1. Baker SM, Pizzorno J. {{Autism Spectrum Disorder as a Model for Thinking Differently About Patients With Complex Disease}}. {Integrative medicine (Encinitas, Calif)}. 2018; 17(4): 8-15.
The rising prevalence of chronic diseases, complex diseases, unknown etiologies, and comorbidities have made efforts to practice curative medicine ever-more difficult to achieve. Autism spectrum disorder illustrates this challenge well as procedures, protocols, and algorithms that were successful in the past are no longer effective. The time has come for our health care system to fundamentally rethink how we assess and care for patients. In this editorial, we present a powerful, patient-centered, data-driven approach.
2. Bolognani F, Del Valle Rubido M, Squassante L, Wandel C, Derks M, Murtagh L, Sevigny J, Khwaja O, Umbricht D, Fontoura P. {{A phase 2 clinical trial of a vasopressin V1a receptor antagonist shows improved adaptive behaviors in men with autism spectrum disorder}}. {Science translational medicine}. 2019.
There are no approved pharmacological therapies to address the core symptoms of autism spectrum disorder (ASD), namely, persistent deficits in social communication and social interaction and the presence of restricted, repetitive patterns of behaviors, interests, or activities. The neuropeptide vasopressin has been implicated in the regulation of social behaviors, and its modulation has emerged as a therapeutic target for ASD. The phase 2 VANILLA clinical trial reported here evaluated balovaptan, an orally administered selective vasopressin V1a receptor antagonist, in 223 men with ASD and intelligence quotient >/=70. The drug was administered daily for 12 weeks and was compared with placebo. Participants were randomized to placebo (n = 75) or one of three balovaptan dose arms (1.5 mg, n = 32; 4 mg, n = 77; 10 mg, n = 39). Balovaptan treatment was not associated with a change from baseline compared with placebo at 12 weeks in the primary efficacy endpoint (Social Responsiveness Scale, 2nd Edition). However, dose-dependent and clinically meaningful improvements on the Vineland-II Adaptive Behavior Scales composite score were observed for participants treated with balovaptan 4 or 10 mg compared with placebo. This was driven principally by improvements in the Vineland-II socialization and communication scores. Balovaptan was well tolerated across all doses, and no drug-related safety concerns were identified. These results support further study of balovaptan as a potential treatment for the socialization and communication deficits in ASD.
Lien vers le texte intégral (Open Access ou abonnement)
3. Bos DJ, Silverman MR, Ajodan EL, Martin C, Silver BM, Brouwer GJ, Di Martino A, Jones RM. {{Rigidity coincides with reduced cognitive control to affective cues in children with autism}}. {Journal of abnormal psychology}. 2019.
The present study tested whether salient affective cues would negatively influence cognitive control in children with and without autism spectrum disorder (ASD). One hundred children aged 6-12 years who were either typically developing or had ASD performed a novel go/no-go task to cues of their interest versus cues of noninterest. Linear mixed-effects (LME) models for hit rate, false alarms, and the sensitivity index d’ were used to test for group differences. Caregivers completed the Repetitive Behavior Scale-Revised to test associations between repetitive behaviors and task performance. Children with ASD had reduced cognitive control toward their interests compared with typically developing children. Further, children with ASD showed reduced cognitive control to interests compared with noninterests, a pattern not observed in typically developing children. Decreased cognitive control toward interests was associated with higher insistence on sameness behavior in ASD, but there was no association between sameness behavior and cognitive control for noninterests. Together, children with ASD demonstrated decreased cognitive flexibility in the context of increased affective salience related to interests. These results provide a mechanism for how salient affective cues, such as interests, interfere with daily functioning and social communication in ASD. Further, the findings have broader clinical implications for understanding how affective cues can drive interactions between restricted patterns of behavior and cognitive control. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
Lien vers le texte intégral (Open Access ou abonnement)
4. Cloete LG, Obaigwa EO. {{Lived experiences of caregivers of children with autism spectrum disorder in Kenya}}. {African journal of disability}. 2019; 8: 435.
