1. Ahmad SF, Nadeem A, Ansari MA, Bakheet SA, Alshammari MA, Attia SM. {{The PPARdelta agonist GW0742 restores neuroimmune function by regulating Tim-3 and Th17/Treg-related signaling in the BTBR autistic mouse model}}. {Neurochem Int};2018 (Sep 15)
Autism spectrum disorders (ASD) are neurodevelopmental disorders that are characterized by repetitive behaviors, and impairments in communication and social interaction. Studies have shown that activation of peroxisome proliferator-activated receptor-delta (PPARdelta) causes anti-inflammatory effects in animal models of neuroinflammatory diseases. We investigated the possible anti-inflammatory effect of a PPARdelta agonist, GW0742 in the BTBR T(+) Itpr3tf/J (BTBR) mouse model of autism. BTBR and C57BL/6 (B6) mice were treated orally with GW0742 (30mg/kg, p.o., once daily) for 7 days. Effect of GW0742 treatment on repetitive behavior, marble burying, and thermal sensitivity response was assessed on day 8. We further examined the effect of GW0742 treatment on immunological parameters in splenocytes using flow cytometry (CD4(+)TIM-3(+), IL-17A(+)TIM-3(+), IL-17A(+)CD4(+), RORgammaT(+)TIM-3(+), RORgammaT(+)CD4(+), Stat3(+)TIM-3(+), Foxp3(+)TIM-3(+), Foxp3(+)CD4(+), and IFN-gamma(+)CD4(+)). We also explored the effects of GW0742 on mRNA and protein expression of TIM-3, IL-17A, RORgammaT, Stat3, IFN-gamma, Foxp3, and IL-10 in the brain tissue using RT-PCR and western blot analyses. GW0742 treatment substantially decreased repetitive behaviors, and lowered thermal sensitivity response in BTBR mice. GW0742 attenuated the expression of inflammatory markers such as IL-17A, RORgammaT, Stat3, TIM-3, and IFN-gamma, while upregulating anti-inflammatory markers such as IL-10/Foxp3 both in the brain and periphery of BTBR mice. In conclusion, this study suggests that GW0742 corrects neurobehavioral dysfunction in BTBR mice which is concurrent with modulation of multiple signaling pathways.
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2. Brondino N, Rocchetti M, Fusar-Poli L, Damiani S, Goggi A, Chiodelli G, Corti S, Visai L, Politi P. {{Increased CNTF levels in adults with autism spectrum disorders}}. {World J Biol Psychiatry};2018 (Sep 19):1-5.
OBJECTIVES: Ciliary neurotrophic factor (CNTF) is a neurotrophin which could signal neuronal suffering and at the same time acts as a neuroprotective agent. In the present study we aimed to evaluate CNTF serum levels in autism spectrum disorders (ASDs). In fact, considering the role of CNTF as a neuronal damage signal and the role of neuroinflammation, excito-inhibitory imbalance and excitotoxicity in the pathogenesis of ASDs, a possible alteration of CNTF in ASDs could be hypothesised. METHODS: We recruited 23 individuals with ASDs and intellectual disability (ID), 20 ID subjects and 26 typical adults. A complete medical and psychopathological characterisation of the participants was performed. CNTF serum levels were measured with ELISA. RESULTS: CNTF serum levels were significantly higher in the ASD + ID group compared to ID (p < .001) or typically developed subjects (p < .001). CONCLUSIONS: CNTF may be considered as a potential biomarker candidate for ASDs in the context of severe ID. Our results support the hypothesis of neurotrophic imbalance in ASDs. Lien vers le texte intégral (Open Access ou abonnement)
3. Chenausky K, Norton A, Tager-Flusberg H, Schlaug G. {{Behavioral predictors of improved speech output in minimally verbal children with autism}}. {Autism Res};2018 (Sep 19)
