1. Aaronson B, Glick SN, Kirk CJ, McCloud WAt, Sasser TR, Zerr DM, Englund JA. Assessment of Feasibility of Face Covering in School-Aged Children With Autism Spectrum Disorders and Attention-Deficit/Hyperactivity Disorder. JAMA network open. 2021; 4(5): e2110281.

This cohort study reports the outcomes of using positive behavior supports to promote masking in school-aged children with autism spectrum disorders (ASD) and/or attention-deficit/hyperactivity disorder (ADHD) attending a summer day treatment program.

Lien vers le texte intégral (Open Access ou abonnement)

2. Bekkers S, Pruijn IMJ, van der Burg JJW, van Hulst K, Kok SE, Delsing CP, Scheffer ART, van den Hoogen FJA. Surgery versus botulinum neurotoxin A to reduce drooling and improve daily life for children with neurodevelopmental disabilities: a randomized controlled trial. Developmental medicine and child neurology. 2021; 63(11): 1351-9.

AIM: To compare the effect of bilateral submandibular duct ligation and botulinum neurotoxin A (BoNT-A) on drooling severity and its impact on daily life and care in children and adolescents with moderate-to-severe drooling. METHOD: This was a randomized, interventional, controlled trial in which 53 children and adolescents (31 males, 22 females, mean age 11y, range 8-22y, SD 2y 10mo) with cerebral palsy (58.5%) or other non-progressive developmental disorders (41.5%) were randomized to BoNT-A (n=26) or bilateral submandibular duct ligation (n=27). A parent questionnaire on the severity of drooling in specific positions and daily activities and the impact of drooling on daily life and care was filled out at baseline and 8 and 32 weeks posttreatment. RESULTS: Both BoNT-A and bilateral submandibular duct ligation had a positive effect on daily care, damage to electronic equipment and/or furniture, social interactions, and self-esteem. However, bilateral submandibular duct ligation had a significant greater and longer-lasting short- (8wks) and medium-term (32wks) effect on daily care, reducing damage to electronic devices, and improving social interactions and satisfaction with life in general. INTERPRETATION: This randomized controlled trial confirms reduced drooling by both BoNT-A and bilateral submandibular duct ligation, but provides new evidence on improved well-being through a reduction in drooling. Even though there is a greater risk of complications and morbidity after bilateral submandibular duct ligation, compared to BoNT-A there was a significantly greater and longer-lasting positive effect on most outcomes. What this paper adds Bilateral botulinum neurotoxin A (BoNT-A) and submandibular duct ligation had a positive effect on the well-being of individuals with moderate-to-severe drooling. Bilateral submandibular duct ligation had a greater effect on the impact of drooling during daily care than BoNT-A. Bilateral submandibular duct ligation reduced damage to electronic devices and improved social interactions and satisfaction with life. Publisher: Abstract available from the publisher. spa por.

Lien vers le texte intégral (Open Access ou abonnement)

3. Boksha IS, Prokhorova TA, Tereshkina EB, Savushkina OK, Burbaeva GS. Protein Phosphorylation Signaling Cascades in Autism: The Role of mTOR Pathway. Biochemistry Biokhimiia. 2021; 86(5): 577-96.

The mammalian target of rapamycin (mTOR) signaling pathway is a central regulator of cell metabolism, growth, and survival in response to hormones, growth factors, nutrients, and stress-induced signals. In this review, we analyzed the studies on the molecular abnormalities of the mTOR-associated signaling cascades in autism spectrum disorders (ASDs) and outlined the prospects for the pathogenicity-targeting pharmacotherapeutic approaches to ASDs, in particular syndromic ASDs. Based on available experimental and clinical data, we suggest that very early detection of molecular abnormalities in the ASD risk groups can be facilitated by using peripheral blood platelets. Also, identification of the time window of critical dysregulations in the described pathways in the ASD risk groups might suggest further research directions leading to more efficacious pharmacotherapeutic interventions in ASDs.

Lien vers le texte intégral (Open Access ou abonnement)

4. Brehm B, Schill J, Rauh R, Fleischhaker C, Biscaldi M. Preliminary Evaluation of the FETASS Training for Parents of Children With Autism Spectrum Disorder: A Pilot Study. Frontiers in psychology. 2021; 12: 604851.

