1. Arbab T, Battaglia FP, Pennartz CMA, Bosman CA. {{Abnormal hippocampal theta and gamma hypersynchrony produces network and spike timing disturbances in the Fmr1-KO mouse model of Fragile X syndrome}}. {Neurobiology of disease}. 2018; 114: 65-73.
Neuronal networks can synchronize their activity through excitatory and inhibitory connections, which is conducive to synaptic plasticity. This synchronization is reflected in rhythmic fluctuations of the extracellular field. In the hippocampus, theta and gamma band LFP oscillations are a hallmark of the processing of spatial information and memory. Fragile X syndrome (FXS) is an intellectual disability and the most common genetic cause of autism spectrum disorder (Belmonte and Bourgeron, 2006). Here, we investigated how neuronal network synchronization in the mouse hippocampus is compromised by the Fmr1 mutation that causes FXS (Santos et al., 2014), relating recently observed single-cell level impairments (Arbab et al., 2017) to neuronal network aberrations. We implanted tetrodes in hippocampus of freely moving Fmr1-KO and littermate wildtype (WT) mice (Mientjes et al., 2006), to record spike trains from multiple, isolated neurons as well as LFPs in a spatial exploration paradigm. Compared to wild type mice, Fmr1-KO mice displayed greater power of hippocampal theta oscillations, and higher coherence in the slow gamma band. Additionally, spike trains of Fmr1-KO interneurons show decreased spike-count correlations and they are hypersynchronized with theta and slow gamma oscillations. The hypersynchronization of Fmr1-KO oscillations and spike timing reflects functional deficits in local networks. This network hypersynchronization pathologically decreases the heterogeneity of spike-LFP phase coupling, compromising information processing within the hippocampal circuit. These findings may reflect a pathophysiological mechanism explaining cognitive impairments in FXS and autism, in which there is anomalous processing of social and environmental cues and associated deficits in memory and cognition.
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2. Arpone M, Baker EK, Bretherton L, Bui M, Li X, Whitaker S, Dissanayake C, Cohen J, Hickerton C, Rogers C, Field M, Elliott J, Aliaga SM, Ling L, Francis D, Hearps SJC, Hunter MF, Amor DJ, Godler DE. {{Intragenic DNA methylation in buccal epithelial cells and intellectual functioning in a paediatric cohort of males with fragile X}}. {Sci Rep}. 2018; 8(1): 3644.
Increased intragenic DNA methylation of the Fragile X Related Epigenetic Element 2 (FREE2) in blood has been correlated with lower intellectual functioning in females with fragile X syndrome (FXS). This study explored these relationships in a paediatric cohort of males with FXS using Buccal Epithelial Cells (BEC). BEC were collected from 25 males with FXS, aged 3 to 17 years and 19 age-matched male controls without FXS. Methylation of 9 CpG sites within the FREE2 region was examined using the EpiTYPER approach. Full Scale IQ (FSIQ) scores of males with FXS were corrected for floor effect using the Whitaker and Gordon (WG) extrapolation method. Compared to controls, children with FXS had significant higher methylation levels for all CpG sites examined (p < 3.3 x 10(-7)), and within the FXS group, lower FSIQ (WG corrected) was associated with higher levels of DNA methylation, with the strongest relationship found for CpG sites within FMR1 intron 1 (p < 5.6 x 10(-5)). Applying the WG method to the FXS cohort unmasked significant epi-genotype-phenotype relationships. These results extend previous evidence in blood to BEC and demonstrate FREE2 DNA methylation to be a sensitive epigenetic biomarker significantly associated with the variability in intellectual functioning in FXS. Lien vers le texte intégral (Open Access ou abonnement)
3. Bernas A, Barendse EM, Aldenkamp AP, Backes WH, Hofman PAM, Hendriks MPH, Kessels RPC, Willems FMJ, de With PHN, Zinger S, Jansen JFA. {{Brain resting-state networks in adolescents with high-functioning autism: Analysis of spatial connectivity and temporal neurodynamics}}. {Brain and behavior}. 2018; 8(2): e00878.
