1. Ainsworth K, Bertone A. Audiovisual temporal binding window narrows with age in autistic individuals. Autism research : official journal of the International Society for Autism Research. 2022.
Atypical sensory perception has been recognized in autistic individuals since its earliest descriptions and is now considered a key characteristic of autism. Although the integration of sensory information (multisensory integration; MSI) has been demonstrated to be altered in autism, less is known about how this perceptual process differs with age. This study aimed to assess the integration of audiovisual information across autistic children and adolescents. MSI was measured using a non-social, simultaneity judgment task. Variation in temporal sensitivity was evaluated via Gaussian curve fitting procedures, allowing us to compare the width of temporal binding windows (TBWs), where wider TBWs indicate less sensitivity to temporal alignment. We compared TBWs in age and IQ matched groups of autistic (n = 32) and neurotypical (NT; n = 73) children and adolescents. The sensory profile of all participants was also measured. Across all ages assessed (i.e., 6 through 18 years), TBWs were negatively correlated with age in the autistic group. A significant correlation was not found in the NT group. When compared as a function of child (6-12 years) and adolescent (13-18 years) age groups, a significant interaction of group (autism vs NT) by age group was found, whereby TBWs became narrower with age in the autistic, but not neurotypical group. We also found a significant main effect of age and no significant main effect of group. Results suggest that TBW differences between autistic and neurotypical groups diminishes with increasing age, indicating an atypical developmental profile of MSI in autism which ameliorates across development.
2. Clavagnier I. [Disability, a factor of vulnerability to incest]. Revue de l’infirmiere. 2022; 71(283): 39-42.
Disability, a factor of vulnerability to incestThere is a lack of visibility on the issue of sexual violence among people with disabilities. There is an omerta on this subject within the social and medico-social establishments that receive them. Intra-family sexual violence is kept silent, as it is everywhere else. The vulnerability of children with disabilities is a risk factor for rape and sexual assault, and communication problems hinder their disclosure. Interview with Marie Rabatel, President of the Francophone Association of Autistic Women, expert of the High Authority of Health on the issues of violence against women with disabilities, member of the Independent Commission on incest and sexual violence against children.
3. Dardani C, Schalbroeck R, Madley-Dowd P, Jones HJ, Strelchuk D, Hammerton G, Croft J, Sullivan SA, Zammit S, Selten JP, Rai D. Childhood Trauma As a Mediator of the Association Between Autistic Traits and Psychotic Experiences: Evidence From the Avon Longitudinal Study of Parents and Children Cohort. Schizophrenia bulletin. 2022.
BACKGROUND: Little is known on whether associations between childhood autistic traits and psychotic experiences persist into adulthood and whether genetic confounding and childhood trauma influence them. Here we investigate the associations between childhood autistic traits and psychotic experiences until young adulthood and assess the influence of schizophrenia polygenic risk and childhood traumatic experiences, using the Avon Longitudinal Study of Parents and Children (ALSPAC) population-based birth cohort. STUDY DESIGN: We used a measure of broad autistic traits (autism factor mean score), and four dichotomised measures of autistic traits capturing social communication difficulties (age 7), repetitive behaviours (age 5), sociability (age 3), and pragmatic language (age 9). Psychotic experiences were assessed at ages 18 and 24 using the semi-structured Psychosis-Like Symptoms interview (PLIKSi). Traumatic experiences between ages 5 and 11 were assessed with questionnaires and interviews administered to children and parents at multiple ages. STUDY RESULTS: Broad autistic traits, as well as social communication difficulties, were associated with psychotic experiences that were distressing and/or frequent until age 24 (autism factor mean score, n = 3707: OR 1.19, 95%CI 1.01-1.39; social communication difficulties, n = 3384: OR 1.54, 95%CI 0.97-2.45). Childhood trauma mediated a substantial proportion of the identified associations (~28% and 36% respectively, maximum n = 3577). Schizophrenia polygenic risk did not appear to confound the associations. Multiple imputation analyses (maximum n = 13 105) yielded comparable results. CONCLUSIONS: Childhood trauma may be an important, potentially modifiable pathway between autistic features and later onset of psychotic psychopathology.
