Pubmed du 26/02/20

mercredi 26 février 2020

1. Brumbaugh JE, Weaver AL, Myers SM, Voigt RG, Katusic SK. Gestational Age, Perinatal Characteristics, and Autism Spectrum Disorder : A Birth Cohort Study. J Pediatr ;2020 (Feb 21)

OBJECTIVE : To determine how gestational age relates to research-identified autism spectrum disorder (ASD-R) in the context of perinatal risk factors. STUDY DESIGN : This is a population-based cohort study using the 1994-2000 Olmsted County Birth Cohort. Children included were born and remained in Olmsted County after age 3 years. ASD-R status was determined from signs and symptoms abstracted from medical and educational records. Cox proportional hazards models were fit to identify associations between perinatal characteristics and ASD-R. RESULTS : The incidence of preterm birth (<37 weeks’ gestation) was 8.6% among 7876 children. The cumulative incidence of ASD-R was 3.8% (95% CI 3.3-4.2) at 21 years of age. Compared with children born at full term, the risk of ASD-R appeared to be increased for children born preterm with unadjusted hazard ratios (HRs) of 2.62 (95% CI 0.65-10.57), 1.68 (95% CI 0.54-5.29), and 1.60 (95% CI 1.06-2.40) for children born extremely preterm, very preterm, and moderate-to-late preterm, respectively. In a multivariable model adjusted for perinatal characteristics, the associations were attenuated with adjusted HRs of 1.75 (95% CI 0.41-7.40), 1.24 (95% CI 0.38-4.01), and 1.42 (95% CI 0.93-2.15), for children born extremely preterm, very preterm, and moderate-to-late preterm, respectively. Among children with maternal history available (N = 6851), maternal psychiatric disorder was associated with ASD-R (adjusted HR 1.73, 95% CI 1.24-2.42). CONCLUSIONS : The increased risk of ASD-R among children born preterm relative to children born full term was attenuated by infant and maternal characteristics.

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2. Chen K, Fu Y, Wang Y, Liao L, Xu H, Zhang A, Zhang J, Fan L, Ren J, Fang B. Therapeutic Effects of the In Vitro Cultured Human Gut Microbiota as Transplants on Altering Gut Microbiota and Improving Symptoms Associated with Autism Spectrum Disorder. Microb Ecol ;2020 (Feb 26)

Autism spectrum disorder (ASD) is a brain-based neurodevelopmental disorder characterized by behavioral abnormalities. Accumulating studies show that the gut microbiota plays a vital role in the pathogenesis of ASD, and gut microbiota transplantation (GMT) is a promising technique for the treatment of ASD. In clinical applications of GMT, it is challenging to obtain effective transplants because of the high costs of donor selection and heterogeneity of donors’ gut microbiota, which can cause different clinical responses. In vitro batch culture is a fast, easy-to-operate, and repeatable method to culture gut microbiota. Thus, the present study investigates the feasibility of treating ASD with in vitro cultured gut microbiota as transplants. We cultured gut microbiota via the in vitro batch culture method and performed GMT in the maternal immune activation (MIA)-induced ASD mouse model with original donor microbiota and in vitro cultured microbiota. Open field, three-chamber social, marble burying, and self-grooming tests were used for behavioral improvement assessment. Serum levels of chemokines were detected. Microbial total DNA was extracted from mouse fecal samples, and 16S rDNA was sequenced using Illumina. Our results showed that GMT treatment with original and cultured donor gut microbiota significantly ameliorated anxiety-like and repetitive behaviors and improved serum levels of chemokines including GRO-alpha (CXCL1), MIP-1alpha (CCL3), MCP-3 (CCL7), RANTES (CCL5), and Eotaxin (CCL11) in ASD mice. Meanwhile, the gut microbial communities of the two groups that received GMT treatment were changed compared with the ASD mice groups. In the group treated with in vitro cultured donor gut microbiota, there was a significant decrease in the relative abundance of key differential taxa, including S24-7, Clostridiaceae, Prevotella_other, and Candidatus Arthromitus. The relative abundance of these taxa reached close to the level of healthy mice. Prevotella_other also decreased in the group treated with original donor gut microbiota, with a significant increase in Ruminococcaceae and Oscillospira. The present study demonstrated that GMT with in vitro cultured microbiota also improved behavioral abnormalities and chemokine disorders in an ASD mouse model compared with GMT with original donor gut microbiota. In addition, it significantly modified several key differential taxa in gut microbial composition.

