1. Benevides TW, Shore SM, Andresen ML, Caplan R, Cook B, Gassner DL, Erves JM, Hazlewood TM, King MC, Morgan L, Murphy LE, Purkis Y, Rankowski B, Rutledge SM, Welch SP, Wittig K. {{Interventions to address health outcomes among autistic adults: A systematic review}}. {Autism}. 2020: 1362361320913664.
LAY ABSTRACT: Autistic adults have more health problems then their same-aged peers. Yet little research has been conducted that focuses on addressing these health problems. In order to guide future research, it is important to know what intervention studies have been done to improve health outcomes among autistic adults. The project team and student assistants read studies that were published between 2007 and 2018 in the online research database, PubMed. We looked for studies published in English, which were peer-reviewed and included (1) an intervention, (2) an outcome that was related to health, and (3) a study group that included autistic adults. We did not include studies that had outcomes about employment (unless there was a health outcome), studies about caregivers or caregiving, or expert opinions about interventions. Of 778 reviewed articles, 19 studies met all of the criteria above. Within these studies, two approaches were found to have emerging evidence for their use in autistic adults: cognitive behavioral interventions and mindfulness-based approaches for improved mental health outcomes. The remaining intervention approaches did not have enough articles to support their use. Many of the outcomes were about reduced symptoms of co-occurring mental health diagnoses (e.g. reduced anxiety, depression). Most of the participants in these studies were male and did not have intellectual disability. Most study participants were adults younger than 40. There are not many intervention studies that address health outcomes among autistic adults. More research is needed on interventions which are desired by the adult autism community and address preferred health outcomes such as increased quality of life or well-being.
Lien vers le texte intégral (Open Access ou abonnement)
2. Cadieux L, Keenan M. {{Can Social Communication Skills for Children Diagnosed With Autism Spectrum Disorder Rehearsed Inside the Video Game Environment of Minecraft Generalize to the Real World?}}. {JMIR serious games}. 2020; 8(2): e14369.
In this paper, we outline opportunities within the video game environment for building skills applicable to real-world issues faced by some children. The game Minecraft is extremely popular and of particular interest to children diagnosed with autism spectrum disorder. Although the game has been used by support communities to facilitate the social interaction of children and peer support for their parents, little has been done to examine how social skills developed within the game environment generalize to the real world. Social Craft aims to establish a framework in which key social communication skills would be rehearsed in-game with a view to facilitating their replication in a similarly contained real-world environment. Central to this approach is an understanding of the basic principles of behavior and the engagement of a sound methodology for the collection of data inside and outside the respective environments.
Lien vers le texte intégral (Open Access ou abonnement)
3. Chetcuti L, Uljarevic M, Varcin KJ, Boutrus M, Wan MW, Slonims V, Green J, Segal L, Iacono T, Dissanayake C, Whitehouse AJO, Hudry K. {{The Role of Negative Affectivity in Concurrent Relations Between Caregiver Psychological Distress and Social-Emotional Difficulties in Infants With Early Signs of Autism}}. {Autism Res}. 2020.
Recent evidence suggests the link between caregiver psychological distress and offspring social-emotional difficulties may be accounted for by offspring temperament characteristics. However, existing studies have only focused on neurotypical children; thus, the current study sought to provide an initial examination of this process among children with varying levels of early autism features. Participants included 103 infants aged 9-16 months (M = 12.39, SD = 1.97; 68% male) and their primary caregiver (96% mothers) referred to a larger study by community healthcare professionals. We utilized caregiver-reported measures of psychological distress (Depression Anxiety Stress Scales), infant temperament (Infant Behavior Questionnaire-Revised) and internalizing and externalizing symptoms (Infant-Toddler Social and Emotional Assessment) and administered the Autism Observation Schedule for Infants (AOSI) at an assessment visit to quantify autism features. Infant negative affectivity was found to mediate positive concurrent relations between caregiver psychological distress and infant internalizing and externalizing symptoms, irrespective of the infants’ AOSI score. While preliminary and cross-sectional, these results replicate and extend previous findings suggesting that the pathway from caregiver psychological distress to negative affectivity to social-emotional difficulties might also be apparent among infants with varying levels of autism features. More rigorous tests of causal effects await future longitudinal investigation. LAY SUMMARY: Offspring of caregivers experiencing psychological distress (i.e., symptoms of depression, anxiety, and/or stress) may themselves be at increased risk of poor mental health outcomes. Several previous studies conducted with neurotypical children suggest that this link from caregiver-to-child may be facilitated by children’s temperament qualities. This study was a preliminary cross-sectional exploration of these relationships in infants with features of autism. We found that infants’ elevated negative emotions were involved in the relation between caregiver heightened psychological distress and children’s mental health difficulties, consistent with neurotypical development.
