1. Alessio N, Riccitiello F, Squillaro T, Capasso S, Del Gaudio S, Di Bernardo G, Cipollaro M, Melone MAB, Peluso G, Galderisi U. {{Neural stem cells from a mouse model of Rett syndrome are prone to senescence, show reduced capacity to cope with genotoxic stress, and are impaired in the differentiation process}}. {Experimental & molecular medicine}. 2018; 50(3): 1.
Several aspects of stem cell life are governed by epigenetic variations, such as DNA methylation, histone modifications, and chromatin remodeling. Epigenetic events are also connected with the impairment of stem cell functions. For example, during senescence, there are significant changes in chromatin organization that alter transcription. The MECP2 protein can bind methylated cytosines and contribute to regulating gene expression at one of the highest hierarchical levels. Researchers are particularly interested in this protein, as up to 90% of Rett syndrome patients have an MECP2 gene mutation. Nevertheless, the role of MECP2 in this disease remains poorly understood. We used a mouse model of Rett syndrome to evaluate whether residual MECP2 activity in neural stem cells (NSCs) induced the senescence phenomena that could affect stem cell function. Our study clearly demonstrated that the reduced expression of MECP2 is connected with an increase in senescence, an impairment in proliferation capacity, and an accumulation of unrepaired DNA foci. Mecp2 (+/-) NSCs did not cope with genotoxic stress in the same way as the control cells did. Indeed, after treatment with different DNA-damaging agents, the NSCs from mice with mutated Mecp2 accumulated more DNA damage foci (gamma-H2AX+) and were more prone to cell death than the controls. Senescence in Mecp2 (+/-) NSCs decreased the number of stem cells and progenitors and gave rise to a high percentage of cells that expressed neither stem/progenitor nor differentiation markers. These cells could be senescent and dysfunctional.
Lien vers le texte intégral (Open Access ou abonnement)
2. Alhazmi A, Petersen R, Donald KA. {{Quality of life among parents of South African children with autism spectrum disorder}}. {Acta neuropsychiatrica}. 2018: 1-6.
OBJECTIVE: To describe the quality of life (QOL) of South African parents caring for children with autism spectrum disorder (ASD) as compared with parents of typically developing (TD) children from the same community. METHODS: A cross-sectional study was done evaluating the QOL of parents of 52 children (26 parents of children with ASD versus 26 parents of TD children) using a structured measure, (World Health Organization Quality of Life Assessment-BREF). RESULTS: The mean age of the children with ASD was 64.9 months (SD 14.5) versus 60.1 months (SD 13.5) for TD group. There was a male predominance among group of children with ASD (48 boys, four girls). The mean parental age of the ASD group was 32.9 years (SD 7.8) compared with 33.8 years (SD 6.8) for the TD group. As compared with parents of the TD children, parents of children with ASD had lower mean QOL scores in the four QOL domains: physical, psychological, social and environmental health (p<0.0001). the domain where the discrepancy between groups was greatest was the physical domain Where the mean score was 52.1 (SD 18.7) in the ASD group and 92 (SD 10.4) in the TD group. Lower income, severity level of ASD and lack of access to school placement of children with ASD were found significantly associated with parents' QOL domains. CONCLUSION: QOL of parents of children with ASD is significant lower than that of the parents of their TD peers across all domains and is an important component in management of the family which needs to be explored and addressed. Lien vers le texte intégral (Open Access ou abonnement)
3. Avino TA, Barger N, Vargas MV, Carlson EL, Amaral DG, Bauman MD, Schumann CM. {{Neuron numbers increase in the human amygdala from birth to adulthood, but not in autism}}. {Proceedings of the National Academy of Sciences of the United States of America}. 2018.
