1. Du Y, Li B, Hou Y, Calhoun VD. A deep learning fusion model for brain disorder classification : Application to distinguishing schizophrenia and autism spectrum disorder. ACM BCB ;2020 (Sep) ;2020

Deep learning has shown a great promise in classifying brain disorders due to its powerful ability in learning optimal features by nonlinear transformation. However, given the high-dimension property of neuroimaging data, how to jointly exploit complementary information from multimodal neuroimaging data in deep learning is difficult. In this paper, we propose a novel multilevel convolutional neural network (CNN) fusion method that can effectively combine different types of neuroimage-derived features. Importantly, we incorporate a sequential feature selection into the CNN model to increase the feature interpretability. To evaluate our method, we classified two symptom-related brain disorders using large-sample multi-site data from 335 schizophrenia (SZ) patients and 380 autism spectrum disorder (ASD) patients within a cross-validation procedure. Brain functional networks, functional network connectivity, and brain structural morphology were employed to provide possible features. As expected, our fusion method outperformed the CNN model using only single type of features, as our method yielded higher classification accuracy (with mean accuracy >85%) and was more reliable across multiple runs in differentiating the two groups. We found that the default mode, cognitive control, and subcortical regions contributed more in their distinction. Taken together, our method provides an effective means to fuse multimodal features for the diagnosis of different psychiatric and neurological disorders.

Lien vers le texte intégral (Open Access ou abonnement)

2. Kopp N, Amarillo I, Martinez-Agosto J, Quintero-Rivera F. Pathogenic paternally inherited NLGN4X deletion in a female with autism spectrum disorder : Clinical, cytogenetic, and molecular characterization. Am J Med Genet A ;2020 (Dec 24):e62025.

Neuroligin 4 X-linked (NLGN4X) is an X-linked postsynaptic scaffolding protein, with functional role in excitatory synapsis development and maintenance, that has been associated with neuropsychiatric disorders such as intellectual disability, autism spectrum disorders (ASD), anxiety, attention deficit hyperactivity disorder (ADHD), and Tourette’s syndrome. Chromosomal microarray analysis identified a paternally inherited, 445 Kb deletion on Xp22.3 that includes the entire NLGN4X in a 2.5 year old female (46,XX) with congenital hypotonia, strabismus, ASD, and increased aggressive behavioral issues. Her family history is significant for a mother with learning disabilities, a father with anxiety, major depressive disorder, and substance abuse, as well as two maternal half-brothers with developmental delays. X-inactivation studies in the proband’s blood showed random X-inactivation despite the presence of an abnormal X chromosome. Furthermore, trio exome sequencing did not reveal any other deleterious variant that could explain her phenotype. Our report describes the first example of a paternally inherited NLGN4X microdeletion as the genetic etiology of ASD in a female proband, and the psychiatric phenotypes in the father. It also provides further evidence that NLGN4X is sensitive to dosage changes in females, and can contribute to a variety of psychiatric features within the same family.

Lien vers le texte intégral (Open Access ou abonnement)

3. Turner M. The role of drugs in the treatment of autism. Aust Prescr ;2020 (Dec) ;43(6):185-190.

Lien vers le texte intégral (Open Access ou abonnement)

4. Venker CE, Mathée J, Neumann D, Edwards J, Saffran J, Ellis Weismer S. Competing Perceptual Salience in a Visual Word Recognition Task Differentially Affects Children With and Without Autism Spectrum Disorder. Autism Res ;2020 (Dec 28)

Differences in visual attention have long been recognized as a central characteristic of autism spectrum disorder (ASD). Regardless of social content, children with ASD show a strong preference for perceptual salience-how interesting (i.e., striking) certain stimuli are, based on their visual properties (e.g., color, geometric patterning). However, we do not know the extent to which attentional allocation preferences for perceptual salience persist when they compete with top-down, linguistic information. This study examined the impact of competing perceptual salience on visual word recognition in 17 children with ASD (mean age 31 months) and 17 children with typical development (mean age 20 months) matched on receptive language skills. A word recognition task presented two images on a screen, one of which was named (e.g., Find the bowl !). On Neutral trials, both images had high salience (i.e., were colorful and had geometric patterning). On Competing trials, the distracter image had high salience but the target image had low salience, creating competition between bottom-up (i.e., salience-driven) and top-down (i.e., language-driven) processes. Though both groups of children showed word recognition in an absolute sense, competing perceptual salience significantly decreased attention to the target only in the children with ASD. These findings indicate that perceptual properties of objects can disrupt attention to relevant information in children with ASD, which has implications for supporting their language development. Findings also demonstrate that perceptual salience affects attentional allocation preferences in children with ASD, even in the absence of social stimuli. LAY SUMMARY : This study found that visually striking objects distract young children with autism spectrum disorder (ASD) from looking at relevant (but less striking) objects named by an adult. Language-matched, younger children with typical development were not significantly affected by this visual distraction. Though visual distraction could have cascading negative effects on language development in children with ASD, learning opportunities that build on children’s focus of attention are likely to support positive outcomes.

Lien vers le texte intégral (Open Access ou abonnement)

5. Yang JQ, Yang CH, Yin BQ. Combined the GABA-A and GABA-B receptor agonists attenuates autistic behaviors in a prenatal valproic acid-induced mouse model of autism. Behav Brain Res ;2020 (Dec 22):113094.

Autism spectrum disorder (ASD) is an immensely challenging developmental disorder characterized primarily by two core behavioral symptoms of social communication deficits and restricted/repetitive behaviors. Investigating the etiological process and identifying an appropriate therapeutic target remain as formidable challenges to overcome ASD due to numerous risk factors and complex symptoms associated with the disorder. Among the various mechanisms that contribute to ASD, the maintenance of excitation and inhibition balance emerged as a key factor to regulate proper functioning of neuronal circuitry. In this study, we employed prenatally exposed to valproic acid (VPA) to establish a validated ASD mouse model and found impaired inhibitory gamma-aminobutyric acid (GABAergic) neurotransmission through a presynaptic mechanism in these model mice, which was accompanied with decreased GABA release and GABA-A and GABA-B receptor subunits expression. And acute administration of individual GABA-A or GABA-B receptor agonists partially reversed autistic-like behaviors in the model mice. Furthermore, acute administration of the combined GABA-A and GABA-B receptor agonists palliated sociability deficits, anxiety and repetitive behaviors in the animal model of autistic-like behaviors, demonstrating the therapeutic potential of above cocktail in the treatment of ASD.

Lien vers le texte intégral (Open Access ou abonnement)

6. Mizukami M, Ishikawa A, Miyazaki S, Tsuzuki A, Saito S, Niihori T, Sakurai A. A de novo CHD3 variant in a child with intellectual disability, autism, joint laxity, and dysmorphisms. Brain Dev ;2020 (Dec 24)

BACKGROUND : Chromodomain helicase DNA-binding (CHD) proteins play important roles in developmental processes. CHD3, a member of the CHD family of proteins, was reported to be a cause of a neurodevelopmental syndrome by Snijders Blok et al., but only a small number of probands have been reported. CASE REPORT : The patient was a 9-year-old female with severe intellectual disability, speech impairment, autism, joint laxity and dysmorphisms. Whole exome sequencing revealed a de novo missense variant in CHD3 (NM_001005273:exon18 : c.2896C > T:p.R966W). CONCLUSION : We report a case with a pathogenic variant in the CHD3 gene. Our report indicates that CHD3 analysis is helpful for diagnosis of the cases with neurodevelopmental disorders, joint laxity, and coarse facial phenotype.

