1. Abrams DA, Padmanabhan A, Chen T, Odriozola P, Baker AE, Kochalka J, Phillips JM, Menon V. {{Impaired voice processing in reward and salience circuits predicts social communication in children with autism}}. {Elife};2019 (Feb 26);8
Engaging with vocal sounds is critical for children’s social-emotional learning, and children with autism spectrum disorder (ASD) often ‘tune out’ voices in their environment. Little is known regarding the neurobiological basis of voice processing and its link to social impairments in ASD. Here, we perform the first comprehensive brain network analysis of voice processing in children with ASD. We examined neural responses elicited by unfamiliar voices and mother’s voice, a biologically salient voice for social learning, and identified a striking relationship between social communication abilities in children with ASD and activation in key structures of reward and salience processing regions. Functional connectivity between voice-selective and reward regions during voice processing predicted social communication in children with ASD and distinguished them from typically developing children. Results support the Social Motivation Theory of ASD by showing reward system deficits associated with the processing of a critical social stimulus, mother’s voice, in children with ASD. Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor’s assessment is that minor issues remain unresolved (see decision letter).
Lien vers le texte intégral (Open Access ou abonnement)
2. Adams D, Clark M, Simpson K. {{The Relationship Between Child Anxiety and the Quality of Life of Children, and Parents of Children, on the Autism Spectrum}}. {J Autism Dev Disord};2019 (Feb 25)
Children on the autism spectrum experience high rates of anxiety but little is known about the impact of anxiety on child or parent quality of life (QoL). This study aimed to investigate the relationship between anxiety, autism characteristics, and QoL in children and their parents. Sixty-four parents of children on the spectrum completed questionnaires on their child’s autism characteristics, anxiety symptomatology, and both child (PedsQL) and parent QoL (WHOQoL-BREF). Parents of children with elevated anxiety reported lower child and parent QoL. Regression models highlight specific anxiety subscales as predictive of PedsQL school and emotional functioning but not of parent QoL. Anxiety symptomatology may be a significant factor contributing to specific aspects of QoL for children on the spectrum.
Lien vers le texte intégral (Open Access ou abonnement)
3. Danesi C, Keinanen K, Castren ML. {{Dysregulated Ca(2+)-Permeable AMPA Receptor Signaling in Neural Progenitors Modeling Fragile X Syndrome}}. {Front Synaptic Neurosci};2019;11:2.
Fragile X syndrome (FXS) is a neurodevelopmental disorder that represents a common cause of intellectual disability and is a variant of autism spectrum disorder (ASD). Studies that have searched for similarities in syndromic and non-syndromic forms of ASD have paid special attention to alterations of maturation and function of glutamatergic synapses. Copy number variations (CNVs) in the loci containing genes encoding alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors (AMPARs) subunits are associated with ASD in genetic studies. In FXS, dysregulated AMPAR subunit expression and trafficking affect neural progenitor differentiation and synapse formation and neuronal plasticity in the mature brain. Decreased expression of GluA2, the AMPAR subunit that critically controls Ca(2+)-permeability, and a concomitant increase in Ca(2+)-permeable AMPARs (CP-AMPARs) in human and mouse FXS neural progenitors parallels changes in expression of GluA2-targeting microRNAs (miRNAs). Thus, posttranscriptional regulation of GluA2 by miRNAs and subsequent alterations in calcium signaling may contribute to abnormal synaptic function in FXS and, by implication, in some forms of ASD.
Lien vers le texte intégral (Open Access ou abonnement)
4. Fontil L, Gittens J, Beaudoin E, Sladeczek IE. {{Barriers to and Facilitators of Successful Early School Transitions for Children with Autism Spectrum Disorders and Other Developmental Disabilities: A Systematic Review}}. {J Autism Dev Disord};2019 (Feb 26)
Early school transitions are exciting, yet challenging, experiences for children with special needs, such as autism spectrum disorder (ASD), and their families. Transition to school support practices can help facilitate this difficult process for key stakeholders. The purpose of this systematic review was to synthesize the literature on transition to kindergarten support practice use for children with ASD and other developmental disabilities. Qualitative and quantitative studies were analyzed using textual narrative synthesis, following the guidelines from the Centre for Reviews and Dissemination. Overall, 39 individual studies were included. Results highlighted particular parent, child, and support staff needs during the transition to school, while also emphasizing the importance of collaborative practices in facilitating successful school beginnings.
Lien vers le texte intégral (Open Access ou abonnement)
5. Fuller EA, Kaiser AP. {{The Effects of Early Intervention on Social Communication Outcomes for Children with Autism Spectrum Disorder: A Meta-analysis}}. {J Autism Dev Disord};2019 (Feb 25)
This meta-analysis examined the effects of early interventions on social communication outcomes for young children with autism spectrum disorder. A systematic review of the literature included 1442 children (mean age 3.55 years) across 29 studies. The overall effect size of intervention on social communication outcomes was significant (g = 0.36). The age of the participants was related to the treatment effect size on social communication outcomes, with maximum benefits occurring at age 3.81 years. Results did not differ significantly depending on the person implementing the intervention. However, significantly larger effect sizes were observed in studies with context-bound outcome measures. The findings of this meta-analysis highlight the need for further research examining specific components of interventions associated with greater and more generalized gains.
