1. Abu-Zaid A, Bhagavathula AS, Rahmani J, Alyoubi RA, Alomar O, Baradwan S, Alkhamis WH, Khalifa M, Alshahrani MS, Khadawardi K, Salem H, I AA-B. Maternal polycystic ovary syndrome and the potential risk of attention-deficit/hyperactivity disorder and autism spectrum disorder in the offspring: a systematic review and meta-analysis. The European journal of contraception & reproductive health care : the official journal of the European Society of Contraception. 2022: 1-8.

OBJECTIVE: Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are two increasing important problems among children. This study aims to explore the link between maternal polycystic ovary syndrome (PCOS) and the risk of ASD and ADHD in the offspring. METHOD: The MOOSE guidelines were followed in the conduct of this meta-analysis. A literature search was done in PubMed/MEDLINE, Scopus, and Web of Science from inception until January 2021. The DerSimonian and Laird random-effects model was used to estimate the combined risk ratios (RR) and 95% confidence intervals (CI). Sensitivity analysis was also used to investigate the effect of each study on the combined results. RESULTS: Seven studies, with 1,358,696 participants, comprising 7,334 ADHD cases and 3,920 ASD cases, were included in this study. Children born to mothers with maternal PCOS had higher risks of developing ASD (RR = 1.46, 95% CI: 1.26-1.69, I(2) = 64%) and ADHD (RR = 1.43, 95% CI: 1.35-1.41, I(2) = 0%) when compared with children born to mothers without maternal PCOS. CONCLUSION: This study showed that there might be a link between maternal PCOS and the risk of developing ASD and ADHD in the offspring. This important issue must be considered in PCOS women during and after pregnancy.

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2. Baker-Ericzén MJ, ElShamy R, Kammes RR. Current Status of Evidence-Based Practices to Enhance Employment Outcomes for Transition Age Youth and Adults on the Autism Spectrum. Current psychiatry reports. 2022; 24(3): 161-70.

PURPOSE OF REVIEW: This review provides a highlight of existing evidence-based practices and community support systems that exist to enhance employment outcomes for autistic transition-age youth (TAY) and adults. An update is provided on the current status of these programs and the impact they are having on employment outcomes for this population. RECENT FINDINGS: Many programs exist that prove to be efficacious in improving employment outcomes. These programs can be categorized as vocational rehabilitation service system level interventions, provider and consumer level interventions targeting skills related to employment, and consumer level interventions delivered within community vocational rehabilitation or education settings. A more recent increase in programs is consistent with multiple research and policy calls for amplified programming in this area. Despite these recent increases, there is still a need to further develop effective programming to support employment outcomes as the growing autistic population age into adulthood. Community-based research and practice should continue to be developed and tested.

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3. Gibson JM, Howland CP, Ren C, Howland C, Vernino A, Tsai PT. A Critical Period for Development of Cerebellar-Mediated Autism-Relevant Social Behavior. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2022; 42(13): 2804-23.

The cerebellum has been increasingly implicated in autism spectrum disorder (ASD) with many ASD-linked genes impacting both cerebellar function and development. However, the precise timing and critical periods of when abnormal cerebellar neurodevelopment contributes to ASD-relevant behaviors remains poorly understood. In this study, we identify a critical period for the development of ASD-relevant behaviors in a cerebellar male mouse model of tuberous sclerosis complex (TSC), by using the mechanistic target of rapamycin (mTOR) inhibitor, rapamycin, to pharmacologically inhibit dysregulated downstream signaling. We find independent critical periods during which abnormal ASD-relevant behaviors develop for the two core ASD diagnostic criteria, social impairments and behavioral flexibility, and delineate an anatomic, physiological, and behavioral framework. These findings not only further our understanding of the genetic mechanisms underlying the timing of ASD-relevant behaviors but also have the capacity to inform potential therapies to optimize treatment interventions.SIGNIFICANCE STATEMENT No targeted treatments currently exist for autism spectrum disorder (ASD). This complex developmental disorder has established links to genetic and circuit aberrations, yet the precise timing and coordination of these underlying mechanisms that contribute to the spectrum of physiological and behavioral abnormalities remains unclear. Cerebellar pathology is consistently seen in ASD individuals; therefore, we sought to identify the specific windows for cerebellar involvement in the development of ASD-relevant behaviors. Using pharmacologic treatment paradigms, we outline distinct critical periods of developmental vulnerability for ASD-relevant social and inflexible behaviors. From this study, we posit a refined window of time during which ASD symptoms develop that will inform therapeutic timing.

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4. Kodak T, Bergmann S, Cordeiro MC, Bamond M, Isenhower RW, Fiske KE. Replication of a skills assessment for auditory-visual conditional discrimination training. Journal of applied behavior analysis. 2022; 55(2): 622-38.

