Pubmed du 16/11/19

samedi 16 novembre 2019

1. Carlezon WA, Jr., Kim W, Missig G, Finger BC, Landino SM, Alexander AJ, Mokler EL, Robbins JO, Li Y, Bolshakov VY, McDougle CJ, Kim KS. Maternal and early postnatal immune activation produce sex-specific effects on autism-like behaviors and neuroimmune function in mice. Sci Rep ;2019 (Nov 15) ;9(1):16928.

Increasing evidence suggests a role for inflammation in neuropsychiatric conditions including autism spectrum disorder (ASD), a neurodevelopmental syndrome with higher prevalence in males than females. Here we examined the effects of early-life immune system activation (EIA)-comprising regimens of prenatal, early postnatal, or combined ("two-hit") immune activation-on the core behavioral features of ASD (decreased social interaction, increased repetitive behavior, and aberrant communication) in C57BL/6J mice. We treated timed-pregnant mice with polyinosinic:polycytidylic acid (Poly I:C) on gestational day 12.5 to produce maternal immune activation (MIA). Some offspring also received lipopolysaccharide (LPS) on postnatal day 9 to produce postnatal immune activation (PIA). EIA produced disruptions in social behavior and increases in repetitive behaviors that were larger in males than in females. Ultrasonic vocalizations (USVs) were altered in both sexes. Molecular studies revealed that EIA also produced prominent sex-specific changes in inflammation-related gene expression in the brain. Whereas both sexes showed increases in pro-inflammatory factors, as reflected by levels of mRNA and protein, expression of anti-inflammatory factors was decreased in males but increased in females. Our findings demonstrate that EIA can produce sex-specific behavioral effects and immune responses in the brain, and identify molecular processes that may contribute to resilience in females.

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2. Fallah H, Sayad A, Ranjbaran F, Talebian F, Ghafouri-Fard S, Taheri M. IFNG/IFNG-AS1 expression level balance : implications for autism spectrum disorder. Metab Brain Dis ;2019 (Nov 14)

Autism spectrum disorder (ASD) is a neurodevelopmental disorder associated with different epidemiological, genetic, epigenetic, and environmental factors. Although its etiology is not fully understood, immune dysfunction is implicated in this disease. Recently, a large number of genes encoding long noncoding RNAs (lncRNAs) were discovered which act as positive or negative regulators of neighboring target genes. The lncRNA, Interferon gamma-antisense RNA (IFNG-AS1), regulates expression levels of the Interferon gamma (IFNG) gene. In the present study, we investigated expression of IFNG and IFNG-AS1 in 50 children with ASD (15 females and 35 males, mean age : 6 +/- 1.4 years) and 50 healthy controls (14 females and 36 males, mean age : 6 +/- 1.74 years) by real time PCR technique. The results showed significant up-regulation of IFNG and down-regulation of IFNG-AS1 expression in children with ASD compared to controls (Fold change = 1.5, P < 0.0001 ; Fold change = -0.143, P = 0.013, respectively). The IFNG expression level increase was more pronounced in male ASD children (Fold change = 1.621 ; p < 0.0001). Our data reveal a functional disruption in the interactive network of IFNG/IFNG-AS1 regulation, which could be a contributing factor in the chronic inflammatory aspect of ASD. Our findings can help understanding the underlying contributors to ASD pathogenesis and find novel treatment options for children with ASD.

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3. Fitzpatrick SE, Schmitt LM, Adams R, Pedapati EV, Wink LK, Shaffer RC, Sage J, Weber JD, Dominick KC, Erickson CA. Pediatric Quality of Life Inventory (PedsQL) in Fragile X Syndrome. J Autism Dev Disord ;2019 (Nov 14)

To date, health related quality of life (QoL) has not been systematically evaluated in youth with fragile X syndrome (FXS), the most common single gene cause of autism and the most common inherited form of developmental disability. We describe QoL data gathered using the Pediatric Quality of Life Inventory (PedsQL) completed online by 364 parents of youth with FXS. Parents consistently reported across all gender and age groups that their children experienced the highest QoL in Physical functioning and the lowest QoL in Cognitive functioning. Overall, older children with FXS had increase QoL ratings in the domains of School and Cognitive function.