Lien vers le texte intégral (Open Access ou abonnement)
6. Greene RK, Zheng S, Kinard JL, Mosner MG, Wiesen CA, Kennedy DP, Dichter GS. {{Social and Nonsocial Visual Prediction Errors in Autism Spectrum Disorder}}. {Autism Res};2019 (Feb 25)
Impaired predictive coding has been proposed as a framework to explain discrepancies between expectations and outcomes in autism spectrum disorder (ASD) that may contribute to core symptoms of the disorder. However, no eye tracking study has directly addressed this framework in the context of visual predictions of social and nonsocial stimuli. The current study used eye tracking to examine violations of learned visual associations of both social and nonsocial stimuli. Twenty-six adolescents with ASD and 18 typically developing control (TDC) adolescents completed an outcome expectation eye tracking task in which predictive cues correctly (80% of trials) or incorrectly (20% of trials) indicated the location (left or right) of forthcoming social or nonsocial stimuli. During violation trials, individuals with ASD focused their gaze relatively more often on stimuli presented on locations that violated the learned association and less often on locations that corresponded with the learned association. This finding was not moderated by stimulus type (i.e., social vs. nonsocial). Additionally, participants who looked at incorrectly predicted locations more often had significantly greater ASD symptom severity. These results are consistent with theories that characterize ASD as a disorder of prediction and have potential implications for understanding symptoms related to prediction errors in individuals with ASD. Autism Res 2019. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Individuals with autism spectrum disorder (ASD) exhibit impairments making predictions that may impact learning. In this study, we used eye tracking methodology and found that individuals with ASD were less likely to look at the predicted location when a visual routine was violated. This pattern was evident for both social and nonsocial images and was associated with greater ASD symptom severity. These findings provide additional support for predictive challenges in ASD.
Lien vers le texte intégral (Open Access ou abonnement)
7. Grove J, Ripke S, Als TD, Mattheisen M, Walters RK, Won H, Pallesen J, Agerbo E, Andreassen OA, Anney R, Awashti S, Belliveau R, Bettella F, Buxbaum JD, Bybjerg-Grauholm J, Baekvad-Hansen M, Cerrato F, Chambert K, Christensen JH, Churchhouse C, Dellenvall K, Demontis D, De Rubeis S, Devlin B, Djurovic S, Dumont AL, Goldstein JI, Hansen CS, Hauberg ME, Hollegaard MV, Hope S, Howrigan DP, Huang H, Hultman CM, Klei L, Maller J, Martin J, Martin AR, Moran JL, Nyegaard M, Naerland T, Palmer DS, Palotie A, Pedersen CB, Pedersen MG, dPoterba T, Poulsen JB, Pourcain BS, Qvist P, Rehnstrom K, Reichenberg A, Reichert J, Robinson EB, Roeder K, Roussos P, Saemundsen E, Sandin S, Satterstrom FK, Davey Smith G, Stefansson H, Steinberg S, Stevens CR, Sullivan PF, Turley P, Walters GB, Xu X, Stefansson K, Geschwind DH, Nordentoft M, Hougaard DM, Werge T, Mors O, Mortensen PB, Neale BM, Daly MJ, Borglum AD. {{Identification of common genetic risk variants for autism spectrum disorder}}. {Nat Genet};2019 (Mar);51(3):431-444.
Autism spectrum disorder (ASD) is a highly heritable and heterogeneous group of neurodevelopmental phenotypes diagnosed in more than 1% of children. Common genetic variants contribute substantially to ASD susceptibility, but to date no individual variants have been robustly associated with ASD. With a marked sample-size increase from a unique Danish population resource, we report a genome-wide association meta-analysis of 18,381 individuals with ASD and 27,969 controls that identified five genome-wide-significant loci. Leveraging GWAS results from three phenotypes with significantly overlapping genetic architectures (schizophrenia, major depression, and educational attainment), we identified seven additional loci shared with other traits at equally strict significance levels. Dissecting the polygenic architecture, we found both quantitative and qualitative polygenic heterogeneity across ASD subtypes. These results highlight biological insights, particularly relating to neuronal function and corticogenesis, and establish that GWAS performed at scale will be much more productive in the near term in ASD.
Lien vers le texte intégral (Open Access ou abonnement)
8. Hwang YIJ, Srasuebkul P, Foley KR, Arnold S, Trollor JN. {{Mortality and cause of death of Australians on the autism spectrum}}. {Autism Res};2019 (Feb 25)
Focused investigations regarding mortality rates, risk factors, and cause of death in autistic populations remain scarce. The present study used large linked datasets spanning 2001-2015 to report the rates and risk factors for mortality and cause of death in individuals on the autism spectrum (n = 35,929 age range 5-64) with and without concurrent intellectual disability (ID) in New South Wales, Australia. Mortality rates for those on the autism spectrum were 2.06 times that of the general population. Concurrent ID, epilepsy, mental health conditions, and chronic physical health conditions were associated with a higher risk of death for those on the spectrum, whereas demographic variables such as gender and socioeconomic status were not. A differing profile of top causes of death was found for autistic individuals relative to the general population, with « nervous system and sense disorders » and « injury and poisoning » being the top-ranked causes for those on the spectrum. The findings alert the need for health promotion and management of concurrent physical and mental health conditions for those on the autism spectrum. There is also a need for better identification, diagnosis, and documentation of older adults on the autism spectrum. Autism Res 2019, 9999: 1-10. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Rates of death are higher for autistic individuals compared to the general population. There is higher risk of death for autistic individuals who have additional mental and physical health conditions. The leading causes of death for autistic individuals with and without ID are « nervous system and sense disorders », which includes epilepsy and « injury and poisoning », respectively. To minimize risk of death, it is important to manage the mental and physical health individuals on the autism spectrum and to better understand the circumstances surrounding preventable deaths for this population.
