1. Bianco V, Finisguerra A, Betti S, D’Argenio G, Urgesi C. {{Autistic Traits Differently Account for Context-Based Predictions of Physical and Social Events}}. {Brain Sci}. 2020; 10(7).
Autism is associated with difficulties in making predictions based on contextual cues. Here, we investigated whether the distribution of autistic traits in the general population, as measured through the Autistic Quotient (AQ), is associated with alterations of context-based predictions of social and non-social stimuli. Seventy-eight healthy participants performed a social task, requiring the prediction of the unfolding of an action as interpersonal (e.g., to give) or individual (e.g., to eat), and a non-social task, requiring the prediction of the appearance of a moving shape as a short (e.g., square) or a long (e.g., rectangle) figure. Both tasks consisted of (i) a familiarization phase, in which the association between each stimulus type and a contextual cue was manipulated with different probabilities of co-occurrence, and (ii) a testing phase, in which visual information was impoverished by early occlusion of video display, thus forcing participants to rely on previously learned context-based associations. Findings showed that the prediction of both social and non-social stimuli was facilitated when embedded in high-probability contexts. However, only the contextual modulation of non-social predictions was reduced in individuals with lower ‘Attention switching’ abilities. The results provide evidence for an association between weaker context-based expectations of non-social events and higher autistic traits.
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2. Boada L, Lahera G, Pina-Camacho L, Merchán-Naranjo J, Díaz-Caneja CM, Bellón JM, Ruiz-Vargas JM, Parellada M. {{Social Cognition in Autism and Schizophrenia Spectrum Disorders: The Same but Different?}}. {J Autism Dev Disord}. 2020.
Social cognition impairment is a core shared phenotype in both schizophrenia spectrum disorders (SSD) and autism spectrum disorders (ASD). This study compares social cognition performance through four different instruments in a sample of 147 individuals with ASD or SSD and in healthy controls. We found that both clinical groups perform similarly to each other and worse than healthy controls in all social cognition tasks. Only performance on the Movie for the Assessment of Social Cognition (MASC) test was independent of age and intelligence. Proportionately, individuals in the control group made significantly more overmentalization errors than both patients group did and made fewer undermentalization errors than patients with SSD did. AUC analyses showed that the MASC was the instrument that best discriminated between the clinical and control groups. Multivariate analysis showed negative symptom severity as a potential mediator of the association between social cognition deficit and poor global functioning.
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3. Burke SL, Li T, Grudzien A, Garcia S. {{Brief Report: Improving Employment Interview Self-efficacy Among Adults with Autism and Other Developmental Disabilities Using Virtual Interactive Training Agents (ViTA)}}. {J Autism Dev Disord}. 2020.
This study evaluated the measurable impact of the use of virtual interactive training agents (ViTA) as a way to practice interviewing and gain confidence in responding to questions asked during job interviews. Of the total participants (n = 153), the majority were male (72.55%) with an average age of 21.71 years old (SD = 3.14 years). Autism spectrum disorders (ASDs; 64.71%) and intellectual disability (40%) were the most frequently reported diagnoses. Using a within-subjects repeated measures design, the repeated measures linear regression analysis found that the average self-efficacy score increased by 0.31 (p = 0.002), and statistically significant increases were found in all three subscales. Further development of virtual reality interventions like ViTA, that improve outcomes for adults with ASDs and other developmental disabilities, is warranted.
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4. Carbone PS, Campbell K, Wilkes J, Stoddard GJ, Huynh K, Young PC, Gabrielsen TP. {{Primary Care Autism Screening and Later Autism Diagnosis}}. {Pediatrics}. 2020.
