1. Alaimo H, Geller E, Mahalingam R, Rodriguez A, Goldberg R, Bojko A, Nadkarni M, Joshi P, Devinsky O. {{Ictal EEG in patients with autistic spectrum disorder and epilepsy}}. {Epilepsy research}. 2020; 168: 106482.
OBJECTIVE: Autism spectrum disorder (ASD) is a neurodevelopmental disorder frequently associated with epilepsy and epilepsy is a leading cause of death in ASD patients. Despite growing interest in genetic, neurophysiological and clinical overlaps, data on ictal electroencephalographic (EEG) recordings in ASD are lacking since behavioral disorders often make it difficult to obtain EEG recordings. We examined ictal EEG features in a consecutive series of patients with ASD and epilepsy. METHODS: We retrospectively identified 400 consecutive patients with ASD and epilepsy at our Level 4 Epilepsy center between 2015 and 2019; 45 had at least one EEG-recorded seizure captured. Demographics, age of nonfebrile seizure onset, age of ASD diagnosis, language, magnetic resonance imagining findings, genetic testing and EEG studies were reviewed. Seizures were classified by semiologic and electrographic features. Ictal findings were analyzed. RESULTS: A total of 497 seizures were captured in 45 patients: 20 patients with focal onset epilepsy had 126 seizures (median: 1, range: 1-30), 17 patients with generalized onset epilepsy had 88 seizures (median: 2, range: 1-15), 7 patients with Lennox-Gastaut syndrome had 270 seizures (median: 12, range: 1-74) and one patient had both right hemisphere focal and generalized onsets (12 focal, 1 generalized). SIGNIFICANCE: Our study is the first to analyze a large set of ictal data in patients with autism spectrum disorder, a population traditionally difficult to obtain ictal recordings. Our results confirm the diverse spectrum of seizure types and provide clinical-EEG correlates of seizures in ASD patients. Both focal-onset and generalized-onset seizures were recorded, confirming that ASD patients have higher rates of both focal and generalized epilepsy syndromes. Among patients with focal epilepsy, temporal and frontal onsets were frequent, suggesting the possibility of epilepsy surgery or brain stimulation. EEG to classify seizures and epilepsies is critical to determine therapeutic options and effort should be made to obtain EEGs in this heterogenous population.
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2. Auberry K. {{Educating behavior clinicians in a community behavior care center for children with autism spectrum disorder: Medication administration a pilot study in the United States}}. {Journal of intellectual disabilities : JOID}. 2020: 1744629520967176.
Autism Spectrum Disorder (ASD) is a multifaceted developmental disability requiring specialized supports. Due to the growing diagnoses of ASD, the demand for behavior treatment centers has also grown. These centers offer a wide range of beneficial services to children with ASD, including medication administration and management. While centers may employ highly educated and certified employees, there may be a gap in education related to medication administration and medication management knowledge. Using an evidence based education tool, this study sought to explore if clinicians in a behavior care center could gain knowledge in their ability to accurately administer and manage medications for children with ASD, and postulate if existing post-secondary curricula for behavior clinicians should be enriched to include medication administration and management training. This comprised two separate day long sessions of an implementation pilot study of best practice education in medication administration and medication management for behavior clinicians employed at a community behavior care center for children with ASD in the United States. Using the Statistical Package for the Social Sciences, 25 (SPSS), the paired samples t-test was applied for analysis. The quantitative results demonstrated the skill level treatment effect was statistically significant (p < .001). On the basis of the results the author makes recommendations regarding how to include medication administration and medication management education into existing behavior clinician curricula in the United States. Lien vers le texte intégral (Open Access ou abonnement)
3. Ebrahimi Meimand S, Rostam-Abadi Y, Rezaei N. {{Autism Spectrum Disorders and Natural Killer Cells: A Review on Pathogenesis and Treatment}}. {Expert review of clinical immunology}. 2020.
Introduction: Autism spectrum disorder (ASD), as a wide spectrum of neurodevelopmental disorders, is characterized by early-onset impairments in social-communication, repetitive behaviors, and restrictive interests. Areas covered: Although still unknown, there are some pieces of evidence suggesting altered immune function in the etiology of ASD. This review aims to summarize studies linking Natural Killer (NK) cells to ASD by searching through databases like MEDLINE and Scopus up to October 2020. NK cells play important roles in the innate immune system and immune regulation. As parts of the immune system, they interact with the neural system as well. Immune dysregulations such as autoimmunity and improper immune responses to both internal and external stimulations, especially in early developmental stages of the brain, may induce neurodevelopmental disorders. NK cells’ dysfunction in children with ASD as well as their parents have been highlighted in many studies. Expert opinion: Changes in the frequency, gene expressions, cytotoxicity features, and receptors of NK cells are reported in children with ASD. Immune therapy for children with ASD with immune abnormality has shown promising results. However, further studies are needed to elucidate the exact role of NK cells in the pathogenesis of ASD providing future treatment options for these children.
