1. Alkhalidy H, Abushaikha A, Alnaser K, Obeidat MD, Al-Shami I. Nutritional Status of Pre-school Children and Determinant Factors of Autism : A Case-Control Study. Frontiers in nutrition. 2021 ; 8 : 627011.

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder triggered by several factors, including those of genetic and environmental nature. ASD can alter communication, behavior, and children’s nutritional status, placing them at high risk for nutritional imbalances. Therefore, this study aims to assess preschool autistic children’s nutritional status as compared to that of Typically Developing (TD) children of the same age. The study also revealed some of the ASD risk factors among the Jordanian population. It included 52 ASD and 51 TD children (3-6 years), and considered sociodemographic, obstetric, and nutritional factors of the two groups, stratified by gender. Nutritional status was evaluated through a comprehensive questionnaire, 3-day food record, and anthropometric and biochemical measurements. Differences between groups were identified using the chi-square and independent-sample t-test. The logistic regression model was used after the adjustment of confounders to detect an autistic child’s determinants. The study showed little difference between ASD and TD children with respect to nutrients’ intake inadequacy and biochemical-nutritional deficiencies, but did reveal gender-based differences. Autistic girls were at higher risk of inadequate carbohydrate intake, while autistic boys were at higher risk of inadequate vitamin E, vitamin K, and fluoride compared to TD children. More autistic children had been treated in neonatal care units after birth than had TD children. The regression analysis revealed that lower maternal education level (OR, 12.25 ; 95% CI, 1.18-126.91), vaginal delivery (OR, 0.273 ; 95% CI, 0.105-0.712), family history of autism (OR, 0.189 ; 95% CI, 0.059-0.612), and taking dietary supplements during pregnancy (OR, 4.665 ; 95% CI, 1.158-18.79) were all determinants of ASD in children. In conclusion, maternal nutrition, postnatal conditions, and nutritional status might be contributors to ASD in children. Pre-school children are at high risk for developing nutritional deficiencies. It is therefore important to maintain optimal nutritional status in pregnant patients, and in children after delivery and during early childhood. Future studies that investigate the role of nutrient deficiencies and nutritional interventions in ASD are necessary. Also required are studies that focus on gender differences in the prevalence of ASD, types and severity of symptoms, and ASD nutrition-related problems.

Lien vers le texte intégral (Open Access ou abonnement)

2. Arinda A, Nakasujja N, Odokonyero R. Prevalence of autism spectrum disorder symptoms in a paediatric neurology clinic at a tertiary hospital in Uganda. The South African journal of psychiatry : SAJP : the journal of the Society of Psychiatrists of South Africa. 2021 ; 27 : 1548.

BACKGROUND : Children with neurological disorders are more likely to present with autism spectrum disorder (ASD) symptoms and get an ASD diagnosis. Despite the large burden of childhood neurological disorders in Uganda, there is limited information on ASD amongst children with neurological disorders in Uganda. AIM : The aim of this study was to determine the prevalence and factors associated with ASD symptoms amongst children attending the paediatric neurology clinic. SETTING : The study was conducted at the paediatric neurology clinic of Mulago National Referral Hospital in Uganda. METHODS : This was a cross-sectional study of 318 children aged 2-9 years. After obtaining consent, a socio-demographic questionnaire and the Social Communication Questionnaire were administered to the caregivers of the children. Additional questions were administered to assess the prenatal, birth and postnatal characteristics of the children. Sample characteristics were described using frequencies and means. Bivariate analysis was carried out using chi-square test and Fisher’s exact test. Multiple logistic regression models were used to assess which factors were independently associated with ASD symptoms. RESULTS : The mean age of the children was 5 years and 58.2% were males. The prevalence of significant ASD symptoms was found to be 45%. Factors negatively associated with significant ASD symptoms were female sex (odds ratio [OR] 0.48 [95% CI 0.24, 0.98]) and ability to speak (OR 0.09 [95% CI 0.04, 0.2]). The history of delayed developmental milestones was positively associated with significant ASD symptoms (OR 3.3 [95% CI 1.59, 6.84]). CONCLUSION : The prevalence of ASD symptoms is high in children with neurological disorders. Children, especially those with delayed developmental milestones, should routinely be screened for ASD.