Remarkably little is known about the postnatal cellular development of the human amygdala. It plays a central role in mediating emotional behavior and has an unusually protracted development well into adulthood, increasing in size by 40% from youth to adulthood. Variation from this typical neurodevelopmental trajectory could have profound implications on normal emotional development. We report the results of a stereological analysis of the number of neurons in amygdala nuclei of 52 human brains ranging from 2 to 48 years of age [24 neurotypical and 28 autism spectrum disorder (ASD)]. In neurotypical development, the number of mature neurons in the basal and accessory basal nuclei increases from childhood to adulthood, coinciding with a decrease of immature neurons within the paralaminar nucleus. Individuals with ASD, in contrast, show an initial excess of amygdala neurons during childhood, followed by a reduction in adulthood across nuclei. We propose that there is a long-term contribution of mature neurons from the paralaminar nucleus to other nuclei of the neurotypical human amygdala and that this growth trajectory may be altered in ASD, potentially underlying the volumetric changes detected in ASD and other neurodevelopmental or neuropsychiatric disorders.
Lien vers le texte intégral (Open Access ou abonnement)
4. Barton-Hulsey A, Sevcik RA, Romski M. {{The Relationship Between Speech, Language, and Phonological Awareness in Preschool-Age Children With Developmental Disabilities}}. {American journal of speech-language pathology}. 2018: 1-17.
Purpose: A number of intrinsic factors, including expressive speech skills, have been suggested to place children with developmental disabilities at risk for limited development of reading skills. This study examines the relationship between these factors, speech ability, and children’s phonological awareness skills. Method: A nonexperimental study design was used to examine the relationship between intrinsic skills of speech, language, print, and letter-sound knowledge to phonological awareness in 42 children with developmental disabilities between the ages of 48 and 69 months. Hierarchical multiple regression was done to determine if speech ability accounted for a unique amount of variance in phonological awareness skill beyond what would be expected by developmental skills inclusive of receptive language and print and letter-sound knowledge. Results: A range of skill in all areas of direct assessment was found. Children with limited speech were found to have emerging skills in print knowledge, letter-sound knowledge, and phonological awareness. Speech ability did not predict a significant amount of variance in phonological awareness beyond what would be expected by developmental skills of receptive language and print and letter-sound knowledge. Conclusion: Children with limited speech ability were found to have receptive language and letter-sound knowledge that supported the development of phonological awareness skills. This study provides implications for practitioners and researchers concerning the factors related to early reading development in children with limited speech ability and developmental disabilities.
Lien vers le texte intégral (Open Access ou abonnement)
5. Chen CT, Chen YL, Lin YC, Hsieh CL, Tzeng JY, Chen KL. {{Item-saving assessment of self-care performance in children with developmental disabilities: A prospective caregiver-report computerized adaptive test}}. {PLoS One}. 2018; 13(3): e0193936.
OBJECTIVE: The purpose of this study was to construct a computerized adaptive test (CAT) for measuring self-care performance (the CAT-SC) in children with developmental disabilities (DD) aged from 6 months to 12 years in a content-inclusive, precise, and efficient fashion. METHODS: The study was divided into 3 phases: (1) item bank development, (2) item testing, and (3) a simulation study to determine the stopping rules for the administration of the CAT-SC. A total of 215 caregivers of children with DD were interviewed with the 73-item CAT-SC item bank. An item response theory model was adopted for examining the construct validity to estimate item parameters after investigation of the unidimensionality, equality of slope parameters, item fitness, and differential item functioning (DIF). In the last phase, the reliability and concurrent validity of the CAT-SC were evaluated. RESULTS: The final CAT-SC item bank contained 56 items. The stopping rules suggested were (a) reliability coefficient greater than 0.9 or (b) 14 items administered. The results of simulation also showed that 85% of the estimated self-care performance scores would reach a reliability higher than 0.9 with a mean test length of 8.5 items, and the mean reliability for the rest was 0.86. Administering the CAT-SC could reduce the number of items administered by 75% to 84%. In addition, self-care performances estimated by the CAT-SC and the full item bank were very similar to each other (Pearson r = 0.98). CONCLUSION: The newly developed CAT-SC can efficiently measure self-care performance in children with DD whose performances are comparable to those of TD children aged from 6 months to 12 years as precisely as the whole item bank. The item bank of the CAT-SC has good reliability and a unidimensional self-care construct, and the CAT can estimate self-care performance with less than 25% of the items in the item bank. Therefore, the CAT-SC could be useful for measuring self-care performance in children with DD in clinical and research settings.
