1. Caldani S, Humeau E, Delorme R, Bucci MP. Inhibition functions can be improved in children with autism spectrum disorders: An eye-tracking study. Int J Dev Neurosci;2023 (May 23)

Cognitive remediation therapy interventions could improve cognitive functioning in subjects with autism. To investigate the benefit of a short cognitive training rehabilitation in children with autism spectrum disorder (ASD) on pursuit and fixation performances. We recruited two groups (G1 and G2) of 30 children with ASD, sex-, IQ- and age-matched (mean 11.6 ± 0.5 years), and pursuit and fixation eye movements were recorded twice at T1 and T2. Between T1 and T2, a 10-min cognitive training was performed by the G1 group only, whereas the G2 group had a 10-min of rest. For all children with ASD enrolled in the study, there was a positive correlation between restricted and repetitive behaviour scores of both Autism Diagnostic Interview-Revised (ADI-R) and the Autism Diagnostic Observation Schedule (ADOS) and the number of saccades recorded during the fixation task at T1. At T1, oculomotor performances were similar for both groups of ASD children (G1 and G2). At T2, we observed a significant reduction in the number of saccades made during both pursuit and fixation tasks. Our findings underlined the importance to promote cognitive training rehabilitation for children with ASD, leading to a better performance in inhibitory and attention functioning responsible for pursuit and fixation eye movement’s performance.

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2. Cao C, Wang D, Zou M, Sun C, Wu L. Untargeted metabolomics reveals hepatic metabolic disorder in the BTBR mouse model of autism and the significant role of liver in autism. Cell Biochem Funct;2023 (May 22)

Autism spectrum disorder (ASD) is a neurodevelopmental disorder, and the etiology is unknown. Metabolic dysfunction is present in patients with ASD. In the current study, untargeted metabolomics was employed to screen the differential metabolites in the liver of BTBR mouse model of autism, and MetaboAnalyst 4.0 was used for metabolic pathway analysis. Mice were killed, and liver samples were collected for untargeted metabolomics analysis and examination of histopathology. Finally, 12 differential metabolites were identified. The intensities of phenylethylamine, 4-Guanidinobutanoic acid, leukotrieneD4, and SM(d18:1/24:1(15Z)) were significantly upregulated (p < .01), and the intensities of estradiol, CMP-N-glycoloylneuraminate, retinoyl β-glucuronide,4-phosphopantothenoylcysteine, aldophosphamide, taurochenodesoxycholic acid, taurocholic acid, and dephospho-CoA were significantly downregulated (p < .01) in the BTBR group compared with C57 control group, indicating that differences between BTBR and C57 groups were observed in metabolic patterns. Disturbed pathways of the BTBR mice involved lipid metabolism, retinol metabolism, and amino acid and energy metabolism, revealing that bile acid-mediated activation of LXRα might contribute to metabolic dysfunction of lipid and leukotriene D4 produced by the activation of 5-LOX led to hepatic inflammation. Pathological changes in the liver tissue, such as hepatocyte vacuolization, and small amounts of inflammatory and cell necrosis, further supported metabolomic results. Moreover, Spearman's rank correlation revealed that there is a strong relationship between metabolites across liver and cortex, suggesting liver may exert action by connecting peripheral and neural systems. These findings were likely to be of pathological importance or a cause/consequence of autism, and may provide insight into key metabolic dysfunction to target potential therapeutic strategies relating to ASD.