We investigated the relationship between eight theoretically motivated behavioral variables and a spoken-language-related outcome measure, after 25 sessions of treatment for speech production in 38 minimally verbal children with autism. After removing potential predictors that were uncorrelated with the outcome variable, two remained. We used both complete-case and multiple-imputation analyses to address missing predictor data and performed linear regressions to identify significant predictors of change in percent syllables approximately correct after treatment. Baseline phonetic inventory (the number of English phonemes repeated correctly) was the most robust predictor of improvement. In the group of 17 participants with complete data, ADOS score also significantly predicted the outcome. In contrast to some earlier studies, nonverbal IQ, baseline levels of expressive language, and younger age did not significantly predict improvement. The present results are not only consistent with previous studies showing that verbal imitation and autism severity significantly predict spoken language outcomes in preschool-aged minimally verbal children with autism, but also extend these findings to older minimally verbal children with autism. Autism Res 2018. (c) 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: We wished to understand what baseline factors predicted whether minimally verbal children with autism would improve after treatment for spoken language. The outcome measure was change in percentage (%) syllables approximately correct on a set of 30 two-syllable words or phrases. Fifteen were both practiced in treatment and tested; the remainder were not practiced in treatment, but only tested, to assess how well children were able to generalize their new skills to an untrained set of words. Potential predictors tested were sex, age, expressive language, phonetic inventory (the number of English speech sounds repeated correctly), autism severity, and nonverbal IQ. Phonetic inventory and (for some children) autism severity predicted children’s posttreatment improvement. Nonverbal IQ and expressive language ability did not predict improvement, nor did younger age, suggesting that some older children with autism may be candidates for speech therapy.
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4. Donato C, Spencer E, Arthur-Kelly M. {{A critical synthesis of barriers and facilitators to the use of AAC by children with autism spectrum disorder and their communication partners}}. {Augment Altern Commun};2018 (Sep 19):1-12.
The aim of this review was to critically synthesize barriers and facilitators to the use of AAC systems by children with autism spectrum disorder (ASD) and their communication partners. Qualitative data related to barriers and facilitators were synthesized from 42 studies located using a systematic search. A diverse range of studies was examined in order to identify the span of barriers and facilitators reported in the literature. Included studies comprised quasi-experimental, non-experimental, and qualitative study designs. The full range of unaided, low-tech aided, and high-tech aided AAC systems were reported across the included studies. The critical synthesis identified 5 themes to which barriers and facilitators are related: (a) Intervention Services and Service Providers, (b) AAC Systems and Technologies (c), Communication Partners of Children with ASD, (d) Parents of Children with ASD, and (e) Children with ASD. The findings suggest that barriers and facilitators to the use of AAC vary across individuals, AAC modalities, and environments. By identifying barriers and facilitators to the use of AAC experienced by children with ASD and their communication partners, service providers might be better equipped to support these children and their communication partners. Clinical implications and future research directions are discussed.
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5. Gorker I, Gurkan H, Ulusal S, Atli E, Ayaz G, Ceylan C, Tozkir H, Altay MA, Erol A, Yildiz N, Direk C, Akkopru H, Kilit N, Aykutlu HC, Bozatli L, Celik Z, Berberoglu KK. {{Investigation of Copy Number Variation by arrayCGH in Turkish Children and Adolescents Diagnosed with Autism Spectrum Disorders}}. {Noro Psikiyatr Ars};2018 (Sep);55(3):215-219.