Lien vers le texte intégral (Open Access ou abonnement)
4. Chu SY, Park H, Lee J, Shaharuddin KKB, Gan CH. {{Self-stigma and its associations with stress and quality of life among Malaysian parents of children with autism}}. {Child Care Health Dev}. 2020.
BACKGROUND: This study explored the relationship between self-perceived stigmatisation (affiliate stigma), stress, and quality of life among parents of children with Autism Spectrum Disorder (ASD). METHOD: Participants (N = 110) filled-in the Affiliate Stigma Scale, the Caregiver Burden Inventory, and the CarerQOL scale. RESULTS: Parents reported low scores on stigma and fair levels of stress and quality of life, indicating that parents do not feel stigmatised by affiliation with a child with ASD nor are they stressed from affiliate stigma. After controlling for demographic factors, both the relationships of affiliate stigma with stress and with quality of life were weak, indicating that stigma may have little to no effect on stress and quality of life. CONCLUSION: Cultural and religious beliefs may play a part in the acceptance of a child’s condition resulting in less impact of stigma on the parents.
Lien vers le texte intégral (Open Access ou abonnement)
5. Dias CM, Walsh CA. {{Recent Advances in Understanding the Genetic Architecture of Autism}}. {Annual review of genomics and human genetics}. 2020.
Recent advances in understanding the genetic architecture of autism spectrum disorder have allowed for unprecedented insight into its biological underpinnings. New studies have elucidated the contributions of a variety of forms of genetic variation to autism susceptibility. While the roles of de novo copy number variants and single-nucleotide variants-causing loss-of-function or missense changes-have been increasingly recognized and refined, mosaic single-nucleotide variants have been implicated more recently in some cases. Moreover, inherited variants (including common variants) and, more recently, rare recessive inherited variants have come into greater focus. Finally, noncoding variants-both inherited and de novo-have been firmly implicated in the last few years. This work has revealed a convergence of diverse genetic drivers on common biological pathways and has highlighted the ongoing importance of increasing sample size and experimental innovation. Continuing to synthesize these genetic findings with functional and phenotypic evidence and translating these discoveries to clinical care remain considerable challenges for the field. Expected final online publication date for the Annual Review of Genomics and Human Genetics, Volume 21 is August 31, 2020. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
Lien vers le texte intégral (Open Access ou abonnement)
6. Dietz PM, Rose CE, McArthur D, Maenner M. {{National and State Estimates of Adults with Autism Spectrum Disorder}}. {J Autism Dev Disord}. 2020.
U.S. national and state population-based estimates of adults living with autism spectrum disorder (ASD) are nonexistent due to the lack of existing surveillance systems funded to address this need. Therefore, we estimated national and state prevalence of adults 18-84 years living with ASD using simulation in conjunction with Bayesian hierarchal models. In 2017, we estimated that approximately 2.21% (95% simulation interval (SI) 1.95%, 2.45%) or 5,437,988 U.S. adults aged 18 and older have ASD, with state prevalence ranging from 1.97% (95% SI 1.55%, 2.45%) in Louisiana to 2.42% (95% SI 1.93%, 2.99%) in Massachusetts. Prevalence and case estimates of adults living with ASD (diagnosed and undiagnosed) can help states estimate the need for diagnosing and providing services to those unidentified.
Lien vers le texte intégral (Open Access ou abonnement)
7. Donovan J. {{Childbirth Experiences of Women With Autism Spectrum Disorder in an Acute Care Setting}}. {Nursing for women’s health}. 2020.