Lien vers le texte intégral (Open Access ou abonnement)

3. Berger NI, Wainer AL, Kuhn J, Bearss K, Attar S, Carter AS, Ibanez LV, Ingersoll BR, Neiderman H, Scott S, Stone WL. Characterizing Available Tools for Synchronous Virtual Assessment of Toddlers with Suspected Autism Spectrum Disorder : A Brief Report. J Autism Dev Disord. 2021 : 1-12.

The COVID-19 pandemic, and associated social distancing mandates, has placed significant limitations on in-person health services, requiring creative solutions for supporting clinicians engaged in the diagnosis of autism spectrum disorder (ASD). This report describes the five virtual instruments available at the time of manuscript development for use by experienced clinicians making diagnostic determinations of ASD for toddlers across the 12- to 36-months age range. We focus on synchronous virtual assessments in which clinicians guide the child’s caregiver through a range of assessment activities and observe spontaneous and elicited behaviors. Assessments are compared on dimensions of targeted behavioral domains, specific activities and presses employed, scoring approaches, and other key logistical considerations to guide instrument selection for use in varied clinical and research contexts.

Lien vers le texte intégral (Open Access ou abonnement)

4. Blackard KR, Krahn KN, Andris RT, Lake DE, Fairchild KD. Autism risk in neonatal intensive care unit patients associated with novel heart rate patterns. Pediatr Res. 2021.

BACKGROUND : Neonatal intensive care unit (NICU) patients are at increased risk for autism spectrum disorder (ASD). Autonomic nervous system aberrancy has been described in children with ASD, and we aimed to identify heart rate (HR) patterns in NICU patients associated with eventual ASD diagnosis. METHODS : This retrospective cohort study included NICU patients from 2009 to 2016 with archived HR data and follow-up beyond age 3 years. Medical records provided clinical variables and ASD diagnosis. HR data were compared in infants with and without ASD. RESULTS : Of the 2371 patients, 88 had ASD, and 689,016 h of data were analyzed. HR skewness (HRskw) was significantly different between ASD and control infants. Preterm infants at early postmenstrual ages (PMAs) had negative HRskw reflecting decelerations, which increased with maturation. From 34 to 42 weeks PMA, positive HRskw toward accelerations was higher in males with ASD. In 931 males with at least 4 days of HR data, overall ASD prevalence was 5%, whereas 11% in the top 5th HRskw percentile had ASD. CONCLUSION : High HRskw in NICU males, perhaps representing autonomic imbalance, was associated with increased ASD risk. Further study is needed to determine whether HR analysis identifies highest-risk infants who might benefit from earlier screening and therapies. IMPACT : In a large retrospective single-center cohort of NICU patients, we found that high positive skewness of heart rate toward more accelerations was significantly associated with increased risk of eventual autism spectrum disorder diagnosis in male infants but not in females. Existing literature describes differences in heart rate characteristics in children, adolescents, and adults with autism spectrum disorders, but the finding from our study in NICU infants is novel. Heart rate analysis during the NICU stay might identify, among an inherently high-risk population, those infants with especially high risk of ASD who might benefit from earlier screening and therapies.

Lien vers le texte intégral (Open Access ou abonnement)

5. Brilhante AVM, Filgueira LMA, Lopes S, Vilar NBS, Nóbrega LRM, Pouchain A, Sucupira LCG. « I am not a blue angel » : Sexuality from the perspective of autistic adolescentes. Ciencia & saude coletiva. 2021 ; 26(2) : 417-23.

Despite the difficulties in living their sexualities, the sexual education of autistic people is often neglected. In this sense, this research aims to identify autistic people’s demands on their sexualities, in line with the neurodiversity paradigm. This qualitative research was carried out from September 2017 to October 2018, with 14 autistic children aged 15 to 17 enrolled in regular schools. Data were collected by semi-structured interviews and analyzed according to the thematic content analysis. Two analytical categories were identified : « discursive processes and the ‘blue angel’ imagery » ; and « diversity in diversity : the sexuality of autistic people as singular processes ». The results show that, while autistic people grow physically and sexually according to the typical development stages, some singularities should not be ignored. However, the construction of false beliefs encourages the denial of autistic people’s sexuality. We can conclude that the establishment of effective actions of sexual education and support to the sexuality of the autistic person requires a paradigmatic change anchored in the social model of disability.