Aim: The development of whole-genome screening methodologies for the detection of copy number variations (CNVs), such as array-based comparative genomic hybridization (aCHG), provides a much higher resolution than karyotyping leading to the identification of novel microdeletion and microduplication syndromes often associated with an autism spectrum disease (ASD) phenotype. The aim of the study was to determine CNVs of patients with ASD by using array-based comparative genomic hybridization. Methods: Fifty-three patients diagnosed with ASD between 20.01.2014 and 14.01.2015 were included in the study. Chromosome analysis of the patients was performed from peripheral blood cultures and analysed as normal. All patients were evaluated with P064C1 and P096A2 MLPA probes in terms of 16 mental retardation related syndromes. For aCGH method, SurePrint G3 Human microarrays 8x60K were used with genomic DNA isolated from peripheral blood. Results: According to results of 53 patients who were included in and performed with arrayCGH, 8 (15%) patients had CNVs classified as pathogenic or variant of unknown significance (VOUS) in the study. We detected a pathogenic NRXN1 gene partial CNV deletion (2p16.3) in two patients. Also we identified a 900 kb duplication of 4p15.31 including SLIT2 gene, and a 245 kb duplication of 15q11.2 including PWRN1 gene in one patient. Our other findings are considered to be a variant of unknown significance (VOUS). Conclusion: The results of the study support the literature knowledge, where the copy number variations that cannot be detected with conventional cytogenetics methods in terms of size may happen in patients with ASD.
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6. Hollander E, Uzunova G, Taylor BP, Noone R, Racine E, Doernberg E, Freeman K, Ferretti CJ. {{Randomized Crossover Feasibility Trial of Helminthic Trichuris Suis Ova vs. Placebo for Repetitive Behaviors in Adult Autism Spectrum Disorder}}. {World J Biol Psychiatry};2018 (Sep 19):1-25.
OBJECTIVES: Inflammatory mechanisms are implicated in the etiology of Autism Spectrum Disorder (ASD), and use of the immunomodulator Trichuris Suis Ova (TSO) is a novel treatment approach. This pilot study determined the effect sizes for TSO vs. placebo on repetitive behaviors, irritability and global functioning in adults with ASD. METHODS: A 28-week double-blind, randomized two-period crossover study of TSO vs. placebo in 10 ASD adults, ages 17 to 35, was completed, with a 4-week washout between each 12-week period at Montefiore Medical Center, Albert Einstein College of Medicine. Subjects with ASD, history of seasonal, medication or food allergies, Y-BOCS >/= 6 and IQ >/=70 received 2500 TSO ova or matching placebo every two weeks of each 12-week period. RESULTS: Large effect sizes for improvement in repetitive behaviors (d = 1.0), restricted interests (d = 0.82), rigidity (d = 0.79), and irritability (d = 0.78) were observed after 12 weeks of treatment. No changes were observed in the social-communication domain. Differences between treatment groups did not reach statistical significance. TSO had only minimal, non-serious side effects. CONCLUSIONS: This proof-of-concept study demonstrates the feasibility of TSO for the treatment of ASD, including a favorable safety profile, and moderate to large effect sizes for reducing repetitive behaviors and irritability.
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7. Li C, Zhu G, Feng J, Xu Q, Zhou Z, Zhou B, Hu C, Liu C, Li H, Wang Y, Yan W, Ge X, Xu X. {{Improving the early screening procedure for autism spectrum disorder in young children: Experience from a community-based model in shanghai}}. {Autism Res};2018 (Sep 19)
Most children with autism spectrum disorder (ASD) are not diagnosed until the age of 4, thus missing the opportunity for early intervention. The objective of this study was to investigate the feasibility of an early screening program for ASD applied during well-child visits in a community-based sample. The study lasted for 4 years and was divided into two stages. Stage I involved the implementation of the basic screening model in 2014. Toddlers received level 1 screening via section A of the Chinese-validated version of the Checklist for Autism in Toddlers (CHAT-23) during 18- and 24-month well-child visits in Xuhui District, Shanghai, China. Screen-positive children were referred to receive section B of the CHAT-23 for level 2 screening, and those still screen-positive were referred to undergo diagnosis and evaluation. Stage II involved the implementation of the improved screening model from 2015 to 2017 with the following modifications: (a) an added observational component in level 1 screening; (b) telephone follow-ups with the screen-positive families; and (c) dissemination of information on ASD to families. The results showed that 42 of 22,247 screened children were diagnosed with ASD. The ASD diagnosis rates were 0.1% in Stage I and 0.21% in Stage II. The screen-positive rate and the show rate of referral for level 1 screening increased by 76.92% and 58.43%, respectively, in Stage II compared to Stage I. Our results suggest that with appropriate logistic support, this two-level screening model is feasible and effective for the early screening of ASD during well-child visits. Autism Res 2018. (c) 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Difficulty in the timely identification of autism spectrum disorder (ASD) results in missed opportunities for many ASD children to receive early intervention. In this study, we established an early screening model for ASD among children aged 18-24 months in the community by relying on the three-level child healthcare system in China. The results showed that this model can effectively identify and diagnose ASD in children at an early age and thus enable early intervention.
