Pubmed du 24/10/21
1. Adayev T, LaFauci G, Xu W, Dobkin C, Kascsak R, Brown WT, Goodman JH. Development of a Quantitative FMRP Assay for Mouse Tissue Applications. Genes. 2021; 12(10).
Fragile X syndrome results from the absence of the FMR1 gene product-Fragile X Mental Retardation Protein (FMRP). Fragile X animal research has lacked a reliable method to quantify FMRP. We report the development of an array of FMRP-specific monoclonal antibodies and their application for quantitative assessment of FMRP (qFMRPm) in mouse tissue. To characterize the assay, we determined the normal variability of FMRP expression in four brain structures of six different mouse strains at seven weeks of age. There was a hierarchy of FMRP expression: neocortex > hippocampus > cerebellum > brainstem. The expression of FMRP was highest and least variable in the neocortex, whereas it was most variable in the hippocampus. Male C57Bl/6J and FVB mice were selected to determine FMRP developmental differences in the brain at 3, 7, 10, and 14 weeks of age. We examined the four structures and found a developmental decline in FMRP expression with age, except for the brainstem where it remained stable. qFMRPm assay of blood had highest values in 3 week old animals and dropped by 2.5-fold with age. Sex differences were not significant. The results establish qFMRPm as a valuable tool due to its ease of methodology, cost effectiveness, and accuracy.
Lien vers le texte intégral (Open Access ou abonnement)
2. Agrawal D, Chaudhary P, Pathak P. Promoting Nurturing Care for Early Childhood Development Through India’s Public Health System. Indian pediatrics. 2021; 58 Suppl 1: S23-s7.
Implementing the nurturing care framework (NCF) for early childhood development (ECD) is essentially multisectoral, requiring coordination amongst all sectors and harmoniously integrating it within the existing contact opportunities in the health sector. This paper discusses the relative strengths, persisting gaps, challenges, and the way forward to implement nurturing care for ECD through the public health system. The vast network of frontline health workers and health facilities; community, home, and center-based service delivery; health and wellness centers located close to the communities have the potential to promote nurturing care. Persisting gaps include limited capacities of health workers in the nurturing care domains, lack of community engagement for ECD, weak referral linkages, inability to reach the most vulnerable children, missed opportunities for early identification of children at risk, and early intervention for children developmental delays and difficulties. Moving forward, incorporating nurturing care components into essential services packages, enhancing competencies of health workers, engaging with parents, establishing a mechanism for tracking children at risk, and developmental surveillance by trained service providers can provide the much-needed impetus to ECD.
Lien vers le texte intégral (Open Access ou abonnement)
3. Bellato A, Norman L, Idrees I, Ogawa CY, Waitt A, Zuccolo PF, Tye C, Radua J, Groom MJ, Shephard E. A systematic review and meta-analysis of altered electrophysiological markers of performance monitoring in Obsessive-Compulsive Disorder (OCD), Gilles de la Tourette Syndrome (GTS), Attention-Deficit/Hyperactivity disorder (ADHD) and Autism. Neuroscience and biobehavioral reviews. 2021; 131: 964-87.
Altered performance monitoring is implicated in obsessive-compulsive disorder (OCD), Gilles de la Tourette syndrome (GTS), attention-deficit/hyperactivity disorder (ADHD) and autism. We conducted a systematic review and meta-analysis of electrophysiological correlates of performance monitoring (error-related negativity, ERN; error positivity, Pe; feedback-related negativity, FRN; feedback-P3) in individuals with OCD, GTS, ADHD or autism compared to control participants, or associations between correlates and symptoms/traits of these conditions. Meta-analyses on 97 studies (5890 participants) showed increased ERN in OCD (Hedge’s g = 0.54[CIs:0.44,0.65]) and GTS (g = 0.99[CIs:0.05,1.93]). OCD also showed increased Pe (g = 0.51[CIs:0.21,0.81]) and FRN (g = 0.50[CIs:0.26,0.73]). ADHD and autism showed reduced ERN (ADHD: g=-0.47[CIs:-0.67,-0.26]; autism: g=-0.61[CIs:-1.10,-0.13]). ADHD also showed reduced Pe (g=-0.50[CIs:-0.69,-0.32]). These findings suggest overlap in electrophysiological markers of performance monitoring alterations in four common neurodevelopmental conditions, with increased amplitudes of the markers in OCD and GTS and decreased amplitudes in ADHD and autism. Implications of these findings in terms of shared and distinct performance monitoring alterations across these neurodevelopmental conditions are discussed. PROSPERO pre-registration code: CRD42019134612.
Lien vers le texte intégral (Open Access ou abonnement)
4. Bervoets J, Milton D, Van de Cruys S. Autism and intolerance of uncertainty: an ill-fitting pair. Trends in cognitive sciences. 2021; 25(12): 1009-10.
Lien vers le texte intégral (Open Access ou abonnement)
5. Bührer C, Endesfelder S, Scheuer T, Schmitz T. Paracetamol (Acetaminophen) and the Developing Brain. International journal of molecular sciences. 2021; 22(20).
Paracetamol is commonly used to treat fever and pain in pregnant women, but there are growing concerns that this may cause attention deficit hyperactivity disorder and autism spectrum disorder in the offspring. A growing number of epidemiological studies suggests that relative risks for these disorders increase by an average of about 25% following intrauterine paracetamol exposure. The data analyzed point to a dose-effect relationship but cannot fully account for unmeasured confounders, notably indication and genetic transmission. Only few experimental investigations have addressed this issue. Altered behavior has been demonstrated in offspring of paracetamol-gavaged pregnant rats, and paracetamol given at or prior to day 10 of life to newborn mice resulted in altered locomotor activity in response to a novel home environment in adulthood and blunted the analgesic effect of paracetamol given to adult animals. The molecular mechanisms that might mediate these effects are unknown. Paracetamol has diverse pharmacologic actions. It reduces prostaglandin formation via competitive inhibition of the peroxidase moiety of prostaglandin H2 synthase, while its metabolite N-arachidonoyl-phenolamine activates transient vanilloid-subtype 1 receptors and interferes with cannabinoid receptor signaling. The metabolite N-acetyl-p-benzo-quinone-imine, which is pivotal for liver damage after overdosing, exerts oxidative stress and depletes glutathione in the brain already at dosages below the hepatic toxicity threshold. Given the widespread use of paracetamol during pregnancy and the lack of safe alternatives, its impact on the developing brain deserves further investigation.