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4. Endres D, Decher N, Röhr I, Vowinkel K, Domschke K, Komlosi K, Tzschach A, Gläser B, Schiele MA, Runge K, Süß P, Schuchardt F, Nickel K, Stallmeyer B, Rinné S, Schulze-Bahr E, Tebartz van Elst L. {{New Cav1.2 Channelopathy with High-Functioning Autism, Affective Disorder, Severe Dental Enamel Defects, a Short QT Interval, and a Novel CACNA1C Loss-Of-Function Mutation}}. {International journal of molecular sciences}. 2020; 21(22).
Complex neuropsychiatric-cardiac syndromes can be genetically determined. For the first time, the authors present a syndromal form of short QT syndrome in a 34-year-old German male patient with extracardiac features with predominant psychiatric manifestation, namely a severe form of secondary high-functioning autism spectrum disorder (ASD), along with affective and psychotic exacerbations, and severe dental enamel defects (with rapid wearing off his teeth) due to a heterozygous loss-of-function mutation in the CACNA1C gene (NM_000719.6: c.2399A > C; p.Lys800Thr). This mutation was found only once in control databases; the mutated lysine is located in the Cav1.2 calcium channel, is highly conserved during evolution, and is predicted to affect protein function by most pathogenicity prediction algorithms. L-type Cav1.2 calcium channels are widely expressed in the brain and heart. In the case presented, electrophysiological studies revealed a prominent reduction in the current amplitude without changes in the gating behavior of the Cav1.2 channel, most likely due to a trafficking defect. Due to the demonstrated loss of function, the p.Lys800Thr variant was finally classified as pathogenic (ACMG class 4 variant) and is likely to cause a newly described Cav1.2 channelopathy.
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5. Gardner RM, Lee BK, Brynge M, Sjöqvist H, Dalman C, Karlsson H. {{Neonatal Levels of Acute Phase Proteins and Risk of Autism Spectrum Disorder}}. {Biol Psychiatry}. 2020.
BACKGROUND: Immune signaling pathways influence neurodevelopment and are hypothesized to contribute to the etiology of autism spectrum disorder (ASD). We aimed to assess risk of ASD in relation to levels of neonatal acute phase proteins (APPs), key components of innate immune function, measured in neonatal dried blood spots. METHODS: We included 924 ASD cases, 1092 unaffected population-based controls, and 203 unaffected siblings of ASD cases in this case-control study nested within the register-based Stockholm Youth Cohort. Concentrations of 9 different APPs were measured in eluates from neonatal dried blood spots from cases, controls, and siblings using a bead-based multiplex assay. RESULTS: Neonatal C-reactive protein was consistently associated with odds of ASD in case-control comparisons, with higher odds associated with the highest quintile compared with the middle quintile (odds ratio [OR] = 1.50, 95% confidence interval [CI] = 1.10-2.04) in adjusted analyses. In contrast, the lowest quintiles of α-2-macroglobulin (OR = 3.71, CI = 1.21-11.33), ferritin (OR = 4.20, CI = 1.40-12.65), and serum amyloid P (OR = 3.05, CI = 1.16-8.01) were associated with odds of ASD in the matched sibling comparison. Neonatal APPs varied with perinatal environmental factors and maternal/fetal phenotypes. Significant interactions in terms of risk for ASD were observed between neonatal APPs and maternal infection during late pregnancy, maternal anemia, and maternal psychiatric history. CONCLUSIONS: Indicators of the neonatal innate immune response are associated with risk of ASD, although the nature of these associations varies considerably with factors in the perinatal environment and the genetic background of the comparison group.
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6. Gridina MM, Orlova PA, Minina JM, Shitik EM, Lemskaya NA, Grishchenko IV, Dolskiy AA, Shorina AR, Maksimova YV, Yudkin DV, Serov OL. {{Establishment of an induced pluripotent stem cell line (ICGi026-A) from peripheral blood mononuclear cells of a patient with fragile X syndrome}}. {Stem cell research}. 2020; 49: 102070.
Expansion over 200 CGG repeats in FMR1 gene causes inherited intellectual disability or autism spectrum disorder named as fragile X syndrome. Despite the known cause fragile X syndrome pathogenesis has not been specified yet. The ICGi026-A iPSCs line was obtained by the reprogramming of the peripheral blood mononuclear cells from a 9-year-old boy with fragile X syndrome. The ICGi026-A iPSCs expressed pluripotency markers, had a normal male karyotype (46, XY) and had the capacity to in vivo differentiate into the cells of three germ layers.
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7. Hoyle JN, Laditka JN, Laditka SB. {{Mental health risks of parents of children with developmental disabilities: A nationally representative study in the United States}}. {Disability and health journal}. 2020: 101020.
