linked to a mechanism other than autoimmune response to gluten consumption. Alteration of duodenal histology, but not the HLA-DQ2/DQ8 status, was associated with clinical response to the diet.
Lien vers le texte intégral (Open Access ou abonnement)
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. Bobrowska-Korczak B, Gatarek P, Rosiak A, Giebultowicz J, Kaluzna-Czaplinska J. {{Reduced levels of modified nucleosides in the urine of autistic children. Preliminary studies}}. {Analytical biochemistry}. 2019.
The aim of this study was to investigate and compare the levels of concentration of modified nucleosides in the urine of autistic and healthy children. The compounds have never been analyzed before. The levels of nucleosides in the urine of both groups were determined by validated high performance liquid chromatography coupled to mass spectrometry (LC-MS/MS) method using multiple reaction monitoring (MRM) mode. Chromatographic separation was achieved with HILIC column and tubercidin was used as the internal standard for the quantification of urinary nucleosides. The within run accuracy and precision ranged from 89 to 106% and from 0.8% to 4.9%, respectively. Lower levels of O-methylguanosine, 7-methylguanosine, 1-methyladenosine, 1-methylguanine, 7-methylguanine and 3-methyladenine in the urine of 22 children with autism, aged 3 to 16 were observed. The differences were not observed in 20 healthy volunteers, in a similar age group. These findings show that modified nucleosides there are metabolic disturbances and nutritional deficiencies in autistic children.
Lien vers le texte intégral (Open Access ou abonnement)
6. Cloarec R, Riffault B, Dufour A, Rabiei H, Gouty-Colomer LA, Dumon C, Guimond D, Bonifazi P, Eftekhari S, Lozovaya N, Ferrari DC, Ben-Ari Y. {{Pyramidal neuron growth and increased hippocampal volume during labor and birth in autism}}. {Science advances}. 2019; 5(1): eaav0394.
We report that the apical dendrites of CA3 hippocampal pyramidal neurons are increased during labor and birth in the valproate model of autism but not in control animals. Using the iDISCO clearing method, we show that hippocampal, especially CA3 region, and neocortical volumes are increased and that the cerebral volume distribution shifts from normal to lognormal in valproate-treated animals. Maternal administration during labor and birth of the NKCC1 chloride transporter antagonist bumetanide, which reduces [Cl(-)]i levels and attenuates the severity of autism, abolished the neocortical and hippocampal volume changes and reduced the whole-brain volume in valproate-treated animals. These results suggest that the abolition of the oxytocin-mediated excitatory-to-inhibitory shift of GABA actions during labor and birth contributes to the pathogenesis of autism spectrum disorders by stimulating growth during a vulnerable period.
Lien vers le texte intégral (Open Access ou abonnement)
7. 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)
8. D’Amanda CS, Peay HL, Wheeler AC, Turbitt E, Biesecker BB. {{Fragile X syndrome clinical trials: exploring parental decision-making}}. {J Intellect Disabil Res}. 2019.
BACKGROUND: The objective of this research was to understand parental proxy decision-making for drug trial participation for children with Fragile X syndrome (FXS). Specifically, we aimed to capture preferences, motivations, influencing factors and barriers related to trial involvement among trial joiners and decliners and describe ease of trial decision-making and decisional regret. METHODS: Interviews were conducted with parents from two groups: those who chose to enrol their child with FXS in a trial (N = 16; Joiners) and those who declined trial participation (N = 15; Decliners). Data were coded and interpreted through inductive content analysis. RESULTS: Prominent decisional factors included attitudes about medicating FXS symptoms, potential for direct benefit (primarily evaluated through the degree of match between target outcomes and child symptomatology and drug mechanism), logistical convenience and perceived risks of side effects. The ultimate motivation for participation was potential for direct benefit. None of the parents reported decisional regret, and ease of decision-making ranged from easy to difficult for our participants. CONCLUSIONS: Therapeutic optimism was high among those who elected participation. Parents may benefit from an explanation of the rationale behind chosen outcome variables and may be more interested in trials that target or measure as an exploratory outcome the symptoms they find most concerning. Our findings reinforce the need for future trials to reduce participant inconvenience. Our results contrast with what has previously been observed in parents of children with life-threatening conditions; parents of children with FXS may be more trial risk averse and find trial decisions to be harder. Parents of children with FXS considering trials may benefit from a decisional intervention aimed at deliberating motivations and barriers.
Lien vers le texte intégral (Open Access ou abonnement)
9. Deneault E, Faheem M, White SH, Rodrigues DC, Sun S, Wei W, Piekna A, Thompson T, Howe JL, Chalil L, Kwan V, Walker S, Pasceri P, Roth FP, Yuen RK, Singh KK, Ellis J, Scherer SW. {{CNTN5(-)(/+)or EHMT2(-)(/+)human iPSC-derived neurons from individuals with autism develop hyperactive neuronal networks}}. {eLife}. 2019; 8.
