1. Berry CA, Kwok L, Gofine M, Kaufman M, Williams DA, Terlizzi K, Alvaro M, Neighbors CJ. Utilization and Staff Perspectives on an On-Demand Telemedicine Model for People with Intellectual and Developmental Disabilities Who Reside in Certified Group Residences. Telemed Rep;2023;4(1):204-214.

BACKGROUND: Non-emergent medical problems that arise when a usual provider is unavailable can often result in emergency department or urgent care visits, which can be particularly distressing to people with intellectual and developmental disabilities (PIDD). On-demand, synchronous telemedicine may be a promising supplement when immediate care from usual sources is unavailable. Prior research demonstrated that high-quality telemedicine can be effectively delivered to PIDD. The aim of this article is to describe the utilization and staff perspectives on the implementation of the Telemedicine Triage Project (TTP), an innovative model that provides telemedicine consultations for PIDD who reside in state-certified group residences and present with an urgent but non-emergent medical concern when their usual provider is unavailable. METHODS: Call frequency data for calendar years 2020 and 2021 were reviewed. The study team conducted semi-structured interviews, with 19 key informants representing organizational- and agency-level leadership and staff. The interview data were analyzed using a protocol-driven, rapid qualitative methodology. RESULTS: Telemedicine consultations increased from 7953 in 2020 to 15,011 calls in 2021, and call volume peaked between 10 am and 1 pm. Key informants reported high satisfaction with TTP; universal benefits and a few barriers to implementation; and strong interest in maintaining the program beyond the grant period. DISCUSSION: Over the first 2 years of its implementation, the TTP program was widely utilized and proved extremely feasible and acceptable to staff. This model is a promising and highly feasible way to provide equitable access to telemedicine for PIDD by addressing barriers to and disparities in access to health care that affect PIDD.

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2. Crane L, Hearst C, Ashworth M, Davies J. Evaluating the online delivery of an autistic-led programme to support newly diagnosed or identified autistic adults. Autism Dev Lang Impair;2023 (Jan-Dec);8:23969415231189608.

BACKGROUND & AIMS: Exploring Being Autistic is an autistic-led group-based programme providing psychoeducation and peer support to newly identified/diagnosed autistic adults. In 2020, due to social distancing measures implemented following the coronavirus pandemic, Exploring Being Autistic was adapted for online delivery. Here, we aimed to replicate previous research into the in-person delivery of Exploring Being Autistic, to determine whether similar results were obtained when the programme was delivered online. Further, we aimed to identify the unique opportunities and challenges that online delivery afforded. METHODS: We used a community-based participatory research (CBPR) approach, whereby the autistic developer and facilitator of Exploring Being Autistic worked collaboratively with a team of academic researchers throughout the research process. Together, we evaluated two iterations of the online Exploring Being Autistic programme, involving 16 attendees. Attendees completed questionnaires before, during and after the programme. Attendees were also invited to participate in two post-programme (group or individual) interviews: one following the completion of the programme (time one) and another 6-8 months later (time two). Attendees were included in the research if they completed at least one questionnaire or interview. Data were analysed qualitatively, using reflexive thematic analysis. RESULTS: Experiences of participating in the programme tended to be positive. Participants appreciated the autistic-led nature of the programme, found unity in the diversity of the group, and developed a positive and practical outlook as a result of the programme. Further analyses of our data revealed mixed views regarding the online delivery of the programme. Opportunities of online delivery were noted, such as this mode of participation reducing cognitive load, enabling the programme to be accessible to more participants, and fostering meaningful social connections among participants. However, technology and practical issues were felt to cause barriers, and some human aspects of participation were felt to be ‘lost in translation’ (e.g., in breakout groups). CONCLUSIONS: The online delivery of the Exploring Being Autistic programme yielded similar results to previous, in-person evaluations of the programme. While we identified positive aspects of online delivery, this mode did not entirely suit everyone’s needs. IMPLICATIONS: From the current findings, we can make several recommendations to develop online support for autistic people. First, flexibility is key. To make support accessible and inclusive to a broad range of autistic people, the option for attendees to engage in-person, online or in hybrid formats should be considered. Second, if delivering support online, the use of breakout rooms should be carefully considered. While participants appreciated the opportunity to meet different people, some participants found the unpredictability and lack of scaffolding associated with breakout rooms challenging. To mitigate these challenges, groups could be pre-determined and shared with the attendees in advance (although consideration should be given to how the groups ‘fit’ together, and whether groupings should be changed at set intervals). Gentle warnings should also be given to those in breakout rooms, to alert them of the need to re-join the main group. Finally, support with technological aspects relating to engagement should be prioritised.

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3. De Francesco S, Morello L, Fioravanti M, Cassaro C, Grazioli S, Busti Ceccarelli S, Nobile M, Molteni M, Crippa A. A multimodal approach can identify specific motor profiles in autism and attention-deficit/hyperactivity disorder. Autism Res;2023 (Aug);16(8):1550-1560.

It is still unclear whether and to what extent the motor difficulties are specific to autism. This study aimed to determine whether a multimodal assessment of motor skills could accurately discriminate autistic children from attention-deficit/hyperactivity disorder (ADHD) and typically developing (TD) peers. Seventy-five children, aged 7-13, equally divided into three groups, were assessed with the developmental coordination disorder questionnaire (DCDQ), the movement assessment battery for children 2 (MABC2), the sensorimotor subtests of NEPSY-II, and the kinematic analysis of a reach-to-drop task. Principal component analysis (PCA) on DCDQ subscales revealed one factor-Caregiver Report-, whereas MABC2/NEPSY-II scores identified three factors-namely, Object Interception and Balance, Motor Imitation, and Fine-Motor Skills-. Lastly, PCA on kinematic variables identified four factors: PC1, loaded by the parameters of velocity and acceleration throughout the task, PC2 and PC3 involved the temporal parameters of the two submovements, and PC4 accounted for the wrist inclination at ball drop. When comparing autistic and TD children, Caregiver Report and Motor Imitation factors predicted membership with 87.2% of accuracy. In the model comparing ADHD and TD groups, Caregiver Report and Fine-Motor Skills predicted membership with an accuracy of 73.5%. In the last model, the Object Interception and Balance factor differentiated autistic children from ADHD with an accuracy of 73.5%. In line with our previous findings, kinematics did not differentiate school-aged autistic children from ADHD and TD peers. The present findings show that specific motor profiles in autism and ADHD can be isolated with a multimodal investigation of motor skills.