OBJECTIVE: To describe the childbirth experiences of women with autism spectrum disorder. DESIGN: Qualitative interpretive description design and data analysis using Knafl and Webster. SETTING: Women were interviewed in the environment of their choosing: in the home, over the telephone, or via Skype or Facebook Messenger. PARTICIPANTS: Twenty-four women ages 29 to 65 years from the United States, United Kingdom, and Australia, all of whom gave birth to healthy newborns in an acute care setting. METHOD: Interviews were conducted using a semistructured interview guide. RESULTS: Three main themes emerged from the data: Having Difficulty Communicating, Feeling Stressed in an Uncertain Environment, and Being an Autistic Mother. Each of these themes also included several subthemes. CONCLUSION: Study participants expressed difficulty communicating with nurses in a variety of ways. The degree of difficulty in communication varied among participants. Problems in communication included trouble conveying needs, alerting nurses when they felt ill, or not understanding what was said to them. Ineffective communication with nurses resulted in feelings of anxiety and being scared and inhibited participants in further attempts at communication. Nurses caring for women with ASD through the childbirth period should be aware that communication needs will vary for each woman, and interventions to facilitate safe and effective communication in labor should be individualized to each woman.
Lien vers le texte intégral (Open Access ou abonnement)
8. Hernandez LM, Green SA, Lawrence KE, Inada M, Liu J, Bookheimer SY, Dapretto M. {{Social Attention in Autism: Neural Sensitivity to Speech Over Background Noise Predicts Encoding of Social Information}}. {Frontiers in psychiatry}. 2020; 11: 343.
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by lack of attention to social cues in the environment, including speech. Hypersensitivity to sensory stimuli, such as loud noises, is also extremely common in youth with ASD. While a link between sensory hypersensitivity and impaired social functioning has been hypothesized, very little is known about the neural mechanisms whereby exposure to distracting sensory stimuli may interfere with the ability to direct attention to socially-relevant information. Here, we used functional magnetic resonance imaging (fMRI) in youth with and without ASD (N=54, age range 8-18 years) to (1) examine brain responses during presentation of brief social interactions (i.e., two-people conversations) shrouded in ecologically-valid environmental noises, and (2) assess how brain activity during encoding might relate to later accuracy in identifying what was heard. During exposure to conversation-in-noise (vs. conversation or noise alone), both neurotypical youth and youth with ASD showed robust activation of canonical language networks. However, the extent to which youth with ASD activated temporal language regions, including voice-selective cortex (i.e., posterior superior temporal sulcus), predicted later discriminative accuracy in identifying what was heard. Further, relative to neurotypical youth, ASD youth showed significantly greater activity in left-hemisphere speech-processing cortex (i.e., angular gyrus) while listening to conversation-in-noise (vs. conversation or noise alone). Notably, in youth with ASD, increased activity in this region was associated with higher social motivation and better social cognition measures. This heightened activity in voice-selective/speech-processing regions may serve as a compensatory mechanism allowing youth with ASD to hone in on the conversations they heard in the context of non-social distracting stimuli. These findings further suggest that focusing on social and non-social stimuli simultaneously may be more challenging for youth with ASD requiring the recruitment of additional neural resources to encode socially-relevant information.
Lien vers le texte intégral (Open Access ou abonnement)
9. Jaswal VK, Wayne A, Golino H. {{Eye-tracking reveals agency in assisted autistic communication}}. {Sci Rep}. 2020; 10(1): 7882.
About one-third of autistic people have limited ability to use speech. Some have learned to communicate by pointing to letters of the alphabet. But this method is controversial because it requires the assistance of another person-someone who holds a letterboard in front of users and so could theoretically cue them to point to particular letters. Indeed, some scientists have dismissed the possibility that any nonspeaking autistic person who communicates with assistance could be conveying their own thoughts. In the study reported here, we used head-mounted eye-tracking to investigate communicative agency in a sample of nine nonspeaking autistic letterboard users. We measured the speed and accuracy with which they looked at and pointed to letters as they responded to novel questions. Participants pointed to about one letter per second, rarely made spelling errors, and visually fixated most letters about half a second before pointing to them. Additionally, their response times reflected planning and production processes characteristic of fluent spelling in non-autistic typists. These findings render a cueing account of participants’ performance unlikely: The speed, accuracy, timing, and visual fixation patterns suggest that participants pointed to letters they selected themselves, not letters they were directed to by the assistant. The blanket dismissal of assisted autistic communication is therefore unwarranted.