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4. Katz-Nave G, Adini Y, Hetzroni OE, Bonneh YS. Sequence Learning in Minimally Verbal Children With ASD and the Beneficial Effect of Vestibular Stimulation. Autism Res ;2019 (Nov 14)

People with autism spectrum disorder (ASD) and especially the minimally verbal, often fail to learn basic perceptual and motor skills. This deficit has been demonstrated in several studies, but the findings could have been due to the nonoptimal adaptation of the paradigms. In the current study, we sought to characterize the skill learning deficit in young minimally verbal children with ASD and explore ways for improvement. For this purpose, we used vestibular stimulation (VS) whose beneficial effects have been demonstrated in the typical population, but the data regarding ASD are limited. We trained 36 children ages 6-13 years, ASD (N = 18, 15 of them minimally verbal) and typical development (TD, N = 18), on a touch version of the visual-motor Serial-Reaction-Time sequence-learning task, in 10 short (few minutes) weekly practice sessions. A subgroup of children received VS prior to each training block. All the participants but two ASD children showed gradual median reaction time improvement with significant speed gains across the training period. The ASD children were overall slower (by 250 msec). Importantly, those who received VS (n = 10) showed speed gains comparable to TD, which were larger (by 100%) than the ASD controls, and partially sequence-specific. VS had no effect on the TD group. These results suggest that VS has a positive effect on learning in minimally verbal ASD children, which may have important therapeutic implications. Furthermore, contrary to some previous findings, minimally verbal children with ASD can acquire, in optimal conditions, procedural skills with few short training sessions, spread over weeks, and with a similar time course as non-ASD controls. Autism Res 2019. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY : Minimally verbal children with ASD who received specially adjusted learning conditions showed significant learning of a visual-motor sequence across 10 practice days. This learning was considerably improved with vestibular stimulation before each short learning session. This may have important practical implications in the education and treatment of ASD children.

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5. Leong D, Hedley D, Uljarevic M. Poh-tay-toe, Poh-tah-toe : Autism Diagnosis and Conceptualization. J Child Neurol ;2019 (Nov 15):883073819887587.

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6. Parmeggiani A, Corinaldesi A, Posar A. Early features of autism spectrum disorder : a cross-sectional study. Ital J Pediatr ;2019 (Nov 14) ;45(1):144.

BACKGROUND : Autism spectrum disorder is characterized by impairment in social interaction and communication along with repetitive, restricted, and stereotyped behaviors, interests and activities. It is important to detect this condition as soon as possible and promptly begin targeted treatments. This study aimed to report on age at onset, early signs, and mode at onset in 105 Italian patients with autism spectrum disorder, searching for correlations with a series of clinical and instrumental variables. METHODS : This retrospective cross-sectional study considered the following five categories of symptoms at onset : language, social interaction and relationships, stereotyped behavior and activities, motor skills, and regulation. Three modes of presentation were considered : a delay, a stagnation, or a regression of development, which were defined modes of onset of autism spectrum disorder. The age at onset, the category of clinical features, and the mode at onset were considered in the entire sample and statistically analyzed for several clinical variables. Statistical analysis was performed utilizing Fisher Exact test and Chi Square test. RESULTS : The first symptoms between 7 and 12 months were evident in 41.9% of cases, and between 13 and 24 months in 27.6% ; no significant differences for the age at onset related to diagnosis, etiopathogenesis, early onset epilepsy, and intelligence quotient level emerged. Social interaction and relationships (93.3%) and language (92.4%) were the categories of early signs more represented in our sample. Delay in spoken language (to be understood as both verbal production and verbal comprehension) was one of the most common (even though not specific) symptoms prompting initial medical consultation for a possible diagnosis of autism spectrum disorder. At onset, patients without intellectual disability manifested stagnation more often than delay or regression of development ; patients with a severe/profound intellectual disability more frequently showed delay or regression of development. Language signs at onset were less frequent in cases with regression, whereas motor skill disorders prevailed in cases with delay at onset. Feeding problems were more numerous in cases with delay and stagnation of development. CONCLUSIONS : These data contribute to identifying an early trend of autism spectrum disorder, useful also for pediatricians.

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7. Pearson JN, Traficante AL, Denny LM, Malone K, Codd E. Meeting FACES : Preliminary Findings from a Community Workshop for Minority Parents of Children with Autism in Central North Carolina. J Autism Dev Disord ;2019 (Nov 15)

In North Carolina (NC), there are many resources designed to support the needs of children with autism and their families, and yet a troubling gap in underserved families’ access to those services. To address this gap, the Meeting FACES workshop was designed to : (a) provide an opportunity for parents, educators, and service providers to build partnerships, (b) provide parents with opportunities to learn about available autism services in their communities, and (c) assess the needs of underrepresented families of children with autism in NC. Findings indicate that minority families of children with autism in central NC require more supports to access and navigate services. Additionally, participants were very satisfied with Meeting FACES and were interested in participating in future FACES programming.