4. Dawson G, Rieder AD, Johnson MH. Prediction of autism in infants: progress and challenges. The Lancet Neurology. 2022.
Autism spectrum disorder (henceforth autism) is a neurodevelopmental condition that can be reliably diagnosed in children by age 18-24 months. Prospective longitudinal studies of infants aged 1 year and younger who are later diagnosed with autism are elucidating the early developmental course of autism and identifying ways of predicting autism before diagnosis is possible. Studies that use MRI, EEG, and near-infrared spectroscopy have identified differences in brain development in infants later diagnosed with autism compared with infants without autism. Retrospective studies of infants younger than 1 year who received a later diagnosis of autism have also showed an increased prevalence of health conditions, such as sleep disorders, gastrointestinal disorders, and vision problems. Behavioural features of infants later diagnosed with autism include differences in attention, vocalisations, gestures, affect, temperament, social engagement, sensory processing, and motor abilities. Although research findings offer insight on promising screening approaches for predicting autism in infants, individual-level predictions remain a future goal. Multiple scientific challenges and ethical questions remain to be addressed to translate research on early brain-based and behavioural predictors of autism into feasible and reliable screening tools for clinical practice.
5. Hannon B, Mandy W, Hull L. A comparison of methods for measuring camouflaging in autism. Autism research : official journal of the International Society for Autism Research. 2022.
Interest in social camouflaging has led to a multiplicity of measurement methods of uncertain validity. This two-part investigation first used a systematic review (« Study 1 ») to identify and appraise methods used to quantify camouflaging of autistic traits, using the Consensus-based Standards for the Selection of Health Status Measurement Instruments checklist. A total of 16 distinct measurement tools were identified; all are in the preliminary phases of psychometric evaluation. The systematic review highlighted: (1) the need for parent-report tools which specifically measure camouflaging; and (2) a lack of studies looking at associations between different methods of camouflaging, which limits understanding of their validity. « Study 2 » aimed to begin to address these gaps in knowledge. We created a parent-report version of the Camouflaging Autistic Traits Questionnaire (CAT-Q) and evaluated its concurrent validity in autistic young people by examining associations with the self-report CAT-Q and a discrepancy measure. Discriminant validity was investigated by comparing all three methods of measuring camouflaging to a measure of social skills, to test whether they assess a construct distinct from social ability. The self- and parent-report CAT-Q were significantly related (r = 0.47, 95% CI = 0.24-0.65), and were related weakly (r = 0.20, 95% CI = -0.06 to 0.43) and strongly (r = 0.46, 95% CI = 0.23-0.64), respectively, to the discrepancy approach. No measure was associated with social skills. Improving the psychometric properties of these methods, and introducing a novel parent-report measure, may help selection of appropriate methods in future research and integration into clinical practice.
6. Kushner EH, Britsch ER, Iverson JM. Caregiver object labels within supported and coordinated joint engagement during interaction with toddlers at elevated and typical likelihood of autism. International journal of language & communication disorders. 2022.