Lien vers le texte intégral (Open Access ou abonnement)

7. Zwaigenbaum L, Bryson SE, Brian J, Smith IM, Sacrey L, Armstrong V, Roberts W, Szatmari P, Garon N, Vaillancourt T, Roncadin C. Assessment of Autism Symptoms From 6 to 18 Months of Age Using the Autism Observation Scale for Infants in a Prospective High-Risk Cohort. Child Dev ;2020 (Dec 25)

The objectives were to characterize behavioral signs of autism spectrum disorder (ASD) in younger siblings of diagnosed children (high-risk ; HR) and examine classification features of the Autism Observation Scale for Infants (AOSI). Participants (501 HR and 180 low-risk [LR]) were assessed between 6 and 18 months using the AOSI and at age 3 for ASD diagnoses. Total AOSI scores differentiated HR infants later diagnosed with ASD starting at 12 months. ROC analyses identified 12- and 18-month cutoff scores associated with 0.52 sensitivity and 0.74 specificity and 0.73 sensitivity and 0.65 specificity, respectively. Although classification accuracy does not support use as a standalone screen, the AOSI identifies features associated with ASD starting at 6 months and differentiates HR infants with ASD by 12 months.

Lien vers le texte intégral (Open Access ou abonnement)

8. Lopergolo D, Privitera F, Castello G, Lo Rizzo C, Mencarelli MA, Pinto AM, Ariani F, Currò A, Lamacchia V, Canitano R, Vaghi E, Ferrarini A, Baltodano GM, Lederer D, Van Maldergem L, Serrano M, Pineda M, Fons-Estupina MDC, Van Esch H, Breckpot J, Kumps C, Callewaert B, Mueller S, Ramelli GP, Armstrong J, Renieri A, Mari F. IQSEC2 disorder : A new disease entity or a Rett spectrum continuum ?. Clin Genet ;2020 (Dec 28)

IQSEC2 mutations are associated with IQSEC2-related intellectual disability (ID). Phenotypic spectrum has been better defined in the last few years by the increasing number of reported cases although the genotype-phenotype relationship for IQSEC2 remains overall complex. As for IQSEC2-related ID a wide phenotypic diversity has been described in Rett syndrome (RTT). Several patients harboring IQSEC2 mutations present with clinical symptoms similar to RTT and some cases meet most of the criteria for classic RTT. With the aim of establishing a genotype-phenotype correlation, we collected data of 16 patients harboring IQSEC2 point mutations (15 of them previously unreported) and of five novel patients carrying CNVs encompassing IQSEC2. Most of our patients surprisingly shared a moderate-to-mild phenotype. The similarities in the clinical course between our mild cases and patients with milder forms of atypical RTT reinforce the hypothesis that also IQSEC2 mutated patients may lay under the wide clinical spectrum of RTT and thus IQSEC2 should be considered in the differential diagnosis. Our data confirm that position, type of variant and gender are crucial for IQSEC2-associated phenotype delineation.

Lien vers le texte intégral (Open Access ou abonnement)

9. McGoldrick E, Stewart F, Parker R, Dalziel SR. Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database Syst Rev ;2020 (Dec 25) ;12:CD004454.

BACKGROUND : Respiratory morbidity including respiratory distress syndrome (RDS) is a serious complication of preterm birth and the primary cause of early neonatal mortality and disability. Despite early evidence indicating a beneficial effect of antenatal corticosteroids on fetal lung maturation and widespread recommendations to use this treatment in women at risk of preterm delivery, some uncertainty remains about their effectiveness particularly with regard to their use in lower-resource settings, different gestational ages and high-risk obstetric groups such as women with hypertension or multiple pregnancies. This updated review (which supersedes an earlier review Crowley 1996) was first published in 2006 and subsequently updated in 2017. OBJECTIVES : To assess the effects of administering a course of corticosteroids to women prior to anticipated preterm birth (before 37 weeks of pregnancy) on fetal and neonatal morbidity and mortality, maternal mortality and morbidity, and on the child in later life. SEARCH METHODS : We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (3 September 2020), ClinicalTrials.gov, the databases that contribute to the WHO International Clinical Trials Registry Platform (ICTRP) (3 September 2020), and reference lists of the retrieved studies. SELECTION CRITERIA : We considered all randomised controlled comparisons of antenatal corticosteroid administration with placebo, or with no treatment, given to women with a singleton or multiple pregnancy, prior to anticipated preterm delivery (elective, or following rupture of membranes or spontaneous labour), regardless of other co-morbidity, for inclusion in this review. DATA COLLECTION AND ANALYSIS : We used standard Cochrane Pregnancy and Childbirth methods for data collection and analysis. Two review authors independently assessed trials for inclusion, assessed risk of bias, evaluated trustworthiness based on predefined criteria developed by Cochrane Pregnancy and Childbirth, extracted data and checked them for accuracy, and assessed the certainty of the evidence using the GRADE approach. Primary outcomes included perinatal death, neonatal death, RDS, intraventricular haemorrhage (IVH), birthweight, developmental delay in childhood and maternal death. MAIN RESULTS : We included 27 studies (11,272 randomised women and 11,925 neonates) from 20 countries. Ten trials (4422 randomised women) took place in lower- or middle-resource settings. We removed six trials from the analysis that were included in the previous version of the review ; this review only includes trials that meet our pre-defined trustworthiness criteria. In 19 trials the women received a single course of steroids. In the remaining eight trials repeated courses may have been prescribed. Fifteen trials were judged to be at low risk of bias, two had a high risk of bias in two or more domains and we ten trials had a high risk of bias due to lack of blinding (placebo was not used in the control arm. Overall, the certainty of evidence was moderate to high, but it was downgraded for IVH due to indirectness ; for developmental delay due to risk of bias and for maternal adverse outcomes (death, chorioamnionitis and endometritis) due to imprecision. Neonatal/child outcomes Antenatal corticosteroids reduce the risk of : – perinatal death (risk ratio (RR) 0.85, 95% confidence interval (CI) 0.77 to 0.93 ; 9833 infants ; 14 studies ; high-certainty evidence ; 2.3% fewer, 95% CI 1.1% to 3.6% fewer), – neonatal death (RR 0.78, 95% CI 0.70 to 0.87 ; 10,609 infants ; 22 studies ; high-certainty evidence ; 2.6% fewer, 95% CI 1.5% to 3.6% fewer), – respiratory distress syndrome (RR 0.71, 95% CI 0.65 to 0.78 ; 11,183 infants ; studies = 26 ; high-certainty evidence ; 4.3% fewer, 95% CI 3.2% to 5.2% fewer). Antenatal corticosteroids probably reduce the risk of IVH (RR 0.58, 95% CI 0.45 to 0.75 ; 8475 infants ; 12 studies ; moderate-certainty evidence ; 1.4% fewer, 95% CI 0.8% to1.8% fewer), and probably have little to no effect on birthweight (mean difference (MD) -14.02 g, 95% CI -33.79 to 5.76 ; 9551 infants ; 19 studies ; high-certainty evidence). Antenatal corticosteroids probably lead to a reduction in developmental delay in childhood (RR 0.51, 95% CI 0.27 to 0.97 ; 600 children ; 3 studies ; moderate-certainty evidence ; 3.8% fewer, 95% CI 0.2% to 5.7% fewer). Maternal outcomes Antenatal corticosteroids probably result in little to no difference in maternal death (RR 1.19, 95% CI 0.36 to 3.89 ; 6244 women ; 6 studies ; moderate-certainty evidence ; 0.0% fewer, 95% CI 0.1% fewer to 0.5% more), chorioamnionitis (RR 0.86, 95% CI 0.69 to 1.08 ; 8374 women ; 15 studies ; moderate-certainty evidence ; 0.5% fewer, 95% CI 1.1% fewer to 0.3% more), and endometritis (RR 1.14, 95% CI 0.82 to 1.58 ; 6764 women ; 10 studies ; moderate-certainty ; 0.3% more, 95% CI 0.3% fewer to 1.1% more) The wide 95% CIs in all of these outcomes include possible benefit and possible harm. AUTHORS’ CONCLUSIONS : Evidence from this updated review supports the continued use of a single course of antenatal corticosteroids to accelerate fetal lung maturation in women at risk of preterm birth. Treatment with antenatal corticosteroids reduces the risk of perinatal death, neonatal death and RDS and probably reduces the risk of IVH. This evidence is robust, regardless of resource setting (high, middle or low). Further research should focus on variations in the treatment regimen, effectiveness of the intervention in specific understudied subgroups such as multiple pregnancies and other high-risk obstetric groups, and the risks and benefits in the very early or very late preterm periods. Additionally, outcomes from existing trials with follow-up into childhood and adulthood are needed in order to investigate any longer-term effects of antenatal corticosteroids. We encourage authors of previous studies to provide further information which may answer any remaining questions about the use of antenatal corticosteroids without the need for further randomised controlled trials. Individual patient data meta-analyses from published trials are likely to provide answers for most of the remaining clinical uncertainties.