Induced pluripotent stem cell (iPSC)-derived neurons are increasingly used to model Autism Spectrum Disorder (ASD), which is clinically and genetically heterogeneous. To study the complex relationship of penetrant and weaker polygenic risk variants to ASD, ‘isogenic’ iPSC-derived neurons are critical. We developed a set of procedures to control for heterogeneity in reprogramming and differentiation, and generated 53 different iPSC-derived glutamatergic neuronal lines from 25 participants from 12 unrelated families with ASD. Heterozygous de novo and rare-inherited presumed-damaging variants were characterized in ASD risk genes/loci. Combinations of putative etiologic variants (GLI3/KIF21A or EHMT2/UBE2I) in separate families were modeled. We used a multi-electrode array, with patch-clamp recordings, to determine a reproducible synaptic phenotype in 25% of the individuals with ASD (other relevant data on the remaining lines was collected). Our most compelling new results revealed a consistent spontaneous network hyperactivity in neurons deficient for CNTN5 or EHMT2. The biobank of iPSC-derived neurons and accompanying genomic data are available to accelerate ASD research. Editorial note: This article has been through an editorial process in which authors decide how to respond to the issues raised during peer review. The Reviewing Editor’s assessment is that all the issues have been addressed (see decision letter).
Lien vers le texte intégral (Open Access ou abonnement)
10. Emberti Gialloreti L, Mazzone L, Benvenuto A, Fasano A, Alcon AG, Kraneveld A, Moavero R, Raz R, Riccio MP, Siracusano M, Zachor DA, Marini M, Curatolo P. {{Risk and Protective Environmental Factors Associated with Autism Spectrum Disorder: Evidence-Based Principles and Recommendations}}. {J Clin Med}. 2019; 8(2).
Autism Spectrum Disorder (ASD) is a complex condition with early childhood onset, characterized by a set of common behavioral features. The etiology of ASD is not yet fully understood; however, it reflects the interaction between genetics and environment. While genetics is now a well-established risk factor, several data support a contribution of the environment as well. This paper summarizes the conclusions of a consensus conference focused on the potential pathogenetic role of environmental factors and on their interactions with genetics. Several environmental factors have been discussed in terms of ASD risk, namely advanced parental age, assisted reproductive technologies, nutritional factors, maternal infections and diseases, environmental chemicals and toxicants, and medications, as well as some other conditions. The analysis focused on their specific impact on three biologically relevant time windows for brain development: the periconception, prenatal, and early postnatal periods. Possible protective factors that might prevent or modify an ASD trajectory have been explored as well. Recommendations for clinicians to reduce ASD risk or its severity have been proposed. Developments in molecular biology and big data approaches, which are able to assess a large number of coexisting factors, are offering new opportunities to disentangle the gene(-)environment interplay that can lead to the development of ASD.
Lien vers le texte intégral (Open Access ou abonnement)
11. Gohel D, Sripada L, Prajapati P, Singh K, Roy M, Kotadia D, Tassone F, Charlet-Berguerand N, Singh R. {{FMRpolyG alters mitochondrial transcripts level and respiratory chain complex assembly in Fragile X associated tremor/ataxia syndrome [FXTAS]}}. {Biochimica et biophysica acta Molecular basis of disease}. 2019.
Fragile X-associated tremor/ataxia syndrome (FXTAS) is an inherited neurodegenerative disorder caused by an expansion of 55 to 200 CGG repeats (premutation) in FMR1. These CGG repeats are Repeat Associated non-ATG (RAN) translated into a small and pathogenic protein, FMRpolyG. The cellular and molecular mechanisms of FMRpolyG toxicity are unclear. Various mitochondrial dysfunctions have been observed in FXTAS patients and animal models. However, the causes of these mitochondrial alterations are not well understood. In the current study, we investigated interaction of FMRpolyG with mitochondria and its role in modulating mitochondrial functions. Beside nuclear inclusions, FMRpolyG also formed small cytosolic aggregates that interact with mitochondria both in cell and mouse model of FXTAS. Importantly, expression of FMRpolyG reduces ATP levels, mitochondrial transmembrane potential, mitochondrial supercomplexes assemblies and activities and expression of mitochondrial DNA encoded transcripts in cell and animal models of FXTAS, as well as in FXTAS patient brain tissues. Overall, these results suggest that FMRpolyG alters mitochondrial functions, bioenergetics and initiates cell death. The further study in this direction will help to establish the role of mitochondria in FXTAS conditions.
Lien vers le texte intégral (Open Access ou abonnement)
12. Gumus E. {{A Hemizygous 370 Kilobase Microduplication at Xq13.1 in a Three-Year-Old Boy With Autism and Speech Delay}}. {Fetal and pediatric pathology}. 2019: 1-6.
BACKGROUND: Alterations of Neuroligin 3 (NLGN3), located on Xq13, have been reported in autism spectrum disorder (ASD), and include the less frequent Xq13 duplication. CASE REPORT: A boy with an aggressive behavior, no speech and weak social relationships had a de novo Xq13.1 microduplication detected by microarray analysis. CONCLUSION: NLGN3, TAF1, and MED12 alterations, located on Xq13.1, have been associated with ASD. TAF and MED12 have other clinical features not present in our case. This supports that duplication of NLGN3 may be associated with ASD.
