1. Arnold LE, Ober N, Aman MG, Handen B, Smith T, Pan X, Hyman SL, Hollway J, Lecavalier L, Page K, Rice R, Jr. {{A 1.5-Year Follow-Up of Parent Training and Atomoxetine for Attention-Deficit/Hyperactivity Disorder Symptoms and Noncompliant/Disruptive Behavior in Autism}}. {J Child Adolesc Psychopharmacol};2018 (Apr 25)
OBJECTIVE: To examine status of children with autism spectrum disorder (ASD) 10 months after a 34-week clinical trial of atomoxetine (ATX) and parent training (PT). METHODS: In a 2 x 2 design, 128 children with ASD and attention-deficit/hyperactivity disorder (ADHD) were randomly assigned ATX, PT+placebo, PT+ATX, or placebo alone. PT was weekly for 10 weeks, and then monthly. ATX/placebo was titrated over 6 weeks [/=30% from baseline (67% did at week 34); on noncompliance, 56% improved >/=30% from baseline (77% did at week 34). Outcomes with PT were not significantly better than without PT (SNAP p = 0.30; HSQ p = 0.27). Originally assigned treatment groups did not differ significantly. Only 34% still took ATX; 27% were taking stimulants; and 25% took no medication. CONCLUSIONS: The majority retained their 34-week end-of-study improvement 10 months later, even though most participants stopped ATX. For some children, ATX continuation may not be necessary for continued benefit or other drugs may be necessary. Cautious individual clinical experimentation may be justified. Twelve sessions of PT made little long-term difference. ClinicalTrials.gov Identifier: Atomoxetine, Placebo and Parent Management Training in Autism (Strattera) (NCT00844753).
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2. Bjorklund G, Kern JK, Urbina MA, Saad K, El-Houfey AA, Geier DA, Chirumbolo S, Geier MR, Mehta JA, Aaseth J. {{Cerebral hypoperfusion in autism spectrum disorder}}. {Acta Neurobiol Exp (Wars)};2018;78(1):21-29.
Cerebral hypoperfusion, or insufficient blood flow in the brain, occurs in many areas of the brain in patients diagnosed with autism spectrum disorder (ASD). Hypoperfusion was demonstrated in the brains of individuals with ASD when compared to normal healthy control brains either using positron emission tomography (PET) or singlephoton emission computed tomography (SPECT). The affected areas include, but are not limited to the: prefrontal, frontal, temporal, occipital, and parietal cortices; thalami; basal ganglia; cingulate cortex; caudate nucleus; the limbic system including the hippocampal area; putamen; substantia nigra; cerebellum; and associative cortices. Moreover, correlations between symptom scores and hypoperfusion in the brains of individuals diagnosed with an ASD were found indicating that the greater the autism symptom pathology, the more significant the cerebral hypoperfusion or vascular pathology in the brain. Evidence suggests that brain inflammation and vascular inflammation may explain a part of the hypoperfusion. There is also evidence of a lack of normal compensatory increase in blood flow when the subjects are challenged with a task. Some studies propose treatments that can address the hypoperfusion found among individuals diagnosed with an ASD, bringing symptom relief to some extent. This review will explore the evidence that indicates cerebral hypoperfusion in ASD, as well as the possible etiological aspects, complications, and treatments.
3. Bryn V, Verkerk R, Skjeldal OH, Saugstad OD, Ormstad H. {{Kynurenine Pathway in Autism Spectrum Disorders in Children}}. {Neuropsychobiology};2018 (Apr 25):1-7.
BACKGROUND: There is increasing evidence that altered immune responses play a role in the pathogenesis of autism spectrum disorders (ASD), together with dysfunction of the serotonergic and glutamatergic systems. Since the kynurenine (KYN) pathway that degrades tryptophan (TRP) is activated in various neuroinflammatory states, we aimed to determine whether this pathway is activated in ASD. METHODS: Sixty-five pediatric ASD patients (including 52 boys) were enrolled from an epidemiological survey covering 2 counties in Norway; 30 (46.5%) of these patients were diagnosed with childhood autism, 16 (24.6%) with Asperger syndrome, 12 (18.5%) with atypical autism, 1 (1.5%) with Rett syndrome, and 6 (9.2%) with other ASD. The serum levels of the following markers were measured in the children with ASD and compared to those in 30 healthy children: TRP, KYN, kynurenic acid (KA), 3-hydroxykynurenine, and quinolinic acid. RESULTS: The mean serum level of KA was significantly lower in the ASD group than in the healthy controls (28.97 vs. 34.44 nM, p = 0.040), while the KYN/KA ratio was significantly higher in the ASD group (61.12 vs. 50.39, p = 0.006). The same relative values were found when comparing the childhood autism subgroup with the controls. Also, the mean serum level of TRP was significantly lower in children with a subdiagnosis of childhood autism than in those with Asperger syndrome (67.26 vs. 77.79 muM, p = 0.020). CONCLUSION: Our study indicates that there is an increased neurotoxic potential and also a possible lower KYN aminotransferase activity in ASD.
