1. Balaan C, Corley MJ, Eulalio T, Leite-Ahyo K, Pang APS, Fang R, Khadka VS, Maunakea AK, Ward MA. {{Juvenile Shank3b deficient mice present with behavioral phenotype relevant to autism spectrum disorder}}. {Behav Brain Res}. 2018.
Autism spectrum disorder (ASD) is a pervasive, multifactorial neurodevelopmental disorder diagnosed according to deficits in three behavioral domains: communication, social interaction, and stereotyped/repetitive behaviors. Mutations in Shank genes account for ~1% of clinical ASD cases with Shank3 being the most common gene variant. In addition to maintaining synapses and facilitating dendritic maturation, Shank genes encode master scaffolding proteins that build core complexes in the postsynaptic densities of glutamatergic synapses. Male mice with a deletion of the PDZ domain of Shank3 (Shank3B KO) were previously shown to display ASD-like behavioral phenotypes with reported self-injurious repetitive grooming and aberrant social interactions. Our goal was to extend these previous findings and use a comprehensive battery of highly detailed ASD-relevant behavioral assays including an assessment of mouse ultrasonic communication carried out on key developmental days and male and female Shank3B KO mice. We demonstrate that ASD-related behaviors, atypical reciprocal social interaction and indiscriminate repetitive grooming, are apparent in juvenile stages of development of Shank3B KO mice. Our findings underscore the importance of utilizing Shank mutant models to understand the impact of this gene in ASD etiology, which may enable future studies focusing on etiological gene-environment interactions in ASD.
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2. Bury SM, Hedley D, Uljarevic M, Dissanayake C, Gal E. {{If you’ve employed one person with autism …: An individual difference approach to the autism advantage at work}}. {Autism}. 2018: 1362361318794937.
In this letter to the editor, we comment on the ‘autism advantage’ – the idea that superior skills associated with autism (e.g. attention to detail) present a talent in employment – an example of which is a recent discussion by Austin and Pisano. We welcome advocacy that raises awareness around the strengths and capabilities of people with autism, and also the need to reform human resource management processes that disadvantage them. However, we are concerned that, by highlighting certain stereotypes (e.g. the ‘talented nerd lacking social graces’), the heterogeneity of autism may be overlooked and support needs downplayed. Furthermore, not appreciating individual differences might result in a misalignment between work-profile and employment, pressure to outperform peers without autism and a failure to appreciate the diverse interests of people with autism. We argue that an individual differences approach will prove more sustainable for improving long-term employment outcomes.
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3. Chandrashekhar S, J SB. {{Management of Autistic Patients in Dental Office: A Clinical Update}}. {International journal of clinical pediatric dentistry}. 2018; 11(3): 219-27.
Autism is an intellectual developmental disorder characterized by insidious disability in communication, social interaction, and using language and abstract concepts. This organic disorder is known to have deformities in brain, i.e., cerebellum and limbic system, showing wide spectrum of systemic and behavioral symptoms. The oral health care of such patients can be complicated as they cannot verbalize complaints about any dental problems they may be experiencing and can display a variety of behaviors and reactions to small changes also. This study summarizes etiology and diagnosis of this disorder with the special emphasis on the issues encountered while coping with children with autistic spectrum. How to cite this article: Chandrashekhar S, Bommangoudar JS. Management of Autistic Patients in Dental Office: A Clinical Update. Int J Clin Pediatr Dent 2018;11(3):219-227.
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4. Hassani Nia F, Kreienkamp HJ. {{Functional Relevance of Missense Mutations Affecting the N-Terminal Part of Shank3 Found in Autistic Patients}}. {Front Mol Neurosci}. 2018; 11: 268.