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8. Persico AM, Ricciardello A, Cucinotta F. The psychopharmacology of autism spectrum disorder and Rett syndrome. Handb Clin Neurol ;2019 ;165:391-414.

Autism spectrum disorder (ASD) appears in early childhood and is characterized by persistent deficits in communication and social interaction, as well as restricted interests, repetitive behaviors, and unusual sensory issues. ASD can be idiopathic or syndromic, in the latter case representing one of the many manifestations of a genetic disorder, such as Rett syndrome. Psychopharmacology cannot directly ameliorate core autistic symptoms, but rather aims at treating comorbid disorders, such as ADHD, sleep disturbances, psychomotor agitation and aggressiveness, seizures, and anxiety. Until the 1990s, it was mainly based on typical neuroleptics and tricyclic antidepressants, whereas second-generation antipsychotics later became first-line drugs for these same indications. In general, selective serotonin reuptake inhibitors have not proven effective in ASD patients. Psychostimulants are frequently prescribed, but display modest efficacy and enhanced potential for side effects and noncompliance. Targeted patients benefit from mood stabilizers and antiepileptic drugs. Experimental drug treatments for ASD include oxytocin and vasopressin, bumetanide, sulforaphane, nutritional supplements, memantine, and d-cycloserine. Work performed on syndromic forms, represents an important source of information for experimental therapies of ASD and knowledge of the unique mechanisms underlying autism in each individual patient may in the future pave the path to personalized drug treatments.

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9. Ruiz-Martinez FJ, Rodriguez-Martinez EI, Wilson CE, Yau S, Saldana D, Gomez CM. Impaired P1 Habituation and Mismatch Negativity in Children with Autism Spectrum Disorder. J Autism Dev Disord ;2019 (Nov 15)

Passive testing of auditory function is an important objective in individuals with ASD due to known difficulties in understanding and/or following task instructions. In present study the habituation to standard tones following deviants and the auditory discriminative processes were examined in two conditions : electronic and human sounds, in a sample of 16 ASD children. ASD children presented a reduced habituation in the P1 component and a decrease in the amplitude of the mismatch negativity indicating a lower auditory discrimination with respect to controls. MMN amplitude was related to sensory sensitivity. Results suggest an increased activation to repeatedly auditory stimulus and a poor auditory discrimination, for both : electronic and human sounds with consequences on the impaired sensory behavior of ASD subjects.

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10. Shulman L, Valicenti-McDermott MR, Seijo R. Response to Letter to the Editor "ASD Diagnosis and Conceptualization". J Child Neurol ;2019 (Nov 15):883073819887848.

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11. Suelzer EM, Deal J, Hanus KL, Ruggeri B, Sieracki R, Witkowski E. Assessment of Citations of the Retracted Article by Wakefield et al With Fraudulent Claims of an Association Between Vaccination and Autism. JAMA Netw Open ;2019 (Nov 1) ;2(11):e1915552.

Importance : The number of citations can be used to show the influence of an article or to measure the validity of a research study. The article by Wakefield et al that fraudulently reported an association between vaccination and autism continues to accumulate citations even after it was retracted. Objectives : To examine the characteristics of citations from scholarly literature that reference the 1998 article by Wakefield et al and to investigate whether authors are accurately citing retracted references. Design, Setting, and Participants : In this cross-sectional bibliographic analysis of the scholarly publications that cited a 1998 article by Wakefield et al, cited references were collected from a Web of Science Core Collection search performed on March 11, 2019. A total of 1211 articles were identified, with 58 citing works excluded because they were non-English-language publications or the citation to the study by Wakefield et al could not be located by reviewers. Citing works consisted of books, research articles, letters, editorials, news items, and other scholarly literature. Citations to the article by Wakefield et al were identified and analyzed by 2 reviewers in a blinded screening. Reviewers assigned a characteristic to each citation and indicated whether the retraction was documented. Main Outcomes and Measures : The characteristics of citations to the article by Wakefield et al, were categorized as negative, affirmative, or contrastive ; if not, persuasive ; and if not, assumptive, perfunctory, methodologic, or conceptual. Whether the partial retraction or notice of retraction was included in the citing work was also documented. Results : Among the 1153 citing works included in this analysis, the most common citation characteristics were negative (838 [72.7%]) followed by perfunctory (106 [9.2%]) and affirmative (94 [8.2%]). A total of 123 of 322 citing works (38.2%) published between 2005 and 2010 documented the partial retraction. After the notice of retraction was published in 2010, the percentage of citing works that documented the partial retraction and/or notice of retraction between 2011 and 2018 increased to 360 of 502 (71.7%). Conclusions and Relevance : Since the article by Wakefield et al was initially published, authors have mostly negated the findings of the study. A significant number of authors did not document retractions of the article by Wakefield et al. The findings suggest that improvements are needed from publishers, bibliographic databases, and citation management software to ensure that retracted articles are accurately documented.

