1. Chen YL. Implementation of a Peer-Mediated Intervention to Teach Behavioral Expectations for Two Students on Autism Spectrum and a Student with ADHD in an Inclusive Elementary Classroom in Taiwan. Journal of autism and developmental disorders. 2022.

One of the characteristics of individuals on the autism spectrum is the restricted, repetitive patterns of behaviors, interests, or activities which have been considered the result of a direct deficit in self-regulation skills. Peer-mediated intervention (PMI) is one of the ways to support young children on the autism spectrum for following school routines independently. PMI is an evidence-based practice based on behavioral principles to train typical peers to help with students on the autism spectrum. By using PMI, students on the autism spectrum can have more interaction opportunities with typical peers. Students on the autism spectrum can become less dependent on adult support to complete the expectations independently or with peers’ support. The aim of this study is to use PMI to support students with autism and ADHD aged 7-8 in a regular classroom to complete the behavioral expectations in Taiwan. This study used a multiple probe design across three participants to determine the effects of the intervention. The researchers trained seven typically developing peers on how to prompt and reinforce the target children. This study took both peers and target children’s data. The data shows a positive result for target children to follow the expectations independently and most peer models can prompt and reinforce the target children after being trained. Our study has extended the effectiveness and usage of PMI in teaching behavioral expectations in Taiwan.

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2. Gioia R, Seri T, Diamanti T, Fimmanò S, Vitale M, Ahlenius H, Kokaia Z, Tirone F, Micheli L, Biagioni S, Lupo G, Rinaldi A, De Jaco A, Cacci E. Adult hippocampal neurogenesis and social behavioural deficits in the R451C Neuroligin3 mouse model of autism are reverted by the antidepressant Fluoxetine. Journal of neurochemistry. 2022.

Neuron generation persists throughout life in the hippocampus but is altered in animal models of neurological and neuropsychiatric diseases, suggesting that disease-associated decline in cognitive and emotional hippocampal-dependent behaviours might be functionally linked with dysregulation of post-natal neurogenesis. Depletion of the adult neural stem/progenitor cell (NSPCs) pool and neurogenic decline have been recently described in mice expressing synaptic susceptibility genes associated with autism spectrum disorder (ASDs). To gain further insight into mechanisms regulating neurogenesis in mice carrying mutations in synaptic genes related to monogenic ASDs, we used the R451C Neuroligin3 knock-in (Nlgn3 KI) mouse, which is characterized by structural brain abnormalities, deficits in synaptic functions, and reduced sociability. We show that the number of adult-born neurons, but not the size of the NSPC pool, was reduced in the ventral dentate gyrus in knock-in mice. Notably, this neurogenic decline was rescued by daily injecting mice with 10 mg/Kg of the antidepressant fluoxetine for twenty consecutive days. Sustained treatment also improved KI mice sociability and increased the number of c-Fos active adult-born neurons, compared with vehicle-injected KI mice. Our study uncovers neurogenesis-mediated alterations in the brain of R451C KI mouse, showing that the R451C Nlgn3 mutation leads to lasting, albeit pharmacologically reversible, changes in the brain, affecting neuron formation in the adult hippocampus. Our results suggest that fluoxetine can ameliorate social behaviour in KI mice, at least in part, by rescuing adult hippocampal neurogenesis, which may be relevant for the pharmacological treatment of ASDs.

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3. Idema WJ, Konz DN, Mulder AF, Kattentidt-Mouravieva AA, Kasius MC, Ester WA. [Care for adolescents with an autism spectrum disorder and an intellectual disability]. Tijdschrift voor psychiatrie. 2022; 64(10): 643-9.

