1. Bataveljic D, Pivonkova H, de Concini V, Hébert B, Ezan P, Briault S, Bemelmans AP, Pichon J, Menuet A, Rouach N. Astroglial Kir4.1 potassium channel deficit drives neuronal hyperexcitability and behavioral defects in Fragile X syndrome mouse model. Nat Commun. 2024; 15(1): 3583.

Fragile X syndrome (FXS) is an inherited form of intellectual disability caused by the loss of the mRNA-binding fragile X mental retardation protein (FMRP). FXS is characterized by neuronal hyperexcitability and behavioral defects, however the mechanisms underlying these critical dysfunctions remain unclear. Here, using male Fmr1 knockout mouse model of FXS, we identify abnormal extracellular potassium homeostasis, along with impaired potassium channel Kir4.1 expression and function in astrocytes. Further, we reveal that Kir4.1 mRNA is a binding target of FMRP. Finally, we show that the deficit in astroglial Kir4.1 underlies neuronal hyperexcitability and several behavioral defects in Fmr1 knockout mice. Viral delivery of Kir4.1 channels specifically to hippocampal astrocytes from Fmr1 knockout mice indeed rescues normal astrocyte potassium uptake, neuronal excitability, and cognitive and social performance. Our findings uncover an important role for astrocyte dysfunction in the pathophysiology of FXS, and identify Kir4.1 channel as a potential therapeutic target for FXS.

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2. Bee Wah Y, Mohd Nasir NN, Hadrawi MF, Kamaruddin AA, Jannoo Z, Afthanorhan A. Effects of stress and self-efficacy on quality of life of mothers with autistic children: Covariance-Based Structural Equation Modeling (CB-SEM) approach. Belitung Nurs J. 2024; 10(2): 201-8.

BACKGROUND: Mothers who have children with autism encounter significant difficulties in caring for their autistic youngsters, leading to higher stress levels and a reduced overall quality of life. External or internal factors can cause and respond to stress, affecting an individual’s physical, psychological, and emotional health. Thus, it is crucial to examine the quality of life of mothers with autistic children. OBJECTIVES: This study aimed to investigate the relationships between stress, self-efficacy, and quality of life (QoL) in mothers of children with autism. METHODS: A cross-sectional study design was used. Self-administered questionnaires were distributed from October to November 2019 to mothers with autistic children using cluster sampling techniques to capture their demographics and perceptions of stress, self-efficacy, and QoL. The data analysis was performed using covariance-based structural equation modeling (CB-SEM). RESULTS: Of the 290 questionnaires distributed, 238 (response rate of 82%) sets were returned, but only 181 questionnaires were usable for further analysis. The findings demonstrated a notable impact of stress and self-efficacy on quality of life and an adverse effect of stress on self-efficacy. Self-efficacy serves as an intermediary in the relationship between stress and quality of life. CONCLUSION: In general, mothers of autistic children typically face moderate stress levels, but they have low levels of self-efficacy and quality of life. Mothers of children with autism need assistance and support from healthcare professionals, such as doctors, nurses, and psychiatrists, so that they can bear the challenges of raising children with special needs and enjoy a higher standard of living with less emotional and physical strain.

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3. Chamberlain A, D’Arcy E, Whitehouse AJ, Wallace K, Hayden-Evans M, Girdler S, Milbourn B, Bölte S, Evans K. Reliability, Validity and Acceptability of the PEDI-CAT with ASD Scales for Australian Children and Youth on the Autism Spectrum. J Autism Dev Disord. 2024.

PURPOSE: The PEDI-CAT (ASD) is used to assess functioning of children and youth on the autism spectrum; however, current psychometric evidence is limited. This study aimed to explore the reliability, validity and acceptability of the PEDI-CAT (ASD) using a large Australian sample. METHODS: Caregivers of 134 children and youth on the spectrum participated in clinical assessments involving the administration of the PEDI-CAT (ASD), Vineland-3, PEDI-CAT (Original) and a feedback instrument. The PEDI-CAT (ASD) content was compared to the ICF Core Sets for ASD to summarize areas of functioning assessed and relevance to autism. RESULTS: The PEDI-CAT (ASD) demonstrated good to excellent internal consistency and test-re-test reliability. Parallel forms reliability with the PEDI-CAT (Original) included significant correlations (good to excellent), however, t-tests showed significantly higher Social/Cognitive scores for the ASD version. Convergent validity results demonstrated that most PEDI-CAT (ASD) and Vineland-3 core domains were significantly correlated (poor to good). Content analysis revealed that the PEDI-CAT (ASD) covered less than half of the ICF Core Sets for ASD (mostly Activities and Participation codes). Just over half the codes assigned to the PEDI-CAT (ASD) were represented in the ICF Core Sets for ASD. Feedback on the acceptability of the measure was mixed, but overall was it was considered user-friendly and efficient. CONCLUSION: The PEDI-CAT (ASD) had adequate psychometric properties and acceptability as a measure of Activities and Participation codes. However, it lacks comprehensiveness and relevance when compared to the ICF Core Sets for ASD and has the potential to overestimate functioning.

