1. Bezabih YS, Wonde TE, Ebrahim SH. Perforation of the cecum from ingested foreign body in a 14 year old adolescent with autism spectrum disorder and epilepsy: A case report. International journal of surgery case reports. 2021; 88: 106580.

INTRODUCTION AND IMPORTANCE: Although foreign body ingestion is a common medical issue, intestinal perforations following foreign body ingestion are rare. Diagnosing foreign body ingestion is challenging especially in children with neurodevelopmental disorders such as Autism Spectrum Disorder (ASD). It is believed that approximately 80-90% of ingested foreign bodies pass through the gastrointestinal tract without causing any luminal damage, and only approximately 1% of foreign bodies are known to remain lodged within the bowel and cause luminal erosion and perforation. CASE PRESENTATION: A 14-year-old boy, diagnosed to have Autism Spectrum Disorder was brought in by his parents to our hospital with right lower quadrant (RLQ) abdominal pain and fever. On examination, he was tachycardic and there was direct tenderness over the RLQ of the abdomen. Acute appendicitis was entertained and the patient was examined with ultrasound. The ultrasound reported, « The tip of the appendix was dilated (0.62cm) and there is minimal RLQ intra-peritoneal fluid collection ». With the impression of acute appendicitis, the patient was explored and he was found to have a cecum perforation due to an ingested foreign body (twig). Initially we did tube cecostomy but later we did right hemicolectomy because the cecostomy tube had leaked. CONCLUSION: Foreign body ingestion should be taken into account during the evaluation of children and adolescents with neurodevelopmental disorders who presented with acute abdominal pain. Since diagnosis is difficult clinicians who are involved in acute care medicine should take a thorough history with a high index of suspicion for foreign body ingestion.

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2. Bleuzé L, Triaca V, Borreca A. FMRP-Driven Neuropathology in Autistic Spectrum Disorder and Alzheimer’s disease: A Losing Game. Frontiers in molecular biosciences. 2021; 8: 699613.

Fragile X mental retardation protein (FMRP) is an RNA binding protein (RBP) whose absence is essentially associated to Fragile X Syndrome (FXS). As an RNA Binding Protein (RBP), FMRP is able to bind and recognize different RNA structures and the control of specific mRNAs is important for neuronal synaptic plasticity. Perturbations of this pathway have been associated with the autistic spectrum. One of the FMRP partners is the APP mRNA, the main protagonist of Alzheimer’s disease (AD), thereby regulating its protein level and metabolism. Therefore FMRP is associated to two neurodevelopmental and age-related degenerative conditions, respectively FXS and AD. Although these pathologies are characterized by different features, they have been reported to share a number of common molecular and cellular players. The aim of this review is to describe the double-edged sword of FMRP in autism and AD, possibly allowing the elucidation of key shared underlying mechanisms and neuronal circuits. As an RBP, FMRP is able to regulate APP expression promoting the production of amyloid β fragments. Indeed, FXS patients show an increase of amyloid β load, typical of other neurological disorders, such as AD, Down syndrome, Parkinson’s Disease, etc. Beyond APP dysmetabolism, the two neurodegenerative conditions share molecular targets, brain circuits and related cognitive deficits. In this review, we will point out the potential common neuropathological pattern which needs to be addressed and we will hopefully contribute to clarifying the complex phenotype of these two neurorological disorders, in order to pave the way for a novel, common disease-modifying therapy.

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3. Chaware SH, Dubey SG, Kakatkar V, Jankar A, Pustake S, Darekar A. The Systematic Review and Meta-analysis of Oral Sensory Challenges in Children and Adolescents with Autism Spectrum Disorder. Journal of International Society of Preventive & Community Dentistry. 2021; 11(5): 469-80.

OBJECTIVES: The purpose of the systematic review was to provide a summary and evaluation of oral sensory challenges in children and adolescents with autism spectrum disorder (ASD). MATERIALS AND METHODS: The review evaluated 19 studies that met the inclusion and search criteria. The review is registered in Prospero Database (CRD42020179852). The 14 studies (8 case-control, 4 cohort, 1 observational, and 1 randomized clinical trial) were related to speech disorders and five studies (case-control studies) were associated with feeding and eating behavior in ASD. The meta-analysis of speech and feeding behavior was analyzed by using risk ratios (RRs) and standardized mean difference (SMD), with 95% confidence interval (CI). RESULTS: The meta-analysis found a statistically significant difference of speech disorder between children and adolescents of ASD when compared with typically developed or other neurotypical children of similar age [0.4891 (95% CI = -2.4580; 1.4799), fixed effect; -0.1726 (95% CI = -14.2925; 7.5697), random effect]. Feeding and eating behavior reported a statistically significant difference between ASD children and adolescents with similar age group of typically developed controls [0.0433 (95% CI = -0.3531; 0.4398), fixed-effect; 0.3711 (95% CI = -3.0751; 3.8172), random effect]. CONCLUSION: The speech errors and feeding behavior were more consistent in ASD than in typically developed controls. The oral sensory challenges such as speech disorder and feeding behavior were more prevalent in ASD children and adolescents than in typically developed children and adolescents of the same age group. There was a significant lack in oral sensory-motor synchronization, incomplete motor planning, and poor oral neuromuscular coordination.