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3. Clarke KA, Williams DL. Instruction Using Augmentative and Alternative Communication Supports : Description of Current Practices by Speech-Language Pathologists Who Work With Children With Autism Spectrum Disorder. Am J Speech Lang Pathol ;2020 (Feb 26):1-11.

Purpose The aim of this research study was to examine common practices of speech-language pathologists (SLPs) who work with children with autism spectrum disorder (ASD) with respect to whether or not SLPs consider processing differences in ASD or the effects of input during their instruction. Method Following a qualitative research method, how SLPs instruct and present augmentative and alternative communication systems to individuals with ASD, their rationale for method selection, and their perception of the efficacy of selected interventions were probed. Semistructured interviews were conducted as part of an in-depth case report with content analysis. Results Based on completed interviews, 4 primary themes were identified : (a) instructional method, (b) input provided, (c) decision-making process, and (d) perceived efficacy of treatment. Additionally, one secondary theme, training and education received, was identified. Conclusions Clinicians reported making decisions based on the needs of the child ; however, they also reported making decisions based on the diagnostic category that characterized the child (i.e., ASD). The use of modeling when teaching augmentative and alternative communication to individuals with ASD emerged as a theme, but variations in the method of modeling were noted. SLPs did not report regularly considering processing differences in ASD, nor did they consider the effects of input during instruction.

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4. de la Cruz BM, Ding Y, McInerney V, Krawczyk J, Lu Y, Yang G, Qian X, Li W, Howard L, Allen NM, O’Brien T, Gallagher L, Shen S. Derivation of two iPSC lines from a sporadic ASD patient (NUIGi033-A) and a paternal control (NUIGi034-A). Stem Cell Res ;2020 (Feb 4) ;44:101722.

Hundreds of rare risk factors have been identified for ASD, however, the underlying causes for 70% of sporadic cases are unknown. Sporadic ASD models are thus essential for validating phenotypic commonality and drug suitability to the majority of patients. Here, we derived induced pluripotent stem cells (iPSCs) from one sporadic ASD child and one paternal control, using non-integrating Sendai viral methods. The iPSCs strongly expressed pluripotency markers and could be differentiated into three germ layers. Their normal karyotype was validated by genome SNP array. The availability of sporadic ASD-derived iPSCs offers an opportunity for phenotypic comparison with genetic ASD models.

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5. DiBlasi E, Kirby AV, Gaj E, Docherty AR, Keeshin BR, Bakian AV, Coon H. Brief Report : Genetic Links Between Autism and Suicidal Behavior-A Preliminary Investigation. J Autism Dev Disord ;2020 (Feb 24)

Evidence suggests there may be increased risk for suicidal behavior among individuals with autism spectrum disorder (ASD). An emerging body of research explores social factors that may contribute to increased risk, however little is known about the potential role of biological factors. The current project addresses this knowledge gap through a preliminary study of genes associated with both ASD and suicidal behavior. Gene set enrichment tests of eight genes strongly associated with both ASD and suicidal behavior revealed overrepresentation of nine biological processes, including cognition and synapse function, and 14 cellular components, including the neuron, the synapse, and the synaptic and postsynaptic membrane. These results can be used to inform future investigations of the biological underpinnings of suicidal behavior and ASD.

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6. Dubreucq J, Plasse J, Gabayet F, Faraldo M, Blanc O, Chereau I, Cervello S, Couhet G, Demily C, Guillard-Bouhet N, Gouache B, Jaafari N, Legrand G, Legros-Lafarge E, Pommier R, Quiles C, Straub D, Verdoux H, Vignaga F, Massoubre C, Franck N. Self-stigma in serious mental illness and autism spectrum disorder : Results from the REHABase national psychiatric rehabilitation cohort. Eur Psychiatry ;2020 (Feb 7) ;63(1):e13.