Background: Autism spectrum disorder (ASD) is a global public health concern. In African countries such as Kenya, there is a greater need for establishing support services for developmental disorders such as ASD. The emotional, social and economic burden of ASD on caregivers is unknown because of a number of challenges. Citizens of Kenya have a unique view of disability and inclusion. Objectives: To explore the perspectives of caregivers who are responsible for caring for both family and children living with ASD and to highlight the needs of children with ASD as well as the needs of their caregivers. Method: A qualitative, descriptive phenomenological study utilising focus group discussions (FGDs) was conducted. Verbatim transcription was used. QSR N ‘Vivo 10 was used to organise and analyse the data. Content analysis was used to identify important ideas and concepts. Results: One theme, namely ‘the burden of caring for children with ASD’, was identified. Children with ASD and their caregivers experience isolation and stigmatisation. Conclusion: Occupational therapists in Kenya should collaborate with the relevant national and global stakeholders for the promotion of the inclusion of children with ASD and their families. Responsive and context-appropriate occupational therapy interventions may begin to address service barriers. Keywords: autism spectrum disorder; children; needs of caregivers; context-appropriate services.
Lien vers le texte intégral (Open Access ou abonnement)
5. Edmunds SR, Kover ST, Stone WL. {{The relation between parent verbal responsiveness and child communication in young children with or at risk for autism spectrum disorder: A systematic review and meta-analysis}}. {Autism Res}. 2019; 12(5): 715-31.
Among preschool-age children with autism spectrum disorder (ASD) and typically developing children, parents’ verbal responsiveness (PVR) has long been shown to predict children’s later language ability. However, before the age of three, when language develops most rapidly, the early social communication deficits associated with ASD may impact parents’ opportunities to facilitate early language development. The aim of this review was to characterize the relation between PVR and the vocal communication ability of children with or at high risk for ASD early in development. Specifically, we examined whether the relation between PVR and child communication varied by type of PVR and by child diagnostic status, as well as whether interventions increased PVR. A systematic multi-database search yielded 25 empirical studies (804 parent-toddler dyads; 30 effect sizes) that met inclusion criteria and related a variable of PVR to a variable of child vocalization or language. Meta-regression analyses revealed that the relation between PVR and child communication was significant regardless of PVR type or child diagnostic status. To date, interventions targeting both PVR and child communication were found to significantly increase PVR, but not child communication, for these populations. Future research should examine parent-child communication in a transactional, longitudinal manner. In addition, these findings have implications for interventions designed to target parents’ responsiveness and child communication. Autism Research 2019, 12: 715-731. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: For families with children under 3 years old who are at risk for or diagnosed with ASD, this study revealed empirical evidence of a robust relation between parents » verbal responsiveness to their children’s play and communication and children’s communication ability. This relation is similar to that reported in research on typically developing children. Interventions designed to improve parent-child interaction in children with or at risk for ASD may be effective in increasing parents’ responsiveness.
Lien vers le texte intégral (Open Access ou abonnement)
6. Fan X. {{Citalopram attenuates social behavior deficits in the BTBR T(+)Itpr3(tf)/J mouse model of autism}}. {Brain Res Bull}. 2019.
Autism spectrum disorder (ASD) is diagnosed by two core symptoms: impaired social communication and the presence of repetitive, stereotyped behaviors and/or restricted interests. Alterations in serotonergic signaling are involved in the genesis of ASD. Selective serotonin reuptake inhibitors (SSRIs) have been reported to reduce repetitive behaviors and rescue social deficits in ASD mouse models and patients. In the present study, we examined the potential of citalopram (a representative selective serotonin reuptake inhibitor) on sociability and repetitive behaviors in the BTBR T(+)Itpr3(tf)/J (BTBR) mouse model of ASD. We found that the deficits of sociability in the BTBR mice were reversed by a 20 mg/kg dose of citalopram treatment without any adverse effects on locomotor activity or anxiety level. In addition, both high (20 mg/kg) and low (10 mg/kg) doses decreased the repetitive behavior of marble burying but did not affect self-grooming behavior. Furthermore, both doses were shown to have antidepressant-like activity in both the B6 and the BTBR mice in the tail suspension test. Taken together, these findings further demonstrate that citalopram can rescue behavioral abnormalities in the BTBR autism model and lend support to the hypothesis that SSRIs may be potential therapeutic drugs for the treatment of behavioral dysfunctions in ASD.
