Pubmed du 26/07/23

Pubmed du jour

1. Alam S, Westmark CJ, McCullagh EA. Diet in treatment of autism spectrum disorders. Frontiers in neuroscience. 2022; 16: 1031016.

Altering the diet to treat disease dates to c. 400 BC when starvation was used to reduce seizures in persons with epilepsy. The current diversity of symptomology and mechanisms underlying autism spectrum disorders (ASDs) and a corresponding lack of disorder-specific effective treatments prompts an evaluation of diet as a therapeutic approach to improve symptoms of ASDs. In this review article, we summarize the main findings of nutritional studies in ASDs, with an emphasis on the most common monogenic cause of autism, Fragile X Syndrome (FXS), and the most studied dietary intervention, the ketogenic diet as well as other dietary interventions. We also discuss the gut microbiota in relation to pre- and probiotic therapies and provide insight into future directions that could aid in understanding the mechanism(s) underlying dietary efficacy.

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2. Giesbrecht GF, Lebel C, Dennis CL, Silang K, Xie EB, Tough S, McDonald S, Tomfohr-Madsen L. Risk for Developmental Delay Among Infants Born During the COVID-19 Pandemic. Journal of developmental and behavioral pediatrics : JDBP. 2023; 44(6): e412-e20.

OBJECTIVE: Attempts by governments around the world to mitigate the spread of COVID-19 have substantially altered the early rearing environment, raising concerns about potential negative consequences for babies born during this time. The objective of this study was to determine whether infants born during the COVID-19 pandemic were at greater risk of screening positive for developmental delay compared with infants born before the pandemic. METHODS: Participants were from 2 longitudinal cohorts. The prepandemic cohort, Impact of Maternal and Paternal Postpartum Depression, recruited postpartum individuals in the period between 2015 and 2018. Infant development milestone data (Ages and Stages Questionnaire [ASQ-3]) were collected at 1-year postpartum (n = 2903), between 2016 and 2019. The pandemic cohort, Pregnancy during the Pandemic, recruited pregnant individuals between April 2020 and April 2021. Infant development milestone data (ASQ-3) were collected at 1-year postpartum (n = 3742), between May 2021 and December 2022. Sociodemographic information, pregnancy outcomes, and depression symptom data were also collected. RESULTS: In covariate-adjusted analyses, pandemic-born infants had lower mean scores and higher odds of screening positive for delay on the Communication, Gross Motor, and Personal-Social domains of the ASQ-3 compared with prepandemic infants. Sex differences showed that males and females screened « at risk » in different domains. CONCLUSION: Most pandemic-born infants display typical development, and differences between prepandemic and pandemic-born infants were small. Nevertheless, an increased risk for delayed development among pandemic-born infants suggests the need for ongoing monitoring to determine what, if any, resources and interventions are needed to support healthy child development.

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3. Goel A, Cantu DA, Guilfoyle J, Chaudhari GR, Newadkar A, Todisco B, de Alba D, Kourdougli N, Schmitt LM, Pedapati E, Erickson CA, Portera-Cailliau C. Author Correction: Impaired perceptual learning in a mouse model of Fragile X syndrome is mediated by parvalbumin neuron dysfunction and is reversible. Nature neuroscience. 2023.

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4. Hotez E, Giwa Onaiwu M. A Neurodiversity-Oriented Approach to Address Autism Wandering as a « Problem Behavior » in Pediatrics. Cureus. 2023; 15(6): e40862.

Pediatricians are frequently tasked with addressing autism « problem behaviors, » including wandering, defined as leaving the safety of a responsible person’s care or a safe area (alternatively referred to as elopement). In the following commentary, we – as autism researchers and individuals with lived experience – discuss the prevalence and public health consequences of wandering. We conceptualize wandering in the context of « problem behaviors » for autistic individuals and describe the current state of the evidence on wandering prevention and intervention. We emphasize that pediatricians have a unique opportunity to optimize their efforts to address wandering – as well as related « problem behaviors » – utilizing a neurodiversity orientation. This will allow them to enact approaches that address the potential upstream mechanisms underlying wandering to make these efforts more effective and provide critical assistance to families. In this manuscript, we provide recommendations to pediatricians to more effectively address the mechanisms underlying and exacerbating these challenges to improve the health, well-being, and quality of life of autistic children and their families. In particular, we recommend that pediatricians focus efforts toward 1) addressing the link between chronic stress and « problem behaviors »; 2) engaging individuals, caregivers, and families as experts in their health and development; and 3) collaborating with the systems and sectors relevant to autistic individuals and their families.

