Pubmed du 30/10/19

mercredi 30 octobre 2019

1. Adams JB, Borody TJ, Kang DW, Khoruts A, Krajmalnik-Brown R, Sadowsky MJ. Microbiota transplant therapy and autism : lessons for the clinic. Expert Rev Gastroenterol Hepatol ;2019 (Oct 30)

Introduction : The purpose of this review is to discuss Microbiota Transplant Therapy (MTT), a type of intensive intestinal microbiota transplantation (IMT), for people with autism spectrum disorders (ASD) and chronic gastrointestinal disorders (constipation and/or diarrhea).Areas covered : This paper briefly reviews IMT, gastrointestinal symptoms and gastrointestinal bacteria in children with ASD, and results and lessons learned from intensive MTT for autism.Expert opinion : An open-label study and a two-year follow-up suggests that MTT is relatively safe and effective in significantly reducing gastrointestinal disorders and autism symptoms, changing the gut microbiome structure, and increasing gut microbial diversity. Further research with larger, randomized, double-blind, placebo-controlled studies is warranted.

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2. Anderson AH, Carter M, Stephenson J. An On-Line Survey of University Students with Autism Spectrum Disorder in Australia and New Zealand : Characteristics, Support Satisfaction, and Advocacy. J Autism Dev Disord ;2019 (Oct 28)

An on-line survey of 102 (51 females ; undergraduate and graduate) university students with ASD across Australia and New Zealand examined student characteristics and satisfaction with academic and non-academic supports. A broad range of disciplines were studied, and the participants’ reported strengths included a passion for learning, strong technology skills, and creative thoughts. The participants’ greatest concerns were academic requirements and mental health, including high rates of self-harm and suicidal ideation. Despite support satisfaction ratings being high, support usage was low, possibly indicating a mismatch of supports and needs, lack of awareness of available supports, and/or poor advocacy skills.

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3. Bremer E, Cairney J. Adaptive Behavior Moderates Health-Related Pathways in Children with Autism Spectrum Disorder. J Autism Dev Disord ;2019 (Oct 30)

The purpose of this study was to examine the moderating role of adaptive behavior on the pathways connecting motor competence, physical activity, and health-related fitness in 7-12 year old children with ASD (N = 27). Results demonstrate that motor competence and health-related fitness were positively related (r = .42, p < .05), and this relationship was moderated by adaptive behavior. Specifically, we found that motor competence and health-related fitness were significantly related for those participants scoring approximately one or more standard deviations below the mean on adaptive behavior. No other significant pathways were present. Implications of these associations and directions for future research are discussed.

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4. Brian JA, Zwaigenbaum L, Ip A. Standards of diagnostic assessment for autism spectrum disorder. Paediatr Child Health ;2019 (Nov) ;24(7):444-460.

The rising prevalence of autism spectrum disorder (ASD) has created a need to expand ASD diagnostic capacity by community-based paediatricians and other primary care providers. Although evidence suggests that some children can be definitively diagnosed by 2 years of age, many are not diagnosed until 4 to 5 years of age. Most clinical guidelines recommend multidisciplinary team involvement in the ASD diagnostic process. Although a maximal wait time of 3 to 6 months has been recommended by three recent ASD guidelines, the time from referral to a team-based ASD diagnostic evaluation commonly takes more than a year in many Canadian communities. More paediatric health care providers should be trained to diagnose less complex cases of ASD. This statement provides community-based paediatric clinicians with recommendations, tools, and resources to perform or assist in the diagnostic evaluation of ASD. It also offers guidance on referral for a comprehensive needs assessment both for treatment and intervention planning, using a flexible, multilevel approach.

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5. Cappuccio G, Donti T, Pinelli M, Bernardo P, Bravaccio C, Elsea SH, Brunetti-Pierri N. Sphingolipid Metabolism Perturbations in Rett Syndrome. Metabolites ;2019 (Oct 10) ;9(10)

Rett syndrome is a severe neurodevelopmental disorder affecting mostly females and is caused by loss-of-function mutations in the MECP2 gene that encoded the methyl-CpG-binding protein 2. The pathogenetic mechanisms of Rett syndrome are not completely understood and metabolic derangements are emerging as features of Rett syndrome. We performed a semi-quantitative tandem mass spectrometry-based analysis that measured over 900 metabolites on blood samples from 14 female subjects with Rett syndrome carrying MECP2 mutations. The metabolic profiling revealed alterations in lipids, mostly involved in sphingolipid metabolism, and sphinganine/sphingosine, that are known to have a neurotrophic role. Further investigations are required to understand the mechanisms underlying such perturbations and their significance in the disease pathogenesis. Nevertheless, these metabolites are attractive for studies on the disease pathogenesis and as potential disease biomarkers.