Lien vers le texte intégral (Open Access ou abonnement)

10. Horiuchi F, Kawabe K, Oka Y, Nakachi K, Hosokawa R, Ueno SI. The Association between Autistic Traits and Sleep Habits/Problems in Toddlers. Dev Neuropsychol ;2020 (Dec 25):1-11.

Sleep disturbances are the comorbid conditions most frequently associated with autism spectrum disorder (ASD). Sleep problems might precede and worsen the behavioral outcomes of ASD. This study examined the association between sleep habits/problems and autistic traits in toddlers. Eighteen-month-old toddlers (N = 426 ; boys/girls, 204/222) were assessed for autistic traits using the Japanese version of the Modified Checklist for Autism in Toddlers and sleep habits/problems using the Child and Adolescent Sleep Checklist during health checkups. There were no significant differences in sleep habits, including total sleep time, wake time, bedtime, and naps, between autistic toddlers (n= 26) and non-autistic toddlers (n= 400). However, toddlers with autistic traits more commonly exhibited bedtime resistance, abnormality in circadian rhythm, and sleepiness outside of naptime than toddlers without autistic traits. Moreover, autistic traits were significantly associated with daytime sleepiness. Autistic traits are associated with sleep problems in toddlers. In particular, daytime sleepiness might be avisible symptom that enables the earlier detection of ASD in children.

Lien vers le texte intégral (Open Access ou abonnement)

11. Liu J, Tsang T, Ponting C, Jackson L, Jeste SS, Bookheimer SY, Dapretto M. Lack of neural evidence for implicit language learning in 9-month-old infants at high risk for autism. Dev Sci ;2020 (Dec 24):e13078.

Word segmentation is a fundamental aspect of language learning, since identification of word boundaries in continuous speech must occur before the acquisition of word meanings can take place. We previously used functional magnetic resonance imaging (fMRI) to show that youth with autism spectrum disorder (ASD) are less sensitive to statistical and speech cues that guide implicit word segmentation. However, little is known about the neural mechanisms underlying this process during infancy and how this may be associated with ASD risk. Here, we examined early neural signatures of language-related learning in 9-month-old infants at high (HR) and low familial risk (LR) for ASD. During natural sleep, infants underwent fMRI while passively listening to three speech streams containing strong statistical and prosodic cues, strong statistical cues only, or minimal statistical cues to word boundaries. Compared to HR infants, LR infants showed greater activity in the left amygdala for the speech stream containing statistical and prosodic cues. While listening to this same speech stream, LR infants also showed more learning-related signal increases in left temporal regions as well as increasing functional connectivity between bilateral primary auditory cortex and right anterior insula. Importantly, learning-related signal increases at 9 months positively correlated with expressive language outcome at 36 months in both groups. In the HR group, greater signal increases were additionally associated with less severe ASD symptomatology at 36 months. These findings suggest that early differences in the neural networks underlying language learning may predict subsequent language development and altered trajectories associated with ASD risk.

Lien vers le texte intégral (Open Access ou abonnement)

12. Adams I, Yang T, Longo FM, Katz DM. Restoration of motor learning in a mouse model of Rett syndrome following long-term treatment with a novel small-molecule activator of TrkB. Dis Model Mech ;2020 (Nov 27) ;13(11)

Reduced expression of brain-derived neurotrophic factor (BDNF) and impaired activation of the BDNF receptor, tropomyosin receptor kinase B (TrkB ; also known as Ntrk2), are thought to contribute significantly to the pathophysiology of Rett syndrome (RTT), a severe neurodevelopmental disorder caused by loss-of-function mutations in the X-linked gene encoding methyl-CpG-binding protein 2 (MeCP2). Previous studies from this and other laboratories have shown that enhancing BDNF expression and/or TrkB activation in Mecp2-deficient mouse models of RTT can ameliorate or reverse abnormal neurological phenotypes that mimic human RTT symptoms. The present study reports on the preclinical efficacy of a novel, small-molecule, non-peptide TrkB partial agonist, PTX-BD4-3, in heterozygous female Mecp2 mutant mice, a well-established RTT model that recapitulates the genetic mosaicism of the human disease. PTX-BD4-3 exhibited specificity for TrkB in cell-based assays of neurotrophin receptor activation and neuronal cell survival and in in vitro receptor binding assays. PTX-BD4-3 also activated TrkB following systemic administration to wild-type and Mecp2 mutant mice and was rapidly cleared from the brain and plasma with a half-life of ∼2 h. Chronic intermittent treatment of Mecp2 mutants with a low dose of PTX-BD4-3 (5 mg/kg, intraperitoneally, once every 3 days for 8 weeks) reversed deficits in two core RTT symptom domains – respiration and motor control – and symptom rescue was maintained for at least 24 h after the last dose. Together, these data indicate that significant clinically relevant benefit can be achieved in a mouse model of RTT with a chronic intermittent, low-dose treatment paradigm targeting the neurotrophin receptor TrkB.