Lien vers le texte intégral (Open Access ou abonnement)
9. Kamita MK, Silva LAF, Magliaro FCL, Kawai RYC, Fernandes FDM, Matas CG. {{Brainstem auditory evoked potentials in children with autism spectrum disorder}}. {J Pediatr (Rio J)};2019 (Feb 22)
OBJECTIVES: This study aimed to analyze the neural encoding of verbal and nonverbal stimuli in individuals with autism spectrum disorder using brainstem auditory evoked potentials. METHODOLOGY: Thirty individuals between 7 and 12 years of age and of both genders participated in this study. Fifteen were diagnosed with autism spectrum disorder, and 15 had typical development. All subjects had normal hearing and no other impairments. An electrophysiological hearing assessment was performed using brainstem auditory evoked potentials with click and speech stimuli. RESULTS: In the brainstem auditory evoked potentials with click stimuli, the mean wave I latency was longer for the right ear in both groups, and interpeak intervals III-V were greater for the individuals with autism spectrum disorder. For brainstem auditory evoked potentials with speech stimuli, wave V latency was shorter in individuals with autism spectrum disorder. CONCLUSION: These data suggest that individuals with autism spectrum disorder may have a dysfunction of the central auditory nervous system for nonverbal stimuli and faster neural encoding of the initial part of the verbal stimulus, suggesting hypersensitivity to complex sounds such as speech.
Lien vers le texte intégral (Open Access ou abonnement)
10. Landes SD, Stevens JD, Turk MA. {{Obscuring effect of coding developmental disability as the underlying cause of death on mortality trends for adults with developmental disability: a cross-sectional study using US Mortality Data from 2012 to 2016}}. {BMJ Open};2019 (Feb 24);9(2):e026614.
OBJECTIVE: To determine whether coding a developmental disability as the underlying cause of death obscures mortality trends of adults with developmental disability. DESIGN: National Vital Statistics System 2012-2016 US Multiple Cause-of-Death Mortality files. SETTING: USA. PARTICIPANTS: Adults with a developmental disability indicated on their death certificate aged 18 through 103 at the time of death. The study population included 33 154 adults who died between 1 January 2012 and 31 December 2016. PRIMARY OUTCOME AND MEASURES: Decedents with a developmental disability coded as the underlying cause of death on the death certificate were identified using the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision code for intellectual disability, cerebral palsy, Down syndrome or other developmental disability. Death certificates that coded a developmental disability as the underlying cause of death were revised using a sequential underlying cause of death revision process. RESULTS: There were 33 154 decedents with developmental disability: 7901 with intellectual disability, 11 895 with cerebral palsy, 9114 with Down syndrome, 2479 with other developmental disabilities and 1765 with multiple developmental disabilities. Among all decedents, 48.5% had a developmental disability coded as the underlying cause of death, obscuring higher rates of choking deaths among all decedents and dementia and Alzheimer’s disease among decedents with Down syndrome. CONCLUSION: Death certificates that recorded the developmental disability in Part I of the death certificate were more likely to code disability as the underlying cause of death. While revising these death certificates provides a short-term corrective to mortality trends for this population, the severity and extent of this problem warrants a long-term change involving more precise instructions to record developmental disabilities only in Part II of the death certificate.
Lien vers le texte intégral (Open Access ou abonnement)
11. Modgil A, Vien TN, Ackley MA, Doherty JJ, Moss SJ, Davies PA. {{Neuroactive Steroids Reverse Tonic Inhibitory Deficits in Fragile X Syndrome Mouse Model}}. {Front Mol Neurosci};2019;12:15.
Fragile X syndrome (FXS) is the most common form of inherited intellectual disability. A reduction in neuronal inhibition mediated by gamma-aminobutyric acid type A receptors (GABAARs) has been implicated in the pathophysiology of FXS. Neuroactive steroids (NASs) are known allosteric modulators of GABAAR channel function, but recent studies from our laboratory have revealed that NASs also exert persistent metabotropic effects on the efficacy of tonic inhibition by increasing the protein kinase C (PKC)-mediated phosphorylation of the alpha4 and beta3 subunits which increase the membrane expression and boosts tonic inhibition. We have assessed the GABAergic signaling in the hippocampus of fragile X mental retardation protein (FMRP) knock-out (Fmr1 KO) mouse. The GABAergic tonic current in dentate gyrus granule cells (DGGCs) from 3- to 5-week-old (p21-35) Fmr1 KO mice was significantly reduced compared to WT mice. Additionally, spontaneous inhibitory post synaptic inhibitory current (sIPSC) amplitudes were increased in DGGCs from Fmr1 KO mice. While sIPSCs decay in both genotypes was prolonged by the prototypic benzodiazepine diazepam, those in Frm1-KO mice were selectively potentiated by RO15-4513. Consistent with this altered pharmacology, modifications in the expression levels and phosphorylation of receptor GABAAR subtypes that mediate tonic inhibition were seen in Fmr1 KO mice. Significantly, exposure to NASs induced a sustained elevation in tonic current in Fmr1 KO mice which was prevented with PKC inhibition. Likewise, exposure reduced elevated membrane excitability seen in the mutant mice. Collectively, our results suggest that NAS act to reverse the deficits of tonic inhibition seen in FXS, and thereby reduce aberrant neuronal hyperexcitability seen in this disorder.