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4. Goel R, Hong JS, Findling RL, Ji NY. {{An update on pharmacotherapy of autism spectrum disorder in children and adolescents}}. {Int Rev Psychiatry};2018 (Apr 25):1-18.
To date, no medication is proven to be effective in treating core symptoms of autism spectrum disorder (ASD). Psychotropic medications are widely used to target emotional and behavioural symptoms in ASD. This article reviewed evidence for pharmacotherapy, novel therapeutic agents, and Complementary and Alternative Medicine (CAM) in children and adolescents with ASD. Currently, only risperidone and aripiprazole have been approved by the US Food and Drug Administration (FDA) for treatment of irritability associated with ASD in children and adolescents. However, associated metabolic side-effects are concerning. Evidence supports use of methylphenidate and atomoxetine for attention deficit hyperactivity disorder (ADHD) symptoms and clonidine and guanfacine ER appear to be helpful. SSRIs are poorly tolerated and lack evidence in reducing restricted repetitive behaviours (RRB), anxiety, and depression. Buspirone shows promise in the treatment of RRB. The evidence is inconsistent for the effectiveness of anti-epileptic medications. Recent studies of glutamatergic, Gamma-aminobutyric acid (GABA)ergic, and cholinergic agents and oxytocin show inconsistent results. Despite wide use of CAM agents, the evidence is inconclusive. Melatonin can be helpful in reducing sleep problems. Overall, the evidence is limited for pharmacotherapy in children with ASD, and side-effects with long-term use can be burdensome.
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5. Hall SS, Hustyi KM, Barnett RP. {{Examining the influence of social-environmental variables on self-injurious behaviour in adolescent boys with fragile X syndrome}}. {J Intellect Disabil Res};2018 (Apr 25)
BACKGROUND: Individuals with fragile X syndrome (FXS), the most common known inherited form of intellectual disability, are at increased risk for showing specific forms of self-injurious behaviour (SIB) such as hand biting and head hitting, suggesting that biological factors associated with the syndrome confers increased risk for SIB. Few studies, however, have examined the extent to which social-environmental variables can influence the occurrence of these behaviours in this population. METHOD: Twenty-two adolescent boys with FXS, aged 10 to 18 years were systematically exposed to seven environmental conditions in functional analyses of SIB conducted over 2 days at our research centre. RESULTS: Fourteen (63.6%) boys with FXS engaged in SIB during the functional analyses. Ten (45.5%) boys engaged in SIB that was maintained by social-environmental variables, that is, gaining access to attention/tangibles and/or escaping from social interaction, task demands and/or transition demands. For two boys, SIB was undifferentiated across conditions, and for two boys, SIB appeared to be maintained by automatic reinforcement. CONCLUSIONS: Social-environmental variables appeared to maintain SIB in a significant proportion of boys with FXS. Given that pharmacological treatments for SIB have limited efficacy in this population, the potential role of social-environmental factors on SIB should be examined before pharmacological treatments are implemented for these behaviours.