Lien vers le texte intégral (Open Access ou abonnement)

6. Di Renzo M, Guerriero V, Pagnacco A, Petrillo M, Racinaro L, D’Errico S, Bianchi di Castelbianco F. Attunement and Paternal Characteristics in Care Relationships in the Presence of Children Diagnosed with Autism. Int J Environ Res Public Health. 2021 ; 18(4).

Parents of children with autism spectrum disorder (ASD) have to address various challenges mainly due to their children’s atypia related to communication, emotion regulation and behaviors, arising also within the relationship with their caregivers. Several studies have pointed out that children with ASD can exhibit many difficulties regarding initiating and maintaining meaningful relationships with others. To date, little research has explored the interactions between children with ASD and their fathers, focusing more on mothers. In the context of parent-child interactions in the presence of autism, recent studies have highlighted the importance of parental attunement but there is little research considering solely the affective-bodily dimension. Therefore, the aim of the present study was to explore the parental attunement in fathers of children with ASD observed during play interactions and to investigate the relationship between paternal attunement and the perception of their psychological characteristics related to care relationships. The results highlight that fathers who describe themselves as better in affective care and sensitivity toward others more likely have an absence of paternal attunement during play interactions. The data presented are discussed in the light of intervention hypotheses, aimed at improving the relationship between fathers and children with autism.

Lien vers le texte intégral (Open Access ou abonnement)

7. Feige E, Mattingly R, Pitts T, Smith AF. Autism Spectrum Disorder : Investigating Predictive Adaptive Behavior Skill Deficits in Young Children. Autism research and treatment. 2021 ; 2021 : 8870461.

Autism spectrum disorder (ASD) is a lifelong neurodevelopmental disorder that consists of difficulties with social communication and language, as well as the presence of restricted and repetitive behaviors. These deficits tend to present in early childhood and usually lead to impairments in functioning across various settings. Moreover, these deficits have been shown to negatively impact adaptive behavior and functioning. Thus, early diagnosis and intervention is vital for future success within this population. The purpose of this study was to further examine the subscales that comprise the adaptive behavior section of the Bayley®-III to determine which of the ten subscales are predictive of ASD in young children (i.e., ≤ three years of age). A retrospective file review of 273 children participating in Kentucky’s early intervention program, First Steps, was completed. The children ranged in age from 18 to 35 months. A binary logistic regression was used to assess the subscales that comprise the adaptive behavior of the section of the Bayley®-III to determine which of the ten subscales are predictive of ASD in young children (i.e., ≤ three years of age). The results indicated that individual lower raw scores in communication, community use, functional preacademics, home living, health and safety, leisure, self-care, self-direction, and social subscales were predictive of an autism diagnosis.

Lien vers le texte intégral (Open Access ou abonnement)

8. Hassiotis A, Langdon PE, Courtenay K. UK Mental Health Act reform : implications for people with intellectual disabilities and autism. Lancet Psychiatry. 2021.

Lien vers le texte intégral (Open Access ou abonnement)

9. İnci A, Özaslan A, Okur İ, Biberoğlu G, Güney E, Ezgü FS, Tümer L, İşeri E. Autism : Screening of inborn errors of metabolism and unexpected results. Autism Res. 2021.

In this study, the aim was to examine patients with inborn errors of metabolism (IEM) who presented with only autism, without any other findings, to suggest any other neurological and genetic disorders. To investigate IEM, data of the hospital records of 247 patients who were referred from pediatric psychiatric to pediatric metabolism outpatient clinics due to further evaluation of autism spectrum disorders (ASD) were examined. Among them, 237 patients were evaluated for IEM leading to ASDs. Organic acidemias, phenylketonuria, tetrahydrobiopterin and neutrotransmitter disorders, biotinidase deficiency, Smith-Lemni-Opitz syndrome, disorders of cerebral creatine metabolism, urea cycle defects, homocystinuria, purine-pyrimidine metabolism disorders, mitochondrial disorders, cerebrotendinous xantomatosis, mucopolysaccaridosis, and glucose 6 phosphate dehydrogenase deficiency were screened with complete blood counts, complete biochemical analyses, homocysteine levels, an arterial blood gase, and metabolic investigations. Six patients were diagnosed as follows : one with phenylketonuria (PKU), one with cerebral creatine deficiency, one with hypobetalipoproteinemia, one with glycogen storage disease type IX-a, one with dihydropyrimidine dehydrogenase deficiency, and one with succinic semialdehyde dehydrogenase deficiency (SSADHD). Forty-six patients screened for IEM were from consanguineous families, among them, one was diagnosed with FKU and the other was with SSADHD. It would not be expected to find PKU in a 5-year-old patient as a result of newborn screening, but she could not been screened due to being a refugee. The diagnosed diseases were rare presentations of the diseases and furthermore, the diagnosis of hypobetalipoproteinemia and glycogen storage disease type IX-a were surprising with the only presentation of ASDs. LAY SUMMARY : It is well-known that some types of inborn errors of metabolism (IEM) may present with that of autism spectrum disorders (ASDs). This study suggests that in countries where consanguinity marriages are common such as Turkey and refugees whose escaped from neonatal screening are present, patients with ASD should be screened for IEMs. The results can surprise the physicians with a very rare cause of autism that has never been thought.