Lien vers le texte intégral (Open Access ou abonnement)
10. Le J, Kou J, Zhao W, Fu M, Zhang Y, Becker B, Kendrick KM. {{Oxytocin biases eye-gaze to dynamic and static social images and the eyes of fearful faces: associations with trait autism}}. {Translational psychiatry}. 2020; 10(1): 142.
A key functional effect of intranasal oxytocin with potential therapeutic relevance for autism-spectrum disorder is its reported facilitation of attention towards social stimuli, notably the eye region of faces. In the current randomized placebo-controlled within-subject experiment on 40 healthy males, we investigated the robustness of this facilitation of attention by intranasal oxytocin (24IU) towards social cues. Eye-tracking measures of preference for dynamic and static social vs. non-social stimuli were taken in four different paradigms where autistic individuals tend to exhibit reduced interest in social stimuli. Additionally, we investigated whether oxytocin increases attention towards the eyes relative to other salient face regions in an emotional face paradigm. Results showed that the time spent viewing both dynamic and static social vs. non-social stimuli was negatively associated with trait autism and significantly increased following intranasal oxytocin. For face stimuli, oxytocin primarily increased gaze towards the eyes of fearful expression faces but not for other face emotions. Overall, our findings demonstrate that oxytocin significantly shifts gaze preference towards social vs. non-social stimuli and to the eyes of fearful faces. Importantly, oxytocin appears generally to shift attention more towards salient social stimuli of particular relevance in the context of autism providing further support for its potential therapeutic use in autism-spectrum disorder.
Lien vers le texte intégral (Open Access ou abonnement)
11. Leibson C, Weaver A, Myers S, Long K, Ransom J, Voigt R, Katusic S. {{Objective Estimates of Direct-Medical Costs Among Persons Aged 3 to 38 Years With and Without Research-Defined Autism Spectrum Disorder Ascertained During Childhood: A Population-Based Birth-Cohort Study}}. {Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research}. 2020; 23(5): 595-605.
OBJECTIVES: Accurate estimates of autism spectrum disorder (ASD)-associated medical costs are essential for predicting future care needs, allocating resources, identifying best practices, and modeling cost-effectiveness. Most existing studies have either employed subjective cost data or ascertained ASD using self-reported or International Classification of Diseases-coded diagnoses. Such ascertainment is especially problematic for identifying milder ASD among older individuals never diagnosed with ASD. METHODS: This 1976 through 2000 population-based birth-cohort study was set in Olmsted County, Minnesota. ASD cases and age- and sex-matched unaffected controls were identified by applying uniform operational research criteria for ASD (using the guidelines of the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision) after rigorous review of provider-linked medical and public, private, or home school records available for all members from birth to a maximum age of 21 years. Medical cost estimates for the 901 case-control pairs used line-item provider-linked billing data (including all payers) from 2003 through 2014 (ages 3-38 years). Outpatient pharmaceutical costs were unavailable. Temporal changes in diagnostic criteria, clinical practice, public awareness, and access were addressed by separating analyses into 5-year age group and 4-year calendar period cells. Unadjusted and adjusted (age and age plus co-occurring conditions) cost estimates were provided for cases, controls, and case-control differences. Additional factors (co-occurring conditions, percentage hospitalized, intellectual disability) were investigated using unadjusted descriptive analyses. RESULTS: Cell sample sizes ranged from 93 to 402 for age groups 3 through 19 years and from 45 to 395 for age groups 20 through 38 years. Unadjusted, age-adjusted, and fully adjusted medical costs were significantly higher for cases versus controls in 100% of cells for age groups 3 through 19 years and in 50% (unadjusted), 38% (age adjusted), and 12% (fully adjusted) of cells for age groups 20 through 38 years. CONCLUSIONS: These unique estimates can help inform the construction of cost-effectiveness models; decisions by payers, providers, and policy makers; and predictions of lifetime costs.
Lien vers le texte intégral (Open Access ou abonnement)
12. Oztan O, Garner JP, Constantino JN, Parker KJ. {{Neonatal CSF vasopressin concentration predicts later medical record diagnoses of autism spectrum disorder}}. {Proceedings of the National Academy of Sciences of the United States of America}. 2020; 117(19): 10609-13.