Lien vers le texte intégral (Open Access ou abonnement)

13. Fields VL, Soke GN, Reynolds A, Tian LH, Wiggins L, Maenner M, DiGuiseppi C, Kral TVE, Hightshoe K, Ladd-Acosta C, Schieve LA. Association between pica and gastrointestinal symptoms in preschoolers with and without autism spectrum disorder, Study to Explore Early Development. Disabil Health J ;2020 (Dec 13):101052.

BACKGROUND : Pica, the repeated ingestion of nonfood items, can result in gastrointestinal (GI) outcomes. Children with autism spectrum disorder (ASD) and other developmental disabilities (DDs) are disproportionately affected by both pica and GI symptoms. Study of the inter-relationship between pica, GI symptoms, and ASD/DD is limited. OBJECTIVE/HYPOTHESIS : We assessed associations between pica and GI symptoms in preschool-aged children with and without ASD and other (non-ASD) DDs in the Study to Explore Early Development. METHODS : Our sample included children with ASD (n = 1244), other DDs (n = 1593), and population (POP) controls (n = 1487). Data to define final case-control status, pica, and GI symptoms were from standardized developmental assessments/questionnaires. Prevalence ratios, adjusted for sociodemographic factors (aPRs), and 95% confidence intervals were derived from modified Poisson regression. RESULTS : Within each group (ASD, DD, POP) and for the total sample, pica was associated with vomiting (aPR for total sample 2.6 [1.7, 4.0]), diarrhea (1.8 [1.4, 2.2]), and loose stools (1.8 [1.4, 2.2]). In the DD group, pica was associated with constipation (1.4 [1.03, 1.9]) and pain on stooling (1.8 [1.2, 2.6]). In analyses of the subgroup without pica, increases in GI symptoms were still evident in the ASD and DD groups compared to POP group. CONCLUSION : These findings highlight an important adverse effect of pica, GI symptoms, in children with and without ASD and DDs ; nonetheless, pica does not fully explain the increased risk for GI symptoms among children with ASD and DDs. These findings inform the specialized healthcare needs of children with ASD and other DDs.

Lien vers le texte intégral (Open Access ou abonnement)

14. Settanni CR, Bibbò S, Ianiro G, Rinninella E, Cintoni M, Mele MC, Cammarota G, Gasbarrini A. Gastrointestinal involvement of autism spectrum disorder : focus on gut microbiota. Expert Rev Gastroenterol Hepatol ;2021 (Jan 5):1-24.

INTRODUCTION : Autism spectrum disorder (ASD) is a neurodevelopmental disorder typical of early age, characterized by impaired communication, social interaction, and repetitive behaviors. ASD patients frequently suffer from gastrointestinal (GI) symptoms. Neuro-psychological functions, intestinal homeostasis, and functional GI disturbances are modulated by the gut microbiota through the so-called ‘microbiota-gut-brain axis’. AREAS COVERED : Literature regarding GI symptoms among the ASD community as well as the involvement and modulation of the gut microbiota in GI disturbances of ASD patients was searched. Constipation, diarrhea, reflux, abdominal bloating, pain, and discomfort are reported with variable prevalence. ASD is characterized by a reduction of Bacteroidetes/Firmicutes, of the abundance of Bacteroidetes and other imbalances. ASD patients with GI symptoms present microbial changes with plausible relation with deficiency of digestive enzymes, carbohydrate malabsorption, selective eating, bacterial toxins, serotonin metabolism, and inflammation. The strategies to mitigate the GI distress through the gut microbiota modulation comprise antimicrobials, probiotics, prebiotics, fecal microbiota transplantation, and dietary intervention. EXPERT OPINION : The modulation of the gut microbiota in ASD individuals with GI disturbances seems a promising target for the future medicine. A standardization of the research strategies for large-scale studies together with a focus on poorly explored fields is necessary to strengthen this hypothesis.

Lien vers le texte intégral (Open Access ou abonnement)

15. Gomes AR, Fernandes TG, Vaz SH, Silva TP, Bekman EP, Xapelli S, Duarte S, Ghazvini M, Gribnau J, Muotri AR, Trujillo CA, Sebastião AM, Cabral JMS, Diogo MM. Modeling Rett Syndrome With Human Patient-Specific Forebrain Organoids. Front Cell Dev Biol ;2020 ;8:610427.

Engineering brain organoids from human induced pluripotent stem cells (hiPSCs) is a powerful tool for modeling brain development and neurological disorders. Rett syndrome (RTT), a rare neurodevelopmental disorder, can greatly benefit from this technology, since it affects multiple neuronal subtypes in forebrain sub-regions. We have established dorsal and ventral forebrain organoids from control and RTT patient-specific hiPSCs recapitulating 3D organization and functional network complexity. Our data revealed a premature development of the deep-cortical layer, associated to the formation of TBR1 and CTIP2 neurons, and a lower expression of neural progenitor/proliferative cells in female RTT dorsal organoids. Moreover, calcium imaging and electrophysiology analysis demonstrated functional defects of RTT neurons. Additionally, assembly of RTT dorsal and ventral organoids revealed impairments of interneuron’s migration. Overall, our models provide a better understanding of RTT during early stages of neural development, demonstrating a great potential for personalized diagnosis and drug screening.

Lien vers le texte intégral (Open Access ou abonnement)

16. Sanjeevan T, Hammill C, Brian J, Crosbie J, Schachar R, Kelley E, Liu X, Nicolson R, Iaboni A, Day Fragiadakis S, Ristic L, Lerch JP, Anagnostou E. Exploring the Neural Structures Underlying the Procedural Memory Network as Predictors of Language Ability in Children and Adolescents With Autism Spectrum Disorder and Attention Deficit Hyperactivity Disorder. Front Hum Neurosci ;2020 ;14:587019.

Introduction : There is significant overlap in the type of structural language impairments exhibited by children with autism spectrum disorder (ASD) and children with attention deficit hyperactivity disorder (ADHD). This similarity suggests that the cognitive impairment(s) contributing to the structural language deficits in ASD and ADHD may be shared. Previous studies have speculated that procedural memory deficits may be the shared cognitive impairment. The procedural deficit hypothesis (PDH) argues that language deficits can be explained by differences in the neural structures underlying the procedural memory network. This hypothesis is based on the premise that the neural structures comprising the procedural network support language learning. In this study, we aimed to test the PDH in children with ASD, ADHD, and typical development (TD). Methods : One hundred and sixty-three participants (ages 10-21) : 91 with ASD, 26 with ADHD, and 46 with TD, completed standardized measures of cognitive and language ability as well as structural magnetic resonance imaging. We compared the structural language abilities, the neural structures underlying the procedural memory network, and the relationship between structural language and neural structure across diagnostic groups. Results : Our analyses revealed that while the structural language abilities differed across ASD, ADHD, and TD groups, the thickness, area, and volume of the structures supporting the procedural memory network were not significantly different between diagnostic groups. Also, several neural structures were associated with structural language abilities across diagnostic groups. Only two of these structures, the inferior frontal gyrus, and the left superior parietal gyrus, are known to be linked to the procedural memory network. Conclusions : The inferior frontal gyrus and the left superior parietal gyrus, have well-established roles in language learning independent of their role as part of the procedural memory system. Other structures such as the caudate and cerebellum, with critical roles in the procedural memory network, were not associated with structural language abilities across diagnostic groups. It is unclear whether the procedural memory network plays a fundamental role in language learning in ASD, ADHD, and TD.