BACKGROUND. : Self-stigma is a major issue in serious mental illness (SMI) and is negatively associated with patient outcomes. Most studies have been conducted in schizophrenia (SZ). Less is known about self-stigma in other SMI and autism spectrum disorder (ASD). The objectives of this study are : (i) to assess the frequency of self-stigma in a multicentric nonselected psychiatric rehabilitation SMI and ASD sample ; and (ii) to investigate the correlates of elevated self-stigma in different SMI conditions and in ASD. METHODS. : A total of 738 SMI or ASD outpatients were recruited from the French National Centers of Reference for Psychiatric Rehabilitation cohort (REHABase). Evaluations included sociodemographic data, illness characteristics, and standardized scales for clinical severity, quality of life, satisfaction with life, wellbeing, personal recovery, a large cognitive battery, and daily functioning assessment. RESULTS. : 31.2% of the total sample had elevated self-stigma. The highest prevalence (43.8%) was found in borderline personality disorder and the lowest (22.2%) in ASD. In the multivariate analysis, elevated self-stigma was best predicted by early stages of personal recovery (moratorium, p = 0.001, OR = 4.0 [1.78-8.98] ; awareness, p = 0.011, OR = 2.87 [1.28-6.44]), history of suicide attempt (p = 0.001, OR = 2.27 [1.37-3.76]), insight (p = 0.002, OR = 1.22 [1.08-1.38]), wellbeing (p = 0.037, OR = 0.77 [0.60-0.98]), and satisfaction with interpersonal relationships (p < 0.001, OR = 0.85 [0.78-0.93]). CONCLUSIONS. : The present study has confirmed the importance of addressing self-stigma in SMI and ASD patients enrolled in psychiatric rehabilitation. The effectiveness of psychiatric rehabilitation on self-stigma and the potential mediating effects of changes in self-stigma on treatment outcomes should be further investigated.

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7. Fombonne E, Green Snyder L, Daniels A, Feliciano P, Chung W. Psychiatric and Medical Profiles of Autistic Adults in the SPARK Cohort. J Autism Dev Disord ;2020 (Feb 24)

This study examined lifetime medical and psychiatric morbidity reported by caregivers of 2917 autistic adults participating in the US research cohort SPARK. Participants were 78.4% male, 47.3% had intellectual disability, and 32.1% had persistent language impairments. Childhood language disorders (59.7%), speech/articulation problems (32.8%), sleep (39.4%) and eating problems (29.4%), motor delays (22.8%) and history of seizure (15.5%) were the most frequently reported clinical features. Over two thirds (67.2%) had been diagnosed with at least one psychiatric disorder (anxiety disorders : 41.1% ; ADHD : 38.7%). Compared to verbally fluent participants, those with language impairments had lower frequencies of almost all psychiatric disorders. Female sex and older age were associated with higher medical and psychiatric morbidity.

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8. Guler HA, Turkoglu S, Cetin FH, Ucar HN, Erdogan Y. Olanzapine-Associated Pisa Syndrome in an Autistic Adolescent. Clin Neuropharmacol ;2020 (Feb 24)

OBJECTIVES : The objective of this study is to report a case of Pisa syndrome due to olanzapine use in an autistic adolescent. METHODS : The patient was a 12-year-old adolescent girl who was taking olanzapine for autism-related behavioral problems. Abnormal posture and balance problems appeared in the third month of olanzapine treatment. The patient was diagnosed as having Pisa syndrome after clinical evaluation. Biperiden was started on the patient whose complaints continued despite olanzapine treatment was stopped. Patient’s complaints regressed with biperiden treatment. RESULTS : According to our knowledge, there is no an autistic adolescent case of Pisa syndrome previously reported in the literature. Further studies are needed to clarify the etiology and treatment of Pisa syndrome. CONCLUSIONS : In patients with balance problems and abnormal posture as a result of olanzapine use, the clinician should keep in mind Pisa syndrome.