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8. Mendonsa LE, Tiwari S. {{A Survey of Knowledge and Beliefs regarding Autism in Speech-Language Pathologists in India}}. {Folia Phoniatr Logop};2018 (Sep 19);70(3-4):191-202.
BACKGROUND: Speech-language pathologists (SLPs) are significant team members in the identification, assessment, and rehabilitation of children with autism. With a recent upsurge in the number of children with autism, there arises a need to examine SLPs knowledge and skills in identification and intervention of children with autism. AIM: The present study is, thus, a novel attempt aimed to investigate knowledge and belief of SLPs in the assessment and intervention of autism in the Indian context. METHOD: A total of 219 SLPs participated in a web-based online survey. The study adopted a cross-sectional observational research design. RESULTS: The results of the study showed around 43% of the total SLPs obtained a good score on the knowledge section and 27% received a positive rating for the belief section. Additionally, factors like « educational qualification, » « duration of clinical experience, » and « caseload of children with autism » influenced knowledge and beliefs of SLPs about autism. CONCLUSION: The study results indicate that SLPs practicing in India show average and below average scores on a questionnaire assessing knowledge and beliefs regarding autism. The study findings have implications towards developing improved training and course structure related to assessment and intervention of children with autism for SLPs practicing in India.
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9. Neuhofer D, Lassalle O, Manzoni OJ. {{Muscarinic M1 Receptor Modulation of Synaptic Plasticity in Nucleus Accumbens of Wild-Type and Fragile X Mice}}. {ACS Chem Neurosci};2018 (Sep 19);9(9):2233-2240.
We investigated how metabotropic acetylcholine receptors control excitatory synaptic plasticity in the mouse nucleus accumbens core. Pharmacological and genetic approaches revealed that M1 mAChRs (muscarinic acetylcholine receptors) trigger multiple and interacting forms of synaptic plasticity. As previously described in the dorsal striatum, moderate pharmacological activation of M1 mAChR potentiated postsynaptic NMDARs. The M1-potentiation of NMDAR masked a previously unknown coincident TRPV1-mediated long-term depression (LTD). In addition, strong pharmacological activation of M1 mAChR induced canonical retrograde LTD, mediated by presynaptic CB1R. In the fmr1-/y mouse model of Fragile X, we found that CB1R but not TRPV1 M1-LTD was impaired. Finally, pharmacological blockade of the degradation of anandamide and 2-arachidonylglycerol, the two principal endocannabinoids restored fmr1-/y LTD to wild-type levels. These findings shed new light on the complex influence of acetylcholine on excitatory synapses in the nucleus accumbens core and identify new substrates of the synaptic deficits of Fragile X.
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10. Ozyurt G, Elikucuk CD. {{Comparison of Language Features, Autism Spectrum Symptoms in Children Diagnosed with Autism Spectrum Disorder, Developmental Language Delay, and Healthy Controls}}. {Noro Psikiyatr Ars};2018 (Sep);55(3):205-210.