Genetic defects in SHANK genes are associated with autism. Deletions and truncating mutations suggest haploinsufficiency for Shank3 as a major cause of disease which may be analyzed in appropriate Shank deficient mouse models. Here we will focus on the functional analysis of missense mutations found in SHANK genes. The relevance of most of these mutations for Shank function, and their role in autism pathogenesis is unclear. This is partly due to the fact that mutations spare the most well studied functional domains of Shank3, such as the PDZ and SAM domains, or the short proline-rich motifs which are required for interactions with postsynaptic partners Homer, Cortactin, dynamin, IRSp53 and Abi-1. One set of mutations affects the N-terminal part, including the highly conserved SPN domain and ankyrin repeats. Functional analysis from several groups has indicated that these mutations (e.g., R12C; L68P; R300C, and Q321R) interfere with the critical role of Shank3 for synapse formation. More recently the structural analysis of the SPN-ARR module has begun to shed light on the molecular consequences of mutations in the SPN of Shank3. The SPN was identified as a Ras association domain, with high affinities for GTP-bound, active forms of Ras and Rap. The two autism related mutations in this part of the protein, R12C and L68P, both abolish Ras binding. Further work is directed at identifying the consequences of Ras binding to Shank proteins at postsynaptic sites.
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5. Hens K, Langenberg R. {{[Biology and context. Experiences of adults diagnosed with autism]}}. {Tijdschrift voor psychiatrie}. 2018; 60(8): 536-43.
BACKGROUND: Most of the research in autism focuses on finding biological explanations. Far less is known about what it means to live with the diagnosis.
AIM: To describe the impact of diagnosing autism during adulthood.
METHOD: We interviewed 22 adults diagnosed with autism in order to understand how people experience and evaluate themselves, how they experienced the diagnostic process and how the diagnosis helps them to tackle problems in their everyday functioning.
RESULTS: A diagnosis of autism has an impact on how people reflect on their identity and on their relation to others in their environment.
CONCLUSION: Autism is a complex and multilayered concept that is biologically real and yet flexible enough to help people understand themselves better without having to coincide with the diagnosis.
6. Jung CR, Lin YT, Hwang BF. {{Correction: Air Pollution and Newly Diagnostic Autism Spectrum Disorders: A Population-Based Cohort Study in Taiwan}}. {PLoS One}. 2018; 13(8): e0202996.
[This corrects the article DOI: 10.1371/journal.pone.0075510.].
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7. Lewis LF. {{Identifying autism spectrum disorder in undiagnosed adults}}. {The Nurse practitioner}. 2018; 43(9): 14-8.
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8. Maia FA, Almeida MTC, Alves MR, Bandeira LVS, Silva VBD, Nunes NF, Cardoso LCG, Silveira MF. {{[Autism spectrum disorder and parents’ age: a case-control study in Brazil]}}. {Cadernos de saude publica}. 2018; 34(8): e00109917.
Autism spectrum disorder (ASD) has become a public health problem with major family, social, and economic impacts. This study aimed to estimate the association between ASD and parents’ age at the time of their child’s birth. A case-control study was performed, consisting of 243 individuals with ASD (cases) and 886 neurotypical controls. A semi-structured questionnaire was applied, following by multiple logistic regression. Associations between ASD and paternal age (in years) from 25 to 34 (OR = 1.65; 95%CI: 1.01-2.71), 35 to 44 (OR = 1.62; 95%CI: 0.96-2.73), and >/= 45 (OR = 2.44; 95%CI: 1.14-5.00); and maternal age from 25 to 34 (OR = 2.38; 95%CI: 1.54-3.37) and >/= 35 (OR = 2.09; 95%CI: 1.29-3.39) were significant when assessed in independent models. However, when included in a single model, only maternal age from 25 to 34 (OR = 2.27; 95%CI: 1.45-3.55) and >/= 35 years (OR = 2.15; 95%CI: 1.21-3.83) remained associated with ASD. The association was stronger when both parents were older (OR = 4.87; 95%CI: 1.71-13.80). The results have important implications for clinical psychiatry and public health, since parents’ age at childbirth has increased. Emphasis is needed on the prevention of late childbearing and screening and follow-up of children born to these couples.
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9. Maras A, Schroder CM, Malow BA, Findling RL, Breddy J, Nir T, Shahmoon S, Zisapel N, Gringras P. {{Long-Term Efficacy and Safety of Pediatric Prolonged-Release Melatonin for Insomnia in Children with Autism Spectrum Disorder}}. {J Child Adolesc Psychopharmacol}. 2018.
