1. Correction to « Prevalence of gastrointestinal symptoms among autistic individuals, with and without co-occurring intellectual disability ». Autism Res;2024 (Feb 2)

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2. Borreca A, Mantovani C, Desiato G, Corradini I, Filipello F, Elia C, D’Autilia F, Santamaria G, Garlanda C, Morini R, Pozzi D, Matteoli M. Loss of interleukin 1 signaling causes impairment of microglia- mediated synapse elimination and autistic-like behaviour in mice. Brain Behav Immun;2024 (Jan 31)

In the last year, the hypothesis that elevated levels of proinflammatory cytokines contribute to the pathogenesis of neurodevelopmental diseases has gained popularity. IL-1 is one of the main cytokines found to be elevated in ASD Autism spectrum disorder, a complex neurodevelopmental condition characterized by defects in social communication and cognitive impairments. In this study, we demonstrate that mice lacking IL-1 signaling display autistic-like defects associated with an excessive number of synapses. We also show that microglia lacking IL-1 signaling at early neurodevelopmental stages are unable to properly perform the process of synapse engulfment and display excessive activation of mammalian target of rapamycin (mTOR) signaling. Notably, even the acute inhibition of IL-1R1 by IL-1Ra is sufficient to enhance mTOR signaling and reduce synaptosome phagocytosis in WT microglia. Finally, we demonstrate that rapamycin treatment rescues the defects in IL-1R deficient mice. These data unveil an exclusive role of microglial IL-1 in synapse refinement via mTOR signaling and indicate a novel mechanism possibly involved in neurodevelopmental disorders associated with defects in the IL-1 pathway.

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3. Koehler JC, Dong MS, Bierlich AM, Fischer S, Späth J, Plank IS, Koutsouleris N, Falter-Wagner CM. Machine learning classification of autism spectrum disorder based on reciprocity in naturalistic social interactions. Transl Psychiatry;2024 (Feb 3);14(1):76.

Autism spectrum disorder is characterized by impaired social communication and interaction. As a neurodevelopmental disorder typically diagnosed during childhood, diagnosis in adulthood is preceded by a resource-heavy clinical assessment period. The ongoing developments in digital phenotyping give rise to novel opportunities within the screening and diagnostic process. Our aim was to quantify multiple non-verbal social interaction characteristics in autism and build diagnostic classification models independent of clinical ratings. We analyzed videos of naturalistic social interactions in a sample including 28 autistic and 60 non-autistic adults paired in dyads and engaging in two conversational tasks. We used existing open-source computer vision algorithms for objective annotation to extract information based on the synchrony of movement and facial expression. These were subsequently used as features in a support vector machine learning model to predict whether an individual was part of an autistic or non-autistic interaction dyad. The two prediction models based on reciprocal adaptation in facial movements, as well as individual amounts of head and body motion and facial expressiveness showed the highest precision (balanced accuracies: 79.5% and 68.8%, respectively), followed by models based on reciprocal coordination of head (balanced accuracy: 62.1%) and body (balanced accuracy: 56.7%) motion, as well as intrapersonal coordination processes (balanced accuracy: 44.2%). Combinations of these models did not increase overall predictive performance. Our work highlights the distinctive nature of non-verbal behavior in autism and its utility for digital phenotyping-based classification. Future research needs to both explore the performance of different prediction algorithms to reveal underlying mechanisms and interactions, as well as investigate the prospective generalizability and robustness of these algorithms in routine clinical care.

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4. Lai B, Yi A, Zhang F, Wang S, Xin J, Li S, Yu L. Atypical brain lateralization for speech processing at the sublexical level in autistic children revealed by fNIRS. Sci Rep;2024 (Feb 2);14(1):2776.

Autistic children often exhibit atypical brain lateralization of language processing, but it is unclear what aspects of language contribute to this phenomenon. This study employed functional near-infrared spectroscopy to measure hemispheric lateralization by estimating hemodynamic responses associated with processing linguistic and non-linguistic auditory stimuli. The study involved a group of autistic children (N = 20, mean age = 5.8 years) and a comparison group of nonautistic peers (N = 20, mean age = 6.5 years). The children were presented with stimuli with systematically decreasing linguistic relevance: naturalistic native speech, meaningless native speech with scrambled word order, nonnative speech, and music. The results revealed that both groups showed left lateralization in the temporal lobe when listening to naturalistic native speech. However, the distinction emerged between autism and nonautistic in terms of processing the linguistic hierarchy. Specifically, the nonautistic comparison group demonstrated a systematic reduction in left lateralization as linguistic relevance decreased. In contrast, the autism group displayed no such pattern and showed no lateralization when listening to scrambled native speech accompanied by enhanced response in the right hemisphere. These results provide evidence of atypical neural specialization for spoken language in preschool- and school-age autistic children and shed new light on the underlying linguistic correlates contributing to such atypicality at the sublexical level.

