1. Alberts L. {{Evidence-Based Approaches for Prescribing Psychotropic Medications in Individuals With Autism Spectrum Disorders}}. {Journal of doctoral nursing practice}. 2020; 13(3): 216-23.
BACKGROUND: Treating children and adults with autism spectrum disorders (ASDs) is challenging, whether for mental health concerns, underlying healthcare conditions, or a variety of behavioral challenges, such as self-injury, aggression, or irritability. OBJECTIVE: This article highlights evidence-based approaches to inform prescribing practices in treating children and adults with ASDs and mental health or behavioral challenges. METHODS: Current and historical literature focusing on treating individuals with ASDs using psychotropic medications was analyzed. RESULTS: Psychotropic medications may not be the best choice for treating individuals with ASDs and mental health or behavioral challenges. Inappropriate use of psychotropic medications in this population can cause significant side effects and lead to long-term health related issues. CONCLUSIONS: Prescribers should use evidence-based approaches when treating this population. IMPLICATIONS FOR NURSING: Nurse practitioners are likely to encounter patients with ASDs in their practice. Understanding special considerations in prescribing for this population is highly relevant and important to improve health outcomes.
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2. Colón-Rodríguez A, Uribe-Salazar JM, Weyenberg KB, Sriram A, Quezada A, Kaya G, Jao E, Radke B, Lein PJ, Dennis MY. {{Assessment of Autism Zebrafish Mutant Models Using a High-Throughput Larval Phenotyping Platform}}. {Frontiers in cell and developmental biology}. 2020; 8: 586296.
In recent years, zebrafish have become commonly used as a model for studying human traits and disorders. Their small size, high fecundity, and rapid development allow for more high-throughput experiments compared to other vertebrate models. Given that zebrafish share >70% gene homologs with humans and their genomes can be readily edited using highly efficient CRISPR methods, we are now able to rapidly generate mutations impacting practically any gene of interest. Unfortunately, our ability to phenotype mutant larvae has not kept pace. To address this challenge, we have developed a protocol that obtains multiple phenotypic measurements from individual zebrafish larvae in an automated and parallel fashion, including morphological features (i.e., body length, eye area, and head size) and movement/behavior. By assaying wild-type zebrafish in a variety of conditions, we determined optimal parameters that avoid significant developmental defects or physical damage; these include morphological imaging of larvae at two time points [3 days post fertilization (dpf) and 5 dpf] coupled with motion tracking of behavior at 5 dpf. As a proof-of-principle, we tested our approach on two novel CRISPR-generated mutant zebrafish lines carrying predicted null-alleles of syngap1b and slc7a5, orthologs to two human genes implicated in autism-spectrum disorder, intellectual disability, and epilepsy. Using our optimized high-throughput phenotyping protocol, we recapitulated previously published results from mouse and zebrafish models of these candidate genes. In summary, we describe a rapid parallel pipeline to characterize morphological and behavioral features of individual larvae in a robust and consistent fashion, thereby improving our ability to better identify genes important in human traits and disorders.
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3. Fernell E, Gustafsson P, Gillberg C. {{Bumetanide for autism: open-label trial in six children}}. {Acta paediatrica (Oslo, Norway : 1992)}. 2020.
AIM: Bumetanide, a diuretic agent, that reduces intracellular chloride – thereby reinforcing GABAergic inhibition – has been reported to improve core symptoms of autism in children. Given the positive results reported from French trials of bumetanide in children with autism, we decided to evaluate its effects in a small-scale pilot study, in advance of a larger randomised controlled study (RCT). METHODS: This was an open-label, three-month trial of bumetanide on six children (five boys), aged 3-14 years with autism. Ratings according to the PArental Satisfaction Survey (PASS) were used after four and twelve weeks to assess symptom change. Blood electrolyte status was monitored. RESULTS: Improvement in the PASS domain « Communicative and cognitive abilities » was marked or very marked in four children and two had some improvements. Few negative side effects were reported. CONCLUSION: Our small cohort responded well to bumetanide, particularly with regard to « Communicative and cognitive abilities ». Taken with the evidence from larger-scale RCTs, we suggest that bumetanide should be considered for inclusion in ethically approved treatment/management trials for children with autism, subject to rigorous follow-up in large scale RCTs.
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4. Horiai M, Otsuka A, Hidema S, Hiraoka Y, Hayashi R, Miyazaki S, Furuse T, Mizukami H, Teruyama R, Tamura M, Bito H, Maejima Y, Shimomura K, Nishimori K. {{Targeting oxytocin receptor (Oxtr)-expressing neurons in the lateral septum to restore social novelty in autism spectrum disorder mouse models}}. {Sci Rep}. 2020; 10(1): 22173.