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4. Dewinter J, Onaiwu MG, Massolo ML, Caplan R, Van Beneden E, Brörmann N, Crehan ET, Croen LA, Faja S, Gassner DL, Graham Holmes L, Hughes C, Hunter M, Huysamen M, Jelonche P, Lai MC, Noens I, Pukki H, Stokes MA, Strang JF, van der Miesen AI. Short report: Recommendations for education, clinical practice, research, and policy on promoting well-being in autistic youth and adults through a positive focus on sexuality and gender diversity. Autism;2023 (Aug 2):13623613231188349.

In this article, we propose recommendations on what we can do to promote that autistic people can enjoy their sexuality and gender identity, because that contributes to overall well-being.First, we briefly summarize the existing research on sexuality and gender diversity in autistic individuals.Next, we propose recommendations for how to promote sexual and gender diversity-related health and well-being. Based on what is known about sexuality, gender diversity, and relationships in autistic adolescents and adults, we convened an international group of autistic and non-autistic researchers, advocates, parents, and professionals to develop recommendations to promote sexual and gender health in autistic people.The resulting recommendations were checked through an online survey distributed to autistic people across the world. The online participants endorsed the importance of eight final recommendations related to:1. Providing education and information on sexuality, relationships, and gender diversity to autistic individuals and their families;2. Improving expertise in and accessibility to healthcare for sexuality, relationships, and gender-related questions, with specific attention to prevention of and support after sexual victimization; and3. Meaningfully including the autism community in future research that addresses well-being relating to sexuality, relationships, and gender diversity.These community-driven recommendations aim to promote sexual health and well-being in autistic individuals internationally.

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5. Godugu S, Vudugula SA, Neupane B, Esarla K, Bathina VR, Vajje J, Mohan A, Raghu Kumar BR, Gowda S, Gopisetti S. Association between severe retinopathy of prematurity (ROP) and poor motor neurodevelopmental outcome. Indian J Ophthalmol;2023 (Aug);71(8):2944-2946.

During the final (third) trimester outside of the womb, the retina develops significantly and is vulnerable to problems. Similar to how the cerebral cortex does, the cerebellum also grows quickly during this time and is susceptible to upsetting environmental influences. The only factors that show promise for lowering the incidence and retinopathy of prematurity (ROP) severity among high-risk infants are prematurity prevention, preeclampsia control, and prudent use of oxygen therapy and ventilation. The third trimester is when the cerebral cortex, cerebellum, and retina develop. These areas are vulnerable to environmental influences if their development is interrupted. Throughout childhood and adolescence, neurodevelopmental defects have been linked to impaired cortical development and smaller brain volumes. Reduced cerebellar volumes have been linked to an increased risk of autism spectrum disorder, lower motor performance, impaired executive functioning, and poorer cognitive outcomes. The complete avascular retina, as well as the peripheral retina, should be treated during retinal ablation with laser photocoagulation (using a transpupillary diode, 11 argon, and three FD-YAG) or cryoablation as failing to do so promotes disease progression and results in unfavorable anatomical and refractive outcomes.

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6. Harrop C, Bodfish J, Lecavalier L, Dallman AR, Jones D, Pritchett J, Whitten A, Boyd BA. Refining our Understanding of Anxiety in Autistic Youth: Examining the Role of Behavioral Inflexibility. J Autism Dev Disord;2023 (Aug 2)

Prior research has demonstrated that cognitive inflexibility is associated with anxiety in autistic individuals. Everyday patterns of behavioral inflexibility (e.g. observable inflexible behavior in the context of the need to change or adapt and that is manifested in real-world everyday settings) is common in autism and can be distinguished from performance on discrete cognitive tasks that tap flexible attention, learning, or decision-making. The purpose of this study was to extend this prior work on inflexibility in autism but with measures specifically developed with input from stakeholders (caregivers and clinicians) for autistic youth designed to measure everyday behavioral inflexibility (BI). We characterized anxiety in a large sample of autistic (N = 145) and non-autistic youth (N = 91), ages 3 to 17 years, using the Parent Rated Anxiety Scale for Autism Spectrum Disorder (PRAS-ASD). Further, we sought to understand how BI, measured via the Behavioral Inflexibility Scale (BIS), predicted anxiety compared to other variables known to increase anxiety in youth (chronological age, IQ, autism diagnosis, assigned sex at birth). Autistic youth had higher parent-related anxiety and BI compared to non-autistic youth. BI was the strongest predictor of anxiety scores, irrespective of diagnosis. Overall, our findings highlight the importance of BI to the understanding of anxiety in autistic youth.

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7. Healthcare Engineering JO. Retracted: Intelligent Somatosensory Interactive Activities Restore Motor Function to Children with Autism. J Healthc Eng;2023;2023:9857376.

[This retracts the article DOI: 10.1155/2022/4516005.].

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8. Im-Bolter N, de la Roche L. What parents want: A qualitative analysis of a parent-implemented intervention for autistic children. Autism Dev Lang Impair;2023 (Jan-Dec);8:23969415231189606.

