1. Arslan A, Fang Z, Wang M, Tan Y, Cheng Z, Chen X, Guan Y, L JP, Yoo B, Bejerano G, Peltz G. Analysis of structural variation among inbred mouse strains. BMC Genomics;2023 (Mar 2);24(1):97.

BACKGROUND: ‘Long read’ sequencing methods have been used to identify previously uncharacterized structural variants that cause human genetic diseases. Therefore, we investigated whether long read sequencing could facilitate genetic analysis of murine models for human diseases. RESULTS: The genomes of six inbred strains (BTBR T + Itpr3tf/J, 129Sv1/J, C57BL/6/J, Balb/c/J, A/J, SJL/J) were analyzed using long read sequencing. Our results revealed that (i) Structural variants are very abundant within the genome of inbred strains (4.8 per gene) and (ii) that we cannot accurately infer whether structural variants are present using conventional short read genomic sequence data, even when nearby SNP alleles are known. The advantage of having a more complete map was demonstrated by analyzing the genomic sequence of BTBR mice. Based upon this analysis, knockin mice were generated and used to characterize a BTBR-unique 8-bp deletion within Draxin that contributes to the BTBR neuroanatomic abnormalities, which resemble human autism spectrum disorder. CONCLUSION: A more complete map of the pattern of genetic variation among inbred strains, which is produced by long read genomic sequencing of the genomes of additional inbred strains, could facilitate genetic discovery when murine models of human diseases are analyzed.

Lien vers le texte intégral (Open Access ou abonnement)

2. Arutiunian V, Arcara G, Buyanova I, Davydova E, Pereverzeva D, Sorokin A, Tyushkevich S, Mamokhina U, Danilina K, Dragoy O. Neuromagnetic 40 Hz Auditory Steady-State Response in the left auditory cortex is related to language comprehension in children with Autism Spectrum Disorder. Prog Neuropsychopharmacol Biol Psychiatry;2023 (Mar 2);122:110690.

Language impairment is comorbid in most children with Autism Spectrum Disorder (ASD), but its neural mechanisms are still poorly understood. Some studies hypothesize that the atypical low-level sensory perception in the auditory cortex accounts for the abnormal language development in these children. One of the potential non-invasive measures of such low-level perception can be the cortical gamma-band oscillations registered with magnetoencephalography (MEG), and 40 Hz Auditory Steady-State Response (40 Hz ASSR) is a reliable paradigm for eliciting auditory gamma response. Although there is research in children with and without ASD using 40 Hz ASSR, nothing is known about the relationship between this auditory response in children with ASD and their language abilities measured directly in formal assessment. In the present study, we used MEG and individual brain models to investigate 40 Hz ASSR in primary-school-aged children with and without ASD. It was also used to assess how the strength of the auditory response is related to language abilities of children with ASD, their non-verbal IQ, and social functioning. A total of 40 children were included in the study. The results demonstrated that 40 Hz ASSR was reduced in the right auditory cortex in children with ASD when comparing them to typically developing controls. Importantly, our study provides the first evidence of the association between 40 Hz ASSR in the language-dominant left auditory cortex and language comprehension in children with ASD. This link was domain-specific because the other brain-behavior correlations were non-significant.

Lien vers le texte intégral (Open Access ou abonnement)

3. Chen YJ, Duku E, Zaidman-Zait A, Szatmari P, Smith IM, Ungar WJ, Zwaigenbaum L, Vaillancourt T, Kerns C, Bennett T, Elsabbagh M, Thompson A, Georgiades S. Variable patterns of daily activity participation across settings in autistic youth: A latent profile transition analysis. Autism;2023 (Feb 28):13623613231154729.

What people do or engage in in their daily lives, or daily life participation, is often linked to their state of being happy and healthy, as well as potential for living independently. To date, little research has been conducted on daily activity participation by autistic youth at home, at school or in the community. Learning more about individual differences in participation levels and what might influence them can help to create custom supports for autistic youth and their families. In this study, 158 caregivers of autistic youth were asked how often their children took part in 25 common activities at two assessments, about one year apart. The analysis showed three profiles for each of the home and school settings and two profiles for the community setting. These profiles reflected distinct patterns in how often autistic youth took part in various daily activities, particularly in doing homework, school club activities and community gatherings. Most autistic youth were in profiles marked by often taking part at home but less often at school and in the community, and about three-fourths of them tended to stay in the same profile over time. Autistic youth with limited participation profiles were more likely to have lower scores on measures of cognitive ability and daily life skills and more challenging behaviour, and faced more barriers in their environment. These findings show how important it is to think about each autistic person’s strengths and weaknesses, and changing needs, to better support their daily life participation.

Lien vers le texte intégral (Open Access ou abonnement)

4. Eckes T, Buhlmann U, Holling HD, Möllmann A. Comprehensive ABA-based interventions in the treatment of children with autism spectrum disorder – a meta-analysis. BMC Psychiatry;2023 (Mar 2);23(1):133.

BACKGROUND: Many studies display promising results for interventions that are based on Applied Behavior Analysis (ABA) in the treatment of autism spectrum disorder (ASD). METHODS: This meta-analysis assessed the effects of such treatments on developmental outcomes in children with ASD and on parental stress based on 11 studies with 632 participants. RESULTS: Compared to treatment as usual, minimal or no treatment, comprehensive ABA-based interventions showed medium effects for intellectual functioning (standardized mean difference SMD = 0.51, 95% CI [0.09; 0.92]) and adaptive behavior (SMD = 0.37, 95% CI [0.03; 0.70]). Language abilities, symptom severity or parental stress did not improve beyond the improvement in control groups. Moderator analyses indicate that language abilities at intake could influence the effect sizes and the influence of treatment intensity might decrease with older age. CONCLUSIONS: Practical implications and limitations are discussed.