Lien vers le texte intégral (Open Access ou abonnement)
12. Pavlopoulou G, Dimitriou D. {{‘I don’t live with autism; I live with my sister’. Sisters’ accounts on growing up with their preverbal autistic siblings}}. {Res Dev Disabil};2019 (Feb 22);88:1-15.
BACKGROUND: The experiences of siblings in early adolescent years who grow up with an autistic brother or sister have received very little research interest, especially in terms of sisters’ experiences. Hence our understanding of wellbeing opportunities and challenges in siblings’ everyday life is inadequate and not reflected in the current clinical practices. METHODS: Semi-structured interviews utilising an active, non-judgemental and curious stance to explore how sisters make sense of their everyday experiences (inspired by the notion of mentalizing) were conducted to capture important experiences of nine typically developing female siblings. RESULTS: Interpretative Phenomenological Analysis (IPA) was employed. The master themes included: (i) sisters’ interactions with their siblings- ‘I don’t live with autism, I live with my sister’ (ii) sisters’ interactions with their parents- ‘Always there for us, but often asking too much’, (iii) practical struggles of caring- ‘Like a lonely fighter, tired but always on duty’, (iv) perceived sisters’ needs- ‘I care about my brother and I want society to care about us’. DISCUSSION: As experts of their own lived experience, sisters shed light on their day-to-day experiences. The themes derived from their experiences may help to draw attention to an appreciation of everyday life including planning for the parts that remain a struggle. This latter point is discussed in terms of implications and adoption of an existential view of wellbeing for future research and practice.
Lien vers le texte intégral (Open Access ou abonnement)
13. Pequegnat B, Monteiro MA. {{Carbohydrate Scaffolds for the Study of the Autism-associated Bacterium, Clostridium bolteae}}. {Curr Med Chem};2019 (Feb 25)
A large number of children in the autism spectrum disorder suffer from gastrointestinal (GI) conditions, such as constipation and diarrhea. Clostridium bolteae is part of a set of pathogens being regularly detected in the stool samples of hosts affected by GI and autism symptoms. Accompanying studies have pointed to the possibility that such microbes affect behaviour through the production of neurotoxic metabolites in a so-called, gut-brain connection. As an extension of our Clostridium difficile polysaccharide (PS)-based vaccine research, we engaged in the discovery of C. bolteae surface carbohydrates. So far, studies revealed that C. bolteae produces a specific immunogenic PS capsule comprised of disaccharide repeating blocks of mannose (Manp) and rhamnose (Rhap) units: alpha-D-Manp-(1–>[-4)-beta-D-Rhap-(1–>3)-alpha-D-Manp-(1–>]n. For vaccinology and further immunogenic experiments, a method to produce C. bolteae PS conjugates has been developed, along with the chemical syntheses of the PS non-reducing end linkage, with D-Rha or L-Rha, alpha-D-Manp-(1–>4)-beta-D-Rhap-(1–>O(CH2)5NH2 and alpha-D-Manp-(1–>4)-beta-L-Rhap-(1–>O(CH2)5NH2, equipped with an aminopentyl linker at the reducing end for conjugation purposes. The discovery of C. bolteae PS immunogen opens the door to the creation of non-evasive diagnostic tools to evaluate the frequency and role of this microbe in autistic subjects and to a vaccine to reduce colonization levels in the GI tract, thus impeding the concentration of neurotoxins.
Lien vers le texte intégral (Open Access ou abonnement)
14. Poot M. {{HNRNPU: Key to Neurodevelopmental Disorders such as Intellectual Delay, Epilepsy, and Autism}}. {Mol Syndromol};2019 (Jan);9(6):275-278.
Lien vers le texte intégral (Open Access ou abonnement)
15. Pote I, Wang S, Sethna V, Blasi A, Daly E, Kuklisova-Murgasova M, Lloyd-Fox S, Mercure E, Busuulwa P, Stoencheva V, Charman T, Williams SCR, Johnson MH, Murphy DGM, McAlonan GM. {{Familial risk of autism alters subcortical and cerebellar brain anatomy in infants and predicts the emergence of repetitive behaviors in early childhood}}. {Autism Res};2019 (Feb 22)
Autism spectrum disorder (ASD) is a common neurodevelopmental condition, and infant siblings of children with ASD are at a higher risk of developing autistic traits or an ASD diagnosis, when compared to those with typically developing siblings. Reports of differences in brain anatomy and function in high-risk infants which predict later autistic behaviors are emerging, but although cerebellar and subcortical brain regions have been frequently implicated in ASD, no high-risk study has examined these regions. Therefore, in this study, we compared regional MRI volumes across the whole brain in 4-6-month-old infants with (high-risk, n = 24) and without (low-risk, n = 26) a sibling with ASD. Within the high-risk group, we also examined whether any regional differences observed were associated with autistic behaviors at 36 months. We found that high-risk infants had significantly larger cerebellar and subcortical volumes at 4-6-months of age, relative to low-risk infants; and that larger volumes in high-risk infants were linked to more repetitive behaviors at 36 months. Our preliminary observations require replication in longitudinal studies of larger samples. If correct, they suggest that the early subcortex and cerebellum volumes may be predictive biomarkers for childhood repetitive behaviors. Autism Res 2019. (c) 2019 The Authors. Autism Research published by International Society for Autism Research published byWiley Periodicals, Inc. LAY SUMMARY: Individuals with a family history of autism spectrum disorder (ASD) are at risk of ASD and related developmental difficulties. This study revealed that 4-6-month-old infants at high-risk of ASD have larger cerebellum and subcortical volumes than low-risk infants, and that larger volumes in high-risk infants are associated with more repetitive behaviors in childhood.