Introduction: Autism spectrum disorder (ASD) is mainly characterized by functional and communication impairments as well as restrictive and repetitive behavior. The leading hypothesis for the neural basis of autism postulates globally abnormal brain connectivity, which can be assessed using functional magnetic resonance imaging (fMRI). Even in the absence of a task, the brain exhibits a high degree of functional connectivity, known as intrinsic, or resting-state, connectivity. Global default connectivity in individuals with autism versus controls is not well characterized, especially for a high-functioning young population. The aim of this study is to test whether high-functioning adolescents with ASD (HFA) have an abnormal resting-state functional connectivity. Materials and Methods: We performed spatial and temporal analyses on resting-state networks (RSNs) in 13 HFA adolescents and 13 IQ- and age-matched controls. For the spatial analysis, we used probabilistic independent component analysis (ICA) and a permutation statistical method to reveal the RSN differences between the groups. For the temporal analysis, we applied Granger causality to find differences in temporal neurodynamics. Results: Controls and HFA display very similar patterns and strengths of resting-state connectivity. We do not find any significant differences between HFA adolescents and controls in the spatial resting-state connectivity. However, in the temporal dynamics of this connectivity, we did find differences in the causal effect properties of RSNs originating in temporal and prefrontal cortices. Conclusion: The results show a difference between HFA and controls in the temporal neurodynamics from the ventral attention network to the salience-executive network: a pathway involving cognitive, executive, and emotion-related cortices. We hypothesized that this weaker dynamic pathway is due to a subtle trigger challenging the cognitive state prior to the resting state.
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4. Braam W, Ehrhart F, Maas A, Smits MG, Curfs L. {{Low maternal melatonin level increases autism spectrum disorder risk in children}}. {Res Dev Disabil}. 2018.
BACKGROUND: It is assumed that autism spectrum disorder (ASD) is caused by a combination of de novo inherited variation and common variation as well as environmental factors. It often co-occurs with intellectual disability (ID). Almost eight hundred potential causative genetic variations have been found in ASD patients. However, not one of them is responsible for more than 1% of ASD cases. Low melatonin levels are a frequent finding in ASD patients. Melatonin levels are negatively correlated with severity of autistic impairments, it is important for normal neurodevelopment and is highly effective in protecting DNA from oxidative damage. Melatonin deficiency could be a major factor, and well a common heritable variation, that increases the susceptibility to environmental risk factors for ASD. ASD is already present at birth. As the fetus does not produce melatonin, low maternal melatonin levels may be involved. METHODS: We measured 6-sulfatoxymelatonin in urine of 60 mothers of a child with ASD and controls. RESULTS: 6-sulfatoxymelatonin levels were significantly lower in mothers with an ASD child than in controls (p=0.012). CONCLUSIONS: Low parental melatonin levels could be one of the contributors to ASD and possibly ID etiology. Our findings need to be duplicated on a larger scale. If our hypothesis is correct, this could lead to policies to detect future parents who are at risk and to treatment strategies to ASD and intellectual disability risk.
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5. Chabrol H, Raynal P. {{The co-occurrence of autistic traits and borderline personality disorder traits is associated to increased suicidal ideation in nonclinical young adults}}. {Comprehensive psychiatry}. 2018; 82: 141-3.
BACKGROUND: The co-occurrence of Autism Spectrum Disorder (ASD) and Borderline Personality Disorder (BPD) is not rare and has been linked to increased suicidality. Despite this significant comorbidity between ASD and BPD, no study had examined the co-occurrence of autistic traits and borderline personality disorder traits in the general population. The aim of the present study was to examine the co-occurrence of autistic and borderline traits in a non-clinical sample of young adults and its influence on the levels of suicidal ideation and depressive symptomatology. PROCEDURES: Participants were 474 college students who completed self-report questionnaires. Data were analysed using correlation and cluster analyses. MAIN FINDINGS: Borderline personality traits and autistic traits were weakly correlated. However, cluster analysis yielded four groups: a low traits group, a borderline traits group, an autistic traits group, and a group characterized by high levels of both traits. Cluster analysis revealed that autistic and borderline traits can co-occur in a significant proportion of young adults. The high autistic and borderline traits group constituted 17% of the total sample and had higher level of suicidal ideation than the borderline traits group, despite similar levels of depressive symptoms. CONCLUSION: This result suggests that the higher suicidality observed in patients with comorbid ASD and BPD may extent to non-clinical individuals with high levels of co-occurrent autistic and borderline traits.