Lien vers le texte intégral (Open Access ou abonnement)

5. Feil D, Abrishamcar S, Christensen GM, Vanker A, Koen N, Kilanowski A, Hoffman N, Wedderburn CJ, Donald KA, Kobor MS, Zar HJ, Stein DJ, Hüls A. DNA methylation as a potential mediator of the association between indoor air pollution and neurodevelopmental delay in a South African birth cohort. Clin Epigenetics;2023 (Feb 28);15(1):31.

BACKGROUND: Exposure to indoor air pollution during pregnancy has been linked to neurodevelopmental delay in toddlers. Epigenetic modification, particularly DNA methylation (DNAm), may explain this link. In this study, we employed three high-dimensional mediation analysis methods (HIMA, DACT, and gHMA) followed by causal mediation analysis to identify differentially methylated CpG sites and genes that mediate the association between indoor air pollution and neurodevelopmental delay. Analyses were performed using data from 142 mother to child pairs from a South African birth cohort, the Drakenstein Child Health Study. DNAm from cord blood was measured using the Infinium MethylationEPIC and HumanMethylation450 arrays. Neurodevelopment was assessed at age 2 years using the Bayley Scores of Infant and Toddler Development, 3rd edition across four domains (cognitive development, general adaptive behavior, language, and motor function). Particulate matter with an aerodynamic diameter of 10 μm or less (PM(10)) was measured inside participants’ homes during the second trimester of pregnancy. RESULTS: A total of 29 CpG sites and 4 genes (GOPC, RP11-74K11.1, DYRK1A, RNMT) were identified as significant mediators of the association between PM(10) and cognitive neurodevelopment. The estimated proportion mediated (95%-confidence interval) ranged from 0.29 [0.01, 0.86] for cg00694520 to 0.54 [0.11, 1.56] for cg05023582. CONCLUSIONS: Our findings suggest that DNAm may mediate the association between prenatal PM(10) exposure and cognitive neurodevelopment. DYRK1A and several genes that our CpG sites mapped to, including CNKSR1, IPO13, IFNGR1, LONP2, and CDH1, are associated with biological pathways implicated in cognitive neurodevelopment and three of our identified CpG sites (cg23560546 [DAPL1], cg22572779 [C6orf218], cg15000966 [NT5C]) have been previously associated with fetal brain development. These findings are novel and add to the limited literature investigating the relationship between indoor air pollution, DNAm, and neurodevelopment, particularly in low- and middle-income country settings and non-white populations.

Lien vers le texte intégral (Open Access ou abonnement)

6. Forby L, Anderson NC, Cheng JT, Foulsham T, Karstadt B, Dawson J, Pazhoohi F, Kingstone A. Reading the room: Autistic traits, gaze behaviour, and the ability to infer social relationships. PLoS One;2023;18(3):e0282310.

Individuals high in autistic traits can have difficulty understanding verbal and non-verbal cues, and may display atypical gaze behaviour during social interactions. The aim of this study was to examine differences among neurotypical individuals with high and low levels of autistic traits with regard to their gaze behaviour and their ability to assess peers’ social status accurately. Fifty-four university students who completed the 10-item Autism Quotient (AQ-10) were eye-tracked as they watched six 20-second video clips of people (« targets ») involved in a group decision-making task. Simulating natural, everyday social interactions, the video clips included moments of debate, humour, interruptions, and cross talk. Results showed that high-scorers on the AQ-10 (i.e., those with more autistic traits) did not differ from the low-scorers in either gaze behaviour or assessing the targets’ relative social status. The results based on this neurotypical group of participants suggest that the ability of individuals high in autistic traits to read social cues may be preserved in certain tasks crucial to navigating day-to-day social relationships. These findings are discussed in terms of their implications for theory of mind, weak central coherence, and social motivation theories of autism.

Lien vers le texte intégral (Open Access ou abonnement)

7. Guo P, Yang X, Guo X, Yang H, Pan J, Li Y. Dietary fish oil improves autistic behaviors and gut homeostasis by altering the gut microbial composition in a mouse model of fragile X syndrome. Brain Behav Immun;2023 (Feb 28);110:140-151.

Fragile X syndrome (FXS) is the most common inherited intellectual disability, caused by a lack of the fragile X mental retardation protein (FMRP). Individuals with neurodevelopmental disorders frequently experience gastrointestinal problems that are primarily linked to gut microbial dysbiosis, inflammation, and increased intestinal permeability. Omega-3 polyunsaturated fatty acids (omega-3 PUFAs) are non-pharmacological agents that exert potential therapeutic effects against neurological disorders. However, it is unclear whether omega-3 PUFAs improve autistic behaviors in fragile X syndrome (FXS) by altering the gut microbial composition. Here, we describe gastrointestinal problems in Fmr1 knockout (KO) mice. FMRP deficiency causes intestinal homeostasis dysfunction in mice. Fish oil (FO) as a source of omega-3 PUFAs reduces intestinal inflammation but increases the mRNA and protein levels of TJP3 in the colon of juvenile Fmr1 KO mice. Fecal microbiota transplantation from FO-fed Fmr1 KO mice increased the gut abundance of Akkermansia and Gordonibacter in recipient Fmr1 KO mice and improved gut homeostasis and autistic behaviors. Our findings demonstrate that omega-3 PUFAs improve autistic behaviors and gut homeostasis in FMRP-deficient mice by suppressing gut microbiota dysbiosis, thereby presenting a novel therapeutic approach for juvenile FXS treatment.

Lien vers le texte intégral (Open Access ou abonnement)

8. Guo X, Tang P, Hou C, Li R. Mendelian randomization investigation highlights different roles of selenium status in mental disorders. Prog Neuropsychopharmacol Biol Psychiatry;2023 (Mar 2);122:110694.