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6. Cramm H, Smith G, Samdup D, Williams A, Ruhland L. Navigating health care systems for military-connected children with autism spectrum disorder : A qualitative study of military families experiencing mandatory relocation. Paediatr Child Health ;2019 (Nov) ;24(7):478-484.

Background : Most military families experience mandatory relocation, or posting, several times during the military career. For Canadian military families who must access provincial or territorial health care systems, maintaining reasonable continuity of care is a persistent issue. Such challenges may be amplified when a child in a military family has special needs within the health and educational systems. Objective : The purpose of this qualitative study was to gain a better understanding of Canadian Armed Forces families’ experiences in navigating health care systems on behalf of a child with autism spectrum disorder (ASD) in the context of mandatory relocation. Methods : Parents of children with ASD, where at least one parent serves in the Canadian Armed Forces and had faced military-related relocation, were recruited. Semi-structured interviews were recorded, transcribed verbatim, and analyzed thematically. Results : Twelve participants represented 12 families and 15 children with ASD. Participants discussed two primary themes. (1) High mobility inherent in the military lifestyle can create disruptions and discontinuities to service, including delays in diagnosis or intervention, losses and gains in available services determined by the direction of posting, and the need to start health care access processes over again when relocating. (2) Navigating health systems for children with ASD creates personal stress and frustration related to relocating, and has career implications for both parents. Conclusions : Military-related relocation can create significant disruption in access to health and educational services for Canadian military families who have a child with ASD, and take a personal toll on these families.

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7. Crehan ET, Althoff RR, Riehl H, Prelock PA, Hutchins T. Brief Report : Me, Reporting on Myself : Preliminary Evaluation of the Criterion-Related Validity of the Theory of Mind Inventory-2 when Completed by Autistic Young Adults. J Autism Dev Disord ;2019 (Oct 30)

There is a need for increased understanding of self-report measures for autistic individuals. In this preliminary study, we examine how a theory of mind self-report relates to other self-report measures for groups of autistic and neurotypical individuals, as well as eye tracking outcomes. Expected patterns of relatedness emerged between self-reports and the eye tracking findings, which lends validity to the theory of mind measure. Self-report measures are critical for autistic individuals to share their own experiences and this is the first step in establishing a theory of mind self-report tool.

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8. Foster NC, Bennett SJ, Causer J, Elliott D, Bird G, Hayes SJ. Getting Off to a Shaky Start : Specificity in Planning and Feedforward Control During Sensorimotor Learning in Autism Spectrum Disorder. Autism Res ;2019 (Oct 29)

Whilst autistic individuals develop new internal action models during sensorimotor learning, the acquired movements are executed less accurately and with greater variability. Such movement profiles are related to differences in sensorimotor integration and/or altered feedforward/feedback sensorimotor control. We investigated the processes underlying sensorimotor learning in autism by quantifying accuracy and variability, relative timing, and feedforward and feedback control. Although autistic individuals demonstrated significant sensorimotor learning across trials, which was facilitated by processing knowledge-of-results feedback, motor execution was less accurate than non-autistic individuals. Kinematic analysis indicated that autistic individuals showed significantly greater spatial variability at peak acceleration, but comparable spatial variability at peak velocity. These kinematic markers suggest that autistic movement profiles are driven by specific differences in sensorimotor control processes (i.e., internal action models) associated with planning and regulating the forces required to execute the movement. The reduction of variability at peak velocity indicates intact early feedback-based sensorimotor control in autism. Understanding how feedforward and feedback-based control processes operate provides an opportunity to explore how these control processes influence the acquisition of socio-motor actions in autism. Autism Res 2019. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY : Autistic adults successfully learned a new movement skill by physically practising it, and using feedback about how well they had done to become more accurate. When looking at the movements in detail, autistic adults were more variable than non-autistic adults when planning (e.g., how much force to use), and performing, the movement. These differences impact how autistic individuals learn different types of movement skills, which might influence how other behaviours (e.g., imitation) are acquired that support social interaction.