Lien vers le texte intégral (Open Access ou abonnement)
16. Powell G, Jones CRG, Hedge C, Charman T, Happe F, Simonoff E, Sumner P. {{Face processing in autism spectrum disorder re-evaluated through diffusion models}}. {Neuropsychology};2019 (Feb 25)
OBJECTIVE: Research using cognitive or perceptual tasks in autism spectrum disorder (ASD) often relies on mean reaction time (RT) and accuracy derived from alternative-forced choice paradigms. However, these measures can confound differences in task-related processing efficiency with caution (i.e., preference for speed or accuracy). We examined whether computational models of decision-making allow these components to be isolated. METHOD: Using data from two face-processing tasks (face recognition and egocentric eye-gaze discrimination), we explored whether adolescents with ASD and wide-ranging intellectual ability differed from an age and IQ matched comparison group on model parameters that are thought to represent processing efficiency, caution, and perceptual encoding/motor output speed. RESULTS: We found evidence that autistic adolescents had lower processing efficiency and caution but did not differ from nonautistic adolescents in the time devoted to perceptual encoding/motor output. These results were more consistent across tasks when we only analyzed participants with IQ above 85. Cross-task correlations suggested that processing efficiency and caution parameters were relatively stable across individuals and tasks. Furthermore, logistic classification with model parameters improved discrimination between individuals with and without ASD relative to classification using mean RT and accuracy. Finally, previous research has found that ADHD symptoms are associated with lower processing efficiency, and we observed a similar relationship in our sample, but only for autistic adolescents. CONCLUSIONS: Together, these results suggest that models of decision-making could provide both better discriminability between autistic and nonautistic individuals on cognitive tasks and also a more specific understanding of the underlying mechanisms driving these differences. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
Lien vers le texte intégral (Open Access ou abonnement)
17. Robison JE. {{Autism prevalence and outcomes in older adults}}. {Autism Res};2019 (Feb 25)
Recent studies of mortality, illness, and suicide among autistic adults paint an alarming picture. Autistic people appear to die much earlier than the general population, and they seem to be far more vulnerable to a surprising range of medical problems. Suicide and depression seem far more common than in the general population. If correct, that suggests an older autistic population in silent crisis, with few if any supports. If so, older autistic people should be a focus for public health and human service agencies. But is the picture complete? Autism researchers ask for answers, identifying problems and their scope. This article discusses the limitations of our adult autism knowledge, and the challenges we will face studying adults. Researching and ultimately serving older autistic adults presents a unique set of problems that have not yet been addressed by scientists or clinicians. Autism Res 2019. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Public policy toward autistic people is driven by data. Most autism data to date have been derived from and about children, because autism tends to be identified and supported in the public school system. This has created a public perception of autism as a childhood problem. In fact, autism is a lifelong difference or disability, and recent studies suggest serious overlooked concerns for autistic adults. This commentary discusses how we have evaluated adult autism so far, limitations of our knowledge, and how we might evaluate adult needs going forward. The commentary makes a case for specific new adult prevalence and outcome studies to inform public policy.
Lien vers le texte intégral (Open Access ou abonnement)
18. Salcedo-Arellano MJ, Hagerman RJ, Martinez-Cerdeno V. {{[Fragile X associated tremor/ataxia syndrome: its clinical presentation, pathology, and treatment]}}. {Rev Neurol};2019 (Mar 1);68(5):199-206.
The fragile X associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disease associated with the repetition of CGG triplets (55-200 CGG repetitions) in the FMR1 gene. The premutation of the FMR1 gene, contrasting with the full mutation (more than 200 CGG repetitions), presents an increased production of messenger and a similar or slightly decreased production of FMRP protein. FXTAS affects 40% of men and 16% of women carriers of the premutation. It presents with a wide constellation of neurological signs such as intention tremor, cerebellar ataxia, parkinsonism, executive function deficits, peripheral neuropathy and cognitive decline leading to dementia among others. In this review, we present what is currently known about the molecular mechanism, the radiological findings and the pathology, as well as the complexity of the diagnosis and management of FXTAS.