While several recent evaluation studies have shown the efficacy of parent training programs for children with neurodevelopmental disorders, manual-based training in German is still scarce. To address this gap, we developed a specific modularized training program for parents of children from preschool to pre-adolescent age with Autism Spectrum Disorder (FETASS). The overarching purpose of the FETASS intervention is to enhance social communication behavior and quality of life of the child by coaching parents. As a proximal target, the FETASS training aims to provide families with behavior management and communication strategies. The development of the training was influenced by published behavioral parent trainings and autism-specific interventions. The training comprises eight weekly sessions and targets families whose children have a diagnosis of Autism Spectrum Disorder (ASD) without intellectual and language impairments. As a preliminary pilot study, the purpose was to evaluate the acceptability of the training. Furthermore, the study aimed at initially evaluating social communication behavior, quality of life of the child, parental stress level, and parenting after training in comparison to a treatment as usual (TAU) group. Exploratively, long-term effects were investigated after 6 months of training as well. In total, 57 families participated (n[TAU] = 29, n[FETASS] = 28). Questionnaires about social communication behavior and quality of life of the child, parental stress, and parenting were administered at three time points (t1: baseline TAU/FETASS, t2: post TAU/FETASS; and t3: 6-month follow-up after FETASS). Primary outcome measures were the social communication behavior of the child and the parent’s proxy report on quality of life of the child. Secondary outcome measures were changes in parental stress and parenting behavior. Acceptability of the training was very high and we had almost no dropouts during training. Results for the primary outcome measure of social communication behavior, overall quality of life of the child, and long-term effects on social communication behavior were not significant. While long-term findings for parent stress reduction and for the quality of life of the child are promising, further research has to be done in a future randomized controlled trial.

Lien vers le texte intégral (Open Access ou abonnement)

5. Burke MM, Rossetti Z, Aleman-Tovar J, Rios K. Examining the relation between empowerment and civic engagement among parents of individuals with intellectual and developmental disabilities. Journal of applied research in intellectual disabilities : JARID. 2021; 34(6): 1569-81.

Internationally, parents of children with intellectual and developmental disabilities have historically engaged in advocacy leading to compulsory education for their children. However, few parents have reported civic engagement. Although empowerment is related to parent advocacy, it is unclear whether empowerment relates to civic engagement. Thus, our study examined parent and child correlates of empowerment and civic engagement, and the relation between empowerment and civic engagement among 235 parents of children with intellectual and developmental disabilities across five states in the United States. Gender and special education knowledge were significant correlates of empowerment and civic engagement. There was a significant positive correlation between empowerment and civic engagement. Implications regarding future research and ways to promote parent empowerment and civic engagement are discussed.

Lien vers le texte intégral (Open Access ou abonnement)

6. Chakrabarty M, Atsumi T, Kaneko A, Fukatsu R, Ide M. State anxiety modulates the effect of emotion cues on visual temporal sensitivity in autism spectrum disorder. The European journal of neuroscience. 2021; 54(2): 4682-94.

Atypical processing of stimulus inputs across a range of sensory modalities in autism spectrum disorder (ASD) is widely reported. Sensory processing is known to be influenced by bodily internal states such as physiological arousal and anxiety. As a sizeable proportion of ASD reportedly have co-morbid anxiety disorders that are linked with dysregulated arousal, we investigated if face emotion arousal cues influenced visual sensory sensitivity (indexed by temporal resolution) in ASD (n = 20) compared to a matched group of typically developed individuals (TD, n = 21). We asked further if emotion-cued changes in visual sensitivity were associated with individual differences in state and trait anxiety. Participants reported the laterality of the second of two consecutive Gaussian-blob flashes in a visual temporal order judgment task (v-TOJ), demanding higher-level visual processing. The key manipulation was presenting a task-irrelevant face emotion cue briefly at unexpected time points preceding the task-relevant flashes. Disgust vs. Neutral emotion signals significantly enhanced the visual temporal resolution in ASD. Individual state-anxiety scores showed a fair correlative trend with the emotion-cued changes in temporal resolution (Disgust versus Neutral) in ASD but missed statistical significance. Both these effects were absent in TD. The results show that individual state-anxiety levels likely modulate the effect of emotions on visual temporal sensitivity in ASD. The findings support a nuanced approach to understand the disparate sensory features in ASD, by factoring in the interplay of the individual reactivity to environmental affective information and the severity of anxiety.