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9. Ip A, Zwaigenbaum L, Brian JA. Post-diagnostic management and follow-up care for autism spectrum disorder. Paediatr Child Health ;2019 (Nov) ;24(7):461-477.

Paediatricians and other primary care providers are well positioned to provide or coordinate ongoing medical and psychosocial care and support services for children with autism spectrum disorder (ASD). This statement provides recommendations and information on a range of interventions and resources, to help paediatric care providers optimize care for children with ASD and support their families. The management of ASD includes treating medical and psychiatric co-morbidities, behavioural and developmental interventions, and providing supportive social care services to enhance quality of life for affected children and families.

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10. Ivashko-Pachima Y, Hadar A, Grigg I, Korenkova V, Kapitansky O, Karmon G, Gershovits M, Sayas CL, Kooy RF, Attems J, Gurwitz D, Gozes I. Discovery of autism/intellectual disability somatic mutations in Alzheimer’s brains : mutated ADNP cytoskeletal impairments and repair as a case study. Mol Psychiatry ;2019 (Oct 30)

With Alzheimer’s disease (AD) exhibiting reduced ability of neural stem cell renewal, we hypothesized that de novo mutations controlling embryonic development, in the form of brain somatic mutations instigate the disease. A leading gene presenting heterozygous dominant de novo autism-intellectual disabilities (ID) causing mutations is activity-dependent neuroprotective protein (ADNP), with intact ADNP protecting against AD-tauopathy. We discovered a genomic autism ADNP mutation (c.2188C>T) in postmortem AD olfactory bulbs and hippocampi. RNA-Seq of olfactory bulbs also identified a novel ADNP hotspot mutation, c.2187_2188insA. Altogether, 665 mutations in 596 genes with 441 mutations in AD patients (389 genes, 38% AD-exclusive mutations) and 104 genes presenting disease-causing mutations (OMIM) were discovered. OMIM AD mutated genes converged on cytoskeletal mechanisms, autism and ID causing mutations (about 40% each). The number and average frequencies of AD-related mutations per subject were higher in AD subjects compared to controls. RNA-seq datamining (hippocampus, dorsolateral prefrontal cortex, fusiform gyrus and superior frontal gyrus-583 subjects) yielded similar results. Overlapping all tested brain areas identified unique and shared mutations, with ADNP singled out as a gene associated with autism/ID/AD and presenting several unique aging/AD mutations. The large fusiform gyrus library (117 subjects) with high sequencing coverage correlated the c.2187_2188insA ADNP mutation frequency to Braak stage (tauopathy) and showed more ADNP mutations in AD specimens. In cell cultures, the ADNP-derived snippet NAP inhibited mutated-ADNP-microtubule (MT) toxicity and enhanced Tau-MT association. We propose a paradigm-shifting concept in the perception of AD whereby accumulating mosaic somatic mutations promote brain pathology.

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11. Ji Y, Azuine RE, Zhang Y, Hou W, Hong X, Wang G, Riley A, Pearson C, Zuckerman B, Wang X. Association of Cord Plasma Biomarkers of In Utero Acetaminophen Exposure With Risk of Attention-Deficit/Hyperactivity Disorder and Autism Spectrum Disorder in Childhood. JAMA Psychiatry ;2019 (Oct 30):1-11.