Autism spectrum disorder (ASD) is a continuum of neurodevelopmental disorders and needs new therapeutic approaches. Recently, oxytocin (OXT) showed potential as the first anti-ASD drug. Many reports have described the efficacy of intranasal OXT therapy to improve the core symptoms of patients with ASD; however, the underlying neurobiological mechanism remains unknown. The OXT/oxytocin receptor (OXTR) system, through the lateral septum (LS), contributes to social behavior, which is disrupted in ASD. Therefore, we selectively express hM3Dq in OXTR-expressing (OXTR+) neurons in the LS to investigate this effect in ASD mouse models developed by environmental and genetic cues. In mice that received valproic acid (environmental cue), we demonstrated successful recovery of impaired social memory with three-chamber test after OXTR+ neuron activation in the LS. Application of a similar strategy to Nl3(R451C) knock-in mice (genetic cue) also caused successful recovery of impaired social memory in single field test. OXTR+ neurons in the LS, which are activated by social stimuli, are projected to the CA1 region of the hippocampus. This study identified a candidate mechanism for improving core symptoms of ASD by artificial activation of DREADDs, as a simulation of OXT administration to activate OXTR+ neurons in the LS.
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5. Kalb LG, Beasley JB, Caoili A, McLaren JL, Barnhill J. {{Predictors of Mental Health Crises Among Individuals With Intellectual and Developmental Disabilities Enrolled in the START Program}}. {Psychiatr Serv}. 2020: appips202000301.
OBJECTIVE: Individuals with intellectual and developmental disabilities disproportionately use emergency psychiatric services compared with their neurotypical peers, suggesting that such individuals and their supports are at increased risk for crisis events. This prospective study examined the timing, outcomes, and predictors of mental health crises for this population. METHODS: The data came from Systemic, Therapeutic, Assessment, Resources, and Treatment (START), a national model that provides mental health crisis services for those with intellectual and developmental disabilities in the United States. The study included 1,188 individuals from four U.S. regions enrolled between 2018 and 2019. The outcome was urgent crisis contacts with the START program. Baseline and clinical predictors were examined with multivariate regression analyses. RESULTS: More than a quarter had at least one crisis contact, and 9% had three or more. Contacts increased within the initial 3 months of START enrollment, followed by a steep drop-off thereafter; few contacts happened after 1 year. Almost 45% of the contacts occurred after hours, and 30% involved police. Clinical factors predicted crisis contact most robustly, followed by lack of occupational supports. After START crisis intervention, 73% of individuals remained in their primary setting. CONCLUSIONS: For individuals with intellectual and developmental disabilities and mental health needs, crisis stabilization resources are needed, including after hours. Results clearly identify times and risk factors for mental health crisis contacts, including frequent involvement with emergency responders. Importantly, gainful employment conveyed benefits for community stabilization. Findings may be leveraged to develop effective mental health crisis intervention services and supports for this underserved group.
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6. Krishna D, Muthukaruppan SS, Bharathwaj A, Ponnusamy R, Poomariappan BM, Mariappan S, Beevi A, MacLachlan J, Campbell Z, Anthonypillai C, Brien M, Cameron C, Flatman M, Perlman L, Seilman S, Jeyapragash A, van der Haar L, Krapels J, Srinivasan SR. {{Rapid-Cycle Evaluation in an Early Intervention Program for Children With Developmental Disabilities in South India: Optimizing Service Providers’ Quality of Work-Life, Family Program Engagement, and School Enrollment}}. {Frontiers in public health}. 2020; 8: 567907.