Lien vers le texte intégral (Open Access ou abonnement)
13. Hamad AF, Alessi-Severini S, Mahmud SM, Brownell M, Kuo IF. {{Annual trends in prevalence and incidence of autism spectrum disorders in Manitoba preschoolers and toddlers: 2004-2015}}. {Canadian journal of public health = Revue canadienne de sante publique}. 2019.
OBJECTIVES: Autism spectrum disorders (ASD) are among the leading causes of disabilities in children. We examined the annual prevalence and incidence rate of ASD between 2004 and 2015 in children aged 1 to 5 years residing in Manitoba. METHODS: A population-based study was conducted using the Manitoba Population Research Data Repository. The study included children aged 1 to 5 years residing in Manitoba between 2004 and 2015. Standard identification algorithm was used to identify ASD cases from hospital abstracts and medical claims. Annual prevalence and incidence rates were calculated for the overall population and then stratified according to sex, region, and socio-economic status (SES). Multivariable negative binomial regression models, adjusted for sex, region, and SES, were used to examine changes in prevalence and incidence over study years. RESULTS: Among children aged 1 to 5 years, 1685 ASD cases were diagnosed between 2004 and 2015. The crude ASD prevalence increased from 0.46% in 2004 to 0.97% in 2015 (p = 0.002). The crude incidence rate increased from 0.16% in 2004 to 0.39% in 2015 (p = 0.002). The increase in ASD prevalence and incidence was observed in all subgroups based on sex, region, and SES. The adjusted negative binomial model showed an annual relative risk increase, since 2004, for both prevalence and incidence of 1.69 (95% CI 1.56-1.83) and 1.84 (95% CI 1.62-2.09), respectively. CONCLUSION: During the period from 2004 to 2015, both prevalence and incidence rates of diagnosed ASD in preschoolers and toddlers residing in Manitoba increased significantly.
Lien vers le texte intégral (Open Access ou abonnement)
14. Hetzroni OE, Hessler M, Shalahevich K. {{Learning new relational categories by children with autism spectrum disorders, children with typical development and children with intellectual disabilities: effects of comparison and familiarity on systematicity}}. {J Intellect Disabil Res}. 2019.
BACKGROUND: Systematicity principle, used during analogical reasoning, enables building up deeper abstract concepts as part of structure mapping. The purpose of this study was to investigate structure mapping processes that occur during acquisition of new relational categories and to identify the learning patterns and systematicity of children with autism spectrum disorder (ASD) compared with intellectual and developmental disabilities (IDD) and typical development (TD). Comparison effect and level of familiarity were used to investigate structural mapping processes. METHODS: Three groups of 24 children participated in the study. Using a computer program, participants were asked to select a perceptual or relational choice based on one or two standards using illustrations depicting new relational categories in various spatial configurations. Known, partially known and unknown illustrations were used in depicting three levels of familiarity. RESULTS: All three groups selected perceptual choices when one standard was available (no comparison). However, when two standards were available, enabling a comparison, children with IDD and TD increased their tendency for selecting abstract relational categories, while children with ASD did not change their preference and continued selecting perceptual choices. Level of familiarity increased selection of relational choices among children with TD and IDD but not among children with ASD. CONCLUSIONS: Systematicity principle was evident mostly in the selection of relational choices by children with TD and IDD when the illustrations were known or partially known. Hence, even when an opportunity to compare and to use previously known information was available, structure mapping processes and systematicity were implemented to align information among children TD and IDD but failed to assist the learning of new relational categories among children with ASD.
Lien vers le texte intégral (Open Access ou abonnement)
15. Hswen Y, Gopaluni A, Brownstein JS, Hawkins JB. {{Using Twitter to Detect Psychological Characteristics of Self-Identified Persons With Autism Spectrum Disorder: A Feasibility Study}}. {JMIR mHealth and uHealth}. 2019; 7(2): e12264.
BACKGROUND: More than 3.5 million Americans live with autism spectrum disorder (ASD). Major challenges persist in diagnosing ASD as no medical test exists to diagnose this disorder. Digital phenotyping holds promise to guide in the clinical diagnoses and screening of ASD. OBJECTIVE: This study aims to explore the feasibility of using the Web-based social media platform Twitter to detect psychological and behavioral characteristics of self-identified persons with ASD. METHODS: Data from Twitter were retrieved from 152 self-identified users with ASD and 182 randomly selected control users from March 22, 2012 to July 20, 2017. We conducted a between-group comparative textual analysis of tweets about repetitive and obsessive-compulsive behavioral characteristics typically associated with ASD. In addition, common emotional characteristics of persons with ASD, such as fear, paranoia, and anxiety, were examined between groups through textual analysis. Furthermore, we compared the timing of tweets between users with ASD and control users to identify patterns in communication. RESULTS: Users with ASD posted a significantly higher frequency of tweets related to the specific repetitive behavior of counting compared with control users (P<.001). The textual analysis of obsessive-compulsive behavioral characteristics, such as fixate, excessive, and concern, were significantly higher among users with ASD compared with the control group (P<.001). In addition, emotional terms related to fear, paranoia, and anxiety were tweeted at a significantly higher rate among users with ASD compared with control users (P<.001). Users with ASD posted a smaller proportion of tweets during time intervals of 00:00-05:59 (P<.001), 06:00-11:59 (P<.001), and 18:00-23.59 (P<.001), as well as a greater proportion of tweets from 12:00 to 17:59 (P<.001) compared with control users. CONCLUSIONS: Social media may be a valuable resource for observing unique psychological characteristics of self-identified persons with ASD. Collecting and analyzing data from these digital platforms may afford opportunities to identify the characteristics of ASD and assist in the diagnosis or verification of ASD. This study highlights the feasibility of leveraging digital data for gaining new insights into various health conditions. Lien vers le texte intégral (Open Access ou abonnement)
16. Huang Q, Lin LY, Lin XZ. {{Comparison of Remifentanil-Based Fast-Track and Fentanyl-Based Routine Cardiac Anesthesia for Intraoperative Device Closure of Atrial Septal Defect (ASD) in Pediatric Patients}}. {Medical science monitor : international medical journal of experimental and clinical research}. 2019; 25: 1187-93.