BACKGROUND AND AIMS: Guidelines regarding social cognitive interventions for autistic children suggest incorporating a holistic approach. This includes increasing the family’s understanding of difficulties associated with autism, integrations of natural environments, and parents as active agents in the intervention while being supported for their well-being. The current availability of holistic parent-implemented interventions for autistic children is limited, with no qualitative understanding of how parents view the benefits for themselves or their children. METHOD: The current study expands the literature regarding holistic approaches through a qualitative understanding of parent perceptions of a parent-implemented social communication intervention for autistic children (TalkAbility™), which incorporates a 6-month follow-up. This study sought to gain a deeper understanding from parents on their perceptions of a holistic approach, including the impact on themselves, their families, and their autistic child. RESULTS: Following Braun and Clarke’s model of thematic analysis, data was coded into four themes: (a) communication difficulties, frustrations, and progress, (b) social relationships and concerns, (c) communication strategies, and (d) thoughts and emotions surrounding TalkAbility™. CONCLUSIONS: Parents report that many components of a holistic approach are instrumental in encouraging social communication in their autistic child. Results highlight the importance of considering parent experiences regarding interventions for their child’s social communication skills through a qualitative viewpoint. IMPLICATIONS: Knowing the intervention aspects that parents view as most valuable allows targeted program modifications that reflect actual parent needs. Further understanding regarding the influence of holistic parent-implemented social communication interventions on child communication skills, parenting frustrations, and parent-child relationships is needed.

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9. Jacinto M, Monteiro D, Antunes R, Ferreira JP, Matos R, Campos MJ. Effects of exercise on body mass index and waist circumference of individuals with intellectual and developmental disabilities: a systematic review with meta-analysis. Front Physiol;2023;14:1236379.

Introduction/Methods: This systematic review with meta-analysis aims to assess the magnitude of the effects of physical exercise programs on body mass index (BMI) and waist circumference (WC) of individuals with Intellectual and Developmental Disabilities (IDD), metabolic and cardiovascular health markers. Results: Considering the eligibility criteria, a final sample of nine articles was obtained. For BMI, the Z-value obtained to test the null hypothesis (difference between means is zero), showed a Z = -2.176 and p = 0.03. The highest magnitude of the effect was from the intervention with combined training (difference in means: -0.399), with a value of Z = -1.815 and p = 0.07. For WC, the Z-value is zero, showing a Z = -3.306 and p = 0.001. The highest magnitude of the effect was from the intervention with continuous cardiorespiratory training of -0.786, with a value of Z = -2.793 and p = 0.005. Discussion: Physical exercise prevents increases in BMI and WC in individuals with IDD. Aerobic training seems to be more effective in promoting WC and combined training in BMI. Systematic Review Registration: [PROSPERO], identifier [CRD42021255316].

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10. Krijnen LJG, Greaves-Lord K, Mandy W, Mataw KJS, Hartog P, Begeer S. How Well Can we Diagnose Autism in Adults? Evaluating an Informant-based Interview: The Dutch Developmental, Dimensional and Diagnostic Interview – Adult Version (3Di-Adult). J Autism Dev Disord;2023 (Aug 2)

The current study evaluated a brief, informant-based autism interview: the Developmental, Dimensional and Diagnostic Interview – Adult Version (3Di-Adult). Feasibility, reliability and validity of the Dutch 3Di-Adult was tested amongst autistic participants (n = 62) and a non-autistic comparison group (n = 30) in the Netherlands. The 3Di-Adult consists of two scales based on DSM-5 criteria: A scale ‘Social communication and social interaction’ and B scale ‘Restricted, repetitive patterns of behavior, interests or activities’. ROC curves were used to determine cut-off scores for the A and the B scale, using an ASD diagnosis made by an independent clinician as the criterion. Mean administration time was 42 min. Internal consistency of the A scale (α = 0.92) and the B scale (α = 0.85) were good. Inter-rater reliability (ICCs = 0.99) and inter-rater agreement (ICCs ≥ 0.90) were promising. The 3Di-Adult showed good sensitivity (80.6%) and specificity (93.3%). Positive and negative predictive value were 96.2% and 70.0% respectively. Comparisons with the Autism-Spectrum Quotient-Short to investigate the convergent validity showed moderate, significant correlations with the 3Di-Adult in the total sample. Males, as compared to females, displayed significantly more autistic features on the 3Di-Adult. No relationship was found of the 3Di-Adult with education level, intelligence and age of the participants or informants. The feasibility and psychometric properties of the Dutch 3Di-Adult are promising, indicating that it can be a time-efficient, valid and reliable tool to use in diagnosing autism in adults according to DSM-5 criteria.

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11. Leung BK, Merlin S, Walker AK, Lawther AJ, Paxinos G, Eapen V, Clarke R, Balleine BW, Furlong TM. Immp2l knockdown in male mice increases stimulus-driven instrumental behaviour but does not alter goal-directed learning or neuron density in cortico-striatal circuits in a model of Tourette syndrome and autism spectrum disorder. Behav Brain Res;2023 (Aug 24);452:114610.

Cortico-striatal neurocircuits mediate goal-directed and habitual actions which are necessary for adaptive behaviour. It has recently been proposed that some of the core symptoms of autism spectrum disorder (ASD) and Gilles de la Tourette syndrome (GTS), such as tics and other repetitive behaviours, may emerge because of imbalances in these neurocircuits. We have recently developed a model of ASD and GTS by knocking down Immp2l, a mitochondrial gene frequently associated with these disorders. The current study sought to determine whether Immp2l knockdown (KD) in male mice alters flexible, goal- or cue- driven behaviour using procedures specifically designed to examine response-outcome and stimulus-response associations, which underlie goal-directed and habitual behaviour, respectively. Whether Immp2l KD alters neuron density in cortico-striatal neurocircuits known to regulate these behaviours was also examined. Immp2l KD mice and wild type-like mice (WT) were trained on Pavlovian and instrumental learning procedures where auditory cues predicted food delivery and lever-press responses earned a food outcome. It was demonstrated that goal-directed learning was not changed for Immp2l KD mice compared to WT mice, as lever-press responses were sensitive to changes in the value of the food outcome, and to contingency reversal and degradation. There was also no difference in the capacity of KD mice to form habitual behaviours compared to WT mice following extending training of the instrumental action. However, Immp2l KD mice were more responsive to auditory stimuli paired with food as indicated by a non-specific increase in lever response rates during Pavlovian-to-instrumental transfer. Finally, there were no alterations to neuron density in striatum or any prefrontal cortex or limbic brain structures examined. Thus, the current study suggests that Immp2l is not necessary for learned maladaptive goal or stimulus driven behaviours in ASD or GTS, but that it may contribute to increased capacity for external stimuli to drive behaviour. Alterations to stimulus-driven behaviour could potentially influence the expression of tics and repetitive behaviours, suggesting that genetic alterations to Immp2l may contribute to these core symptoms in ASD and GTS. Given that this is the first application of this battery of instrumental learning procedures to a mouse model of ASD or GTS, it is an important initial step in determining the contribution of known risk-genes to goal-directed versus habitual behaviours, which should be more broadly applied to other rodent models of ASD and GTS in the future.