Lien vers le texte intégral (Open Access ou abonnement)

17. Behl S, Mehta S, Pandey MK. Abnormal Levels of Metal Micronutrients and Autism Spectrum Disorder : A Perspective Review. Front Mol Neurosci ;2020 ;13:586209.

The aim of the present review is to summarize the prevalence of abnormal levels of various metal micronutrients including copper (Cu), iron (Fe), magnesium (Mg), zinc (Zn), and selenium (Se) in Autism Spectrum Disorder (ASD) using hair, nail and serum samples. A correlation of selected abnormal metal ions with known neurodevelopmental processes using Gene Ontology (GO) term was also conducted. Data included in this review are derived from ASD clinical studies performed globally. Metal ion disparity data is also analyzed and discussed based on gender (Male/Female) to establish any gender dependent correlation. Finally, a rational perspective and possible path to better understand the role of metal micronutrients in ASD is suggested.

Lien vers le texte intégral (Open Access ou abonnement)

18. Brewer N, Young RL, Lucas CA. Autism Screening in Early Childhood : Discriminating Autism From Other Developmental Concerns. Front Neurol ;2020 ;11:594381.

Early identification of autism, followed by appropriate intervention, has the potential to improve outcomes for autistic individuals. Numerous screening instruments have been developed for children under 3 years of age. Level 1 screeners are used in large-scale screening to detect at-risk children in the general population ; Level 2 screeners are concerned with distinguishing children with signs of autism from those with other developmental problems. The focus here is evaluation of Level 2 screeners. However, given the contributions of Level 1 screeners and the necessity to understand how they might interface with Level 2 screeners, we briefly review Level 1 screeners and consider instrument characteristics and system variables that may constrain their effectiveness. The examination of Level 2 screeners focuses on five instruments associated with published evaluations in peer-reviewed journals. Key criteria encompass the traditional indices of test integrity such as test reliability (inter-rater, test-retest) and construct validity, including concurrent and predictive validity, sensitivity (SE), and specificity (SP). These evaluations reveal limitations, including inadequate sample sizes, reliability issues, and limited involvement of independent researchers. Also lacking are comparative test evaluations under standardized conditions, hindering interpretation of differences in discriminative performance across instruments. Practical considerations constraining the use of such instruments-such as the requirements for training in test administration and test administration time-are canvassed. Published Level 2 screener short forms are reviewed and, as a consequence of that evaluation, future directions for assessing the discriminative capacity of items and measures are suggested. Suggested priorities for future research include targeting large and diverse samples to permit robust appraisals of Level 2 items and scales across the 12-36 month age range, a greater focus on precise operationalization of items and response coding to enhance reliability, ongoing exploration of potentially discriminating items at the younger end of the targeted age range, and trying to unravel the complexities of developmental trajectories in autistic infants. Finally, we emphasize the importance of understanding how screening efficacy is dependent on clinicians’ and researchers’ ability not only to develop screening tests but also to negotiate the complex organizational systems within which screening procedures must be implemented.

Lien vers le texte intégral (Open Access ou abonnement)

19. Kiselev Y, Handal M, Hjellvik V, Reichborn-Kjennerud T, Stoltenberg C, Suren P, Havdahl A, Skurtveit S. Nationwide Study of Neuropsychiatric Comorbidity and Medicines Use in Children With Autism Spectrum Disorder in Norway. Front Psychiatry ;2020 ;11:596032.

Purpose : Autism spectrum disorder (ASD) has a high rate of comorbidity. While many children with ASD are exposed to psychotropic medicines, their efficacy and safety in these patients are unclear. There is a need for more detailed knowledge on which medicines are most commonly used and for which disorders. We aimed to investigate (a) prevalence and incidence rate of ASD among Norwegian children, and further, among newly diagnosed ASD children in 2014, study the (b) co-occurrence of neuropsychiatric disorders, (c) use of psychotropic drugs, and (d) the relationship between co-occurring diagnoses and use of psychotropic drugs. Method : Nationwide registry-based study of children 2-17 years old in Norway. Results : The ASD prevalence was 0.76% and the incidence rate was 0.12% in 2014. Of the children who received an initial ASD diagnosis in 2014 (n = 1,234), 64.8% had one or more co-occurring neuropsychiatric diagnosis. Psychotropic medication use was moderate ( 20% used stimulants or hypnotics) in general, and low in children without comorbidity (nearly only hypnotics). There was a good accordance between co-occurring diagnoses and indication for the prescribed medications. Conclusions : Children with newly diagnosed ASD mainly received psychotropic drugs to treat co-occurring neuropsychiatric conditions.

Lien vers le texte intégral (Open Access ou abonnement)

20. Rafiei Milajerdi H, Sheikh M, Najafabadi MG, Saghaei B, Naghdi N, Dewey D. The Effects of Physical Activity and Exergaming on Motor Skills and Executive Functions in Children with Autism Spectrum Disorder. Games Health J ;2020 (Dec 23)

Objective : This study aims at investigating the effects of two types of interventions, Sports, Play and Active Recreation for Kids (SPARK) and exergaming (Kinect), on motor skills (MS) and executive functions (EF) in children with autism spectrum disorder (ASD). Materials and Methods : Sixty children, aged 6-10 years were randomly assigned to SPARK (n = 20), Kinect (n = 20), or a control group (n = 20). Children’s MS and EF were assessed before and after the intervention. The SPARK and Kinect groups participated in an 8-week intervention ; the control group received treatment as usual. Intention-to-treat repeated-measures ANOVA was used to examine the effects of the intervention. Results : For MS, a significant group X time interaction was observed for aiming and catching skills [F(2, 53) = 4.12, P < 0.05] ; the SPARK group improved significantly from pre- to post-test compared with the other groups. For EF, a main effect of group was found for correct responses [F(2, 53) = 5.43, P < 0.01]. The Kinect group showed more correct responses than the SPARK and control groups. A main effect of time was significant for conceptual responses [F(1, 53) = 10.61, P < 0.01] and perseverative errors [F(1, 53) = 14.31, P < 0.01]. Conclusion : This study suggests that structured physical activity (PA) interventions that target specific MS improve motor function in children with ASD and exergaming could be effective for improving EF. Future research is needed to untangle the interaction between the type of exercise, traditional PA versus exergaming, and the dose associated with improvements in MS and EF in children with ASD.

Lien vers le texte intégral (Open Access ou abonnement)

21. Taurines R, Radtke F, Romanos M, König S. Using real patients in e-learning : case-based online training in child and adolescent psychiatry. GMS J Med Educ ;2020 ;37(7):Doc96.