BACKGROUND: Due to an experienced gap in care for adolescents with an autism spectrum disorder (ASD) and an intellectual disability (ID), an interdisciplinary outpatient clinic was initiated by child- and adolescent psychiatry services together with intellectual disability physicians in the Rotterdam region in 2017. AIM: Evaluation of the ASD-ID outpatient clinic. METHOD: A retrospective chart review study of the first year of the ASD-ID outpatient clinic was performed. The care specific traits of the adolescents who visited the ASD-ID outpatient clinic, their health care costs and the effect of the ASD-ID outpatient clinic on both the health care costs and the patient outflow was compared to the traits of the adolescents of the autism outpatient clinic. RESULTS: 32 adolescents who were referred to the ASD-ID outpatient clinic were comparable to 204 adolescents of the autism outpatient clinic in age (mean 16.5 years) and gender (75% male). They had 39% more DSM-IV classifications, were in care 3.7 years longer and had 44% more health care costs. After visiting the ASD-ID outpatient clinic, 50% of the adolescents were transferred within a year and 100% within three years to a intellectual disability physician. CONCLUSION: Adolescents with ASD and ID are a group with a substantial demand for care who deserve specific attention. An integrated ASD-ID outpatient clinic contributes to this demand.

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4. Kloosterboer SM, BC PK, Hillegers MHJ, van Gelder T, Dierckx B. [Improving the safety of antipsychotic drugs in children and adolescents by antipsychotic drug concentration measurements using a fingerprick]. Tijdschrift voor psychiatrie. 2022; 64(10): 684-91.

BACKGROUND: Antipsychotic drugs are associated with serious side effects in children and adolescents including weight gain. It is still unknown whether therapeutic drug monitoring (TDM) can improve patient outcomes. AIM: To test whether the dried blood spot method is a valid and feasible method to measure antipsychotic drug concentrations with a fingerprick; to assess the relationship between antipsychotic drug concentrations, side-effects and effectiveness in minors. METHOD: A dried blood spot (DBS) method was developed and tested for validity and feasibility. 89 children and adolescents with autism spectrum disorder (ASD) and behavioral problems were included in the multicenter, prospective, observational study SPACe (NTR6050). Antipsychotic drug concentrations, side-effects and effectiveness were measured during a 6-month follow-up. RESULTS: The DBS method showed a higher variability than venipuncture in measuring antipsychotic drug concentrations, but seemed feasible in minors with behavioral problems. Higher risperidon trough concentrations were associated with more weight gain and more effectiveness. A therapeutic window with optimal effectiveness and minimal side-effects was defined. CONCLUSION: The DBS method can be used to measure antipsychotic drug concentrations in children and adolescents with ASD and behavioral problems. As a relationship between antipsychotic drug concentrations and clinical outcomes was established, TDM might improve safety and effectiveness of antipsychotic drugs in this population.

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5. Miclea D, Osan S, Bucerzan S, Stefan D, Popp R, Mager M, Puiu M, Zimbru C, Chirita-Emandi A, Alkhzouz C. Copy number variation analysis in 189 Romanian patients with global developmental delay/intellectual disability. Italian journal of pediatrics. 2022; 48(1): 207.

BACKGROUND: Developmental delay and intellectual disability represent a common pathology in general population, involving about 3% of the pediatric age population, the genetic etiology being often involved. The aim of this study was to determine the clinically relevant copy number variants in patients diagnosed with global developmental delay/intellectual disability in our population, using the chromosomal microarray analysis. METHODS: We analyzed 189 patients diagnosed with global developmental delay/intellectual disability, presented in Clinical Emergency Hospital for Children, Cluj-Napoca. The patients were completely clinically investigated, including dysmorphic and internal malformations evaluation, psychiatric, neuropsychological and metabolic evaluation, standard karyotyping. Genomic analysis was done using chromosomal microarray analysis. RESULTS: Pathogenic findings (including uniparental disomy) and variants of unknown significance were detected in 53 of 189 patients (28.04%). Pathogenic copy number variants and uniparental disomy were observed in 35 of 189 patients (18.51%). Two patients presented uniparental disomy for chromosome 15, one with clinical phenotype of Prader-Willi syndrome and the other with clinical phenotype with Angelman syndrome. Within the category of pathogenic findings, the recurrent copy number variants were seen in 21 of 35 patients (60%). CONCLUSIONS: The increased percentage of pathogenic structural variants observed in patients with global developmental delay/intellectual disability analyzed by chromosomal microarray technique supports its use in patients with a non-specific phenotype such as these neurodevelopmental disorders. The high percentage of recurrent pathogenic variants between these findings is a finding that support their initial evaluation when a genetic testing algorithm could be a useful option.

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6. Nogueira HA, de Castro CT, da Silva DCG, Pereira M. Melatonin for sleep disorders in people with autism: Systematic review and meta-analysis. Progress in neuro-psychopharmacology & biological psychiatry. 2022; 123: 110695.