Lien vers le texte intégral (Open Access ou abonnement)
6. He N, Li BM, Li ZX, Wang J, Liu XR, Meng H, Tang B, Bian WJ, Shi YW, Liao WP. {{Few individuals with Lennox-Gastaut syndrome have autism spectrum disorder: a comparison with Dravet syndrome}}. {J Neurodev Disord}. 2018; 10(1): 10.
BACKGROUND: Autism spectrum disorder (ASD) in epilepsy has been a topic of increasing interest, which in general occurs in 15-35% of the patients with epilepsy, more frequently in those with intellectual disability (ID). Lennox-Gastaut syndrome (LGS) and Dravet syndrome (DS) are two typical forms of intractable epileptic encephalopathy associated with ID. We previously reported that ASD was diagnosed in 24.3% of patients with DS, higher in those with profound ID. Given the severe epilepsy and high frequency of ID in LGS, it is necessary to know whether ASD is a common psychomotor co-morbidity of LGS. This study evaluated the autistic behaviors and intelligence in patients with LGS and further compared that between LGS and DS, aiming to understand the complex pathogenesis of epilepsy-ASD-ID triad. METHODS: A total of 50 patients with LGS and 45 patients with DS were enrolled and followed up for at least 3 years. The clinical characteristics were analyzed, and evaluations of ASD and ID were performed. RESULTS: No patients with LGS fully met the diagnostic criteria for ASD, but three of them exhibited more or less autistic behaviors. Majority (86%) of LGS patients presented ID, among which moderate to severe ID was the most common. Early onset age and symptomatic etiology were risk predictors for ID. The prevalence of ASD in LGS was significantly lower than that in DS (0/50 vs. 10/45, p < 0.001), while the prevalence and severity of ID showed no significant difference between the two forms of epileptic encephalopathy. CONCLUSIONS: This study demonstrated a significant difference in the co-morbidity of ASD between LGS and DS, although they had a similar prevalence and severity of ID, refuting the proposal that the prevalence of ASD in epilepsy is accounted for by ID. These findings suggest that the co-morbidity of ASD, ID, and epilepsy may result from multifaceted pathogenic mechanisms. Lien vers le texte intégral (Open Access ou abonnement)
7. O’Leary HM, Kaufmann WE, Barnes KV, Rakesh K, Kapur K, Tarquinio DC, Cantwell NG, Roche KJ, Rose SA, Walco AC, Bruck NM, Bazin GA, Holm IA, Alexander ME, Swanson LC, Baczewski LM, Mayor Torres JM, Nelson CA, 3rd, Sahin M. {{Placebo-controlled crossover assessment of mecasermin for the treatment of Rett syndrome}}. {Annals of clinical and translational neurology}. 2018; 5(3): 323-32.
Objective: To measure the efficacy of mecasermin (recombinant human insulin-like growth factor 1, rhIGF-1), for treating symptoms of Rett syndrome (RTT) in a pediatric population using a double-blind crossover study design. Methods: Thirty girls with classic RTT in postregression stage were randomly assigned to placebo or rhIGF-1 in treatment period 1 and crossed over to the opposite assignment for period 2 (both 20 weeks), separated by a 28-week washout period. The primary endpoints were as follows: Anxiety Depression and Mood Scale (ADAMS) Social Avoidance subscale, Rett Syndrome Behaviour Questionnaire (RSBQ) Fear/Anxiety subscale, Parent Target Symptom Visual Analog Scale (PTSVAS) top three concerns, Clinical Global Impression (CGI), Parent Global Impression (PGI), and the Kerr severity scale. Cardiorespiratory- and electroencephalography (EEG)-based biomarkers were also analyzed. Results: There were no significant differences between randomization groups. The majority of AEs were mild to moderate, although 12 episodes of serious AEs occurred. The Kerr severity scale, ADAMS Depressed Mood subscale, Visual Analog Scale Hyperventilation, and delta average power change scores significantly increased, implying worsening of symptoms. Electroencephalography (EEG) parameters also deteriorated. A secondary analysis of subjects who were not involved in a placebo recall confirmed most of these findings. However, it also revealed improvements on a measure of stereotypic behavior and another of social communication. Interpretation: As in the phase 1 trial, rhIGF-1 was safe; however, the drug did not reveal significant improvement, and some parameters worsened.
