1. Anna Nagy C, Hann F, Brezóczki B, Farkas K, Vékony T, Pesthy O, Németh D. Intact ultrafast memory consolidation in adults with autism and neurotypicals with autism traits. Brain Res;2024 (Oct 30):149299.

The processes of learning and memory consolidation are closely interlinked. Therefore, to uncover statistical learning in autism spectrum disorder (ASD), an in-depth examination of memory consolidation is essential. Studies of the last five years have revealed that learning can take place not only during practice but also during micro (<1 min) rests between practice blocks, termed micro offline gains. The concept of micro offline gains refers to performance improvements during short rest periods interspersed with practice, rather than during practice itself. This phenomenon is crucial for the acquisition and consolidation of motor skills and has been observed across various learning contexts. Numerous studies on learning in autism have identified intact learning but there has been no investigation into this fundamental aspect of memory consolidation in autistic individuals to date. We conducted two studies with two different samples: 1) neurotypical adults with distinct levels of autistic traits (N = 166) and 2) ASD-diagnosed adults (n(ASD) = 22, n(NTP) = 20). Participants performed a well-established probabilistic learning task, allowing us to measure two learning processes separately in the same experimental design: statistical learning (i.e., learning probability-based regularities) and visuomotor performance (i.e., speed-up regardless of probabilities). Here we show considerable individual differences in offline (between blocks) changes during statistical learning and between-blocks improvement during visuomotor performance. However, cumulative evidence from individual studies suggests that the degree of autistic traits and ASD status are not associated with micro offline gains, suggesting that, like statistical learning, rapid memory consolidation is intact.

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2. Chen Y, Yang C, Gao B, Chen K, Jao Keehn RJ, Müller RA, Yuan LX, You Y. Altered functional connectivity of unimodal sensory and multisensory integration networks is related to symptom severity in autism spectrum disorders. Biol Psychiatry Cogn Neurosci Neuroimaging;2024 (Nov 2)

BACKGROUND: Atypical sensory processing is a prevalent feature in autism spectrum disorders (ASD) and constitutes a core diagnostic criterion in the Diagnostic and Statistical Manual of Mental of Disorders, 5th edition (DSM-5). However, neurocognitive underpinnings of atypical unimodal and multimodal sensory processing and their relationships with autism symptoms remain unclear. METHODS: This study examined intrinsic functional connectivity (FC) patterns among five unimodal sensory and multisensory integration (MSI) networks in ASD with a large multi-site dataset (n = 646), and investigated the relationships among altered FC, atypical sensory processing, social communicative deficits, and overall autism symptoms with correlation and mediation analyses. RESULTS: Relative to typically developing (TD) controls, the ASD group demonstrated increased FC of the olfactory network, decreased FC within the MSI network, and decreased FC of the MSI-unimodal-sensory networks. Furthermore, altered FC was positively associated with autism symptom severity, and such associations were completely mediated by atypical sensory processing and social communicative deficits. CONCLUSIONS: ASD-specific olfactory overconnectivity and MSI-unimodal-sensory underconnectivity lend support to the Intense World Theory and Weak Central Coherence Theory, suggesting olfactory hypersensitivity at the expense of multisensory integration as potential neural mechanisms underlying atypical sensory processing in ASD. These atypical FC patterns further suggest potential targets for psychological and neuromodulatory interventions.

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3. Cheng Y, Dwyer P, Keating CT. Factors underlying differences in knowledge, explicit stigma and implicit biases towards autism across Hong Kong, the United Kingdom and the United States. Autism;2024 (Nov 2):13623613241290565.

Attitudes towards autism vary across countries. Some of this variation could reflect differences in cultural values across countries, or differences in how much people know about autism. Until now, most research on this topic has asked people directly about their attitudes towards interacting with autistic people. As a result, we understand little about why some people unconsciously hold negative attitudes towards autism, and whether these unconscious attitudes vary across countries. We studied explicit attitudes (willingness to interact), implicit attitudes (unconscious beliefs), knowledge about autism, and cultural values in university students from Hong Kong, the United Kingdom and the United States. We found that people were less willing to interact with autistic people if they knew less about autism, aligned with a competitive and hierarchical society (‘vertical individualism’), did not see themselves as part of a collective whose members are equal (less ‘horizontal collectivism’), and if they unconcsciously associated autism with negative attributes. Students in Hong Kong were less willing to interact with autistic people and had less understanding of autism compared to those in the United Kingdom and the United States. Unconscious biases did not differ across countries. Our findings highlight the need to combat misconceptions about autism to improve attitudes towards autistic people, especially in Hong Kong. Unfortunately, our results suggest that acquiring more accurate knowledge may not be sufficient to alter unconscious biases. Further research is needed to determine the factors underlying unconscious biases.