Melatonin is a potential therapeutic intervention for improving sleep quality in people with autistic spectrum disorder (ASD). We investigate the effect of using melatonin as a sleep disorder treatment in people with ASD. Interventionist studies were searched in seven databases. A total of 595 references were identified, 15 of which were eligible for the systemic review and meta-analysis. Melatonin use presented a positive effect on total sleep time (standardized mean difference- SMD = 0.78; 95%CI = 0.35; 1.21; I(2) = 91%), on sleep latency (SMD = 1.23; 95%CI = 0.35; 2.11; I(2) = 94%), and on sleep efficiency (SMD = -0.70; 95%CI = -1.23; -0.16; I(2) = 91%) when comparing the intervention group with the placebo/control group via the global analysis. According to the global analysis, the wake after sleep onset and night awakening parameters were not statistically significant. Melatonin has possible efficacy over total time, latency, and efficiency sleep parameters.

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7. O’Brien AM, Perrachione TK, Wisman Weil L, Sanchez Araujo Y, Halverson K, Harris A, Ostrovskaya I, Kjelgaard M, Kenneth W, Tager-Flusberg H, Gabrieli JDE, Qi Z. Altered engagement of the speech motor network is associated with reduced phonological working memory in autism. NeuroImage Clinical. 2022; 37: 103299.

Nonword repetition, a common clinical measure of phonological working memory, involves component processes of speech perception, working memory, and speech production. Autistic children often show behavioral challenges in nonword repetition, as do many individuals with communication disorders. It is unknown which subprocesses of phonological working memory are vulnerable in autistic individuals, and whether the same brain processes underlie the transdiagnostic difficulty with nonword repetition. We used functional magnetic resonance imaging (fMRI) to investigate the brain bases for nonword repetition challenges in autism. We compared activation during nonword repetition in functional brain networks subserving speech perception, working memory, and speech production between neurotypical and autistic children. Autistic children performed worse than neurotypical children on nonword repetition and had reduced activation in response to increasing phonological working memory load in the supplementary motor area. Multivoxel pattern analysis within the speech production network classified shorter vs longer nonword-repetition trials less accurately for autistic than neurotypical children. These speech production motor-specific differences were not observed in a group of children with reading disability who had similarly reduced nonword repetition behavior. These findings suggest that atypical function in speech production brain regions may contribute to nonword repetition difficulties in autism.

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8. Runge K, Fiebich BL, Kuzior H, Rausch J, Maier SJ, Dersch R, Nickel K, Domschke K, Tebartz van Elst L, Endres D. Altered cytokine levels in the cerebrospinal fluid of adult patients with autism spectrum disorder. Journal of psychiatric research. 2022; 158: 134-42.

BACKGROUND: Despite intensive research, the etiological causes of autism spectrum disorder (ASD) remain elusive. Immunological mechanisms have recently been studied more frequently in the context of maternal autoantibodies and infections, as well as altered cytokine profiles. For the detection of immunological processes in the central nervous system, analyses of cerebrospinal fluid (CSF) are advantageous due to its proximity to the brain. However, cytokine studies in the CSF of ASD patients are sparse. METHODS: CSF was collected from a patient sample of 24 adults (m = 16, f = 8, age: 30.3 ± 11.6 years) with ASD and compared to a previously published mentally healthy control sample of 39 neurological patients with idiopathic intracranial hypertension. A magnetic bead multiplexing immunoassay was used to measure multiple cytokines in CSF. RESULTS: Significantly decreased interferon-γ-induced protein-10 (p = 0.001) and monocyte chemoattractant protein-1 (p = 0.041) levels as well as significantly higher interleukin-8 levels (p = 0.041) were detected in patients with ASD compared with the control group. CONCLUSION: The main finding of this study is an altered cytokine profile in adult patients with ASD compared to the control group. This may indicate immune dysregulation in a subgroup of adult ASD patients. Further studies in larger cohorts that examine a broader spectrum of chemokines and cytokines in general are needed to detect possible specific immune signatures in ASD.