Lien vers le texte intégral (Open Access ou abonnement)
7. Frullanti E, Papa FT, Grillo E, Clarke A, Ben-Zeev B, Pineda M, Bahi-Buisson N, Bienvenu T, Armstrong J, Roche Martinez A, Mari F, Nissenkorn A, Lo Rizzo C, Veneselli E, Russo S, Vignoli A, Pini G, Djuric M, Bisgaard AM, Ravn K, Bosnjak VM, Hayek J, Khajuria R, Montomoli B, Cogliati F, Pintaudi M, Hadzsiev K, Craiu D, Voinova V, Djukic A, Villard L, Renieri A. {{Analysis of the Phenotypes in the Rett Networked Database}}. {International journal of genomics}. 2019; 2019: 6956934.
Rett spectrum disorder is a progressive neurological disease and the most common genetic cause of intellectual disability in females. MECP2 is the major causative gene. In addition, CDKL5 and FOXG1 mutations have been reported in Rett patients, especially with the atypical presentation. Each gene and different mutations within each gene contribute to variability in clinical presentation, and several groups worldwide performed genotype-phenotype correlation studies using cohorts of patients with classic and atypical forms of Rett spectrum disorder. The Rett Networked Database is a unified registry of clinical and molecular data of Rett patients, and it is currently one of the largest Rett registries worldwide with several hundred records provided by Rett expert clinicians from 13 countries. Collected data revealed that the majority of MECP2-mutated patients present with the classic form, the majority of CDKL5-mutated patients with the early-onset seizure variant, and the majority of FOXG1-mutated patients with the congenital form. A computation of severity scores further revealed significant differences between groups of patients and correlation with mutation types. The highly detailed phenotypic information contained in the Rett Networked Database allows the grouping of patients presenting specific clinical and genetic characteristics for studies by the Rett community and beyond. These data will also serve for the development of clinical trials involving homogeneous groups of patients.
Lien vers le texte intégral (Open Access ou abonnement)
8. Ghanouni P, Jarus T, Zwicker JG, Lucyshyn J, Chauhan S, Moir C. {{Perceived Barriers and Existing Challenges in Participation of Children with Autism Spectrum Disorders: « He Did Not Understand and No One Else Seemed to Understand Him »}}. {J Autism Dev Disord}. 2019.
Social participation is one of the most important predictors of the children’s physical and mental health. Although it is evidenced that children with autism spectrum disorder (ASD) have restricted social participation, it is unclear which factors play a significant role. This research aimed to uncover perceived barriers of social participation by involving 26 stakeholders including parents of children with ASD, youth with ASD, and clinicians working with individuals with ASD in focus groups and interviews. Using thematic analysis yielded three themes including (a) difficulty understanding social situations; (b) maladaptive behaviours; and (c) conflicting priorities and restricted nature of training. This project was the first study to involve key stakeholders to highlight barriers of social participation among individuals with ASD.
Lien vers le texte intégral (Open Access ou abonnement)
9. Giachetto G, Casuriaga AL, Santoro A, Kanopa V, Garrido G, Fernandez J, Cohen H, Sohl K. {{Extension for Community Healthcare Outcomes Uruguay: A New Strategy to Promote Best Primary Care Practice for Autism}}. {Global pediatric health}. 2019; 6: 2333794×19833734.
Introduction. In Uruguay, the special care required for children with neurodevelopmental disorders presents difficulties including lack of access to specialists and rehabilitation services. Project ECHO (Extension for Community Healthcare Outcomes) connects primary care clinicians from remote areas to specialists to enable them to treat complex conditions through ongoing education and mentoring. Objective. To share the experience of the ECHO Autism program during the first 2 years of implementation. Methods. Analysis of ECHO Autism clinics from June 2015 to June 2017 including clinical cases presented participants’ self-perception of changes in skills and competences. Results. Twenty clinical cases were presented: mean age 4.5 years; 15 were males; and 17 with medical and psychiatric comorbidities. After ECHO Autism implementation, a statistically significant improvement in participants’ self-perception of skills and competences was observed. Conclusions. ECHO Autism in Uruguay is a meaningful approach to autism care and offers improved access to best practice care.
Lien vers le texte intégral (Open Access ou abonnement)
10. Heinicke MR, Carr JE, Copsey CJ. {{Assessing preferences of individuals with developmental disabilities using alternative stimulus modalities: A systematic review}}. {Journal of applied behavior analysis}. 2019.