Importance : Prior studies have raised concern about maternal acetaminophen use during pregnancy and increased risk of attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) in their children ; however, most studies have relied on maternal self-report. Objective : To examine the prospective associations between cord plasma acetaminophen metabolites and physician-diagnosed ADHD, ASD, both ADHD and ASD, and developmental disabilities (DDs) in childhood. Design, Setting, and Participants : This prospective cohort study analyzed 996 mother-infant dyads, a subset of the Boston Birth Cohort, who were enrolled at birth and followed up prospectively at the Boston Medical Center from October 1, 1998, to June 30, 2018. Exposures : Three cord acetaminophen metabolites (unchanged acetaminophen, acetaminophen glucuronide, and 3-[N-acetyl-l-cystein-S-yl]-acetaminophen) were measured in archived cord plasma samples collected at birth. Main Outcomes and Measures : Physician-diagnosed ADHD, ASD, and other DDs as documented in the child’s medical records. Results : Of 996 participants (mean [SD] age, 9.8 [3.9] years ; 548 [55.0%] male), the final sample included 257 children (25.8%) with ADHD only, 66 (6.6%) with ASD only, 42 (4.2%) with both ADHD and ASD, 304 (30.5%) with other DDs, and 327 (32.8%) who were neurotypical. Unchanged acetaminophen levels were detectable in all cord plasma samples. Compared with being in the first tertile, being in the second and third tertiles of cord acetaminophen burden was associated with higher odds of ADHD diagnosis (odds ratio [OR] for second tertile, 2.26 ; 95% CI, 1.40-3.69 ; OR for third tertile, 2.86 ; 95% CI, 1.77-4.67) and ASD diagnosis (OR for second tertile, 2.14 ; 95% CI, 0.93-5.13 ; OR for third tertile, 3.62 ; 95% CI, 1.62-8.60). Sensitivity analyses and subgroup analyses found consistent associations between acetaminophen buden and ADHD and acetaminophen burden and ASD across strata of potential confounders, including maternal indication, substance use, preterm birth, and child age and sex, for which point estimates for the ORs vary from 2.3 to 3.5 for ADHD and 1.6 to 4.1 for ASD. Conclusions and Relevance : Cord biomarkers of fetal exposure to acetaminophen were associated with significantly increased risk of childhood ADHD and ASD in a dose-response fashion. Our findings support previous studies regarding the association between prenatal and perinatal acetaminophen exposure and childhood neurodevelopmental risk and warrant additional investigations.

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12. Kim I, Dababnah S, Lee J. The Influence of Race and Ethnicity on the Relationship between Family Resilience and Parenting Stress in Caregivers of Children with Autism. J Autism Dev Disord ;2019 (Oct 30)

We examined the relationship between family resilience and parenting stress among parents of children with autism spectrum disorder, with a specific focus on race/ethnicity as a moderator. Multivariate models indicated that family resilience was associated with parenting stress. Race/ethnicity significantly moderated the relationship between family resilience and parenting stress. The effects of family resilience on parenting stress were significantly different among parents of African American, Hispanic, and white children. These effects were strongest for parents of African American children. Compared to white and Hispanic children, parents of African American children with low levels of family resilience had 60-82% higher probability of parenting stress ; while those with high levels of family resilience had 15-18% lower probability for parenting stress.

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13. Krans A, Skariah G, Zhang Y, Bayly B, Todd PK. Neuropathology of RAN translation proteins in fragile X-associated tremor/ataxia syndrome. Acta Neuropathol Commun ;2019 (Oct 30) ;7(1):152.

CGG repeat expansions in FMR1 cause the neurodegenerative disorder Fragile X-associated Tremor/Ataxia Syndrome (FXTAS). Ubiquitinated neuronal intranuclear inclusions (NIIs) are the neuropathological hallmark of FXTAS. Both sense strand derived CGG repeats and antisense strand derived CCG repeats support non-AUG initiated (RAN) translation of homopolymeric proteins in potentially 6 different reading frames. However, the relative abundance of these proteins in FXTAS brains and their co-localization with each other and NIIs is lacking. Here we describe rater-blinded assessment of immunohistochemical and immunofluorescence staining with newly generated antibodies to different CGG RAN translation products in FXTAS and control brains as well as co-staining with ubiquitin, p62/SQSTM1, and ubiquilin 2. We find that both FMRpolyG and a second CGG repeat derived RAN translation product, FMRpolyA, accumulate in aggregates in FXTAS brains. FMRpolyG is a near-obligate component of both ubiquitin-positive and p62-positive NIIs in FXTAS, with occurrence of aggregates in 20% of all hippocampal neurons and > 90% of all inclusions. A subset of these inclusions also stain positive for the ALS/FTD associated protein ubiquilin 2. Ubiquitinated inclusions and FMRpolyG+ aggregates are rarer in cortex and cerebellum. Intriguingly, FMRpolyG staining is also visible in control neuronal nuclei. In contrast to FMRpolyG, staining for FMRpolyA and CCG antisense derived RAN translation products were less abundant and less frequent components of ubiquitinated inclusions. In conclusion, RAN translated FMRpolyG is a common component of ubiquitin and p62 positive inclusions in FXTAS patient brains.