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4. Danforth A. Psychedelic-Assisted Therapy for Social Adaptability in Autistic Adults. Current topics in behavioral neurosciences. 2021.

Access to the Internet has upended long-standing myths and misconceptions about autism as autistic individuals are enabled through technology increasingly to influence the dialog around neurodiversity, the experience of being autistic, and the effectiveness of mental health interventions for autistic adults. Autistic self-advocates are speaking up in support of including neurodivergent adults as a population that might benefit from the burgeoning psychedelic medicine field, in an absence of many other mental health treatment options that have been researched and shown to be effective for them. Autism is a genetically-determined neurocognitive variant with considerable heterogeneity across the broad autistic phenotype spectrum. Therefore, enthusiasm for investigating psychedelics to cure or alter the course of autism is most likely ill-informed and misdirected; psychiatric and psychopharmacological interventions do not alter the genome. However, autism frequently co-occurs with clinical conditions such as anxiety, depression, obsessive-compulsive disorder, and trauma that have been investigated as indications for clinical trials with classic and atypical psychedelics. The purpose of this chapter will be to inform researchers and clinicians on the history of clinical research with classic psychedelics with autistic minors, recent and current clinical trials of atypical psychedelics with autistic adults, and considerations for providing psychedelic-assisted psychotherapies that are compatible with autism.

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5. Levi Mortera S, Vernocchi P, Basadonne I, Zandonà A, Chierici M, Durighello M, Marzano V, Gardini S, Gasbarrini A, Urbani A, Vicari S, Roncada P, Furlanello C, Venuti P, Putignani L. A metaproteomic-based gut microbiota profiling in children affected by autism spectrum disorders. Journal of proteomics. 2022; 251: 104407.

During the last decade, the evidences on the relationship between neurodevelopmental disorders and the microbial communities of the intestinal tract have considerably grown. Particularly, the role of gut microbiota (GM) ecology and predicted functions in Autism Spectrum Disorders (ASD) has been especially investigated by 16S rRNA targeted and shotgun metagenomics, trying to assess disease signature and their correlation with cognitive impairment or gastrointestinal (GI) manifestations of the disease. Herein we present a metaproteomic approach to point out the microbial gene expression profiles, their functional annotations, and the taxonomic distribution of gut microbial communities in ASD children. We pursued a LC-MS/MS based investigation, to compare the GM profiles of patients with those of their respective relatives and aged-matched controls, providing a quantitative evaluation of bacterial metaproteins by SWATH analysis. All data were managed by a multiple step bioinformatic pipeline, including network analysis. In particular, comparing ASD subjects with CTRLs, up-regulation was found for some metaproteins associated with Clostridia and with carbohydrate metabolism (glyceraldehyde-3-phosphate and glutamate dehydrogenases), while down-regulation was observed for others associated with Bacteroidia (SusC and SusD family together with the TonB dependent receptor). Moreover, network analysis highlighted specific microbial correlations among ASD subgroups characterized by different functioning levels and GI symptoms. SIGNIFICANCE: To the best of our knowledge, this study represents the first metaproteomic investigation on the gut microbiota of ASD children compared with relatives and age-matched CTRLs. Remarkably, the applied SWATH methodology allowed the attribution of differentially regulated functions to specific microbial taxa, offering a novel and complementary point of view with respect to previous studies.

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6. Mignogna ML, Ficarella R, Gelmini S, Marzulli L, Ponzi E, Gabellone A, Peschechera A, Alessio M, Margari L, Gentile M, D’Adamo P. Clinical characterization of a novel RAB39B nonstop mutation in a family with ASD and severe ID causing RAB39B downregulation and study of a Rab39b knock down mouse model. Human molecular genetics. 2022; 31(9): 1389-406.

Autism spectrum disorder (ASD) and intellectual disability (ID) often exist together in patients. The RAB39B gene has been reported to be mutated in ID patients with additional clinical features ranging from ASD, macrocephaly, seizures and/or early-onset parkinsonism. Here, we describe a novel RAB39B nonstop mutation [Xq28; c.640 T > C; p.(*214Glnext*21)] in a family with ASD, severe ID and poor motor coordination, and we assessed the pathogenicity of the mutation. A heterologous cell system and a Rab39b knockdown (KD) murine model, which mimic the nonstop mutation, were used to validate the deleterious effect of the RAB39B mutation. The mutation led to RAB39B protein instability, resulting in its increased degradation and consequent downregulation. Using a Rab39b KD mouse model, we demonstrated that the downregulation of RAB39B led to increased GluA2 lacking Ca2+-permeable AMPAR composition at the hippocampal neuronal surface and increased dendritic spine density that remained in an immature filopodia-like state. These phenotypes affected behavioural performance in a disease-specific manner. Rab39b KD mice revealed impaired social behaviour but intact social recognition. They also showed normal anxiety-like, exploratory and motivational behaviours but impaired working and associative memories. In conclusion, we found a novel RAB39B nonstop variant that segregated in a family with a clinical phenotype including ID, ASD and poor motor coordination. The pathogenicity of mutations causing the downregulation of RAB39B proteins, impacting AMPAR trafficking and dendritic spine morphogenesis, reinforced the idea that AMPAR modulation and dendritic spine assets could be considered hallmarks of neurodevelopmental disorders.