Background: This paper explores how implementation and refinement of an early intervention (EI) program for children with delayed development was informed by an iterative, intentional and structured process of measurement. Providing access to early intervention therapy for children in rural areas of India is challenging due to a lack of rehabilitation therapists and programs. Following a biopsychosocial framework and principles of community-based rehabilitation, a non-governmental organization, Amar Seva Sangam (ASSA), overcame those barriers by designing a digital technology supported EI program in rural Tamil Nadu, India. Program objectives included providing service access; supporting program engagement, child development and school enrollment; and positioning the intervention for scale-up. This paper contributes to a growing body of literature on how program design and implementation can be informed through a cyclical process of data collection, analysis, reflection, and adaptation. Methods: Through several strands of data collection, the design and implementation of the EI program was adapted and improved. This included qualitative data from focus groups and interviews with caregivers and service providers, and a mobile application that collected and monitored longitudinal quantitative data, including program engagement rates, developmental progression, caregiver outcomes, and school enrollment status. Results: Measurements throughout the program informed decision-making by identifying facilitators and barriers to service providers’ quality of work-life, family program engagement, and school enrollment. Consultation with key stakeholders, including caregivers and service providers, and data driven decision making led to continual program changes that improved service provider quality of work-life, program engagement and school enrollment. These changes included addressing gender-related work challenges for service providers; forming caregiver support networks; introducing psychological counseling for caregivers; providing medical consultations and assistive devices; creating community awareness programs; improving access to therapy services; focusing on caregiver education, motivation and support; and advocacy for accessibility in schools. Conclusion: The process of using evidence-informed and stakeholder driven adaptations to the early intervention program, led to improved service provider quality of work-life, greater program engagement, improved school enrollment and positioned the intervention for scale-up, providing lessons that may be beneficial in other contexts.
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7. Kwan V, Rosa E, Xing S, Murtaza N, Singh K, Holzapfel NT, Berg T, Lu Y, Singh KK. {{Proteomic Analysis Reveals Autism-Associated Gene DIXDC1 Regulates Proteins Associated with Mitochondrial Organization and Function}}. {Journal of proteome research}. 2020.
DIX-domain containing 1 (Dixdc1) is an important regulator of neuronal development including cortical neurogenesis, neuronal migration and synaptic connectivity, and sequence variants in the gene have been linked to autism spectrum disorders (ASDs). Previous studies indicate that Dixdc1 controls neurogenesis through Wnt signaling, whereas its regulation of dendrite and synapse development requires Wnt and cytoskeletal signaling. However, the prediction of these signaling pathways is primarily based on the structure of Dixdc1. Given the role of Dixdc1 in neural development and brain disorders, we hypothesized that Dixdc1 may regulate additional signaling pathways in the brain. We performed transcriptomic and proteomic analyses of Dixdc1 KO mouse cortices to reveal such alterations. We found that transcriptomic approaches do not yield any novel findings about the downstream impacts of Dixdc1. In comparison, our proteomic approach reveals that several important mitochondrial proteins are significantly dysregulated in the absence of Dixdc1, suggesting a novel function of Dixdc1.
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8. Mayes SD, Calhoun SL, Waschbusch DA. {{Relationship between sluggish cognitive tempo and sleep, psychological, somatic, and cognitive problems and impairment in children with autism and children with ADHD}}. {Clinical child psychology and psychiatry}. 2020: 1359104520978459.
Sluggish cognitive tempo (SCT) is a topic of renewed interest. Much remains to be learned about its association with symptoms and diagnoses that have received little research attention, particularly sleep disturbance, somatic complaints, and autism. Our study is the first to explore the relationship between SCT and sleep, internalizing, externalizing, somatic, and cognitive problems, impairment, and demographics in large samples of children with autism, ADHD-Combined, and ADHD-Inattentive. Mothers rated 1,436 children with autism and 1,056 with ADHD without autism, 2 to 17 years, on the Pediatric Behavior Scale (PBS). Factor analysis yielded a 6-item SCT factor (sluggish/slow moving/low energy, stares/preoccupied/in own world, tires easily, in a fog/confused, drowsy/sleepy/not alert, and apathetic) plus 10 additional factors. SCT was distinct from but related to several factors and was associated with social and academic impairment. The strongest independent predictors of SCT were depression, sleeping more than normal, cognitive problems, autism, and somatic complaints. Scores on the remaining factors (sleep disturbance, attention deficit, impulsivity, hyperactivity, oppositional defiant disorder, conduct disorder, and anxiety) increased explained variance by less than 2%. Findings suggest that SCT is not simply sluggish cognitive tempo, as the name implies, and is a complex construct with behavioral, affective, emotional, cognitive, and somatic components and associations. Given that 49% of children with autism had SCT, SCT symptoms should be considered in all children being evaluated for autism, as well as for ADHD-C and ADHD-I (with SCT percentages of 31% and 40%). Assessing and treating SCT is especially important because of its association with impairment.
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9. Mormando C, Mikoluk C, Garman JC, Rapp M, Murray M, Francis A. {{Electroconvulsive Therapy for Autism-related Stereotyped Emesis After Chiari Malformation Type 1 Craniectomy}}. {The journal of ECT}. 2020; Publish Ahead of Print.