Introduction: Language and communication is very important in social, emotional, and cognitive development of children. Delay in language is the first complaint for children diagnosed with autism spectrum disorder (ASD) or developmental language delay (DLD). In this study it is aimed to evaluate and compare language profiles and autistic symptoms between children diagnosed with ASD, DLD, and healthy controls. Method: Twenty-six children who are diagnosed with ASD, 43 children who are diagnosed with DLD, and 47 healthy controls are included to study; and all children are in the age of 48-72 months. Test of Early Language Development was used to evaluate language profiles, and autism spectrum symptoms were evaluated with social communication questionnaire (SCQ). Results: The sociodemographic features of groups were similar. The statistical significant differences were found in all language subscales and subscales of SCQ among three groups. Both children who were diagnosed with ASD and DLD had more autism spectrum symptoms when compared to controls. Discussion: In present study, it is indicated that developmental language trajectories are different in ASD and DLD group. Children, who are diagnosed with ASD, have more receptive language difficulties while children, who are diagnosed with DLD, have more language difficulties in expressive language area. The finding, children who are diagnosed with DLD have more autistic symptoms, shows that autistic symptoms are related with language development, and it is very important to give preference to language education in the treatment.
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11. Poquerusse J, Pastore L, Dellantonio S, Esposito G. {{Corrigendum: Alexithymia and Autism Spectrum Disorder: A Complex Relationship}}. {Front Psychol};2018;9:1638.
[This corrects the article DOI: 10.3389/fpsyg.2018.01196.].
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12. Rubenstein E, Schieve L, Wiggins L, Rice C, Van Naarden Braun K, Christensen D, Durkin M, Daniels J, Lee LC. {{Trends in documented co-occurring conditions in children with autism spectrum disorder, 2002-2010}}. {Res Dev Disabil};2018 (Sep 15);83:168-178.
BACKGROUND: Autism spectrumdisorder (ASD) commonly presents with co-occurring medical conditions (CoCs). Little is known about patterns in CoCs in a time of rising ASD prevalence. AIMS: To describe trends in number and type of documented CoCs in 8-year-old children with ASD. METHODS: We used Autism and Developmental Disabilities Monitoring Network (ADDM) data, a multi-source active surveillance system monitoring ASD prevalence among 8-year-old children across the US. Data from surveillance years 2002, 2006, 2008, and 2010 were used to describe trends in count, categories, and individual CoCs. RESULTS: Mean number of CoCs increased from 0.94 CoCs in 2002 to 1.06 CoCs in 2010 (p < 0.001). The percentage of children with ASD with any CoC increased from 44.5% to 56.4% (p < 0.001). CoCs with the greatest increases were in general developmental disability (10.4% to 14.5%), language disorder (18.9% to 23.6%), and motor developmental disability (10.5% to 15.6%). Sex modified the relationship between developmental (P = 0.02) and psychiatric (P < 0.001) CoCs and surveillance year. Race/ethnicity modified the relationship between neurological conditions (P = 0.04) and surveillance year. CONCLUSIONS: The increase in the percentage of children with ASD and CoCs may suggest the ASD phenotype has changed over time or clinicians are more likely to diagnose CoCs. Lien vers le texte intégral (Open Access ou abonnement)
13. Shizawa M, Yoshimura S, Zhao S, Toichi M, Hoshino A, Katsura T. {{[Factors related to eating behaviors in early childhood: Relationships between autistic tendency, sensory characteristics, and childcare environment]}}. {Nihon Koshu Eisei Zasshi};2018;65(8):411-420.