OBJECTIVES: To describe the proportion of children screened by the Modified Checklist for Autism in Toddlers (M-CHAT), identify characteristics associated with screen completion, and examine associations between autism spectrum disorder (ASD) screening and later ASD diagnosis. METHODS: We examined data from children attending 18- and 24-month visits between 2013 and 2016 from 20 clinics within a health care system for evidence of screening with the M-CHAT and subsequent coding of ASD diagnosis at age >4.75 years. We interviewed providers for information about usual methods of M-CHAT scoring and ASD referral. RESULTS: Of 36 233 toddlers, 73% were screened and 1.4% were later diagnosed with ASD. Hispanic children were less likely to be screened (adjusted prevalence ratio [APR]: 0.95, 95% confidence interval [CI]: 0.92-0.98), and family physicians were less likely to screen (APR: 0.12, 95% CI: 0.09-0.15). Compared with unscreened children, screen-positive children were more likely to be diagnosed with ASD (APR: 10.3, 95% CI: 7.6-14.1) and were diagnosed younger (38.5 vs 48.5 months, P < .001). The M-CHAT's sensitivity for ASD diagnosis was 33.1%, and the positive predictive value was 17.8%. Providers routinely omitted the M-CHAT follow-up interview and had uneven referral patterns. CONCLUSIONS: A majority of children were screened for ASD, but disparities exist among those screened. Benefits for screen-positive children are improved detection and younger age of diagnosis. Performance of the M-CHAT can be improved in real-world health care settings by administering screens with fidelity and facilitating timely ASD evaluations for screen-positive children. Providers should continue to monitor for signs of ASD in screen-negative children. Lien vers le texte intégral (Open Access ou abonnement)
5. Caria A, Ciringione L, Falco S. {{Morphofunctional Alterations of the Hypothalamus and Social Behavior in Autism Spectrum Disorders}}. {Brain Sci}. 2020; 10(7).
An accumulating body of evidence indicates a tight relationship between the endocrine system and abnormal social behavior. Two evolutionarily conserved hypothalamic peptides, oxytocin and arginine-vasopressin, because of their extensively documented function in supporting and regulating affiliative and socio-emotional responses, have attracted great interest for their critical implications for autism spectrum disorders (ASD). A large number of controlled trials demonstrated that exogenous oxytocin or arginine-vasopressin administration can mitigate social behavior impairment in ASD. Furthermore, there exists long-standing evidence of severe socioemotional dysfunctions after hypothalamic lesions in animals and humans. However, despite the major role of the hypothalamus for the synthesis and release of oxytocin and vasopressin, and the evident hypothalamic implication in affiliative behavior in animals and humans, a rather small number of neuroimaging studies showed an association between this region and socioemotional responses in ASD. This review aims to provide a critical synthesis of evidences linking alterations of the hypothalamus with impaired social cognition and behavior in ASD by integrating results of both anatomical and functional studies in individuals with ASD as well as in healthy carriers of oxytocin receptor (OXTR) genetic risk variant for ASD. Current findings, although limited, indicate that morphofunctional anomalies are implicated in the pathophysiology of ASD and call for further investigations aiming to elucidate anatomical and functional properties of hypothalamic nuclei underlying atypical socioemotional behavior in ASD.
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6. Chen YY, Chen YL, Gau SS. {{Suicidality in Children with Elevated Autistic Traits}}. {Autism Res}. 2020.
By using a nationally representative school-based sample (4,816 children aged 8-14 years), we examined the risk of suicidality in children with elevated autistic traits and assessed the mediation of anxiety/depression and moderation effects of family function and academic performance. The Chinese version of the Social Responsiveness Scale (SRS-C) was used to measure autistic features. Logistic regression models were applied to assess associations between autistic traits and suicidality (suicidal ideation, suicide plans, and suicide attempts) for estimating the mediation effects of anxiety/depression and moderation effects of academic performance and family function after adjustment for control variables. Every 10-point increase in the SRS-C score was associated with a 1.3-1.4-fold increase in suicidality risk. Associations relating to suicide plans and attempts were fully mediated; however, the association with ideation was partially mediated by anxiety/depression. Academic performance and family function did not appear to moderate associations between autistic traits and suicidality. In conclusion, children with elevated autistic traits exhibited increased risk of suicidality, which could be generally attributed to symptoms of anxiety/depression. Because adequate family function and academic performance did not mitigate the link between elevated autistic traits and suicidality, in-depth exploration into specific protective factors in children with elevated autistic traits is warranted. LAY SUMMARY: By using a nationally representative school-based sample (4,816 children aged 8-14 years), we observed that the risk of suicidality increased in children with elevated autistic traits. This association was generally explained by increased levels of anxiety/depression. Furthermore, better family function and academic performance did not appear to mitigate the link between autistic traits and suicidality.