Lien vers le texte intégral (Open Access ou abonnement)
8. Qasem H, Al-Ayadhi L, Bjorklund G, Chirumbolo S, El-Ansary A. {{Impaired lipid metabolism markers to assess the risk of neuroinflammation in autism spectrum disorder}}. {Metabolic brain disease}. 2018.
Autism spectrum disorder (ASD) is a multifactorial disorder caused by an interaction between environmental risk factors and a genetic background. It is characterized by impairment in communication, social interaction, repetitive behavior, and sensory processing. The etiology of ASD is still not fully understood, and the role of neuroinflammation in autism behaviors needs to be further investigated. The aim of the present study was to test the possible association between prostaglandin E2 (PGE2), cyclooxygenase-2 (COX-2), microsomal prostaglandin E synthase-1 (mPGES-1), prostaglandin PGE2 EP2 receptors and nuclear kappa B (NF-kappaB) and the severity of cognitive disorders, social impairment, and sensory dysfunction. PGE2, COX-2, mPGES-1, PGE2-EP2 receptors and NF-kappaB as biochemical parameters related to neuroinflammation were determined in the plasma of 47 Saudi male patients with ASD, categorized as mild to moderate and severe as indicated by the Childhood Autism Rating Scale (CARS) or the Social Responsiveness Scale (SRS) or the Short Sensory Profile (SSP) and compared to 46 neurotypical controls. The data indicated that ASD patients have remarkably higher levels of the measured parameters compared to neurotypical controls, except for EP2 receptors that showed an opposite trend. While the measured parameter did not correlate with the severity of social and cognitive dysfunction, PGE2, COX-2, and mPGES-1 were remarkably associated with the dysfunction in sensory processing. NF-kappaB was significantly increased in relation to age. Based on the discussed data, the positive correlation between PGE2, COX-2, and mPGES-1 confirm the role of PGE2 pathway and neuroinflammation in the etiology of ASD, and the possibility of using PGE2, COX-2 and mPGES-1 as biomarkers of autism severity. NF-kappaB as inflammatory inducer showed an elevated level in plasma of ASD individuals. Receiver operating characteristic analysis together with predictiveness diagrams proved that the measured parameters could be used as predictive biomarkers of biochemical correlates to ASD.
Lien vers le texte intégral (Open Access ou abonnement)
9. Shepherd D, Csako R, Landon J, Goedeke S, Ty K. {{Brief Report: Parent’s Assessments of Their Care-Related Stress and Child’s ASD Symptoms in Relation to Their child’s Intervention History}}. {J Autism Dev Disord}. 2018.
Parenting a child with autism spectrum disorder (ASD) can be stressful. Understanding parent’s perceptions of their stress and their child’s ASD-related symptoms is important for both the well-being of parent and child and for other reasons, such as intervention adherence and diagnostic accuracy. We report parent (N = 570) ratings of both their ASD Care-Related Stress scores and their child’s symptoms in relation to the child’s exposure to five mainstream ASD interventions. Differences across intervention history in the way parents perceive their child’s symptoms and rate the stressfulness of performing ASD-related parenting duties were found.
Lien vers le texte intégral (Open Access ou abonnement)
10. Simoes M, Bernardes M, Barros F, Castelo-Branco M. {{Virtual Travel Training for Autism Spectrum Disorder: Proof-of-Concept Interventional Study}}. {JMIR serious games}. 2018; 6(1): e5.
