1. Baspinar B, Yardimci H. {{Gluten-Free Casein-Free Diet for Autism Spectrum Disorders: Can It Be Effective in Solving Behavioural and Gastrointestinal Problems?}}. {The Eurasian journal of medicine}. 2020; 52(3): 292-7.
Autism spectrum disorder [ASD] is characterized by deficits in communication and social interactions combined with repetitive and restricted patterns of behaviors. Bidirectional changes in brain-gut microbiota are known to be responsible for the pathophysiology of many brain-related disorders, such as autism, as well as well-known gastrointestinal diseases, including gut disorders. Imbalance in the composition of gut microbiota is frequently observed in individuals with ASD. It is therefore believed that this imbalance is significant in the frequent occurrence of gastrointestinal symptoms. The integrity of the intestinal barrier and the blood-brain barrier [BBB] in individuals with ASD is affected. Incompletely digested peptides, toxins, and proinflammatory cytokines cross the BBB by entering the bloodstream and reach the central nervous system. As a result of the accumulation of these elements, brain function is adversely affected. It is hypothesized that incompletely digested peptides acting as opioid agonists reduce pain sensitivity and increase the severity of autism-specific behaviors. However, it is not known exactly how opioid peptides trigger ASD symptoms after they reach the brain. Diet therapies, especially elimination diets, are considered to be an alternative treatment to prevent this condition. Gluten-free casein-free [GFCF] diet is an elimination diet that involves the removal of certain proteins from the normal diet, such as gluten and casein. However, studies that demonstrate the beneficial effects of the GFCF diet on ASD patients and explain its mechanism is limited, which supports the opioid theory. This review aims to investigate the gastrointestinal and behavioral problems that are frequently observed in ASD, the possible action mechanisms of GFCF diets, and the efficacy of these elimination diets.
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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. Clin E, Maes P, Stercq F, Kissine M. {{No preference for direct versus averted gaze in autistic adults: a reinforced preferential looking paradigm}}. {Mol Autism}. 2020; 11(1): 91.
BACKGROUND: With the overarching objective to gain better insights into social attention in autistic adults, the present study addresses three outstanding issues about face processing in autism. First, do autistic adults display a preference for mouths over eyes; second, do they avoid direct gaze; third, is atypical visual exploration of faces in autism mediated by gender, social anxiety or alexithymia? METHODS: We used a novel reinforced preferential looking paradigm with a group of autistic adults (n = 43, 23 women) pairwise matched on age with neurotypical participants (n = 43, 21 women). Participants watched 28 different pairs of 5 s video recordings of a speaking person: the two videos, simultaneously displayed on the screen, were identical except that gaze was directed at the camera in one video and averted in the other. After a 680 ms transition phase, a short reinforcement animation appeared on the side that had displayed the direct gaze. RESULTS: None of the groups showed a preference for mouths over eyes. However, neurotypical participants fixated significantly more the stimuli with direct gaze, while no such preference emerged in autistic participants. As the experiment progressed, neurotypical participants also increasingly anticipated the appearance of the reinforcement, based on the location of the stimulus with the direct gaze, while no such anticipation emerged in autistic participants. LIMITATIONS: Our autistic participants scored higher on the social anxiety and alexithymia questionnaires than neurotypicals. Future studies should match neurotypical and autistic participants on social anxiety and alexithymia and complement questionnaires with physiological measures of anxiety. CONCLUSIONS: The absence of preference for direct versus averted gaze in the autistic group is probably due to difficulties in distinguishing eye gaze direction, potentially linked to a reduced spontaneous exploration or avoidance of the eye region. Social attention and preference for direct versus averted gaze correlated with alexithymia and social anxiety scores, but not gender.
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4. Dohrn S, Luebbert C, Lehmkemper K, Kyeremateng SO, Degenhardt M, Sadowski G. {{Solvent influence on the phase behavior and glass transition of ASDs}}. {European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik eV}. 2020.