BACKGROUND: Early in development, caregivers’ object labelling contributes to children’s word learning. Language development is a bi-directional process, and differences in joint engagement (JE) and language among children with developmental disabilities such as autism spectrum disorder (ASD) may provide caregivers varying contexts and opportunities to provide object labels. However, potential variation in caregivers’ production of object labels and its relation to language development remain relatively unexplored among toddlers with ASD. AIMS: This study characterized the structural and functional features of object labels produced by parents of children with typical (TL) or elevated likelihood (EL) of ASD during naturalistic toy play. We examined features of object labels within two JE contexts, supported and coordinated JE, which are differentiated by a child’s use of eye contact, as well as their relations with concurrent and future child language skills. METHODS & PROCEDURES: The present study included 55 (TL = 12, EL = 43) children who completed a naturalistic parent-child interaction in the home at 18 months of age. Children’s expressive and receptive language was assessed at 18, 24 and 36 months. At 36 months, EL children were assessed for ASD and classified as either EL-No Diagnosis, EL-Language Delay or EL-ASD. Videos of interactions were divided into discrete engagement states, including supported and coordinated JE. All parent speech was transcribed and coded to capture structural (types, tokens, mean length of utterance (MLU), sentence position) and functional (follow-in comments, directives, lead-in labels) features of object labels as well as parent prompts for the child to produce a label. OUTCOMES & RESULTS: Parents of toddlers across outcome groups labelled objects at similar rates within each engagement state. However, parents of EL-ASD children provided the lowest rates of prompts for labels in supported JE and the highest rate of labels as the final word of an utterance (sentence-final position) in coordinated JE. Additionally, parent prompts in supported JE were related to concurrent child expressive language. Labels in sentence-final position were positively related to later language outcome when delivered in supported JE but were associated with poorer language outcomes when delivered in coordinated JE. CONCLUSIONS & IMPLICATIONS: Subtle differences in parent object labels across outcome groups demonstrate the role that child language and social engagement can play in influencing parent input and the cascading impact of this input on language development. WHAT THIS PAPER ADDS: What is already known on this subject Variations in caregiver object labelling can impact child language development. However, child characteristics such as language ability also actively shape the input caregivers provide, demonstrating the bi-directionality of language development. What this paper adds to existing knowledge The present study demonstrates that characteristics of the engagement context in which a label is delivered may be important for understanding how object labelling relates to child language acquisition and whether this relation varies for children who face challenges in language learning. What are the potential or actual clinical implications of this work? As child differences in social engagement emerge, parents may be more attuned to moments their children are engaging with eye contact. Caregiver-mediated interventions might consider strategies that guide caregivers in recognizing engagement without eye contact as a similarly meaningful opportunity for learning and encourage the use of rich input within these moments.
7. Menees KB, Otero BA, Tansey MG. Microbiome influences on neuro-immune interactions in neurodegenerative disease. International review of neurobiology. 2022; 167: 25-57.
Mounting evidence points to a role for the gut microbiome in a wide range of central nervous system diseases and disorders including depression, multiple sclerosis, Alzheimer’s disease, Parkinson’s disease, and autism spectrum disorder. Moreover, immune system involvement has also been implicated in these diseases, specifically with inflammation being central to their pathogenesis. In addition to the reported changes in gut microbiome composition and altered immune states in many neurological diseases, how the microbiome and the immune system interact to influence disease onset and progression has recently garnered much attention. This chapter provides a review of the literature related to gut microbiome influences on neuro-immune interactions with a particular focus on neurological diseases. Gut microbiome-derived mediators, including short-chain fatty acids and other metabolites, lipopolysaccharide, and neurotransmitters, and their impact on neuro-immune interactions as well as routes by which these interactions may occur are also discussed.
8. Ou J, Smith RC, Tobe RH, Lin J, Arriaza J, Fahey JW, Liu R, Zeng Y, Liu Y, Huang L, Shen Y, Li Y, Cheng D, Cornblatt B, Davis JM, Zhao J, Wu R, Jin H. Efficacy of Sulforaphane in Treatment of Children with Autism Spectrum Disorder: A Randomized Double-Blind Placebo-Controlled Multi-center Trial. Journal of autism and developmental disorders. 2022.
Sulforaphane has been reported to possibly improve core symptoms associated with autism spectrum disorders from mostly small size studies. Here we present results of a larger randomized clinical trial (N = 108) in China. There were no significant changes in caregiver rated scales between sulforaphane and placebo groups. However, clinician rated scales showed a significant improvement in the sulforaphane group, and one third of participants showed at least a 30% decrease in score by 12 weeks treatment. The effects of sulforaphane were seen across the full range of intelligence and greater in participants over 10 years. Sulforaphane was safe and well-tolerated even for young children. The inconsistent results between caregiver and clinician rated scales suggest more clinical trials are needed to confirm our findings.