Observational studies have suggested a relationship between selenium status and mental disorders (MDs). However, it remains unclear whether selenium status was causally associated with MDs. Thus, we performed a two-sample Mendelian randomization analysis using genome-wide association studies (GWAS) summary statistics to investigate the causal effects of selenium levels on seven MDs, including schizophrenia, major depressive disorder (MDD), autism spectrum disorder (ASD), bipolar disorder (BD), anorexia nervosa (AN), attention-deficit/hyperactivity disorder (ADHD), and panic disorder (PD). Strong genetic instruments of blood selenium (n = 9) and blood-toenail selenium (n = 12) were applied to the above seven MDs GWAS datasets from Psychiatric Genomics Consortium, which were further replicated in the FinnGen Biobank. The inverse-variance weighted method was employed to calculate the causal effects. The results showed that genetically predicted blood selenium levels were associated with a decreased risk of schizophrenia (odds ratio [OR] = 0.90, 95% CI: 0.87-0.95) and AN (OR = 0.87, 95% CI: 0.77-0.97). However, both blood and blood-toenail selenium levels were linked to an increased risk of MDD (blood: OR = 1.08, 95% CI: 1.05-1.12; blood-toenail: OR = 1.08, 95% CI: 1.04-1.13) and ASD (blood: OR = 1.11, 95% CI: 1.05-1.17; blood-toenail: OR = 1.13, 95% CI: 1.05-1.21), respectively. No obvious associations were found between selenium levels and BD as well as ADHD. Our findings highlighted a protective role of selenium in SZ and AN, while a risk effect in MDD and ASD. Further studies are required to verify the underlying mechanism mediating the unequal effects of Se on different MDs, which will pave a new path for the intervention of MDs.

Lien vers le texte intégral (Open Access ou abonnement)

9. Hensley JL, Beydoun HA. Quasi-experimental Controlled Study on the Effect of Autism Resource Clinic Guardian Attendance at a Military Treatment Facility. Mil Med;2023 (Feb 28)

INTRODUCTION: Autism spectrum disorder (ASD) is a complex neurodevelopmental condition that requires multidisciplinary care. Evidence-based practice indicates that early intervention may improve long-term ASD outcomes. The Autism Resource Clinic (ARC) provides an educational session for guardians empowering them to build a personalized ASD team for their child. We examined the impact of guardian attendance of an ARC at a Military Treatment Facility on time to initiation of patient services and guardian stress level. MATERIALS AND METHODS: A quasi-experimental controlled study was conducted comparing a group of guardians attending the ARC with a group of guardians not attending the ARC following a child’s initial ASD diagnosis. ARC speakers included medical, county/state, community/military, and advocacy experts. Surveys were completed at diagnosis, 1, 2, and 3 mo postdiagnosis. Initiation of patient services and Parental Stress Scale scores were compared between groups using independent samples t-test, chi-square tests, or nonparametric tests, as appropriate. RESULTS: Use of Applied Behavioral Analysis was significantly higher among ARC attendees vs. nonattendees (73.3% vs. 33.3%, P = 0.028). County early intervention was more frequent among ARC attendees versus nonattendees (40% vs. 13.3%, P = 0.09). Of borderline significance, median time to initiation of genetics services was greater in ARC attendees vs. nonattendees (106 vs. 65.5, P = 0.10). The two groups did not differ on changes in Parental Stress Scale score from baseline to follow-up months 1, 2, or 3. CONCLUSIONS: Although ARC did not influence time to initiation of patient services or guardian stress level, attendance of ARC was associated with more frequent use of Applied Behavioral Analysis services and county early intervention services. This pilot study is unique as it targets guardians of ASD patients within military treatment facilities. Study limitations include data collection during the coronavirus disease 2019 pandemic, sequential evaluation of experimental and control groups, sample size and generalizability. A large, multicenter, randomized controlled trial is required to better assess the impact of this educational opportunity among military populations.

Lien vers le texte intégral (Open Access ou abonnement)

10. Ivanoff AE, Ivanoff CS. Ring chromosome 14 syndrome: what the dentist should know to manage children with r(14) effec-tively. Folia Med (Plovdiv);2023 (Feb 28);65(1):20-29.

INTRODUCTION: Ring chromosome 14 syndrome, or r(14), is a rare genetic disorder characterized by distinctive facial features, intractable epilepsy, delayed development, intellectual disability, and autism spectrum disorder. With less than 100 documented cases worldwide, the disease is not well known or fully studied. Furthermore, the literature offers little guidance to aid dentists in the management of these patients as r(14) remains undocumented in the dental literature. AIM: To investigate the manifestations and challenges faced by a group of subjects suffering from r(14), to raise awareness of this syndrome, and to provide tips and suggestions that dentists may find helpful to manage r(14) children effectively. MATERIALS AND METHODS: A voluntary survey was administered to the caretakers of 13 r(14) patients who, as of 2019, were registered in the NORD (National Organization for Rare Diseases) global data bank (Ring 14 USA Outreach). The patients were assessed for age, gender, geographic distribution, phenotype, physical appearance, maxillofacial characteristics, presence of oral conditions and abnormalities, malocclusion, epileptic seizures, cognitive abilities, speech, muscle tone, nutrition, autism, and other developmental and behavioral points of interest. RESULTS: Of the 13 patients queried, 7 were male and 6 were female. The age of the patients ranged from 5 to 49 years. Ten patients were of European ancestry and three were Hispanic, all residing across the U.S. The majority of patients were diagnosed as infants, shortly after commencement of uncontrollable seizures. All the patients had microcephaly and presented with Class II malocclusions. More frequent occlusal anomalies and conditions included diastemata of the anterior teeth, congenitally missing teeth, crowding, and drooling. The majority of subjects was unable to speak, suffered from intractable seizures, and frequently exhibited behavioral outbursts. CONCLUSIONS: A child with r(14) may present a considerable challenge to the dentist and staff, but the dental problems of r(14) children are, for the most part, like those of any other patient and can often be handled by the dentist. Depending on the severity of symptoms, some children with r(14) may be as treatable in the dental office as any other child.