Lien vers le texte intégral (Open Access ou abonnement)

7. Dubreucq M, Dubreucq J. Toward a Gender-Sensitive Approach of Psychiatric Rehabilitation in Autism Spectrum Disorder (ASD): A Systematic Review of Women Needs in the Domains of Romantic Relationships and Reproductive Health. Frontiers in psychiatry. 2021; 12: 630029.

Later age of diagnosis, better expressive behaviors, increased use of camouflage strategies but also increased psychiatric symptoms, more unmet needs, and a general lower quality of life are characteristics often associated with female gender in autism spectrum disorder (ASD). Psychiatric rehabilitation has shown small to moderate effectiveness in improving patients’ outcomes in ASD. Few gender differences have been found in the response to psychiatric rehabilitation. This might be related to the predominance of males in research samples, but also to the lack of programs directly addressing women’s unmet needs. The objectives of the present paper were: (i) to review the needs for care of autistic women in romantic relationships and reproductive health; (ii) to review the existing psychosocial treatments in these domains; and (iii) to evaluate the strengths and limitations of the current body of evidence to guide future research. A systematic electronic database search (PubMed and PsycINFO), following PRISMA guidelines, was conducted on autistic women’s needs for care relating to psychiatric rehabilitation in romantic relationships and reproductive health. Out of 27 articles, 22 reported on romantic relationships and 16 used a quantitative design. Most studies were cross-sectional (n = 21) and conducted in North America or Europe. Eight studies reported on interventions addressing romantic relationships; no published study reported on interventions on reproductive health or parenting. Most interventions did not include gender-sensitive content (i.e., gender variance and gender-related social norms, roles, and expectations). Autistic women and autistic gender-diverse individuals may face unique challenges in the domains of romantic relationships and reproductive health (high levels of stigma, high risk of sexual abuse, increased psychiatric symptoms, and more unmet needs). We discussed the potential implications for improving women’s access to psychiatric and psychosocial treatment, for designing gender-sensitive recovery-oriented interventions, and for future research.

Lien vers le texte intégral (Open Access ou abonnement)

8. Earl RK, Ward T, Gerdts J, Eichler EE, Bernier RA, Hudac CM. Sleep Problems in Children with ASD and Gene Disrupting Mutations. The Journal of genetic psychology. 2021; 182(5): 317-34.

Sleep difficulties are pervasive in autism spectrum disorder (ASD), yet how sleep problems relate to underlying biological mechanisms such as genetic etiology is unclear, despite recent reports of profound sleep problems in children with ASD-associated de novo likely gene disrupting (dnLGD) mutations, CHD8, DYRK1A, and ADNP. We aimed to inform etiological contributions to ASD and sleep by characterizing sleep problems in individuals with dnLGD mutations. Participants (N = 2886) were families who completed dichotomous questions about sleep problems within a medical history interview for their child with ASD (age 3-28 years). Confirmatory factor analyses compared between those with ASD and a dnLGD mutation and those with idiopathic ASD (i.e., no known genetic event, NON) highlighted four domains (sleep onset, breathing issues, nighttime awakenings, and daytime tiredness) with sleep onset as a strong factor for both groups. Overall, participant predictors indicated that internalizing behavioral problems and lower cognitive scores were related to increased sleep problems. Internalizing problems were also related to increase nighttime awakenings in the dnLGD group. As an exploratory aim, patterns of sleep issues are described for genetic subgroups with unique patterns including more overall sleep issues in ADNP (n = 19), problems falling asleep in CHD8 (n = 22), and increased daytime naps in DYRK1A (n = 23). Implications for considering genetically defined subgroups when approaching sleep problems in children with ASD are discussed.

Lien vers le texte intégral (Open Access ou abonnement)

9. Hanswijk SI, van Rooij D, Oosterlaan J, Luman M, Hoekstra PJ, Hartman CA, Franke B, Sprooten E, Homberg JR, Buitelaar JK. Maternal serotonin transporter genotype and offsprings’ clinical and cognitive measures of ADHD and ASD. Progress in neuro-psychopharmacology & biological psychiatry. 2021; 110: 110354.