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6. Delhey LM, Tippett M, Rose S, Bennuri SC, Slattery JC, Melnyk S, James SJ, Frye RE. {{Comparison of Treatment for Metabolic Disorders Associated with Autism:Reanalysis of Three Clinical Trials}}. {Front Neurosci}. 2018; 12: 19.
Autism spectrum disorder (ASD) affects about 1 in 45 individuals in the United States, yet effective treatments are yet to be defined. There is growing evidence that ASD is associated with abnormalities in several metabolic pathways, including the inter-connected folate, methylation and glutathione pathways. Several treatments that can therapeutically target these pathways have been tested in preliminary clinical trials. The combination of methylcobalamin (mB12) with low-dose folinic acid (LDFA) and sapropterin, a synthetic form of tetrahydrobiopterin (BH4) have been studied in open-label trials while high-dose folinic acid has been studied in a double-blind placebo controlled trial. All of these treatments have the potential to positively affect folate, methylation and glutathione pathways. Although the effect of mB12/LDFA and BH4 on methylation and glutathione metabolism have been examined in the open-label studies, these changes have not been compared to controls who received a placebo in order to account for the natural variation in the changes in these pathways. Furthermore, the recent study using high-dose folinic acid (HDFA) did not analyze the change in metabolism resulting from the treatment. Thus, we compared changes in methylation and glutathione metabolism and biomarkers of chronic oxidative stress as a result of these three treatments to individuals receiving placebo. In general, mB12/LDFA treatment had a significant effect on glutathione and cysteine metabolism with a medium effect size while BH4 had a significant effect on methylation and markers of chronic oxidative stress with a large effect size. HDFA treatment did not significantly influence biomarkers of methylation, glutathione or chronic oxidative stress. One caveat was that participants in the mB12/LDFA and BH4 studies had significantly worse markers of glutathione metabolism and chronic oxidative stress at baseline, respectively. Thus, the participants selected in these two clinical trials may have been those with the most severe metabolic abnormalities and most expected to respond to these treatments. Overall this study supports the notion that metabolic abnormalities in individuals with ASD may be amenable to targeted treatments and provide some insight into the mechanism of action of these treatments.
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7. Fernandes IR, Cruz AC, Ferrasa A, Phan D, Herai RH, Muotri AR. {{Genetic variations on SETD5 underlying autistic conditions}}. {Dev Neurobiol}. 2018.
The prevalence of autism spectrum disorders (ASD) and the number of identified ASD-related genes have increased in recent years. The SETD5 gene encodes a SET-containing-domain 5 protein, a likely reader enzyme. Genetic evidences suggest that SETD5 malfunction contributes to ASD phenotype, such as on intellectual disability (ID) and facial dysmorphism. In this review, we mapped the clinical phenotypes of individuals carrying mutations on the SETD5 gene that are associated with ASD and other chromatinopathies (mutation in epigenetic modifiers that leads to the development of neurodevelopmental disorders such as ASD). After a detailed systematic literature review and analysis of public disease-related databank, we found so far 42 individuals carrying mutations on the SETD5 gene, with 23.8% presenting autistic-like features. Furthermore, most of mutations occurred between positions 9,480,000-9,500,000 bp on chromosome 3 (3p25.3) at the SETD5 gene locus. In all males, mutations in SETD5 presented high penetrance, while in females the clinical phenotype seems more variable with two reported cases showing normal female carriers and not presenting ASD or any ID-like symptoms. At the molecular level, SETD5 interacts with proteins of PAF1C and N-CoR complexes, leading to a possible involvement with chromatin modification pathway, which plays important roles for brain development. Together, we propose that mutations on the SETD5 gene could lead to a new syndromic condition in males, which is linked to 3p25 syndrome, and can leads to ASD-related intellectual disability and facial dysmorphism. (c) 2018 Wiley Periodicals, Inc. Develop Neurobiol, 2018.
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8. Gettis MA, Wittling K, Palumbo-Dufur J, McClain A, Riley L. {{Identifying Best Practice for Healthcare Providers Caring for Autistic Children Perioperatively}}. {Worldviews on evidence-based nursing}. 2018.
This column shares the best evidence-based strategies and innovative ideas on how to facilitate the learning and implementation of EBP principles and processes by clinicians as well as nursing and interprofessional students. Guidelines for submission are available at https://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1741-6787.