Autism spectrum disorder (ASD) is a brain disorder characterized by social impairments. ASD is currently diagnosed on the basis of behavioral criteria because no robust biomarkers have been identified. However, we recently found that cerebrospinal fluid (CSF) concentration of the « social » neuropeptide arginine vasopressin (AVP) is significantly lower in pediatric ASD cases vs. controls. As an initial step in establishing the direction of causation for this association, we capitalized upon a rare biomaterials collection of newborn CSF samples to conduct a quasi-prospective test of whether this association held before the developmental period when ASD first manifests. CSF samples had been collected in the course of medical care of 0- to 3-mo-old febrile infants (n = 913) and subsequently archived at -70 degrees C. We identified a subset of CSF samples from individuals later diagnosed with ASD, matched them 1:2 with appropriate controls (n = 33 total), and quantified their AVP and oxytocin (OXT) concentrations. Neonatal CSF AVP concentrations were significantly lower among ASD cases than controls and individually predicted case status, with highest precision when cases with comorbid attention-deficit/hyperactivity disorder were removed from the analysis. The associations were specific to AVP, as ASD cases and controls did not differ in neonatal CSF concentrations of the structurally related neuropeptide, OXT. These preliminary findings suggest that a neurochemical marker of ASD may be present very early in life, and if replicated in a larger, prospective study, this approach could transform how ASD is detected, both in behaviorally symptomatic children, and in infants at risk for developing it.
Lien vers le texte intégral (Open Access ou abonnement)
13. Pu Y, Yang J, Chang L, Qu Y, Wang S, Zhang K, Xiong Z, Zhang J, Tan Y, Wang X, Fujita Y, Ishima T, Wang D, Hwang SH, Hammock BD, Hashimoto K. {{Maternal glyphosate exposure causes autism-like behaviors in offspring through increased expression of soluble epoxide hydrolase}}. {Proceedings of the National Academy of Sciences of the United States of America}. 2020.
Epidemiological studies suggest that exposure to herbicides during pregnancy might increase risk for autism spectrum disorder (ASD) in offspring. However, the precise mechanisms underlying the risk of ASD by herbicides such as glyphosate remain unclear. Soluble epoxide hydrolase (sEH) in the metabolism of polyunsaturated fatty acids is shown to play a key role in the development of ASD in offspring after maternal immune activation. Here, we found ASD-like behavioral abnormalities in juvenile offspring after maternal exposure to high levels of formulated glyphosate. Furthermore, we found higher levels of sEH in the prefrontal cortex (PFC), hippocampus, and striatum of juvenile offspring, and oxylipin analysis showed decreased levels of epoxy-fatty acids such as 8 (9)-EpETrE in the blood, PFC, hippocampus, and striatum of juvenile offspring after maternal glyphosate exposure, supporting increased activity of sEH in the offspring. Moreover, we found abnormal composition of gut microbiota and short-chain fatty acids in fecal samples of juvenile offspring after maternal glyphosate exposure. Interestingly, oral administration of TPPU (an sEH inhibitor) to pregnant mothers from E5 to P21 prevented ASD-like behaviors such as social interaction deficits and increased grooming time in the juvenile offspring after maternal glyphosate exposure. These findings suggest that maternal exposure to high levels of glyphosate causes ASD-like behavioral abnormalities and abnormal composition of gut microbiota in juvenile offspring, and that increased activity of sEH might play a role in ASD-like behaviors in offspring after maternal glyphosate exposure. Therefore, sEH may represent a target for ASD in offspring after maternal stress from occupational exposure to contaminants.
Lien vers le texte intégral (Open Access ou abonnement)
14. Ross PJ, Mok RSF, Smith BS, Rodrigues DC, Mufteev M, Scherer SW, Ellis J. {{Modeling neuronal consequences of autism-associated gene regulatory variants with human induced pluripotent stem cells}}. {Mol Autism}. 2020; 11(1): 33.