Lien vers le texte intégral (Open Access ou abonnement)

11. Jin X, Zhu H, Cao W, Zou X, Chen J. Identifying activity level related movement features of children with ASD based on ADOS videos. Sci Rep;2023 (Mar 1);13(1):3471.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that affects about 2% of children. Due to the shortage of clinicians, there is an urgent demand for a convenient and effective tool based on regular videos to assess the symptom. Computer-aided technologies have become widely used in clinical diagnosis, simplifying the diagnosis process while saving time and standardizing the procedure. In this study, we proposed a computer vision-based motion trajectory detection approach assisted with machine learning techniques, facilitating an objective and effective way to extract participants’ movement features (MFs) to identify and evaluate children’s activity levels that correspond to clinicians’ professional ratings. The designed technique includes two key parts: (1) Extracting MFs of participants’ different body key points in various activities segmented from autism diagnostic observation schedule (ADOS) videos, and (2) Identifying the most relevant MFs through established correlations with existing data sets of participants’ activity level scores evaluated by clinicians. The research investigated two types of MFs, i.e., pixel distance (PD) and instantaneous pixel velocity (IPV), three participants’ body key points, i.e., neck, right wrist, and middle hip, and five activities, including Table-play, Birthday-party, Joint-attention, Balloon-play, and Bubble-play segmented from ADOS videos. Among different combinations, the high correlations with the activity level scores evaluated by the clinicians (greater than 0.6 with p < 0.001) were found in Table-play activity for both the PD-based MFs of all three studied key points and the IPV-based MFs of the right wrist key point. These MFs were identified as the most relevant ones that could be utilized as an auxiliary means for automating the evaluation of activity levels in the ASD assessment.

Lien vers le texte intégral (Open Access ou abonnement)

12. Knight EJ, Freedman EG, Myers EJ, Berruti AS, Oakes LA, Cao CZ, Molholm S, Foxe JJ. Severely attenuated visual feedback processing in children on the autism spectrum. J Neurosci;2023 (Feb 27)

Individuals on the autism spectrum often exhibit atypicality in their sensory perception, but the neural underpinnings of these perceptual differences remain incompletely understood. One proposed mechanism is an imbalance in higher-order feedback re-entrant inputs to early sensory cortices during sensory perception, leading to increased propensity to focus on local object features over global context. We explored this theory by measuring visual evoked potentials during contour integration as considerable work has revealed that these processes are largely driven by feedback inputs from higher-order ventral visual stream regions. We tested the hypothesis that autistic individuals would have attenuated evoked responses to illusory contours compared to neurotypical controls. Electrophysiology was acquired while 29 autistic and 31 neurotypical children (7-17 years-old, inclusive of both males and females) passively viewed a random series of Kanizsa figure stimuli, each consisting of four inducers that were aligned either at random rotational angles or such that contour integration would form an illusory square. Autistic children demonstrated attenuated automatic contour integration over lateral occipital regions relative to neurotypical controls. The data are discussed in terms of the role of predictive feedback processes on perception of global stimulus features and the notion that weakened « priors » may play a role in the visual processing anomalies seen in autism.SIGNIFICANCE STATEMENT:Children on the autism spectrum differ from typically developing children in many aspects of their processing of sensory stimuli. One proposed mechanism for these differences is an imbalance in higher order feedback to primary sensory regions, leading to an increased focus on local object features rather than global context. However, systematic investigation of these feedback mechanisms remains limited. Using electroencephalography (EEG) and a visual illusion paradigm that is highly dependent on intact feedback processing, we demonstrated significantly disruptions to visual feedback processing in children with autism. This provides much needed experimental evidence that advances our understanding of the contribution of feedback processing to visual perception in autism spectrum disorder.

Lien vers le texte intégral (Open Access ou abonnement)

13. Luo L, Chen J, Wu Q, Yuan B, Hu C, Yang T, Wei H, Li T. Prenatally VPA exposure is likely to cause autistic-like behavior in the rats offspring via TREM2 down-regulation to affect the microglial activation and synapse alterations. Environ Toxicol Pharmacol;2023 (Mar 2):104090.

Microglial dysfunction has been reported in the valproic acid (VPA)-induced autism spectrum disorder (ASD) rat models. However, how does prenatal VPA exposure affect microglia remains to be elucidated. The triggering receptor expressed on myeloid cells 2 (TREM2) is revealed to be implicated in a range of microglia functions. However, reports on the association between TREM2 and VPA-induced ASD rat models are scarce. Our results showed that prenatal VPA exposure induced autistic-like behaviors, downregulated the levels of TREM2, up-regulated microglial activation, dysregulated microglial polarization, and altered synapse in offspring. TREM2 overexpression partly ameliorated microglia dysfunction and autistic-like behaviors in prenatal VPA-exposed rats. Our findings demonstrated that prenatally VPA exposure is likely to cause autistic-like behavior in the rat offspring via TREM2 down-regulation to affect the microglial activation, microglial polarization and synaptic pruning of microglia for the first time.

Lien vers le texte intégral (Open Access ou abonnement)

14. Magán-Maganto M, Canal-Bedia R, Bejarano-Martín Á, Martín-Cilleros MV, Hernández-Fabián A, Calvarro-Castañeda AL, Roeyers H, Jenaro-Río C, Posada de la Paz M. Predictors of autism spectrum disorder diagnosis in a spanish sample of preterm children with very low birthweight: A cross-sectional study. Health Sci Rep;2023 (Mar);6(3):e1143.