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9. Godar DE, Merrill SJ. {{Untangling the most probable role for vitamin D3 in autism}}. {Dermato-endocrinology}. 2017; 9(1): e1387702.
Recent studies indicate an important role for vitamin D3 in autism spectrum disorder (ASD), although its mechanism is not completely understood. The most puzzling aspect of ASD is that identical twins, who share identical DNA, do not have 100% concordance rates ( approximately 88% for identical and approximately 31% for fraternal twins). These findings provide major clues into the etiology: ASD must involve an environmental factor present in the prenatal milieu that both identical twins are not always exposed to because they do not always share it (i.e., placentas). Combined with the exponential increasing rates of ASD around the world, these observations suggest a contagious disease is probably transferred to the fetus via the placenta becoming infected by a cervical virus. Vitamin D3 boosts immune responses clearing viral infections and increases serotonin and estrogen brain levels. Here we review the different roles and untangle the most probable one vitamin D3 plays in ASD.
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10. Hadjikhani N, Asberg Johnels J, Lassalle A, Zurcher NR, Hippolyte L, Gillberg C, Lemonnier E, Ben-Ari Y. {{Bumetanide for autism: more eye contact, less amygdala activation}}. {Sci Rep}. 2018; 8(1): 3602.
We recently showed that constraining eye contact leads to exaggerated increase of amygdala activation in autism. Here, in a proof of concept pilot study, we demonstrate that administration of bumetanide (a NKCC1 chloride importer antagonist that restores GABAergic inhibition) normalizes the level of amygdala activation during constrained eye contact with dynamic emotional face stimuli in autism. In addition, eye-tracking data reveal that bumetanide administration increases the time spent in spontaneous eye gaze during in a free-viewing mode of the same face stimuli. In keeping with clinical trials, our data support the Excitatory/Inhibitory dysfunction hypothesis in autism, and indicate that bumetanide may improve specific aspects of social processing in autism. Future double-blind placebo controlled studies with larger cohorts of participants will help clarify the mechanisms of bumetanide action in autism.
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11. Im WY, Ha JH, Kim EJ, Cheon KA, Cho J, Song DH. {{Impaired White Matter Integrity and Social Cognition in High-Function Autism: Diffusion Tensor Imaging Study}}. {Psychiatry investigation}. 2018.
Objective: It is known that many of the cognitive and social deficits associated with autism can arise from abnormal functional connectivity between brain networks. This aberrant functional connectivity in autism spectrum disorders (ASD) can be explained by impaired integrity of white matter tracts that link distant regions of the networks. Methods: We investigated white matter in 9 children with high-function autism (HFA) compared to 13 typically developing controls using diffusion tensor imaging (DTI). The aim of this research is to provide supporting evidence for abnormalities in neural connectivity as an underlying pathophysiology of the main characteristics of ASD. Results: We found impairment of neural connectivity, mainly in association fiber tracts as evidenced by decreased fractional anisotropy (FA), the index of white matter integrity, of these tracts. Among them, inferior fronto-occipital fasciculus (IFOF) had a significant relationship with ADI-R score. The inferior longitudinal fasciculus (ILF) and superior longitudinal fasciculus (SLF) also showed decreased FA. Decreased FA of ILF and SLF had negative correlations with scores of social interaction. Conclusion: These findings suggest that widespread abnormalities in association fiber tracts may contribute to both core and associated symptoms of ASD.
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12. Lemcke S, Parner ET, Bjerrum M, Thomsen PH, Lauritsen MB. {{EARLY REGULATION IN CHILDREN WHO ARE LATER DIAGNOSED WITH AUTISM SPECTRUM DISORDER. A LONGITUDINAL STUDY WITHIN THE DANISH NATIONAL BIRTH COHORT}}. {Infant mental health journal}. 2018; 39(2): 170-82.
Studies have shown that children later diagnosed with autism spectrum disorders (ASD) in their first years of life might show symptoms in main developmental areas and that these signs might be sensed by the parents. The present study investigated in a large birth cohort if children later diagnosed with ASD had deviations at 6 and 18 months in areas such as the ability to self-regulate emotions, feeding, and sleeping. The study was based on prospective information collected from 76,322 mothers who participated in the Danish National Birth Cohort. When the children reached an average age of 11 years, 973 children with ASD and a control group of 300 children with intellectual disability (IDnoASD) were identified via Danish health registries. Associations were found between short periods of breast-feeding and the children later diagnosed with ASD and IDnoASD as well as associations at 18 months to deviations in regulation of emotions and activity. The similarities in these associations emphasize how difficult it is to distinguish between diagnoses early in life.