Lien vers le texte intégral (Open Access ou abonnement)

10. Joga-Elvira L, Roche-Martínez A, Joga ML, Jacas-Escarcelle C, Brun-Gasca C. Language in young females with fragile X syndrome : Influence on the neurocognitive profile and adaptive behavior. Am J Med Genet A. 2021.

Fragile X syndrome (FXS) is the leading cause of inherited intellectual disability. The objective of this research is to analyze the relationship between linguistic functions and performance of the following neuropsychological functions : executive, quantitative reasoning, social perception, behavior, social skills, and adaptive behavior. A neuropsychological and behavioral evaluations were carried out with a group of 26 girls with FXS, and 14 girls without FXS as a control group, using standardized tests. The two groups were homogeneous in age and IQ. Significant differences were found between groups in the relationship between some language processes : inhibition, auditory working memory, cognitive flexibility, level of social adaptation, self-direction, conceptual adaptation, academic skills, leadership ability, theory of mind, and arithmetic. In the group of girls with FXS, it was found that different aspects of language influence some of the executive functions evaluated, in addition to some specific aspects of social perception, adaptive behavior, and quantitative reasoning, in different ways. Future research should incorporate the study of the influence of other cognitive variables such as visual perception and executive function on behavioral, social, and adaptive aspects to know the real influence of all the cognitive variables on the behavior of girls with FXS.

Lien vers le texte intégral (Open Access ou abonnement)

11. Kindgren E, Quiñones Perez A, Knez R. Prevalence of ADHD and Autism Spectrum Disorder in Children with Hypermobility Spectrum Disorders or Hypermobile Ehlers-Danlos Syndrome : A Retrospective Study. Neuropsychiatr Dis Treat. 2021 ; 17 : 379-88.

INTRODUCTION : Hypermobility spectrum disorders (HSD) and hypermobile Ehlers-Danlos syndrome (hEDS) are both characterized by generalized hypermobility, in combination with pain, affected proprioception, and pronounced fatigue. Clinical observation indicates that behavioral problems, hyperactivity, and autistic traits are overrepresented in children with those conditions. The purpose of this retrospective study was to establish the prevalence of attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) among children with HSD and hEDS treated in our clinic since 2012. SUBJECTS AND METHODS : Since Ehlers-Danlos syndrome (EDS) diagnostic criteria and international classification were changed in 2017, we equate the older diagnosis EDS hypermobility type with the newer hEDS and the older hypermobility syndrome with HSD. A registry search from the computerized medical record system found 201 children (88 boys, 113 girls) aged 6-18 years who were treated at our pediatrics department with the diagnoses HSD or EDS. All medical records (113 with HSD, 88 with EDS) were reviewed, and key symptoms such as fatigue and pain, as well as diagnosis of ADHD/ASD, were recorded. RESULTS : All EDS cases could be classified as hEDS. Of the entire study cohort, 16% had a verified ADHD diagnosis and a further 7% were undergoing ADHD diagnostic investigation. Significantly more children with hEDS had ADHD compared to children with HSD (p=0.02). In the age group 15-16 years, 35% of those with hEDS had ADHD and, among those aged 17-18 years, ADHD was present in 46%. Children with coexisting ADHD showed a significantly higher proportion of associated symptoms such as fatigue, sleep-problems, and urinary tract problems. ASD had been verified in 6% of the children. Of those with ASD, 92% had sleep problems. CONCLUSION : This study shows a strong association between HSD or hEDS and ADHD or ASD. Therefore, children with HSD or hEDS may need to be routinely screened for neuropsychiatric symptoms.