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5. Jiang P, Zhou L, Zhao L, Fei X, Wang Z, Liu T, Tang Y, Li D, Gong H, Luo Y, Li S, Yang H, Liao H, Fan X. Puerarin attenuates valproate-induced features of ASD in male mice via regulating Slc7a11-dependent ferroptosis. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. 2023.

Autism spectrum disorder (ASD) is a complicated, neurodevelopmental disorder characterized by social deficits and stereotyped behaviors. Accumulating evidence suggests that ferroptosis is involved in the development of ASD, but the underlying mechanism remains elusive. Puerarin has an anti-ferroptosis function. Here, we found that the administration of puerarin from P12 to P15 ameliorated the autism-associated behaviors in the VPA-exposed male mouse model of autism by inhibiting ferroptosis in neural stem cells of the hippocampus. We highlight the role of ferroptosis in the hippocampus neurogenesis and confirm that puerarin treatment inhibited iron overload, lipid peroxidation accumulation, and mitochondrial dysfunction, as well as enhanced the expression of ferroptosis inhibitory proteins, including Nrf2, GPX4, Slc7a11, and FTH1 in the hippocampus of VPA mouse model of autism. In addition, we confirmed that inhibition of xCT/Slc7a11-mediated ferroptosis occurring in the hippocampus is closely related to puerarin-exerted therapeutic effects. In conclusion, our study suggests that puerarin targets core symptoms and hippocampal neurogenesis reduction through ferroptosis inhibition, which might be a potential drug for autism intervention.

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6. Kalb LG, Kramer JM, Goode TD, Black SJ, Klick S, Caoili A, Klipsch S, Klein A, Urquilla MP, Beasley JB. Evaluation of telemental health services for people with intellectual and developmental disabilities: protocol for a randomized non-inferiority trial. BMC health services research. 2023; 23(1): 795.

BACKGROUND: Roughly 40% of those with intellectual/developmental disabilities (IDD) have mental health needs, twice the national average. Unfortunately, outpatient mental health services are often inaccessible, increasing reliance on hospital-based services. While telemental health services hold potential to address this gap, little is known about the effectiveness of telemental health for the diversity of persons with IDD, especially as it relates to crisis prevention and intervention services. Accordingly, the aims of this study are to: (1) compare telemental health versus in-person crisis prevention and intervention services among people with IDD; and (2) understand if outcomes vary across subpopulations, in order to identify potential disparities. METHODS: This study will take place within START (Systemic, Therapeutic, Assessment, Resources, and Treatment), a national evidence-based model of mental health crisis prevention and intervention for people with IDD. A total of 500 youth and adults, located across nine states, will be randomized 1:1 to telemental health vs. in-person. Participant inclusion criteria are ages 12-45 years, living in a family setting, and newly enrolled (within 90 days) to START. Outcomes will be assessed, using a non-inferiority design, for up to 1 year or until discharge. The intervention is comprised of four components: (1) outreach; (2) consultation/coping skills; (3) intake/assessment; and, (4) 24-hour crisis response. The in-person condition will deliver all components in-person. The telemental health condition will deliver components 1 & 2, via telephonic or other communication technology, and components 3 & 4 in-person. Outcomes include mental health crisis contacts, mental health symptoms, emergency psychiatric service use, perceived quality of mental healthcare, and time to discharge. DISCUSSION: To our knowledge, this will be the first trial of a telemental health crisis program for the IDD population. The study will be executed by an interdisciplinary team of experts that includes persons with lived experience of disability. Understanding the benefits of specific telemental health methods has important implications to the design of interventions. This telemental health study offers promise to address disparities in access to mental health care for people with IDD across diverse racial, ethnic, linguistic, and cultural groups. TRIAL REGISTRATION: Clinicaltrials.gov ( #NCT05336955 ; Registration Date: 4/20/2022).

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7. Leng LL, Zhu YW, Zhou LG. Explaining differences in autism detection timing: Age of diagnosis and associated individual and socio-familial factors in Chinese children. Autism : the international journal of research and practice. 2023: 13623613231187184.