Genetic factors contribute to the development of autism spectrum disorder (ASD), and although non-protein-coding regions of the genome are being increasingly implicated in ASD, the functional consequences of these variants remain largely uncharacterized. Induced pluripotent stem cells (iPSCs) enable the production of personalized neurons that are genetically matched to people with ASD and can therefore be used to directly test the effects of genomic variation on neuronal gene expression, synapse function, and connectivity. The combined use of human pluripotent stem cells with genome editing to introduce or correct specific variants has proved to be a powerful approach for exploring the functional consequences of ASD-associated variants in protein-coding genes and, more recently, long non-coding RNAs (lncRNAs). Here, we review recent studies that implicate lncRNAs, other non-coding mutations, and regulatory variants in ASD susceptibility. We also discuss experimental design considerations for using iPSCs and genome editing to study the role of the non-protein-coding genome in ASD.
Lien vers le texte intégral (Open Access ou abonnement)
15. Roux AM, Rast JE, Anderson KA, Garfield T, Shattuck PT. {{Vocational Rehabilitation Service Utilization and Employment Outcomes Among Secondary Students on the Autism Spectrum}}. {J Autism Dev Disord}. 2020.
U.S. policy interventions encourage earlier provision of Vocational Rehabilitation (VR) services to support students and youth with disabilities such as autism spectrum disorder (ASD) during the transition from school to work. We analyzed Rehabilitation Services Administration (RSA-911) data using multivariable logistic regression to determine the association of VR services receipt with employment outcomes for students ages 16-21, same-age non-student youth and young adults with ASD. Students with autism received job-related services (job search, job placement, and on-the-job supports) at rates significantly below comparison groups, even though odds of successful employment at VR exit were significantly higher if they received these services. Findings suggest that rates of employment among students with autism might be improved with intentional delivery of job-related services.
Lien vers le texte intégral (Open Access ou abonnement)
16. Smith AL, Jung EM, Jeon BT, Kim WY. {{Arid1b haploinsufficiency in parvalbumin- or somatostatin-expressing interneurons leads to distinct ASD-like and ID-like behavior}}. {Sci Rep}. 2020; 10(1): 7834.
Inhibitory interneurons are essential for proper brain development and function. Dysfunction of interneurons is implicated in several neurodevelopmental disorders, including autism spectrum disorder (ASD) and intellectual disability (ID). We have previously shown that Arid1b haploinsufficiency interferes with interneuron development and leads to social, cognitive, and emotional impairments consistent with ASD and ID. It is unclear, however, whether interneurons play a major role for the behavioral deficits in Arid1b haploinsufficiency. Furthermore, it is critical to determine which interneuron subtypes contribute to distinct behavioral phenotypes. In the present study, we generated Arid1b haploinsufficient mice in which a copy of the Arid1b gene is deleted in either parvalbumin (PV) or somatostatin (SST) interneurons, and examined their ASD- and ID-like behaviors. We found that Arid1b haploinsufficiency in PV or SST interneurons resulted in distinct features that do not overlap with one another. Arid1b haploinsufficiency in PV neurons contributed to social and emotional impairments, while the gene deletion in the SST population caused stereotypies as well as learning and memory dysfunction. These findings demonstrate a critical role of interneurons in Arid1b haploinsufficient pathology and suggest that PV and SST interneurons may have distinct roles in modulating neurological phenotypes in Arid1b haploinsufficiency-induced ASD and ID.
Lien vers le texte intégral (Open Access ou abonnement)
17. van Deurs JR, McLay LK, France KG, Blampied NM. {{Sequential Implementation of Functional Behavior Assessment-Informed Treatment Components for Sleep Disturbance in Autism: A Case Study}}. {Behavioral sleep medicine}. 2020: 1-19.
Background: Sleep disturbances are a significant problem for people with autism spectrum disorder (ASD). Existing research supports the use of parent-implemented, functional behavior assessment (FBA)-informed interventions for sleep problems in children with ASD. There is also emerging evidence for combined parent- and young person-implemented behavioral sleep interventions for older children and adolescents with ASD. However, the active treatment components of such interventions have not been identified in previous studies, as components have not been evaluated independently of one another.Methods: The current study sequentially implemented FBA-informed treatment components (in the order of least to most restrictive and time intensive) within a single-case AB design, to evaluate at which point treatment resulted in a statistically and clinically substantive reduction in target sleep variables. Combined parent- and young person-implemented intervention components consisted of: (a) white noise; (b) white noise and relaxation instruction; and (c) white noise, relaxation instruction, and stimulus control.Participant: The participant was a 9-year-old girl with autism and selective mutism.Results: The combined use of white noise, relaxation instruction, and stimulus control resolved the participant’s sleep problems. Other more restrictive and/or time intensive interventions were unnecessary. Treatment effects were maintained at 10-week follow-up.Conclusions: The current study illustrates the feasibility of administering FBA-informed treatment components sequentially, to ensure application of minimally sufficient interventions.