ObjectiveThe objective of this study was to examine the influence of environmental factors on eating behaviors of children.MethodThe participants were the caregivers of 1,678 children attending nursery schools or kindergartens in two different cities of a prefecture. We distributed several self-administered questionnaires to the caregivers in conjunction with collaborating organizations. The participants returned the questionnaires either to collection boxes placed at the collaborating organizations facilities or by mailing them. The questionnaires included assessment of the child’s basic attributes, caregiver assessments of eating behaviors, the Social Responsiveness Scale (SRS) measure of autistic traits, the Japanese Sensory Inventory-Revised (JSI-R), and the Index of Child Care Environment (ICCE). We conducted a chi-square (chi(2)) test, Fisher’s exact test, and a multiple regression analysis.ResultsWe received responses from 843 participants (response rate=50.4%), and of those, 583 were considered valid (34.7%). The mean number of problematic eating behaviors for each child as perceived by the caregivers was 2.43+/-2.26. In general, caregivers thought that about 40% of the children had an unbalanced diet and about 30% had a problem of « not being able to sit still. » The multiple regression analysis showed that the number of problematic eating behaviors was significantly and positively affected by the SRS T-score total (beta=0.188, P<0.001), sense of taste (beta=0.319, P<0.001) and auditory sense (beta=0.168, P<0.001) in JSI-R. A positive relationship was found between the environmental factors of human stimulation (beta=0.096, P=0.010) and social support (beta=0.085, P=0.022). A negative relationship was found between sense of smell (beta=-0.108, P=0.013), number of siblings (beta=-0.100, P=0.005), age (beta=-0.077, P=0.029), and sex (beta=-0.091, P=0.010).ConclusionOur study results showed that having an unbalanced diet and "not being able to sit still" were typical features of eating behaviors. The number of problematic eating behaviors was associated with personal factors such as autistic tendency and sensory characteristics, and also with environmental factors, such as human stimulation and social support. Our findings show the importance of evaluating all relevant factors when dietary guidance is provided in the treatment of problematic eating behaviors. Lien vers le texte intégral (Open Access ou abonnement)
14. Smith E, Zhang S, Bennetto L. {{Temporal synchrony and audiovisual integration of speech and object stimuli in autism}}. {Res Autism Spectr Disord};2017 (Jul);39:11-19.
Background: Individuals with Autism Spectrum Disorders (ASD) have been shown to have multisensory integration deficits, which may lead to problems perceiving complex, multisensory environments. For example, understanding audiovisual speech requires integration of visual information from the lips and face with auditory information from the voice, and audiovisual speech integration deficits can lead to impaired understanding and comprehension. While there is strong evidence for an audiovisual speech integration impairment in ASD, it is unclear whether this impairment is due to low level perceptual processes that affect all types of audiovisual integration or if it is specific to speech processing. Method: Here, we measure audiovisual integration of basic speech (i.e., consonant-vowel utterances) and object stimuli (i.e., a bouncing ball) in adolescents with ASD and well-matched controls. We calculate a temporal window of integration (TWI) using each individual’s ability to identify which of two videos (one temporally aligned and one misaligned) matches auditory stimuli. The TWI measures tolerance for temporal asynchrony between the auditory and visual streams, and is an important feature of audiovisual perception. Results: While controls showed similar tolerance of asynchrony for the simple speech and object stimuli, individuals with ASD did not. Specifically, individuals with ASD showed less tolerance of asynchrony for speech stimuli compared to object stimuli. In individuals with ASD, decreased tolerance for asynchrony in speech stimuli was associated with higher ratings of autism symptom severity. Conclusions: These results suggest that audiovisual perception in ASD may vary for speech and object stimuli beyond what can be accounted for by stimulus complexity.
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15. Thabtah F. {{An accessible and efficient autism screening method for behavioural data and predictive analyses}}. {Health Informatics J};2018 (Sep 19):1460458218796636.
Autism spectrum disorder is associated with significant healthcare costs, and early diagnosis can substantially reduce these. Unfortunately, waiting times for an autism spectrum disorder diagnosis are lengthy due to the fact that current diagnostic procedures are time-consuming and not cost-effective. Overall, the economic impact of autism and the increase in the number of autism spectrum disorder cases across the world reveal an urgent need for the development of easily implemented and effective screening methods. This article proposes a new mobile application to overcome the problem by offering users and the health community a friendly, time-efficient and accessible mobile-based autism spectrum disorder screening tool called ASDTests. The proposed ASDTests app can be used by health professionals to assist their practice or to inform individuals whether they should pursue formal clinical diagnosis. Unlike existing autism screening apps being tested, the proposed app covers a larger audience since it contains four different tests, one each for toddlers, children, adolescents and adults as well as being available in 11 different languages. More importantly, the proposed app is a vital tool for data collection related to autism spectrum disorder for toddlers, children, adolescent and adults since initially over 1400 instances of cases and controls have been collected. Feature and predictive analyses demonstrate small groups of autistic traits improving the efficiency and accuracy of screening processes. In addition, classifiers derived using machine learning algorithms report promising results with respect to sensitivity, specificity and accuracy rates.