Lien vers le texte intégral (Open Access ou abonnement)
6. Candon M, Shen S, Fadeyibi O, Smith JL, Rothbard A. Trends in antipsychotic prescribing for approved and unapproved indications to Medicaid-enrolled youth in Philadelphia, Pennsylvania between 2014 and 2018. BMC psychiatry. 2021; 21(1): 524.
BACKGROUND: Antipsychotic prescribing to Medicaid-enrolled youth has been the target of numerous policy initiatives, including prior authorization and quality monitoring programs, which often target specific populations. Whether these efforts have changed the level or composition of antipsychotic prescribing is unclear. METHODS: Using 2014-2018 administrative claims data for Medicaid enrollees aged 21 years and under in Philadelphia, Pennsylvania, we measured antipsychotic prescription fills overall and for youth without an approved indication (autism, bipolar disorder, or psychosis). We then assessed whether trends differed for populations that have been targeted by policy initiatives, including younger children and foster care-enrolled youth. We also identified the most common approved and unapproved indications and examined whether the treatment duration of antipsychotic prescriptions differed based on whether the youth had an approved or unapproved indication. RESULTS: Overall, the number of Medicaid youth with an antipsychotic prescription fill halved between 2014 and 2018. Youth aged 17 years and under and foster care-enrolled youth, who were targeted by prior authorization and quality improvement efforts, experienced larger declines. Roughly half of prescriptions were for unapproved indications in both 2014 and 2018; the most common unapproved indication was ADHD, and the treatment duration was shorter for unapproved indications compared to approved indications. CONCLUSIONS: Antipsychotic prescribing to Medicaid-enrolled youth is declining, particularly among populations that have been targeted by policy initiatives like prior authorization and quality monitoring programs. Despite the fact that these initiatives often assess diagnostic criteria, half of antipsychotic prescriptions were for unapproved indications in both 2014 and 2018. More research is needed to gauge whether this prescribing is appropriate.
Lien vers le texte intégral (Open Access ou abonnement)
7. Costescu C, Șogor M, Thill S, Roșan A. Emotional Dysregulation in Preschoolers with Autism Spectrum Disorder-A Sample of Romanian Children. International journal of environmental research and public health. 2021; 18(20).
Emotional dysregulation problems seem to affect more than 80% of people with autism spectrum disorder (ASD) and may include irritability, aggressive behaviors, self-injury, and anxiety. Even though these types of problems are very common and affect the well-being of individuals with ASD, there are no objective assessment tools developed for this population and there are only a few intervention techniques meant to address these symptoms. This study investigates the feasibility of using off-the-shelf wearable devices to accurately measure heart rate, which has been associated with emotional dysregulation, and to test the effectiveness of functional communication training in reducing the emotional outburst in preschoolers with ASD. We used a single-case experiment design with three preschoolers with ASD to test if the duration of the emotional outburst and the elevated heart rate levels can be reduced by using functional communication training. Our results show that for two of the participants, the intervention was effective in reducing the duration of behaviors associated with emotional outburst, and that there were significant differences between baseline and intervention phase in terms of heart rate levels. However, our results are inconclusive regarding the association between elevated heart rates and the occurrence of the emotional outburst. Nevertheless, more research is needed to investigate the use of off-the-shelf wearable devices in predicting challenging behaviors in children with ASD.
Lien vers le texte intégral (Open Access ou abonnement)
8. Cupaioli FA, Fallerini C, Mencarelli MA, Perticaroli V, Filippini V, Mari F, Renieri A, Mezzelani A. Autism Spectrum Disorders: Analysis of Mobile Elements at 7q11.23 Williams-Beuren Region by Comparative Genomics. Genes. 2021; 12(10).
Autism spectrum disorders (ASD) are a group of complex neurodevelopmental disorders, characterized by a deficit in social interaction and communication. Many genetic variants are associated with ASD, including duplication of 7q11.23 encompassing 26-28 genes. Symmetrically, the hemizygous deletion of 7q11.23 causes Williams-Beuren syndrome (WBS), a multisystem disorder characterized by « hyper-sociability » and communication skills. Interestingly, deletion of four non-exonic mobile elements (MEs) in the « canine WBS locus » were associated with the behavioral divergence between the wolf and the dog and dog sociability and domestication. We hypothesized that indel of these MEs could be involved in ASD, associated with its different phenotypes and useful as biomarkers for patient stratification and therapeutic design. Since these MEs are non-exonic they have never been discovered before. We searched the corresponding MEs and loci in humans by comparative genomics. Interestingly, they mapped on different but ASD related genes. The loci in individuals with phenotypically different autism and neurotypical controls were amplified by PCR. A sub-set of each amplicon was sequenced by Sanger. No variant resulted associated with ASD and neither specific phenotypes were found but novel small-scale insertions and SNPs were discovered. Since MEs are hyper-methylated and epigenetically modulate gene expression, further investigation in ASD is necessary.
Lien vers le texte intégral (Open Access ou abonnement)
9. Defrin R, Beshara H, Benromano T, Hssien K, Pick CG, Kunz M. Pain Behavior of People with Intellectual and Developmental Disabilities Coded with the New PAIC-15 and Validation of Its Arabic Translation. Brain sciences. 2021; 11(10).