Timely detection is an issue of paramount importance in the care of children with autism spectrum disorder. Whether the delayed autism spectrum disorder diagnosis can be explained by children’s clinical presentations and socio-familial status in China is a question to be addressed. We investigated 1235 autism spectrum disorder children from 132 rehabilitation organisations in Shenzhen, China. These children were found to have a mean age of diagnosis of 31.4 ± 12.7 months and a median age of diagnosis of 30.0 months. The majority of these children were able to receive their diagnosis during toddlerhood. However, about one in six were not diagnosed until they entered preschool or later, thus missing the golden window of opportunity for early intervention. The age of diagnosis was likely to be late if the children were older, were less severe and presented with no intellectual impairment. The odds of having a delayed autism spectrum disorder diagnosis were more than 9 times higher among migrant autism spectrum disorder children than among those with local household registrations, thus underscoring the importance of identifying culturally sensitive socio-economic determinants in autism spectrum disorder detection, as these factors are likely to affect the quality of life of many autism spectrum disorder children and their families.

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8. Mann A, Aghababaie A, Kalitsi J, Martins D, Paloyelis Y, Kapoor RR. Neurodevelopmental impairments in children with septo-optic dysplasia spectrum conditions: a systematic review. Molecular autism. 2023; 14(1): 26.

BACKGROUND: Septo-optic dysplasia (SOD) is a rare condition diagnosed in children with two or more of the following: hypopituitarism, midline brain abnormalities, and optic nerve hypoplasia. Children with SOD experience varied visual impairment and endocrine dysfunction. Autistic-like behaviours have been reported; however, their nature and prevalence remain to be fully understood. The present systematic review aimed to explore the type and prevalence of neurodevelopmental impairments in children with SOD spectrum conditions. METHODS: The search was conducted in PubMed, EMBASE, and PsycInfo. Hand-searching reference lists of included studies was conducted. All peer-reviewed, observational studies assessing behavioural and cognitive impairments or autism spectrum disorder (ASD) symptoms in children (< 18 years) with SOD, optic nerve hypoplasia, and SOD-plus were included. Studies were excluded if they did not report standardised measures of neurodevelopmental impairments or ASD outcomes. RESULTS: From 2132 screened articles, 20 articles reporting data from a total of 479 children were included in prevalence estimates. Of 14 studies assessing cognitive-developmental outcomes, 175 of 336 (52%) children presented with intellectual disability or developmental delay. A diagnosis of ASD or clinical level of symptoms was observed in 65 of 187 (35%) children across five studies. Only five studies assessed for dysfunction across behavioural, emotional, or social domains and reported impairments in 88 of 184 (48%) of children assessed. LIMITATIONS: Importantly, high heterogeneity among the samples in relation to their neuroanatomical, endocrine, and optic nerve involvement meant that it was not possible to statistically assess the relative contribution of these confounding factors to the specific neurodevelopmental phenotype. This was further limited by the variation in study designs and behavioural assessments used across the included studies, which may have increased the risk of information bias. CONCLUSIONS: This systematic review suggests that the prevalence of neurodevelopmental impairments in children within the SOD spectrum may be high. Clinicians should therefore consider including formal assessments of ASD symptoms and neurodevelopmental impairments alongside routine care. There is, additionally, a need for further research to define and validate a standardised battery of tools that accurately identify neurodevelopmental impairments in SOD spectrum conditions, and for research to identify the likely causal mechanisms.

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9. Must A, Eliasziw M, Stanish H, Curtin C, Bandini LG, Bowling A. Passive and social screen time in children with autism and in association with obesity. Frontiers in pediatrics. 2023; 11: 1198033.