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9. Husson T, Lecoquierre F, Cassinari K, Charbonnier C, Quenez O, Goldenberg A, Guerrot AM, Richard AC, Drouin-Garraud V, Brehin AC, Soleimani M, Taton R, Rotharmel M, Rosier A, Chambon P, Le Meur N, Joly-Helas G, Saugier-Veber P, Boland A, Deleuze JF, Olaso R, Frebourg T, Nicolas G, Guillin O, Campion D. Rare genetic susceptibility variants assessment in autism spectrum disorder : detection rate and practical use. Transl Psychiatry ;2020 (Feb 24) ;10(1):77.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with a strong genetic component whose knowledge evolves quickly. Next-generation sequencing is the only effective technology to deal with the high genetic heterogeneity of ASD in a clinical setting. However, rigorous criteria to classify rare genetic variants conferring ASD susceptibility are currently lacking. We have performed whole-exome sequencing to identify both nucleotide variants and copy number variants (CNVs) in 253 ASD patients, including 68 patients with intellectual disability (ID) and 90 diagnosed as Asperger syndrome. Using explicit criteria to classify both susceptibility genes and susceptibility variants we prioritized 217 genes belonging to the following categories : syndromic genes, genes with an excess of de novo protein truncating variants and genes targeted by rare CNVs. We obtained a susceptibility variant detection rate of 19.7% (95% CI : [15-25.2%]). The rate for CNVs was 7.1% (95% CI : [4.3-11%]) and 12.6% (95% CI : [8.8-17.4%]) for nucleotide variants. The highest rate (30.1%, 95% CI : [20.2-43.2%]) was obtained in the ASD + ID subgroup. A strong contributor for at risk nucleotide variants was the recently identified set of genes (n = 81) harboring an excess of de novo protein truncating variants. Since there is currently no evidence that the genes targeted here are necessary and sufficient to cause ASD, we recommend to avoid the term "causative of ASD" when delivering the information about a variant to a family and to use instead the term "genetic susceptibility factor contributing to ASD".

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10. Kaur S, Silver G, Samuels S, Rosen AH, Weiss M, Mauer EA, Gerber LM, Greenwald BM, Traube C. Delirium and Developmental Disability : Improving Specificity of a Pediatric Delirium Screen. Pediatr Crit Care Med ;2020 (Feb 26)

OBJECTIVES : Children with developmental disabilities are at high risk for developing delirium when critically ill. However, existing pediatric delirium screening tools were designed for children with typical development. The objective of this study was to improve the specificity of the Cornell Assessment for Pediatric Delirium, to allow for accurate detection of delirium in developmentally delayed children admitted to the PICU. We hypothesized that the Cornell Assessment for Pediatric Delirium, when combined with fluctuation in level of awareness as measured by the Richmond Agitation-Sedation Scale, would be valid and reliable for the diagnosis of delirium in developmentally delayed children. DESIGN : Prospective observational double-blind cohort study. SETTING : Tertiary care academic PICU. PATIENTS : Children with moderate to severe developmental delay. INTERVENTIONS : Each child was evaluated by the bedside nurse with the Cornell Assessment for Pediatric Delirium once every 12 hours and the Richmond Agitation-Sedation Scale every 4 hours. Cornell Assessment for Pediatric Delirium (score >/= 9) + Richmond Agitation-Sedation Scale fluctuation (change in Richmond Agitation-Sedation Scale score of at least 2 points during a 24-hr period) was compared with the criterion standard psychiatric evaluation for diagnosis of delirium. MEASUREMENTS AND MAIN RESULTS : Forty children participated ; 94 independent paired assessments were completed. The psychiatrists’ diagnostic evaluations were compared with the detection of delirium by the Cornell Assessment for Pediatric Delirium and Richmond Agitation-Sedation Scale. Specificity of the Cornell Assessment for Pediatric Delirium + Richmond Agitation-Sedation Scale fluctuation was 97% (CI, 90-100%), positive predictive value of Cornell Assessment for Pediatric Delirium + Richmond Agitation-Sedation Scale fluctuation was 89% (CI, 65-99%) ; and negative predictive value remained acceptable at 87% (95% CI, 77-94%). In addition, to confirm interrater reliability of the criterion standard, 11 assessments were performed by two or more psychiatrists in a blinded fashion. There was perfect agreement (kappa = 1), indicating reliability in psychiatric diagnosis of delirium in developmentally delayed children. CONCLUSION : When used in conjunction with Richmond Agitation-Sedation Scale score fluctuation, the Cornell Assessment for Pediatric Delirium is a sensitive and specific tool for the detection of delirium in children with developmental delay. This allows for reliable delirium screening in this hard-to-assess population.

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11. Kitzerow J, Hackbusch M, Jensen K, Kieser M, Noterdaeme M, Frohlich U, Taurines R, Geissler J, Wolff N, Roessner V, Bast N, Teufel K, Kim Z, Freitag CM. Study protocol of the multi-centre, randomised controlled trial of the Frankfurt Early Intervention Programme A-FFIP versus early intervention as usual for toddlers and preschool children with Autism Spectrum Disorder (A-FFIP study). Trials ;2020 (Feb 24) ;21(1):217.