BACKGROUND The aim of this study was to evaluate the effectiveness and safety of remifentanil-based fast-track anesthesia for intraoperative device closure of atrial septal defects (ASDs). MATERIAL AND METHODS The clinical data of 152 pediatric patients who received intraoperative device closure of ASD in our hospital from January 2015 to December 2017 were retrospectively analyzed. Patients were divided into 2 groups: group F (remifentanil-based fast-track anesthesia group, n=72) and group C (fentanyl-based routine anesthesia group, n=80). The relevant data from 2 groups were collected and analyzed. RESULTS No significant differences were found in the preoperative data or intraoperative hemodynamic index between these 2 groups. Group C was significantly inferior to group F regarding the duration of mechanical ventilation, length of intensive care unit (ICU) stay, length of hospital stay, and hospitalization expenses (P<0.05). In terms of postoperative complications, no death, third-degree atrioventricular block, occluder detachment, or residual leakage was reported in either group. The incidence of lung infections and bronchospasm was significantly higher in group C than in group F. There were no anesthetic-related complications. CONCLUSIONS The application of remifentanil-based fast-track anesthesia for intraoperative device closure of ASD is as effective and safe as fentanyl-based routine anesthesia. Moreover, remifentanil-based fast-track anesthesia has the advantages of shorter duration of mechanical ventilation, shorter length of hospital and ICU stay, fewer postoperative complications, and lower hospitalization expenses, and is therefore worthy of promotion in clinical practice. Lien vers le texte intégral (Open Access ou abonnement)
17. Lord C. {{Taking Sleep Difficulties Seriously in Children With Neurodevelopmental Disorders and ASD}}. {Pediatrics}. 2019.
Lien vers le texte intégral (Open Access ou abonnement)
18. Luisier AC, Petitpierre G, Berod AC, Richoz AR, Lao J, Caldara R, Bensafi M. {{Visual and Hedonic Perception of Food Stimuli in Children with Autism Spectrum Disorders and their Relationship to Food Neophobia}}. {Perception}. 2019: 301006619828300.
The present study examined whether children with autism spectrum disorder (ASD) and typically developing (TD) children differed in visual perception of food stimuli at both sensorimotor and affective levels. A potential link between visual perception and food neophobia was also investigated. To these aims, 11 children with ASD and 11 TD children were tested. Visual pictures of food were used, and food neophobia was assessed by the parents. Results revealed that children with ASD explored visually longer food stimuli than TD children. Complementary analyses revealed that whereas TD children explored more multiple-item dishes (vs. simple-item dishes), children with ASD explored all the dishes in a similar way. In addition, children with ASD gave more negative appreciation in general. Moreover, hedonic rating was negatively correlated with food neophobia scores in children with ASD, but not in TD children. In sum, we show here that children with ASD have more difficulty than TD children in liking a food when presented visually. Our findings also suggest that a prominent factor that needs to be considered is time management during the food choice process. They also provide new ways of measuring and understanding food neophobia in children with ASD.
Lien vers le texte intégral (Open Access ou abonnement)
19. Mahapatra P, Pati S, Sinha R, Chauhan AS, Nanda RR, Nallala S. {{Parental care-seeking pathway and challenges for autistic spectrum disorders children: A mixed method study from Bhubaneswar, Odisha}}. {Indian journal of psychiatry}. 2019; 61(1): 37-44.
Background: Autism spectrum disorder (ASD) is globally a major cause of childhood disability. It is estimated that in India approximately 1.7-2 million children are affected with this disorder. Early diagnosis is an important criterion to start early interventions for ASD treatment. However, for every childhood problem that receives a medical diagnosis, there is a period between a parents’ first recognition of unusual symptoms and the eventual diagnosis. Several factors influence this initial symptoms recognition and final diagnosis. Aims: The present study attempts to decipher parents’ perception regarding ASD and to understand the early signs of ASD recognition among parents, treatment-seeking pathways adopted their experiences and challenges in the overall process. Setting and Design: A facility-based cross-sectional study was undertaken at Bhubaneswar, Odisha. Methodology: Parents of children with ASD were recruited for this study. Seventy-six interviews were conducted, and the data were analyzed. Results: The major symptom identified by the majority of the parents was social difficulty among their children. Maximum parents had not heard about ASD before their child was diagnosed with the disorder. Parents consulted multiple professionals or traveled long distances to confirm the diagnosis. Child psychiatrists often confirmed the diagnosis and referred patients to rehabilitation centers. Conclusion: Lack of awareness, unavailability of services, and stress contributed to the delay in ASD diagnosis. There is a need for designing proper awareness and genuine center for the treatment. Similarly, referral and counter-referral mechanism is also required to be established to save delay in diagnosis and initiate prompt treatment in the field of ASD.