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13. Liggett AP, Nastri R, Podlesnik CA. {{Assessing the combined effects of resurgence and reinstatement in children diagnosed with autism spectrum disorder}}. {Journal of the experimental analysis of behavior}. 2018.
Resurgence and reinstatement are laboratory models of relapse following treatments for problem behavior that arrange alternative sources of reinforcement, such as differential reinforcement of alternative behavior and noncontingent reinforcement. Resurgence models the elimination or reduction of reinforcers during treatment and reinstatement models the re-presentation of reinforcers previously maintaining problem behavior. The present study examined individual and combined effects of resurgence and reinstatement in a translational model of treatment relapse with three children diagnosed with Autism Spectrum Disorder. We first reinforced and then extinguished an arbitrary response while providing access to a preferred toy to model a version of noncontingent reinforcement with extinction. In the following phases, we examined resurgence by removing the toy, reinstatement by presenting the training reinforcer response-independently, and a combination of resurgence and reinstatement. Overall, relapse of target responding reliably exceeded functionally similar responses never reinforced in the experimental situation. Most importantly, relapse tended to be greater when combining resurgence and reinstatement than when assessing either alone. These findings support previous studies showing that combinations of operations can increase treatment relapse. This translational model arranging simulated problem behavior with arbitrary tasks provides a platform from which to thoroughly and systematically assess methods for understanding and improving behavioral treatments.
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14. Lo FS, Erzurumlu RS. {{Insulin receptor sensitization restores neocortical excitation/inhibition balance in a mouse model of autism}}. {Mol Autism}. 2018; 9: 13.
Background: Met receptor tyrosine kinase regulates neurogenesis, differentiation, migration, connectivity, and synaptic plasticity. The human Met gene has been identified as a prominent risk factor for autism spectrum disorder (ASD). Met gene-altered mice serve as useful models for mechanistic studies of ASD. Inactivation of Met in excitatory cortical neurons in mice (Emx1(cre)/Met(flox) mice) yields a phenotype in which significantly decreased GABAA receptor-mediated inhibition shifts the excitation/inhibition (E/I) balance toward excitation in the somatosensory cortex. Further, unlike that seen in wild-type mice, insulin does not increase inhibition in the mutant cortex, suggesting that one of the consequences of kinase inactive Met gene could be desensitization of insulin receptors. To test this hypothesis, we investigated the effects of insulin receptor sensitizer, pioglitazone, on inhibition in the somatosensory thalamocortical circuitry. Methods: We used whole-cell patch clamp electrophysiology and analyzed excitatory and inhibitory responses of cortical layer IV excitatory cells following stimulation of their thalamic input in thalamocortical pathway intact brain slices. We applied insulin alone and insulin + a thiazolidinedione, pioglitazone (PIO), to test the effects of sensitizing insulin receptors on inhibitory responses mediated by GABAA receptors in the somatosensory cortex of Emx1(cre)/Met(flox) mice. Results: In WT brain slices, application of insulin together with PIO did not enhance the effect of insulin alone. In contrast, PIO application induced a much larger inhibition than that of insulin alone in Met-defective cortex. Thus, insulin resistance of GABAA receptor-mediated response in Met mutant mice may result from desensitized insulin receptors. Conclusions: Sporadic clinical studies reported improved behavioral symptoms in children with autism following PIO treatment. We show that PIO can aid in normalization of the E/I balance in the primary somatosensory cortex, a potential physiological mechanism underlying the positive effects of PIO treatment.
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15. Merbler AM, Byiers BJ, Garcia JJ, Feyma TJ, Symons FJ. {{The feasibility of using actigraphy to characterize sleep in Rett syndrome}}. {J Neurodev Disord}. 2018; 10(1): 8.