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12. Tunesi S, Bosio M, Russo AG. Do autistic patients change healthcare services utilisation through the transition age ? An Italian longitudinal retrospective study. BMJ Open ;2019 (Nov 14) ;9(11):e030844.

OBJECTIVES : This paper aims to provide an estimate of the prevalence rate of autism spectrum disorder (ASD) in 8-year-olds in 2017 based on administrative databases and to investigate the change in healthcare service use during the healthcare transition age of 18. DESIGN : This research is based on a longitudinal retrospective cohort study. SETTING : The data is drawn from the Italian Administrative Healthcare Database (2010-2017). PARTICIPANTS : We identified 5607 ASD patients ; 331 ASD patients from 2012 to 2015 in the calendar year of their 18th birthday were selected and their health service utilisation during a 5-year period-ranging from 2 years preceding and succeeding their 18th year-were investigated. INTERVENTIONS : None. PRIMARY AND SECONDARY OUTCOME MEASURES : Prevalence, incidence and proportion of ASD patients receiving specific healthcare services were included in the outcome measures. RESULTS : Prevalence of ASD at age 8 was 5.4/1000. Global access to health and social services was lower both before and after age 18 (46.5% at 16 ; 68.0% at 18 ; 54.1% at 20). The percentage of patients receiving a neuropsychiatric consultation decreased after age 18 (30.8% at 18 ; 5.4% at 20). Community mental health services (CMHS) utilisation rate increased above 18 years of age. Regarding psychiatric visits, for both outpatient and CMHS, an increase was observed from 17.8% at age 18 to 25.4% at age 20. The utilisation of rehabilitation services decreased with age, dropping from 17.8% at age 16 to 1.8% at age 20. Psychiatric outpatient services remained stable across ages at about 14%. CONCLUSION : Our findings suggest that ASD patients changed clinical reference services with age from neuropsychiatric and rehabilitative services towards psychiatric and community-based services as they transitioned from paediatric to adult healthcare services.

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13. Varela RE, DuPont R, Kamps JL, Weems CF, Niditch L, Beaton EA, Pucci G. Age Differences in Expression of Generalized and Social Anxiety Among Youth with Autism Spectrum Disorder. J Autism Dev Disord ;2019 (Nov 15)

This study examined differences in generalized and social anxiety symptoms across two age groups of children with autism spectrum disorder (ASD) while accounting for overall anxiety level, gender, and intellectual functioning. Older children (12-18 years) expressed more overall and social anxiety symptoms than younger children (6-11 years), and social anxiety symptoms were predominant in the older group. Younger children expressed more generalized anxiety symptoms than the older youth, and there was a trend for generalized anxiety symptoms to be more dominant in the younger group. Findings are consistent with theory of differential expression of specific anxiety symptoms across different ages seen with typically developing children, yet social evaluative concerns may be even stronger for adolescents with ASD.

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14. Wang J, Feng S, Li M, Liu Y, Yan J, Tang Y, Du D, Chen F. Increased Expression of Kv10.2 in the Hippocampus Attenuates Valproic Acid-Induced Autism-Like Behaviors in Rats. Neurochem Res ;2019 (Nov 15)

The role of potassium channels provides suggestive evidence for the etiology of autism. The voltage-gated potassium channel Kv10.2 (KCNH5) is widely expressed in the brain. However, the inherent relationship between Kv10.2 and autism is still unclear. Herein, a rat valproic acid (VPA)-induced autism spectrum disorder model was established. The expression level of Kv10.2 was obviously decreased in the hippocampus of VPA rats. Kv10.2 was mainly localized in neurons. Subsequently, a recombinant lentivirus expressing Kv10.2 was used to upregulate the expression of Kv10.2 in the hippocampus of VPA-exposed rats. The results were promising as injection of the Kv10.2 lentivirus in the hippocampus relieved anxiety and stereotypical behavior, and improved the social and exploratory abilities of rats that were prenatally exposed to VPA. In addition, spectral analysis of electroencephalogram data revealed that animals exposed to VPA exhibited increased high-frequency activity compared with the control rats, and this activity recovered to a certain extent after upregulation of Kv10.2 expression by lentivirus injection. These results suggest that changes in Kv10.2 may play an important role in the etiology of autism, thus providing a promising direction for further research on autism.