Objectives : In undergraduate medical education and in the subject of child and adolescent psychiatry, examining young patients face-to-face is a key element of teaching. With the abrupt shutdown of face-to-face teaching caused by the SARS-CoV-2 pandemic, a case-based online training program integrating audio and video of real patients was developed. Methods : The blended learning platform CaseTrain guides medical students in their final year through real child-psychiatric patient cases, such as anorexia, autism, or attention deficit disorder, through presentation of video and audio of real patients and parents. The teaching format complements lectures on child psychiatric topics, comprising asynchronous elements (self-study using the digital material) as well as synchronous elements (web-conferences with a specialist). Learning objectives for students were set to develop knowledge of the spectra of psychiatric disorders that affect children and to recognize approaches how to assess and manage common psychiatric problems of childhood and adolescence. Results : The feedback from medical students through oral and written evaluation was positive. They appreciated getting to know ‘real-world patients’ in times of such a pandemic, to learn explorative techniques from role models, and to be in close contact with the supervising specialist. In consequence of critical feedback on the length of some video sequences, these training units will undergo revision. Conclusions : Case-based online training may continue to be a useful option in a post-pandemic future as integral part of medical education, complementing face-to-face lectures and training in (child) psychiatry.

Lien vers le texte intégral (Open Access ou abonnement)

22. Sener EF, Onal MG, Dal F, Nalbantoglu U, Ozkul Y, Canatan H, Oztop DB. Novel alterations of CC2D1A as a candidate gene in a Turkish sample of patients with autism spectrum disorder. Int J Neurosci ;2020 (Dec 28):1-8.

BACKGROUND : Autism spectrum disorder (ASD) is a neurodevelopmental disorder with large genetic background, but identification of pathogenic variants has proceeded slowly because hundreds of loci are involved in this complex disorder. CC2D1A gene firstly associated with the intellectual disability (ID) in a family with a large deletion. We aimed to contribute to the literature by sequencing this gene and by this way we report novel CC2D1A variations in patients with ASD. METHODS : Forty families who have a child with a diagnosis of ASD were enrolled to the study. DNA samples were obtained from each family member. Bidirectional CC2D1A gene sequencing was performed with CEQ Cycle Sequencing Kit, and the products were analyzed on the Beckman CEQ 8000. All of the genetic analysis was conducted in Erciyes University Genome and Stem Cell Center (GENKOK). RESULTS : According to the sequencing results, we defined new alterations in this gene with two SNPs in exon 15 and 19 (rs747172992 and rs1364074600) in our patients. We found a pathogenic variant in one patient. This variant was located in the acceptor region. Six of the variants were missense mutations. Additionally, six different benign variants were detected in 30 patients ; however, they were not associated with ASD. Two patients carried multiple rare variants. CONCLUSION : In vitro and in vivo functional analysis with this gene will help to understand its contribution to ASD pathogenesis. Future studies may help to elucidate the underlying biological mechanisms of these variants leading to the autism phenotype.

Lien vers le texte intégral (Open Access ou abonnement)

23. Balboni G, Bacherini A, Rebecchini G, Cagiano R, Mancini A, Tancredi R, Igliozzi R, Muratori F. Individual and Environmental Factors Affecting Adaptive Behavior of Toddlers with Autism Spectrum Disorder : Role of Parents’ Socio-cultural Level. J Autism Dev Disord ;2020 (Dec 23)

The effects of environmental factors [including Socio-Economic Status, Cultural Capital, and Social Capital (Socio-Cultural Level) of both parents] on the Vineland-II adaptive behavior dimensions of toddlers with autism spectrum disorder (ASD), in addition to individual factors, was investigated in 148 Italian toddlers (82% males), aged 18 to 37 months with ASD. Toddlers’ age and Griffiths Mental Development Scales general development affected all of the adaptive behavior dimensions, with negative and positive associations, respectively. The Child Behavior Checklist comorbid conditions were negatively associated with some adaptive behavior dimensions while the ADOS-2 Social affect only with the communication dimension. Mothers’ and fathers’ specific Socio-Cultural Level dimensions were positively associated with toddlers’ specific adaptive behavior dimensions with the same magnitude as comorbid conditions.

Lien vers le texte intégral (Open Access ou abonnement)

24. Bertrams A. Less Illusion of a Just World in People with Formally Diagnosed Autism and Higher Autistic Traits. J Autism Dev Disord ;2020 (Dec 23)

People differ in how strongly they believe that, in general, one gets what (s)he deserves (i.e., individual differences in the general belief in a just world). In this study (N = 588 ; n = 60 with a formal autism diagnosis), whether or not autistic people and those with high autistic traits have a relatively low general belief in a just world is examined. The results revealed the expected relationship between autism/higher autistic traits and a lower general belief in a just world. In a subsample (n = 388), personal belief in a just world, external locus of control, and self-deception mediated this relationship. These findings are discussed in terms of autistic strengths (less biased information processing) and problems (lowered well-being).

Lien vers le texte intégral (Open Access ou abonnement)

25. Havdahl A, Farmer C, Schjølberg S, Øyen AS, Surén P, Reichborn-Kjennerud T, Magnus P, Bresnahan M, Hornig M, Susser E, Lipkin WI, Lord C, Stoltenberg C, Thurm A, Bishop S. Age of walking and intellectual ability in autism spectrum disorder and other neurodevelopmental disorders : a population-based study. J Child Psychol Psychiatry ;2020 (Dec 28)

BACKGROUND : Delayed walking is common in intellectual disability (ID) but may be less common when ID occurs with autism spectrum disorder (ASD). Previous studies examining this were limited by reliance on clinical samples and exclusion of children with severe motor deficits. OBJECTIVE : To examine in a population-based sample if age of walking is differentially related to intellectual ability in children with ASD versus other neurodevelopmental disorders (NDD). METHODS : Participants were from the nested Autism Birth Cohort Study of the Norwegian Mother, Father and Child Cohort Study (MoBa). Cox proportional hazards regression assessed if diagnosis (ASD n = 212 vs. NDD n = 354), continuous nonverbal IQ, and their interaction, were associated with continuous age of walking. RESULTS : The relationship between nonverbal IQ and age of walking was stronger for NDD than for ASD (Group × nonverbal IQ interaction, χ(2) = 13.93, p = .0002). This interaction was characterized by a 21% decrease in the likelihood of walking onset at any given time during the observation period per 10-point decrease in nonverbal IQ (hazard ratio = 0.79, 95% CI : 0.78-0.85) in the NDD group compared to 8% (hazard ratio = 0.92, 95% CI : 0.86-0.98) in the ASD group. CONCLUSIONS : The finding that age of walking is less strongly related to low intellectual ability in children with ASD than in children without other NDDs supports the hypothesis that ID in ASD may result from heterogeneous developmental pathways. Late walking may be a useful stratification variable in etiological research focused on ASD and other NDDs.