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10. Nayan NS, Yazid MAM, Nallappan K, Amran AA, Zaidi NS, Zakaria F, Hassan H, Karim NA. {{In Vitro Modulation of Endogenous Antioxidant Enzyme Activities and Oxidative Stress in Autism Lymphoblastoid Cell Line (ALCL) by Stingless Bee Honey Treatment}}. {Oxidative medicine and cellular longevity}. 2020; 2020: 4539891.
Autism has been associated with a low antioxidant defense mechanism, while honey has been known for decades for its antioxidant and healing properties. Determination of stingless bee honey (KH) effects on antioxidant enzyme activities and oxidative damage in Autism Lymphoblastoid Cell Line (ALCL) was performed. ALCL and its normal sibling pair (NALCL) were cultured in RPMI-1640 medium at 37°C and 5% CO(2). ALCL was treated with 400 μg/mL KH (24 h), and oxidative stress marker, malondialdehyde (MDA), and antioxidant enzyme activities (catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD)) were measured via enzyme-linked immunosorbent assay (ELISA), while deoxyribonucleic acid (DNA) damage was determined via comet assay. Low SOD activity (p < 0.05) and high MDA level (p < 0.05) were observed in ALCL compared to NALCL. Higher grade (Grades 2 and 3) of DNA damage was highly observed (p < 0.05) in ALCL compared to NALCL, whereas lower grade (Grades 0 and 1) DNA damage was highly detected (p < 0.05) in NALCL compared to ALCL. KH treatment caused a significant increase in SOD and GPx activities (p < 0.05) in ALCL compared to untreated ALCL. Correspondingly, KH treatment reduced the Grade 2 DNA damage (p < 0.05) in ALCL compared to untreated ALCL. CAT activity showed no significant difference between all three groups, while the MDA level showed no significant difference between treated and untreated ALCL. In conclusion, KH treatment significantly reduced the oxidative stress in ALCL by increasing the SOD and GPx antioxidant enzyme activities, while reducing the DNA damage. Lien vers le texte intégral (Open Access ou abonnement)
11. Pillay S, Duncan M, de Vries PJ. {{Autism in the Western Cape province of South Africa: Rates, socio-demographics, disability and educational characteristics in one million school children}}. {Autism}. 2020: 1362361320978042.
There is very little information about autism spectrum disorder in South Africa and not much is known about children with autism spectrum disorder and their educational needs. In this study, we searched for all children with autism spectrum disorder attending schools in the Western Cape province of South Africa and compared our findings with the profile of people living in the province. We found fewer children with autism spectrum disorder in schools than expected (0.08%) and co-occurring conditions (intellectual disability = 22.2%, attention-deficit/hyperactivity disorder = 2.6% and epilepsy = 0.7%) were reported at lower rates. More children were from White racial groups and from English-speaking homes compared with the Western Cape population demographics. Most of the children (89%) attended schools for children with Special Educational Needs and only 10% were in Ordinary/Mainstream schools. Eighty-three percent attended schools in urban areas and 17% in rural areas. There was a 76.03% increase in children with autism spectrum disorder in schools between 2012 and 2016. Our findings support the need for better identification and reporting of children with autism spectrum disorder in the education system. We propose urgent review and strengthening of education systems for children with autism spectrum disorder in the Western Cape province and in other parts of South Africa.
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12. Reilly J, Gallagher L, Leader G, Shen S. {{Coupling of autism genes to tissue-wide expression and dysfunction of synapse, calcium signalling and transcriptional regulation}}. {PLoS One}. 2020; 15(12): e0242773.
Autism Spectrum Disorder (ASD) is a heterogeneous disorder that is often accompanied with many co-morbidities. Recent genetic studies have identified various pathways from hundreds of candidate risk genes with varying levels of association to ASD. However, it is unknown which pathways are specific to the core symptoms or which are shared by the co-morbidities. We hypothesised that critical ASD candidates should appear widely across different scoring systems, and that comorbidity pathways should be constituted by genes expressed in the relevant tissues. We analysed the Simons Foundation for Autism Research Initiative (SFARI) database and four independently published scoring systems and identified 292 overlapping genes. We examined their mRNA expression using the Genotype-Tissue Expression (GTEx) database and validated protein expression levels using the human protein atlas (HPA) dataset. This led to clustering of the overlapping ASD genes into 2 groups; one with 91 genes primarily expressed in the central nervous system (CNS geneset) and another with 201 genes expressed in both CNS and peripheral tissues (CNS+PT geneset). Bioinformatic analyses showed a high enrichment of CNS development and synaptic transmission in the CNS geneset, and an enrichment of synapse, chromatin remodelling, gene regulation and endocrine signalling in the CNS+PT geneset. Calcium signalling and the glutamatergic synapse were found to be highly interconnected among pathways in the combined geneset. Our analyses demonstrate that 2/3 of ASD genes are expressed beyond the brain, which may impact peripheral function and involve in ASD co-morbidities, and relevant pathways may be explored for the treatment of ASD co-morbidities.