Auditory-visual conditional discrimination training (e.g., receptive identification training, listener responses; AVCD) is ubiquitous in early intervention and special education programs. Nevertheless, some learners with Autism Spectrum Disorder (ASD) do not appear to benefit from this training despite use of empirically validated treatments. To prevent exposure to extended training that does not lead to learning, a skills assessment that measures skills related to AVCD training will be useful for educators and practitioners. The current study replicated the skills assessment developed and evaluated by Kodak et al. (2015) with 8 participants with ASD who received behavior analytic intervention that included at least 1 goal related to AVCD training. Two of the 8 participants mastered all skills included in the assessment except scanning. In addition, 5 participants’ responding failed to reach mastery during subsequent exposure to AVCD training, which further demonstrated the predictive utility of the skills assessment.

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5. Mulay KV, Karthik SV. Managing constipation in children with ASD – A challenge worth tackling. Pediatrics and neonatology. 2022.

Autism Spectrum disorder (ASD) is well known to be associated with significantly high rates of gastrointestinal problems, constipation being common among them, imposing a significant burden on child and the family. On account of multiple underlying factors, both diagnosis and subsequent management of constipation in children with ASD are much more challenging as compared to managing constipation in ‘neurotypical’ children. Associated higher rate of presentation to the hospital emergency and subsequent hospital admission rates add to the burden. Hence, there is a need for recognizing constipation as a problem in children with ASD. This review summarizes optimization of its management by adopting a multidisciplinary holistic approach to achieve good outcomes and enhance the quality of life for the child and the family.

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6. Ptomey LT, Helsel BC, White DA, Lee J, Sherman JR, Washburn RA, Gorczyca AM, Donnelly JE. Intrapersonal, interpersonal and environmental correlates of moderate to vigorous physical activity and sedentary time in adolescents with intellectual and developmental disabilities. Journal of intellectual disability research : JIDR. 2022.

BACKGROUND: Although correlates of physical activity (PA) have been extensively examined in both children and adolescents who are typically developing, little is known about correlates of moderate to vigorous physical activity (MVPA) and sedentary time in adolescents with intellectual and developmental disabilities (IDD). Therefore, we examined intrapersonal, interpersonal and environmental factors and their association with device-based MVPA and sedentary time in adolescents with IDD. METHODS: MVPA and sedentary time was assessed using a hip-worn ActiGraph model wGT3x-BT tri-axial accelerometer across a 7-day period in adolescents with IDD and one of their parents. Pearson and point-biserial correlations were calculated to inspect the associations of PA (MVPA, sedentary time) with intrapersonal factors (demographic characteristic, BMI, waist circumference, motor ability, muscle strength, grip strength, cardiovascular fitness and self-efficacy for PA), interpersonal factors (parent demographics, parent BMI, parent MVPA and sedentary time, family social support for PA, parent barriers and support for PA, parent’s beliefs/attitudes towards PA and number of siblings), and environmental factors (meteorologic season and COVID-19). Ordinary least squares regression was used to estimate the unique contributions of key factors to PA after controlling for participants’ age, sex, race, waist circumference and total wear time. RESULTS: Ninety-two adolescents (15.5 ± 3.0 years old, 21.7% non-White, 6.5% Hispanic, 56.5% female) provided valid accelerometer data. Average sedentary time was 494.6 ± 136.4 min/day and average MVPA was 19.8 ± 24.2 min/day. Age (r = 0.27, P = 0.01), diagnosis of congenital heart disease (r = -0.26, P = 0.01) and parent sedentary time (r = 0.30, P = 0.01) were correlated with sedentary time. BMI (r = -0.24, P = 0.03), waist circumference (r = -0.28, P = 0.01), identifying as White (r = -0.23, P = 0.03) and parent MVPA (r = 0.56, P < 0.001) were correlated with MVPA. After adjusting for the adolescent's age, sex, race, waist circumference, and total wear time, the association between parent and adolescent MVPA remained significant (b = 0.55, P < 0.01, partial η(2) = 0.11). CONCLUSION: The results of this study provide evidence that race, waist circumference and parental MVPA may influence the amount of MVPA in adolescents with IDD. The limited available information and the potential health benefits of increased MVPA highlight the need to evaluate the effectiveness of multi-component interventions targeting both intrapersonal and interpersonal levels to promote increased PA in adolescents with IDD.

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7. Toupin A, Benachenhou S, Abolghasemi A, Laroui A, Galarneau L, Fülöp T, Corbin F, Çaku A. Association of lipid rafts cholesterol with clinical profile in fragile X syndrome. Scientific reports. 2022; 12(1): 2936.