9. Perinelli MG, Cloherty M. Identification of autism in cognitively able adults with epilepsy: A narrative review and discussion of available screening and diagnostic tools. Seizure. 2022; 104: 6-11.
The recent NICE epilepsy Guideline (NG217; 2022) recommends that epilepsy professionals need to be alert to autism when considering mental health presentations, behavioural difficulties and as a marker for referral for whole genome sequencing for those patients with epilepsy of unknown cause. However, this relies upon the existence of valid autism screens for people with epilepsy (PWE). We found few studies of autism in cognitively able PWE. This represents an important gap in the literature. We describe different autism screening and diagnostic tools; two screening tools have been used specifically for adult PWE who are cognitively able (AQ, SRS-AS). The AQ is more psychometrically robust, but there may be an overlap between these screening questions and questions relevant to some psychiatric disorders. Formal gold-standard diagnostic tools (module 4 of ADOS-2, ADI-R or 3Di or 3Di-Adult) would benefit from studies of their application to cognitively able PWE. More research is needed to understand the characteristics of autism in cognitively able PWE and to ascertain the appropriate screening and diagnostic tools for this cohort.
10. Politano D, Gana S, Pezzotti E, Berardinelli A, Pasca L, Carmen Barbero V, Pichiecchio A, Maria Valente E, Errichiello E. A novel variant in NEUROD2 in a patient with Rett-like phenotype points to Glu130 codon as a mutational hotspot. Brain & development. 2022.
BACKGROUND: NEUROD2, encoding the neurogenic differentiation factor 2, is essential for neurodevelopment. To date, heterozygous missense variants in this gene have been identified in eight patients (from six unrelated families) with epileptic encephalopathy and developmental delay. CASE REPORT: We describe a child with initial clinical suspicion of Rett/Rett-like syndrome, in whom exome sequencing detected a novel de novo variant (c.388G > A, p.Glu130Lys) in NEUROD2. Interestingly, a missense change affecting the same codon, c.388G > C (p.Glu130Gln), was previously identified in other two patients. CONCLUSIONS: Our results suggest that Glu130 might represent a potential mutational hotspot of NEUROD2. Furthermore, the clinical findings (especially the absence of clinically overt seizures) strengthen the NEUROD2-phenotypic spectrum, implying that developmental delay may also manifest isolatedly. We suggest inclusion of NEUROD2-associated developmental and epileptic encephalopathies (DEEs) in the differential diagnosis of atypical Rett syndrome as well as gene panels related to autism spectrum disorder.
11. Schuck RK, Dwyer P, Baiden KMP, Williams ZJ, Wang M. Social Validity of Pivotal Response Treatment for Young Autistic Children: Perspectives of Autistic Adults. Journal of autism and developmental disorders. 2022.
The social validity of autism behavioral intervention has been questioned. Naturalistic Developmental Behavioral Interventions (NDBIs) attempt to address some concerns, but it is unclear whether autistic people consider NDBIs socially valid. Social validity of an NDBI, Pivotal Response Treatment (PRT), was investigated through autistic adults commenting on videos of autistic children receiving PRT. Qualitative coding of responses generated three themes: respect for individuals; assessment of intervention implementation; and socioemotional considerations. Although video brevity limits the scope of the present study’s conclusions, participants highlighted PRT components that appeared socially valid (e.g., reinforcing attempts, following the child’s lead) and aspects appearing invalid (e.g., overemphasis on spoken language). Therefore, adjustments appear necessary for PRT to be fully acceptable to the autistic community.
12. Sydnor LM, Aldinger KA. Structure, Function, and Genetics of the Cerebellum in Autism. Journal of psychiatry and brain science. 2022; 7.