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14. Li YJ, Zhang X, Li YM. Antineuroinflammatory therapy : potential treatment for autism spectrum disorder by inhibiting glial activation and restoring synaptic function. CNS Spectr ;2019 (Oct 29):1-9.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that is characterized by deficits in social interactions and perseverative and stereotypical behavior. Growing evidence points toward a critical role for synaptic dysfunction in the onset of ASD, and synaptic function is influenced by glial cells. Considering the evidence that neuroinflammation in ASD is mediated by glial cells, one hypothesis is that reactive glial cells, under inflammatory conditions, contribute to the loss of synaptic functions and trigger ASD. Ongoing pharmacological treatments for ASD, including oxytocin, vitamin D, sulforaphane, and resveratrol, are promising and are shown to lead to improvements in behavioral performance in ASD. More importantly, their pharmacological mechanisms are closely related to anti-inflammation and synaptic protection. We focus this review on the hypothesis that synaptic dysfunction caused by reactive glial cells would lead to ASD, and discuss the potentials of antineuroinflammatory therapy for ASD.

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15. Ogawa S, Iriguchi M, Lee YA, Yoshikawa S, Goto Y. Atypical Social Rank Recognition in Autism Spectrum Disorder. Sci Rep ;2019 (Oct 30) ;9(1):15657.

Social animals, including humans, structure social groups where social hierarchy exists. Recognizing social rank of other group members is a crucial ability to subsist in such environments. Here we show preliminary evidence with a relatively small number of samples that children with autism spectrum disorder, a neurodevelopmental disorder involving social dysfunction, exhibit atypical, and more robust recognition of social rank than normal children, which may be developed to compensate deficits of the neural systems processing social information.

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16. Piwowarczyk A, Horvath A, Pisula E, Kawa R, Szajewska H. Gluten-Free Diet in Children with Autism Spectrum Disorders : A Randomized, Controlled, Single-Blinded Trial. J Autism Dev Disord ;2019 (Oct 28)

To determine whether a gluten-free diet (GFD) compared with a gluten-containing diet (GD) influences functioning of children with autism spectrum disorders (ASD), we performed a randomized, controlled, single-blinded trial. Sixty-six children (36-69 months) with ASD, within the normal IQ (> 70) range, who had been on a GFD for at least 8 weeks before enrollment were eligible for inclusion. After an 8-week run-in period on a GFD, the GFD group continued this diet and the GD group consumed at least one normal meal containing gluten per day for 6 months. There were no differences between groups in autistic symptoms, maladaptive behaviors, or intellectual abilities after the intervention. A GFD compared with a GD did not affect functioning of children with ASD.Trial registration ClinicalTrials.gov, number NCT02280746.

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17. Ramassamy E, Gajula Shivashankarappa P, Adimoulame S, Meena R, Elangovan H, Govindasamy E. Yoga therapy as an adjunct to traditional tooth brushing training methods in children with autism spectrum disorder. Spec Care Dentist ;2019 (Oct 30)

AIM : To evaluate if yoga could be an adjunct to regular training methods in training brushing skill to children with autism spectrum disorder (ASD). METHODS : Seventy-two children with ASD aged 7-15 years were selected and divided into two groups (N = 36). Children in Group I received visual pedagogy and video modeling and children in Group II received visual pedagogy and video modeling with yoga. Plaque and gingival indices (PI and GI) were recorded at baseline and at the end of first, second, third, and sixth month. The scores were summarized as mean and standard deviation and inter-group comparison was done using independent t-test. RESULTS : Inter-group comparison of mean plaque and gingival indices scores were statistically significant at second month (P = .039 for PI and P = .009 for GI). The scores were statistically significant even at third month (P = .001 for PI and P = .002 for GI) and sixth month (P = .001 PI and GI), with children in Group II demonstrating better oral hygiene. CONCLUSION : Yoga training can be used as an adjunct to enhance tooth brushing learning capabilities of children with ASD in addition to visual modeling and pedagogy.

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18. Sacino AN, Prokop S, Walsh MA, Adamson J, Subramony SH, Krans A, Todd PK, Giasson BI, Yachnis AT. Fragile X-associated tremor ataxia syndrome with co-occurrent progressive supranuclear palsy-like neuropathology. Acta Neuropathol Commun ;2019 (Oct 30) ;7(1):158.