BACKGROUND : Naturalistic developmental behavioural interventions (NDBI) have been shown to improve autism-specific symptoms in young children with Autism Spectrum Disorder (ASD). NDBI approaches, such as the ASD-specific Frankfurt Early Intervention Programme for ASD (A-FFIP), are based on ASD-specific developmental and learning aspects. A-FFIP is a low-intensity intervention which can easily be implemented in the local health care/social welfare system. The aim of the present study is to establish 1-year efficacy of the manualised early intervention programme A-FFIP in toddlers and preschool children with ASD. It is hypothesised that A-FFIP will result in improved ASD-specific symptoms compared to early intervention as usual (EIAU). Child- and family-specific secondary outcomes, as well as moderators and mediators of outcome, will be explored. METHODS/DESIGN : A prospective, multi-centre, parallel-group, randomised controlled, phase-III trial comparing A-FFIP versus EIAU. A total of 134 children (A-FFIP : 67, EIAU : 67) aged 24-66 months at baseline assessment meeting the criteria for ASD (DSM-5) will be included. The primary outcome is the absolute change of the total score of the Brief Observation of Social Communication Change (BOSCC-AT) between baseline (T2) and 1-year follow-up (T6). The treatment effect will be tested, adjusted for relevant covariates applying a mixed model for repeated measures. Secondary outcomes are BOSCC social communication and repetitive-behaviour scores, single ASD symptoms, language, cognition, psychopathology, parental well-being and family quality of life. Predictors, moderators and mediating mechanisms will be explored. DISCUSSION : If efficacy of the manualised A-FFIP early intervention is established, the current study has the potential to change clinical practice strongly towards the implementation of a low-intensity, evidence-based, natural early intervention in ASD. Early intervention in ASD requires specialist training, which subsequently needs to be developed or included into current training curricula. TRIAL REGISTRATION : German Registry for Clinical Trials (Deutscher Register Klinischer Studien, DRKS) ; ID : 00016330. Retrospectively registered on 4 January 2019. URL : 16330.

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12. Kozlowski KF, Lopata C, Donnelly JP, Thomeer ML, Rodgers JD, Seymour C. Feasibility and Associated Physical Performance Outcomes of a High-Intensity Exercise Program for Children With Autism. Res Q Exerc Sport ;2020 (Feb 26):1-12.

Purpose : Children with autism spectrum disorder (ASD) without intellectual disability (ID) exhibit social and motor impairments and circumscribed interests/behaviors that contribute to lower physical activity (PA) levels. Despite the need for exercise interventions for these children, there is a dearth of evidence-based treatments. This study tested the feasibility of a high-intensity exercise program for children with ASD without ID, and associated changes in physical performance. Method : Fifty-eight children, ages 7-12 with ASD without ID participated. The intervention (5 weeks, 19 sessions, 60 mins ea.) was conducted during the summer. Each session was manualized (operationalized instructional procedure and curriculum) and targeted components of fitness and motor performance using skill development exercises, workouts, and game-related activities. Feasibility was assessed via fidelity (implementation accuracy), satisfaction surveys, attrition, and injuries. Physical performance was tested at baseline and posttest using measures of work production (completed rounds of an exercise circuit) and within-session activity levels (time in moderate-to-vigorous PA), and six exercise tests (sit and reach, push-ups, sit-ups, air squats, long jump, and PACER). Results : Results indicated high levels of fidelity (93.7%) and child and staff satisfaction, and no attrition or injuries, supporting the feasibility, tolerability, and safety of the protocol. Significant increases were found in work production and activity levels (ds 0.83 and 1.05, respectively) and on three exercise tests (sit ups, air squats, and long jump ; ds 0.29-0.37). Conclusion : The exercise program was feasible and safe, and completion was associated with significant improvements in multiple areas of performance ; a randomized controlled trial appears warranted.

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13. La Valle C, Plesa-Skwerer D, Tager-Flusberg H. Comparing the Pragmatic Speech Profiles of Minimally Verbal and Verbally Fluent Individuals with Autism Spectrum Disorder. J Autism Dev Disord ;2020 (Feb 25)

Although pragmatic speech impairments have been found across the autism spectrum, how these manifest in minimally verbal (MV) individuals with autism spectrum disorder (ASD) has not been studied. We compared the pragmatic speech profiles of MV (n = 50) and verbally fluent (VF) individuals with ASD (n = 50 ; 6-21 years-old) based on natural language sampling during the Autism Diagnostic Observation Schedule-2. MV individuals with ASD primarily used their speech to agree/acknowledge/disagree, respond to a question, and request. In contrast, the primary pragmatic function used by VF individuals was commenting. Out of the total non-echolalic speech, groups did not differ proportionally in labeling and response to questions. Findings highlight the importance of investigating multiple aspects of pragmatic communication across different conversational partners and contexts.