Serotonin (5-HT) is an important factor for prenatal neurodevelopment whereby its neurotrophic actions can be regulated through maternal-fetal interactions. We explored if maternal 5-HTTLPR genotype is associated with clinical and cognitive measures of attention-deficit/hyperactivity disorder (ADHD) and comorbid autism spectrum disorder (ASD) in typically-developing and ADHD-diagnosed offspring, beyond classical inheritance and environmental- and comorbidity-mediators/confounders. Family-based variance decomposition analyses were performed incorporating 6-31 year-old offsprings’ as well as parental genotypes of 462 ADHD and control families from the NeuroIMAGE cohort. Dependent measures were offsprings’ ADHD symptom- and ASD trait-scores and cognitive measures including executive functioning (including response inhibition and cognitive flexibility), sustained attention, reward processing, motor control, and emotion recognition. Offsprings’ stereotyped behavior was predicted by an interaction between maternal 5-HTTLPR genotype and offsprings’ sex. Furthermore, offspring of mothers with low-expressing genotypes demonstrated larger reward-related reductions in reaction time. While specifically adult male offspring of these mothers reported a faster reversal learning with less errors, specifically young female offspring of these mothers were more accurate in identifying happy faces. Adult offspring from the mothers with low-expressing 5-HTTLPR genotypes were also slower in identifying happy faces. However, this association seemed to be mediated by offsprings’ high anxiety levels. In sum, we found some support for a role of the maternal 5-HT system in modulating fetal brain development and behavior. Offsprings’ cognitive measures might be more sensitive to small alterations within the maternal 5-HT system than their ADHD and ASD clinical phenotypes. Further studies are needed to specify the association between maternal genotype and risk for neurodevelopmental disorders.

Lien vers le texte intégral (Open Access ou abonnement)

10. Lanyi J, Mannion A, Chen JL, Leader G. Relationship between Comorbid Psychopathology in Children and Adolescents with Autism Spectrum Disorder and Parental Well-being. Developmental neurorehabilitation. 2022; 25(3): 151-61.

AIM: Frequency and relationship between child comorbid psychopathology and parental stress, quality of life (QoL), anxiety, depression, and social support were examined in parents of children and adolescents with autism spectrum disorder (ASD). METHOD: Parents of 152 children and adolescents with ASD completed the Autism Spectrum Disorder-Comorbid for Children, Parenting Stress Index-Short Form, World Health Organization Quality of Life Abbreviated Version, Hospital Anxiety and Depression Scale, and the Multidimensional Scale of Perceived Social Support. RESULTS: A series of one-way multivariate analysis of variance was conducted to examine the relationship between child comorbid psychopathology and parental well-being. A relationship was found between parental QoL, depression and anxiety and child comorbid psychopathology. Results showed a relationship between parental stress and the severity of child conduct, and repetitive behaviors. CONCLUSION: This study adds to existing literature by demonstrating the relationship between comorbid psychopathology in children and adolescents in ASD and parental well-being.

Lien vers le texte intégral (Open Access ou abonnement)

11. Liu H, Tan M, Cheng B, Wang S, Xiao L, Zhu J, Wu Q, Lai X, Zhang Q, Chen J, Li T. Valproic Acid Induces Autism-Like Synaptic and Behavioral Deficits by Disrupting Histone Acetylation of Prefrontal Cortex ALDH1A1 in Rats. Frontiers in neuroscience. 2021; 15: 641284.

OBJECTIVES: This study aimed to investigate the impact of valproic acid (VPA) on the histone acetylation of acetaldehyde dehydrogenase 1A1 (ALDH1A1) and the mechanism underlying VPA-induced autism-like behavior. METHODS: Female Sprague-Dawley rats were intraperitoneally injected with VPA during gestation to establish an autism model in their offspring. Some offspring prenatally exposed to VPA were randomly treated with MS-275, one histone deacetylase (HDAC) inhibitor, or retinoic acid (RA) after birth. Behavioral tests were conducted on the offspring 6 weeks after birth. Electrophysiological experiments were performed to investigate long-term potentiation (LTP) in the prefrontal cortex (PFC). The expression levels of AMPA receptors (GluA1 and 2), NMDA receptors (GluN1 and 2), synapsin 1 (SYN1), HDAC, acetylated histone 3 (AcH3), RA receptor alpha (RARα), and ALDH1A1 in the PFC were measured by Western blotting and quantitative polymerase chain reaction. ALDH enzyme activity in PFC tissue was detected using a Micro ALDH Assay Kit. The RA level in the PFC was measured using ultrahigh-performance liquid chromatography/tandem mass spectrometry. A chromatin immunoprecipitation (ChIP) experiment explored the interaction between the ALDH1A1 gene and AcH3. RESULTS: Offspring prenatally exposed to VPA showed autism-like behavior, upregulated the levels of LTP and GluN2A, GluA1, and SYN1 proteins relevant to synaptic plasticity in the PFC. The expression levels of HDAC3 mRNA and protein were increased. On the other hand, there was a significant reduction in the levels of AcH3, RARα, RA, ALDH1A1 mRNA and protein, the level of ALDH activity and AcH3 enrichment in the ALDH1A1 promoter region in VPA-induced offspring. Administration of MS-275 in VPA offspring significantly elevated the levels of AcH3, ALDH1A1 mRNA and protein, ALDH activity, RA, the level of RARα protein and the binding of AcH3 to the ALDH1A1 promoter. In addition, the GluA1 protein level and LTP were reduced, and most behavioral deficits were reversed. After RA supplementation in the VPA-treated offspring, the RA and RARα protein levels were significantly upregulated, GluA1 protein and LTP were downregulated, and most autism-like behavioral deficits were effectively reversed. CONCLUSION: These findings suggest that VPA impairs histoneacetylation of ALDH1A1 and downregulates the RA-RARα pathway. Such epigenetic modification of ALDH1A1 by VPA leads to autism-like synaptic and behavioral deficits.