Understanding the long-term stability of amorphous solid dispersions (ASDs) is important for their successful approval for market. ASD stability does not only depend on the interplay between the active pharmaceutical ingredient (API) and the polymer in the final formulation but may already be disadvantageously affected by process steps during the production (e.g. selection of inappropriate solvent for spray drying). Residual solvent can affect the API solubility in the polymer, molecular mobility (by influencing the glass-transition temperature) and induce liquid-liquid phase separation. Enhanced mobility in the ASD due to residual solvent can promote recrystallization in ASDs. The removal of residual solvent can be expensive, time-consuming, and usually requires secondary drying procedures to fulfil the regulatory requirements. The aim of this work is to predict the API solubility in polymer-solvent mixtures, solvent influence on the glass transition, and the occurrence of liquid-liquid phase separation of solvent-loaded ASDs using the thermodynamic model PC-SAFT and to experimentally validate these predictions. ASDs containing the APIs ritonavir or naproxen and the polymers poly(vinyl pyrrolidone), poly (vinyl pyrrolidone- co- vinyl acetate), or hydroxypropyl methylcellulose acetate succinate were spray-dried using the solvents acetone, ethanol, and dichloromethane. API solubility, sorption behavior, liquid-liquid phase separation and glass transition in the ternary API/polymer/solvent mixtures were predicted based on the binary phase behavior between API/solvent, API/polymer, and polymer/solvent and successfully validated experimentally using dynamic vapor sorption (DVS), and Raman spectroscopy. Thus, the presented methodology allows for an in-silico selection of appropriate solvent systems for solvent-based ASD preparation based on a limited amount of experimental data for binary systems only.
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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. El Bouchikhi I, Bouguenouch L, Moufid FZ, Belhassan K, Samri I, Chaouti A, Houssaïni MI, Atmani S, Ouldim K. {{Absence of GATA4 Mutations in Moroccan Patients with Atrial Septal Defect (ASD) Provides Further Evidence of Limited Involvement of GATA4 in Major Congenital Heart Defects}}. {The Eurasian journal of medicine}. 2020; 52(3): 283-7.
OBJECTIVE: Atrial septal defect (ASD) is one of the most common types of congenital heart disease (CHD). It is mainly caused by mutations of NK2 homeobox 5, GATA binding protein 4 (GATA4), and myosin heavy chain 6 in non-syndromic cases. This study aims to carry out, for the first time, the GATA4 mutation screening in a Moroccan population affected by ASD and compare the obtained mutation rate across populations. MATERIALS AND METHODS: A total of 33 patients were enrolled in this study. DNAs were extracted from peripheral blood samples, and we performed PCR-sequencing for GATA4 coding regions. Sequences were analyzed by sequence alignment and functional impact prediction tools. Mutation rate comparisons were performed by R software using the appropriate statistical tests. RESULTS: We detected 7 variants, but no pathogenic mutation was revealed, except for Asn352= that was assessed by human splicing finder algorithms to have a potential impairing effect on the splicing mechanism. Until proven by in vitro functional studies, the current pathogenic mutation rate in our cohort seems to be 0%. Statistical comparison with previous studies from all over the world shows no significant difference. Seemingly, comparison of previous GATA4 mutation rates among tetralogy of Fallot (TOF) populations shows no significant difference. CONCLUSION: The low rates of GATA4 mutations observed throughout ASD and TOF international populations may suggest a limited causality of GATA4 mutations in the main CHDs, which further confirms the co-involvement of additional genetic and/or environmental factors in the manifestation of these phenotypes.
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7. Ethridge L, Thaliath A, Kraff J, Nijhawan K, Berry-Kravis E. {{Development of Neural Response to Novel Sounds in Fragile X Syndrome: Potential Biomarkers}}. {Am J Intellect Dev Disabil}. 2020; 125(6): 449-64.