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14. Leane M. "I don’t care anymore if she wants to cry through the whole conversation, because it needs to be addressed" : Adult siblings’ experiences of the dynamics of future care planning for brothers and sisters with a developmental disability. J Appl Res Intellect Disabil ;2020 (Feb 25)

BACKGROUND : In families with a member with a developmental disability (DD), future care planning is limited (Brennan et al., Journal of Applied Research in Intellectual Disabilities, 31, 2018, 226 ; Bowey and McGlaughlin, British Journal of Social Work, 31, 2007, 39 ; Davys et al., Journal of Intellectual Disability, 14, 2010, 167 ; Davys et al., British Journal of Learning Disabilities, 43, 2014, 219 ; Davys et al., Journal of Applied Research in Intellectual Disabilities, 29, 2016, 220). However, most siblings without disabilities (SWD) expect to be involved in the future care of their brother or sister with DD (Benderix and Sivberg, International Paediatric Nursing, 22, 2007, 410 ; Gomez de la Cuesta and Cos, We exist too : Valuing the contributions of siblings, UK, National Autistic Society, 2012 ; Heller and Arnold, Journal of Policy and Practice in Intellectual Disabilities, 7, 2010, 16). MATERIALS AND METHODS : Based on qualitative interviews with 25 SWD in Ireland, this article explores how SWD experience future planning. RESULTS AND DISCUSSION : The findings indicate that SWD experience care planning as an ongoing, fluid and emotionally charged process. Parental fears, about future care landscapes they do not control and about passing on intergenerational care responsibilities, emerge as key factors inhibiting planning. CONCLUSION : Attention to the highly emotive nature of care concerns, and to the tentative pace of planning that is comfortable for families, will help professionals provide optimum planning support.

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15. Matsumura K, Seiriki K, Okada S, Nagase M, Ayabe S, Yamada I, Furuse T, Shibuya H, Yasuda Y, Yamamori H, Fujimoto M, Nagayasu K, Yamamoto K, Kitagawa K, Miura H, Gotoda-Nishimura N, Igarashi H, Hayashida M, Baba M, Kondo M, Hasebe S, Ueshima K, Kasai A, Ago Y, Hayata-Takano A, Shintani N, Iguchi T, Sato M, Yamaguchi S, Tamura M, Wakana S, Yoshiki A, Watabe AM, Okano H, Takuma K, Hashimoto R, Hashimoto H, Nakazawa T. Pathogenic POGZ mutation causes impaired cortical development and reversible autism-like phenotypes. Nat Commun ;2020 (Feb 26) ;11(1):859.

Pogo transposable element derived with ZNF domain (POGZ) has been identified as one of the most recurrently de novo mutated genes in patients with neurodevelopmental disorders (NDDs), including autism spectrum disorder (ASD), intellectual disability and White-Sutton syndrome ; however, the neurobiological basis behind these disorders remains unknown. Here, we show that POGZ regulates neuronal development and that ASD-related de novo mutations impair neuronal development in the developing mouse brain and induced pluripotent cell lines from an ASD patient. We also develop the first mouse model heterozygous for a de novo POGZ mutation identified in a patient with ASD, and we identify ASD-like abnormalities in the mice. Importantly, social deficits can be treated by compensatory inhibition of elevated cell excitability in the mice. Our results provide insight into how de novo mutations on high-confidence ASD genes lead to impaired mature cortical network function, which underlies the cellular pathogenesis of NDDs, including ASD.

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16. Ne’eman A, Albrecht K, Kapp SK. Obsessive-Compulsive Behaviors in Autism. Jama ;2020 (Feb 25) ;323(8):790.

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17. Rahman R, Kodesh A, Levine SZ, Sandin S, Reichenberg A, Schlessinger A. Identification of newborns at risk for autism using electronic medical records and machine learning. Eur Psychiatry ;2020 (Feb 26) ;63(1):e22.