Lien vers le texte intégral (Open Access ou abonnement)
19. Shaia WE, Nichols HM, Dababnah S, Campion K, Garbarino N. {{Brief Report: Participation of Black and African-American Families in Autism Research}}. {J Autism Dev Disord};2019 (Feb 25)
Black and African-American families are underrepresented in research on autism spectrum disorder (ASD) and few studies have explored how to increase their involvement. To address this gap in the literature, this study explored the perspectives of 22 Black families raising children with ASD in order to identify facilitators and barriers to research participation; as well as suggestions to increase their involvement in ASD studies. Facilitators to research involvement included a desire to contribute to ASD research inclusive of Black families; to seek information and support for child and/or caregiver; and, to engage with culturally responsive research team members. Barriers to research involvement included stigma; denial, shame, and/or embarrassment; distrust of the research process; lack of time/interest; and research material inaccessibility or literacy issues.
Lien vers le texte intégral (Open Access ou abonnement)
20. Shomrat T, Nesher N. {{Updated View on the Relation of the Pineal Gland to Autism Spectrum Disorders}}. {Front Endocrinol (Lausanne)};2019;10:37.
Identification of the biological features of autism is essential for designing an efficient treatment and for prevention of the disorder. Though the subject of extensive research, the neurophysiological features of autism remain unclear. One of the proposed biological causes of autism is malfunction of the pineal gland and deficiency of its principal hormone, melatonin. The main function of melatonin is to link and synchronize the body’s homeostasis processes to the circadian and seasonal rhythms, and to regulate the sleep-wake cycle. Therefore, pineal dysfunction has been implicated based on the common observation of low melatonin levels and sleep disorders associated with autism. In this perspective, we highlight several recent findings that support the hypothesis of pineal gland/melatonin involvement in autism. Another common symptom of autism is abnormal neuroplasticity, such as cortical overgrowth and dendritic spine dysgenesis. Here, we synthesize recent information and speculate on the possibility that this abnormal neuroplasticity is caused by hyperactivity of endogenous N,N-dimethyltryptamine (DMT). The pineal gland was proposed as the source of DMT in the brain and therefore, our assumption is that besides melatonin deficiency, pineal dysfunction might also play a part in the development of autism through abnormal metabolism of DMT. We hope that this manuscript will encourage future research of the DMT hypothesis and reexamination of several observations that were previously attributed to other factors, to see if they could be related to pineal gland/melatonin malfunction. Such research could contribute to the development of autism treatment by exogenous melatonin and monitored light exposure.
Lien vers le texte intégral (Open Access ou abonnement)
21. Stein Duker LI, Florindez LI, Como DH, Tran CF, Henwood BF, Polido JC, Cermak SA. {{Strategies for Success: A Qualitative Study of Caregiver and Dentist Approaches to Improving Oral Care for Children with Autism}}. {Pediatr Dent};2019 (Jan 15);41(1):4e-12e.
Purpose: Oral health is important to physical and psychological health. Individuals with autism spectrum disorder (ASD) experience significant oral care challenges, but little research exists that examines efficacious interventions to improve care. The purpose of this study was to qualitatively explore parental and dentist reports of successful strategies implemented during dental care with children with ASD. Methods: Focus groups were conducted with parents of children with ASD (N = two groups) and dentists treating children with ASD (N = two groups). Focus group transcripts were transcribed verbatim and analyzed using a thematic analysis approach. Results: Three key themes were identified from the parent focus groups: (1) what makes a good dentist; (2) flexibility and techniques-strategies used by the dentist; and (3) preparation-strategies for parents and caregivers of children with ASD. Four themes emerged from the dentist groups: (1) parents know best; (2) practice; (3) flexibility; and (4) a network of colleagues. Areas of overlap between the parents and dental providers included the importance of preparation, necessity of flexibility and creativity, and value of collaboration. Conclusions: Our findings provide insight into techniques perceived by parents and dental providers to facilitate successful dental encounters for children with ASD.
22. Sutoko S, Monden Y, Tokuda T, Ikeda T, Nagashima M, Kiguchi M, Maki A, Yamagata T, Dan I. {{Distinct Methylphenidate-Evoked Response Measured Using Functional Near-Infrared Spectroscopy During Go/No-Go Task as a Supporting Differential Diagnostic Tool Between Attention-Deficit/Hyperactivity Disorder and Autism Spectrum Disorder Comorbid Children}}. {Front Hum Neurosci};2019;13:7.
Attention deficit/hyperactivity disorder (ADHD) has been frequently reported as co-occurring with autism spectrum disorder (ASD). However, ASD-comorbid ADHD is difficult to diagnose since clinically significant symptoms are similar in both disorders. Therefore, we propose a classification method of differentially recognizing the ASD-comorbid condition in ADHD children. The classification method was investigated based on functional brain imaging measured by near-infrared spectroscopy (NIRS) during a go/no-go task. Optimization and cross-validation of the classification method was carried out in medicated-naive and methylphenidate (MPH) administered ADHD and ASD-comorbid ADHD children (randomized, double-blind, placebo-controlled, and crossover design) to select robust parameters and cut-off thresholds. The parameters could be defined as either single or averaged multi-channel task-evoked activations under an administration condition (i.e., pre-medication, post-MPH, and post-placebo). The ADHD children were distinguished by significantly high MPH-evoked activation in the right hemisphere near the midline vertex. The ASD-comorbid ADHD children tended to have low activation responses in all regions. High specificity (86 +/- 4.1%; mean +/- SD), sensitivity (93 +/- 7.3%), and accuracy (82 +/- 1.6%) were obtained using the activation of oxygenated-hemoglobin concentration change in right middle frontal, angular, and precentral gyri under MPH medication. Therefore, the significantly differing MPH-evoked responses are potentially effective features and as supporting differential diagnostic tools.