BACKGROUND AND AIMS: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with a higher likelihood of being diagnosed in preterm populations. Likewise, low birthweight has also been connected with an increased likelihood of ASD. The objectives were to study the frequency and define the relationship between ASD, gestational age, birthweight, and growth percentiles for preterm children. METHODS: A sample of preterm children with very low birthweight was selected from the Spanish population at 7-10 years old. Families were contacted from the hospital, and they were offered an appointment to conduct a neuropsychological assessment. The children who showed signs of ASD were referred to the diagnostic unit for differential diagnosis. RESULTS: A total of 57 children completed full assessments, with 4 confirmed ASD diagnoses. The estimated prevalence was 7.02%. There were statistically significant weak correlations between ASD and gestational age (τb = -0.23), and birthweight (τb = -0.25), suggesting there is a higher likelihood of developing ASD for those born smaller or earlier in their gestation. CONCLUSION: These results could improve ASD detection and outcomes for this vulnerable population while also supporting and enhancing previous findings.

Lien vers le texte intégral (Open Access ou abonnement)

15. Mesa A. Euphemism has no place in the pages of autism research. Autism Res;2023 (Mar 2)

Lien vers le texte intégral (Open Access ou abonnement)

16. Min S, Gandal MJ, Kopp RF, Liu C, Chen C. No Increased Detection of Nucleic Acids of CNS-related Viruses in the Brains of Patients with Schizophrenia, Bipolar Disorder, and Autism Spectrum Disorder. Schizophr Bull;2023 (Feb 28)

BACKGROUND AND HYPOTHESIS: Viral infections are increasingly recognized in the etiology of psychiatric disorders based on epidemiological and serological studies. Few studies have analyzed viruses directly within the brain and no comprehensive investigation of viral infection within diseased brains has been completed. This study aims to determine whether viral infection in brain tissues is a risk factor for 3 major psychiatric disorders, including schizophrenia, bipolar disorder, and autism spectrum disorder. STUDY DESIGN: This study directly evaluated the presence of viral DNA or RNA in 1569 brains of patients and controls using whole-genome sequencing and RNA sequencing data with 4 independent cohorts. The PathSeq tool was used to identify known human viruses in the genome and transcriptome of patients and controls. STUDY RESULTS: A variety of DNA and RNA viruses related to the central nervous system were detected in the brains of patients with major psychiatric disorders, including viruses belonging to Herpesviridae, Polyomaviridae, Retroviridae, Flaviviridae, Parvoviridae, and Adenoviridae. However, no consistent significant differences were found between patients and controls in terms of types and amount of virus detected at both DNA and RNA levels. CONCLUSIONS: The findings of this study do not suggest an association between viral infection in postmortem brains and major psychiatric disorders.

Lien vers le texte intégral (Open Access ou abonnement)

17. Nakai N, Takumi T. [Analysis of cortical network dynamics in the behavioral state of a mouse model of autism]. Nihon Yakurigaku Zasshi;2023;158(2):150-153.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by behavioral abnormalities such as poor social communication and stereotyped/repetitive behaviors. Functional dynamics among multiple cortical areas are associated with processing sensory information and planning and executing behavioral expressions. However, the reconfiguration of large-scale functional network dynamics during behaviors remains to be elucidated in ASD. In this review, we describe our virtual reality (VR) based real-time imaging system which allowed us to investigate wide-field cortical activity in voluntarily behaving mice. We previously generated a mouse model of ASD with chromosome 15q11-13 duplication (15q dup), one of the most frequent genomic abnormalities, and reported that 15q dup mice display ASD-like behaviors. Using this system, we examined the functional cortical network during behaviors in 15q dup mice. Pair-wise correlation of cortical area activity on a time scale of a second was calculated to represent the dynamic state of cortical functional connectivity (FC). A graph theoretical network analysis was then conducted to illustrate rapid and robust behavior-state-dependent cortical network reconfiguration. Our VR-based real-time imaging system provides invaluable information to understand FC dynamics linked to a behavioral abnormality of neuropsychiatric disorders.

Lien vers le texte intégral (Open Access ou abonnement)

18. O’Donoghue M, Kennedy N, Forbes J, Murphy CA. Stakeholder Perceptions of the Acceptability of Peer-Mediated Intervention for Minimally Speaking Preschoolers on the Autism Spectrum. J Autism Dev Disord;2023 (Mar 1):1-18.

Peer mediated intervention (PMI) is an evidence-based approach to supporting social and communication development for children on the autism spectrum. For PMI to be integrated into everyday practice, it needs to be acceptable to stakeholders. This article engaged with autistic individuals, early childhood educators, parents, and speech and language pathologists on the prospective acceptability of implementing PMI with minimally speaking preschoolers in inclusive preschool settings. Focus groups and semi-structured interviews were conducted. The transcriptions were analyzed qualitatively using reflexive thematic analysis. Stakeholders described PMI as an acceptable intervention approach for this population and provided valuable insights to inform the development and implementation of PMIs. Attention needs to be paid to how to support preschools to adopt a PMI-friendly philosophy.

Lien vers le texte intégral (Open Access ou abonnement)

19. Rodgers J, Goodwin J, Nielsen E, Bhattarai N, Heslop P, Kharatikoopaei E, O’Connor RC, Ogundimu E, Ramsay SE, Steele K, Townsend E, Vale L, Walton E, Wilson C, Cassidy S. Adapted suicide safety plans to address self-harm, suicidal ideation, and suicide behaviours in autistic adults: protocol for a pilot randomised controlled trial. Pilot Feasibility Stud;2023 (Feb 28);9(1):31.