Pain management necessitates assessment of pain; the gold standard being self-report. Among individuals with intellectual and developmental disabilities (IDD), self-report may be limited and therefore indirect methods for pain assessment are required. A new, internationally agreed upon and user-friendly observational tool was recently published-the Pain Assessment in Impaired Cognition (PAIC-15). The current study’s aims were: to test the use of the PAIC-15 in assessing pain among people with IDD and to translate the PAIC-15 into Arabic for dissemination among Arabic-speaking professionals. Pain behavior following experimental pressure stimuli was analyzed among 30 individuals with IDD and 15 typically developing controls (TDCs). Translation of the PAIC followed the forward-backward approach; and reliability between the two versions and between raters was calculated. Observational scores with the PAIC-15 exhibited a stimulus-response relationship with pressure stimulation. Those of the IDD group were greater than those of the TDC group. The overall agreement between the English and Arabic versions was high (ICC = 0.89); single items exhibited moderate to high agreement levels. Inter-rater reliability was high (ICC = 0.92). Both versions of the PAIC-15 are feasible and reliable tools to record pain behavior in individuals with IDD. Future studies using these tools in clinical settings are warranted.
Lien vers le texte intégral (Open Access ou abonnement)
10. Dimachkie Nunnally A, Nguyen V, Anglo C, Sterling A, Edgin J, Sherman S, Berry-Kravis E, Del Hoyo Soriano L, Abbeduto L, Thurman AJ. Symptoms of Autism Spectrum Disorder in Individuals with Down Syndrome. Brain sciences. 2021; 11(10).
There is a growing body of evidence to suggest that individuals with Down syndrome (DS) are diagnosed with autism spectrum disorders (ASD) at a higher rate than individuals in the general population. Nonetheless, little is known regarding the unique presentation of ASD symptoms in DS. The current study aims to explore the prevalence and profiles of ASD symptoms in a sample of individuals with DS (n = 83), aged between 6 and 23 years. Analysis of this sample (M(Age) = 15.13) revealed that approximately 37% of the sample met the classification cut-off for ASD using the Autism Diagnostic Observation Schedule 2 (ADOS-2) Calibrated Severity Score (CSS), an indicator of the participants’ severity of ASD-related symptoms. Item-level analyses revealed that multiple items on Module 2 and Module 3 of the ADOS-2, mostly in the Social Affect (SA) subdomain, differentiated the children with DS who did not meet ASD classification (DS-only) from those who did (DS + ASD). Lastly, comparisons of individuals with DS-only and those with DS + ASD differed significantly on the syntactic complexity of their expressive language. These findings shed light on the unique presentation of ASD symptoms in a sample of individuals with DS and suggest that expressive language abilities may play a pivotal role in the presentation of ASD symptoms in DS.
Lien vers le texte intégral (Open Access ou abonnement)
11. Ding N, Gao H, Jiang J, Zhai M, Shao H, Fu L, Li C, Ren Y, Li Y, Feng M, Cui X, Qiu N, Jin P, Ke X. The characteristics and factors of the internalizing and externalizing behaviours of children at high risk for autism spectrum disorder. BMC psychiatry. 2021; 21(1): 523.
BACKGROUND: The behavioral characteristics of children with autism spectrum disorder (ASD) are not only affected by their disease, but also by their parenting environment. HR-ASD has the risk of developing internalization and externalization problems. How the early development of these behavioral problems is affected by parent-child interaction is worth exploring. We tested whether parent-child interactions and parenting characteristics were associated with behavioural problems during the infant periods. METHODS: This study collected data from 91 infants at high risk for ASD and 68 matched typically developing (TD) infants, about their internalizing and externalizing behavioural problems and engagement states (i.e. positive, negative, and parent-child interactions), using free play paradigm. Parent measures were assessed using the Broad Autism Phenotypic Questionnaire (BAPQ) and Parenting Stress Index Short Form (PSI-SF) questionnaire. The core symptoms of ASD were assessed using the the Autism Diagnostic Observational Schedule (ADOS). RESULTS: During free play, infants in the HR-ASD group showed more internalizing (P < 0.001) and externalizing (P < 0.05) behaviours and less positive engagement (P < 0.01) than the TD group. In the regression analysis, we found that parenting stress had an impact on the infants' externalizing behaviours (△R(2) = 0.215). Parent negative engagement had an impact on the infants' internalizing behaviours (△R(2) = 0.451). CONCLUSIONS: The present study revealed that children at high risk for ASD exhibited more severe internalizing and externalizing behavioural problems than TD group. The parent negative engagement is associated with behavioural problems. The findings on the contribution of parents' factors to behavioural problems suggests that the parenting stress and parent-child interactions are important factors for mitigating behavioural problems.
Lien vers le texte intégral (Open Access ou abonnement)
12. Djerassi M, Ophir S, Atzil S. What Is Social about Autism? The Role of Allostasis-Driven Learning. Brain sciences. 2021; 11(10).
Scientific research on neuro-cognitive mechanisms of autism often focuses on circuits that support social functioning. However, autism is a heterogeneous developmental variation in multiple domains, including social communication, but also language, cognition, and sensory-motor control. This suggests that the underlying mechanisms of autism share a domain-general foundation that impacts all of these processes. In this Perspective Review, we propose that autism is not a social deficit that results from an atypical « social brain ». Instead, typical social development relies on learning. In social animals, infants depend on their caregivers for survival, which makes social information vitally salient. The infant must learn to socially interact in order to survive and develop, and the most prominent learning in early life is crafted by social interactions. Therefore, the most prominent outcome of a learning variation is atypical social development. To support the hypothesis that autism results from a variation in learning, we first review evidence from neuroscience and developmental science, demonstrating that typical social development depends on two domain-general processes that determine learning: (a) motivation, guided by allostatic regulation of the internal milieu; and (b) multi-modal associations, determined by the statistical regularities of the external milieu. These two processes are basic ingredients of typical development because they determine allostasis-driven learning of the social environment. We then review evidence showing that allostasis and learning are affected among individuals with autism, both neurally and behaviorally. We conclude by proposing a novel domain-general framework that emphasizes allostasis-driven learning as a key process underlying autism. Guided by allostasis, humans learn to become social, therefore, the atypical social profile seen in autism can reflect a domain-general variation in allostasis-driven learning. This domain-general view raises novel research questions in both basic and clinical research and points to targets for clinical intervention that can lower the age of diagnosis and improve the well-being of individuals with autism.