BACKGROUND: Rett syndrome (RTT) is a neurodevelopmental disorder primarily caused by mutations in the MECP2 gene. Sleep problems are reported by the majority of caregivers of individuals with RTT. METHODS: The present study aimed to replicate and extend previous work about the feasibility of measuring sleep with an actigraph device in a sample of girls with clinically diagnosed RTT (N = 13, mean age = 9 years, 5 months). Participants wore an actigraph device day and night for seven consecutive days. Materials also included a parent-completed sleep diary to measure bedtime, duration of nighttime sleep, and daytime sleep, and the Child Sleep Habit’s Questionnaire (CSHQ). RESULTS: The means for the sample as measured by actigraphy were 492.3 min (SD = 47.3) of total night sleep (TNS), 76.0% (SD = 6.7) sleep efficiency, 86.0 min (SD = 34.2) of wake after sleep onset, and 46.1 min (50.8) of sleep when parents reported a nap occurring. Parents reported 589.7 min (SD = 53.6) of TNS, 15.9 min (SD = 12.0) of WASO, and 93.6 min (SD = 66.8) of daytime sleep according to sleep diaries, with all parents reporting at least one nap during the week. Relations were found between sleep characteristics and seizure status and CSHQ total scores. No age-related changes were observed for any sleep characteristic, regardless of collection method. Five of nine participants above the cutoff score on the CSHQ indicate the need for further evaluation for a sleep disorder. CONCLUSIONS: Overall, actigraphy was feasible in this community-based sample of girls with RTT. The results replicated some aspects of previous studies of sleep in RTT (e.g., no age-related changes in total nighttime sleep or efficiency). Some participants met the American Academy of Sleep Medicine guidelines for recommended total sleep time, with others showing too much or too little sleep. Each of the three methods for describing sleep presented its own advantages and challenges. Future work should be prospectively designed, validate the use of actigraphy in this population, and include a typically developing comparison sample to improve the precision of our understanding of sleep in RTT.
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16. Rogerson J, Falkmer M, Cuomo B, Falkmer T, Whitehouse AJO, Granich J, Vaz S. {{Parental experiences using the Therapy Outcomes by You (TOBY) application to deliver early intervention to their child with autism}}. {Dev Neurorehabil}. 2018: 1-9.
PURPOSE: As computer-based interventions become commonplace for parents of children with neurodevelopmental disorders, this study sought to understand the experience of using a parent-delivered supplementary early intervention therapy for children with autism spectrum disorder grounded in a variety of behavioral, sensory, developmental, and relationship-based approaches and delivered via a tablet device. METHODS: Parental experiences using the ‘Therapy Outcomes by You’ (TOBY) application were collected through semi-structured interviews with 17 parents. RESULTS: Parents reported TOBY facilitated parent-child engagement, provided ideas for therapeutic activities, created feelings of empowerment, and positively impacted their child’s development. Barriers to use included preparation time, execution of the intervention, and individual strengths and weaknesses of their child. CONCLUSION: The overall parental experience of TOBY was positive when use of the application aligned with parental proficiency, opportunities for use, and importantly, the needs of the child.
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17. Romero-Garcia R, Warrier V, Bullmore ET, Baron-Cohen S, Bethlehem RAI. {{Synaptic and transcriptionally downregulated genes are associated with cortical thickness differences in autism}}. {Mol Psychiatry}. 2018.
Differences in cortical morphology-in particular, cortical volume, thickness and surface area-have been reported in individuals with autism. However, it is unclear what aspects of genetic and transcriptomic variation are associated with these differences. Here we investigate the genetic correlates of global cortical thickness differences (DeltaCT) in children with autism. We used Partial Least Squares Regression (PLSR) on structural MRI data from 548 children (166 with autism, 295 neurotypical children and 87 children with ADHD) and cortical gene expression data from the Allen Institute for Brain Science to identify genetic correlates of DeltaCT in autism. We identify that these genes are enriched for synaptic transmission pathways and explain significant variation in DeltaCT. These genes are also significantly enriched for genes dysregulated in the autism post-mortem cortex (Odd Ratio (OR) = 1.11, Pcorrected 10(-14)), driven entirely by downregulated genes (OR = 1.87, Pcorrected 10(-15)). We validated the enrichment for downregulated genes in two independent data sets: Validation 1 (OR = 1.44, Pcorrected = 0.004) and Validation 2 (OR = 1.30; Pcorrected = 0.001). We conclude that transcriptionally downregulated genes implicated in autism are robustly associated with global changes in cortical thickness variability in children with autism.