BACKGROUND. : Current approaches for early identification of individuals at high risk for autism spectrum disorder (ASD) in the general population are limited, and most ASD patients are not identified until after the age of 4. This is despite substantial evidence suggesting that early diagnosis and intervention improves developmental course and outcome. The aim of the current study was to test the ability of machine learning (ML) models applied to electronic medical records (EMRs) to predict ASD early in life, in a general population sample. METHODS. : We used EMR data from a single Israeli Health Maintenance Organization, including EMR information for parents of 1,397 ASD children (ICD-9/10) and 94,741 non-ASD children born between January 1st, 1997 and December 31st, 2008. Routinely available parental sociodemographic information, parental medical histories, and prescribed medications data were used to generate features to train various ML algorithms, including multivariate logistic regression, artificial neural networks, and random forest. Prediction performance was evaluated with 10-fold cross-validation by computing the area under the receiver operating characteristic curve (AUC ; C-statistic), sensitivity, specificity, accuracy, false positive rate, and precision (positive predictive value [PPV]). RESULTS. : All ML models tested had similar performance. The average performance across all models had C-statistic of 0.709, sensitivity of 29.93%, specificity of 98.18%, accuracy of 95.62%, false positive rate of 1.81%, and PPV of 43.35% for predicting ASD in this dataset. CONCLUSIONS. : We conclude that ML algorithms combined with EMR capture early life ASD risk as well as reveal previously unknown features to be associated with ASD-risk. Such approaches may be able to enhance the ability for accurate and efficient early detection of ASD in large populations of children.

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18. Reddihough DS, Marraffa C, Whitehouse AJO. Obsessive-Compulsive Behaviors in Autism-Reply. Jama ;2020 (Feb 25) ;323(8):790-791.

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19. Welch C, Cameron D, Fitch M, Polatajko H. Living in autistic bodies : bloggers discuss movement control and arousal regulation. Disabil Rehabil ;2020 (Feb 25):1-9.

Aim : We sought to deepen understanding of embodied experiences of autism by examining how autistic bloggers describe and discuss autism.Methods : Working within a qualitative description approach, we sampled 40 blogs written by people who identify as autistic. We conducted a directed content analysis, applying a codebook that was generated using themes from a previous study, while remaining open to additional theme generation and elimination.Results : The rich description in the blog posts support our previous finding that autism is a highly embodied experience including challenges with movement control. Additionally, we found arousal regulation (ability to maintain a calm yet alert state) to be an important embodied experience for the bloggers.Conclusions : Our findings support a conceptualization of autism that sees embodiment, movement and arousal regulation as important elements of autism. Rehabilitation researchers and professionals should note that autistic insider perspectives can and must be accessed for optimal outcomes.IMPLICATIONS FOR REHABILITATIONClinicians should consider movement control (starting and stopping movement at will) difficulties as possible barriers to function for some autistic people.Clinicians should consider arousal regulation (ability to govern physiological and psychological activation level) difficulties as a possible barrier to function for some autistic people.Clinicians should be cautious when interpreting observed behaviours of autistic people and should make every effort to get explanations for behaviour directly from the perspective of individual clients.

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20. Zhang L, Qin Z, Ricke KM, Cruz SA, Stewart AFR, Chen HH. Hyperactivated PTP1B phosphatase in parvalbumin neurons alters anterior cingulate inhibitory circuits and induces autism-like behaviors. Nat Commun ;2020 (Feb 24) ;11(1):1017.

Individuals with autism spectrum disorder (ASD) have social interaction deficits and difficulty filtering information. Inhibitory interneurons filter information at pyramidal neurons of the anterior cingulate cortex (ACC), an integration hub for higher-order thalamic inputs important for social interaction. Humans with deletions including LMO4, an endogenous inhibitor of PTP1B, display intellectual disabilities and occasionally autism. PV-Lmo4KO mice ablate Lmo4 in PV interneurons and display ASD-like repetitive behaviors and social interaction deficits. Surprisingly, increased PV neuron-mediated peri-somatic feedforward inhibition to the pyramidal neurons causes a compensatory reduction in (somatostatin neuron-mediated) dendritic inhibition. These homeostatic changes increase filtering of mediodorsal-thalamocortical inputs but reduce filtering of cortico-cortical inputs and narrow the range of stimuli ACC pyramidal neurons can distinguish. Simultaneous ablation of PTP1B in PV-Lmo4KO neurons prevents these deficits, indicating that PTP1B activation in PV interneurons contributes to ASD-like characteristics and homeostatic maladaptation of inhibitory circuits may contribute to deficient information filtering in ASD.

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