Lien vers le texte intégral (Open Access ou abonnement)
13. Grivas G, Frye R, Hahn J. Pregnant Mothers’ Medical Claims and Associated Risk of Their Children being Diagnosed with Autism Spectrum Disorder. Journal of personalized medicine. 2021; 11(10).
A retrospective analysis of administrative claims containing a diverse mixture of ages, ethnicities, and geographical regions across the United States was conducted in order to identify medical events that occur during pregnancy and are associated with autism spectrum disorder (ASD). The dataset used in this study is comprised of 123,824 pregnancies of which 1265 resulted in the child being diagnosed with ASD during the first five years of life. Logistic regression analysis revealed significant relationships between several maternal medical claims, made during her pregnancy and segmented by trimester, and the child’s diagnosis of ASD. Having a biological sibling with ASD, maternal use of antidepressant medication and psychiatry services as well as non-pregnancy related claims such hospital visits, surgical procedures, and radiology exposure were related to an increased risk of ASD regardless of trimester. Urinary tract infections during the first trimester and preterm delivery during the second trimester were also related to an increased risk of ASD. Preventative and obstetrical care were associated with a decreased risk for ASD. A better understanding of the medical factors that increase the risk of having a child with ASD can lead to strategies to decrease risk or identify those children who require increased surveillance for the development of ASD to promote early diagnosis and intervention.
Lien vers le texte intégral (Open Access ou abonnement)
14. Ha S, Oh D, Lee S, Park J, Ahn J, Choi S, Cheon KA. Altered Gut Microbiota in Korean Children with Autism Spectrum Disorders. Nutrients. 2021; 13(10).
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social and behavioral impairments. Recent studies have suggested that gut microbiota play a critical role in ASD pathogenesis. Herein, we investigated the fecal microflora of Korean ASD children to determine gut microbiota profiles associated with ASD. Specifically, fecal samples were obtained from 54 children with ASD and 38 age-matched children exhibiting typical development. Systematic bioinformatic analysis revealed that the composition of gut microbiota differed between ASD and typically developing children (TDC). Moreover, the total amounts of short-chain fatty acids, metabolites produced by bacteria, were increased in ASD children. At the phylum level, we found a significant decrease in the relative Bacteroidetes abundance of the ASD group, whereas Actinobacteria abundance was significantly increased. Furthermore, we found significantly lower Bacteroides levels and higher Bifidobacterium levels in the ASD group than in the TDC group at the genus level. Functional analysis of the microbiota in ASD children predicted that several pathways, including genetic information processing and amino acid metabolism, can be associated with ASD pathogenesis. Although more research is needed to determine whether the differences between ASD and TDC are actually related to ASD pathogenesis, these results provide further evidence of altered gut microbiota in children with ASD, possibly providing new perspectives on the diagnosis and therapeutic approaches for ASD patients.
Lien vers le texte intégral (Open Access ou abonnement)
15. Hayward BE, Usdin K. Mechanisms of Genome Instability in the Fragile X-Related Disorders. Genes. 2021; 12(10).
The Fragile X-related disorders (FXDs), which include the intellectual disability fragile X syndrome (FXS), are disorders caused by expansion of a CGG-repeat tract in the 5′ UTR of the X-linked FMR1 gene. These disorders are named for FRAXA, the folate-sensitive fragile site that localizes with the CGG-repeat in individuals with FXS. Two pathological FMR1 allele size classes are distinguished. Premutation (PM) alleles have 54-200 repeats and confer the risk of fragile X-associated tremor/ataxia syndrome (FXTAS) and fragile X-associated primary ovarian insufficiency (FXPOI). PM alleles are prone to both somatic and germline expansion, with female PM carriers being at risk of having a child with >200+ repeats. Inheritance of such full mutation (FM) alleles causes FXS. Contractions of PM and FM alleles can also occur. As a result, many carriers are mosaic for different sized alleles, with the clinical presentation depending on the proportions of these alleles in affected tissues. Furthermore, it has become apparent that the chromosomal fragility of FXS individuals reflects an underlying problem that can lead to chromosomal numerical and structural abnormalities. Thus, large numbers of CGG-repeats in the FMR1 gene predisposes individuals to multiple forms of genome instability. This review will discuss our current understanding of these processes.
Lien vers le texte intégral (Open Access ou abonnement)
16. Iyer R, Petrovska Jovanovska V, Berginc K, Jaklič M, Fabiani F, Harlacher C, Huzjak T, Sanchez-Felix MV. Amorphous Solid Dispersions (ASDs): The Influence of Material Properties, Manufacturing Processes and Analytical Technologies in Drug Product Development. Pharmaceutics. 2021; 13(10).
Poorly water-soluble drugs pose a significant challenge to developability due to poor oral absorption leading to poor bioavailability. Several approaches exist that improve the oral absorption of such compounds by enhancing the aqueous solubility and/or dissolution rate of the drug. These include chemical modifications such as salts, co-crystals or prodrugs and physical modifications such as complexation, nanocrystals or conversion to amorphous form. Among these formulation strategies, the conversion to amorphous form has been successfully deployed across the pharmaceutical industry, accounting for approximately 30% of the marketed products that require solubility enhancement and making it the most frequently used technology from 2000 to 2020. This article discusses the underlying scientific theory and influence of the active compound, the material properties and manufacturing processes on the selection and design of amorphous solid dispersion (ASD) products as marketed products. Recent advances in the analytical tools to characterize ASDs stability and ability to be processed into suitable, patient-centric dosage forms are also described. The unmet need and regulatory path for the development of novel ASD polymers is finally discussed, including a description of the experimental data that can be used to establish if a new polymer offers sufficient differentiation from the established polymers to warrant advancement.