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4. Cosgrove KT, Middleton C, Thompson TG, Be B, DeVries L. « It’s Really Complicated »: Engaging Key Stakeholders to Inform a Novel Parent-led Sexual Health Education Program for Autistic Youth. J Autism Dev Disord;2024 (Nov 2)

Autistic adolescents frequently encounter difficulties in managing changes associated with puberty, sexuality, and relationships, and parents may be a useful source of sexual and reproductive health education (SRE) for this population. Despite this, few evidence-based programs exist to support parents in this role. Thus, there is a need for the development of such programs, particularly those incorporating the lived experiences of key stakeholders. The present qualitative investigation aimed to determine the SRE needs of autistic youth and to inform a novel, parent-led SRE program. Data were collected through semi-structured interviews conducted with two rounds of focus groups with two stakeholder groups: parents of autistic children (N = 4) and adult autistic self-advocates (N = 4). Focus groups were recorded and transcribed verbatim. The research team conducted rapid qualitative analysis on all four transcripts, and major findings were summarized and triangulated across groups. Four overarching themes were identified: « Empower parents as educators, » « Individualize supports and education, » « Consider cultural and intersecting identities, » and « Prioritize safety. » Parents can serve a primary role in providing SRE to autistic youth and would likely benefit from participating in a tailored program that prioritizes safety and considers the influence of culture and other aspects of identity on content delivery. Future research on the implementation of such a program is needed.

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5. Dewitte MMJ, Warreyn P, Prinzie P, De Pauw SSW. Exploring Personality Profiles as a Source of Phenotypic Diversity in Autistic Children and Adolescents. J Autism Dev Disord;2024 (Nov 2)

This study adopts a person-centered approach to evaluate personality diversity as a source of interpersonal variability in autistic children and adolescents, and how personality subgroup membership relates to variability in autistic characteristics, social-emotional presentations, and parenting outcomes. Latent Profile Analysis was used to analyze 569 parent reports on a child-based Five-Factor-Model personality measure (aged 6-18 years; M(age) = 11.8 years, SD = 3.1; 70% boys). Four distinct personality profile groups were identified, showing varying levels in the low to average range of all five personality domains. All groups scored lowest on Extraversion and Emotional Stability. They differed the most in Imagination and the least in Emotional Stability. Group 1 (n = 72) exhibited the lowest mean-level scores on all five domains, whereas Group 4 (n = 90) had the highest domain scores. Group 2 (n = 307) and Group 3 (n = 100) showed more diverse patterns. Group membership was meaningfully associated with variation in characteristics of social interaction and communication, internalizing, externalizing, and attentional problems, psychosocial strengths, and positive parenting strategies. Only modest group differences were found in parenting stress. All groups had similar scores on repetitive and restrictive behaviors. These findings help to better understand and support natural subgroups within the autism phenotype by exploring shared personality attributes.

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6. Langdon PE, Apanasionok MM, Scripps E, Bunning K, Filipczuk M, Gillespie D, Hastings RP, Jahoda A, McNamara R, Rai D, Gray KM. Behavioural interventions to treat anxiety in adults with autism and moderate to severe intellectual disabilities: the BEAMS-ID feasibility study. Health Technol Assess;2024 (Oct);28(72):1-147.