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6. Healy S, Nacario A, Braithwaite RE, Hopper C. {{The effect of physical activity interventions on youth with autism spectrum disorder: A meta-analysis}}. {Autism Res};2018 (Apr 25)
The purpose of this meta-analysis was to examine the effect of physical activity interventions on youth diagnosed with autism spectrum disorder. Standard meta-analytical procedures determining inclusion criteria, literature searches in electronic databases, coding procedures, and statistical methods were used to identify and synthesize articles retained for analysis. Hedge’s g (1988) was utilized to interpret effect sizes and quantify research findings. Moderator and outcome variables were assessed using coding procedures. A total of 29 studies with 30 independent samples (N = 1009) were utilized in this analysis. Results from meta-analyses indicated an overall moderate effect (g = 0.62). Several outcomes indicated moderate-to-large effects (g >/= 0.5); specifically, moderate to large positive effects were revealed for participants exposed to interventions targeting the development of manipulative skills, locomotor skills, skill-related fitness, social functioning, and muscular strength and endurance. Moderator analyses were conducted to explain variance between groups; environment was the only subgrouping variable (intervention characteristics) to produce a significant difference (QB = 5.67, P < 0.05) between moderators. While no significant differences were found between other moderators, several trends were apparent within groups in which experimental groups outperformed control groups. Autism Res 2018, 0: 000-000. (c) 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Results of the meta-analysis-a method for synthesizing research-showed physical activity interventions to have a moderate or large effect on a variety of outcomes, including for the development of manipulative skills, locomotor skills, skill-related fitness, social functioning, and muscular strength and endurance. The authors conclude that physical activity's standing as an evidence-based strategy for youth with ASD is reinforced. Lien vers le texte intégral (Open Access ou abonnement)
7. Okyere C, Aldersey HM, Lysaght R, Sulaiman SK. {{Implementation of inclusive education for children with intellectual and developmental disabilities in African countries: a scoping review}}. {Disabil Rehabil};2018 (Apr 25):1-18.
PURPOSE: To advance understanding of practices that support inclusion of children with intellectual and developmental disabilities in inclusive education classrooms in Africa by conducting a review of the extant literature. METHODS: Five academic databases were searched supplemented by a hand search of key journals and references of included studies. Two authors independently screened studies via a reference manager (Covidence) which allowed for blinding. A third author was consulted in cases of conflict. RESULTS: Thirty articles that provided empirical evidence of inclusive education implementation were included. Eight articles highlighted practices that support inclusion of children with intellectual and developmental disabilities. Using Bronfenbrenner’s bioecological framework, findings revealed that inclusive education implementation is influenced by factors on the bio level, micro level, meso level, and macro level. Recommendations for promoting inclusive education implementation are provided. CONCLUSIONS: Inclusion goes beyond teachers and requires strong commitment of other stakeholders such as families and governments. To guarantee the smooth inclusion of children with special education needs and particularly with intellectual and developmental disabilities, a set of practices validated through rigorous research as supportive and unique and that can be universal to Africa is wise. Implications for rehabilitation A number of strategies were identified that can improve the classroom inclusion of children with intellectual and developmental disabilities. Development of policies that support such strategies could improve implementation. Inclusion goes beyond teachers. Rehabilitation professionals (i.e. occupational therapists) and educational professionals should partner to identify practical solutions to the challenges of creating inclusive environments for children with special education needs. Committing more resources and time towards the development and implementation of special education policies can advance the successful inclusion of children with special education needs.
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8. Rhee J, Park K, Kim KC, Shin CY, Chung C. {{Impaired Hippocampal Synaptic Plasticity and Enhanced Excitatory Transmission in a Novel Animal Model of Autism Spectrum Disorders with Telomerase Reverse Transcriptase Overexpression}}. {Mol Cells};2018 (Apr 26)
Recently, we have reported that animals with telomerase reverse transcriptase (TERT) overexpression exhibit reduced social interaction, decreased preference for novel social interaction and poor nest-building behaviors-symptoms that mirror those observed in human autism spectrum disorders (ASD). Overexpression of TERT also alters the excitatory/inhibitory (E/I) ratio in the medial prefrontal cortex. However, the effects of TERT overexpression on hippocampal-dependent learning and synaptic efficacy have not been investigated. In the present study, we employed electrophysiological approaches in combination with behavioral analysis to examine hippocampal function of TERT transgenic (TERT-tg) mice and FVB controls. We found that TERT overexpression results in enhanced hippocampal excitation with no changes in inhibition and significantly impairs long-term synaptic plasticity. Interestingly, the expression levels of phosphorylated CREB and phosphorylated CaMKIIalpha were significantly decreased while the expression level of CaMKIIalpha was slightly increased in the hippocampus of TERT-overexpressing mice. Our observations highlight the importance of TERT in normal synaptic function and behavior and provide additional information on a novel animal model of ASD associated with TERT overexpression.