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16. Varcin KJ, Newnham JP, Whitehouse AJO. {{Maternal pre-pregnancy weight and autistic-like traits among offspring in the general population}}. {Autism Res};2018 (Sep 19)
There is an emerging body of evidence demonstrating that maternal obesity at the time of conception increases the risk for Autism Spectrum Disorders (ASD) among offspring. We explored whether pre-pregnancy weight was related to autistic-like traits among offspring not diagnosed with ASD. A large sample of women, recruited during the second trimester of pregnancy, had their height measured and reported their pre-pregnancy weight. These measurements were then converted to a Body Mass Index (BMI) using the formula: (weight in kilograms)/(height in metres(2) ). At 19-20 years of age, 1238 offspring of these women completed a measure of autistic-like traits, the Autism-Spectrum Quotient (AQ). Regression analyses identified a positive association between increasing maternal pre-pregnancy BMI and increasing AQ Total Score amongst offspring; this association was maintained even after controlling for a range of variables including maternal/obstetric factors (age at conception, education, smoking, alcohol consumption, hypertensive diseases, diabetes, threatened abortion), paternal BMI at pregnancy, and child factors (parity, sex) (P < .01, R(2) =.03). Chi-square analyses found that women with pre-pregnancy obesity (BMI >/= 30) were more likely to have offspring with high scores (>/=26) on the AQ (P = .01). Follow-up binary logistic regression analyses also accounting for the same obstetric and sociodemographic variables found that the offspring of women with pre-pregnancy obesity were at a statistically significantly increased risk of having high scores (>/=26) on the AQ (OR: 2.80; 95% CI: 1.06, 7.43). This study provides further evidence that maternal pre-pregnancy obesity is associated with autism-like behaviors in offspring. LAY SUMMARY: The current study explored whether pre-pregnancy weight was related to autistic-like traits among offspring not diagnosed with ASD. We found that pre-pregnancy body mass index in women is associated with the amount of autistic-like traits in their children in early adulthood. Specifically, women who were obese at the time of conception were more likely to have a child who had high levels of autistic-like traits in early adulthood.
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17. Westmark CJ. {{Fragile X and APP: a Decade in Review, a Vision for the Future}}. {Mol Neurobiol};2018 (Sep 17)
Fragile X syndrome (FXS) is a devastating developmental disability that has profound effects on cognition, behavior, and seizure susceptibility. There are currently no treatments that target the underlying cause of the disorder, and recent clinical trials have been unsuccessful. In 2007, seminal work demonstrated that amyloid-beta protein precursor (APP) is dysregulated in Fmr1(KO) mice through a metabotropic glutamate receptor 5 (mGluR5)-dependent pathway. These findings raise the hypotheses that: (1) APP and/or APP metabolites are potential therapeutic targets as well as biomarkers for FXS and (2) mGluR5 inhibitors may be beneficial in the treatment of Alzheimer’s disease. Herein, advances in the field over the past decade that have reproduced and greatly expanded upon these original findings are reviewed, and required experimentation to validate APP metabolites as potential disease biomarkers as well as therapeutic targets for FXS are discussed.
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18. Xu C, Cao H, Zhang F, Cheadle C. {{Comprehensive literature data-mining analysis reveals a broad genetic network functionally associated with autism spectrum disorder}}. {Int J Mol Med};2018 (Nov);42(5):2353-2362.