Auditory processing abnormalities in fragile X syndrome (FXS) may contribute to difficulties with language development, pattern identification, and contextual updating. Participants with FXS (N = 41) and controls (N = 27) underwent auditory event-related potentials during presentation of an oddball paradigm. Data was adequate for analysis for 33 participants with FXS and 27 controls (age 4-51 y, 13 females [FXS]; 4-54 y, 11 females [control]). Participants with FXS showed larger N1 and P2 amplitudes, abnormal lack of modulation of P1 and P2 amplitudes and P2 latency in response to oddball stimuli ) relative to controls: Females with FXS were more similar to controls. Participants with FXS showed a marginal speeding of the P2 latency, suggesting potentiation to oddball stimuli rather than habituation. Participants with FXS showed a heightened N1 habituation effect compared to controls. Gamma power was significantly higher for participants with FXS. Groups did not differ on mismatch negativity. Both controls and participants with FXS showed similar developmental trajectories in P1 and N1 amplitude, P2 latency, and gamma power, but not for P2 amplitude. One month retest analyses performed in 14 participants suggest strong test-retest reliability for most measures. Individuals with FXS show previously demonstrated increased response amplitude and high frequency neural activity. Despite an overall normal developmental trajectory for most measures, individuals with FXS show age-independent but gender-dependent decreases in complex processing of novel stimuli. Many markers show strong retest reliability even in children and thus are potential biomarkers for clinical trials in FXS.
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8. Glezerson BA, Trivedi V, McIsaac DI. {{On the stated association between labour epidural analgesia and risk of autism spectrum disorder in offspring}}. {Canadian journal of anaesthesia = Journal canadien d’anesthesie}. 2020.
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9. Holland CM, Blanche EI, Thompson BL. {{Quantifying Therapists’ Activities during Sensory Integration Treatment for Young Children with Autism}}. {Phys Occup Ther Pediatr}. 2020: 1-16.
AIMS: There is limited research on the type and quantity of actions (activities) occupational therapy practitioners utilize when providing sensory integration treatment to children with Autism Spectrum Disorders (ASD). METHODS: A coding scheme identifying specific aspects of sensory integration treatment was developed and used to analyze 34 videos of 9 children with ASD, aged between 18 and 56 months, treated by 8 occupational therapists. Occupational therapists providing sensory integration treatment to children with ASD were behaviorally coded and rated using Observer XT, a software package designed for analysis of behavioral processes. RESULTS: Verbal communications, including offers, positive commands, and feedback, to facilitate engagement were the most frequent actions enacted by therapists. Proprioceptive activities were the most frequent sensory opportunities presented. Therapists received high ratings for sensitivity qualities. CONCLUSIONS: The number of sensory opportunities and interactions the therapists provided suggest concordance with sensory integration treatment components in the clinical setting. General impression ratings indicate engagement between child and therapist may be an important aspect of sensory integration treatment for young children with ASD. Quantification of therapists’ actions can provide insight into the moment-to-moment decision-making and relationships between therapist and child during daily practice of sensory integration treatment.
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10. 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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11. Kuru Y, Nishiyama T, Sumi S, Suzuki F, Shiino T, Kimura T, Hirai K, Kuroda M, Kamio Y, Kikuchi S. {{Practical applications of brief screening questionnaires for autism spectrum disorder in a psychiatry outpatient setting}}. {International journal of methods in psychiatric research}. 2020: e1857.
OBJECTIVES: This study was designed to examine the diagnostic performance of the social and communication disorders checklist (SCDC) and strength and difficulties questionnaire (SDQ) to detect autism spectrum conditions (ASC), along with the social responsiveness scale-second edition (SRS-2) as reference, in a psychiatry outpatient setting. METHODS: We translated the SCDC into Japanese since its Japanese version was unavailable. We examined its test-retest reliability as well as the internal consistency reliability and diagnostic performance of the three questionnaires among 41 Japanese psychiatric outpatients, using the best-estimate diagnosis of ASC based on the diagnostic interview for social and communication disorders, as a gold standard. RESULTS: The test-retest reliability was high for the SCDC. Although the internal consistency reliability was high for the SCDC and SRS-2, that was low for the prosocial and peer problem subscales of the SDQ. The performance of the SCDC, SDQ, and SRS-2 to detect ASC was moderate: the area under the ROC curve of 0.78, 0.78, and 0.84, respectively. CONCLUSIONS: Although questionnaires to detect ASC, including the three examined, generally have only moderate performance in this setting, these can be successfully applied to high-risk populations such as psychiatry outpatients, when multi-level rather than dichotomous likelihood ratios are used.