BACKGROUND: Interventions for anxiety need to be adapted to meet the needs of autistic people with moderate to severe learning disabilities and successfully modelled before evidence about efficacy can be generated from clinical trials. OBJECTIVES: The objectives were to: (1) adapt a behavioural intervention for anxiety, develop an intervention fidelity checklist and logic model, and appraise candidate outcome measures, together with carers, autistic people, and clinicians, (2) characterise treatment-as-usual, (3) model the adapted intervention to determine the acceptability and feasibility for all stakeholders, judge the appropriateness of outcome measures, examine the feasibility and acceptability of consent and associated processes and (4) describe factors that facilitate or challenge intervention delivery. DESIGN: This study had two phases. Phase 1a: using consensus methods, an intervention adaptation group was formed who met to adapt the intervention, appraise candidate outcome measures, and contribute to the development of the intervention fidelity checklists and logic model. Phase 1b: a national online survey was conducted with professionals to characterise treatment-as-usual. Phase 2: this was a single-group non-randomised feasibility study designed to model the intervention to test intervention feasibility and acceptability, outcome measures, and aspects of the research process. SETTING: Participants were recruited from National Health Service community adult learning disabilities teams in England. PARTICIPANTS: Participants aged 16 and over with a diagnosis of autism, moderate to severe learning disabilities, an anxiety disorder, and a carer who was available to take part in the intervention. For those who lacked capacity to make a decision about taking part, a consultee had to provide advice that the participant should be included in the study. INTERVENTIONS: The intervention comprised 12 sessions alongside treatment-as-usual. MAIN OUTCOME MEASURES: The feasibility and acceptability of the intervention and research processes, outcome measure completion rates, and intervention adherence. RESULTS: The intervention was successfully adapted and modelled with 28 autistic participants with moderate to severe learning disabilities. The intervention was judged to be feasible and acceptable by autistic adults with learning disabilities, carers, and therapists. Carers and therapists suggested minor intervention revisions. Carers completed 100% of outcome measures and the missing data rate was low; however, they indicated that some of the questions were repetitive and said they had difficulty responding to some items. The use of the Mental Capacity Act, 2005, led to an average 5-week delay to participant enrolment. The accrual rate was affected by the COVID-19 pandemic and improved during the summer and early autumn of 2022. LIMITATIONS: Randomisation was not modelled within this feasibility study, although carers and therapists indicated that this would be acceptable. CONCLUSIONS: The BEAMS-ID intervention and associated study processes were judged to be feasible and acceptable. The intervention required minor revision. FUTURE WORK: The BEAMS-ID intervention should be tested further within a trial. STUDY REGISTRATION: This study is registered as ISRCTN12637590. FUNDING: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: NIHR129804) and is published in full in Health Technology Assessment; Vol. 28, No. 72. See the NIHR Funding and Awards website for further award information. This study was about autistic adults with moderate to severe learning disabilities who have anxiety. There are good interventions for anxiety, but these need to change to meet the needs of autistic adults with moderate to severe learning disabilities. An example of such an intervention is called exposure therapy. This study had two parts. In the first part, we worked with autistic adults, carers and family members, and professionals to adapt an existing anxiety intervention. We also completed a national survey to find out what interventions people are getting now. In the second part, the intervention was tested with 28 autistic adults with moderate to severe learning disabilities. We asked participants, carers and clinicians about their experiences of being part of the study and receiving the intervention. We successfully changed an existing intervention together with autistic adults, carers and family members, and professionals. The intervention included relaxation training and exposure therapy. From our national survey, we found out that autistic people with moderate to severe learning disabilities who have problems with anxiety are most often offered psychological interventions (e.g. relaxation) or medication (e.g. sertraline) for anxiety. Exposure therapy was not offered very frequently. We tried out our intervention and autistic people with moderate to severe learning disabilities told us that they liked coming to the intervention and liked that their carer attended. Carers liked taking part in the research and were positive about the intervention. Therapists told us that the intervention was suitable and were positive about the training they received in delivering the intervention. Both carers and therapists suggested some changes to the intervention to help improve it in the future. We recommended that a larger study should now be completed. eng

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7. Larson E, Mattie RL, Riffkin SA. Assessment of Acceptability, Usage, and Impact on Caregivers of Children With Autism’s Stress and Mindfulness: Multiple-Method Feasibility Study of the 5Minutes4Myself App’s Mindfulness Module. JMIR Hum Factors;2024 (Oct 31);11:e54171.