Lien vers le texte intégral (Open Access ou abonnement)
20. Mazahery H, Conlon CA, Beck KL, Mugridge O, Kruger MC, Stonehouse W, Camargo CA, Jr., Meyer BJ, Jones B, von Hurst PR. {{A randomised controlled trial of vitamin D and omega-3 long chain polyunsaturated fatty acids in the treatment of irritability and hyperactivity among children with autism spectrum disorder}}. {The Journal of steroid biochemistry and molecular biology}. 2019; 187: 9-16.
Irritability and hyperactivity are common in children with Autism Spectrum Disorder (ASD). Because pharmacological treatments may have adverse effects, and despite limited evidence, caregivers/parents often use dietary supplements such as vitamin D and omega-3 fatty acids to address these behavioural symptoms. As a secondary objective of the VIDOMA (Vitamin D and Omega-3 in ASD) trial, we evaluated the efficacy of vitamin D, omega-3 long chain polyunsaturated fatty acid [omega-3 LCPUFA; docosahexaenoic acid (DHA)], or both on irritability and hyperactivity. New Zealand children with ASD (aged 2.5-8 years) participated in a 12-month randomized, double-blind, placebo-controlled trial of vitamin D (2000 IU/day, VID), omega-3 LCPUFA (722 mg/day DHA, OM), or both (2000 IU/day vitamin D + 722 mg/day DHA, VIDOM). The primary outcomes were the Aberrant Behaviour Checklist (ABC) domains of irritability and hyperactivity. Biomarkers (serum 25-hydroxyvitamin D [25(OH)D] and omega-3 index) and primary outcomes were measured at baseline and 12-months. Out of 111 children who completed baseline data collection, 66% completed the study (VID = 19, OM = 23, VIDOM = 15, placebo = 16). After 12 months, children receiving OM (-5.0 +/- 5.0, P = 0.001) and VID (-4.0+/-4.9, P = 0.01) had greater reduction in irritability than placebo (0.8+/-6.1). Compared to placebo, children on VID also had greater reduction in hyperactivity (-5.2+/-6.3 vs. -0.8+/-5.6, P = 0.047). Serum 25(OH)D concentration (nmol/L, mean+/-SD) increased by 27+/-14 in VID and by 36+/-17 in VIDOM groups (P < 0.0001), and omega-3 index (%, median (25th, 75th percentiles)) by 4.4 (3.3, 5.9) in OM and by 4.0 (2.0, 6.0) in VIDOM groups (P < 0.0001), indicating a good compliance rate. The results indicate that vitamin D and omega-3 LCPUFA reduced irritability symptoms in children with ASD. Vitamin D also reduced hyperactivity symptoms in these children. Lien vers le texte intégral (Open Access ou abonnement)
21. Morris R, Greenblatt A, Saini M. {{Healthcare Providers’ Experiences with Autism: A Scoping Review}}. {J Autism Dev Disord}. 2019.
Gaps in research knowledge exist regarding patient-provider interactions with individuals with autism in healthcare settings. To address this, a scoping review was conducted focusing on the experiences of healthcare professionals working with individuals with autism. A systematic search and screen of the literature resulted in 27 relevant studies. Six key themes were found across these 27 studies including (1) complexity beyond usual role, (2) limited knowledge and resources, (3) training/prior experience, (4) communication and collaboration, (5) need for information and training, and (6) need for care coordination and systemic changes. The results of this review have implications for future research and practice and should be considered when reflecting on opportunities to enhance research and service provision with individuals with autism.
Lien vers le texte intégral (Open Access ou abonnement)
22. 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.
Lien vers le texte intégral (Open Access ou abonnement)
23. Peisley M, Foster TM, Sargisson RJ. {{Reinforcing the prospective remembering of children with autism spectrum disorder}}. {Journal of applied behavior analysis}. 2019.
Prospective memory is remembering to carry out a behavior on a particular occasion or at a specific time in the future. This form of remembering is critical for the daily functioning of children with autism spectrum disorder (ASD) and their functional independence from caregivers. We used a single-subject design to investigate whether reinforcement increased the accuracy of prospective remembering in the context of a computerized board game, Virtual Week, of four 6- to 7-year-old children diagnosed with ASD. Reinforcement increased accuracy for all participants compared to baseline performance and effects were maintained after reinforcement was discontinued for three of four children. This is the first study of which we are aware to use a reinforcement-based behavioral intervention to improve the prospective remembering of children with ASD. Limitations and areas for future research are discussed.