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4. Fu X, Platt E, Shic F, Bradshaw J. Infant Social Attention Associated with Elevated Likelihood for Autism Spectrum Disorder: A Multi-Method Comparison. J Autism Dev Disord. 2024.

PURPOSE: The study aimed to compare eye tracking (ET) and manual coding (MC) measures of attention to social and nonsocial information in infants with elevated familial likelihood (EL) of autism spectrum disorder (ASD) and low likelihood of ASD (LL). ET provides a temporally and spatially sensitive tool for measuring gaze allocation. Existing evidence suggests that ET is a promising tool for detecting distinct social attention patterns that may serve as a biomarker for ASD. However, ET is prone to data loss, especially in young EL infants. METHODS: To increase evidence for ET as a viable tool for capturing atypical social attention in EL infants, the current prospective, longitudinal study obtained ET and MC measures of social and nonsocial attention in 25 EL and 47 LL infants at several time points between 3 and 24 months of age. RESULTS: ET data was obtained with a satisfactory success rate of 95.83%, albeit with a higher degree of data loss compared to MC. Infant age and ASD likelihood status did not impact the extent of ET or MC data loss. There was a significant positive association between the ET and MC measures of attention, and separate analyses of attention using ET and AC measures yielded comparable findings. These analyses indicated group differences (EL vs. LL) in age-related change in attention to social vs. nonsocial information. CONCLUSION: Together, the findings support infant ET as a promising approach for identifying very early markers associated with ASD likelihood.

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5. Maitin-Shepard M, O’Tierney-Ginn P, Kraneveld AD, Lyall K, Fallin D, Arora M, Fasano A, Mueller NT, Wang X, Caulfield LE, Dickerson AS, Diaz Heijtz R, Tarui T, Blumberg JB, Holingue C, Schmidt RJ, Garssen J, Almendinger K, Lin PD, Mozaffarian D. Report of a Meeting: Food, Nutrition, and Autism: From Soil to Fork. Am J Clin Nutr. 2024.

Food and nutrition-related factors have the potential to impact development of autism spectrum disorder (ASD) and quality of life for people with ASD, but gaps in evidence exist. On November 10, 2022, Tufts University’s Friedman School of Nutrition Science and Policy and Food and Nutrition Innovation Institute hosted a one-day meeting to explore the evidence and evidence gaps regarding the relationships of food and nutrition with ASD. This meeting report summarizes the presentations and deliberations from the meeting. Topics addressed included prenatal and child dietary intake, the microbiome, obesity, food-related environmental exposures, mechanisms and biological processes linking these factors and ASD, food-related social factors, and data sources for future research. Presentations highlighted evidence for protective associations with prenatal folic acid supplementation and ASD development, increases in risk of ASD with maternal gestational obesity, and the potential for exposure to environmental contaminants in foods and food packaging to influence ASD development. The importance of the maternal and child microbiome in ASD development or ASD-related behaviors in the child was reviewed, as was the role of discrimination in leading to disparities in environmental exposures and psychosocial factors that may influence ASD. The role of child diet and high prevalence of food selectivity in children with ASD and its association with adverse outcomes were also discussed. Priority evidence gaps identified by participants include further clarifying ASD development, including biomarkers and key mechanisms; interactions among psychosocial, social, and biological determinants; interventions addressing diet, supplementation, and the microbiome to prevent and improve quality of life for people with ASD; and mechanisms of action of diet-related factors associated with ASD. Participants developed research proposals to address the priority evidence gaps. The workshop findings serve as a foundation for future prioritization of scientific research to address evidence gaps related to food, nutrition, and ASD.