BACKGROUND: Caregiver wellness programs need to be easily accessible to address caregivers’ constraints to participation. OBJECTIVE: We aimed to assess the feasibility of 5Minutes4Myself app’s mindfulness module (usability, usage, and impact on caregivers’ levels of mindfulness and perceived stress). METHODS: Before and after participation in the 5Minutes4Myself program, 15 participants were asked to complete the Perceived Stress Scale (PSS) and Five Facet Mindfulness Questionnaire (FFMQ). Data on the usage of app-delivered meditations were collected electronically via the app, and app usability was rated on the Modified System Usability Scale. Analyses assessed participants’ frequency of use of app-delivered meditations, app usability, and changes in participants’ stress and mindfulness post intervention. RESULTS: Overall, participants completed 10.9 minutes of mindfulness meditations per week and rated the app 76.7, indicating above-average usability. Related samples t tests (2-tailed) found that group PSS (t10=1.20, P=.26) and FFMQ (t10=-1.57, P=.15) pre- or postintervention mean scores were not significantly different. However, a visualization of pre- and post-PSS and mindfulness scores suggested there was a group of responders who had decreased stress with increased mindfulness. This was confirmed via an individual change analysis. The effect size of the FFMQ scores (d=0.47) suggests there may be treatment effects with a larger sample. A hierarchical multiple regression analysis examined the degree mindfulness impacted perceived stress; 20% of the variance in participants’ perceived stress could be attributed to increases in self-rated mindfulness (P=.04) when controlling for preintervention stress levels. CONCLUSIONS: Caregivers found the app highly usable and on average used low-dose levels of mindfulness meditations (10 min/wk). For responders, increased mindfulness was related to stress reduction to population-based levels.

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8. Lievore R, Maffei A, Sessa P, Mammarella IC. A Comprehensive Investigation of Social Anxiety and Social Evaluative Stress in Autistic Children and Adolescents and Specific Learning Disorders. J Autism Dev Disord;2024 (Nov 2)

The aim was to investigate trait social anxiety and social evaluative stress in autistic children and adolescents and Specific Learning Disorders (SLD). This was done by evaluating behavioral, subjective, and autonomic responses to the Trier Social Stress Test (TSST). Study 1 included 280 children and adolescents: 60 autistic without intellectual disability (ID), 70 SLD, and 150 non-diagnosed (ND) peers. Study 2 involved 55 participants: 15 autistic without ID, 15 SLD, and 20 ND. The sample was predominantly male. In Study 1, behavioral (quality of public speech) and subjective (valence, arousal, perceived competence, and worries) aspects of social stress were examined. Study 2 expands upon the first study, as physiological responses to social stress were also measured. Trait social anxiety was investigated using both parents’ and children’s reports in the two studies. Parents of autistic participants and with SLD reported higher trait social anxiety in their children than the parents of ND. No differences emerged from the participants’ self-reports, though those autistic and with SLD were assigned lower scores in the public speech quality than ND. Autistic children and adolescents reported lower arousal and higher perceived competence than ND, while those with SLD reported a lower perception of competence. Autistic participants had a decreased cardiac reactivity across the TSST when compared to SLD and ND. Our findings show unique patterns of responses within each group, confirming that the combined investigation of trait anxiety and social stress responses could be a valuable insight in research and clinical practice.

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9. Noori AS, Rajabi P, Sargolzaei J, Alaghmand A. Correlation of biochemical markers and inflammatory cytokines in autism spectrum disorder (ASD). BMC Pediatr;2024 (Nov 1);24(1):696.

INTRODUCTION: Autism Spectrum Disorder (ASD) is a disorder that severely affects neurodevelopment, and its underlying causes are not yet entirely understood. Research suggests that there may be a connection between the occurrence of ASD and changes in immune responses. This study aims to know if some biochemical and inflammatory cytokines are promising biomarkers for ASD and whether they are involved in the pathogenesis of ASD. METHODS: The serum levels of CRP, TNF-α, TGF-β, IL-1β, IL-10, 1 L-8, and IL-6 were measured in all of the patients (n = 22) and in the healthy (n = 12) children using ELISA method. RESULTS: The serum concentrations of IL-10 and IL-8 were significantly lower in the ASD patients compared to the control group (p < 0.05) and there were not significant differences between CRP, TNF-α, TGF-β, IL-6 and IL-1β levels in two groups. There were positive correlations between CRP and IL-10, also CRP and IL-8, in ASD group. In contrast to the ASD patients, the correlations of IL-8, IL-10, and CRP were not significant in the control group. CONCLUSION: In conclusion, this study highlights the potential role of certain biochemical markers and inflammatory cytokines in ASD. Specifically, the lower levels of IL-10 and IL-8 in ASD patients, along with the significant correlations between CRP and these cytokines, suggest an altered immune response in individuals with ASD. These findings support the hypothesis that immune dysregulation may be involved in ASD pathogenesis. Further research is needed to explore these biomarkers and their mechanistic links to ASD, which could lead to improved diagnostics or therapeutic strategies.