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7. Darnell RB. {{The Genetic Control of Stoichiometry Underlying Autism}}. {Annual review of neuroscience}. 2020; 43: 509-33.
Autism is a common and complex neurologic disorder whose scientific underpinnings have begun to be established in the past decade. The essence of this breakthrough has been a focus on families, where genetic analyses are strongest, versus large-scale, case-control studies. Autism genetics has progressed in parallel with technology, from analyses of copy number variation to whole-exome sequencing (WES) and whole-genome sequencing (WGS). Gene mutations causing complete loss of function account for perhaps one-third of cases, largely detected through WES. This limitation has increased interest in understanding the regulatory variants of genes that contribute in more subtle ways to the disorder. Strategies combining biochemical analysis of gene regulation, WGS analysis of the noncoding genome, and machine learning have begun to succeed. The emerging picture is that careful control of the amounts of transcription, mRNA, and proteins made by key brain genes-stoichiometry-plays a critical role in defining the clinical features of autism.
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8. Dimian AF, Symons FJ, Wolff JJ. {{Delay to Early Intensive Behavioral Intervention and Educational Outcomes for a Medicaid-Enrolled Cohort of Children with Autism}}. {J Autism Dev Disord}. 2020.
Increased prevalence of autism spectrum disorder (ASD) has underscored the need for early intervention services. Early Intensive Behavioral Intervention (EIBI) is among the most common evidence-based approaches, however, stakeholders report significant waitlists. The effects of these delays to intervention are unknown. The purpose of this study was to evaluate the effects of delay to EIBI for preschool aged children with ASD on later educational outcomes. Medicaid records from Minnesota (2008-2010) were used to evaluate a cohort diagnosed with ASD and their later educational outcomes from 2010 to 2014 (n = 667) using generalized estimating equations. Approximately 70% of children experienced a delay to EIBI and children that experienced less delay and started EIBI at a younger age had better educational outcomes.
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9. Fonzo M, Sirico F, Corrado B. {{Evidence-Based Physical Therapy for Individuals with Rett Syndrome: A Systematic Review}}. {Brain Sci}. 2020; 10(7).
Rett syndrome is a rare genetic disorder that affects brain development and causes severe mental and physical disability. This systematic review analyzes the most recent evidence concerning the role of physical therapy in the management of individuals with Rett syndrome. The review was carried out in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. A total of 17319 studies were found in the main scientific databases. Applying the inclusion/exclusion criteria, 22 studies were admitted to the final phase of the review. Level of evidence of the included studies was assessed using the Oxford Centre for Evidence-Based Medicine-Levels of Evidence guide. Nine approaches to physical therapy for patients with Rett syndrome were identified: applied behavior analysis, conductive education, environmental enrichment, traditional physiotherapy with or without aids, hydrotherapy, treadmill, music therapy, computerized systems, and sensory-based treatment. It has been reported that patients had clinically benefited from the analysed approaches despite the fact that they did not have strong research evidence. According to the results, a multimodal individualized physical therapy program should be regularly recommended to patients with Rett syndrome in order to preserve autonomy and to improve quality of life. However, more high-quality studies are needed to confirm these findings.
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10. García-Domínguez I, Suárez-Pereira I, Santiago M, Pérez-Villegas EM, Bravo L, López-Martín C, Roca-Ceballos MA, García-Revilla J, Espinosa-Oliva AM, Rodríguez-Gómez JA, Joseph B, Berrocoso E, Armengol J, Venero JL, Ruiz R, de Pablos RM. {{Selective deletion of Caspase-3 gene in the dopaminergic system exhibits autistic-like behaviour}}. {Prog Neuropsychopharmacol Biol Psychiatry}. 2020; 104: 110030.