Lien vers le texte intégral (Open Access ou abonnement)
23. Tang S, Powell EM, Zhu W, Lo FS, Erzurumlu RS, Xu S. {{Altered Forebrain Functional Connectivity and Neurotransmission in a Kinase-Inactive Met Mouse Model of Autism}}. {Mol Imaging};2019 (Jan-Dec);18:1536012118821034.
MET, the gene encoding the tyrosine kinase receptor for hepatocyte growth factor, is a susceptibility gene for autism spectrum disorder (ASD). Genetically altered mice with a kinase-inactive Met offer a potential model for understanding neural circuit organization changes in autism. Here, we focus on the somatosensory thalamocortical circuitry because distinct somatosensory sensitivity phenotypes accompany ASD, and this system plays a major role in sensorimotor and social behaviors in mice. We employed resting-state functional magnetic resonance imaging and in vivo high-resolution proton MR spectroscopy to examine neuronal connectivity and neurotransmission of wild-type, heterozygous Met-Emx1, and fully inactive homozygous Met-Emx1 mice. Met-Emx1 brains showed impaired maturation of large-scale somatosensory network connectivity when compared with wild-type controls. Significant sex x genotype interaction in both network features and glutamate/gamma-aminobutyric acid (GABA) balance was observed. Female Met-Emx1 brains showed significant connectivity and glutamate/GABA balance changes in the somatosensory thalamocortical system when compared with wild-type brains. The glutamate/GABA ratio in the thalamus was correlated with the connectivity between the somatosensory cortex and the thalamus in heterozygous Met-Emx1 female brains. The findings support the hypothesis that aberrant functioning of the somatosensory thalamocortical system is at the core of the conspicuous somatosensory behavioral phenotypes observed in Met-Emx1 mice.
Lien vers le texte intégral (Open Access ou abonnement)
24. Underwood JFG, Kendall KM, Berrett J, Lewis C, Anney R, van den Bree MBM, Hall J. {{Autism spectrum disorder diagnosis in adults: phenotype and genotype findings from a clinically derived cohort}}. {Br J Psychiatry};2019 (Feb 26):1-7.
BACKGROUND: The past decade has seen the development of services for adults presenting with symptoms of autism spectrum disorder (ASD) in the UK. Compared with children, little is known about the phenotypic and genetic characteristics of these patients.AimsThis e-cohort study aimed to examine the phenotypic and genetic characteristics of a clinically presenting sample of adults diagnosed with ASD by specialist services. METHOD: Individuals diagnosed with ASD as adults were recruited by the National Centre for Mental Health and completed self-report questionnaires, interviews and provided DNA; 105 eligible individuals were matched to 76 healthy controls. We investigated demographics, social history and comorbid psychiatric and physical disorders. Samples were genotyped, copy number variants (CNVs) were called and polygenic risk scores were calculated. RESULTS: Of individuals with ASD, 89.5% had at least one comorbid psychiatric diagnosis, with depression (62.9%) and anxiety (55.2%) being the most common. The ASD group experienced more neurological comorbidities than controls, particularly migraine headache. They were less likely to have married or be in work, and had more alcohol-related problems. There was a significantly higher load of autism common genetic variants in the adult ASD group compared with controls, but there was no difference in the rate of rare CNVs. CONCLUSIONS: This study provides important information about psychiatric comorbidity in adult ASD, which may inform clinical practice and patient counselling. It also suggests that the polygenic load of common ASD-associated variants may be important in conferring risk within the non-intellectually disabled population of adults with ASD.Declaration of interestNone.
Lien vers le texte intégral (Open Access ou abonnement)
25. van Laarhoven T, Stekelenburg JJ, Eussen M, Vroomen J. {{Electrophysiological Alterations in Motor-Auditory Predictive Coding in Autism Spectrum Disorder}}. {Autism Res};2019 (Feb 23)
The amplitude of the auditory N1 component of the event-related potential (ERP) is typically attenuated for self-initiated sounds, compared to sounds with identical acoustic and temporal features that are triggered externally. This effect has been ascribed to internal forward models predicting the sensory consequences of one’s own motor actions. The predictive coding account of autistic symptomatology states that individuals with autism spectrum disorder (ASD) have difficulties anticipating upcoming sensory stimulation due to a decreased ability to infer the probabilistic structure of their environment. Without precise internal forward prediction models to rely on, perception in ASD could be less affected by prior expectations and more driven by sensory input. Following this reasoning, one would expect diminished attenuation of the auditory N1 due to self-initiation in individuals with ASD. Here, we tested this hypothesis by comparing the neural response to self- versus externally-initiated tones between a group of individuals with ASD and a group of age matched neurotypical controls. ERPs evoked by tones initiated via button-presses were compared with ERPs evoked by the same tones replayed at identical pace. Significant N1 attenuation effects were only found in the TD group. Self-initiation of the tones did not attenuate the auditory N1 in the ASD group, indicating that they may be unable to anticipate the auditory sensory consequences of their own motor actions. These results show that individuals with ASD have alterations in sensory attenuation of self-initiated sounds, and support the notion of impaired predictive coding as a core deficit underlying autistic symptomatology. Autism Res 2019, 9999: 1-11. (c) 2019 The Authors. Autism Research published by International Society for Autism Research published by Wiley Periodicals, Inc. LAY SUMMARY: Many individuals with ASD experience difficulties in processing sensory information (for example, increased sensitivity to sound). Here we show that these difficulties may be related to an inability to anticipate upcoming sensory stimulation. Our findings contribute to a better understanding of the neural mechanisms underlying the different sensory perception experienced by individuals with ASD.