Lien vers le texte intégral (Open Access ou abonnement)

26. Kerns CM, Rast JE, Shattuck PT. Prevalence and Correlates of Caregiver-Reported Mental Health Conditions in Youth With Autism Spectrum Disorder in the United States. J Clin Psychiatry ;2020 (Dec 22) ;82(1)

OBJECTIVE : Mental health conditions (MHCs) have substantial personal and economic costs for children with autism spectrum disorder (ASD) ; yet, a current population-based prevalence estimate is lacking. METHODS : This study included 42,283 caregivers of children (ages 3-17 years) from the 2016 population-based National Survey of Children’s Health. Prevalence and correlates of caregiver-reported MHCs were estimated in children with ASD and compared with those in children with intellectual disability (ID), children with special health care needs (SHCN), and « all others » (no ASD, SHCN, or ID). RESULTS : 77.7% of children with ASD had ≥ 1 MHC ; 49.1% had ≥ 2. The most common MHCs were behavior/conduct problem (60.8%), anxiety problem (39.5%), attention deficit disorder (ADD)/attention-deficit/hyperactivity disorder (ADHD) (48.4%), and depression (15.7%). Substance abuse was the only MHC less common in ASD. MHCs were more common in youth with ASD versus SHCN, « all other » youth, and those with ID. MHCs were common in ASD by ages 3-5 years (44.8% ≥ 1 condition) and increased with age (85.9% ≥ 1 condition, ages 12-17 years). Among children with ASD, girls had twice the odds of an anxiety problem, those with ID had 4 times the odds of behavior/conduct problem, and those with childhood adversity had greater odds of an anxiety problem (odds ratio [OR] = 2.66) and ADD/ADHD (OR = 1.99). CONCLUSIONS : Caregiver-reported MHCs are prevalent in children with ASD in the US from a young age and characterize > 85% by adolescence. There is an outsized need for effective MHC assessment and treatment of these youth that demands expedient innovation in both MHC and developmental disability policy and practice.

Lien vers le texte intégral (Open Access ou abonnement)

27. Johansson V, Sandin S, Chang Z, Taylor MJ, Lichtenstein P, D’Onofrio BM, Larsson H, Hellner C, Halldner L. Medications for attention-deficit/hyperactivity disorder in individuals with or without coexisting autism spectrum disorder : analysis of data from the Swedish prescribed drug register. J Neurodev Disord ;2020 (Dec 23) ;12(1):44.

BACKGROUND : Clinical studies found that medication for attention-deficit/hyperactivity disorder (ADHD) is effective in coexisting autism spectrum disorder (ASD), but current research is based on small clinical studies mainly performed on children or adolescents. We here use register data to examine if individuals with ADHD and coexisting ASD present differences in the prescribing patterns of ADHD medication when compared to individuals with pure ADHD. METHODS : Data with information on filled prescriptions and diagnoses was retrieved from the Swedish Prescribed Drug Register and the National Patient Register. We identified 34,374 individuals with pure ADHD and 5012 individuals with ADHD and coexisting ASD, aged between 3 and 80 years. The first treatment episode with ADHD medications (≥ 2 filled prescriptions within 90 days) and daily doses of methylphenidate during a 3-year period was measured. Odds ratios (ORs) were calculated for the likelihood of being prescribed ADHD medication in individuals with and without ASD and Wilcoxon rank-sum test was used to compare group differences in dose per day. RESULTS : Individuals with ADHD and coexisting ASD were less likely to start continuous treatment with ADHD medication (ADHD 80.5% ; ADHD with ASD 76.2% ; OR, 0.80 ; 95% confidence interval, 0.75-0.86), were less likely to be prescribed methylphenidate, and were more commonly prescribed second line treatments such as dexamphetamine, amphetamine, or modafinil. No group difference was observed for atomoxetine. In adults with ADHD and coexisting ASD, methylphenidate was prescribed in lower daily doses over three years as compared to individuals with pure ADHD. CONCLUSIONS : The findings indicate that there are differences in the medical treatment of individuals with or without ASD. If these differences are due to different medication responses in ASD or due to other factors such as clinicians’ perceptions of medication effects in patients with ASD, needs to be further studied.

Lien vers le texte intégral (Open Access ou abonnement)

28. Dumas G, Goubran-Botros H, Matondo M, Pagan C, Boulègue C, Chaze T, Chamot-Rooke J, Maronde E, Bourgeron T. Mass-spectrometry analysis of the human pineal proteome during night and day and in autism. J Pineal Res ;2020 (Dec 23):e12713.

The human pineal gland regulates day-night dynamics of multiple physiological processes, especially through the secretion of melatonin. Using mass-spectrometry-based proteomics and dedicated analysis tools, we identify proteins in the human pineal gland and analyze systematically their variation throughout the day and compare these changes in the pineal proteome between control specimens and donors diagnosed with autism. Results reveal diverse regulated clusters of proteins with, among others, catabolic carbohydrate process and cytoplasmic membrane-bounded vesicle-related proteins differing between day and night and/or control versus autism pineal glands. These data show novel and unexpected processes happening in the human pineal gland during the day/night rhythm as well as specific differences between autism donor pineal glands and those from controls.

Lien vers le texte intégral (Open Access ou abonnement)

29. Matagne V, Borloz E, Ehinger Y, Saidi L, Villard L, Roux JC. Severe offtarget effects following intravenous delivery of AAV9-MECP2 in a female mouse model of Rett syndrome. Neurobiol Dis ;2021 (Feb) ;149:105235.

Rett syndrome (RTT) is a severe X-linked neurodevelopmental disorder that is primarily caused by mutations in the methyl CpG binding protein 2 gene (MECP2). RTT is the second most prevalent genetic cause of intellectual disability in girls, and there is currently no cure for the disease. We have previously shown that gene therapy using a self-complementary AAV9 viral vector expressing a codon-optimized Mecp2 version (AAV9-MCO) significantly improved symptoms and increased survival in male Mecp2-deficient mice. Here, we pursued our studies and investigated the safety and efficacy of long-term gene therapy in the genetically relevant RTT mouse model : the heterozygous (HET) Mecp2 deficient female mouse. These mice were injected with the AAV9-MCO vector through the tail vein and an array of behavioral tests was performed. At 16- and 30-weeks post-injection, this treatment was able to rescue apneas and improved the spontaneous locomotor deficits and circadian locomotor activity in Mecp2 HET mice treated with AAV9-MCO at a dose of 5 × 10(11) vg/mouse. To examine whether a higher dose of vector could result in increased improvements, we injected Mecp2 HET mice with a higher MCO vector dose (10(12) vg/mouse), which resulted in some severe, sometimes lethal, side effects. In order to confirm these effects, a new cohort of Mecp2 HET mice were administered increasing doses of MCO vector (10(11), 5 × 10(11) and 10(12) vg/mouse). Again, two weeks after vector administration, some Mecp2 HET mice were found dead while others displayed severe side effects and had to be euthanized. These deleterious effects were not observed in Mecp2 HET mice injected with a high dose of AAV9-GFP and were directly proportionate to vector dosage (0, 23 or 54% mortality at an AAV9-MCO dose of 10(11), 5 × 10(11), 10(12) vg/mouse, respectively), and no such lethality was observed in wild-type (WT) mice. In the Mecp2 HET mice treated with the high and medium AAV9-MCO doses, blood chemistry analysis and post-mortem histology showed liver damage with drastically elevated levels of liver transaminases and disorganized liver architecture. Apoptosis was confirmed by the presence of TUNEL- and cleaved-caspase 3-positive cells in the Mecp2 HET mice treated with the higher doses of AAV9-MCO. We then studied the involvement of the unfolded protein response (UPR) in triggering apoptosis since it can be activated by AAV vectors. Increased expression of the C/EBP homologous protein (CHOP), one of UPR downstream effectors, was confirmed in Mecp2 HET mice after vector administration. The toxic reaction seen in some treated mice indicates that, although gene therapy for RTT improved breathing deficits observed in Mecp2 HET mice, further studies are needed to better understand the underlying mechanisms and caution must be exercised before similar attempts are undertaken in female Rett patients.