Lien vers le texte intégral (Open Access ou abonnement)
17. Kozlova EV, Valdez MC, Denys ME, Bishay AE, Krum JM, Rabbani KM, Carrillo V, Gonzalez GM, Lampel G, Tran JD, Vazquez BM, Anchondo LM, Uddin SA, Huffman NM, Monarrez E, Olomi DS, Chinthirla BD, Hartman RE, Kodavanti PRS, Chompre G, Phillips AL, Stapleton HM, Henkelmann B, Schramm KW, Curras-Collazo MC. Persistent autism-relevant behavioral phenotype and social neuropeptide alterations in female mice offspring induced by maternal transfer of PBDE congeners in the commercial mixture DE-71. Archives of toxicology. 2022; 96(1): 335-65.
Polybrominated diphenyl ethers (PBDEs) are ubiquitous persistent organic pollutants (POPs) that are known neuroendocrine disrupting chemicals with adverse neurodevelopmental effects. PBDEs may act as risk factors for autism spectrum disorders (ASD), characterized by abnormal psychosocial functioning, although direct evidence is currently lacking. Using a translational exposure model, we tested the hypothesis that maternal transfer of a commercial mixture of PBDEs, DE-71, produces ASD-relevant behavioral and neurochemical deficits in female offspring. C57Bl6/N mouse dams (F0) were exposed to DE-71 via oral administration of 0 (VEH/CON), 0.1 (L-DE-71) or 0.4 (H-DE-71) mg/kg bw/d from 3 wk prior to gestation through end of lactation. Mass spectrometry analysis indicated in utero and lactational transfer of PBDEs (in ppb) to F1 female offspring brain tissue at postnatal day (PND) 15 which was reduced by PND 110. Neurobehavioral testing of social novelty preference (SNP) and social recognition memory (SRM) revealed that adult L-DE-71 F1 offspring display deficient short- and long-term SRM, in the absence of reduced sociability, and increased repetitive behavior. These effects were concomitant with reduced olfactory discrimination of social odors. Additionally, L-DE-71 exposure also altered short-term novel object recognition memory but not anxiety or depressive-like behavior. Moreover, F1 L-DE-71 displayed downregulated mRNA transcripts for oxytocin (Oxt) in the bed nucleus of the stria terminalis (BNST) and supraoptic nucleus, and vasopressin (Avp) in the BNST and upregulated Avp1ar in BNST, and Oxtr in the paraventricular nucleus. Our work demonstrates that developmental PBDE exposure produces ASD-relevant neurochemical, olfactory processing and behavioral phenotypes that may result from early neurodevelopmental reprogramming within central social and memory networks.
Lien vers le texte intégral (Open Access ou abonnement)
18. Leonardi E, Cerasa A, Servidio R, Costabile A, Famà FI, Carrozza C, Spadaro L, Scifo R, Baieli S, Aiello S, Marino F, Tartarisco G, Vagni D, Pioggia G, Ruta L. The Route of Stress in Parents of Young Children with and without Autism: A Path-Analysis Study. International journal of environmental research and public health. 2021; 18(20).
We provide a conceptual model on the complex interaction between stress, psychological predisposition, and personality traits, accounting for gender, in parents of children with and without autism. We performed a path analysis using a structural equation modeling approach in a sample of parents including 60 ASD and 53 TD couples. In parents of typically developing children (TD), depression level and age are the main direct predictors of stress through the mediating effect of anxiety. Otherwise, in the ASD parent group, the personality trait ‘openness’ directly predicts the defensive response and stress levels without the mediating effect of anxiety. Our data suggest a route of action in promoting new behavioral strategies to prevent parenting stress, making families run smoothly.
Lien vers le texte intégral (Open Access ou abonnement)
19. Li J, Kells PA, Osgood AC, Gautam SH, Shew WL. Collapse of complexity of brain and body activity due to excessive inhibition and MeCP2 disruption. Proceedings of the National Academy of Sciences of the United States of America. 2021; 118(43).
Complex body movements require complex dynamics and coordination among neurons in motor cortex. Conversely, a long-standing theoretical notion supposes that if many neurons in motor cortex become excessively synchronized, they may lack the necessary complexity for healthy motor coding. However, direct experimental support for this idea is rare and underlying mechanisms are unclear. Here we recorded three-dimensional body movements and spiking activity of many single neurons in motor cortex of rats with enhanced synaptic inhibition and a transgenic rat model of Rett syndrome (RTT). For both cases, we found a collapse of complexity in the motor system. Reduced complexity was apparent in lower-dimensional, stereotyped brain-body interactions, neural synchrony, and simpler behavior. Our results demonstrate how imbalanced inhibition can cause excessive synchrony among movement-related neurons and, consequently, a stereotyped motor code. Excessive inhibition and synchrony may underlie abnormal motor function in RTT.
Lien vers le texte intégral (Open Access ou abonnement)
20. Lin X, Liang Y, Herrera-Molina R, Montag D. Neuroplastin in Neuropsychiatric Diseases. Genes. 2021; 12(10).
Molecular mechanisms underlying neuropsychiatric and neurodegenerative diseases are insufficiently elucidated. A detailed understanding of these mechanisms may help to further improve medical intervention. Recently, intellectual abilities, creativity, and amnesia have been associated with neuroplastin, a cell recognition glycoprotein of the immunoglobulin superfamily that participates in synapse formation and function and calcium signaling. Data from animal models suggest a role for neuroplastin in pathways affected in neuropsychiatric and neurodegenerative diseases. Neuroplastin loss or disruption of molecular pathways related to neuronal processes has been linked to various neurological diseases, including dementia, schizophrenia, and Alzheimer’s disease. Here, we review the molecular features of the cell recognition molecule neuroplastin, and its binding partners, which are related to neurological processes and involved in learning and memory. The emerging functions of neuroplastin may have implications for the treatment of diseases, particularly those of the nervous system.