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12. Liu T, Martinez-Torres K, Mazzone J, Camarata S, Lense M. Brief Report: Telehealth Music-Enhanced Reciprocal Imitation Training in Autism: A Single-Subject Feasibility Study of a Virtual Parent Coaching Intervention. J Autism Dev Disord;2023 (Aug 2)

PURPOSE: Telehealth delivery increases accessibility of parent-mediated interventions that teach parents skills and support autistic children’s social communication. Reciprocal Imitation Training (RIT), an evidence-based Naturalistic Developmental Behavioral Intervention (NDBI) focused on imitation skills, a common difficulty in autism, holds promise for telehealth-based parent training. Imitation is also a core component of musical play during childhood and the affordances of musical play/song naturally shape parent-child interactions. We evaluate the feasibility of a music-based, telehealth adaptation of RIT-music-enhanced RIT (tele-meRIT)-as a novel format for coaching parents in NDBI strategies. METHODS: This single-subject, multiple baseline design study included 4 autistic children (32-53 months old) and their mothers. Parent-child dyads were recorded during 10-min free play probes at baseline, weekly tele-meRIT sessions, and one-week and one-month follow-up. Probes were coded for parents’ RIT implementation fidelity, parent vocal musicality, and children’s rate of spontaneous imitation. RESULTS: No parent demonstrated implementation fidelity during baseline. All parents increased their use of RIT strategies, met fidelity by the end of treatment, and maintained fidelity at follow-up. Parent vocal musicality also increased from baseline. Intervention did not consistently increase children’s imitation skills. A post-intervention evaluation survey indicated high parent satisfaction with tele-meRIT and perceived benefits to their children’s social and play skills more broadly. CONCLUSION: Implementing tele-meRIT is feasible. Although tele-meRIT additionally involved coaching in incorporating rhythmicity and song into play interactions, parents achieved fidelity in the RIT principles, suggesting one avenue by which music can be integrated within evidence-based parent-mediated NDBIs.

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13. Liu Z, Xin B, Smith IN, Sency V, Szekely J, Alkelai A, Shuldiner A, Efthymiou S, Rajabi F, Coury S, Brownstein CA, Rudnik-Schöneborn S, Bruel AL, Thevenon J, Zeidler S, Jayakar P, Schmidt A, Cremer K, Engels H, Peters SO, Zaki MS, Duan R, Zhu C, Xu Y, Gao C, Sepulveda-Morales T, Maroofian R, Alkhawaja IA, Khawaja M, Alhalasah H, Houlden H, Madden JA, Turchetti V, Marafi D, Agrawal PB, Schatz U, Rotenberg A, Rotenberg J, Mancini GMS, Bakhtiari S, Kruer M, Thiffault I, Hirsch S, Hempel M, Stühn LG, Haack TB, Posey JE, Lupski JR, Lee H, Sarn NB, Eng C, Gonzaga-Jauregui C, Zhang B, Wang H. Hemizygous variants in protein phosphatase 1 regulatory subunit 3F (PPP1R3F) are associated with a neurodevelopmental disorder characterized by developmental delay, intellectual disability, and autistic features. Hum Mol Genet;2023 (Aug 2)

PPP1R3F (R3F) is a member of the glycogen targeting subunits (GTSs), which belong to the large group of regulatory subunits of protein phosphatase 1 (PP1), a major eukaryotic serine/threonine protein phosphatase that regulates diverse cellular processes. Here, we describe the identification of hemizygous variants in PPP1R3F associated with a novel X-linked recessive neurodevelopmental disorder in 13 unrelated individuals. This disorder is characterized by developmental delay, mild intellectual disability, neurobehavioral issues such as autism spectrum disorder, seizures, and other neurological findings including tone, gait, and cerebellar abnormalities. PPP1R3F variants segregated with disease in affected hemizygous males that inherited the variants from their heterozygous carrier mothers. We show that R3F is predominantly expressed in brain astrocytes and localizes to the endoplasmic reticulum in cells. Glycogen content in PPP1R3F knockout astrocytoma cells appears to be more sensitive to fluxes in extracellular glucose levels than in wild-type cells, suggesting that R3F functions in maintaining steady brain glycogen levels under changing glucose conditions. We performed functional studies on nine of the identified variants and observed defects in PP1 binding, protein stability, subcellular localization, and regulation of glycogen metabolism in most of them. Collectively, the genetic and molecular data indicate that deleterious variants in PPP1R3F are associated with a new X-linked disorder of glycogen metabolism, highlighting the critical role of GTSs in neurological development. This research expands our understanding of neurodevelopmental disorders and the role of PP1 in brain development and proper function.

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14. Mantas V, Kotoula V, Pehlivanidis A. Exploring randomness in autism. PeerJ;2023;11:e15751.