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3. Cha JH, Cho Y, Moon JH, Lee J, Na JY, Kim YJ. Feeding practice during infancy is associated with attention-deficit/hyperactivity disorder and autism spectrum disorder: a population-based study in South Korea. Eur J Pediatr;2023 (May 23)

Attention-deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are representative neurodevelopmental disorders. Using a nationwide database, we aimed to investigate whether feeding practices in infancy (breastfeeding and the timing of supplementary food introduction) could impact ADHD or ASD development. We evaluated 1,173,448 children aged 4-6 months who were included in the National Screening Program for Infants and Children (NHSPIC) between 2008 and 2014. We observed individuals until 6-7 years of age. Data on feeding type (milk feeding: exclusive breastfeeding [EBF], partial breastfeeding [PBF], exclusive formula feeding [EFF] at 4-6 months of age; supplementary food introduction: < 6 or > 6 months of age) were obtained from the NHSPIC, and diagnoses were based on the International Classification of Diseases, Tenth Revision. In a generalized linear model, children who received EBF had significantly lower incidence of both ADHD (odds ratio [OR]: 0.77, 95% confidence interval [CI]: 0.72-0.82) and ASD (OR: 0.64, 95% CI: 0.60-0.67) than that of children who received EFF. PBF also had a significant protective effect on both ADHD (0.91; 0.85-0.98), and ASD (0.89; 0.83-0.95). The timing of supplementary food introduction was not associated with either ADHD or ASD, although there was an increased risk of ASD in the EFF infants who had supplementary food introduced at > 6 months of age. Conclusion: Our study strengthens and supports the beneficial effect of breastfeeding on neurodevelopmental disorders in children. Breastfeeding should be encouraged and recommended to promote desirable neurodevelopmental outcomes. What is Known: • Breastfeeding is beneficial for the overall health of children, including neurodevelopmental outcomes and cognitive functions. What is New: • Breastfeeding, especially exclusive breastfeeding, was protective against neurodevelopmental disorders. • The effect of the timing of supplementary food introduction was limited.

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4. Chen M, Lin Y, Yu C, Fu R, Shentu H, Yao J, Huang J, He Y, Yu M. Effect of cesarean section on the risk of autism spectrum disorders/attention deficit hyperactivity disorder in offspring: a meta-analysis. Arch Gynecol Obstet;2023 (May 23)

PURPOSE: This study was conducted to investigate the relationship between cesarean section (CS) offspring and autism spectrum disorders (ASD)/attention deficit hyperactivity disorder (ADHD). METHODS: Searching of the databases (PubMed, Web of Science, Embase, and Cochrane Library) for studies on the relationship between mode of delivery and ASD/ADHD until August 2022. The primary outcome was the incidence of ASD/ADHD in the offspring. RESULTS: This meta-analysis included 35 studies (12 cohort studies and 23 case-control studies). Statistical results showed a higher risk of ASD (odds ratio (OR) = 1.25, P < 0.001) and ADHD (OR = 1.11, P < 0.001) in CS offspring compared to the VD group. Partial subgroup analysis showed no difference in ASD risk between CS and VD offspring in sibling-matched groups (OR = 0.98, P = 0.625). The risk of ASD was higher in females (OR = 1.66, P = 0.003) than in males (OR = 1.17, P = 0.004) in the CS offspring compared with the VD group. There was no difference in the risk of ASD between CS under regional anesthesia group and VD group (OR = 1.07, P = 0.173). However, the risk of ASD was higher in the CS offspring under general anesthesia than in the VD offspring (OR = 1.62, P < 0.001). CS offspring developed autism (OR = 1.38, P = 0.011) and pervasive developmental disorder-not otherwise specified (OR = 1.46, P = 0.004) had a higher risk than VD offspring, but there was no difference in Asperger syndrome (OR = 1.19, P = 0.115). Offspring born via CS had a higher incidence of ADHD in different subgroup analyses (sibling-matched, type of CS, and study design). CONCLUSIONS: In this meta-analysis, CS was a risk factor for ASD/ADHD in offspring compared with VD.