The purpose of this systematic review was to identify investigations comparing the efficacy of alternative modality (e.g., pictorial, verbal, video) stimulus preference assessments for individuals with developmental disabilities. We identified articles by searching peer-reviewed journals using the PsycINFO and ERIC databases, conducting table of contents searches of common behavioral outlets, and conducting ancestral searches of recent reviews and practitioner summaries of preference assessment methodology. A total of 32 articles met our inclusion criteria. These studies were then coded across a variety of features to gain a better understanding of the efficacy of alternative format preference assessments for individuals with developmental disabilities. In addition, we reviewed this literature for the use of prerequisite-skill assessments and contingent-reinforcer access to further investigate the relation between these variables and the accuracy of pictorial, verbal, and video preference assessments. A variety of methodological concerns are discussed as well as suggestions for future research.
Lien vers le texte intégral (Open Access ou abonnement)
11. Kiely B, Vettam S, Adesman A. {{Correlates of genetic attributions among parents of children in the USA with developmental disabilities}}. {The application of clinical genetics}. 2019; 12: 55-61.
Introduction: As technologies for identifying causal genetic variants in children with autism spectrum disorders (ASD) and other developmental conditions continue to advance, there is a need to understand the factors that influence parental beliefs about the causes of their child’s disabilities. This study assessed the correlates of etiologic attributions among US parents of children with ASD, intellectual disability (ID), and/or developmental delay (DD). Methods: Data were obtained from the Centers for Disease Control and Prevention’s nationally representative Survey of Pathways to Diagnosis and Services. Respondents were classified according to whether their child had ASD without ID or DD (ASD-only), ASD with ID and/or DD (ASD+ID/DD), or ID and/or DD without ASD (ID/DD-only). Respondents rated the extent to which they believed that genetics/heredity and environmental exposures (prenatal and/or postnatal) had contributed to their child’s condition. Logistic regression analyses and chi-square tests were used to assess the relationship between parental beliefs and child characteristics. Results: The parents of children with comorbid ASD and ID/DD were found to be significantly less likely than those in the other condition groups to attribute their child’s condition to genetics. Within the ASD+ID/DD group, parental endorsement of genetics was lower among those who reported a history of language regression (p=0.006). Conclusion: Further research is needed to evaluate the impact of parental genetic attributions on medical decision-making.
Lien vers le texte intégral (Open Access ou abonnement)
12. Kobliner V, Mumper E, Baker SM. {{Reduction in Obsessive Compulsive Disorder and Self-Injurious Behavior With Saccharomyces boulardii in a Child with Autism: A Case Report}}. {Integrative medicine (Encinitas, Calif)}. 2018; 17(6): 38-41.
This case report describes the effective use of Saccharomyces boulardii in a boy with autism spectrum disorder, obsessive compulsive disorder (OCD), and self-injurious behavior (SIB). Gastrointestinal dysfunction and OCD are frequent comorbidities in autism, which may share a common etiology resulting from a disturbance in normal gut microbiota. Alterations in microbial diversity influence neuroinflammation and are linked to mood disorders, abdominal pain, and SIB. S boulardii is a nonpathogenic probiotic yeast that supports a healthy microbiome, enhances immune function, and reduces diarrhea. Treatment with S boulardii successfully reduced OCD and SIB symptoms in this child.
13. Lee EAL, Black MH, Tan T, Falkmer T, Girdler S. {{« I’m Destined to Ace This »: Work Experience Placement During High School for Individuals with Autism Spectrum Disorder}}. {J Autism Dev Disord}. 2019.
As postsecondary outcomes of adolescents with Autism Spectrum Disorder (ASD) are poor, there is a need for programs that aim to improve employment and education outcomes. This study employed a grounded theory approach to explore the key factors contributing to successful work placement experience and the perceived benefits of these placements from the perspective of adolescents with ASD (n = 5), their parents (n = 6) and employers (n = 6). Key factors contributing to success include preparing for the workplace, harnessing strengths and interests and developing work related skills, while the benefits include insight into the workplace, recognising and realising potential, working as a team and the pathway ahead. The findings articulate a framework which could underpin future transition interventions for adolescents with ASD.
Lien vers le texte intégral (Open Access ou abonnement)
14. Luo X, Li C, Wang X, Yu X, Jiang J. {{Tapping-lips aggravated interictal bilateral discharges in EEG in the patients with Rett syndrome: a case report}}. {BMC neurology}. 2019; 19(1): 77.