INTRODUCTION: The fast, intuitive and autonomous system 1 along with the slow, analytical and more logical system 2 constitute the dual system processing model of decision making. Whether acting independently or influencing each other both systems would, to an extent, rely on randomness in order to reach a decision. The role of randomness, however, would be more pronounced when arbitrary choices need to be made, typically engaging system 1. The present exploratory study aims to capture the expression of a possible innate randomness mechanism, as proposed by the authors, by trying to isolate system 1 and examine arbitrary decision making in autistic participants with high functioning Autism Spectrum Disorders (ASD). METHODS: Autistic participants withhigh functioning ASD and an age and gender matched comparison group performed the random number generation task. The task was modified to limit the contribution of working memory and allow any innate randomness mechanisms expressed through system 1, to emerge. RESULTS: Utilizing a standard analyses approach, the random number sequences produced by autistic individuals and the comparison group did not differ in their randomness characteristics. No significant differences were identified when the sequences were examined using a moving window approach. When machine learning was used, random sequences’ features could discriminate the groups with relatively high accuracy. CONCLUSIONS: Our findings indicate the possibility that individual patterns during random sequence production could be consistent enough between groups to allow for an accurate discrimination between the autistic and the comparison group. In order to draw firm conclusions around innate randomness and further validate our experiment, our findings need to be replicated in a bigger sample.

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15. Milla LA, Corral L, Rivera J, Zuñiga N, Pino G, Nunez-Parra A, Cea-Del Rio CA. Neurodevelopment and early pharmacological interventions in Fragile X Syndrome. Front Neurosci;2023;17:1213410.

Fragile X Syndrome (FXS) is a neurodevelopmental disorder and the leading monogenic cause of autism and intellectual disability. For years, several efforts have been made to develop an effective therapeutic approach to phenotypically rescue patients from the disorder, with some even advancing to late phases of clinical trials. Unfortunately, none of these attempts have completely succeeded, bringing urgency to further expand and refocus research on FXS therapeutics. FXS arises at early stages of postnatal development due to the mutation and transcriptional silencing of the Fragile X Messenger Ribonucleoprotein 1 gene (FMR1) and consequent loss of the Fragile X Messenger Ribonucleoprotein (FMRP) expression. Importantly, FMRP expression is critical for the normal adult nervous system function, particularly during specific windows of embryogenic and early postnatal development. Cellular proliferation, migration, morphology, axonal guidance, synapse formation, and in general, neuronal network establishment and maturation are abnormally regulated in FXS, underlying the cognitive and behavioral phenotypes of the disorder. In this review, we highlight the relevance of therapeutically intervening during critical time points of development, such as early postnatal periods in infants and young children and discuss past and current clinical trials in FXS and their potential to specifically target those periods. We also discuss potential benefits, limitations, and disadvantages of these pharmacological tools based on preclinical and clinical research.

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16. Mitroulaki S, Samakouri M, Serdari A. Children with autism in the Greek educational system: ongoing challenges during the COVID-19 pandemic. BJPsych Int;2023 (Aug);20(3):68-70.

The inclusion of children with autism spectrum disorder (ASD) in typical educational settings has only recently gained momentum in Greece, responding to the recommendations of the international conventions. Reform of special education legislation spotlights the inclusion of children with autism in mainstream schools. The principal goal is to accept the diversity and heterogeneity of all students. This paper presents the educational policy for children with ASD in Greece and comments on teachers’ perceptions of inclusion. School closures due to the COVID-19 pandemic had an adverse impact on children’s lives and created a new environment with different demands for educational inclusion.

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17. Pagano J, Landi S, Stefanoni A, Nardi G, Albanesi M, Bauer HF, Pracucci E, Schön M, Ratto GM, Boeckers TM, Sala C, Verpelli C. Shank3 deletion in PV neurons is associated with abnormal behaviors and neuronal functions that are rescued by increasing GABAergic signaling. Mol Autism;2023 (Aug 1);14(1):28.

BACKGROUND: Phelan-McDermid syndrome (PMS) is a neurodevelopmental disorder characterized by developmental delay, intellectual disability, and autistic-like behaviors and is primarily caused by haploinsufficiency of SHANK3 gene. Currently, there is no specific treatment for PMS, highlighting the need for a better understanding of SHANK3 functions and the underlying pathophysiological mechanisms in the brain. We hypothesize that SHANK3 haploinsufficiency may lead to alterations in the inhibitory system, which could be linked to the excitatory/inhibitory imbalance observed in models of autism spectrum disorder (ASD). Investigation of these neuropathological features may shed light on the pathogenesis of PMS and potential therapeutic interventions. METHODS: We recorded local field potentials and visual evoked responses in the visual cortex of Shank3∆11(-/-) mice. Then, to understand the impact of Shank3 in inhibitory neurons, we generated Pv-cre(+/-) Shank3(Fl/Wt) conditional mice, in which Shank3 was deleted in parvalbumin-positive neurons. We characterized the phenotype of this murine model and we compared this phenotype before and after ganaxolone administration. RESULTS: We found, in the primary visual cortex, an alteration of the gain control of Shank3 KO compared with Wt mice, indicating a deficit of inhibition on pyramidal neurons. This alteration was rescued after the potentiation of GABA(A) receptor activity by Midazolam. Behavioral analysis showed an impairment in grooming, memory, and motor coordination of Pv-cre(+/-) Shank3(Fl/Wt) compared with Pv-cre(+/-) Shank3(Wt/Wt) mice. These deficits were rescued with ganaxolone, a positive modulator of GABA(A) receptors. Furthermore, we demonstrated that treatment with ganaxolone also ameliorated evocative memory deficits and repetitive behavior of Shank3 KO mice. LIMITATIONS: Despite the significant findings of our study, some limitations remain. Firstly, the neurobiological mechanisms underlying the link between Shank3 deletion in PV neurons and behavioral alterations need further investigation. Additionally, the impact of Shank3 on other classes of inhibitory neurons requires further exploration. Finally, the pharmacological activity of ganaxolone needs further characterization to improve our understanding of its potential therapeutic effects. CONCLUSIONS: Our study provides evidence that Shank3 deletion leads to an alteration in inhibitory feedback on cortical pyramidal neurons, resulting in cortical hyperexcitability and ASD-like behavioral problems. Specifically, cell type-specific deletion of Shank3 in PV neurons was associated with these behavioral deficits. Our findings suggest that ganaxolone may be a potential pharmacological approach for treating PMS, as it was able to rescue the behavioral deficits in Shank3 KO mice. Overall, our study highlights the importance of investigating the role of inhibitory neurons and potential therapeutic interventions in neurodevelopmental disorders such as PMS.