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12. Lau JCY, To CKS, Kwan JSK, Kang X, Losh M, Wong PCM. {{Lifelong Tone Language Experience does not Eliminate Deficits in Neural Encoding of Pitch in Autism Spectrum Disorder}}. {J Autism Dev Disord}. 2020.
Atypical pitch processing is a feature of Autism Spectrum Disorder (ASD), which affects non-tone language speakers’ communication. Lifelong auditory experience has been demonstrated to modify genetically-predisposed risks for pitch processing. We examined individuals with ASD to test the hypothesis that lifelong auditory experience in tone language may eliminate impaired pitch processing in ASD. We examined children’s and adults’ Frequency-following Response (FFR), a neurophysiological component indexing early neural sensory encoding of pitch. Univariate and machine-learning-based analytics suggest less robust pitch encoding and diminished pitch distinctions in the FFR from individuals with ASD. Contrary to our hypothesis, results point to a linguistic pitch encoding impairment associated with ASD that may not be eliminated even by lifelong sensory experience.
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13. Li J, Jiang RY, Arendt KL, Hsu YT, Zhai SR, Chen L. {{Defective memory engram reactivation underlies impaired fear memory recall in Fragile X syndrome}}. {eLife}. 2020; 9.
Fragile X syndrome (FXS) is an X chromosome-linked disease associated with severe intellectual disabilities. Previous studies using the Fmr1 knockout (KO) mouse, an FXS mouse model, have attributed behavioral deficits to synaptic dysfunctions. However, how functional deficits at neural network level lead to abnormal behavioral learning remains unexplored. Here, we show that the efficacy of hippocampal engram reactivation is reduced in Fmr1 KO mice performing contextual fear memory recall. Experiencing an enriched environment (EE) prior to learning improved the engram reactivation efficacy and rescued memory recall in the Fmr1 KO mice. In addition, chemogenetically inhibiting EE-engaged neurons in CA1 reverses the rescue effect of EE on memory recall. Thus, our results suggest that inappropriate engram reactivation underlies cognitive deficits in FXS, and enriched environment may rescue cognitive deficits by improving network activation accuracy.
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14. Luo T, Ou JN, Cao LF, Peng XQ, Li YM, Tian YQ. {{The Autism-Related lncRNA MSNP1AS Regulates Moesin Protein to Influence the RhoA, Rac1, and PI3K/Akt Pathways and Regulate the Structure and Survival of Neurons}}. {Autism Res}. 2020.
Autism spectrum disorder (ASD) is a complex disease involving multiple genes and multiple sites, and it is closely related to environmental factors. It has been gradually revealed that long noncoding RNAs (lncRNAs) may regulate the pathogenesis of ASD at the epigenetic level. In neuronal cells, the lncRNA moesin pseudogene 1 antisense (MSNP1AS) forms a double-stranded RNA with moesin (MSN) to suppress moesin protein expression. MSNP1AS overexpression can activate the RhoA pathway and inhibit the Rac1 and PI3K/Akt pathways; however, the regulation of Rac1 by MSNP1AS is not associated with MSN, and the effect on the RhoA pathway may also be associated with other factors. MSNP1AS can decrease the number and length of neurites, inhibit neuronal cell viability and migration, and promote apoptosis. Downregulation of MSN expression functions similarly to MSNP1AS, and its overexpression can block the above functions of MSNP1AS. In addition, in vivo experiments show that MSN improves social interactions and reduces repetitive behaviors in BTBR mice, decreases the activity of RhoA and restores the activity of PI3K/Akt pathway. Therefore, the abnormal expression of MSNP1AS in ASD patients might influence the structure and survival of neuronal cells through the regulation of moesin protein expression to facilitate the development and progression of ASD. These findings provide new evidence for studying the mechanisms of lncRNAs in ASD. LAY SUMMARY: Autism spectrum disorder (ASD) is a common neurodevelopmental disease and its neurodevelopmental mechanisms have not been elucidated. More and more studies have found that long noncoding RNAs (lncRNAs) can regulate the development of central nervous system in many ways and affect the pathogenic process of ASD. Moesin pseudogene 1 antisense (MSNP1AS) is an up-regulated lncRNA in ASD patients. In-depth functional experiments showed that MSNP1AS inhibited moesin protein expression and regulated the activation of multiple signaling pathways, thus decreasing the number and length of neurites, inhibiting neuronal cell viability and migration, and promoting apoptosis. Therefore, MSNP1AS is an important lncRNA related to ASD and can regulate the biological function of neurons.