Lien vers le texte intégral (Open Access ou abonnement)
21. Lombardi M, Troisi J. Gut Reactions: How Far Are We from Understanding and Manipulating the Microbiota Complexity and the Interaction with Its Host? Lessons from Autism Spectrum Disorder Studies. Nutrients. 2021; 13(10).
Autism is a group of neurodevelopmental disorders, characterized by early onset difficulties in social communication and restricted, repetitive behaviors and interests. It is characterized by familial aggregation, suggesting that genetic factors play a role in disease development, in addition to developmentally early environmental factors. Here, we review the role of the gut microbiome in autism, as it has been characterized in case-control studies. We discuss how methodological differences may have led to inconclusive or contradictory results, even though a disproportion between harmful and beneficial bacteria is generally described in autism. Furthermore, we review the studies concerning the effects of gut microbial-based and dietary interventions on autism symptoms. Also, in this case, the results are not comparable due to the lack of standardized methods. Therefore, autism-specific microbiome signatures and, consequently, possible microbiome-oriented interventions are far from being recognized. We argue that a multi-omic longitudinal implementation may be useful to study metabolic changes connected to microbiome changes.
Lien vers le texte intégral (Open Access ou abonnement)
22. McCarty PJ, Pines AR, Sussman BL, Wyckoff SN, Jensen A, Bunch R, Boerwinkle VL, Frye RE. Resting State Functional Magnetic Resonance Imaging Elucidates Neurotransmitter Deficiency in Autism Spectrum Disorder. Journal of personalized medicine. 2021; 11(10).
Resting-state functional magnetic resonance imaging provides dynamic insight into the functional organization of the brains’ intrinsic activity at rest. The emergence of resting-state functional magnetic resonance imaging in both the clinical and research settings may be attributed to recent advancements in statistical techniques, non-invasiveness and enhanced spatiotemporal resolution compared to other neuroimaging modalities, and the capability to identify and characterize deep brain structures and networks. In this report we describe a 16-year-old female patient with autism spectrum disorder who underwent resting-state functional magnetic resonance imaging due to late regression. Imaging revealed deactivated networks in deep brain structures involved in monoamine synthesis. Monoamine neurotransmitter deficits were confirmed by cerebrospinal fluid analysis. This case suggests that resting-state functional magnetic resonance imaging may have clinical utility as a non-invasive biomarker of central nervous system neurochemical alterations by measuring the function of neurotransmitter-driven networks. Use of this technology can accelerate and increase the accuracy of selecting appropriate therapeutic agents for patients with neurological and neurodevelopmental disorders.
Lien vers le texte intégral (Open Access ou abonnement)
23. Mehta A, Shirai Y, Kouyama-Suzuki E, Zhou M, Yoshizawa T, Yanagawa T, Mori T, Tabuchi K. IQSEC2 Deficiency Results in Abnormal Social Behaviors Relevant to Autism by Affecting Functions of Neural Circuits in the Medial Prefrontal Cortex. Cells. 2021; 10(10).
IQSEC2 is a guanine nucleotide exchange factor (GEF) for ADP-ribosylation factor 6 (Arf6), of which protein is exclusively localized to the postsynaptic density of the excitatory synapse. Human genome studies have revealed that the IQSEC2 gene is associated with X-linked neurodevelopmental disorders, such as intellectual disability (ID), epilepsy, and autism. In this study, we examined the behavior and synapse function in IQSEC2 knockout (KO) mice that we generated using CRIPSR/Cas9-mediated genome editing to solve the relevance between IQSEC2 deficiency and the pathophysiology of neurodevelopmental disorders. IQSEC2 KO mice exhibited autistic behaviors, such as overgrooming and social deficits. We identified that up-regulation of c-Fos expression in the medial prefrontal cortex (mPFC) induced by social stimulation was significantly attenuated in IQSEC2 KO mice. Whole cell electrophysiological recording identified that synaptic transmissions mediated by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), N-methyl-D-aspartate receptor (NMDAR), and γ-aminobutyric acid receptor (GABAR) were significantly decreased in pyramidal neurons in layer 5 of the mPFC in IQSEC2 KO mice. Reexpression of IQSEC2 isoform 1 in the mPFC of IQSEC2 KO mice using adeno-associated virus (AAV) rescued both synaptic and social deficits, suggesting that impaired synaptic function in the mPFC is responsible for social deficits in IQSEC2 KO mice.
Lien vers le texte intégral (Open Access ou abonnement)
24. Miani A, Imbriani G, De Filippis G, De Giorgi D, Peccarisi L, Colangelo M, Pulimeno M, Castellone MD, Nicolardi G, Logroscino G, Piscitelli P. Autism Spectrum Disorder and Prenatal or Early Life Exposure to Pesticides: A Short Review. International journal of environmental research and public health. 2021; 18(20).
Background: Autism spectrum disorder (ASD) diagnoses have rapidly increased globally. Both environmental and genetic factors appear to contribute to the development of ASD. Several studies have shown a potential association between prenatal or postnatal pesticide exposure and the risk of developing ASD. Methods: We reviewed the available literature concerning the relationship between early life exposure to pesticides used in agriculture, such as organochlorines, organophosphates and pyrethroids, and ASD onset in childhood. We searched on Medline and Scopus for cohort or case-control studies published in English from 1977 to 2020. Results: A total of seven articles were selected for the review. We found a remarkable association between the maternal exposure to pyrethroid, as well as the exposure to organophosphate during pregnancy or in the first years of childhood, and the risk of ASD onset. This association was found to be less evident with organochlorine pesticides. Pregnancy seems to be the time when pesticide exposure appears to have the greatest impact on the onset of ASD in children. Conclusions: Among the different environmental pollutants, pesticides should be considered as emerging risk factors for ASD. The potential association identified between the exposure to pesticides and ASD needs to be implemented and confirmed by further epidemiological studies based on individual assessment both in outdoor and indoor conditions, including multiple confounding factors, and using statistical models that take into account single and multiple pesticide residues.