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18. Rocco K, Drobnyk W, Bruce S, Soumerai SB. Ayres Sensory Integration Therapy for a Child With Rett Syndrome: A Case Report. Clin Med Insights Pediatr;2023;17:11795565231188939.

Rett syndrome (RTT) is a neurodevelopmental disorder characterized by severe dyspraxia, hand stereotypies, and sensory processing issues for which there is no known treatment. This case describes a child with classic RTT and the child’s responses to an Ayres Sensory Integration (ASI) treatment intervention (36 one-hour sessions, 3 per week). We coded and analyzed 36 detailed treatment notes to answer the following questions: What strategies and factors facilitated or interfered with participation in the intervention? What critical elements of treatment documentation might detect small changes in praxis and participation? How do patterns of motor or praxis milestones that emerge over time relate to this child’s level of participation? We observed an increase in participation when the therapist incorporated elements of neurodevelopmental treatment (NDT) and motor learning theory- treatment strategies commonly used with children who have neuromotor conditions. This increase in participation in the ASI intervention emerged at approximately the same time that the therapist documented acquisition of new motor and praxis skills. We observed the importance of using: lateral movement activities to develop weight-shifting and bilateral coordination, rotary play to increase trunk rotation and improve postural transitions, and rhythm to promote continuing or initiating actions. The documentation of the specific amounts of assistance and prompting needed during treatment sessions was an important tool for tracking small yet meaningful responses to treatment. This case illustrates a novel use of ASI intervention supplemented with strategies that developed foundational skills, and the emergence of praxis and participation in the therapeutic intervention. We suggest further research is needed to determine efficacy of ASI for other children with this rare disorder.

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19. Rothwell C, Westermann G, Hartley C. How do Autistic and Neurotypical Children’s Interests Influence their Accuracy During Novel Word Learning?. J Autism Dev Disord;2023 (Aug 2)

Word learning depends on attention – children must focus on the right things at the right times. However, autistic children often display restricted interests, limiting their intake of stimuli during word learning. This study investigates how category interests influence word learning in autism and neurotypical development. Autistic and neurotypical children matched on receptive vocabulary used a touch-screen computer to learn novel words associated with animals (high-interest stimuli) and objects (neutral-interest stimuli) via fast mapping. Response accuracy and speed were examined at referent selection, 5-minute retention, and 24-hour retention. Both groups identified meanings of novel words associated with unfamiliar animals and objects via mutual exclusivity with comparable accuracy. After 5 minutes, autistic children retained animal names with greater accuracy than neurotypical children. Autistic children showed a greater increase in their accuracy between 5-minute and 24-hour retention and outperformed neurotypical children across conditions after a night’s sleep. Across groups, 24-hour retention was predicted by number of target word repetitions heard at referent selection, indicating a relationship between fast mapping input and retention. However, autistic children were slower to respond correctly, particularly in the animal condition. For autistic children, superior word learning associated with high-interest stimuli was relatively short-term, as sleep appeared to consolidate their memory representations for neutral-interest stimuli. Although these results demonstrate that fundamental word learning mechanisms are not atypical in autism, slower response times may signal a speed-accuracy trade-off that could have implications for naturalistic language acquisition. Our findings also indicate favourable environmental conditions to scaffold word learning.

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20. Santos T, Steinway C, Mastrogiannis A, Chen J, Woodward J, Riddle I, Spicer B, Berens J, Davis T, Cornacchia M, Wright C, Lindquist LA, Jan S. Caregiver support, burden, and long-term planning among caregivers of individuals with intellectual and developmental disabilities: A cross-sectional study. J Appl Res Intellect Disabil;2023 (Aug 2)

BACKGROUND: Long-term care planning (LTCP) is critical for individuals with intellectual/developmental disabilities. Objectives of this study were to investigate progression through LTCP, and associations between social support and: (1) LTCP and (2) burden among family caregivers. METHODS: A cross-sectional survey was distributed to caregivers of individuals with intellectual/developmental disabilities in NY, OH, PA, and TX, exploring demographics, supports, burden, and LTCP behaviours. Bivariate and linear multiple regression analyses were used to investigate study objectives. RESULTS: Caregivers (n = 405) were predominantly parents, female, non-Hispanic, and in the ‘learning to plan’ stage of LTCP. Caregiver-identified social support was associated with further progression in LTCP (p = .020) and lower caregiver burden (p < .001). CONCLUSION: Social support was associated with further progression in LTCP, and associated with less burden, however fewer than 40% of caregivers reported having social support. Ongoing exploration of emotional/social needs of caregivers is necessary to better support these families.

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21. Sutherland D, Flynn S, Kurzeja O, Griffin J, Hastings R. Family-systems interventions for families of people with an intellectual disability or who are autistic: a systematic review. J Intellect Disabil Res;2023 (Aug 2)

BACKGROUND: Family-systems interventions have been proposed as one way of supporting families of people with an intellectual disability (ID) or who are autistic. This systematic review aimed to summarise what family-systems interventions have been studied with this population, what evidence there is for their effectiveness and families’ experiences of the interventions. METHODS: The review was preregistered on PROSPERO (CRD42022297516). We searched five electronic databases, identified 6908 records and screened 72 full texts. Study quality was evaluated using the Mixed Methods Appraisal Tool, and a narrative synthesis was used. RESULTS: We identified 13 eligible articles with 292 participating families. Most studies reported positive effects of the interventions on wellbeing and family relationships, and families reported positive experiences. However, research quality was poor and there are no any sufficiently powered randomised controlled trials demonstrating family-systems interventions’ effectiveness for this population. CONCLUSIONS: There is a need for higher-quality research to establish whether family-systems interventions are beneficial for families of people who have an ID or who are autistic.