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15. Mughal R, Hill CM, Joyce A, Dimitriou D. {{Sleep and Cognition in Children with Fetal Alcohol Spectrum Disorders (FASD) and Children with Autism Spectrum Disorders (ASD)}}. {Brain Sci}. 2020; 10(11).
Children with Fetal Alcohol Spectrum Disorders (FASD) and Autism Spectrum Disorders (ASD) experience significantly higher rates of sleep disturbances than their typically developing peers. However, little is known about the association between sleep and the cognitive phenotype in these clinical populations. Structural damage affecting cortical and subcortical connectivity occurs as a result of prenatal alcohol exposure in children with FASD, whilst it is believed an abundance of short-range connectivity explains the phenotypic manifestations of childhood ASD. These underlying neural structural and connectivity differences manifest as cognitive patterns, with some shared and some unique characteristics between FASD and ASD. This is the first study to examine sleep and its association with cognition in individuals with FASD, and to compare sleep in individuals with FASD and ASD. We assessed children aged 6-12 years with a diagnosis of FASD (n = 29), ASD (n = 21), and Typically Developing (TD) children (n = 46) using actigraphy (CamNTech Actiwatch 8), digit span tests of working memory (Weschler Intelligence Scale), tests of nonverbal mental age (MA; Ravens Standard Progressive Matrices), receptive vocabulary (British Picture Vocabulary Scale), and a choice reaction time (CRT) task. Children with FASD and ASD presented with significantly shorter total sleep duration, lower sleep efficiency, and more nocturnal wakings than their TD peers. Sleep was significantly associated with scores on the cognitive tests in all three groups. Our findings support the growing body of work asserting that sleep is significant to cognitive functioning in these neurodevelopmental conditions; however, more research is needed to determine cause and effect.
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16. Qi S, Morris R, Turner JA, Fu Z, Jiang R, Deramus TP, Zhi D, Calhoun VD, Sui J. {{Common and unique multimodal covarying patterns in autism spectrum disorder subtypes}}. {Mol Autism}. 2020; 11(1): 90.
BACKGROUND: The heterogeneity inherent in autism spectrum disorder (ASD) presents a substantial challenge to diagnosis and precision treatment. Heterogeneity across biological etiologies, genetics, neural systems, neurocognitive attributes and clinical subtypes or phenotypes has been observed across individuals with ASD. METHODS: In this study, we aim to investigate the heterogeneity in ASD from a multimodal brain imaging perspective. The Autism Diagnostic Observation Schedule (ADOS) was used as a reference to guide functional and structural MRI fusion. DSM-IV-TR diagnosed Asperger’s disorder (n = 79), pervasive developmental disorder-not otherwise specified [PDD-NOS] (n = 58) and Autistic disorder (n = 92) from ABIDE II were used as discovery cohort, and ABIDE I (n = 400) was used for replication. RESULTS: Dorsolateral prefrontal cortex and superior/middle temporal cortex are the primary common functional-structural covarying cortical brain areas shared among Asperger’s, PDD-NOS and Autistic subgroups. Key differences among the three subtypes are negative functional features within subcortical brain areas, including negative putamen-parahippocampus fractional amplitude of low-frequency fluctuations (fALFF) unique to the Asperger’s subtype; negative fALFF in anterior cingulate cortex unique to PDD-NOS subtype; and negative thalamus-amygdala-caudate fALFF unique to the Autistic subtype. Furthermore, each subtype-specific brain pattern is correlated with different ADOS subdomains, with social interaction as the common subdomain. The identified subtype-specific patterns are only predictive for ASD symptoms manifested in the corresponding subtypes, but not the other subtypes. CONCLUSIONS: Although ASD has a common neural basis with core deficits linked to social interaction, each ASD subtype is strongly linked to unique brain systems and subdomain symptoms, which may help to better understand the underlying mechanisms of ASD heterogeneity from a multimodal neuroimaging perspective. LIMITATIONS: This study is male based, which cannot be generalized to the female or the general ASD population.