Lien vers le texte intégral (Open Access ou abonnement)
25. Mukherjee SB, Mukherjee S, Ghosh S, Singh A. Providing Services for Indian Children With Developmental Delay and Disabilities in the Community: Rashtriya Bal Suraksha Karyakram. Indian pediatrics. 2021; 58 Suppl 1: S73-s9.
Investment in Early Childhood Development (ECD) is essential for the progress of a nation. In 2013, the Rashtriya Bal Suraksha Karyakram (RBSK) was launched for community level screening, early identification and management of chronic diseases (birth defects, diseases, deficiencies, developmental delays and disabilities) from birth to 18 years. Health care is provided in District hospitals with Special Newborn Care Units, and District Early Intervention Centers (DEIC). Infants are screened at delivery points, or at home under the Home-Based New-born Care package. Pre-schoolers and school aged children are evaluated by mobile health teams using standardized tools in anganwadi centers and schools, respectively. Referrals are managed at higher centers. The DEIC uses an evidence based, trans-disciplinary, collaborative approach for delay/disability at zero expense. Other initiatives disseminating awareness about healthy family practices promoting ECD during pregnancy and the first two years of life include: a booklet ‘Journey of First 1000 days’; an android App ‘Ayushman Bhava’; ECD call centers that provide individualized counselling related to queries; the LaQshya program that promotes mother-friendly labour; and a more illustrative ‘Mother and Child Protection Card’ that assists in developmental monitoring. Till date, RBSK has developed two Nodal Collaborating Centers (the Kolkata centre has trained 852 personnel), 234 DEIC’s, and 11,000 mobile health teams. Over 6 years (2014 -2020), cumulatively 45,64,31,984 children < 6 years have been screened, 13,95,618 delays /disabilities identified, and 3,04,300 children managed appropriately. The future holds further expansion, development of state-of-the-art specialized centers, collaborative research, and self-sustaining capacity building of multi-disciplinary personnel.
Lien vers le texte intégral (Open Access ou abonnement)
26. Nomura T. Interneuron Dysfunction and Inhibitory Deficits in Autism and Fragile X Syndrome. Cells. 2021; 10(10).
The alteration of excitatory-inhibitory (E-I) balance has been implicated in various neurological and psychiatric diseases, including autism spectrum disorder (ASD). Fragile X syndrome (FXS) is a single-gene disorder that is the most common known cause of ASD. Understanding the molecular and physiological features of FXS is thought to enhance our knowledge of the pathophysiology of ASD. Accumulated evidence implicates deficits in the inhibitory circuits in FXS that tips E-I balance toward excitation. Deficits in interneurons, the main source of an inhibitory neurotransmitter, gamma-aminobutyric acid (GABA), have been reported in FXS, including a reduced number of cells, reduction in intrinsic cellular excitability, or weaker synaptic connectivity. Manipulating the interneuron activity ameliorated the symptoms in the FXS mouse model, which makes it reasonable to conceptualize FXS as an interneuronopathy. While it is still poorly understood how the developmental profiles of the inhibitory circuit go awry in FXS, recent works have uncovered several developmental alterations in the functional properties of interneurons. Correcting disrupted E-I balance by potentiating the inhibitory circuit by targeting interneurons may have a therapeutic potential in FXS. I will review the recent evidence about the inhibitory alterations and interneuron dysfunction in ASD and FXS and will discuss the future directions of this field.
Lien vers le texte intégral (Open Access ou abonnement)
27. Pasqualotto A, Mazzoni N, Bentenuto A, Mulè A, Benso F, Venuti P. Effects of Cognitive Training Programs on Executive Function in Children and Adolescents with Autism Spectrum Disorder: A Systematic Review. Brain sciences. 2021; 11(10).
BACKGROUND: Autism Spectrum Disorder is often associated with deficits in executive functions (EFs), which is contributing significantly to individuals with ASD’s difficulties in conducting an independent life, particularly considering social skills. Technologies offer promising opportunities to structure EF intervention programs for children on the autistic spectrum. METHODS: This study aimed to review the effectiveness of randomized controlled trials or quasi-experimental studies of EF interventions delivered to children and young people (up to 23 years old) with a diagnosis of ASD. A special focus was dedicated to document the effectiveness of computerized and non-computerized cognitive training on (1) EFs and on (2) ASD symptomatology and social skills. Of 2601 studies retrieved, 19 fulfilled the inclusion criteria. RESULTS: Most of the interventions identified were effective in enhancing EFs and reducing symptoms in children and young people with ASD. Limited evidence is available on their generalization to untrained skills (i.e., social abilities) as well as long-term effects. CONCLUSIONS: There is growing evidence for overall effectiveness of EF training, particularly when computerized. However, caution should be taken when interpreting these findings owing to methodological limitations, the minimal number of papers retrieved, and a small samples of included studies.
Lien vers le texte intégral (Open Access ou abonnement)
28. Pisula E, Niedźwiecka A. Symptoms of Autism, Comorbid Mental Health Conditions and Challenging Behaviors among Toddlers with Down Syndrome at Low Risk for ASD-Characterization Using the BISCUIT-Parts 1-3. International journal of environmental research and public health. 2021; 18(20).
Background: Autism spectrum disorder (ASD) may coexist with Down syndrome (DS). Most studies on this topic involve school-age children, adolescents, or adults with DS. This study looked at ASD symptoms, other mental health problems, and challenging behaviors in toddlers with DS at low risk of ASD. Methods: We used screening tools for autism in toddlers; BISCUIT-Parts 1-3 and Q-CHAT. We compared four groups of children aged 17-37 months: DS, ASD, Atypical Development (AD), and Typically Developing (TD). Results: Children with DS showed lower symptoms of ASD than children with ASD (without DS) and higher than TD children, except for repetitive behaviors/restricted interests. For comorbid mental health problems and difficult behaviors, children with DS scored lower than children with ASD. There were no differences between children with DS and TD children in this regard. Conclusions: The study results indicate that BISCUIT-Parts 1-3 are valid instruments to differentiate toddlers with DS from toddlers with ASD. However, they also show that toddlers with DS at low ASD risk are a very heterogeneous group when the ASD symptoms are considered. Autistic characteristics should be taken into account in supporting young children with this genetic condition.