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22. Tang H, Liang J, Chai K, Gu H, Ye W, Cao P, Chen S, Shen D. Artificial intelligence and bioinformatics analyze markers of children’s transcriptional genome to predict autism spectrum disorder. Front Neurol;2023;14:1203375.

INTRODUCTION: Autism spectrum disorder (ASD), characterized by difficulties in social interaction and communication as well as restricted interests and repetitive behaviors, is extremely challenging to diagnose in toddlers. Early diagnosis and intervention are crucial however. METHODS: In this study, we developed a machine learning classification model based on mRNA expression data from the peripheral blood of 128 toddlers with ASD and 126 controls. Differentially expressed genes (DEGs) between ASD and controls were identified. RESULTS: We identified genes such as UBE4B, SPATA2 and RBM3 as DEGs, mainly involved in immune-related pathways. 21 genes were screened as key biomarkers using LASSO regression, yielding an accuracy of 86%. A neural network model based on these 21 genes achieved an AUC of 0.88. DISCUSSION: Our findings suggest that the identified neurotransmitters and 21 immune-related biomarkers may facilitate the early diagnosis of ASD. The mRNA expression profile sheds light on the biological underpinnings of ASD in toddlers and potential biomarkers for early identification. Nevertheless, larger samples are needed to validate these biomarkers.

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23. Teneqexhi P, Khalid A, Nisbett KE, Job GA, Messer WS, Jr., Ragozzino ME. The Partial M(1) Muscarinic Cholinergic Receptor Agonist, CDD-0102A, Differentially Modulates Glutamate Efflux in Striatal Subregions during Stereotyped Motor Behavior in the BTBR Mouse Model of Autism. ACS Chem Neurosci;2023 (Aug 2);14(15):2699-2709.

The BTBR T(+) Itpr3(tf)/J (BTBR) mouse displays elevated repetitive motor behaviors. Treatment with the partial M(1) muscarinic receptor agonist, CDD-0102A, attenuates stereotyped motor behaviors in BTBR mice. The present experiment investigated whether CDD-0102A modifies changes in striatal glutamate concentrations during stereotyped motor behavior in BTBR and B6 mice. Using glutamate biosensors, change in striatal glutamate efflux was measured during bouts of digging and grooming behavior with a 1 s time resolution. Mice displayed both decreases and increases in glutamate efflux during such behaviors. Magnitude of changes in glutamate efflux (decreases and increases) from dorsomedial and dorsolateral striatum were significantly greater in BTBR mice compared to those of B6 mice. In BTBR mice, CDD-0102A (1.2 mg/kg) administered 30 min prior to testing significantly reduced the magnitude change in glutamate decreases and increases from the dorsolateral striatum and decreased grooming behavior. Conversely, CDD-0102A treatment in B6 mice potentiated glutamate decreases and increases in the dorsolateral striatum and elevated grooming behavior. The findings suggest that activation of M(1) muscarinic receptors modifies glutamate transmission in the dorsolateral striatum and self-grooming behavior.

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24. Tsujita M, Homma M, Kumagaya SI, Nagai Y. Comprehensive intervention for reducing stigma of autism spectrum disorders: Incorporating the experience of simulated autistic perception and social contact. PLoS One;2023;18(8):e0288586.

Stigma of autism spectrum disorders (ASD) is a crucial factor leading to a lower quality of life for individuals with ASD. This research evaluated an intervention effect for the stigma through an experience of simulated autistic visual perception and video-based social contact. The intervention was conducted as an experiential workshop for the ASD simulator. Participants (N = 217; 156 women, 61 men; a mean age of 41.3) voluntarily attended the workshop. In the workshop, they received a short lecture on autistic perception, a simulated experience using the ASD simulator, a narrative video of individuals with ASD, and a group discussion. They completed the multidimensional attitudes scale, which was developed to measure four attitudes toward ASD: negative affect, calm, cognitions, and behaviors. The attitudes were measured three times: the period of registration with the workshop, during participation in the workshop, and six weeks after the workshop. With regard to the measure during participation in the workshop, attendees responded to the attitudes at the beginning or end of the workshop, to confirm whether attitudes changes were attributed to the effectiveness of the intervention or artifacts resulting from participation in the workshop. A significant reduction was observed in negative affective attitudes at the end of the workshop and persisted even six weeks afterward, even though not observed in calm, cognitive, and behavioral attitudes. Our findings suggest that implementation of our intervention can bring about reduction of the stigma associated with ASD. Further studies with a random sampling method are needed to validate its generalizability and elaborate the components of the intervention.

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25. Wang H, Zhao X, Yu D. Nonlinear features of gaze behavior during joint attention in children with autism spectrum disorder. Autism Res;2023 (Aug 2)

Since children with autism spectrum disorder (ASD) might exhibit a variety of aberrant response to joint attention (RJA) behaviors, there is growing interest in identifying robust, reliable and valid eye-tracking metrics for determining differences in RJA behaviors between typically developing (TD) children and those with ASD. Previous eye-tracking studies have not been deeply investigated nonlinear features of gaze time-series during RJA. As a main motivation, this study aimed to extract three nonlinear features (i.e., complexity, long-range correlation, and local instability) of gaze time-series during RJA in children with ASD, which can be measured by fractal dimension (FD), Hurst exponent (H), and largest Lyapunov exponent (LLE), respectively. To illustrate our idea, this study adopted a publicly accessible database, including eye-tracking data collected during RJA from 19 children with ASD (7.74 ± 2.73) and 30 TD children (8.02 ± 2.89), and conducted a battery of nonparametric analysis of covariance (ANCOVA), where gender was used as covariable. Findings showed that gaze time-series during RJA in autistic children may generally have greater FD but lower H than that in TD controls. This implies that children with ASD possess more complex and unpredictable gaze behaviors during RJA than TD children. Furthermore, nonlinear metrics outperformed traditional eye-tracking metrics in obtaining higher identification performance with an accuracy of 82% and an AUC value of 0.81, distinguishing the differences between successful and failed RJA trails, and predicting the severity of ASD symptoms. Findings might bring some new insights into the understanding of the impairments in RJA behaviors for children with ASD.