OBJECTIVE: A recent double-blind randomized placebo-controlled study demonstrated 3-month efficacy and safety of a novel pediatric-appropriate prolonged-release melatonin (PedPRM) for insomnia in children and adolescents with autism spectrum disorder (ASD) and neurogenetic disorders (NGD) with/without attention-deficit/hyperactivity disorder comorbidity. Long-term efficacy and safety of PedPRM treatment was studied. METHODS: A prospective, open-label efficacy and safety follow-up of nightly 2, 5, or 10 mg PedPRM in subjects who completed the 13-week double-blind trial (51 PedPRM; 44 placebo). Measures included caregiver-reported Sleep and Nap Diary, Composite Sleep Disturbance Index (CSDI), caregiver’s Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale, and quality of life (WHO-5 Well-Being Index). RESULTS: Ninety-five subjects (74.7% males; mean [standard deviation] age, 9 [4.24]; range, 2-17.5 years) received PedPRM (2/5 mg) according to the double-blind phase dose, for 39 weeks with optional dose adjustment (2, 5, or 10 mg/day) after the first 13 weeks. After 52 weeks of continuous treatment (PedPRM-randomized group) subjects slept (mean [SE]) 62.08 (21.5) minutes longer (p = 0.007); fell asleep 48.6 (10.2) minutes faster (p < 0.001); had 89.1 (25.5) minutes longer uninterrupted sleep episodes (p = 0.001); 0.41 (0.12) less nightly awakenings (>50% decrease; p = 0.001); and better sleep quality (p < 0.001) compared with baseline. The placebo-randomized group also improved with PedPRM. Altogether, by the end of 39-week follow-up, regardless of randomization assignment, 55/72 (76%) of completers achieved overall improvement of >/=1 hour in total sleep time (TST), sleep latency or both, over baseline, with no evidence of decreased efficacy. In parallel, CSDI child sleep disturbance and caregivers’ satisfaction of their child’s sleep patterns (p < 0.001 for both), PSQI global (p < 0.001), and WHO-5 (p = 0.001) improved in statistically significant and clinically relevant manner (n = 72) compared with baseline. PedPRM was generally safe; most frequent treatment-related adverse events were fatigue (5.3%) and mood swings (3.2% of patients). CONCLUSION: PedPRM, an easily swallowed formulation shown to be efficacious versus placebo, is an efficacious and safe option for long-term treatment (up to 52 weeks reported here) of children with ASD and NGD who suffer from insomnia and subsequently improves caregivers' quality of life. Lien vers le texte intégral (Open Access ou abonnement)
10. Park BY, Misra DP, Moye J, Miller RK, Croen L, Fallin MD, Walker C, Newschaffer CJ, Salafia CM. {{Placental gross shape differences in a high autism risk cohort and the general population}}. {PLoS One}. 2018; 13(8): e0191276.
A growing body of evidence suggests that prenatal environment is important in Autism Spectrum Disorder (ASD) etiology. In this study, we compare placental shape features in younger siblings of children with ASD, who themselves are at high ASD risk, to a sample of low risk peers. Digital photographs of the fetal placenta surface and of the sliced placental disk from 129 high ASD risk newborns and from 267 newborns in the National Children’s Study Vanguard pilot were analysed to extract comparable measures of placental chorionic surface shape, umbilical cord displacement and disk thickness. Placental thickness measures were moderately higher in siblings of ASD cases. The placentas of ASD-case siblings were also rounder and more regular in perimeter than general population placentas. After stratification by sex, these across-group differences persisted for both sexes but were more pronounced in females. No significant differences were observed in cord insertion measures. Variations in placental shape features are generally considered to reflect flexibility in placental growth in response to changes in intrauterine environment as the placenta establishes and matures. Reduced placental shape variability observed in high ASD risk siblings compared to low-risk controls may indicate restricted ability to compensate for intrauterine changes.