BACKGROUND: Suicide prevention is a national priority for the UK government. Autistic people are at greater risk of experiencing self-harm and suicidal thoughts and behaviours than the general population. Safety plans are widely used in suicide prevention but have not yet been designed with and for autistic people. We developed the first safety plan specifically targeting suicidality in autistic adults: the Autism Adapted Safety Plan (AASP). It consists of a prioritised list of hierarchical steps that can be used prior to or during a crisis to mitigate risk of self-harm and suicidal behaviour. This is a pilot study that aims to assess the feasibility and acceptability of the AASPs and the research processes, including the response rates, potential barriers and reach of AASPs, methods of recruitment, what comprises usual care, and economic evaluation methods/tools. METHODS: This is an external pilot randomised controlled trial of a suicide prevention tool aimed at mitigating the risk of self-harm and suicidal behaviour in autistic adults: AASPs. Participants will be assessed at baseline and followed up 1 month and 6 months later. Assessments include questions about self-harm, suicidality, service use, and their experience of the AASP/taking part in the study. Autistic adults who have a clinical autism diagnosis and self-reported history of self-harm, suicidal thoughts, or suicidal behaviours within the last 6 months will be invited to take part in the study. Informed consent will be obtained. Participants will be recruited via community and third sector services (including community settings, autism charities, and mental health charities). They may also « self-refer » into the study through social media recruitment and word of mouth. Ninety participants will be randomised to either develop an AASP or receive their usual care in a 1:1 ratio. DISCUSSION: The present study will provide an evaluation of the suitability of the processes that would be undertaken in a larger definitive study, including recruitment, randomisation, methods, questionnaires, outcome measures, treatment, and follow-up assessments. TRIAL REGISTRATION: ISRCTN70594445, Protocol v4: 8/2/22.

Lien vers le texte intégral (Open Access ou abonnement)

20. Sato M, Kimura M, Ueda A, Miyamoto Y. [Imaging brain activity in virtual reality: abnormal hippocampal cognitive maps in autism model mice]. Nihon Yakurigaku Zasshi;2023;158(2):139-143.

The symptoms and behavioral abnormalities of brain diseases are thought to be caused by the dysfunction of neural circuits formed by numerous neurons. Virtual reality (VR) is used for behavioral tasks under head fixation and has the advantage of precise control of experimental conditions. In this review, we first overview the application of VR in rodent neuroscience, introduce our research on two-photon calcium imaging of the hippocampus of autism spectrum disorder (ASD) model mice navigating a VR environment, and then discuss how hippocampal dysfunction can relate to ASD phenotypes. By combining a VR system with two-photon microscopy, we clarified the formation of hippocampal CA1 place cell maps in mice undergoing spatial learning in VR. As mice learned, the number of place cells increased, and the density of cells that responded to places with behaviorally relevant features such as rewards and landmarks increased more than cells active elsewhere. Furthermore, many stable place cells responded at landmark and reward locations. Shank2-deficient ASD model mice spent more time running and received more rewards. In their hippocampal maps, the proportion of cells active at landmarks did not increase, whereas the proportion of cells active at rewards excessively increased. Individuals with ASD are known to show unique tendencies in their perception and cognition of the world around them, but the detailed brain mechanisms remain unclear. It is thus possible that some ASD cases involve cognitive mapping abnormalities, such as the distortion of hippocampal information representation that our study revealed.

Lien vers le texte intégral (Open Access ou abonnement)

21. Siafis S, Leucht S. Clinician- versus caregiver-rated scales as outcome measures of repetitive-restricted behaviors in clinical trials of autism: A systematic review and meta-analysis. Eur Neuropsychopharmacol;2023 (Mar 2);70:56-62.

The agreement between treatment effects measured by clinician- and caregiver-ratings of repetitive-restricted behaviors (RRBs) is important for clinical practice and research but is still unclear. Therefore, we conducted a post-hoc meta-analysis of placebo-controlled randomized-controlled trials (RCTs) investigating pharmacological and dietary-supplement treatments for autism that reported both clinician- and caregiver-ratings of RRBs. Treatment effects between medications and placebo were quantified with standardized mean differences (SMDs). The agreement between clinician- and caregiver-rated SMDs was investigated with an intraclass correlation coefficient (ICC) and random-effects meta-analysis of their difference (Δg). A meta-regression investigated the association between clinician (dependent) and caregiver-rated SMDs (independent variable). Certainty in the evidence was evaluated using the GRADE approach. We identified 15 eligible placebo-controlled RCTs with 1567 participants, from which 13 included children/adolescents and 9 reported data for the pair of the clinician-rated Yale-Brown Obsessive Compulsive Scale (YBOCS) and the caregiver-rated Aberrant Behavior Checklist-Stereotypic Behavior (ABC-S). There was on average a good agreement between clinician- and caregiver-rated SMDs (ICC=0.84, 95% confidence intervals [0.55, 0.95]), no clear difference between them (Δg=0.08, 95%CI[-0.06, 0.21], 95% prediction intervals [-0.16, 0.31]), and the beta of the meta-regression was 0.62, 95%CI[0.27, 0.97]. The certainty of the evidence was low due to concerns in imprecision and inconsistency. Our analysis showed on average a good agreement between clinician- and caregiver-rated treatment effects in RRBs, yet discordance could be expected in future RCTs, given the wide prediction intervals. It is also not certain that these results could be generalizable to other rating scales and intervention modalities. Ethics committee approval: Not applicable as a meta-analysis of previously published studies..