Lien vers le texte intégral (Open Access ou abonnement)
18. Vidal V, McAllister A, DeThorne L. {{Communication Profile of a Minimally Verbal School-Age Autistic Child: A Case Study}}. {Language, speech, and hearing services in schools}. 2020: 1-16.
Purpose The present clinical focus draws on an intrinsic case study to provide a thick description of the communication profile of John, a 9-year-old minimally verbal autistic student. Method Specifically, traditional behavioral assessments, classroom video observations, and semistructured interviews were used to gather information regarding John’s communication profile and potential sensory-motor differences. Results Convergent evidence indicated that John’s expressive profile was characterized by single words, emergent word combinations, some conventional gestures, and a low frequency of communicative initiations. Concomitant language comprehension challenges and poor intelligibility associated with motor speech impairment were also indicated. His sensory-motor profile was marked by fine motor impairment, relative strengths in gross motor abilities, and sensory differences across visual, hearing, and tactile modalities. Conclusion Direct implications for supporting minimally verbal autistic students like John include the need to (a) consider sensory-motor influences on social interaction and (b) support flexible use of multimodal communication resources, including augmentative and alternative communication. Supplemental Material https://doi.org/10.23641/asha.12202448.
Lien vers le texte intégral (Open Access ou abonnement)
19. Wang J, Poliquin S, Mermer F, Eissman J, Delpire E, Wang J, Shen W, Cai K, Li BM, Li ZY, Xu D, Nwosu G, Flamm C, Liao WP, Shi YW, Kang JQ. {{Endoplasmic reticulum retention and degradation of a mutation in SLC6A1 associated with epilepsy and autism}}. {Molecular brain}. 2020; 13(1): 76.
Mutations in SLC6A1, encoding gamma-aminobutyric acid (GABA) transporter 1 (GAT-1), have been recently associated with a spectrum of epilepsy syndromes, intellectual disability and autism in clinic. However, the pathophysiology of the gene mutations is far from clear. Here we report a novel SLC6A1 missense mutation in a patient with epilepsy and autism spectrum disorder and characterized the molecular defects of the mutant GAT-1, from transporter protein trafficking to GABA uptake function in heterologous cells and neurons. The heterozygous missense mutation (c1081C to A (P361T)) in SLC6A1 was identified by exome sequencing. We have thoroughly characterized the molecular pathophysiology underlying the clinical phenotypes. We performed EEG recordings and autism diagnostic interview. The patient had neurodevelopmental delay, absence epilepsy, generalized epilepsy, and 2.5-3 Hz generalized spike and slow waves on EEG recordings. The impact of the mutation on GAT-1 function and trafficking was evaluated by (3)H GABA uptake, structural simulation with machine learning tools, live cell confocal microscopy and protein expression in mouse neurons and nonneuronal cells. We demonstrated that the GAT-1(P361T) mutation destabilizes the global protein conformation and reduces total protein expression. The mutant transporter protein was localized intracellularly inside the endoplasmic reticulum (ER) with a pattern of expression very similar to the cells treated with tunicamycin, an ER stress inducer. Radioactive (3)H-labeled GABA uptake assay indicated the mutation reduced the function of the mutant GAT-1(P361T), to a level that is similar to the cells treated with GAT-1 inhibitors. In summary, this mutation destabilizes the mutant transporter protein, which results in retention of the mutant protein inside cells and reduction of total transporter expression, likely via excessive endoplasmic reticulum associated degradation. This thus likely causes reduced functional transporter number on the cell surface, which then could cause the observed reduced GABA uptake function. Consequently, malfunctioning GABA signaling may cause altered neurodevelopment and neurotransmission, such as enhanced tonic inhibition and altered cell proliferation in vivo. The pathophysiology due to severely impaired GAT-1 function may give rise to a wide spectrum of neurodevelopmental phenotypes including autism and epilepsy.