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18. Sagar-Ouriaghli I, Lievesley K, Santosh PJ. {{Propranolol for treating emotional, behavioural, autonomic dysregulation in children and adolescents with autism spectrum disorders}}. {Journal of psychopharmacology (Oxford, England)}. 2018: 269881118756245.
OBJECTIVES: To date, there is no single medication prescribed to alleviate all the core symptoms of Autism Spectrum Disorder (ASD; National Institute of Health and Care Excellence, 2016). Both serotonin reuptake inhibitors and drugs for psychosis possess therapeutic drawbacks when managing anxiety and aggression in ASD. This review sought to appraise the use of propranolol as a pharmacological alternative when managing emotional, behavioural and autonomic dysregulation (EBAD) and other symptoms. MATERIALS AND METHODS: Sixteen reports examined the administration of propranolol in the context of ASD. RESULTS: Sixteen reports broadly covered cognitive domains, neural correlates, and behavioural domains. From the eight single-dose clinical trials, propranolol led to significant improvements in cognitive performance – verbal problem solving, social skills, mouth fixation, and conversation reciprocity; and changes in neural correlates – improvement in semantic networks and functional connectivity. The remaining eight case series and single case reports showed improvements in EBAD, anxiety, aggressive, self-injurious and hypersexual behaviours. Additionally, propranolol significantly improved similar behavioural domains (aggression and self-injury) for those with acquired brain injury. CONCLUSION: This review indicates that propranolol holds promise for EBAD and cognitive performance in ASD. Given the lack of good quality clinical trials, randomised controlled trials are warranted to explore the efficacy of propranolol in managing EBAD in ASD.
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19. Sperdin HF, Coito A, Kojovic N, Rihs TA, Jan RK, Franchini M, Plomp G, Vulliemoz S, Eliez S, Michel CM, Schaer M. {{Early alterations of social brain networks in young children with autism}}. {eLife}. 2018; 7.
Social impairments are a hallmark of Autism Spectrum Disorders (ASD), but empirical evidence for early brain network alterations in response to social stimuli is scant in ASD. We recorded the gaze patterns and brain activity of toddlers with ASD and their typically developing peers while they explored dynamic social scenes. Directed functional connectivity analyses based on electrical source imaging revealed frequency specific network atypicalities in the theta and alpha frequency bands, manifesting as alterations in both the driving and the connections from key nodes of the social brain associated with autism. Analyses of brain-behavioural relationships within the ASD group suggested that compensatory mechanisms from dorsomedial frontal, inferior temporal and insular cortical regions were associated with less atypical gaze patterns and lower clinical impairment. Our results provide strong evidence that directed functional connectivity alterations of social brain networks is a core component of atypical brain development at early stages of ASD.
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20. Stivaros S, Garg S, Tziraki M, Cai Y, Thomas O, Mellor J, Morris AA, Jim C, Szumanska-Ryt K, Parkes LM, Haroon HA, Montaldi D, Webb N, Keane J, Castellanos FX, Silva AJ, Huson S, Williams S, Gareth Evans D, Emsley R, Green J. {{Randomised controlled trial of simvastatin treatment for autism in young children with neurofibromatosis type 1 (SANTA)}}. {Mol Autism}. 2018; 9: 12.