Lien vers le texte intégral (Open Access ou abonnement)
29. Plaza-Diaz J, Flores-Rojas K, Torre-Aguilar MJ, Gomez-Fernández AR, Martín-Borreguero P, Perez-Navero JL, Gil A, Gil-Campos M. Dietary Patterns, Eating Behavior, and Nutrient Intakes of Spanish Preschool Children with Autism Spectrum Disorders. Nutrients. 2021; 13(10).
Eating behavior problems are characteristic of children with autism spectrum disorders (ASD) with a highly restricted range of food choices, which may pose an associated risk of nutritional problems. Hence, detailed knowledge of the dietary patterns (DPs) and nutrient intakes of ASD patients is necessary to carry out intervention strategies if required. The present study aimed to determine the DPs and macro-and micronutrient intakes in a sample of Spanish preschool children with ASD compared to typically developing control children. Fifty-four children with ASD (two to six years of age) diagnosed with ASD according to the Diagnostic Manual-5 criteria), and a control group of 57 typically developing children of similar ages were recruited. A validated food frequency questionnaire was used, and the intake of energy and nutrients was estimated through three non-consecutive 24-h dietary registrations. DPs were assessed using principal component analysis and hierarchical clustering analysis. Children with ASD exhibited a DP characterized by high energy and fat intakes and a low intake of vegetables and fruits. Likewise, meat intake of any type, both lean and fatty, was associated with higher consumption of fish and dietary fat. Furthermore, the increased consumption of dairy products was associated with increased consumption of cereals and pasta. In addition, they had frequent consumption of manufactured products with poor nutritional quality, e.g., beverages, sweets, snacks and bakery products. The percentages of children with ASD complying with the adequacy of nutrient intakes were higher for energy, saturated fat, calcium, and vitamin C, and lower for iron, iodine, and vitamins of group B when compared with control children. In conclusion, this study emphasizes the need to assess the DPs and nutrient intakes of children with ASD to correct their alterations and discard some potential nutritional diseases.
Lien vers le texte intégral (Open Access ou abonnement)
30. Pruccoli J, Graziano C, Locatelli C, Maltoni L, Sheikh Maye HA, Cordelli DM. Expanding the Neurological Phenotype of Ring Chromosome 10 Syndrome: A Case Report and Review of the Literature. Genes. 2021; 12(10).
Ring chromosome 10 [r(10)] syndrome is a rare genetic condition, currently described in the medical literature in a small number of case report studies. Typical clinical features include microcephaly, short stature, facial dysmorphisms, ophthalmologic abnormalities and genitourinary malformations. We report a novel case of r(10) syndrome and review the neurological and neuroradiological phenotypes of the previously described cases. Our patient, a 3 year old Italian girl, represents the 20th case of r(10) syndrome described to date. Intellectual disability/developmental delay (ID/DD), microcephaly, strabismus, hypotonia, stereotyped/aggressive behaviors and electroencephalographic abnormalities were identified in our patient, and in a series of previous cases. A brain MRI disclosed a complex malformation involving both the vermis and cerebellar hemispheres; in the literature, posterior cranial fossa abnormalities were documented by CT scan in another case. Two genes deleted in our case (ZMYND11 in 10p and EBF3 in 10q) are involved in autosomal dominant neurodevelopmental disorders, characterized by different expressions of brain and posterior cranial fossa abnormalities, ID/DD, hypotonia and behavioral problems. Our case expands the neurological and neuroradiological phenotype of r(10) syndrome. Although r(10) syndrome represents an extremely rare condition, with a clinical characterization limited to case reports, the recurrence of specific neurological and neuroradiological features suggests the need for specific genotype-phenotype studies.
Lien vers le texte intégral (Open Access ou abonnement)
31. Rehman IU, Sobnath D, Nasralla MM, Winnett M, Anwar A, Asif W, Sherazi HHR. Features of Mobile Apps for People with Autism in a Post COVID-19 Scenario: Current Status and Recommendations for Apps Using AI. Diagnostics (Basel, Switzerland). 2021; 11(10).
The new ‘normal’ defined during the COVID-19 pandemic has forced us to re-assess how people with special needs thrive in these unprecedented conditions, such as those with Autism Spectrum Disorder (ASD). These changing/challenging conditions have instigated us to revisit the usage of telehealth services to improve the quality of life for people with ASD. This study aims to identify mobile applications that suit the needs of such individuals. This work focuses on identifying features of a number of highly-rated mobile applications (apps) that are designed to assist people with ASD, specifically those features that use Artificial Intelligence (AI) technologies. In this study, 250 mobile apps have been retrieved using keywords such as autism, autism AI, and autistic. Among 250 apps, 46 were identified after filtering out irrelevant apps based on defined elimination criteria such as ASD common users, medical staff, and non-medically trained people interacting with people with ASD. In order to review common functionalities and features, 25 apps were downloaded and analysed based on eye tracking, facial expression analysis, use of 3D cartoons, haptic feedback, engaging interface, text-to-speech, use of Applied Behaviour Analysis therapy, Augmentative and Alternative Communication techniques, among others were also deconstructed. As a result, software developers and healthcare professionals can consider the identified features in designing future support tools for autistic people. This study hypothesises that by studying these current features, further recommendations of how existing applications for ASD people could be enhanced using AI for (1) progress tracking, (2) personalised content delivery, (3) automated reasoning, (4) image recognition, and (5) Natural Language Processing (NLP). This paper follows the PRISMA methodology, which involves a set of recommendations for reporting systematic reviews and meta-analyses.
Lien vers le texte intégral (Open Access ou abonnement)
32. Stark E, Stacey J, Mandy W, Kringelbach ML, Happé F. ‘Uncertainty attunement’ has explanatory value in understanding autistic anxiety. Trends in cognitive sciences. 2021; 25(12): 1011-2.