Lien vers le texte intégral (Open Access ou abonnement)

12. Mehta SQ, Behl S, Day PL, Delgado AM, Larson NB, Stromback LR, Huebner AR, DeGrado TR, Davis JM, Jannetto PJ, Howie F, Pandey MK. Evaluation of Zn, Cu, and Se Levels in the North American Autism Spectrum Disorder Population. Frontiers in molecular neuroscience. 2021; 14: 665686.

Metal ion dyshomeostasis and disparate levels of biometals like zinc (Zn), copper (Cu), and selenium (Se) have been implicated as a potential causative factor for Autism Spectrum Disorder (ASD). In this study, we have enrolled 129 children (aged 2-4 years) in North America, of which 64 children had a diagnosis of ASD and 65 were controls. Hair, nail, and blood samples were collected and quantitatively analyzed for Zn, Cu and Se using inductively coupled plasma mass spectrometry (ICP-MS). Of the analyzed biometals, serum Se (116.83 ± 14.84 mcg/mL) was found to be significantly lower in male ASD cases compared to male healthy controls (128.21 ± 9.11 mcg/mL; p < 0.005). A similar trend was found for nail Se levels in ASD (1.01 ± 0.15 mcg/mL) versus that of controls (1.11 ± 0.17 mcg/mL) with a p-value of 0.0132 using a stratified Wilcoxon rank sum testing. The level of Se in ASD cohort was co-analyzed for psychometric correlation and found a negative correlation between total ADOS score and serum Se levels. However, we did not observe any significant difference in Zn, Cu, and Zn/Cu ratio in ASD cases versus controls in this cohort of North American children. Further studies are recommended to better understand the biology of the relationship between Se and ASD status.

Lien vers le texte intégral (Open Access ou abonnement)

13. Morales DR, Nordeng HM. Commentary: Obstetric oxytocin exposure and risk of attention-deficit hyperactivity disorder and autism spectrum disorder in offspring-case closed. International journal of epidemiology. 2021; 50(2): 457-8.

Lien vers le texte intégral (Open Access ou abonnement)

14. Paakki JJ, Rahko JS, Kotila A, Mattila ML, Miettunen H, Hurtig TM, Jussila KK, Kuusikko-Gauffin S, Moilanen IK, Tervonen O, Kiviniemi VJ. Co-activation pattern alterations in autism spectrum disorder-A volume-wise hierarchical clustering fMRI study. Brain and behavior. 2021; 11(6): e02174.

INTRODUCTION: There has been a growing effort to characterize the time-varying functional connectivity of resting state (RS) fMRI brain networks (RSNs). Although voxel-wise connectivity studies have examined different sliding window lengths, nonsequential volume-wise approaches have been less common. METHODS: Inspired by earlier co-activation pattern (CAP) studies, we applied hierarchical clustering (HC) to classify the image volumes of the RS-fMRI data on 28 adolescents with autism spectrum disorder (ASD) and their 27 typically developing (TD) controls. We compared the distribution of the ASD and TD groups’ volumes in CAPs as well as their voxel-wise means. For simplification purposes, we conducted a group independent component analysis to extract 14 major RSNs. The RSNs’ average z-scores enabled us to meaningfully regroup the RSNs and estimate the percentage of voxels within each RSN for which there was a significant group difference. These results were jointly interpreted to find global group-specific patterns. RESULTS: We found similar brain state proportions in 58 CAPs (clustering interval from 2 to 30). However, in many CAPs, the voxel-wise means differed significantly within a matrix of 14 RSNs. The rest-activated default mode-positive and default mode-negative brain state properties vary considerably in both groups over time. This division was seen clearly when the volumes were partitioned into two CAPs and then further examined along the HC dendrogram of the diversifying brain CAPs. The ASD group network activations followed a more heterogeneous distribution and some networks maintained higher baselines; throughout the brain deactivation state, the ASD participants had reduced deactivation in 12/14 networks. During default mode-negative CAPs, the ASD group showed simultaneous visual network and either dorsal attention or default mode network overactivation. CONCLUSION: Nonsequential volume gathering into CAPs and the comparison of voxel-wise signal changes provide a complementary perspective to connectivity and an alternative to sliding window analysis.