BACKGROUND: Screen time has been identified as a risk factor for childhood obesity, but the media landscape has evolved rapidly. Children with autism tend to be heavy users of screens and have an elevated prevalence of obesity. We know little about screen use patterns among children with autism vs. typically developing (TD) peers and in association with obesity. METHODS: Baseline data from 10,842 participants in the Adolescent Brain Cognition Development Study was used to characterize time spent with child-reported passive screen use (television/movies/watching videos), playing video games, and using social media. Duration of screen time by autism status and gender was summarized as mean time per day; obesity was defined using CDC/WHO criteria. A propensity score analysis was used to create a matched dataset for analysis. RESULTS: Overall, 1.7% of children were was identified as having autism. Significant mean differences were observed by autism status and gender for both passive viewing and playing video games. Compared to TD children, boys with autism spent more time (2.9 vs. 2.3 h, p < 0.001) watching TV, movies or videos, as did girls (3.0 vs. 2.0 h, p = 0.002). Compared to TD peers, boys with autism reported more video game time (102.7 vs. 77.5 min, p = 0.001), as did girls with autism (64.4 vs. 37.9 min, p = 0.03); girls with autism also spent more time on social media sites or video chat (45.5 vs. 21.9 min, p = 0.04). Overall, obesity prevalence increased with increasing screen time duration, significantly for passive screen time (p-value = 0.002) and texting (p-value = 0.02). Associations between obesity and screen time duration did not differ by autism status. DISCUSSION: Children with autism spend more time playing video games and on passive and social screen activities than their TD peers, with some variations by gender. High rates of social media use among girls with autism and multiplayer video game use among both boys and girls with autism may challenge the notion that the high levels of screen time reflect social isolation in the group. Given potential positive aspects of screen time in children with autism movement to focus on content and context is appropriate.

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10. Oates M, Bean A. Qualitative Analysis of the Experiences and Perspectives of Autistic Speech-Language Pathologists. American journal of speech-language pathology. 2023: 1-14.

PURPOSE: Supporting autistic speech-language pathologists (SLPs) is critical to expanding diversity within the field of speech-language pathology. The purpose of this study is to better understand how autistic SLPs reconcile tensions between their personal and professional experiences and negotiate the intersection of these identities. METHOD: Five certified SLPs, each of whom had a formal autism diagnosis or self-identified as autistic, engaged in a one-on-one semistructured conversation. The recorded interviews were transcribed manually. Following grounded theory analysis, multiple levels of coding were performed to construct a theoretical interpretation of the data. RESULTS: Four themes arose from the analysis. In the first, participants described their outlooks on their autistic identities and how these have changed over time. The second theme concerns interpersonal tensions and conflicts related to communication differences across neurotypes. In the third, participants reflected on the stigma and ableism they face in their careers, and concerns about disclosing their autistic identity in the workplace. The fourth comprised participants’ neurodiversity-affirming approaches to clinical practice with autistic clients. CONCLUSIONS: This study represents a first step toward understanding the unique strengths of autistic SLPs and the challenges they face. They can be better supported throughout their education, training, and careers. Our field must embrace and promote the neurodiversity paradigm to truly support all our colleagues and clients.

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11. Perna J, Bellato A, Ganapathy PS, Solmi M, Zampieri A, Faraone SV, Cortese S. Association between Autism Spectrum Disorder (ASD) and vision problems. A systematic review and meta-analysis. Molecular psychiatry. 2023.

AIM: To conduct a systematic review and meta-analysis assessing whether vision and/or eye disorders are associated with Autism Spectrum Disorder (ASD). METHOD: Based on a pre-registered protocol (PROSPERO: CRD42022328485), we searched PubMed, Web of Knowledge/Science, Ovid Medline, Embase and APA PsycINFO up to 5(th) February 2022, with no language/type of document restrictions. We included observational studies 1) reporting at least one measure of vision in people of any age with a diagnosis of ASD based on DSM or ICD criteria, or ADOS; or 2) reporting the prevalence of ASD in people with and without vision disorders. Study quality was assessed with the Appraisal tool for Cross-Sectional Studies (AXIS). Random-effects meta-analyses were used for data synthesis. RESULTS: We included 49 studies in the narrative synthesis and 46 studies in the meta-analyses (15,629,159 individuals distributed across multiple different measures). We found meta-analytic evidence of increased prevalence of strabismus (OR = 4.72 [95% CI: 4.60, 4.85]) in people with versus those without ASD (non-significant heterogeneity: Q = 1.0545, p = 0.7881). We also found evidence of increased accommodation deficits (Hedge’s g = 0.68 [CI: 0.28, 1.08]) (non-significant heterogeneity: Q = 6.9331, p = 0.0741), reduced peripheral vision (-0.82 [CI: -1.32, -0.33]) (non-significant heterogeneity: Q = 4.8075, p = 0.4398), reduced stereoacuity (0.73 [CI: -1.14, -0.31]) (non-significant heterogeneity: Q = 0.8974, p = 0.3435), increased color discrimination difficulties (0.69 [CI: 0.27,1.10]) (non-significant heterogeneity: Q = 9.9928, p = 0.1890), reduced contrast sensitivity (0.45 [CI: -0.60, -0.30]) (non-significant heterogeneity: Q = 9.9928, p = 0.1890) and increased retinal thickness (=0.29 [CI: 0.07, 0.51]) (non-significant heterogeneity: Q = 0.8113, p = 0.9918) in ASD. DISCUSSION: ASD is associated with some self-reported and objectively measured functional vision problems, and structural alterations of the eye, even though we observed several methodological limitations in the individual studies included in our meta-analyses. Further research should clarify the causal relationship, if any, between ASD and problems of vision and if problems of vision during early life. PROSPERO REGISTRATION: CRD42022328485.