Lien vers le texte intégral (Open Access ou abonnement)

12. McLay LK, Schluter PJ, Eggleston MJF, Woodford EC, Bowden N. Melatonin dispensing among New Zealand children aged 0-18 years with autism : a nationwide cross-sectional study. Sleep medicine. 2021 ; 80 : 184-92.

OBJECTIVE/BACKGROUND : Sleep problems in children on the autism spectrum are prevalent and persistent. Such problems are the result of a combination of biopsychosocial factors, including abnormal melatonin secretion. Exogenous melatonin is an empirically supported and popular treatment for sleep problems. However, we know little about rates of melatonin dispensing and associated variables. This study investigated rates of melatonin dispensing and the sociodemographic and child characteristics associated with its use in New Zealand. METHODS : This nationwide cross-sectional study used linked administrative health data obtained via the Integrated Data Infrastructure (IDI). Data were obtained for 11,202, 0-18 year old children on the autism spectrum. Descriptive data, and adjusted and unadjusted risk ratios, were calculated for sociodemographic and child characteristics. RESULTS : Melatonin is accessed by almost one quarter of children on the autism spectrum in New Zealand, with higher observed rates among females and those aged between 5 and 11 years, of European ethnicity, and presenting with co-occurring mental health conditions. CONCLUSIONS : Findings are largely consistent with research investigating both sleep disturbances and psychotropic drug use among children on the autism spectrum. High rates of melatonin use, age- and sex-related differences in its use, and the complexity associated with the presence of co-occurring conditions necessitates development of practice guidelines for melatonin dispensing. Further investigation into the duration of melatonin use and the interaction between child characteristics, co-occurring conditions, sociodemographic variables and melatonin dispensing is warranted.

Lien vers le texte intégral (Open Access ou abonnement)

13. Menezes M, Mazurek MO. Associations between domains of health-related quality of life and comorbid emotional and behavioral problems in youth with autism spectrum disorder. Res Autism Spectr Disord. 2021 ; 82.

BACKGROUND : Health-related quality of life (HRQoL) can be used as a measure of the impact of a particular disorder on one’s daily functioning. Previous studies have found that comorbid psychiatric disorders in children and adolescents with autism spectrum disorder (ASD) are associated with poorer HRQoL than ASD alone. Less is known about potential associations between specific symptoms of comorbid psychopathology (i.e., emotional and behavioral problems) and domains of functioning or HRQoL in youth with ASD. METHOD : Participants were 470 children with ASD 2-14 years old recruited from one of three sites. Hierarchical multiple regressions were conducted with Pediatric Quality of Life Inventory 4.0 (PedsQL ; Varni et al., 2001) HRQoL domains of physical functioning, emotional functioning, school functioning, and social functioning as the dependent variables. Covariates were entered at step 1, followed by the independent variables of interest at step 2 : irritability, social withdrawal, stereotypic behavior, hyperactivity/noncompliance, and inappropriate speech. RESULTS : The study found that increased irritability was associated with poorer emotional and physical functioning and that greater social withdrawal was associated with worse social functioning. Furthermore, findings showed that more hyperactivity/noncompliance was associated with worse school functioning. CONCLUSIONS : Results demonstrated that certain emotional and behavioral symptoms are differentially associated with domains of HRQoL. This indicates that comorbid emotional and behavioral problems should be considered when measuring HRQoL in children with ASD. It also suggests that treating comorbid emotional/behavioral problems could improve HRQoL and functioning in certain domains for this population.

Lien vers le texte intégral (Open Access ou abonnement)

14. Pettit E. Transition to adulthood for individuals with autism : addressing the knowledge gap. Dev Med Child Neurol. 2021.

Lien vers le texte intégral (Open Access ou abonnement)

15. Richter JD, Zhao X. The molecular biology of FMRP : new insights into fragile X syndrome. Nat Rev Neurosci. 2021.

Fragile X mental retardation protein (FMRP) is the product of the fragile X mental retardation 1 gene (FMR1), a gene that – when epigenetically inactivated by a triplet nucleotide repeat expansion – causes the neurodevelopmental disorder fragile X syndrome (FXS). FMRP is a widely expressed RNA-binding protein with activity that is essential for proper synaptic plasticity and architecture, aspects of neural function that are known to go awry in FXS. Although the neurophysiology of FXS has been described in remarkable detail, research focusing on the molecular biology of FMRP has only scratched the surface. For more than two decades, FMRP has been well established as a translational repressor ; however, recent whole transcriptome and translatome analyses in mouse and human models of FXS have shown that FMRP is involved in the regulation of nearly all aspects of gene expression. The emerging mechanistic details of the mechanisms by which FMRP regulates gene expression may offer ways to design new therapies for FXS.