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5. Espelöer J, Proft J, Kemmer P, Falter-Wagner CM, Vogeley K. What is specific about employment status, workplace experiences and requirements in individuals with autism in Germany?. Autism Res;2023 (May 23)

The challenge of sustainably integrating highly educated individuals with ASD without intellectual disabilities in the first labor market is repeatedly described in literature. In a retrospective study, a group of 197 clinically late-diagnosed adults with ASD without intellectual disabilities was compared to a closely matched group of 501 individuals who did not meet the criteria for the diagnosis of ASD within a utilization population of the Cologne Autism Outpatient Clinic. Results indicated that the pronounced demand for reduction of social and interpersonal requirements at the workplace (including planned or limited contact with colleagues and customers) as well as the experience of difficulties following unexpected changes in the daily routine were specific for ASD. In addition, individuals with ASD reported greater difficulties in finding a suitable job and being able to live on their wages, taking age and educational qualification into account. Supported employment measures were provided significantly more frequently to individuals in the ASD group. In conclusion, impairments in social skills emerged as one of the main obstacles of workplace performance for individuals with ASD emphasizing the necessity to develop and apply ASD-specific support services.

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6. Harris E. Autism Prevalence Has Been on the Rise in the US for Decades-And That’s Progress. JAMA;2023 (May 23);329(20):1724-1726.

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7. Husebye ESN, Romanowska J, Bjørke-Monsen AL, Gilhus NE, Selmer K, Gervin K, Riedel B, Bjørk MH. Does maternal genetic liability to folate deficiency influence the risk of antiseizure medication-associated language impairment and autistic traits in children of women with epilepsy?. Am J Clin Nutr;2023 (May 20)

BACKGROUND: Prenatal exposure to antiseizure medication (ASM) may lead to low plasma folate concentrations and is associated with impaired neurodevelopment. OBJECTIVE: To examine whether maternal genetic liability to folate deficiency interacts with ASM-associated risk of language impairment and autistic traits in children of women with epilepsy. METHODS: We included children of women with and without epilepsy and with available genetic data enrolled in the Norwegian Mother, Father, and Child Cohort Study (MoBa). Information on ASM use, folic acid supplement use and dose, dietary folate intake, child autistic traits, and child language impairment was obtained from parent-reported questionnaires. Using logistic regression, we examined the interaction between prenatal ASM exposure and maternal genetic liability to folate deficiency expressed as polygenic risk score (PRS) of low folate concentrations or maternal rs1801133 genotype (CC or CT/TT) on risk of language impairment or autistic traits. RESULTS: We included 96 children of women with ASM-treated epilepsy, 131 children of women with ASM-untreated epilepsy, and 37,249 children of women without epilepsy. The PRS of low folate concentrations or the maternal rs1801133 genotype did not interact with the ASM-associated risk of language impairment or autistic traits in ASM-exposed children of women with epilepsy compared to ASM-unexposed children aged 1.5-8 years. ASM-exposed children had increased risk of adverse neurodevelopment regardless of maternal rs1801133 genotype (adjusted odds ratio (aOR) for language impairment age 8 years was 2.88 (95% confidence interval (CI) 1.00-8.26) if CC and aOR 2.88 (CI 1.10-7.53) if CT/TT genotypes). In children of women without epilepsy aged 3 years, those with maternal rs1801133 CT/TT compared to CC genotype had increased risk of language impairment (aOR 1.18, CI 1.05-1.34). CONCLUSIONS: In this cohort of pregnant women reporting widespread use of folic acid supplements, maternal genetic liability to folate deficiency did not significantly influence the ASM-associated risk of impaired neurodevelopment.

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8. Junttila M, Kielinen M, Jussila K, Joskitt L, Mäntymaa M, Ebeling H, Mattila ML. The traits of Autism Spectrum Disorder and bullying victimization in an epidemiological population. Eur Child Adolesc Psychiatry;2023 (May 23)

Autistic children (Autism Spectrum Disorder, ASD) show an increased risk of bullying victimization and often face challenges in communication and peer relationships. However, it is unclear to what extent the amount and quality of ASD traits are associated with bullying victimization. This study examined the association of bullying victimization and ASD traits in an epidemiological population of 8-year-old children (n = 4408) using parent and teacher completed Autism Spectrum Screening Questionnaires (ASSQs), both separately and combined. The ASSQ items relating to loneliness and social isolation, lack of co-operating skills, clumsiness and lack of common sense were associated with victimization in the study population. The higher the ASSQ scores, the more the children were victimized: the ASSQ scores increased in parallel with victimization from 0 (0% victimized) to 45 (64% victimized). The victimization rate was 46% in ASD sample, 2% in the total population sample and 2% in the non-ASD population sample. The results enable more targeted means for recognizing potential victimization.