Background: Neurofibromatosis 1 (NF1) is a monogenic model for syndromic autism. Statins rescue the social and cognitive phenotype in animal knockout models, but translational trials with subjects > 8 years using cognition/behaviour outcomes have shown mixed results. This trial breaks new ground by studying statin effects for the first time in younger children with NF1 and co-morbid autism and by using multiparametric imaging outcomes. Methods: A single-site triple-blind RCT of simvastatin vs. placebo was done. Assessment (baseline and 12-week endpoint) included peripheral MAPK assay, awake magnetic resonance imaging spectroscopy (MRS; GABA and glutamate+glutamine (Glx)), arterial spin labelling (ASL), apparent diffusion coefficient (ADC), resting state functional MRI, and autism behavioural outcomes (Aberrant Behaviour Checklist and Clinical Global Impression). Results: Thirty subjects had a mean age of 8.1 years (SD 1.8). Simvastatin was well tolerated. The amount of imaging data varied by test. Simvastatin treatment was associated with (i) increased frontal white matter MRS GABA (t(12) = – 2.12, p = .055), GABA/Glx ratio (t(12) = – 2.78, p = .016), and reduced grey nuclei Glx (ANCOVA p < 0.05, Mann-Whitney p < 0.01); (ii) increased ASL perfusion in ventral diencephalon (Mann-Whitney p < 0.01); and (iii) decreased ADC in cingulate gyrus (Mann-Whitney p < 0.01). Machine-learning classification of imaging outcomes achieved 79% (p < .05) accuracy differentiating groups at endpoint against chance level (64%, p = 0.25) at baseline. Three of 12 (25%) simvastatin cases compared to none in placebo met 'clinical responder' criteria for behavioural outcome. Conclusions: We show feasibility of peripheral MAPK assay and autism symptom measurement, but the study was not powered to test effectiveness. Multiparametric imaging suggests possible simvastatin effects in brain areas previously associated with NF1 pathophysiology and the social brain network. Trial registration: EU Clinical Trial Register (EudraCT) 2012-005742-38 (www.clinicaltrialsregister.eu). Lien vers le texte intégral (Open Access ou abonnement)
21. Ward DM, Dill-Shackleford KE, Mazurek MO. {{Social Media Use and Happiness in Adults with Autism Spectrum Disorder}}. {Cyberpsychology, behavior and social networking}. 2018.
Social media (SM) use by adults with autism spectrum disorder (ASD) is not well understood. Co-occurring mental health concerns, such as depression, are common for adults with ASD. The current investigation explored the relationship between SM use and happiness in a population of adults with self-disclosed ASD. Of the 84 percent of the sample who used SM, those who used Facebook, the most popular site, were happier than those who did not. The same relationship did not exist for the second most popular site, Twitter. Happiness and SM use showed a quadratic relationship: Happiness and SM use increased together until they reached a point where happiness fell off. SM use by adults with ASD, specifically Facebook use in moderation, may enhance well-being and may be a protective factor against secondary mental health concerns common in this population.
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22. West MJ, Copland DA, Arnott WL, Nelson NL, Angwin AJ. {{Effects of Prosodic and Semantic Cues on Facial Emotion Recognition in Relation to Autism-Like Traits}}. {J Autism Dev Disord}. 2018.
The current study investigated whether those with higher levels of autism-like traits process emotional information from speech differently to those with lower levels of autism-like traits. Neurotypical adults completed the autism-spectrum quotient and an emotional priming task. Vocal primes with varied emotional prosody, semantics, or a combination, preceded emotional target faces. Prime-target pairs were congruent or incongruent in their emotional content. Overall, congruency effects were found for combined prosody-semantic primes, however no congruency effects were found for semantic or prosodic primes alone. Further, those with higher levels of autism-like traits were not influenced by the prime stimuli. These results suggest that failure to integrate emotional information across modalities may be characteristic of the broader autism phenotype.
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23. Zink AG, Molina EC, Diniz MB, Santos M, Guare RO. {{Communication Application for Use During the First Dental Visit for Children and Adolescents with Autism Spectrum Disorders}}. {Pediatric dentistry}. 2018; 40(1): 18-22.
PURPOSE: The purpose of this study was to develop and evaluate an application (app) facilitating patient-professional communication among individuals with autism spectrum disorder (ASD) and compare it with the Picture Exchange Communication System (PECS). METHODS: Forty nine- to 15-year-olds were randomly divided into two groups: G1 (app; N equals 20) and G2 (PECS; N equals 20). Initially, the visual contact timing of the groups was measured. Pictures of a room, ground, chair, dentist, mouth, low-speed handpiece, and air-water syringe were presented to both groups. Each picture was shown up to three times per appointment to evaluate whether or not the child accepted the procedure. After dental prophylaxis, caries experience was recorded. RESULTS: The prevalence of dental caries was 37.5 percent. Differences in the number of attempts required for each picture to acquire the skill proposed were found between the groups (Mann-Whitney, P<0.05). A significant difference in the median number of attempts (G1 equals 9.5 and G2 equals 15) and appointments (G1 equals three and G2 equals five) was observed (Mann-Whitney, P<0.05). CONCLUSIONS: The app was more effective than the Picture Exchange Communication System for dentist-patient communication, decreasing the number of appointments required for preventive dental care and clinical examinations. Lien vers Pubmed