BACKGROUND: Rett syndrome (RTT) is a severe neurodevelopmental disorder mainly affecting females. One of the main clinical manifestations is hand stereotypies, which is presumed to based on dysfunction rather than on structural impairment. Reflex interictal discharge precipitated by tapping-lips in electroencephalogram (EEG) is a rare phenomenon among RTT. CASE PRESENTATION: We firstly reported a case of RTT concerning interictal reflex discharge precipitated by tapping- lips. The child, female, 5 years old, presented with a significant regression in motor development and language skills. She almost always tapped the lips with the right hand and stopped only when was interrupted. Her EEG results displayed extensive low amplitude fast wave could be elicited by lightly and slowly- rhythm tapping lips and multifocal bilateral discharges could be precipitated by relatively stronger and quicker rhythm action. It was when the movement stopped that corresponding discharges immediately disappeared. Besides, the reflex discharges were not precipitated by tapping- lips using observer’s hand at the certain tempo and intensity. The hand stereotypies did not respond to antiepileptic drugs. CONCLUSIONS: Tapping- lips may be a somatosensory stimulation to precipitate interictal discharges in RTT, which may provide another idea to enrich the insight on hand stereotypies of RTT.
Lien vers le texte intégral (Open Access ou abonnement)
15. Mohamadkhani A. {{Gut Microbiota and Fecal Metabolome Perturbation in Children with Autism Spectrum Disorder}}. {Middle East journal of digestive diseases}. 2018; 10(4): 205-12.
The brain-intestinal axis concept describes the communication between the intestinal microbiota as an ecosystem of a number of dynamic microorganisms and the brain. The composition of the microbial community of the human gut is important for human health by influencing the total metabolomic profile. In children with autism spectrum disorder (ASD), the composition of the fecal microbiota and their metabolic products has a different configuration of the healthy child. An imbalance in the metabolite derived from the microbiota in children with ASD affect brain development and social behavior. In this article, we review recent discoveries about intestinal metabolites derived from microbiota based on high-yield molecular studies in children with ASD as part of the « intestinal brain axis ».
Lien vers le texte intégral (Open Access ou abonnement)
16. Parker KJ, Oztan O, Libove RA, Mohsin N, Karhson DS, Sumiyoshi RD, Summers JE, Hinman KE, Motonaga KS, Phillips JM, Carson DS, Fung LK, Garner JP, Hardan AY. {{A randomized placebo-controlled pilot trial shows that intranasal vasopressin improves social deficits in children with autism}}. {Science translational medicine}. 2019.
The social impairments of autism spectrum disorder (ASD) have a major impact on quality of life, yet there are no medications that effectively treat these core social behavior deficits. Preclinical research suggests that arginine vasopressin (AVP), a neuropeptide involved in promoting mammalian social behaviors, may be a possible treatment for ASD. Using a double-blind, randomized, placebo-controlled, parallel study design, we tested the efficacy and tolerability of a 4-week intranasal AVP daily treatment in 30 children with ASD. AVP-treated participants aged 6 to 9.5 years received the maximum daily target dose of 24 International Units (IU); participants aged 9.6 to 12.9 years received the maximum daily target dose of 32 IU. Intranasal AVP treatment compared to placebo enhanced social abilities as assessed by change from baseline in this phase 2 trial’s primary outcome measure, the Social Responsiveness Scale, 2nd Edition total score (SRS-2 T score; F 1,20 = 9.853; P = 0.0052; etap (2) = 33.0%; Cohen’s d = 1.40). AVP treatment also diminished anxiety symptoms and some repetitive behaviors. Most of these findings were more pronounced when we accounted for pretreatment AVP concentrations in blood. AVP was well tolerated with minimal side effects. No AVP-treated participants dropped out of the trial, and there were no differences in the rate of adverse events reported between treatment conditions. Last, no changes from baseline were observed in vital signs, electrocardiogram tracings, height and body weight, or clinical chemistry measurements after 4 weeks of AVP treatment. These preliminary findings suggest that AVP has potential for treating social impairments in children with ASD.