Lien vers le texte intégral (Open Access ou abonnement)
24. Pulikkan J, Mazumder A, Grace T. {{Role of the Gut Microbiome in Autism Spectrum Disorders}}. {Advances in experimental medicine and biology}. 2019; 1118: 253-69.
Autism spectrum disorder (ASD) is a severe neurodevelopmental or neuropsychiatric disorder with elusive etiology and obscure pathophysiology. Cognitive inabilities, impaired communication, repetitive behavior pattern, and restricted social interaction and communication lead to a debilitating situation in autism. The pattern of co-occurrence of medical comorbidities is most intriguing in autism, compared to any other neurodevelopmental disorders. They have an elevated comorbidity burden among which most frequently are seizures, psychiatric illness, and gastrointestinal disorders. The gut microbiota is believed to play a pivotal role in human health and disease through involvement in physiological homoeostasis, immunological development, glutathione metabolism, amino acid metabolism, etc., which in a reasonable way explain the role of gut-brain axis in autism. Branded as a neurodevelopmental disorder with psychiatric impairment and often misclassified as a mental disorder, many experts in the field think that a therapeutic solution to autism is unlikely to emerge. As the pathophysiology is still elusive, taking into account of the various symptoms that are concurrent in autism is important. Gastrointestinal problems that are seen associated with most of the autism cases suggest that it is not just a psychiatric disorder as many claim but have a physiological base, and alleviating the gastrointestinal problems could help alleviating the symptoms by bringing out the much needed overall improvement in the affected victims. A gut disorder akin to Crohn’s disease is, sometimes, reported in autistic children, an extremely painful gastrointestinal disease which is named as autistic enterocolitis. This disturbed situation hypothesized to be initiated by dysbiosis or microbial imbalance could in turn perturb the coordination of microbiota-gut-brain axis which is important in human mental health as goes the popular dictum: « fix your gut, fix your brain. »
Lien vers le texte intégral (Open Access ou abonnement)
25. Randell E, McNamara R, Delport S, Busse M, Hastings RP, Gillespie D, Williams-Thomas R, Brookes-Howell L, Romeo R, Boadu J, Ahuja AS, McKigney AM, Knapp M, Smith K, Thornton J, Warren G. {{Sensory integration therapy versus usual care for sensory processing difficulties in autism spectrum disorder in children: study protocol for a pragmatic randomised controlled trial}}. {Trials}. 2019; 20(1): 113.
BACKGROUND: Autism spectrum disorder (ASD) is a common lifelong condition affecting 1 in 100 people. ASD affects how a person relates to others and the world around them. Difficulty responding to sensory information (noise, touch, movement, taste, sight) is common, and might include feeling overwhelmed or distressed by loud or constant low-level noise (e.g. in the classroom). Affected children may also show little or no response to these sensory cues. These ‘sensory processing difficulties’ are associated with behaviour and socialisation problems, and affect education, relationships, and participation in daily life. Sensory integration therapy (SIT) is a face-to-face therapy or treatment provided by trained occupational therapists who use play-based sensory-motor activities and the just-right challenge to influence the way the child responds to sensation, reducing distress, and improving motor skills, adaptive responses, concentration, and interaction with others. With limited research into SIT, this protocol describes in detail how the intervention will be defined and evaluated. METHODS: This is a two-arm pragmatic individually 1:1 randomised controlled trial with an internal pilot of SIT versus usual care for primary school aged children (aged 4 to 11 years) with ASD and sensory processing difficulties; 216 children will be recruited from multiple sources. Therapy will be delivered in clinics meeting full fidelity criteria for manualised SIT over 26 weeks (face-to-face sessions: two per week for 10 weeks, two per month for 2 months; telephone call: one per month for 2 months). Follow-up assessments will be completed at 6 and 12 months post-randomisation. Prior to recruitment, therapists will be invited to participate in focus groups/interviews to explore what is delivered as usual care in trial regions; carers will be invited to complete an online survey to map out their experience of services. Following recruitment, carers will be given diaries to record their contact with services. Following intervention, carer and therapist interviews will be completed. DISCUSSION: Results of this trial will provide high-quality evidence on the clinical and cost effectiveness of SIT aimed at improving behavioural, functional, social, educational, and well-being outcomes for children and well-being outcomes for carers and families. TRIAL REGISTRATION: ISRCTN14716440 . Registered on 8 November 2016.
Lien vers le texte intégral (Open Access ou abonnement)
26. Reynolds AM, Soke GN, Sabourin KR, Hepburn S, Katz T, Wiggins LD, Schieve LA, Levy SE. {{Sleep Problems in 2- to 5-Year-Olds With Autism Spectrum Disorder and Other Developmental Delays}}. {Pediatrics}. 2019.