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12. Plueckebaum H, Meyer L, Beck AK, Menn KH. The developmental trajectory of functional excitation-inhibition balance relates to language abilities in autistic and allistic children. Autism research : official journal of the International Society for Autism Research. 2023.

Autism is a neurodevelopmental condition that has been related to an overall imbalance between the brain’s excitatory (E) and inhibitory (I) systems. Such an EI imbalance can lead to structural and functional cortical deviances and thus alter information processing in the brain, ultimately giving rise to autism traits. However, the developmental trajectory of EI imbalances across childhood and adolescence has not been investigated yet. Therefore, its relationship to autism traits is not well understood. In the present study, we determined a functional measure of the EI balance (f-EIB) from resting-state electrophysiological recordings for a final sample of 92 autistic children from 6 to 17 years of age and 100 allistic (i.e., non-autistic) children matched by age, sex, and nonverbal-IQ. We related the developmental trajectory of f-EIB to behavioral assessments of autism traits as well as language ability. Our results revealed differential EI trajectories for autistic compared to allistic children. Importantly, the developmental trajectory of f-EIB values related to individual language ability. In particular, elevated excitability in late childhood and early adolescence was linked to decreased listening comprehension. Our findings provide evidence against a general EI imbalance in autistic children when correcting for non-verbal IQ. Instead, we show that the developmental trajectory of EI balance shares variance with autism trait development at a specific age range. This is consistent with the proposal that the late development of inhibitory brain activity is a key substrate of autism traits.

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13. Rojas-Torres LP, Alonso-Esteban Y, Alcantud-Marín F. Mindfulness Parenting and Childish Play: A Clinical Trial With Parents of Children With Autism Spectrum Disorders. Psicothema. 2023; 35(3): 259-70.

BACKGROUND: Problems of behaviour, communication, and social interaction associated with Autism Spectrum Disorders can overwhelm parents. Disturbances in parents’ psychological well-being (anxiety, depression) affect adherence to treatment, making it less effective. There is a need to investigate how to increase psychological wellbeing in parents of children with autism. METHOD: An 8-week brief training programme using the Mindfulness Parenting (MP) intervention was applied to fourteen parents (6 couples and two mothers). Participants were assigned to one of two groups, both groups received the same treatment but at two different time points. Measures of anxiety (SCAARED), parental stress (PSI-4), autism severity level (AIM) and mindfulness awareness (FFMQ), were assessed. RESULTS: Analysis indicates that MP training increased mindfulness awareness, increasing non-judgment and reactivity, and consequently, reduced anxiety (parental, general, social), improving parent-child interaction. This improvement did not influence parents’ perception of the severity of the disorder. CONCLUSIONS: The small number of participants precludes generalisation of the results. More clinical trials are needed to demonstrate the usefulness of including these programmes in early intervention services, as well as profiles of parents who may potentially benefit from it.

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14. Soeda S, Ito D, Ogushi T, Sano Y, Negoro R, Fujita T, Saito R, Taniura H. Defects in early synaptic formation and neuronal function in Prader-Willi syndrome. Scientific reports. 2023; 13(1): 12053.