Lien vers le texte intégral (Open Access ou abonnement)

22. Sinha C, Lecavalier L, Johnson CR, Taylor C, Mulligan A, Buckley D, Alder ML, Scahill L. Qualitative Exploration Toward the Development of a Parent-Rated Scale for Insomnia in Children with Autism Spectrum Disorder. J Autism Dev Disord;2023 (Mar 1)

Toward the development of a new parent-rating for insomnia, this multi-site qualitative study explored sleep problems and related impacts in children with autism spectrum disorder (ASD) and their families. To ensure content validity of the measure, we conducted six focus groups with caregivers (N = 25) of 24 children (age 3 to 18 years) with ASD. Based on parent report, all children had a history of mild or greater insomnia. The focus group transcripts were systematically coded to identify major themes. Verbatim comments from caretakers were used to generate 134 candidate items. Further review by the research team and an expert panel followed by individual cognitive interviews with 12 parents reduced the item bank to 40. The thematic analysis of focus group transcripts identified 7 categories: (1) Trouble falling asleep; (2) trouble staying asleep; (3) early morning waking; (4) bedtime routines; (5) parental strategies for bedtime management; (6) impact of sleep problems on the child; and (7) impact of sleep problems on the family. The Flesch Kincaid Grade Level of the 40-item version was 7.2 (seventh grade reading level). Insomnia in children with ASD shares features in common with insomnia in the general pediatric population. However, perhaps owing to autistic features such as insistence on sameness, sensory sensitivities, communication impairments, insomnia in children with ASD appears to have unique behavioral manifestations. Content validity and item clarity of the 40-item bank were supported by expert panel review and cognitive interviews with caregivers of children with ASD.

Lien vers le texte intégral (Open Access ou abonnement)

23. Spinazzi NA, Santoro JD, Pawlowski K, Anzueto G, Howe YJ, Patel LR, Baumer NT. Co-occurring conditions in children with Down syndrome and autism: a retrospective study. J Neurodev Disord;2023 (Mar 2);15(1):9.

BACKGROUND: Down syndrome (DS) is one of the most common genetic causes of intellectual disability, and it is associated with an increased incidence of numerous co-occurring conditions. Autism spectrum disorder (ASD) is common in persons with DS, with rates reported as high as 39%. However, little is known regarding co-occurring conditions in children with both DS and ASD. METHODS: A single-center retrospective review of prospective longitudinally collected clinical data was performed. Any patient with a confirmed diagnosis of DS evaluated at a large, specialized Down Syndrome Program in a tertiary pediatric medical center between March 2018 and March 2022 was included. A standardized survey which included demographic and clinical questions was administered during each clinical evaluation. RESULTS: In total, 562 individuals with DS were included. The median age was 10 years (IQR: 6.18-13.92). Of this group, 72 (13%) had a co-occurring diagnosis of ASD (DS+ASD). Individuals with DS+ASD were more likely to be male (OR 2.23, CI 1.29-3.84) and had higher odds of a current or prior diagnosis of constipation (OR 2.19, CI 1.31-3.65), gastroesophageal reflux (OR 1.91, CI 1.14-3.21), behavioral feeding difficulties (OR 2.71, CI 1.02-7.19), infantile spasms (OR 6.03, CI 1.79-20.34) and scoliosis (OR 2.73, CI 1.16-6.40). There were lower odds of congenital heart disease in the DS+ASD group (OR 0.56, CI 0.34-0.93). There was no observed difference in prematurity or Neonatal Intensive Care Unit complications between groups. Individuals with DS+ASD had similar odds of having a history of congenital heart defect requiring surgery to those with DS only. Furthermore, there was no difference in rates of autoimmune thyroiditis or celiac disease. There was also no difference in rates of diagnosed co-occurring neurodevelopmental or mental health conditions in this cohort, including anxiety disorders and attention-deficit/hyperactivity disorder. CONCLUSIONS: This study identifies a variety of medical conditions which are more frequent in children with DS+ASD than DS alone, providing important information for the clinical management of these patients. Future research should investigate the role of some of these medical conditions in the development of ASD phenotypes, and whether there may be distinct genetic and metabolic contributions towards these conditions.

Lien vers le texte intégral (Open Access ou abonnement)

24. Storch EA, Shepherd WS. Improving access in 2023: Evidence-based psychotherapy for autistic youth with anxiety. Bull Menninger Clin;2023 (Winter);87(1):1-5.

Lien vers le texte intégral (Open Access ou abonnement)

25. Suresha PB, O’Leary H, Tarquinio DC, Von Hehn J, Clifford GD. Rett syndrome severity estimation with the BioStamp nPoint using interactions between heart rate variability and body movement. PLoS One;2023;18(3):e0266351.

Rett syndrome, a rare genetic neurodevelopmental disorder in humans, does not have an effective cure. However, multiple therapies and medications exist to treat symptoms and improve patients’ quality of life. As research continues to discover and evaluate new medications for Rett syndrome patients, there remains a lack of objective physiological and motor activity-based (physio-motor) biomarkers that enable the measurement of the effect of these medications on the change in patients’ Rett syndrome severity. In our work, using a commercially available wearable chest patch, we recorded simultaneous electrocardiogram and three-axis acceleration from 20 patients suffering from Rett syndrome along with the corresponding Clinical Global Impression-Severity score, which measures the overall disease severity on a 7-point Likert scale. We derived physio-motor features from these recordings that captured heart rate variability, activity metrics, and the interactions between heart rate and activity. Further, we developed machine learning (ML) models to classify high-severity Rett patients from low-severity Rett patients using the derived physio-motor features. For the best-trained model, we obtained a pooled area under the receiver operating curve equal to 0.92 via a leave-one-out-patient cross-validation approach. Finally, we computed the feature popularity scores for all the trained ML models and identified physio-motor biomarkers for Rett syndrome.

Lien vers le texte intégral (Open Access ou abonnement)

26. Watanabe T. [Autism spectrum disorder and brain state dynamics]. Nihon Yakurigaku Zasshi;2023;158(2):154-158.

In this review, I will present that focusing on global brain state dynamics could bring unique insights into the biological understanding of autism. To this end, I will first introduce energy landscape analysis and a novel brain stimulation method called brain-state-driven neural stimulation. Then, this article will discuss the results of the applications of these methods to autism. Finally, I will also state what such an approach reveals about the brain mechanisms underpinning ADHD.