Lien vers le texte intégral (Open Access ou abonnement)
17. Rodocanachi Roidi ML, Isaias IU, Cozzi F, Grange F, Scotti FM, Gestra VF, Gandini A, Ripamonti E. {{A New Scale to Evaluate Motor Function in Rett Syndrome: Validation and Psychometric Properties}}. {Pediatric neurology}. 2019.
BACKGROUND: We aim to describe and psychometrically validate the Rett Syndrome Motor Evaluation Scale, a 25-item ordinal scale examining (loco-)motor function across six sections: standing, sitting, transitions, walking, running, and walking up or downstairs. METHODS: We illustrate the process of item construction and validation, report findings and normative data obtained on a standardization sample of 60 patients with Rett syndrome. We investigate the validity and reliability of the scale and illustrate its psychometric properties using modern multivariate techniques of data analysis. RESULTS: Sixty patients with Rett syndrome were included (all female; mean age 12.45 (S.D. 8.75) years). The multidimensional latent structure of the scale was supported by the results of the confirmatory factor analysis. Rett Syndrome Motor Evaluation Scale showed strong internal consistency reliability as well as excellent inter-rater agreement. The Rett Syndrome Motor Evaluation Scale scores were not predicted by age, but were associated with disease severity, degree of spasticity, and hand dysfunction. We also identified three latent classes with different degrees of impairment. CONCLUSIONS: Rett Syndrome Motor Evaluation Scale is a new, valid, and reliable scale that can be introduced in clinical practice when assessing (loco-)motor function in Rett syndrome.
Lien vers le texte intégral (Open Access ou abonnement)
18. Rosenbaum P. {{Diagnosis in developmental disability: a perennial challenge, and a proposed middle ground}}. {Dev Med Child Neurol}. 2019; 61(6): 620.
Lien vers le texte intégral (Open Access ou abonnement)
19. Sadek A, Berk LS, Mainess K, Daher NS. {{A Pilot Study: Parent Perceptions of Behavior Change in Their Child With Autism Spectrum Disorder Following High Antioxidant Cacao Consumption}}. {Integrative medicine (Encinitas, Calif)}. 2018; 17(5): 31-8.
Background: Autism spectrum disorder (ASD) is a heterogeneous neurocognitive disorder with primary symptomology related to maladaptive behaviors and communication deficits. Children with ASD tend to have higher free radicals than antioxidants compared with their matched controls. This disequilibrium of oxidative stress has been associated with the pathogenesis of this neurocognitive disorder. The aim of this pilot feasibility study was to examine the effect of high antioxidant cacao consumption on behavior in children with ASD. Methods: This was a 4-wk repeated measures experimental pilot study of high antioxidant cacao and children with ASD. Participants consumed 8 squares (or 16 g) per day of the dark chocolate that had a concentration of 70% cacao and 30% organic cane sugar (total antioxidant activity was 8320 mumoles TE/100 g). The 2 main behavioral measures, Aberrant Behavior Checklist, 2nd ed (ABC-2) and the Autism Spectrum Rating Scale (ASRS), were completed by the child’s parent at baseline, end of week 2, and end of week 4. Results: Seventeen participants were recruited for this study. Follow-up data were available for 16 participants (12 males, 4 females, aged 4 to 17 y). Significant improvements were noted on the ABC-2 subscales of irritability (P = .03, eta(2)= 0.25), social withdrawal (P = .01, eta(2)= 0.29), stereotypic behavior (P = .05, eta(2) = 0.13), hyperactivity/noncompliance (P = .04, eta(2) = 0.20), and inappropriate speech (P = .05, eta(2) = 0.16). Significant improvements were noted on the ASRS subscales of social/communication (P = .04, eta(2) = 0.25), unusual behaviors (P = .003, eta(2)= 0.20), self-regulation (P = .02, eta(2)= 0.32), and total scores (P < .001, eta(2)= 0.54). Conclusion: Results from this study support previous literature on antioxidant intake as an adjunct therapy to improve behaviors of children with ASD. More robust randomized controlled trials are now necessary to validate and elaborate on these findings. Lien vers Pubmed
20. Viljoen M, Mahdi S, Griessel D, Bolte S, de Vries PJ. {{Parent/caregiver perspectives of functioning in autism spectrum disorders: A comparative study in Sweden and South Africa}}. {Autism}. 2019: 1362361319829868.