Autism spectrum disorders are common neurodevelopmental disorders that are defined by core behavioral symptoms but have diverse genetic and environmental risk factors. Despite its etiological heterogeneity, several unifying theories of autism have been proposed, including a central role for cerebellar dysfunction. The cerebellum follows a protracted course of development that culminates in an exquisitely crafted brain structure containing over half of the neurons in the entire brain densely packed into a highly organized structure. Through its complex network of connections with cortical and subcortical brain regions, the cerebellum acts as a sensorimotor regulator and affects changes in executive and limbic processing. In this review, we summarize the structural, functional, and genetic contributions of the cerebellum to autism.
13. Trus M, Servili E, Taieb-Cohen T, Atlas D. Autism associated mutations in β(2) subunit of voltage-gated calcium channels constitutively activate gene expression. Cell calcium. 2022; 108: 102672.
Membrane depolarization triggers gene expression through voltage-gated calcium channels (VGCC) in a process called Excitation-transcription (ET) coupling. Mutations in the channel subunits α(1)1.2, or β(2d), are associated with neurodevelopmental disorders such as ASD. Here, we found that two mutations S143F and G113S within the rat Cavβ(2a) corresponding to autistic related mutations Cavβ(2d)(S197F) and Cavβ(2d)(G167S) in the human Cavβ(2d), activate ET-coupling via the RAS/ERK/CREB pathway. Membrane depolarization of HEK293 cells co-expressing α(1)1.2 and α(2δ) with Cavβ(2a)(S143F) or Cavβ(2a)(G113S) triggers constitutive transcriptional activation, which is correlated with facilitated channel activity. Similar to the Timothy-associated autistic mutation α(1)1.2(G406R), constitutive gene activation is attributed to a hyperpolarizing shift in the activation kinetics of Cav1.2. Pulldown of RasGRF2 and RhoGEF by wt and the Cavβ(2a) autistic mutants is consistent with Cavβ(2)/Ras activation in ET coupling and implicates Rho signaling as yet another molecular pathway activated by Cavα(1)1.2/Cavβ2 . Facilitated spontaneous channel activity preceding enhanced gene activation via the Ras/ERK/CREB pathway, appears a general molecular mechanism for Ca(2+) channel mediated ASD and other neurodevelopmental disorders.
14. Wetzel AS, Darbro BW. A comprehensive list of human microdeletion and microduplication syndromes. BMC genomic data. 2022; 23(1): 82.
OBJECTIVE: The phenotypic spectrum of human microdeletion and microduplication syndromes (MMS) is heterogeneous but often involves intellectual disability, autism spectrum disorders, dysmorphic features and/or multiple congenital anomalies. While the common recurrent copy number variants (CNVs) which underlie these MMS have been well-studied, the expansion of clinical genomic testing has led to the identification of many rare non-recurrent MMS. To date, hundreds of unique MMS have been reported in the medical literature, and no single resource exists which compiles all these MMS in one location. This comprehensive list of MMS will aid further study of CNV disorders as well as serve as a resource for clinical laboratories performing diagnostic CNV testing. DATA DESCRIPTION: Here we provide a comprehensive list of MMS which have been reported in the medical literature to date. This list is sorted by genomic location, and for each MMS, we provide a list of publications for referral, as well as the consensus coordinates, representative region, shortest regions of overlap (SRO), and/or subregions where applicable.
15. Yan F, Shah A, Isaacson G. Tympanostomy Tube Placement in Children with Autism Spectrum Disorder. The Laryngoscope. 2022.