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26. Washington-Nortey M, Anum A, Serpell Z, Xu Y. Expectations for Children with Autism Spectrum Disorders or Intellectual Disabilities in Ghana: A Comparison Between Service Providers and Parents. J Autism Dev Disord;2023 (Aug 2)

Little is known about care providers’ expectations for children with autism spectrum disorders (ASD) and intellectual disabilities (ID) in Ghana. This study used group concept mapping (n = 9) and a quantitative survey (n = 128) to explore and compare service providers’ and parents’ expectations for children with ASD or ID. Data were analyzed using hierarchical clustering procedures and Multivariate Analysis of Variance (MANOVA). Concept mapping results revealed several expectation clusters, including independence, love and acceptance, equal social rights and opportunities, and professional and caregiver training. MANOVA results revealed significant differences between parents, teachers, and healthcare providers in their perceptions of the importance and likelihood of a child achieving these expectations. Results are discussed in reference to the cultural context, and implications are outlined.

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27. Wu F, Ji XN, Shen MX, Gao YY, Zhang PP, Li SP, Chen Q. [A case of intellectual developmental disorder with behavioral abnormalities and craniofacial dysmorphism with or without seizures caused by PHF21A gene variation and review of literature]. Zhonghua Er Ke Za Zhi;2023 (Aug 2);61(8):726-730.

Objective: To discuss the clinical and genetic features of intellectual developmental disorder with behavioral abnormalities and craniofacial dysmorphism with or without seizures (IDDBCS). Methods: The clinical and genetic records of a patient who was diagnosed with IDDBCS caused by PHF21A gene variation at Children’s Hospital Capital Institute of Pediatrics in 2021 were collected retrospectively. Using  » PHF21A gene » as the keyword, relevant articles were searched at CNKI, Wanfang Data and PubMed from establishment of databases to February 2023. Clinical and genetic features of IDDBCS were summarized in the combination of this case. Results: An 8 months of age boy showed overgrowth (height, weight and head circumference were all higher than the 97(th) percentile of children of the same age and sex) and language and motor developmental delay after birth, and gradually showed autism-like symptoms like stereotyped behavior and poor eye contact. At 8 months of age, he began to show epileptic seizures, which were in the form of a series of spastic seizures with no reaction to adrenocorticotropic hormone but a good response to vigabatrin. Physical examination showed special craniofacial appearances including a prominent high forehead, sparse eyebrows, broad nasal bridge, and downturned mouth with a tent-shaped upper lip. The patient also manifested hypotonia. Whole exome sequencing showed a de novo heterogeneous variant, PHF21A (NM_001101802.1): c.54+1G>A, and IDDBCS was diagnosed. A total of 6 articles (all English articles) were collected, involving this case and other 14 patients of IDDBCS caused by PHF21A gene variation. Clinical manifestations were intellectual disability or developmental delay (15 patients), craniofacial anomalies (15 patients), behavioral abnormalities (12 patients), seizures (9 patients), and overgrowth (8 patients). The main pathogenic variations were frameshift variations (8 patients). Conclusions: IDDBCS should be considered when patients show nervous developmental abnormalities, craniofacial anomalies, seizures and overgrowth. PHF21A gene variation detection helps to make a definite diagnosis.

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28. Xavier J, Johnson S, Cohen D. From child-peer similarity in imitative behavior to matched peer-mediated interventions in autism. Front Psychol;2023;14:1173627.

Self-consciousness develops through a long process, from pre-reflexive consciousness relying on body perception, to « meta » self-awareness. It emerges from the imitative experience between children and their peers. This experience linked to the capacity to test structural similarities between oneself and others, is addressed according to the concept of interpersonal affordance. We hypothesize that the opportunity for co-actors to engage in a process of interpersonal coordination is underlined by their similarity in terms of morphological, behavioral and motor features. This experience can sustain the emergence of new affordances for objects for each co-actor, as well as new affordances in terms of joint actions. We apply this idea in the context of peer-mediated interventions (PMI) in autism spectrum disorder (ASD). We argue that, in PMI, an encounter between children with autism and similar peers would foster the opportunity to engage in a spontaneous process of interpersonal coordination. This process would enable the development of self-consciousness and the emergence of perception of interpersonal, self and other’s affordances for children with autism. We conclude that metrics to assess morphological, behavioral and motor similarity should then be defined and used in future studies to test our hypothesis in children with autism versus TD children or between children with autism.

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29. Zhang M, Ming Y, Du Y, Xin Z. Two-sample Mendelian randomization study does not reveal a significant relationship between cytomegalovirus (CMV) infection and autism spectrum disorder. BMC Psychiatry;2023 (Aug 2);23(1):559.

BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental disorder affecting ~ 2% of children worldwide and is characterized by repetitive, stereotypical behaviours and impaired expressive communication. Cytomegalovirus (CMV) is considered a risk factor for ASD; however, published studies are usually limited by covering too few events and have different conclusions, indicating that the relationship between CMV infection and ASD remains elusive. METHODS: To investigate the association between CMV infection and ASD, we conducted this 2-sample Mendelian randomization (MR) study using genome-wide association studies (GWAS) summary data from FinnGen and the IEU Open GWAS project. RESULTS: Our results showed no significant relationship between all 3 CMV infections (unspecified cytomegaloviral diseases, anti-CMV IgG levels, and maternal CMV) and ASD. CONCLUSIONS: Our results indicate that CMV infection does not significantly increase ASD risk. These results show that the relationship between CMV infection and ASD remains elusive and needs to be further clarified.

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