Apoptotic caspases are thought to play critical roles in elimination of excessive and non-functional synapses and removal of extra cells during early developmental stages. Hence, an impairment of this process may thus constitute a basis for numerous neurological and psychiatric diseases. This view is especially relevant for dopamine due to its pleiotropic roles in motor control, motivation and reward processing. Here, we have analysed the effect of caspase-3 depletion on the development of catecholaminergic neurons and performed a wide array of neurochemical, ultrastructural and behavioural assays. To achieve this, we performed selective deletion of the Casp3 gene in tyrosine hydroxylase (TH)-expressing cells using Cre-loxP-mediated recombination. Histological evaluation of most relevant catecholaminergic nuclei revealed the ventral mesencephalon as the most affected region. Stereological analysis demonstrated an increase in the number of TH-positive neurons in both the substantia nigra and ventral tegmental area along with enlarged volume of the ventral midbrain. Analysis of main innervating tissues revealed a rather contrasting profile. In striatum, basal extracellular levels and potassium-evoked DA release were significantly reduced in mice lacking Casp3, a clear indication of dopaminergic hypofunction in dopaminergic innervating tissues. This view was sustained by analysis of TH-labelled dopaminergic terminals by confocal and electron microscopy. Remarkably, at a behavioural level, Casp3-deficient mice exhibited impaired social interaction, restrictive interests and repetitive stereotypies, which are considered the core symptoms of autism spectrum disorder (ASD). Our study revitalizes the potential involvement of dopaminergic transmission in ASD and provides an excellent model to get further insights in ASD pathogenesis.
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11. Genovese A, Butler MG. {{Clinical Assessment, Genetics, and Treatment Approaches in Autism Spectrum Disorder (ASD)}}. {International journal of molecular sciences}. 2020; 21(13).
Autism spectrum disorder (ASD) consists of a genetically heterogenous group of neurobehavioral disorders characterized by impairment in three behavioral domains including communication, social interaction, and stereotypic repetitive behaviors. ASD affects more than 1% of children in Western societies, with diagnoses on the rise due to improved recognition, screening, clinical assessment, and diagnostic testing. We reviewed the role of genetic and metabolic factors which contribute to the causation of ASD with the use of new genetic technology. Up to 40 percent of individuals with ASD are now diagnosed with genetic syndromes or have chromosomal abnormalities including small DNA deletions or duplications, single gene conditions, or gene variants and metabolic disturbances with mitochondrial dysfunction. Although the heritability estimate for ASD is between 70 and 90%, there is a lower molecular diagnostic yield than anticipated. A likely explanation may relate to multifactorial causation with etiological heterogeneity and hundreds of genes involved with a complex interplay between inheritance and environmental factors influenced by epigenetics and capabilities to identify causative genes and their variants for ASD. Behavioral and psychiatric correlates, diagnosis and genetic evaluation with testing are discussed along with psychiatric treatment approaches and pharmacogenetics for selection of medication to treat challenging behaviors or comorbidities commonly seen in ASD. We emphasize prioritizing treatment based on targeted symptoms for individuals with ASD, as treatment will vary from patient to patient based on diagnosis, comorbidities, causation, and symptom severity.
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12. Gillespie-Lynch K, Hotez E, Zajic M, Riccio A, DeNigris D, Kofner B, Bublitz D, Gaggi N, Luca K. {{Comparing the writing skills of autistic and nonautistic university students: A collaboration with autistic university students}}. {Autism}. 2020: 1362361320929453.