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13. Rojas-Torres LP, Alonso-Esteban Y, Alcantud-Marín F. {{Early Intervention with Parents of Children with Autism Spectrum Disorders: A Review of Programs}}. {Children (Basel, Switzerland)}. 2020; 7(12).
The aim of this article was to analyze the evidence regarding the effectiveness of intervention programs for children with autism based on the participation of their parents. To obtain the data, a systematic search was carried out in four databases (PsycARTICLES (ProQuest), ERIC (ProQuest), PubMed (ProQuest), and Scopus). The retrieved documents were refined under the inclusion/exclusion criteria, and a total of 51 empirical studies were selected. These studies were first classified according to the function of the intervention objective and, later, by the methodology applied (19 studies were based on comprehensive interventions, 11 focused on the nuclear symptoms of autism spectrum disorder (ASD), 12 focused on the promotion of positive parenting, and nine interactions focused on child play). Once all of the documents had been analyzed, the evidence indicated scientific efficacy in most studies, mainly in those based on child development and the application of behavioral analysis principles. Moreover, the positive influence of parent participation in such programs was demonstrated.
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14. Tárraga-Mínguez R, Gómez-Marí I, Sanz-Cervera P. {{What Motivates Internet Users to Search for Asperger Syndrome and Autism on Google?}}. {Int J Environ Res Public Health}. 2020; 17(24).
Social campaigns are carried out to promote autism spectrum disorder (ASD) awareness, normalization, and visibility. The internet helps to shape perceptions of Asperger syndrome and autism. In fact, these campaigns often coincide with the increase in searches for both diagnoses on Google. We have two study objectives: to use Google Trends to identify the annual time points from 2015 to 2019 with the highest Google search traffic in Spain for the terms « autism » and « Asperger », and to identify news and trending topics related to ASD that took place during the weeks with the highest number of Google searches for these terms. Google Trend, MyNews and Trendinalia were used to analyze the volume of searches and trending topics related to ASD. As a result, social marketing campaigns, social networks and the publication of news items act as powerful voices that can provide a realistic or sensationalist picture of the disorder. For this reason, we concluded that campaigns play an important role in the normalization of ASD, and that it is important for organizations concerned with the visibility and social inclusion of people with ASD to check the way ASD is portrayed through the internet, media, and social networks.
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15. Trevisan DA, Mehling WE, McPartland JC. {{Adaptive and Maladaptive Bodily Awareness: Distinguishing Interoceptive Sensibility and Interoceptive Attention from Anxiety-Induced Somatization in Autism and Alexithymia}}. {Autism Res}. 2020.
There is growing interest in « interoception » (i.e., detection and interpretation of internal body signals) as a relevant mechanism contributing to certain symptoms and features of autism spectrum disorder (ASD) and alexithymia. However, inconsistent measurement and operationalization of interoception has led to confusion and inconsistent findings in the literature. In this commentary, we present alternative interpretations of findings from existing studies to demonstrate that ASD and alexithymia are conditions associated with reduced adaptive forms of interoceptive attention (i.e., attention toward bodily signals) but heightened maladaptive forms of interoceptive attention related to anxiety-induced somatization. Differentiating adaptive and maladaptive forms of interoceptive attention reveals a clearer pattern of findings in the research literature for further investigation of interoceptive processes that are involved in the neurobiology of ASD. However, interoception is a complex and multi-faceted construct that requires continual refinement in conceptualization and operationalization. Interoception research may benefit from self-report measures that clearly differentiate adaptive and maladaptive forms of bodily awareness. LAY SUMMARY: Some research suggests that autistic people have difficulty understanding bodily feelings such as hunger, illness, or emotions, whereas some studies have reported the opposite pattern of findings. We argue that this latter subset of studies reached false conclusions from using measures of bodily awareness that largely measure physical symptoms of anxiety. While attention to unpleasant bodily signals is an important ability necessary for maintaining healthy bodily functioning, excessive attention, and worry toward bodily signals can increase anxiety and be harmful.