Lien vers le texte intégral (Open Access ou abonnement)

27. Xiao L, Feng J, Zhang W, Pan J, Wang M, Zhang C, Li L, Su X, Yao P. Autism-like behavior of murine offspring induced by prenatal exposure to progestin is associated with gastrointestinal dysfunction due to claudin-1 suppression. FEBS J;2023 (Feb 28)

Autism spectrum disorders (ASD) are associated with the contribution of many prenatal risk factors; in particular, the sex hormone progestin and vitamin D receptor (VDR) are associated with gastrointestinal (GI) symptoms in ASD development, although the related mechanism remains unclear. We investigated the possible role and mechanism of progestin 17-hydroxyprogesterone caproate (17-OHPC) exposure-induced GI dysfunction and autism-like behaviors (ALB) in mouse offspring. An intestine-specific VDR deficient mouse model was established for prenatal treatment, while transplantation of hematopoietic stem cells (HSCT) with related gene manipulation were used for postnatal treatment for 17-OHPC exposure-induced GI dysfunction and ALB in mouse offspring. The in vivo mouse experiments found that VDR deficiency mimics prenatal 17-OHPC exposure-mediated GI dysfunction, but has no effect on 17-OHPC-mediated autism-like behaviors (ALB) in mouse offspring. Furthermore, prenatal 17-OHPC exposure induces CLDN1 suppression in intestine epithelial cells, and transplantation of hematopoietic stem cells (HSCT) with CLDN1 expression ameliorates prenatal 17-OHPC exposure-mediated GI dysfunction, but has no effect on 17-OHPC-mediated ALB in offspring. In conclusion, prenatal 17-OHPC exposure triggers GI dysfunction in autism-like mouse offspring via CLDN1 suppression, providing a possible explanation for the involvement of CLDN1 and VDR in prenatal 17-OHPC exposure-mediated GI dysfunction with ASD.

Lien vers le texte intégral (Open Access ou abonnement)

28. Zeif D, Yakobi O, Yechiam E. Choice behavior in autistic adults: What drives the extreme switching phenomenon?. PLoS One;2023;18(3):e0282296.

BACKGROUND: Previous studies reported that autistic adolescents and adults tend to exhibit extensive choice switching in repeated experiential tasks. However, a recent meta-analysis showed that this switching effect was non-significant across studies. Furthermore, the relevant psychological mechanisms remain unclear. We examined the robustness of the extreme choice-switching phenomenon, and whether it is driven by a learning impairment, feedback-related aspects (e.g., avoiding losses), or alternatively a different information sampling strategy. METHODS: We recruited an online sample of 114 US participants (57 autistic adults and 57 non-autistic). All participants performed the Iowa Gambling task, a four-option repeated choice task. Standard task blocks were followed by a trial block with no feedback. RESULTS: The findings replicate the extreme choice switching phenomenon (Cohen’s d = 0.48). Furthermore, the effect was found with no difference in average choice rates denoting no learning impairment, and was even observed in trial blocks with no feedback (d = 0.52). There was no evidence that the switching strategy of autistic individuals was more perseverative (i.e., that similar switching rates were used in subsequent trial blocks). When adding the current dataset to the meta-analysis, the choice switching phenomenon is significant across studies, d = 0.32. CONCLUSIONS: The findings suggest that the increased choice switching phenomenon in autism may be robust and that it represents a distinct information sampling strategy and not poor implicit learning (or a bias in the sensitivity to losses). Such extended sampling may underlie some of the phenomena previously attributed to poor learning.

Lien vers le texte intégral (Open Access ou abonnement)

29. Zhang P, Omanska A, Ander BP, Gandal MJ, Stamova B, Schumann CM. Neuron-specific transcriptomic signatures indicate neuroinflammation and altered neuronal activity in ASD temporal cortex. Proc Natl Acad Sci U S A;2023 (Mar 7);120(10):e2206758120.

Autism spectrum disorder (ASD) is a highly heterogeneous disorder, yet transcriptomic profiling of bulk brain tissue has identified substantial convergence among dysregulated genes and pathways in ASD. However, this approach lacks cell-specific resolution. We performed comprehensive transcriptomic analyses on bulk tissue and laser-capture microdissected (LCM) neurons from 59 postmortem human brains (27 ASD and 32 controls) in the superior temporal gyrus (STG) of individuals ranging from 2 to 73 years of age. In bulk tissue, synaptic signaling, heat shock protein-related pathways, and RNA splicing were significantly altered in ASD. There was age-dependent dysregulation of genes involved in gamma aminobutyric acid (GABA) (GAD1 and GAD2) and glutamate (SLC38A1) signaling pathways. In LCM neurons, AP-1-mediated neuroinflammation and insulin/IGF-1 signaling pathways were upregulated in ASD, while mitochondrial function, ribosome, and spliceosome components were downregulated. GABA synthesizing enzymes GAD1 and GAD2 were both downregulated in ASD neurons. Mechanistic modeling suggested a direct link between inflammation and ASD in neurons, and prioritized inflammation-associated genes for future study. Alterations in small nucleolar RNAs (snoRNAs) associated with splicing events suggested interplay between snoRNA dysregulation and splicing disruption in neurons of individuals with ASD. Our findings supported the fundamental hypothesis of altered neuronal communication in ASD, demonstrated that inflammation was elevated at least in part in ASD neurons, and may reveal windows of opportunity for biotherapeutics to target the trajectory of gene expression and clinical manifestation of ASD throughout the human lifespan.

Lien vers le texte intégral (Open Access ou abonnement)