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17. Raspa M, Bann CM, Gwaltney A, Benke TA, Fu C, Glaze DG, Haas R, Heydemann P, Jones M, Kaufmann WE, Lieberman D, Marsh E, Peters S, Ryther R, Standridge S, Skinner SA, Percy AK, Neul JL. {{A Psychometric Evaluation of the Motor-Behavioral Assessment Scale for Use as an Outcome Measure in Rett Syndrome Clinical Trials}}. {Am J Intellect Dev Disabil}. 2020; 125(6): 493-509.
Rett syndrome (RTT) is a neurodevelopmental disorder that primarily affects females. Recent work indicates the potential for disease modifying therapies. However, there remains a need to develop outcome measures for use in clinical trials. Using data from a natural history study (n = 1,075), we examined the factor structure, internal consistency, and validity of the clinician-reported Motor Behavior Assessment scale (MBA). The analysis resulted in a five-factor model: (1) motor dysfunction, (2) functional skills, (3) social skills, (4) aberrant behavior, and (5) respiratory behaviors. Item Response Theory (IRT) analyses demonstrated that all items had acceptable discrimination. The revised MBA subscales showed a positive relationship with parent reported items, age, and a commonly used measure of clinical severity in RTT, and mutation type. Further work is needed to evaluate this measure longitudinally and to add items related to the RTT phenotype.
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18. Ryan Idriss C. {{Invisible Autistic Infrastructure: Ethnographic Reflections on an Autistic Community}}. {Medical anthropology}. 2020: 1-12.
In this article, I provide an ethnographic account of an autistic-run community for adults in a North American city. By spending time with each other in loosely structured social interactions, members of this group participate in the ongoing construction of a complex and necessary social infrastructure in the face of often inadequate social and material support from their personal networks, and the larger society in which they live. The work this community does remains largely invisible because it runs counter to dominant biomedical understandings of autism and exists outside of the autism treatment industry.
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19. Sotgiu S, Manca S, Gagliano A, Minutolo A, Melis MC, Pisuttu G, Scoppola C, Bolognesi E, Clerici M, Guerini FR, Carta A. {{Immune regulation of neurodevelopment at the mother-foetus interface: the case of autism}}. {Clinical & translational immunology}. 2020; 9(11): e1211.
Autism spectrum disorder (ASD) is a neurodevelopmental disorder defined by deficits in social communication and stereotypical behaviours. ASD’s aetiology remains mostly unclear, because of a complex interaction between genetic and environmental factors. Recently, a strong consensus has developed around ASD’s immune-mediated pathophysiology, which is the subject of this review. For many years, neuroimmunological studies tried to understand ASD as a prototypical antibody- or cell-mediated disease. Other findings indicated the importance of autoimmune mechanisms such as familial and individual autoimmunity, adaptive immune abnormalities and the influence of infections during gestation. However, recent studies have challenged the idea that autism may be a classical autoimmune disease. Modern neurodevelopmental immunology shows the double-edged nature of many immune effectors, which can be either beneficial or detrimental depending on tissue homeostasis, stressors, neurodevelopmental stage, inherited and de novo gene mutations and other variables. Nowadays, mother-child interactions in the prenatal environment appear to be crucial for the occurrence of ASD. Studies of animal maternal-foetal immune interaction are being fruitfully carried out using different combinations of type and timing of infection, of maternal immune response and foetal vulnerability and of resilience factors to hostile events. The derailed neuroimmune crosstalk through the placenta initiates and maintains a chronic foetal neuroglial activation, eventually causing the alteration of neurogenesis, migration, synapse formation and pruning. The importance of pregnancy can also allow early immune interventions, which can significantly reduce the increasing risk of ASD and its heavy social burden.
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20. Vitiello B. {{Editorial: Targeting the Core Symptoms of Autism Spectrum Disorder With Mechanism-based}}. {J Am Acad Child Adolesc Psychiatry}. 2020.