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10. Norris JE, Berry-Kravis EM, Harnett MD, Reines SA, Reese MA, Outterson AH, Michalak C, Furman J, Gurney ME, Ethridge LE. Auditory N1 event-related potential amplitude is predictive of serum concentration of BPN14770 in fragile X syndrome. Mol Autism;2024 (Nov 2);15(1):47.

Fragile X syndrome (FXS) is a rare neurodevelopmental disorder caused by a CGG repeat expansion ≥ 200 repeats in 5′ untranslated region of the FMR1 gene, leading to intellectual disability and cognitive difficulties, including in the domain of communication. A recent phase 2a clinical trial testing BPN14770, a phosphodiesterase 4D inhibitor, showed improved cognition in 30 adult males with FXS on drug relative to placebo. The initial study found significant improvements in clinical measures assessing cognition, language, and daily functioning in addition to marginal improvements in electroencephalography (EEG) results for the amplitude of the N1 event-related potential (ERP) component. These EEG results suggest BPN14770 improved neural hyperexcitability in FXS. The current study investigated the relationship between BPN14770 pharmacokinetics and the amplitude of the N1 ERP component from the initial data. Consistent with the original group-level finding post-period 1 of the study, participants who received BPN14770 in period 1 showed a significant correlation between N1 amplitude and serum concentration of BPN14770 measured at the end of period 1. These findings strengthen the validity of the original result, indicating that BPN14770 improves cognitive performance by modulating neural hyperexcitability. This study represents the first report of a significant correlation between a reliably abnormal EEG marker and serum concentration of a novel pharmaceutical in FXS.

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11. Uldbjerg CS, Leader J, Minguez-Alarcon L, Chagnon O, Dadd R, Ford J, Fleury E, Williams P, Juul A, Bellinger DC, Calafat AM, Hauser R, Braun JM. Associations of maternal and paternal preconception and maternal pregnancy urinary phthalate biomarker and bisphenol A concentrations with offspring autistic behaviors: The PEACE study. Environ Res;2024 (Oct 30):120253.

BACKGROUND: Environmental chemical exposures in utero may play a role in autism development. While preconception risk factors for autism are increasingly being investigated, little is known about the influence of chemical exposures during the preconception period, particularly for paternal exposures. METHODS: In 195 children from the Preconception Environmental exposures And Childhood health Effects (PEACE) cohort born to parents recruited from a fertility clinic in Boston, Massachusetts between 2004-2017, we quantified concentrations of 11 phthalate metabolites and bisphenol A (BPA) in urine samples collected from mothers and fathers before conception and mothers throughout pregnancy. When children were 6-15 years old, parents completed the Social Responsiveness Scale (SRS) questionnaire assessing autistic behaviors. We used linear mixed effect models to estimate covariate-adjusted associations of phthalate biomarker and BPA concentrations, separately for maternal preconception (n=179), paternal preconception (n=122), and maternal pregnancy (n=177), with SRS T-scores, based on age and gender, in offspring. We used quantile g-computation models for mixture analyses and evaluated modification by selected dietary factors. RESULTS: The mean SRS T-score was 47.7 (±7.4), lower than the normative mean of 50. In adjusted models for individual biomarkers or mixtures, few associations were observed and estimates were generally negative (e.g., lower SRS T-scores) and imprecise. We observed associations of higher mono-isobutyl phthalate (MiBP) concentrations measured in maternal preconception and paternal preconception periods with lower SRS T-scores (β(maternal_precon) = -1.6, 95% CI -2.7; -0.4; β(paternal_precon) = -2.9, 95% CI -4.6; -1.2) for each log(e) increase. In a subset of participants with maternal preconception nutrition information, we generally observed stronger inverse associations with higher folate and iron intake, particularly for folate intake and MiBP concentrations. CONCLUSIONS: Urinary phthalate biomarker and BPA concentrations during preconception (maternal and paternal) and pregnancy (maternal) were not associated with adverse autistic behaviors in these children. Larger studies are needed to elucidate the observed associations, while considering interactions between maternal nutrition and chemical exposures.

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