BACKGROUND: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social interaction and repetitive patterns of behavior, which can lead to deficits in adaptive behavior. In this study, a serious game was developed to train individuals with ASD for an important type of outdoor activity, which is the use of buses as a means of transportation. OBJECTIVE: The aim of this study was to develop a serious game that defines a « safe environment » where the players became familiar with the process of taking a bus and to validate if it could be used effectively to teach bus-taking routines and adaptive procedures to individuals with ASD. METHODS: In the game, players were placed in a three-dimensional city and were submitted to a set of tasks that involved taking buses to reach specific destinations. Participants with ASD (n=10) underwent between 1 to 3 training sessions. Participants with typical development (n=10) were also included in this study for comparison purposes and received 1 control session. RESULTS: We found a statistically significant increase in the measures of knowledge of the process of riding a bus, a reduction in the electrodermal activity (a metric of anxiety) measured inside the bus environments, and a high success rate of their application within the game (93.8%). CONCLUSIONS: The developed game proved to be potentially useful in the context of emerging immersive virtual reality technologies, of which use in therapies and serious games is still in its infancy. Our findings suggest that serious games, using these technologies, can be used effectively in helping people with ASD become more independent in outdoor activities, specifically regarding the use of buses for transportation.
Lien vers le texte intégral (Open Access ou abonnement)
11. Swanson MR, Shen MD, Wolff JJ, Elison JT, Emerson RW, Styner MA, Hazlett HC, Truong K, Watson LR, Paterson S, Marrus N, Botteron KN, Pandey J, Schultz RT, Dager SR, Zwaigenbaum L, Estes AM, Piven J. {{Subcortical Brain and Behavior Phenotypes Differentiate Infants With Autism Versus Language Delay}}. {Biol Psychiatry Cogn Neurosci Neuroimaging}. 2017; 2(8): 664-72.
BACKGROUND: Younger siblings of children with autism spectrum disorder (ASD) are themselves at increased risk for ASD and other developmental concerns. It is unclear if infants who display developmental concerns, but are unaffected by ASD, share similar or dissimilar behavioral and brain phenotypes to infants with ASD. Most individuals with ASD exhibit heterogeneous difficulties with language, and their receptive-expressive language profiles are often atypical. Yet, little is known about the neurobiology that contributes to these language difficulties. METHODS: In this study, we used behavioral assessments and structural magnetic resonance imaging to investigate early brain structures and associations with later language skills. High-risk infants who were later diagnosed with ASD (n = 86) were compared with high-risk infants who showed signs of early language delay (n = 41) as well as with high- and low-risk infants who did not have ASD or language delay (n = 255 and 143, respectively). RESULTS: Results indicated that diminished language skills were evident at 12 months in infants with ASD and infants with early language delay. At 24 months of age, only the infants with ASD displayed atypical receptive-expressive language profiles. Associations between 12-month subcortical volumes and 24-month language skills were moderated by group status, indicating disordinal brain-behavior associations among infants with ASD and infants with language delay. CONCLUSIONS: These results suggest that there are different brain mechanisms influencing language development in infants with ASD and infants with language delay, and that the two groups likely experience unique sets of genetic and environmental risk factors.
Lien vers le texte intégral (Open Access ou abonnement)
12. Zhang L, Warren Z, Swanson A, Weitlauf A, Sarkar N. {{Understanding Performance and Verbal-Communication of Children with ASD in a Collaborative Virtual Environment}}. {J Autism Dev Disord}. 2018.
Collaborative virtual environments (CVEs), which allow naturalistic communication between two or more individuals in a shared virtual environment, hold promise as a tool for measuring and promoting social communication between peers. In this work, a CVE platform and a set of CVE-based collaborative games are designed for children with autism spectrum disorder (ASD). Two groups (7 ASD/TD pairs; 7 TD/TD pairs) participated in a pilot study to establish system feasibility and tolerability. We also designed a methodology for capturing meaningful metrics of social communication. Based on these metrics, we found improved game performance and trends in communication of these participants over time. Although preliminary, these results provide important insights on CVE-based interaction for ASD intervention.