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5. Northrup JB, Mazefsky CA, Day TN. Valence and Intensity of Emotional Expression in Autistic and Non-Autistic Toddlers. J Autism Dev Disord;2024 (Feb 3)

PURPOSE: Differences in emotional experience and expression have long been recognized as common in the presentation of autism, yet research examining emotional expression in early childhood is limited, with mixed findings. Understanding emotional reactivity and expression in autism in early life is an essential step towards uncovering the mechanisms of these risks and identifying targets for intervention. METHODS: The present study examined emotional expression in autistic (N = 17) and non-autistic (N = 20) toddlers (mean age = 25.27; SD = 1.88) during emotion elicitation tasks aimed at eliciting joy, frustration, and unease. Video recorded tasks were coded in ten second intervals for emotional valence and intensity, and the following variables were computed: proportion of time in positive, neutral, and negative affect; maximum intensity of positive and negative affect; and range of affect (i.e., most negative to most positive intensity). RESULTS: Autistic toddlers spent more time in neutral facial expressions, less time displaying positive affect, and had somewhat less intense positive emotional expression than non-autistic peers. Small differences were apparent in intensity of negative affect expression, while no differences emerged in duration of time spent in negative affect. CONCLUSION: Findings emphasize that differences may be more apparent in duration, rather than intensity of emotional expression, and that it may be particularly important to examine periods of « neutral » affect in young autistic children. Future research should consider the best ways to understand emotional reactivity in this population considering their unique interests, challenges, and communication styles.

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6. Ratsapbhayakul T, Keeratitanont K, Chonprai C, Auvichayapat N, Suphakunpinyo C, Patjanasoontorn N, Tiamkao S, Tunkamnerdthai O, Punjaruk W, Auvichayapat P. Anodal transcranial direct-current stimulation and non-verbal intelligence in autism spectrum disorder: A randomized controlled trial. Dev Med Child Neurol;2024 (Feb 2)

AIM: To understand the impact of anodal transcranial direct-current stimulation (tDCS) on non-verbal intelligence in high-functioning young adults with autism spectrum disorder (ASD). METHOD: Thirty individuals with ASD were randomly divided into three groups receiving 2 mA, 20 minutes daily anodal tDCS for 10 sessions. Group A received 10 sham tDCS sessions, group B five real followed by five sham sessions, and group C received 10 real tDCS sessions. The total score of non-verbal intelligence was measured using the Test of Nonverbal Intelligence, Fourth Edition. The left dorsolateral prefrontal cortex (LDLPFC) was targeted using the International 10-20 electroencephalography system, and concurrent cognitive training was avoided. RESULTS: Group C demonstrated a mean difference of 4.10 (95% confidence interval 1.41-6.79; p = 0.005) in Test of Nonverbal Intelligence scores compared with group A, with an effect size of 0.47. No significant differences were observed between groups A and B (p = 0.296), or between groups B and C (p = 0.140). INTERPRETATION: Ten sessions of anodal tDCS to the LDLPFC led to improved non-verbal intelligence among individuals with ASD. These results emphasize the potential of tDCS as a discrete method for boosting cognitive abilities in the high-functioning population with ASD. Future studies with larger groups of participants and extended observation periods are necessary to validate these findings.

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7. Sandhu A, Rawat K, Gautam V, Bhatia A, Grover S, Saini L, Saha L. Ameliorating effect of pioglitazone on prenatal valproic acid-induced behavioral and neurobiological abnormalities in autism spectrum disorder in rats. Pharmacol Biochem Behav;2024 (Feb 1);237:173721.