Lien vers le texte intégral (Open Access ou abonnement)

30. Miike T, Toyoura M, Tonooka S, Konishi Y, Oniki K, Saruwatari J, Tajima S, Kinoshita J, Nakai A, Kikuchi K. Neonatal irritable sleep-wake rhythm as a predictor of autism spectrum disorders. Neurobiol Sleep Circadian Rhythms ;2020 (Nov) ;9:100053.

Recently, it has been suggested that sleep problems in autism spectrum disorder (ASD) not only are associated symptoms, but may be deeply related to ASD pathogenesis. Common clinical practice relating to developmental disorders, has shown that parents of children with ASD have often stated that it is more difficult to raise children in the neonatal period because these children exhibit sleep problems. This study investigated the possibility that abnormal neonatal sleep-wake rhythms are related to future ASD development. We administered questionnaires to assess parent(s) of children with ASD and controls. A retrospective analysis was conducted among 121 children with ASD (94 male and 27 female children) recruited from the K-Development Support Center for Children (K-ASD), 56 children with ASD (40 male and 16 female children) recruited from the H-Children’s Sleep and Development Medical Research Center (H-ASD) and 203 children (104 male and 99 female children) recruited from four nursery schools in T-city (control). Irritable/over-reactive types of sleep-wake rhythms that cause difficulty in raising children, such as 1) frequently waking up, 2) difficulty falling asleep, 3) short sleep hours, and 4) continuous crying and grumpiness, were observed more often in ASD groups than in the control group. Additionally, the number of the mothers who went to bed after midnight during pregnancy was higher in the ASD groups than in the control group. Sleep-wake rhythm abnormalities in neonates may be considerable precursors to future development of ASD. Formation of ultradian and postnatal circadian rhythms should be given more attention when considering ASD development. Although this is a retrospective study, the results suggest that a prospective study regarding this issue may be important in understanding and discovering intervention areas that may contribute to preventing and/or properly treating ASD.

Lien vers le texte intégral (Open Access ou abonnement)

31. Carbone E, Manduca A, Cacchione C, Vicari S, Trezza V. Healing autism spectrum disorder with cannabinoids : a neuroinflammatory story. Neurosci Biobehav Rev ;2021 (Feb) ;121:128-143.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with a multifactorial etiology. Latest researches are raising the hypothesis of a link between the onset of the main behavioral symptoms of ASD and the chronic neuroinflammatory condition of the autistic brain ; increasing evidence of this connection is shedding light on new possible players in the pathogenesis of ASD. The endocannabinoid system (ECS) has a key role in neurodevelopment as well as in normal inflammatory responses and it is not surprising that many preclinical and clinical studies account for alterations of the endocannabinoid signaling in ASD. These findings lay the foundation for a better understanding of the neurochemical mechanisms underlying ASD and for new therapeutic attempts aimed at exploiting the renowned anti-inflammatory properties of cannabinoids to treat pathologies encompassed in the autistic spectrum. This review discusses the current preclinical and clinical evidence supporting a key role of the ECS in the neuroinflammatory state that characterizes ASD, providing hints to identify new biomarkers in ASD and promising therapies for the future.

Lien vers le texte intégral (Open Access ou abonnement)

32. Wilson AC, Bishop DVM. Registered report : investigating a preference for certainty in conversation among autistic adults compared to dyslexic adults and the general population. PeerJ ;2020 ;8:e10398.

Social communication difficulties are a diagnostic feature in autism. These difficulties are sometimes attributed, at least in part, to impaired ability in making inferences about what other people mean. In this registered report, we test a competing hypothesis that the communication profile of adults on the autism spectrum can be more strongly characterised by reduced confidence in making inferences in the face of uncertain information. We will test this hypothesis by comparing the performance of 100 autistic and 100 non-autistic adults on a test of implied meaning, using a test of grammaticality judgements as a control task. We hypothesise that autistic adults will report substantially lower confidence, allowing for differences in accuracy, than non-autistic adults on the test of implied meaning compared to the grammaticality test. In addition, we hypothesise that reduced confidence in drawing inferences will relate to the cognitive trait Intolerance of Uncertainty and self-reported social communication challenges. Finally, we will conduct exploratory analysis to assess the specificity of the communication profile of the autistic adults by comparing their performance to that of dyslexic adults, who might also be expected to experience challenges with language and communication.

Lien vers le texte intégral (Open Access ou abonnement)

33. Kurz EM, Conzelmann A, Barth GM, Renner TJ, Zinke K, Born J. How Do Children with Autism Spectrum Disorder Form Gist Memory During Sleep ? – A Study of Slow Oscillation-Spindle Coupling. Sleep ;2020 (Dec 26)

Sleep is assumed to support memory through an active systems consolidation process that does not only strengthen newly encoded representations but also facilitates the formation of more abstract gist memories. Studies in humans and rodents indicate a key role of the precise temporal coupling of sleep slow oscillations (SO) and spindles in this process. The present study aimed at bolstering these findings in typically developing (TD) children, and at dissecting particularities in SO-spindle coupling underlying signs of enhanced gist memory formation during sleep found in a foregoing study in children with autism spectrum disorder (ASD) without intellectual impairment. Sleep data from 19 boys with ASD and 20 TD boys (9-12 years) were analyzed. Children performed a picture-recognition task and the Deese-Roediger-McDermott (DRM) task before nocturnal sleep (encoding) and in the next morning (retrieval). Sleep-dependent benefits for visual-recognition memory were comparable between groups but were greater for gist abstraction (recall of DRM critical lure words) in ASD than TD children. Both groups showed a closely comparable SO-spindle coupling, with fast spindle activity nesting in SO-upstates, suggesting that a key mechanism of memory processing during sleep is fully functioning already at childhood. Picture-recognition at retrieval after sleep was positively correlated to frontocortical SO-fast-spindle coupling in TD children, and less in ASD children. Critical lure recall did not correlate with SO-spindle coupling in TD children but showed a negative correlation (r=-.64, p=.003) with parietal SO-fast-spindle coupling in ASD children, suggesting other mechanisms specifically conveying gist abstraction, that may even compete with SO-spindle coupling.

Lien vers le texte intégral (Open Access ou abonnement)

34. Borges T, de Oliveira TM, Dos Santos MO, Moro MR. [Between parents and children, stories to escape non-sense]. Soins ;2020 (Nov) ;65(850):43-45.

As part of a clinical practice which aims to alleviate the psychological suffering of children in situations of migration and/or uprooting, a discussion can be undertaken regarding the cultural aetiologies of migrant families whose children present autism spectrum disorders. The transcultural context enables families to travel between worlds as well as share their collective imagination regarding psychological suffering using graphic expression and narrative elements.

Lien vers le texte intégral (Open Access ou abonnement)