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9. Kersten M, Wilson NJ, Pracilio A, Howie V, Trollor J, Buckley T, Morphet J, Bryce J, Griffin K, Cashin A. A scoping review to inform an auditing framework evaluating healthcare environments for inclusion of people with intellectual disability and/or autism. J Intellect Disabil;2023 (May 22):17446295231174282.

People with intellectual disability and/or autism are likely to be in hospital more often, for longer, and have poorer health outcomes. Few audit tools exist to identify their barriers in mainstream healthcare environments. This study aimed to identify evidence of audit characteristics of healthcare contexts specifically for people with intellectual disability and/or autism, for conceptual development of an auditing framework. A scoping review of evaluations of healthcare environments was completed in January 2023. Findings were presented using the PAGER framework. Of the sixteen studies identified, most originated in the UK, nine focused on intellectual disability, four on autism, and three were concerned with mixed diagnosis. Six domains for auditing healthcare environments were identified: care imperatives, communication to individuals, understanding communication from individuals, providing supportive environments of care, supporting positive behaviour, and actions to make things go well. Further research is recommended to refine an audit framework.

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10. Martínez-Castilla P, Campos R, Samson AC, Van Herwegen J, Dukes D. Perceived Anxiety in Family Caregivers of Individuals with Autism Spectrum Disorder, Down Syndrome and Williams Syndrome during the Lockdown of the First COVID-19 Wave in Spain. Actas Esp Psiquiatr;2023 (Mar);51(2):56-64.

The lockdown during the first wave of COV- ID-19 in Spain has been related to higher levels of anxiety in the general population. However, the emotional impact on Spanish caregivers of individuals with neurodevelopmental disorders (NDD) has not been studied so far.

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11. Ni HC, Chen YL, Chao YP, Wu CT, Chen RS, Chou TL, Gau SS, Lin HY. A lack of efficacy of continuous theta burst stimulation over the left dorsolateral prefrontal cortex in autism: A double blind randomized sham-controlled trial. Autism Res;2023 (May 23)

Although previous open-label trials suggest the therapeutic potential of inhibitory repetitive transcranial magnetic stimulation (rTMS) over the dorsolateral prefrontal cortex (DLPFC) in autism spectrum disorder (ASD), methodological caveats exist. We conducted an 8-week randomized, double-blind sham-controlled trial to investigate the efficacy of inhibitory continuous theta burst stimulation (cTBS, a variant of rTMS) over the left DLPFC in individuals with ASD. Sixty children, adolescents and young adults (aged 8-30 years) with ASD without co-occurring intellectual disabilities were randomized to a 16-session 8-week cTBS versus sham stimulation course, with a follow-up 4 weeks after the trial. The Active group was not superior to the Sham group in any clinical or neuropsychological metrics at Week 8 or Week 12. Time effects of 8-week cTBS on symptoms and executive function were remarkable in both Active and Sham groups, with comparable response rates and effect sizes of changes in symptoms/cognition between groups. Our results from a sufficiently powered sample do not endorse the superior efficacy of cTBS over the left DLPFC to the shamed stimulation for children, adolescents and adults with ASD. These findings suggest that earlier positive open-label trial findings may be generalized by generalized/placebo effects. This highlights the urgent need for more rTMS/TBS studies with rigorous trial designs in ASD.