Lien vers le texte intégral (Open Access ou abonnement)

16. Simpraga S, Weiland RF, Mansvelder HD, Polderman TJ, Begeer S, Smit DJ, Linkenkaer-Hansen K. Adults with autism spectrum disorder show atypical patterns of thoughts and feelings during rest. Autism. 2021 : 1362361321990928.

Everyone knows the feeling of letting one’s mind wander freely in a quiet moment. The thoughts and feelings experienced in those moments have been shown to influence our well-being-and vice versa. In this study, we looked at which thoughts and feelings are being experienced by adults with autism spectrum disorder and compared them to adults without autism spectrum disorder. In total, 88 adults with autism spectrum disorder and 90 adults without autism spectrum disorder were asked to rest for 5 min with their eyes closed and let their mind wander. Directly after, they filled in the Amsterdam Resting-State Questionnaire, which probes what participants were feeling and thinking during the period of rest. We found that adults with autism spectrum disorder tend to think less about others, felt less comfortable, and had more disrupted thoughts during the rest compared to adults without autism spectrum disorder. Interestingly, autism spectrum disorder participants reporting lower levels of comfort during the rest also reported more autism spectrum disorder symptoms, specifically in social behaviors and skills, attention switching, and imagination. We propose to use the eyes-closed rest condition in combination with the Amsterdam Resting-State Questionnaire more widely to shed light on aberrant thoughts and feelings in brain disorders and to study the effect of therapeutic interventions.

Lien vers le texte intégral (Open Access ou abonnement)

17. Villa C, Combi R, Conconi D, Lavitrano M. Patient-Derived Induced Pluripotent Stem Cells (iPSCs) and Cerebral Organoids for Drug Screening and Development in Autism Spectrum Disorder : Opportunities and Challenges. Pharmaceutics. 2021 ; 13(2).

Autism spectrum disorder (ASD) represents a group of neurodevelopmental diseases characterized by persistent deficits in social communication, interaction, and repetitive patterns of behaviors, interests, and activities. The etiopathogenesis is multifactorial with complex interactions between genetic and environmental factors. The clinical heterogeneity and complex etiology of this pediatric disorder have limited the development of pharmacological therapies. The major limit to ASD research remains a lack of relevant human disease models which can faithfully recapitulate key features of the human pathology and represent its genetic heterogeneity. Recent advances in induced pluripotent stem cells (iPSCs), reprogrammed from somatic cells of patients into all types of patient-specific neural cells, have provided a promising cellular tool for disease modeling and development of novel drug treatments. The iPSCs technology allowed not only a better investigation of the disease etiopathogenesis but also opened up the potential for personalized therapies and offered new opportunities for drug discovery, pharmacological screening, and toxicity assessment. Moreover, iPSCs can be differentiated and organized into three-dimensional (3D) organoids, providing a model which mimics the complexity of the brain’s architecture and more accurately recapitulates tissue- and organ-level disease pathophysiology. The aims of this review were to describe the current state of the art of the use of human patient-derived iPSCs and brain organoids in modeling ASD and developing novel therapeutic strategies and to discuss the opportunities and major challenges in this rapidly moving field.

Lien vers le texte intégral (Open Access ou abonnement)

18. Vita DJ, Meier CJ, Broadie K. Neuronal fragile X mental retardation protein activates glial insulin receptor mediated PDF-Tri neuron developmental clearance. Nat Commun. 2021 ; 12(1) : 1160.