: media-1vid110.1542/5984243260001PEDS-VA_2018-0492Video Abstract BACKGROUND: Sleep problems can impact daytime behavior, quality of life, and overall health. We compared sleep habits in young children with autism spectrum disorder (ASD) and other developmental delays and disorders and in children from the general population (POP). METHODS: We included 2- to 5-year-old children whose parent completed all items on the Children’s Sleep Habits Questionnaire (CSHQ) in a multisite case-control study: 522 children with ASD; 228 children with other developmental delays and disorders with autism spectrum disorder characteristics (DD w/ASD); 534 children with other developmental delays and disorders without autism spectrum disorder characteristics (DD w/o ASD); and 703 POP. Multivariable analysis of variance compared CSHQ mean total score (TS) and subscale scores between groups. Logistic regression analysis examined group differences by using TS cutoffs of 41 and 48. Analyses were adjusted for covariates. RESULTS: Mean CSHQ TS for children in each group: ASD (48.5); DD w/ASD (50.4); DD w/o ASD (44.4); and POP (43.3). Differences between children with ASD and both children with DD w/o ASD and POP were statistically significant. Using a TS cutoff of 48, the proportion of children with sleep problems was significantly higher in children in the ASD group versus DD w/o ASD and POP groups (adjusted odds ratios [95% confidence intervals]: 2.12 [1.57 to 2.87] and 2.37 [1.75 to 3.22], respectively). CONCLUSIONS: Sleep problems are more than twice as common in young children with ASD and DD w/ASD. Screening for sleep problems is important in young children to facilitate provision of appropriate interventions.
Lien vers le texte intégral (Open Access ou abonnement)
27. Sears JC, Choi WJ, Broadie K. {{Fragile X mental retardation protein positively regulates PKA anchor Rugose and PKA activity to control actin assembly in learning/memory circuitry}}. {Neurobiology of disease}. 2019.
Recent work shows Fragile X Mental Retardation Protein (FMRP) drives the translation of very large proteins (>2000 aa) mediating neurodevelopment. Loss of function results in Fragile X syndrome (FXS), the leading heritable cause of intellectual disability (ID) and autism spectrum disorder (ASD). Using the Drosophila FXS disease model, we discover FMRP positively regulates the translation of the very large A-Kinase Anchor Protein (AKAP) Rugose (>3000 aa), homolog of ASD-associated human Neurobeachin (NBEA). In the central brain Mushroom Body (MB) circuit, where Protein Kinase A (PKA) signaling is necessary for learning/memory, FMRP loss reduces Rugose levels and targeted FMRP over-expression elevates Rugose levels. Using a new in vivo transgenic PKA activity reporter (PKA-SPARK), we find FMRP loss reduces PKA activity in MB Kenyon Cells whereas FMRP overexpression elevates PKA activity. Consistently, loss of Rugose reduces PKA activity, but Rugose overexpression has no independent effect. A well-established PKA output is regulation of F-actin cytoskeleton dynamics. In the FXS disease model, F-actin is aberrantly accumulated in MB lobes and single MB Kenyon cells. Consistently, Rugose loss results in similar F-actin accumulation. Moreover, targeted FMRP, Rugose and PKA overexpression all result in increased F-actin accumulation in the MB circuit. These findings uncover a FMRP-Rugose-PKA mechanism regulating actin cytoskeleton. This study reveals a novel FMRP mechanism controlling neuronal PKA activity, and demonstrates a shared mechanistic connection between FXS and NBEA associated ASD disease states, with a common link to PKA and F-actin misregulation in brain neural circuits. SIGNIFICANCE STATEMENT: Autism spectrum disorder (ASD) arises from a wide array of genetic lesions, and it is therefore critical to identify common underlying molecular mechanisms. Here, we link two ASD states; Neurobeachin (NBEA) associated ASD and Fragile X syndrome (FXS), the most common inherited ASD. Using established Drosophila disease models, we find Fragile X Mental Retardation Protein (FMRP) positively regulates translation of NBEA homolog Rugose, consistent with a recent advance showing FMRP promotes translation of very large proteins associated with ASD. FXS exhibits reduced cAMP induction, a potent activator of PKA, and Rugose/NBEA is a PKA anchor. Consistently, we find brain PKA activity strikingly reduced in both ASD models. We discover this pathway regulation controls actin cytoskeleton dynamics in brain neural circuits.
Lien vers le texte intégral (Open Access ou abonnement)
28. Shen L, Zhao Y, Zhang H, Feng C, Gao Y, Zhao D, Xia S, Hong Q, Iqbal J, Liu XK, Yao F. {{Advances in Biomarker Studies in Autism Spectrum Disorders}}. {Advances in experimental medicine and biology}. 2019; 1118: 207-33.
Autism spectrum disorder (ASD) is a neurological and developmental condition that begins early in childhood and lasts throughout life. The epidemiology of ASD is continuously increasing all over the world with huge social and economical burdens. As the etiology of autism is not completely understood, there is still no medication available for the treatment of this disorder. However, some behavioral interventions are available to improve the core and associated symptoms of autism, particularly when initiated at an early stage. Thus, there is an increasing demand for finding biomarkers for ASD. Although diagnostic biomarkers have not yet been established, research efforts have been carried out in neuroimaging and biological analyses including genomics and gene testing, proteomics, metabolomics, transcriptomics, and studies of the immune system, inflammation, and microRNAs. Here, we will review the current progress in these fields and focus on new methods, developments, research strategies, and studies of blood-based biomarkers.