Lien vers le texte intégral (Open Access ou abonnement)

15. Rancaño KM, Bandini LG, Curtin C, Eliasziw M, Odoms-Young A, Must A. Gender and racial/ethnic differences in food selectivity in children with intellectual disabilities. Journal of applied research in intellectual disabilities : JARID. 2021; 34(6): 1511-20.

BACKGROUND: We examined differences in food selectivity by gender and parent race/ethnicity in children with intellectual disabilities. METHOD: A convenience sample of 56 children with intellectual disabilities was analysed. A modified Youth/Adolescent Food Frequency Questionnaire and a 3-day food record were used to measure child food refusal rate and food repertoire, respectively. RESULTS: Boys were about twice as likely to refuse total foods (rate ratio = 2.34, 95%CI = 1.34-4.09) and fruits (rate ratio = 2.03, 95%CI = 1.04-3.95) and 54% more likely to refuse vegetables (rate ratio = 1.54, 95%CI = 0.93-2.54). Children with Hispanic parents were twice as likely to refuse vegetables compared to children with non-Hispanic White parents (rate ratio = 2.00, 95%CI = 1.03-3.90). In analyses stratified by the presence or absence of co-occurring probable autism spectrum disorder, boys had greater food selectivity than girls. CONCLUSIONS: This study expands our understanding of food selectivity in children with intellectual disabilities.

Lien vers le texte intégral (Open Access ou abonnement)

16. Retzler C, Boehm U, Cai J, Cochrane A, Manning C. Prior information use and response caution in perceptual decision-making: No evidence for a relationship with autistic-like traits. Quarterly journal of experimental psychology (2006). 2021; 74(11): 1953-65.

Interpreting the world around us requires integrating incoming sensory signals with prior information. Autistic individuals have been proposed to rely less on prior information and make more cautious responses than non-autistic individuals. Here, we investigated whether these purported features of autistic perception vary as a function of autistic-like traits in the general population. We used a diffusion model framework, whereby decisions are modelled as noisy evidence accumulation processes towards one of two bounds. Within this framework, prior information can bias the starting point of the evidence accumulation process. Our pre-registered hypotheses were that higher autistic-like traits would relate to reduced starting point bias caused by prior information and increased response caution (wider boundary separation). 222 participants discriminated the direction of coherent motion stimuli as quickly and accurately as possible. Stimuli were preceded with a neutral cue (square) or a directional cue (arrow). 80% of the directional cues validly predicted the upcoming motion direction. We modelled accuracy and response time data using a hierarchical Bayesian model in which starting point varied with cue condition. We found no evidence for our hypotheses, with starting point bias and response caution seemingly unrelated to Adult Autism Spectrum Quotient (AQ) scores. Alongside future research applying this paradigm to autistic individuals, our findings will help refine theories regarding the role of prior information and altered decision-making strategies in autistic perception. Our study also has implications for models of bias in perceptual decision-making, as the most plausible model was one that incorporated bias in both decision-making and sensory processing.

Lien vers le texte intégral (Open Access ou abonnement)

17. Saldarriaga W, González-Teshima LY, Forero-Forero JV, Tang HT, Tassone F. Mosaicism in Fragile X syndrome: A family case series. Journal of intellectual disabilities : JOID. 2021: 1744629521995346.