We do not know very much about the writing skills of autistic university students. Studies with autistic children and teenagers show that some autistic young people have difficulties writing. Other autistic people are talented writers. In fact, some autistic people would rather write than speak. Good writers often imagine other people’s points of view when writing. Autistic people sometimes have difficulties understanding others’ points of view. Yet, autistic people often work much harder to understand others’ points of view than not-autistic people do. We collaborated with autistic university student researchers to see if autistic university students are better or worse at writing than nonautistic students. Autistic university students in our study were better writers than nonautistic students. Autistic students in our study had higher nonverbal intelligence than nonautistic students. Autistic students also put themselves under more pressure to write perfectly than nonautistic students did. Autistic students did not show any difficulties understanding other minds. This study shows that some autistic university students have stronger writing skills and higher intelligence than nonautistic university students. Yet, autistic students may be too hard on themselves about their writing. Fun activities that help students explore their ideas without pressure (like theater games) may help autistic students be less hard on their writing. Teachers can help autistic students express themselves through writing by encouraging them to write about their interests, by giving them enough time to write, and by letting them write using computers if they want to. This study shows that collaborations with autistic people can help us understand strengths that can help autistic people succeed.
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13. Keller R, Chieregato S, Bari S, Castaldo R, Rutto F, Chiocchetti A, Dianzani U. {{Autism in Adulthood: Clinical and Demographic Characteristics of a Cohort of Five Hundred Persons with Autism Analyzed by a Novel Multistep Network Model}}. {Brain Sci}. 2020; 10(7).
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in communication and relational skills, associated with repetitive verbal and motor behaviors, restricted patterns of interest, need for a predictable and stable environment, and hypo- or hypersensitivity to sensory inputs. Due to the challenging diagnosis and the paucity of specific interventions, persons with autism (PWA) reaching the adult age often display a severe functional regression. In this scenario, the Regional Center for Autism in Adulthood in Turin seeks to develop a personalized rehabilitation and enablement program for PWA who received a diagnosis of autism in childhood/adolescence or for individuals with suspected adulthood ASD. This program is based on a Multistep Network Model involving PWA, family members, social workers, teachers, and clinicians. Our initial analysis of 500 PWA shows that delayed autism diagnosis and a lack of specific interventions at a young age are largely responsible for the creation of a « lost generation » of adults with ASD, now in dire need of effective psychosocial interventions. As PWA often present with psychopathological co-occurrences or challenging behaviors associated with lack of adequate communication and relational skills, interventions for such individuals should be mainly aimed to improve their self-reliance and social attitude. In particular, preparing PWA for employment, whenever possible, should be regarded as an essential part of the intervention program given the social value of work. Overall, our findings indicate that the development of public centers specialized in assisting and treating PWA can improve the accuracy of ASD diagnosis in adulthood and foster specific habilitative interventions aimed to improve the quality of life of both PWA and their families.
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14. McNally Keehn R, Ciccarelli M, Szczepaniak D, Tomlin A, Lock T, Swigonski N. {{A Statewide Tiered System for Screening and Diagnosis of Autism Spectrum Disorder}}. {Pediatrics}. 2020.
Although autism spectrum disorder (ASD) can be reliably detected in the second year of life, the average age of diagnosis is 4 to 5 years. Limitations in access to timely ASD diagnostic evaluations delay enrollment in interventions known to improve developmental outcomes. As such, developing and testing streamlined methods for ASD diagnosis is a public health and research priority. In this report, we describe the Early Autism Evaluation (EAE) Hub system, a statewide initiative for ASD screening and diagnosis in the primary care setting. Development of the EAE Hub system involved geographically targeted provision of developmental screening technical assistance to primary care, community outreach, and training primary care clinicians in ASD evaluation. At the EAE Hubs, a standard clinical pathway was implemented for evaluation of children, ages 18 to 48 months, at risk for ASD. From 2012 to 2018, 2076 children were evaluated (mean age: 30 months; median evaluation wait time: 62 days), and 33% of children received a diagnosis of ASD. Our findings suggest that developing a tiered system of developmental screening and early ASD evaluation is feasible in a geographic region facing health care access problems. Through targeted delivery of education, outreach, and intensive practice-based training, large numbers of young children at risk for ASD can be identified, referred, and evaluated in the local primary care setting. The EAE Hub model has potential for dissemination to other states facing similar neurodevelopmental health care system burdens. Implementation lessons learned and key system successes, challenges, and future directions are reviewed.