Lien vers le texte intégral (Open Access ou abonnement)
29. Spikol A, McAteer D, Murphy J. {{Recognising autism: a latent transition analysis of parental reports of child autistic spectrum disorder ‘red flag’ traits before and after age 3}}. {Social psychiatry and psychiatric epidemiology}. 2019.
PURPOSE: It has been proposed that parents should be educated about child autistic spectrum disorder (ASD) ‘red flag’ traits to help professionals identify and address concerning behaviours as early as possible. This study aimed to empirically demonstrate that established/recognised ‘red flag’ traits in the first 3 years of life would reliably predict ASD risk severity in later childhood, associated with established ASD risk correlates and mirroring functioning diagnostic categories. METHODS: Using retrospective parental report data from the Mental Health of Children and Young People in Great Britain survey (N = 7977), latent class analysis (LCA) and a quasi -latent transition analysis were used to (1) identify profiles of variation in parent reports of child ‘red flag’ traits before and after age 3 and (2) model transitions in risk from 3 years and below to >/= 3 years, respectively, per the ‘optimal outcome’ model. RESULTS: Three distinct classes, each characterised by variation in parent ‘red flag’ trait reporting were identified for the ‘/= 3 years of age’ data. Both LCA class profiles comprised groups of children characterised by low, medium and high ASD risk. Dose-response effects for a number of recognised ASD correlates across the low, moderate and high risk ‘>/= 3 years of age’ classes seemed to validate older classes in terms of ASD relevance. Over 54% of children characterised by the highest levels of ASD ‘red flag’ trait probability at 3 years and below (2% of sample), also populated the high-risk class evidenced in the ‘>/= 3 years of age’ LCA. CONCLUSIONS: Retrospective parental reports of child ASD ‘red flag’ traits Lien vers le texte intégral (Open Access ou abonnement)
30. Subramanyam AA, Mukherjee A, Dave M, Chavda K. {{Clinical Practice Guidelines for Autism Spectrum Disorders}}. {Indian journal of psychiatry}. 2019; 61(Suppl 2): 254-69.
Lien vers le texte intégral (Open Access ou abonnement)
31. Yeung MK, Lee TL, Chan AS. {{Impaired Recognition of Negative Facial Expressions is Partly Related to Facial Perception Deficits in Adolescents with High-Functioning Autism Spectrum Disorder}}. {J Autism Dev Disord}. 2019.
Accumulating studies have reported facial emotion recognition or facial perception impairments in autism spectrum disorder (ASD). To clarify the specificity of the emotion recognition impairment, this study examined the relationships between facial emotion recognition and facial perception abilities in ASD. Twenty-two adolescents with high-functioning ASD (20 males) and 22 typically developing (TD) adolescents (16 males) aged 11-18 years undertook a facial emotion labeling task and a facial perception test. We found that adolescents with ASD had deficits in recognizing negative facial expressions, which correlated with both facial perception deficits and severity of social impairment. In addition, the emotion recognition deficits remained after adjusting for facial perception performance. Thus, our findings suggest an emotion-specific impairment in facial emotion recognition in ASD.
Lien vers le texte intégral (Open Access ou abonnement)
32. Yeung MK, Lee TL, Chan AS. {{Frontal Lobe Dysfunction Underlies the Differential Word Retrieval Impairment in Adolescents with High-Functioning Autism}}. {Autism Res}. 2019.
There is substantial evidence of word retrieval impairment as indicated by poor performance on the category fluency test in autism spectrum disorder (ASD). However, little is known about the neural mechanisms underlying this impairment. Functional neuroimaging studies have shown that the lateral frontal cortex plays a key role in flexible word retrieval. Thus, we examined whether individuals with ASD exhibited altered frontal processing during the category fluency test using functional near-infrared spectroscopy (fNIRS). Twenty-two adolescents with high-functioning ASD (20 males) and 22 typically developing (TD) adolescents (16 males) aged 11-18 years were recruited. All underwent a category fluency paradigm, which required production of animal or means of transportation words for 1 min each although their frontal hemodynamic changes were recorded with fNIRS. We found that adolescents with ASD produced fewer animal but not transportation words (group-by-category interaction: P = 0.003), suggesting differential word retrieval impairment. In addition, unlike TD adolescents who exhibited activation primarily in lateral frontal regions during word production, adolescents with ASD had comparable activation across lateral and medial frontal regions. More importantly, this lack of lateral-medial distinction of activation, which was associated with poor word retrieval, differed significantly between groups only in the animal category (group-by-category interaction: P = 0.018). Thus, our findings implicate frontal lobe dysfunction in the impairment of differential word retrieval in adolescents with ASD. The relatively greater involvement of the medial frontopolar cortex might reflect the use of nonspecialized brain regions to compensate for the category-dependent difficulties with word retrieval in ASD. Autism Res 2019. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Using an optical imaging tool, we found that adolescents with autism had difficulties with producing semantically related words and exhibited frontal lobe dysfunction. Nonetheless, poor word production and altered brain processing was only seen when these adolescents were asked to produce words from a category of living things but not nonliving things (i.e., animals but not means of transportation). Category-dependent word retrieval problems and frontal lobe dysfunction might be two features of this disorder.