BACKGROUND: Caring for a child with a developmental disability may affect parents’ mental health. There are few longitudinal or nationally representative studies, none on new mental health problems. Studies have few young children, and few adult children. OBJECTIVE/HYPOTHESES: We hypothesized that parents of children with developmental disability would be more likely to develop mental health problems than other parents. METHODS: We used the Panel Study of Income Dynamics (PSID, 1997-2017) and its Child Development Supplements, defining developmental disability by diagnoses such as autism spectrum disorder or intellectual disability, and requiring additional evidence of lasting impairment. We linked children’s and parents’ data spanning 20 years, including 44,264 mental health measurements for 4024 parents of 7030 children. Discrete-time hazard analysis controlled for child and parent characteristics. RESULTS: About 9.4% of children had developmental disability. Parents of children with developmental disability were more likely to develop mental health problems than other parents. The odds of developing anxiety or depression were higher when an adult child with developmental disability lived independently, nearly 3 times higher for mothers (OR 2.89, CI 2.33-3.59) and more than twice as large for fathers (OR 2.35, CI 1.70-3.26). Compared to fathers whose children did not have developmental disability and challenging behaviors, the odds of psychological distress were over 7 times larger (odds ratio, OR 7.18, 95% confidence interval, CI, 5.37-9.61) for those whose children had developmental disability and challenging behaviors. CONCLUSIONS: Parents of children with developmental disability may benefit from increased emotional support, respite, and interventions addressing challenging behaviors.
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8. Rohatgi RK, Qureshi MY, Taggart NW. {{Limited Utility of Surveillance Echocardiograms in Pediatric Patients with Isolated Secundum ASDs}}. {Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography}. 2020.
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9. Sanchack KE. {{Autism Spectrum Disorder: Updated Guidelines from the American Academy of Pediatrics}}. {American family physician}. 2020; 102(10): 629-31.
10. Traver S, Geoffray MM, Mazières L, Geneviève D, Michelon C, Picot MC, Baghdadli A. {{Association between prenatal and perinatal factors and the severity of clinical presentation of children with ASD: Report from the ELENA COHORT}}. {Journal of psychiatric research}. 2020.
Many studies have suggested that prenatal and perinatal factors increase the risk for autism spectrum disorder (ASD). However, few reports have addressed the question of their influence on the severity of the clinical presentation of children with ASD. Our objective was to determine the prenatal and perinatal factors that are associated with the severity of autistic symptoms and intellectual and adaptive functioning deficits. Data were collected from a subset of 169 children with a confirmed diagnosis of ASD, recruited from the ELENA cohort. A risk of premature delivery was associated, with an increased risk for severe autistic symptoms and placental pathologies and birth complications were associated with an increased risk of communication adaptive deficits, in multivariate analysis. Our results highlight the importance of systematic screening for these pre/perinatal factors, especially in mothers at risk of having a child with ASD.
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11. Tromp A, Mowry B, Giacomotto J. {{Neurexins in autism and schizophrenia-a review of patient mutations, mouse models and potential future directions}}. {Mol Psychiatry}. 2020.
Mutations in the family of neurexins (NRXN1, NRXN2 and NRXN3) have been repeatedly identified in patients with autism spectrum disorder (ASD) and schizophrenia (SCZ). However, it remains unclear how these DNA variants affect neurexin functions and thereby predispose to these neurodevelopmental disorders. Understanding both the wild-type and pathologic roles of these genes in the brain could help unveil biological mechanisms underlying mental disorders. In this regard, numerous studies have focused on generating relevant loss-of-function (LOF) mammalian models. Although this has increased our knowledge about their normal functions, the potential pathologic role(s) of these human variants remains elusive. Indeed, after reviewing the literature, it seems apparent that a traditional LOF-genetic approach based on complete LOF might not be sufficient to unveil the role of these human mutations. First, these genes present a very complex transcriptome and total-LOF of all isoforms may not be the cause of toxicity in patients, particularly given evidence that causative variants act through haploinsufficiency. Moreover, human DNA variants may not all lead to LOF but potentially to intricate transcriptome changes that could also include the generation of aberrant isoforms acting as a gain-of-function (GOF). Furthermore, their transcriptomic complexity most likely renders them prone to genetic compensation when one tries to manipulate them using traditional site-directed mutagenesis approaches, and this could act differently from model to model leading to heterogeneous and conflicting phenotypes. This review compiles the relevant literature on variants identified in human studies and on the mouse models currently deployed, and offers suggestions for future research.
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12. Ziats CA, Patterson WG, Friez M. {{Syndromic Autism Revisited: Review of the Literature and Lessons Learned}}. {Pediatric neurology}. 2020; 114: 21-5.
Autism spectrum disorder is a neurodevelopmental disorder characterized by deficits in communication, stereotyped behaviors, restricted interests, and impaired social skills. The severity of the neurobehavioral phenotype is variable and historically has been distinguished based on the presence or absence of additional symptoms, termed syndromic and nonsyndromic or idiopathic autism, respectively. However, although the advancement in genetic molecular technologies has brought an increased understanding of the pathophysiology of autism, most of this success has been in the diagnosis of syndromic disease, whereas the etiology of nonsyndromic autism remains less understood. Here we review the common and rare genetic syndromes that feature autism, specifically highlighting deletion and duplication syndromes, chromosomal anomalies, and monogenic disorders. We show that the study of syndromic autism provides insight into the phenotypic and molecular heterogeneity of neurodevelopmental disease and suggests how study of these disorders can be helpful in understanding disease mechanisms implicated in nonsyndromic autism.