Co-occurrence of multiple neuropathologic changes is a common phenomenon, most prominently seen in Alzheimer’s disease (AD) and Parkinson’s disease (PD), complicating clinical diagnosis and patient management. Reports of co-occurring pathological processes are emerging in the group of genetically defined repeat-associated non-AUG (RAN)-translation related diseases. Here we report a case of Fragile X-associated tremor-ataxia syndrome (FXTAS) with widespread and abundant nuclear inclusions of the RAN-translation related FMRpolyG-peptide. In addition, we describe prominent neuronal and glial tau pathology representing changes seen in progressive supranuclear palsy (PSP). The highest abundance of the respective pathological changes was seen in distinct brain regions indicating an incidental, rather than causal correlation.

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19. Warrier V, Baron-Cohen S. Childhood trauma, life-time self-harm, and suicidal behaviour and ideation are associated with polygenic scores for autism. Mol Psychiatry ;2019 (Oct 29)

Autistic individuals experience significantly elevated rates of childhood trauma, self-harm and suicidal behaviour and ideation (SSBI). Is this purely the result of negative environmental experiences, or does this interact with genetic predisposition ? In this study we investigated if a genetic predisposition for autism is associated with childhood trauma using polygenic scores (PGS) and genetic correlations in the UK Biobank (105,222 < N < 105,638), and tested potential mediators and moderators of the association between autism, childhood trauma and SSBI. Autism PGS were significantly associated with childhood trauma (max R(2) = 0.096%, P < 2 x 10(-16)), self-harm ideation (max R(2) = 0.108%, P < 2 x 10(-16)), and self-harm (max R(2) = 0.13%, P < 2 x 10(-16)). Supporting this, we identified significant genetic correlations between autism and childhood trauma (rg = 0.36 +/- 0.05, P = 8.13 x 10(-11)), self-harm ideation (rg = 0.49 +/- 0.05, P = 4.17 x 10(-21)) and self-harm (rg = 0.48 +/- 0.05, P = 4.58 x 10(-21)), and an over-transmission of PGS for the two SSBI phenotypes from parents to autistic probands. Male sex negatively moderated the effect of autism PGS on childhood trauma (beta = -0.023 +/- 0.005, P = 6.74 x 10(-5)). Further, childhood trauma positively moderated the effect of autism PGS on self-harm score (beta = 8.37 x 10(-3) +/- 2.76 x 10(-3), P = 2.42 x 10(-3)) and self-harm ideation (beta = 7.47 x 10(-3) +/- 2.76 x 10(-3), P = 6.71 x 10(-3)). Finally, depressive symptoms, quality and frequency of social interactions, and educational attainment were significant mediators of the effect of autism PGS on SSBI, with the proportion of effect mediated ranging from 0.23 (95% CI : 0.09-0.32) for depression to 0.008 (95% CI : 0.004-0.01) for educational attainment. Our findings identify that a genetic predisposition for autism is associated with adverse life-time outcomes, which represent complex gene-environment interactions, and prioritizes potential mediators and moderators of this shared biology. It is important to identify sources of trauma for autistic individuals in order to reduce their occurrence and impact.

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20. Zwaigenbaum L, Brian JA, Ip A. Early detection for autism spectrum disorder in young children. Paediatr Child Health ;2019 (Nov) ;24(7):424-443.

Autism spectrum disorder (ASD) is a life-long neurodevelopmental disorder, characterized by impairments in social communication, repetitive, restricted patterns of behaviour, and unusual sensory sensitivities or interests. ASD significantly impacts the lives of children and their families. Currently, the estimated prevalence of ASD is 1 in 66 Canadians aged 5 to 17 years. General paediatricians, family physicians, and other health care professionals are, therefore, seeing more children with ASD in their practices. The timely diagnosis of ASD, and referral for intensive behavioural and educational interventions at the earliest age possible, may lead to better long-term outcomes by capitalizing on the brain’s neuroplasticity at younger ages. This statement provides clear, comprehensive, evidence-informed recommendations and tools to help community paediatricians and other primary care providers monitor for the earliest signs of ASD-an important step toward an accurate diagnosis and comprehensive needs assessment for intervention planning.

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21. Zwaigenbaum L, Brian JA, Ip A. Canadian Paediatric Society clinical practice recommendations for assessment of children and youth with autism spectrum disorder. Paediatr Child Health ;2019 (Nov) ;24(7):421-423.

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