Fragile X syndrome (FXS) has a classic phenotype, however its expression can be variable among full mutation males. This is secondary to variable methylation mosaicisms and the number of CGG triplet repeats in the non-coding region of the Fragile X Mental Retardation 1 (FMR1) gene, producing a variable expression of the Fragile X Mental Retardation Protein (FMRP). Here we report a family with several individuals affected by FXS: a boy with a hypermethylated FMR1 mutation and a classic phenotype; a man with an FMR1 gene mosaicism in the range of premutation (PM) and full mutation (FM), who has a mild phenotype due to which FXS was initially disregarded; and the cases of four women with a FM and mosaicism. This report highlights the importance of DNA molecular testing for the diagnosis of FXS in patients with developmental delay, intellectual disability and/or autism due to the variable phenotype that occurs in individuals with FMR1 mosaicisms.

Lien vers le texte intégral (Open Access ou abonnement)

18. Tamura Y, Yonehara Y, Horibata Y, Uesugi H, Sawamura T, Sakamoto T. The first described case of late infective endocarditis after implantation of Figulla Flex Ⅱ ASD occluder. Journal of cardiology cases. 2021; 23(5): 214-7.

Infective endocarditis is one of the complications following the percutaneous occlusion of an atrial septal defect (ASD) with a closure device. To the best of our knowledge, no case reports have been published of infective endocarditis associated with the Figulla Flex Ⅱ ASD occluder (FSO; Occlutech GmbH, Jena, Germany). We present the case of a 50-year-old woman who underwent a transcatheter closure of an ASD with FSO almost 2 years prior to presentation to our institution. Echocardiography showed a mobile vegetation (20 × 10 mm), and her blood culture grew β-hemolytic streptococci. Magnetic resonance imaging revealed acute cerebral infarction. Those findings were diagnosed as late infective endocarditis associated with the ASD closure device. The patient was treated with antibiotics and underwent surgical removal of the FSO, which showed incomplete endothelialization, and surgical repair of ASD. After surgery, the patient made a complete recovery without complications or residual shunts. This case highlights the risk of late infective endocarditis in patients after closure of ASD with an FSO with incomplete endothelialization. .

Lien vers le texte intégral (Open Access ou abonnement)

19. Tang L, Levy T, Guillory S, Halpern D, Zweifach J, Giserman-Kiss I, Foss-Feig JH, Frank Y, Lozano R, Belani P, Layton C, Lerman B, Frowner E, Breen MS, De Rubeis S, Kostic A, Kolevzon A, Buxbaum JD, Siper PM, Grice DE. Prospective and detailed behavioral phenotyping in DDX3X syndrome. Molecular autism. 2021; 12(1): 36.

BACKGROUND: DDX3X syndrome is a recently identified genetic disorder that accounts for 1-3% of cases of unexplained developmental delay and/or intellectual disability (ID) in females, and is associated with motor and language delays, and autism spectrum disorder (ASD). To date, the published phenotypic characterization of this syndrome has primarily relied on medical record review; in addition, the behavioral dimensions of the syndrome have not been fully explored. METHODS: We carried out multi-day, prospective, detailed phenotyping of DDX3X syndrome in 14 females and 1 male, focusing on behavioral, psychological, and neurological measures. Three participants in this cohort were previously reported with limited phenotype information and were re-evaluated for this study. We compared results against population norms and contrasted phenotypes between individuals harboring either (1) protein-truncating variants or (2) missense variants or in-frame deletions. RESULTS: Eighty percent (80%) of individuals met criteria for ID, 60% for ASD and 53% for attention-deficit/hyperactivity disorder (ADHD). Motor and language delays were common as were sensory processing abnormalities. The cohort included 5 missense, 3 intronic/splice-site, 2 nonsense, 2 frameshift, 2 in-frame deletions, and one initiation codon variant. Genotype-phenotype correlations indicated that, on average, missense variants/in-frame deletions were associated with more severe language, motor, and adaptive deficits in comparison to protein-truncating variants. LIMITATIONS: Sample size is modest, however, DDX3X syndrome is a rare and underdiagnosed disorder. CONCLUSION: This study, representing a first, prospective, detailed characterization of DDX3X syndrome, extends our understanding of the neurobehavioral phenotype. Gold-standard diagnostic approaches demonstrated high rates of ID, ASD, and ADHD. In addition, sensory deficits were observed to be a key part of the syndrome. Even with a modest sample, we observe evidence for genotype-phenotype correlations with missense variants/in-frame deletions generally associated with more severe phenotypes.