Glia engulf and phagocytose neurons during neural circuit developmental remodeling. Disrupting this pruning process contributes to Fragile X syndrome (FXS), a leading cause of intellectual disability and autism spectrum disorder in mammals. Utilizing a Drosophila FXS model central brain circuit, we identify two glial classes responsible for Draper-dependent elimination of developmentally transient PDF-Tri neurons. We find that neuronal Fragile X Mental Retardation Protein (FMRP) drives insulin receptor activation in glia, promotes glial Draper engulfment receptor expression, and negatively regulates membrane-molding ESCRT-III Shrub function during PDF-Tri neuron clearance during neurodevelopment in Drosophila. In this context, we demonstrate genetic interactions between FMRP and insulin receptor signaling, FMRP and Draper, and FMRP and Shrub in PDF-Tri neuron elimination. We show that FMRP is required within neurons, not glia, for glial engulfment, indicating FMRP-dependent neuron-to-glia signaling mediates neuronal clearance. We conclude neuronal FMRP drives glial insulin receptor activation to facilitate Draper- and Shrub-dependent neuronal clearance during neurodevelopment in Drosophila.

Lien vers le texte intégral (Open Access ou abonnement)

19. Wichers RH, Findon JL, Jelsma A, Giampietro V, Stoencheva V, Robertson DM, Murphy CM, Blainey S, McAlonan G, Ecker C, Rubia K, Murphy DGM, Daly EM. Modulation of atypical brain activation during executive functioning in autism : a pharmacological MRI study of tianeptine. Mol Autism. 2021 ; 12(1) : 14.

BACKGROUND : Autism spectrum disorder (ASD) is associated with deficits in executive functioning (EF), and these have been suggested to contribute to core as well as co-occurring psychiatric symptoms. The biological basis of these deficits is unknown but may include the serotonergic system, which is involved both in regulating EF in neurotypical populations and in the pathophysiology of ASD. We previously demonstrated that reducing serotonin by acute tryptophan depletion (ATD) shifts differences in brain function during performance of EF tasks towards control levels. However, ATD cannot be easily used in the clinic, and we therefore need to adopt alternative approaches to challenge the serotonin system. Hence, we investigated the role of the serotonergic modulator tianeptine on EF networks in ASD. METHOD : We conducted a pharmacological magnetic resonance imaging study, using a randomized double-blind crossover design, to compare the effect of an acute dosage of 12.5 mg tianeptine and placebo on brain activation during two EF tasks (of response inhibition and sustained attention) in 38 adult males : 19 with ASD and 19 matched controls. RESULTS : Under placebo, compared to controls, individuals with ASD had atypical brain activation in response inhibition regions including the inferior frontal cortex, premotor regions and cerebellum. During sustained attention, individuals with ASD had decreased brain activation in the right middle temporal cortex, right cuneus and left precuneus. Most of the case-control differences in brain function observed under placebo conditions were abolished by tianeptine administration. Also, within ASD individuals, brain functional differences were shifted significantly towards control levels during response inhibition in the inferior frontal and premotor cortices. LIMITATIONS : We conducted a pilot study using a single dose of tianeptine, and therefore, we cannot comment on long-term outcome. CONCLUSIONS : Our findings provide the first evidence that tianeptine can shift atypical brain activation during EF in adults with ASD towards control levels. Future studies should investigate whether this shift in the biology of ASD is maintained after prolonged treatment with tianeptine and whether it improves clinical symptoms.

Lien vers le texte intégral (Open Access ou abonnement)

20. Xie LY, Atem FD, Bar S, Mathew MS, Lebron C, Chang C, Natale R, Messiah SE. Relationship between parent perception of child anthropometric phenotype and body mass index change among children with developmental disabilities. World journal of pediatrics : WJP. 2021.

BACKGROUND : Preschool-age children with developmental disabilities (DD) have higher prevalence of obesity than children without DD. This study aimed to explore the relationship between parent perception of their children’s anthropometric phenotype and child body mass index (BMI) z score change over one school year among preschoolers with DD. METHODS : The analysis consisted of a subsample (N = 64) of children with DD from a larger randomized controlled trial to test an obesity prevention program in the childcare center setting. Parents ranks their child’s anthropometric phenotype on a visual silhouette chart on a scale from 1 (underweight) to 7 (obese) and that rank score is compared to their BMI z score change over one school year. RESULTS : The majority (75%) of parents with an obese child underestimated their child’s anthropometric phenotype while 7% parents with a non-obese child overestimated. Parent overestimation of child anthropometric phenotype status is associated with increased BMI z score change over 1 school year among preschool-age children with disabilities. CONCLUSION : Parental overestimation of child anthropometric phenotype status was associated with weight gain in preschool children with DD after one school year.

Lien vers le texte intégral (Open Access ou abonnement)