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15. Watanabe T, Kumazaki H, Muramatsu T, Mimura M. The specific aspects of operating an unfamiliar touchscreen for individuals with autism spectrum disorders. Psychiatry Clin Neurosci ;2019 (Nov 15)

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16. Wilson NJ, Lin Z, Villarosa A, Lewis P, Philip P, Sumar B, George A. Countering the poor oral health of people with intellectual and developmental disability : a scoping literature review. BMC Public Health ;2019 (Nov 15) ;19(1):1530.

BACKGROUND : People with intellectual and developmental disability (IDD) have poor oral health and need support to maintain optimal oral health outcomes. Little is known about how, when and where to intervene for this population. Thus the aim of this review was to summarise the existing evidence surrounding improving oral health outcomes for people with IDD. METHODS : A scoping literature review was conducted focusing on ’oral health’ and ’intellectual disability’. Systematic searches of five electronic databases were conducted in line with the study aims and two authors independently examined all records for relevance, with consensus achieved by a third author. RESULTS : A small number of approaches and interventions were identified to support people with IDD to independently maintain optimal oral hygiene. Identified studies highlighted that caregivers play a vital role in the provision of oral health support, emphasising the effectiveness of educational interventions for caregivers. However, there was uncertainty regarding the efficacy of specific tooth brushing interventions for people with IDD. In cases of more severe IDD and/or dental-related behavioural problems, dental treatment under general anaesthesia was often both a necessary and effective method of oral health care provision. The findings also identified outreach and exclusive oral health services as successful strategies for increasing the limited access of people with IDD to oral care services. CONCLUSIONS : A uniform approach to supporting oral health for people with IDD is unlikely to succeed. A system-based approach is needed to address the diverse needs of the population of people with IDD, their caregivers and service context. Further high quality evidence is required to confirm these findings.

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17. Xu J, Wang C, Xu Z, Li T, Chen F, Chen K, Gao J, Wang J, Hu Q. Specific Functional Connectivity Patterns of Middle Temporal Gyrus Subregions in Children and Adults with Autism Spectrum Disorder. Autism Res ;2019 (Nov 14)

As one of the key regions in the "social brain" network, the middle temporal gyrus (MTG) has been widely reported to be associated with autism spectrum disorder (ASD), but there have been contradictory results in terms of whether it shows hyperconnectivity or hypoconnectivity. Delineating roles of MTG at the subregional level may eliminate the observed inconsistencies and provide a new avenue to reveal the neurophysiologic mechanism of ASD. Thus, we first performed connectivity-based parcellation using the BrainMap database to identify fine-grained functional topography of the MTG. Then, the MTG subregions were used to investigate differences in the functional connectivity in children and adults with ASD using two data sets from Autism Brain Imaging Data Exchange database. Four distinct subregions in the human left and right MTG were identified, including the anterior MTG (aMTG), middle-anterior MTG (maMTG), middle-posterior MTG, and posterior MTG (pMTG). The bilateral pMTG was more vulnerable in both children and adults with ASD than in the typically developing (TD) group, mainly showing hypoconnectivity with different brain regions. In addition, the bilateral aMTG and right maMTG also showed altered functional connectivity in adults with ASD compared to the TD group. Moreover, all these altered MTG subregions were mainly associated with social cognition and language, as revealed by functional characterization. Further correlation analyses also showed trends of association between altered connectivity of the left aMTG and the Autism Diagnostic Observation Schedule scores in adults with ASD. Together, these results suggest a potential objective way to explore sub-regional differences associated with such disorders. Autism Res 2019. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY : Four distinct subregions in the human left and right middle temporal gyrus (MTG) were identified, including the anterior MTG (aMTG), middle-anterior MTG (maMTG), middle-posterior MTG, and posterior MTG (pMTG). The bilateral pMTG was more vulnerable in both children and adults with autism spectrum disorder (ASD) than in the typically developing (TD) group, mainly showing hypoconnectivity with different brain regions. In addition, the bilateral aMTG and right maMTG also showed altered functional connectivity in adults with ASD compared to the TD group. Moreover, all these altered MTG subregions were mainly associated with social cognition and language, as revealed by functional characterization. Further correlation analyses also showed trends of association between altered connectivity of the left aMTG and the Autism Diagnostic Observation Schedule scores in adults with ASD.

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