Fragile X syndrome (FXS) is the most prevalent monogenic cause of intellectual disability and autism spectrum disorder (ASD). Affected individuals have a high prevalence of hypocholesterolemia, however, the underlying mechanisms and the clinical significance remains unknown. We hypothesized that decrease in the plasma cholesterol levels is associated with an alteration of cholesterol content within the lipid rafts (LRs) which ultimately affects the clinical profile of FXS individuals. The platelets LRs were isolated by ultracentrifugation on sucrose gradient from 27 FXS and 25 healthy controls, followed by measurements of proteins, cholesterol, and gangliosides content. Autistic and adaptive behaviour of affected individuals were respectively assessed by the Social Communication Questionnaire and Adaptive Behavior Assessment System. Our results suggest a decrease in the cholesterol content of LRs in FXS individuals as compared to controls. As opposed to controls, LR cholesterol was significantly associated with plasma total cholesterol (r = 0.47; p = 0.042) in the FXS group. Furthermore, the correlation between LRs cholesterol and the clinical profile showed a significant association with autistic traits (r = - 0.67; p < 0.001) and adaptative behavior (r = 0.70; p < 0.001). These results support the clinical significance of LR cholesterol alterations in FXS. Further studies are warranted to investigate the implication of LRs in FXS pathophysiology and ASD.

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8. Tripathi T, Harrison TM, Simsic JM, Cabral TI, Heathcock JC. Screening and Evaluation of Neurodevelopmental Impairments in Infants Under 6 Months of Age with Congenital Heart Disease. Pediatric cardiology. 2022; 43(3): 489-96.

Clinical evaluation of neurodevelopmental impairments before 6 months of age is needed in congenital heart disease (CHD) to promote early referral to developmental interventions. The objective was to identify the risk of cerebral palsy (CP) and to compare neurodevelopment outcomes in infants with and without CHD. In a longitudinal study, 30 infants with CHD and 15 infants without CHD were assessed at 1 month, 3 months, and 6 months of age. Included measures were General Movement Assessment (GMA), Test of Infant Motor Performance (TIMP) and the Bayley Scale of Infant Development, third edition (Bayley-III), selected to identify the risk of CP, document neurodevelopmental impairments and infants’ eligibility for early intervention services. Abnormal GMA categories were found in the CHD group where 48% had poor repertoire and 15% were at high risk of CP. At 3 months of age, CHD group had significantly lower TIMP scores compared to infants without CHD [t(41) = 6.57, p = 0.01]. All infants in the study had higher Bayley-III scores at 6 months than at 3 months of age. Infants with CHD had lower gross motor, fine motor and cognitive Bayley-III scores compared to their peers without CHD. Over time infants without CHD outperformed the CHD group in the gross motor skills [F((1,41)) = 11.76, p = .001]. Higher prevalence of abnormal GMs, lower TIMP and Bayley-III were found in infants with single ventricle physiology compared to two-ventricle physiology. The risk of CP exists in infants with CHD, and these infants have worse outcomes compared to their peers without CHD. These differences are intensified in the single ventricle population.Clinical Trial Registration National Institute of Health, Unique identifier: NCT03104751; Date of registration-April 7, 2017.

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9. Tuncay IO, Parmalee NL, Khalil R, Kaur K, Kumar A, Jimale M, Howe JL, Goodspeed K, Evans P, Alzghoul L, Xing C, Scherer SW, Chahrour MH. Analysis of recent shared ancestry in a familial cohort identifies coding and noncoding autism spectrum disorder variants. NPJ genomic medicine. 2022; 7(1): 13.

Autism spectrum disorder (ASD) is a collection of neurodevelopmental disorders characterized by deficits in social communication and restricted, repetitive patterns of behavior or interests. ASD is highly heritable, but genetically and phenotypically heterogeneous, reducing the power to identify causative genes. We performed whole genome sequencing (WGS) in an ASD cohort of 68 individuals from 22 families enriched for recent shared ancestry. We identified an average of 3.07 million variants per genome, of which an average of 112,512 were rare. We mapped runs of homozygosity (ROHs) in affected individuals and found an average genomic homozygosity of 9.65%, consistent with expectations for multiple generations of consanguineous unions. We identified potentially pathogenic rare exonic or splice site variants in 12 known (including KMT2C, SCN1A, SPTBN1, SYNE1, ZNF292) and 12 candidate (including CHD5, GRB10, PPP1R13B) ASD genes. Furthermore, we annotated noncoding variants in ROHs with brain-specific regulatory elements and identified putative disease-causing variants within brain-specific promoters and enhancers for 5 known ASD and neurodevelopmental disease genes (ACTG1, AUTS2, CTNND2, CNTNAP4, SPTBN4). We also identified copy number variants in two known ASD and neurodevelopmental disease loci in two affected individuals. In total we identified potentially etiological variants in known ASD or neurodevelopmental disease genes for ~61% (14/23) of affected individuals. We combined WGS with homozygosity mapping and regulatory element annotations to identify candidate ASD variants. Our analyses add to the growing number of ASD genes and variants and emphasize the importance of leveraging recent shared ancestry to map disease variants in complex neurodevelopmental disorders.

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