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15. Nunes AS, Vakorin VA, Kozhemiako N, Peatfield N, Ribary U, Doesburg SM. {{Atypical age-related changes in cortical thickness in autism spectrum disorder}}. {Sci Rep}. 2020; 10(1): 11067.
Recent longitudinal neuroimaging and neurophysiological studies have shown that tracking relative age-related changes in neural signals, rather than a static snapshot of a neural measure, could offer higher sensitivity for discriminating typically developing (TD) individuals from those with autism spectrum disorder (ASD). It is not clear, however, which aspects of age-related changes (trajectories) would be optimal for identifying atypical brain development in ASD. Using a large cross-sectional data set (Autism Brain Imaging Data Exchange [ABIDE] repository; releases I and II), we aimed to explore age-related changes in cortical thickness (CT) in TD and ASD populations (age range 6-30 years old). Cortical thickness was estimated from T1-weighted MRI images at three scales of spatial coarseness (three parcellations with different numbers of regions of interest). For each parcellation, three polynomial models of age-related changes in CT were tested. Specifically, to characterize alterations in CT trajectories, we compared the linear slope, curvature, and aberrancy of CT trajectories across experimental groups, which was estimated using linear, quadratic, and cubic polynomial models, respectively. Also, we explored associations between age-related changes with ASD symptomatology quantified as the Autism Diagnostic Observation Schedule (ADOS) scores. While no overall group differences in cortical thickness were observed across the entire age range, ASD and TD populations were different in terms of age-related changes, which were located primarily in frontal and tempo-parietal areas. These atypical age-related changes were also associated with ADOS scores in the ASD group and used to predict ASD from TD development. These results indicate that the curvature is the most reliable feature for localizing brain areas developmentally atypical in ASD with a more pronounced effect with symptomatology and is the most sensitive in predicting ASD development.
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16. Thomaidis L, Mavroeidi N, Richardson C, Choleva A, Damianos G, Bolias K, Tsolia M. {{Autism Spectrum Disorders in Greece: Nationwide Prevalence in 10-11 Year-Old Children and Regional Disparities}}. {J Clin Med}. 2020; 9(7).
Autism spectrum disorders (ASD) constitute a public health concern with increasing prevalence worldwide. We aimed to estimate prevalence and age at diagnosis in Greece, where no large-scale prevalence study has ever been conducted. Aggregate data were collected on ASD diagnoses by gender and calendar year of diagnosis up to 2019, for children born in 2008 and 2009, from the Centers for Educational and Counseling Support, which evaluate children to receive special educational support in school. Coverage was 87.1% of centers and 88.1% of schoolchildren born in 2008-9. ASD prevalence overall was 1.15% (1.83% males, 0.44% females; ratio 4.14:1), ranging from 0.59% to 1.50% in Greece’s 13 regions. In five regions, prevalence differed significantly between centers. Overall, only 3.8% of diagnoses were made before the fourth year after birth and 42.7% before the sixth year, with considerable variation between regions. Approximate mean age at diagnosis was six years and one month, and about three months earlier for girls than for boys. Our results provide evidence-based information to guide service planning and development at national and regional levels. Particular attention should be paid to smoothing out inequalities regarding service accessibility and provision. Emphasis should be given to earlier identification and diagnosis of ASD.
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17. Tse AC, Yu C, Lee PH. {{Comparing sleep patterns between children with autism spectrum disorder and children with typical development: A matched case-control study}}. {Autism}. 2020: 1362361320936827.
This study compared the sleep pattern between children with autism spectrum disorders and children with typical development using a matched case-control design (matched age, gender, and body mass index). Significant differences were found in night-time sleep duration (total amount of sleep at night), sleep efficiency (percentage of time spent asleep), sleep-onset latency (length of time that it takes to transit from awake to asleep), and wake after sleep onset (total amount of time spent awake after defined sleep onset). Findings showed that children with autism spectrum disorder had poorer sleep quality than children with typical development. Mechanisms underlying the differences should be further explored in order to develop an effective treatment intervention.