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6. Marquis S, Marquis NE, Lunsky Y, McGrail KM, Baumbusch J. Prescriptions for Antipsychotics: Youth with Intellectual/Developmental Disabilities Compared to Youth without Intellectual/Developmental Disabilities. J Autism Dev Disord. 2024.

PURPOSE: The purpose of this study was to compare antipsychotic use by youth with intellectual/developmental disabilities to youth without IDD as they transitioned from pediatric to adult health care services. In addition, antipsychotic use was compared between youth with different types of IDD (autism, Fetal Alcohol Syndrome, Down syndrome and ‘other’). METHODS: Population level administrative health data was used to compare the dispensing of antipsychotics for youth aged 15 to 24 years with and without IDD, between 2010 and 2019. Because antipsychotics are associated with metabolic syndrome and type 2 diabetes, we also examined the dispensing data for metformin. In addition, we examined dispensed antipsychotics between different types of IDD. For both dispensing of antipsychotics and metformin, we used multi-variable logistic regression to derive adjusted odds ratios. RESULTS: There were 20,591 youth with IDD and 1,293,791 youth without IDD. Youth with IDD had significantly higher odds of being dispensed an antipsychotic (7.13 (6.82, 7.44)), even when a diagnosis of a psychotic illness was included in the regression. Higher odds were found in all age groups. Youth with IDD also had significantly higher odds of being dispensed metformin (3.739 (3.323, 4.208)) compared to youth without IDD. Youth with autism, FAS and ‘other’ types of IDD diagnoses all had higher odds of being dispensed an antipsychotic compared to youth with Down syndrome. CONCLUSION: Compared to youth without IDD, youth with IDD were more frequently dispensed antipsychotics and metformin. These findings have important implications for the health of youth with IDD.

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7. Rebecchi K. ‘Early childhood autism, Asperger type’, by H. Asperger (1982). Hist Psychiatry. 2024: 957154×241248261.

After his 1944 thesis, Asperger continued to write about autism, but none of these texts have been translated. At a time when autism spectrum disorder faces many challenges (e.g. the nature and measurement of autism), this text tells us more about the particular population that Asperger worked with. He describes sensitive, intelligent, creative and rational children, a far cry from the Wing triad. Moreover, ‘Asperger’s Syndrome’ was introduced after he had died, was included in the DSM-IV in 1994 and was omitted from the DSM-5 in 2013. The question posed by this last text, written before his death, is whether Asperger’s descriptions of autistic children are really part of the autism spectrum disorder or whether they are outside the pathological field.

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8. Rodrigues GD, Cordani R, Veneruso M, Chiarella L, Prato G, Ferri R, Carandina A, Tobaldini E, Nobili L, Montano N. Predominant cardiac sympathetic modulation during wake and sleep in patients with Rett syndrome. Sleep Med. 2024; 119: 188-91.

BACKGROUND: Rett syndrome (RTT) is a rare neurological disorder primarily associated with mutations in the methyl-CpG-binding protein 2 (MECP2) gene. The syndrome is characterized by cognitive, social, and physical impairments, as well as sleep disorders and epilepsy. Notably, dysfunction of the autonomic nervous system is a key feature of the syndrome. Although Heart Rate Variability (HRV) has been used to investigate autonomic nervous system dysfunction in RTT during wakefulness, there is still a significant lack of information regarding the same during sleep. Therefore, our aim was to investigate cardiovascular autonomic modulation during sleep in subjects with RTT compared to an age-matched healthy control group (HC). METHOD: A complete overnight polysomnographic (PSG) recording was obtained from 11 patients with Rett syndrome (all females, 10 ± 4 years old) and 11 HC (all females, 11 ± 4 years old; p = 0.48). Electrocardiogram and breathing data were extracted from PSG and divided into wake, non-REM, and REM sleep stages. Cardiac autonomic control was assessed using symbolic non-linear heart rate variability analysis. The symbolic analysis identified three patterns: 0 V% (sympathetic), 2UV%, and 2LV% (vagal). RESULTS: The 0 V% was higher in the RTT group than in the HC group during wake, non-REM, and REM stages (p < 0.01), while the 2LV and 2UV% were lower during wake and sleep stages (p < 0.01). However, the 0 V% increased similarly from the wake to the REM stage in both RTT and HC groups. CONCLUSIONS: Therefore, the sympatho-vagal balance shifted towards sympathetic predominance and vagal withdrawal during wake and sleep in RTT, although cardiac autonomic dynamics were preserved during sleep.

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