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11. Rubenstein E, Young JC, Croen LA, DiGuiseppi C, Dowling NF, Lee LC, Schieve L, Wiggins LD, Daniels J. {{Brief Report: Maternal Opioid Prescription from Preconception Through Pregnancy and the Odds of Autism Spectrum Disorder and Autism Features in Children}}. {J Autism Dev Disord}. 2018.
Opioid use during pregnancy is associated with suboptimal pregnancy outcomes. Little is known about child neurodevelopmental outcomes. We examined associations between maternal opioid prescriptions preconception to delivery (peri-pregnancy) and child’s risk of ASD, developmental delay/disorder (DD) with no ASD features, or ASD/DD with autism features in the Study to Explore Early Development, a case-control study of neurodevelopment. Preconception opioid prescription was associated with 2.43 times the odds of ASD [95% confidence interval (CI) 0.99, 6.02] and 2.64 times the odds of ASD/DD with autism features (95% CI 1.10, 6.31) compared to mothers without prescriptions. Odds for ASD and ASD/DD were non-significantly elevated for first trimester prescriptions. Work exploring mechanisms and timing between peri-pregnancy opioid use and child neurodevelopment is needed.
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12. Stacey TL, Froude EH, Trollor J, Foley KR. {{Leisure participation and satisfaction in autistic adults and neurotypical adults}}. {Autism}. 2018: 1362361318791275.
Leisure participation is important for well-being and has been attributed to improved quality of life for autistic individuals. Rigorous studies exploring the leisure participation of autistic adults are sparse. This study aimed to compare the type of leisure activity and frequency of participation between autistic adults and neurotypical adults as well as compare and identify factors associated with their leisure satisfaction. Data for 145 autistic and 104 neurotypical adults were obtained from time point one of the Australian Longitudinal Study of Adults with Autism. The primary outcome measure used was the Leisure Satisfaction Scale. Autistic adults were less satisfied with their leisure overall (mean = 3.29, standard deviation = 0.75) compared with neurotypical adults (mean = 3.69, standard deviation = 0.55). Multiple linear regression revealed being younger and reporting less depressive symptoms were significantly associated with higher leisure satisfaction in autistic but not neurotypical adults. Engagement in solitary leisure activities was comparable across participants, but socialising in person was predominated by neurotypical adults. Leisure activity preferences of autistic adults’ and the frequency of their leisure participation are important factors for clinicians to understand when working with this population and tailoring well-being interventions.
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13. Turley JW, Harding TW. {{Vitamin D supplementation and core symptoms of autism? Potential more than promise given study limitations}}. {Journal of paediatrics and child health}. 2018; 54(8): 926.
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14. Wang Y, Zeng C, Li J, Zhou Z, Ju X, Xia S, Li Y, Liu A, Teng H, Zhang K, Shi L, Bi C, Xie W, He X, Jia Z, Jiang Y, Cai T, Wu J, Xia K, Sun ZS. {{PAK2 Haploinsufficiency Results in Synaptic Cytoskeleton Impairment and Autism-Related Behavior}}. {Cell reports}. 2018; 24(8): 2029-41.
Synaptic cytoskeleton dysfunction represents a common pathogenesis in neurodevelopmental disorders, such as autism spectrum disorder (ASD). The serine/threonine kinase PAK2 is a critical regulator of cytoskeleton dynamics. However, its function within the central nervous system and its role in ASD pathogenesis remain undefined. Here, we found that Pak2 haploinsufficiency resulted in markedly decreased synapse densities, defective long-term potentiation, and autism-related behaviors in mice. Phosphorylation levels of key actin regulators LIMK1 and cofilin, together with their mediated actin polymerization, were reduced in Pak2(+/-)mice. We identified one de novo PAK2 nonsense mutation that impaired PAK2 function in vitro and in vivo and four de novo copy-number deletions containing PAK2 in large cohorts of patients with ASD. PAK2 deficiency extensively perturbed functional networks associated with ASD by regulating actin cytoskeleton dynamics. Our genetic and functional results demonstrate a critical role of PAK2 in brain development and autism pathogenesis.