Lien vers le texte intégral (Open Access ou abonnement)
26. Wenzel HJ, Murray KD, Haify SN, Hunsaker MR, Schwartzer JJ, Kim K, La Spada AR, Sopher BL, Hagerman PJ, Raske C, Severijnen L, Willemsen R, Hukema RK, Berman RF. {{Astroglial-targeted expression of the fragile X CGG repeat premutation in mice yields RAN translation, motor deficits and possible evidence for cell-to-cell propagation of FXTAS pathology}}. {Acta Neuropathol Commun};2019 (Feb 26);7(1):27.
The fragile X premutation is a CGG trinucleotide repeat expansion between 55 and 200 repeats in the 5′-untranslated region of the fragile X mental retardation 1 (FMR1) gene. Human carriers of the premutation allele are at risk of developing the late-onset neurodegenerative disorder, fragile X-associated tremor/ataxia syndrome (FXTAS). Characteristic neuropathology associated with FXTAS includes intranuclear inclusions in neurons and astroglia. Previous studies recapitulated these histopathological features in neurons in a knock-in mouse model, but without significant astroglial pathology. To determine the role of astroglia in FXTAS, we generated a transgenic mouse line (Gfa2-CGG99-eGFP) that selectively expresses a 99-CGG repeat expansion linked to an enhanced green fluorescent protein (eGFP) reporter in astroglia throughout the brain, including cerebellar Bergmann glia. Behaviorally these mice displayed impaired motor performance on the ladder-rung test, but paradoxically better performance on the rotarod. Immunocytochemical analysis revealed that CGG99-eGFP co-localized with GFAP and S-100ss, but not with NeuN, Iba1, or MBP, indicating that CGG99-eGFP expression is specific to astroglia. Ubiquitin-positive intranuclear inclusions were found in eGFP-expressing glia throughout the brain. In addition, intracytoplasmic ubiquitin-positive inclusions were found outside the nucleus in distal astrocyte processes. Intriguingly, intranuclear inclusions, in the absence of eGFP mRNA and eGFP fluorescence, were present in neurons of the hypothalamus and neocortex. Furthermore, intranuclear inclusions in both neurons and astrocytes displayed immunofluorescent labeling for the polyglycine peptide FMRpolyG, implicating FMRpolyG in the pathology found in Gfa2-CGG99 mice. Considered together, these results show that Gfa2-CGG99 expression in mice is sufficient to induce key features of FXTAS pathology, including formation of intranuclear inclusions, translation of FMRpolyG, and deficits in motor function.
Lien vers le texte intégral (Open Access ou abonnement)
27. Zabihi M, Oldehinkel M, Wolfers T, Frouin V, Goyard D, Loth E, Charman T, Tillmann J, Banaschewski T, Dumas G, Holt R, Baron-Cohen S, Durston S, Bolte S, Murphy D, Ecker C, Buitelaar JK, Beckmann CF, Marquand AF. {{Dissecting the Heterogeneous Cortical Anatomy of Autism Spectrum Disorder Using Normative Models}}. {Biol Psychiatry Cogn Neurosci Neuroimaging};2018 (Dec 19)
BACKGROUND: The neuroanatomical basis of autism spectrum disorder (ASD) has remained elusive, mostly owing to high biological and clinical heterogeneity among diagnosed individuals. Despite considerable effort toward understanding ASD using neuroimaging biomarkers, heterogeneity remains a barrier, partly because studies mostly employ case-control approaches, which assume that the clinical group is homogeneous. METHODS: Here, we used an innovative normative modeling approach to parse biological heterogeneity in ASD. We aimed to dissect the neuroanatomy of ASD by mapping the deviations from a typical pattern of neuroanatomical development at the level of the individual and to show the necessity to look beyond the case-control paradigm to understand the neurobiology of ASD. We first estimated a vertexwise normative model of cortical thickness development using Gaussian process regression, then mapped the deviation of each participant from the typical pattern. For this, we employed a heterogeneous cross-sectional sample of 206 typically developing individuals (127 males) and 321 individuals with ASD (232 males) (6-31 years of age). RESULTS: We found few case-control differences, but the ASD cohort showed highly individualized patterns of deviations in cortical thickness that were widespread across the brain. These deviations correlated with severity of repetitive behaviors and social communicative symptoms, although only repetitive behaviors survived corrections for multiple testing. CONCLUSIONS: Our results 1) reinforce the notion that individuals with ASD show distinct, highly individualized trajectories of brain development and 2) show that by focusing on common effects (i.e., the « average ASD participant »), the case-control approach disguises considerable interindividual variation crucial for precision medicine.