Prader-Willi syndrome (PWS), which is a complex epigenetic disorder caused by the deficiency of paternally expressed genes in chromosome 15q11-q13, is associated with several psychiatric dimensions, including autism spectrum disorder. We have previously reported that iPS cells derived from PWS patients exhibited aberrant differentiation and transcriptomic dysregulation in differentiated neural stem cells (NSCs) and neurons. Here, we identified SLITRK1 as a downregulated gene in NSCs differentiated from PWS patient iPS cells by RNA sequencing analysis. Because SLITRK1 is involved in synaptogenesis, we focused on the synaptic formation and function of neurons differentiated from PWS patient iPS cells and NDN or MAGEL2 single gene defect mutant iPS cells. Although βIII tubulin expression levels in all the neurons were comparable to the level of differentiation in the control, pre- and postsynaptic markers were significantly lower in PWS and mutant neurons than in control neurons. PSD-95 puncta along βIII tubulin neurites were also decreased. Membrane potential responses were measured while exposed to high K(+) stimulation. The neuronal excitabilities in PWS and mutant neurons showed significantly lower intensity than that of control neurons. These functional defects in PWS neurons may reflect phenotypes of neurodevelopmental disorders in PWS.

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15. Tuncay IO, DeVries D, Gogate A, Kaur K, Kumar A, Xing C, Goodspeed K, Seyoum-Tesfa L, Chahrour MH. The genetics of autism spectrum disorder in an East African familial cohort. Cell genomics. 2023; 3(7): 100322.

Autism spectrum disorder (ASD) is a group of complex neurodevelopmental conditions affecting communication and social interaction in 2.3% of children. Studies that demonstrated its complex genetic architecture have been mainly performed in populations of European ancestry. We investigate the genetics of ASD in an East African cohort (129 individuals) from a population with higher prevalence (5%). Whole-genome sequencing identified 2.13 million private variants in the cohort and potentially pathogenic variants in known ASD genes (including CACNA1C, CHD7, FMR1, and TCF7L2). Admixture analysis demonstrated that the cohort comprises two ancestral populations, African and Eurasian. Admixture mapping discovered 10 regions that confer ASD risk on the African haplotypes, containing several known ASD genes. The increased ASD prevalence in this population suggests decreased heterogeneity in the underlying genetic etiology, enabling risk allele identification. Our approach emphasizes the power of African genetic variation and admixture analysis to inform the architecture of complex disorders.

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16. Walton KM, Borowy AR, Taylor CA. « It just depends »: Parent, teacher, and expert conceptualization of social communication in young autistic children. Autism : the international journal of research and practice. 2023: 13623613231185401.

Improving social communication is often one goal during early autism services. However, researchers do not yet know whether their ideas about which social communication skills should be targeted during services for young autistic children are the same as the goals of autism community members, such as parents, teachers, and expert clinicians. This study used focus groups (meetings of small groups of community members) to ask people from these groups about what aspects of social communication are most important to support in young autistic children. A total of 43 people participated in these focus groups. These groups included parents (three groups; 21 people), teachers (two groups; 8 people), and experts in early social communication and autism (two groups; 14 people). Focus group participants talked about several aspects of social communication that were already familiar to the research team, such as problems with expressive communication, language understanding, and social interaction. However, participants also talked about several parts of social communication that were less familiar to the research team and had usually not been mentioned in previous research. These included (1) considering the value of unusual forms of communication, (2) taking context and setting into account when considering social communication, and (3) how communication and emotion regulation impact one another. The information from these focus groups will be helpful to making sure that researchers and clinicians focus their social communication supports on areas that are most important to parents and teachers.

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17. Zovko M, Šimleša S, Olujić Tomazin M. Parenting stress, coping strategies and social support for mothers of preschool children with autism spectrum disorder in the Republic of Croatia. Clinical child psychology and psychiatry. 2023: 13591045231191802.

Parents of children with autism spectrum disorder (ASD) report experiencing more parenting stress than parents of children with typical development or other developmental disorders. Eighty mothers of preschool children with ASD completed questionnaires with the purpose of exploring the extent and characteristics of parenting stress and the possibility of predicting parenting stress based on the mother’s coping strategies, perceived social and professional support, the severity of the child’s symptoms, and certain sociodemographic characteristics. The results show that 19% of the mothers had clinically significant parental stress. Most of the mothers experienced increased stress levels related to the following: poor interactions with their children (34%), the child’s demandingness (27%), and their personal ability to cope with parental distress (20%). The predictors significantly explained 42.8% of the variance in total parental stress, with support from friends and severity of the child’s symptoms being significant unique contributors.

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