Autism spectrum disorder (ASD) is a neurodevelopment disorder that mainly arises due to abnormalities in different brain regions, resulting in behavioral deficits. Besides its diverse phenotypical features, ASD is associated with complex and varied etiology, presenting challenges in understanding its precise neuro-pathophysiology. Pioglitazone was reported to have a fundamental role in neuroprotection in various other neurological disorders. The present study aimed to investigate the therapeutic potential of pioglitazone in the prenatal valproic acid (VPA)-model of ASD in Wistar rats. Pregnant female Wistar rats received VPA on Embryonic day (E.D12.5) to induce autistic-like-behavioral and neurobiological alterations in their offspring. VPA-exposed rats presented core behavioral symptoms of ASD such as deficits in social interaction, poor spatial and learning behavior, increased anxiety, locomotory and repetitive activity, and decreased exploratory activity. Apart from these, VPA exposure also stimulated neurochemical and histopathological neurodegeneration in various brain regions. We administered three different doses of pioglitazone i.e., 2.5, 5, and 10 mg/kg in rats to assess various parameters. Of all the doses, our study highlighted that 10 mg/kg pioglitazone efficiently attenuated the autistic symptoms along with other neurochemical alterations such as oxidative stress, neuroinflammation, and apoptosis. Moreover, pioglitazone significantly attenuated the neurodegeneration by restoring the neuronal loss in the hippocampus and cerebellum. Taken together, our study suggests that pioglitazone exhibits therapeutic potential in alleviating behavioral abnormalities induced by prenatal VPA exposure in rats. However, further research is needed to fully understand and establish pioglitazone’s effectiveness in treating ASD.

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8. Schulz EG. BREACHing new grounds in fragile X syndrome: Trinucleotide expansion linked to genome-wide heterochromatin domains and genome misfolding. Mol Cell;2024 (Feb 1);84(3):413-414.

In a recent study in Cell, Malachowski et al.(1) show that the trinucleotide expansion in the FMR1 gene underlying fragile X syndrome triggers formation of large heterochromatin domains across the genome, resulting in the repression of synaptic genes housed within these domains.

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9. Wan Y, Zhang L, Xu Z, Su Q, Leung TF, Chan D, Wong OWH, Chan S, Chan FKL, Tun HM, Ng SC. Alterations in fecal virome and bacteriome virome interplay in children with autism spectrum disorder. Cell Rep Med;2024 (Jan 31):101409.

Emerging evidence suggests autism spectrum disorder (ASD) is associated with altered gut bacteria. However, less is known about the gut viral community and its role in shaping microbiota in neurodevelopmental disorders. Herein, we perform a metagenomic analysis of gut-DNA viruses in 60 children with ASD and 64 age- and gender-matched typically developing children to investigate the effect of the gut virome on host bacteria in children with ASD. ASD is associated with altered gut virome composition accompanied by the enrichment of Clostridium phage, Bacillus phage, and Enterobacteria phage. These ASD-enriched phages are largely associated with disrupted viral ecology in ASD. Importantly, changes in the interplay between the gut bacteriome and virome seen in ASD may influence the encoding capacity of microbial pathways for neuroactive metabolite biosynthesis. These findings suggest an impaired bacteriome-virome ecology in ASD, which sheds light on the importance of bacteriophages in pathogenesis and the development of microbial therapeutics in ASD.

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10. Zhang S, Hu R, Zhao S. Autistic traits and ARFID-associated eating behaviors in preschoolers: Mediating effects of sensory processing patterns. Appetite;2024 (Feb 3):107237.

OBJECTIVE: This study aimed to examine the association between autistic traits and Avoidant Restrictive Food Intake Disorder (ARFID)-associated eating behaviors in preschool-age children and investigated whether this association was mediated by sensory processing patterns. METHOD: A cross-sectional, parent-reported study was conducted between July 2022 and March 2023 among 503 preschoolers aged 4-6 years in China. Parents provided assessments of their children’s autistic traits using the Social Responsiveness Scale, sensory processing patterns using the Short Sensory Profile 2, and ARFID-associated eating behaviors using the Nine Items ARFID Screen. The mediation model based on ordinary least squares regression was employed to test the mediating effects of sensory processing patterns between autistic traits and ARFID-associated eating behaviors. RESULTS: The results indicated significant associations among autistic traits, ARFID-associated eating behaviors, and sensory processing patterns. Moreover, mediation analyses revealed that sensory processing patterns played a partial mediating role in the relationship between autistic traits and ARFID-associated eating behaviors. Specifically, autistic traits were observed to weaken ARFID-associated eating behaviors, particularly picky eating and poor appetite, through Registration, while simultaneously fostering them through Sensitivity and Avoiding. DISCUSSION: Our study is limited to some extent by the inability to draw longitudinal conclusions from cross-sectional data. Nevertheless, it underscores the significance of early identification and intervention for food avoidance/restriction behaviors due to sensory processing abnormalities in children with heightened autistic traits. This proactive approach may contribute to mitigating ARFID-associated eating behaviors that might drive clinical symptoms of ARFID.

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