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12. Nisar S, Haris M. Correction to: Neuroimaging genetics approaches to identify new biomarkers for the early diagnosis of autism spectrum disorder. Mol Psychiatry;2023 (May 23)

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13. Tuffrey-Wijne I, Curfs L, Hollins S, Finlay I. Euthanasia and physician-assisted suicide in people with intellectual disabilities and/or autism spectrum disorders: investigation of 39 Dutch case reports (2012-2021). BJPsych Open;2023 (May 23);9(3):e87.

BACKGROUND: Euthanasia review committees (Regionale Toetsingscommissies Euthanasie, RTE) scrutinise all Dutch cases of euthanasia and physician-assisted suicide (EAS) to review whether six legal ‘due care’ criteria are met, including ‘unbearable suffering without prospect of improvement’. There are significant complexities and ethical dilemmas if EAS requests are made by people with intellectual disabilities or autism spectrum disorders (ASD). AIMS: To describe the characteristics and circumstances of people with intellectual disabilities and/or ASD who were granted their EAS request; investigate the main causes of suffering that led to the EAS request; and examine physicians’ response to the request. METHOD: The online RTE database of 927 EAS case reports (2012-2021) was searched for patients with intellectual disabilities and/or ASD (n = 39). Inductive thematic content analysis was performed on these case reports, using the framework method. RESULTS: Factors directly associated with intellectual disability and/or ASD were the sole cause of suffering described in 21% of cases and a major contributing factor in a further 42% of cases. Reasons for the EAS request included social isolation and loneliness (77%), lack of resilience or coping strategies (56%), lack of flexibility (rigid thinking or difficulty adapting to change) (44%) and oversensitivity to stimuli (26%). In one-third of cases, physicians noted there was ‘no prospect of improvement’ as ASD and intellectual disability are not treatable. CONCLUSIONS: Examination of societal support for suffering associated with lifelong disability, and debates around the acceptability of these factors as reasons for granting EAS, are of international importance.

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14. Weiner L, Costache ME, Bemmouna D, Rabot J, Weibel S, Dubreucq M, Dubreucq J, Coutelle R. Emotion dysregulation is heightened in autistic females: A comparison with autistic males and borderline personality disorder. Womens Health (Lond);2023 (Jan-Dec);19:17455057231174763.

BACKGROUND: Emotion dysregulation is increasingly recognized as highly prevalent and impairing in autistic individuals. Yet, a large majority of studies have considered emotion dysregulation in youth only, and most of them did not consider sex differences in emotion dysregulation manifestation. OBJECTIVES: In the present study, we aim to investigate sex differences relative to emotion dysregulation in autistic adults without intellectual disability as well as its relationship with different factors potentially involved in emotion dysregulation (e.g. camouflaging, alexithymia, suicidality, quality of life). Self-reported emotion dysregulation will be assessed in autistic adults but also in females with borderline personality disorder, given that emotion dysregulation is particularly enhanced in this population. DESIGN: Cross-sectional, prospective, controlled. METHODS: Twenty-eight autistic females, 22 autistic males and 24 females with borderline personality disorder were recruited from a dialectical behavior therapy program waiting list. They completed several self-report questionnaires measuring emotion dysregulation, alexithymia, suicidality, quality of life, camouflaging borderline symptoms and autism severity. RESULTS: Most emotion dysregulation subscale scores and alexithymia scores were heightened in autistic females compared to females with borderline personality disorder and, to a lesser extent, compared to autistic males. Independently of borderline personality disorder symptoms, emotion dysregulation was related to alexithymia and poorer psychological health in autistic females, whereas it was mostly related to autism severity, poorer physical health and living conditions in autistic males. CONCLUSION: Our results suggest that emotion dysregulation is a major difficulty of autistic adults without intellectual disability eligible for dialectical behavior therapy, and this is especially the case for autistic females. There seem to be different sex-specific factors involved in emotion dysregulation found in autistic adults, which highlight the need to target-specific domains (e.g. alexithymia) in the treatment of emotion dysregulation in autistic females. ClinicalTrials.gov Identifier: NCT04737707 https://clinicaltrials.gov/ct2/show/NCT04737707.

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