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9. Santamarina-Siurana C, Cloquell-Ballester V, Berenguer-Forner C, Fuentes-Albero M. Effect of vibrostimulatory wearable technology on stereotyped behaviour in a child with autism and intellectual disability. BMJ case reports. 2022; 15(12).

The aim of the work has been to report on the effects of vibrostimulation, administered through wearable technology, on stereotyped behaviour of a child in middle childhood, with autism, intellectual disability and severe behaviour in the ‘stereotypic behaviour’ subscale of the Restricted and Repetitive Behaviour Revised Scale. He received vibrostimulation (210 Hz, 2.8 µm), with a continuous pattern of vibration: three vibrations of 700 ms, each separated by a rest period of 500 ms and a pause of 8000 ms. Vibration was delivered bilaterally by two devices, repeating the vibration pattern for 3 min. The measures were repeated four times alternately, with the device turned off and on. The outcome measure was frequency of stereotyed behaviour, which was evaluated for 3 min with and without vibrostimulation. The results and observations, over 3 min of stimulation, showed the disappearance of stereotyped movements during vibrostimulation and better precision in intentional hand movements. Subjectively, the child enjoyed vibrostimulation.

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10. Sgritta M, Vignoli B, Pimpinella D, Griguoli M, Santi S, Bialowas A, Wiera G, Zacchi P, Malerba F, Marchetti C, Canossa M, Cherubini E. Impaired synaptic plasticity in an animal model of autism exhibiting early hippocampal GABAergic-BDNF/TrkB signaling alterations. iScience. 2023; 26(1): 105728.

In Neurodevelopmental Disorders, alterations of synaptic plasticity may trigger structural changes in neuronal circuits involved in cognitive functions. This hypothesis was tested in mice carrying the human R451C mutation of Nlgn3 gene (NLG3(R451C) KI), found in some families with autistic children. To this aim, the spike time dependent plasticity (STDP) protocol was applied to immature GABAergic Mossy Fibers (MF)-CA3 connections in hippocampal slices from NLG3(R451C) KI mice. These animals failed to exhibit STD-LTP, an effect that persisted in adulthood when these synapses became glutamatergic. Similar results were obtained in mice lacking the Nlgn3 gene (NLG3 KO mice), suggesting a loss of function. The loss of STD-LTP was associated with a premature shift of GABA from the depolarizing to the hyperpolarizing direction, a reduced BDNF availability and TrkB phosphorylation at potentiated synapses. These effects may constitute a general mechanism underlying cognitive deficits in those forms of Autism caused by synaptic dysfunctions.

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11. Wang F, Jin T, Li H, Long H, Liu Y, Jin S, Lu Y, Peng Y, Liu C, Zhao L, Wang X. Cannabidivarin alleviates α-synuclein aggregation via DAF-16 in Caenorhabditis elegans. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2023; 37(2): e22735.

Cannabidivarin (CBDV), a structural analog of cannabidiol (CBD), has received attention in recent years owing to its anticonvulsant property and potential for treating autism spectrum disorder. However, the function and mechanism of CBDV involved in the progression of Parkinson’s disease (PD) remain unclear. In this work, we found that CBDV inhibited α-synuclein (α-syn) aggregation in an established transgenetic Caenorhabditis elegans (C. elegans). The phenolic hydroxyl groups of CBDV are critical for scavenging reactive oxygen species (ROS), reducing the in vivo aggregation of α-syn and preventing DAergic neurons from 6-hydroxydopamine (6-OHDA)-induced injury and degeneration. By combining multiple biophysical approaches, including nuclear magnetic resonance spectrometry, transmission electron microscopy and fibrillation kinetics assays, we confirmed that CBDV does not directly interact with α-syn or inhibit the formation of α-syn fibrils in vitro. Further cellular signaling investigation showed that the ability of CBDV to prevent oxidative stress, the accumulation of α-syn and the degeneration of DAergic neurons was mediated by DAF-16 in the worms. This study demonstrates that CBDV alleviates the aggregation of α-syn in vivo and reveals that the phenolic hydroxyl groups of CBDV are critical for this activity, providing a potential for the development of CBDV as a drug candidate for PD therapeutics.

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12. Wang J, Wang D, Chen Y, Li H, Zhang Y, Wu Y. Rett syndrome with atrial tachycardia in a girl. Pediatric investigation. 2022; 6(4): 302-4.

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