Lien vers le texte intégral (Open Access ou abonnement)

20. Wang T, Zhang Y, Liu L, Wang Y, Chen H, Fan T, Li J, Xia K, Sun Z. Targeted sequencing and integrative analysis of 3,195 Chinese patients with neurodevelopmental disorders prioritized 26 novel candidate genes. Journal of genetics and genomics = Yi chuan xue bao. 2021; 48(4): 312-23.

Neurodevelopmental disorders (NDDs) are a set of complex disorders characterized by diverse and co-occurring clinical symptoms. The genetic contribution in patients with NDDs remains largely unknown. Here, we sequence 519 NDD-related genes in 3,195 Chinese probands with neurodevelopmental phenotypes and identify 2,522 putative functional mutations consisting of 137 de novo mutations (DNMs) in 86 genes and 2,385 rare inherited mutations (RIMs) with 22 X-linked hemizygotes in 13 genes, 2 homozygous mutations in 2 genes and 23 compound heterozygous mutations in 10 genes. Furthermore, the DNMs of 16,807 probands with NDDs are retrieved from public datasets and combine in an integrated analysis with the mutation data of our Chinese NDD probands by taking 3,582 in-house controls of Chinese origin as background. We prioritize 26 novel candidate genes. Notably, six of these genes – ITSN1, UBR3, CADM1, RYR3, FLNA, and PLXNA3 – preferably contribute to autism spectrum disorders (ASDs), as demonstrated by high co-expression and/or interaction with ASD genes confirmed via rescue experiments in a mouse model. Importantly, these genes are differentially expressed in the ASD cortex in a significant manner and involved in ASD-associated networks. Together, our study expands the genetic spectrum of Chinese NDDs, further facilitating both basic and translational research.

Lien vers le texte intégral (Open Access ou abonnement)

21. Whiteley P, Carr K, Shattock P. Research, Clinical, and Sociological Aspects of Autism. Frontiers in psychiatry. 2021; 12: 481546.

The concept of autism continues to evolve. Not only have the central diagnostic criteria that define autism evolved but understanding of the label and how autism is viewed in research, clinical and sociological terms has also changed. Several key issues have emerged in relation to research, clinical and sociological aspects of autism. Shifts in research focus to encompass the massive heterogeneity covered under the label and appreciation that autism rarely exists in a diagnostic vacuum have brought about new questions and challenges. Diagnostic changes, increasing moves towards early diagnosis and intervention, and a greater appreciation of autism in girls and women and into adulthood and old age have similarly impacted on autism in the clinic. Discussions about autism in socio-political terms have also increased, as exemplified by the rise of ideas such as neurodiversity and an increasingly vocal dialogue with those diagnosed on the autism spectrum. Such changes are to be welcomed, but at the same time bring with them new challenges. Those changes also offer an insight into what might be further to come for the label of autism.

Lien vers le texte intégral (Open Access ou abonnement)

22. Williams GL, Wharton T, Jagoe C. Mutual (Mis)understanding: Reframing Autistic Pragmatic « Impairments » Using Relevance Theory. Frontiers in psychology. 2021; 12: 616664.

A central diagnostic and anecdotal feature of autism is difficulty with social communication. We take the position that communication is a two-way, intersubjective phenomenon-as described by the double empathy problem-and offer up relevance theory (a cognitive account of utterance interpretation) as a means of explaining such communication difficulties. Based on a set of proposed heuristics for successful and rapid interpretation of intended meaning, relevance theory positions communication as contingent on shared-and, importantly, mutually recognized-« relevance. » Given that autistic and non-autistic people may have sometimes markedly different embodied experiences of the world, we argue that what is most salient to each interlocutor may be mismatched. Relevance theory would predict that where this salient information is not (mutually) recognized or adjusted for, mutual understanding may be more effortful to achieve. This paper presents the findings from a small-scale, linguistic ethnographic study of autistic communication featuring eight core autistic participants. Each core autistic participant engaged in three naturalistic conversations around the topic of loneliness with: (1) a familiar, chosen conversation partner; (2) a non-autistic stranger and (3) an autistic stranger. Relevance theory is utilized as a frame for the linguistic analysis of the interactions. Mutual understanding was unexpectedly high across all types of conversation pairings. In conversations involving two autistic participants, flow, rapport and intersubjective attunement were significantly increased and in three instances, autistic interlocutors appeared to experience improvements in their individual communicative competence contrasted with their other conversations. The findings have the potential to guide future thinking about how, in practical terms, communication between autistic and non-autistic people in both personal and public settings might be improved.

Lien vers le texte intégral (Open Access ou abonnement)