Previous studies have indicated that genetic factors are the predominate cause of Autism spectrum disorder (ASD). Nevertheless, to the best of our knowledge, to date no systematic study has summarized these data and provided an objective, complete list of genes with demonstrated associations with ASD. The present study included a literature data mining analysis of >2,064 articles including publications from January 2000 to April 2016, which identified 488 ASD target genes. Gene set enrichment analysis (GSEA), subnetwork enrichment analysis (SNEA) and network connectivity analysis (NCA) were conducted to assess the functional profile and pathogenic significance of these genes. A total of 2 literature metrics were proposed to prioritize the curated ASD genes with specific significance. This approach resulted in the development of an ASD genetic database. Subsequent analysis indicated that 391 of the 488 genes were enriched in 97 biological pathways (P<1x108), demonstrating significant functional associations with each other. The majority of these curated ASD genes also serve significant roles in the pathogenesis of other neuropsychiatric disorders. These results suggest that the genetic causes of ASD are within a large network composed of functionallyassociated genes. The genetic database, together with the metric scores developed in the present study, provides a basis for future biological/genetic modeling in the field. Lien vers le texte intégral (Open Access ou abonnement)
19. Yan W, Rangaprakash D, Deshpande G. {{Estimated hemodynamic response function parameters obtained from resting state BOLD fMRI signals in subjects with autism spectrum disorder and matched healthy subjects}}. {Data Brief};2018 (Aug);19:1305-1309.
In Functional magnetic resonance imaging (fMRI), the blood oxygen level dependent (BOLD) signal is modeled as a convolution of the hemodynamic response function (HRF) and the unmeasured latent neural signal. Although most cortical and subcortical brain regions share the canonical shape of the HRF, the temporal structure of HRFs are variable across brain regions and subjects. This variability is induced by both neural and non-neural factors. The variability between subjects can be examined by three parameters that characterize the HRF: response height (RH), time-to-peak (TTP) and full-width at half-max (FWHM). This data provides three HRF parameters at every voxel, obtained from Autism Spectrum Disorder (ASD) patients (N=531), and matched healthy controls (N=571). Since ongoing studies suggest that non-standard populations have important differences in their HRFs when compared with healthy control, this data set is valuable in studying variability of HRF in ASD group and inferring the underlying pathology that also affects the HRF. It also has implications for fMRI analyses like resting-sate connectivity analysis.
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20. Yang YM, Arsenault J, Bah A, Krzeminski M, Fekete A, Chao OY, Pacey LK, Wang A, Forman-Kay J, Hampson DR, Wang LY. {{Identification of a molecular locus for normalizing dysregulated GABA release from interneurons in the Fragile X brain}}. {Mol Psychiatry};2018 (Sep 17)
Principal neurons encode information by varying their firing rate and patterns precisely fine-tuned through GABAergic interneurons. Dysregulation of inhibition can lead to neuropsychiatric disorders, yet little is known about the molecular basis underlying inhibitory control. Here, we find that excessive GABA release from basket cells (BCs) attenuates the firing frequency of Purkinje neurons (PNs) in the cerebellum of Fragile X Mental Retardation 1 (Fmr1) knockout (KO) mice, a model of Fragile X Syndrome (FXS) with abrogated expression of the Fragile X Mental Retardation Protein (FMRP). This over-inhibition originates from increased excitability and Ca(2+) transients in the presynaptic terminals, where Kv1.2 potassium channels are downregulated. By paired patch-clamp recordings, we further demonstrate that acutely introducing an N-terminal fragment of FMRP into BCs normalizes GABA release in the Fmr1-KO synapses. Conversely, direct injection of an inhibitory FMRP antibody into BCs, or membrane depolarization of BCs, enhances GABA release in the wild type synapses, leading to abnormal inhibitory transmission comparable to the Fmr1-KO neurons. We discover that the N-terminus of FMRP directly binds to a phosphorylated serine motif on the C-terminus of Kv1.2; and that loss of this interaction in BCs exaggerates GABA release, compromising the firing activity of PNs and thus the output from the cerebellar circuitry. An allosteric Kv1.2 agonist, docosahexaenoic acid, rectifies the dysregulated inhibition in vitro as well as acoustic startle reflex and social interaction in vivo of the Fmr1-KO mice. Our results unravel a novel molecular locus for targeted intervention of FXS and perhaps autism.