OBJECTIVE: The frequency of tympanostomy tube (TT) placement among United States children with autism spectrum disorder (ASD) is not known. We explored the rate of TT placement in children with ASD in the United States and compared this to children without ASD. We further examined demographic and behavioral factors that might vary between the two groups. METHODS: We utilized data from the National Health Interview Survey (NHIS) administered in 2014. This survey samples a representative population of patients across the United States and includes children under 18 years of age. The 2014 version of the NHIS survey was chosen as it identifies both autism and TT placement among sampled patients. Descriptive statistics and univariable and multivariable logistic regression analyses were performed. RESULTS: In total, 11,730 children (239 [2.0%] with ASD) were included. Overall, 34 (14.2%) children with ASD underwent TT placement versus 987 (8.6%) in children without ASD (p = 0.002) ASD diagnosis was associated with increased odds of TT placement (1.52 OR, 95% CI 1.04-2.22). Male sex, white race, and non-Hispanic ethnicity were also associated with increased odds of TT placement. Age at the time of TT surgery was not different between those with versus without ASD. CONCLUSION: Children with ASD have an increased rate of TT placement compared to children without ASD. The reason(s) for this increased rate might include the following: higher rates of infection in ASD, over-diagnosis of ear infection or hearing disability in a difficult-to-examine population, and/or a predilection toward aggressive treatment in this at-risk group. LEVEL OF EVIDENCE: 3-National database study Laryngoscope, 2022.
16. Ye F, Du L, Liu B, Gao X, Yang A, Liu D, Chen Y, Lv K, Xu P, Chen Y, Liu J, Zhang L, Li S, Shmuel A, Zhang Q, Ma G. Application of pseudocontinuous arterial spin labeling perfusion imaging in children with autism spectrum disorders. Frontiers in neuroscience. 2022; 16: 1045585.
INTRODUCTION: Pseudocontinuous Arterial Spin Labeling (pCASL) perfusion imaging allows non-invasive quantification of regional cerebral blood flow (CBF) as part of a multimodal magnetic resonance imaging (MRI) protocol. This study aimed to compare regional CBF in autism spectrum disorders (ASD) individuals with their age-matched typically developing (TD) children using pCASL perfusion imaging. MATERIALS AND METHODS: This cross-sectional study enrolled 17 individuals with ASD and 13 TD children. All participants underwent pCASL examination on a 3.0 T MRI scanner. Children in two groups were assessed for clinical characteristics and developmental profiles using Autism Behavior Checklist (ABC) and Gesell development diagnosis scale (GDDS), respectively. We compared CBF in different cerebral regions of ASD and TD children. We also assessed the association between CBF and clinical characteristics/developmental profile. RESULTS: Compared with TD children, individuals with ASD demonstrated a reduction in CBF in the left frontal lobe, the bilateral parietal lobes, and the bilateral temporal lobes. Within the ASD group, CBF was significantly higher in the right parietal lobe than in the left side. Correlation analysis of behavior characteristics and CBF in different regions showed a positive correlation between body and object domain scores on the ABC and CBF of the bilateral occipital lobes, and separately, between language domain scores and CBF of the left frontal lobe. The score of the social and self-help domain was negatively correlated with the CBF of the left frontal lobe, the left parietal lobe, and the left temporal lobe. CONCLUSION: Cerebral blood flow was found to be negatively correlated with scores in the social and self-help domain, and positively correlated with those in the body and object domain, indicating that CBF values are a potential MRI-based biomarker of disease severity in ASD patients. The findings may provide novel insight into the pathophysiological mechanisms of ASD.
17. Zamir A, Band-Winterstein T. « I Do Not Think She Will Understand, This is Not a Situation for a Girl Like Her: » Disenfranchised Grief Among Adults with Intellectual and Developmental Disabilities in the Ultra-orthodox Jewish Society. Omega. 2022: 302228221141941.
This article examines the experience of aging ultra-Orthodox families alongside a person with intellectual and developmental disabilities (IDD) in relation to parents’ illness and death, followed by grief. In-depth interviews were conducted with 14 family units. Each family unit included the person with IDD, a parent, and a sibling-a total of 43 participants. Three main themes emerged: A. The difficulty in confronting illness and dying of parents alongside a family member with IDD in an Ultra-Orthodox Context. B. Exclusion of the person with IDD from parents’ memorial events. C. Religious ceremonies as a strategy for coping with mourning among persons with IDD. The discussion focuses on the concept of disenfranchised grief in a religious context and its impact on the family support system. Culturally sensitive therapeutic recommendations are made for professionals working with older ultra-Orthodox Jewish families alongside a person with IDD in the context of the subject.