Functional outcomes in autism spectrum disorder can be highly variable given the heterogeneous nature of autism spectrum disorder and its interaction with environmental factors. We set out to compare parent/caregiver perceptions of functioning in two divergent countries that participated in the International Classification of Functioning Disability and Health (ICF) Core Set for Autism Spectrum Disorder development study. We focused on the frequency and content of items reported, and hypothesized that environmental factors would most frequently be reported as barriers to functioning in low-resource settings. Using frequency and qualitative content analysis, we compared data from South Africa ( n = 22) and Sweden ( n = 13). Frequency agreement was seen in three activities and participation categories, and one environmental factor. Obvious frequency differences were observed in one environmental factors category, six body functions categories and three activities and participation categories. Only three ICF categories (immediate family, attention functions, products and technology for personal use) differed in content. Contrary to our hypotheses, few differences in perspectives about environmental factors emerged. The universality of our findings supports the global usefulness of the recently developed ICF Core Sets for Autism Spectrum Disorder. We recommend that more comparative studies on autism spectrum disorder and functioning should be conducted, and that similar comparisons in other disorders where Core Sets have been developed may be valuable.
Lien vers le texte intégral (Open Access ou abonnement)
21. Wang C, Pan YH, Wang Y, Blatt G, Yuan XB. {{Segregated expressions of autism risk genes Cdh11 and Cdh9 in autism-relevant regions of developing cerebellum}}. {Molecular brain}. 2019; 12(1): 40.
Results of recent genome-wide association studies (GWAS) and whole genome sequencing (WGS) highlighted type II cadherins as risk genes for autism spectrum disorders (ASD). To determine whether these cadherins may be linked to the morphogenesis of ASD-relevant brain regions, in situ hybridization (ISH) experiments were carried out to examine the mRNA expression profiles of two ASD-associated cadherins, Cdh9 and Cdh11, in the developing cerebellum. During the first postnatal week, both Cdh9 and Cdh11 were expressed at high levels in segregated sub-populations of Purkinje cells in the cerebellum, and the expression of both genes was declined as development proceeded. Developmental expression of Cdh11 was largely confined to dorsal lobules (lobules VI/VII) of the vermis as well as the lateral hemisphere area equivalent to the Crus I and Crus II areas in human brains, areas known to mediate high order cognitive functions in adults. Moreover, in lobules VI/VII of the vermis, Cdh9 and Cdh11 were expressed in a complementary pattern with the Cdh11-expressing areas flanked by Cdh9-expressing areas. Interestingly, the high level of Cdh11 expression in the central domain of lobules VI/VII was correlated with a low level of expression of the Purkinje cell marker calbindin, coinciding with a delayed maturation of Purkinje cells in the same area. These findings suggest that these two ASD-associated cadherins may exert distinct but coordinated functions to regulate the wiring of ASD-relevant circuits in the cerebellum.
Lien vers le texte intégral (Open Access ou abonnement)
22. Yamasue H, Aran A, Berry-Kravis E. {{Emerging pharmacological therapies in fragile X syndrome and autism}}. {Current opinion in neurology}. 2019.
PURPOSE OF REVIEW: Research on the pathophysiology of syndromic autism spectrum disorder (ASD) has contributed to the uncovering of mechanisms in nonsyndromic ASD. The current review aims to compare recent progress in therapeutics development for ASD with those for fragile X syndrome (FXS), the most frequent monogenic form of ASD. RECENT FINDINGS: Although candidates such as oxytocin, vasopressin, and cannabinoids are being tested as novel therapeutics, it remains difficult to focus on a specific molecular target of drug development for ASD core symptoms. As the pathophysiology of FXS has been well described as having a causal gene, fragile X mental retardation-1, development of therapeutic agents for FXS is focused on specific molecular targets, such as metabotropic glutamate receptor 5 and GABAB receptor. SUMMARY: There is a large unmet medical need in ASD, a heterogeneous and clinically defined behavioral syndrome, owing to its high prevalence in the general population, lifelong cognitive and behavioral deficits, and no established treatment of ASD core symptoms, such as deficits in social communication and restrictive repetitive behaviors. The molecular pathogenesis of nonsyndromic ASD is largely undefined. Lessons from initial attempts at targeted treatment development in FXS, and new designs resulting from these lessons, will inform trials in nonsyndromic ASD for development of therapeutics for its core symptoms.