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18. Villani C, Sacchetti G, Carli M, Invernizzi RW. {{Fluoxetine rescues rotarod motor deficits in Mecp2 heterozygous mouse model of rett syndrome via brain serotonin}}. {Neuropharmacology}. 2020: 108221.
Motor skill is a specific area of disability of Rett syndrome (RTT), a rare disorder occurring almost exclusively in girls, caused by loss-of-function mutations of the X-linked methyl-CpG-binding protein2 (MECP2) gene, encoding the MECP2 protein, a member of the methyl-CpG-binding domain nuclear proteins family. Brain 5-HT, which is defective in RTT patients and Mecp2 mutant mice, regulates motor circuits and SSRIs enhance motor skill learning and plasticity. In the present study, we used heterozygous (Het) Mecp2 female and Mecp2-null male mice to investigate whether fluoxetine, a SSRI with pleiotropic effects on neuronal circuits, rescues motor coordination deficits. Repeated administration of 10 mg/kg fluoxetine fully rescued rotarod deficit in Mecp2 Het mice regardless of age, route of administration or pre-training to rotarod. The motor improvement was confirmed in the beam walking test while no effect was observed in the hanging-wire test, suggesting a preferential action of fluoxetine on motor coordination. Citalopram mimicked the effects of fluoxetine, while the inhibition of 5-HT synthesis abolished the fluoxetine-induced improvement of motor coordination. Mecp2 null mice, which responded poorly to fluoxetine in the rotarod, showed reduced 5-HT synthesis in the prefrontal cortex, hippocampus and striatum, and reduced efficacy of fluoxetine in raising extracellular 5-HT as compared to female mutants. No sex differences were observed in the ability of fluoxetine to desensitize 5-HT(1A) autoreceptors upon repeated administration. These findings indicate that fluoxetine rescues motor coordination in Mecp2 Het mice through its ability to enhance brain 5-HT and suggest that drugs enhancing 5-HT neurotransmission may have beneficial effects on motor symptoms of RTT.
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19. Wallis KE, Guthrie W. {{Identifying Autism Spectrum Disorder in Real-World Health Care Settings}}. {Pediatrics}. 2020.
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20. Wink LK, Reisinger DL, Horn P, Shaffer RC, O’Brien K, Schmitt L, Dominick KR, Pedapati EV, Erickson CA. {{Brief Report: Intranasal Ketamine in Adolescents and Young Adults with Autism Spectrum Disorder-Initial Results of a Randomized, Controlled, Crossover, Pilot Study}}. {J Autism Dev Disord}. 2020.
Dysregulation of glutamate neurotransmission plays a critical role in autism spectrum disorder (ASD) pathophysiology and is a primary target for core deficit research treatment trials. The mechanism of action of ketamine has striking overlap with the theory of ASD as a disorder of synaptic communication and neuronal networks. This two-dose, double-blind, placebo controlled, cross-over pilot trial of intranasal (IN) ketamine targeting core social impairment included individuals with ASD (N = 21) between 14 and 29 years. Participants were randomized to received two doses of IN ketamine (30 and 50 mg) and two doses of matching placebo. No significant impact was noted on the Aberrant Behavior Checklist Social Withdraw subscale. The IN ketamine was well tolerated, with only transient mild adverse effects.
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21. Yu R, Wu Z, Wang S, Zhang M, Zhou G, Li B. {{Isolation, identification and characterization of propionic acid bacteria associated with autistic spectrum disorder}}. {Microbial pathogenesis}. 2020: 104371.
Autism spectrum disorder (ASD) seriously affects children’s health. Recently, propionic acid (PA) has been reported to play a significant role in the formation of ASD. In this study, we investigated the community structure of PA-related bacteria in healthy and ASD children by isolation and culture, while a group of representative PA-related bacteria were identified and characterized based on colony morphological observation, physiological and biochemical tests, as well as living/dead cells staining analysis and 16S rRNA gene sequencing. The results showed that the number of PA-related bacteria in healthy children was >100-fold higher than that in ASD children, while compared to healthy children, greater diversity was found in PA-associated bacteria from ASD children. The sensitivity of the representative strains to PA was affected by bacterial species, PA concentration and incubation time. The decrease of pH value was found in PA-resistant Lactobacillus plantarum strain 6-1 but not in PA-sensitive Enterococcus lactis strain 4-1, while biofilm formation of both strains were unaffected by PA. Furthermore, PA inhibited the propagation of the two selected bacteria rather than killed them, while the greater inhibitory effect was observed on strain 4-1. Overall, the result is of great significance for revealing the role of PA-related bacteria in development of ASD.
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22. Yui K, Imataka G, Sasaki H, Shiroki R. {{The role of lipid peroxidation in individuals with autism spectrum disorders}}. {Metabolic brain disease}. 2020.
The role of malondialdehyde-modified low-density lipoprotein (MDA-LDL), an oxidized LDL, in the pathophysiology of autism spectrum disorder (ASD) is unclear. We studied association between MDA-LDL and behavioral symptoms in 11 individuals with ASD and 7 age -matched normal controls. Behavioral symptoms were assessed using the Aberrant Behavior Checklists (ABC). Because small sample size in this study, three measures were conducted: first, employment of adaptive Lasso for enhancing the accuracy of prediction and interpretability; second, calculation of coefficient of variation for an appropriate selection of plasma variables; and third, selection of good candidates of plasma variables. Plasma levels of MDA-LDL, eicosapentaenoic acid, docosahexaenoic acid (DHA) and DHA/arachidonic acid ratios were significantly higher, while plasma superoxide dismutase (SOD) levels were significantly lower in the ASD group than in the control group. The total ABC scores were significantly higher in the ASD group than in the control group. Multiple linear regression analysis and the adaptive Lasso revealed association of increased plasma DHA levels with the ABC total scores and increased plasma MDA-LDL levels. Such association between DHA and plasma MDA-LDL levels may contribute to behavior in individuals with ASD.
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23. Zafarullah M, Tang HT, Durbin-Johnson B, Fourie E, Hessl D, Rivera SM, Tassone F. {{FMR1 locus isoforms: potential biomarker candidates in fragile X-associated tremor/ataxia syndrome (FXTAS)}}. {Sci Rep}. 2020; 10(1): 11099.
Fragile X associated tremor/ataxia syndrome (FXTAS) is a late adult-onset neurodegenerative disorder that affects movement and cognition in male and female carriers of a premutation allele of 55-200 CGG repeats in the Fragile X mental retardation (FMR1) gene. It is currently unknown if and when an individual carrier of a premutation allele will develop FXTAS, as clinical assessment fails to identify carriers at risk before significant neurological symptoms are evident. The primary objective of this study was to investigate the alternative splicing landscape at the FMR1 locus in conjunction with brain measures in male individuals with a premutation allele enrolled in a very first longitudinal study, compared to age-matched healthy male controls, with the purpose of identifying biomarkers for early diagnosis, disease prediction and, a progression of FXTAS. Our findings indicate that increased expression of FMR1 mRNA isoforms, including Iso4/4b, Iso10/10b, as well as of the ASFMR1 mRNAs Iso131bp, are present in premutation carriers as compared to non-carrier healthy controls. More specifically, we observed a higher expression of Iso4/4b and Iso10/10b, which encode for truncated proteins, only in those premutation carriers who developed symptoms of FXTAS over time as compared to non-carrier healthy controls, suggesting a potential role in the development of the disorder. In addition, we found a significant association of these molecular changes with various measurements of brain morphology, including the middle cerebellar peduncle (MCP), superior cerebellar peduncle (SCP), pons, and midbrain, indicating their potential contribution to the pathogenesis of FXTAS. Interestingly, the high expression levels of Iso4/4b observed both at visit 1 and visit 2 and found to be associated with a decrease in mean MCP width only in those individuals who developed FXTAS over time, suggests their role as potential biomarkers for early diagnosis of FXTAS.