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7. Nijhof AD, von Trott Zu Solz J, Catmur C, Bird G. Equivalent own name bias in autism: An EEG study of the Attentional Blink. Cognitive, affective & behavioral neuroscience. 2021.

The « Attentional Blink » refers to difficulty in detecting the second of two target stimuli presented in rapid temporal succession. Studies have shown that salient target stimuli, such as one’s own name, reduce the magnitude of this effect. Given indications that self-related processing is altered in autism, it is an open question whether this attentional self-bias is reduced in autism. To investigate this, in the current study we utilised an Attentional Blink paradigm involving one’s own and others’ names, in a group of 24 autistic adults, and 22 neurotypical adults, while measuring EEG. In line with previous studies, the Attentional Blink was reduced when the participant’s own name was the second target, with no differences between autistic and neurotypical participants. ERP results show that the effect on the Attentional Blink of one’s own name was reflected in increased N2 and P3 amplitudes, for both autistic and nonautistic individuals. This is the first event-related potential study of own-name processing in the context of the Attentional Blink. The results provide evidence of an intact attentional self-bias in autism, both at the behavioural and neural level.

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8. Peterson BS, Liu J, Dantec L, Newman C, Sawardekar S, Goh S, Bansal R. Using tissue microstructure and multimodal MRI to parse the phenotypic heterogeneity and cellular basis of autism spectrum disorder. Journal of child psychology and psychiatry, and allied disciplines. 2021.

BACKGROUND: Identifying the brain bases for phenotypic heterogeneity in Autism Spectrum Disorder (ASD) will advance understanding of its pathogenesis and improve its clinical management. METHODS: We compared Diffusion Tensor Imaging (DTI) indices and connectome measures between 77 ASD and 88 Typically Developing (TD) control participants. We also assessed voxel-wise associations of DTI indices with measures of regional cerebral blood flow (rCBF) and N-acetylaspartate (NAA) to understand how tissue microstructure associates with cellular metabolism and neuronal density, respectively. RESULTS: Autism Spectrum Disorder participants had significantly lower fractional anisotropy (FA) and higher diffusivity values in deep white matter tracts, likely representing ether reduced myelination by oligodendrocytes or a reduced density of myelinated axons. Greater abnormalities in these measures and regions were associated with higher ASD symptom scores. Participant age, sex and IQ significantly moderated these group differences. Path analyses showed that reduced NAA levels accounted significantly for higher diffusivity and higher rCBF values in ASD compared with TD participants. CONCLUSIONS: Reduced neuronal density (reduced NAA) likely underlies abnormalities in DTI indices of white matter microstructure in ASD, which in turn are major determinants of elevated blood flow. Together, these findings suggest the presence of reduced axonal density and axonal pathology in ASD white matter. Greater pathology in turn accounts for more severe symptoms, lower intellectual ability, and reduced global efficiency for measures of white matter connectivity in ASD.

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9. Putra PU, Shima K, Alvarez SA, Shimatani K. Identifying autism spectrum disorder symptoms using response and gaze behavior during the Go/NoGo game CatChicken. Scientific reports. 2021; 11(1): 22012.

Previous studies have found that Autism Spectrum Disorder (ASD) children scored lower during a Go/No-Go task and faced difficulty focusing their gaze on the speaker’s face during a conversation. To date, however, there has not been an adequate study examining children’s response and gaze during the Go/No-Go task to distinguish ASD from typical children. We investigated typical and ASD children’s gaze modulation when they played a version of the Go/No-Go game. The proposed system represents the Go and the No-Go stimuli as chicken and cat characters, respectively. It tracks children’s gaze using an eye tracker mounted on the monitor. Statistically significant between-group differences in spatial and auto-regressive temporal gaze-related features for 21 ASD and 31 typical children suggest that ASD children had more unstable gaze modulation during the test. Using the features that differ significantly as inputs, the AdaBoost meta-learning algorithm attained an accuracy rate of 88.6% in differentiating the ASD subjects from the typical ones.

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10. Pye K, Jackson H, Iacono T, Shiell A. Early intervention for young children with autism spectrum disorder: protocol for a scoping review of economic evaluations. Systematic reviews. 2021; 10(1): 295.

BACKGROUND: In many countries, children who are diagnosed with autism during the first 5 years of life are offered a range of early intervention options. These options vary considerably in the theoretical approaches and techniques applied, their intensity and duration, settings, the person/s delivering supports and the training they require. Early interventions are a significant contributor to total autism-related costs in Western countries, but only in the last 10-20 years has there been adequate outcome data to enable the comparison of different interventions’ cost-effectiveness. This protocol describes a scoping review to better understand what economic evaluations have been completed in this field, and the methods used to date. METHODS: We will systematically search the following databases from their inception to 2021 for eligible studies: MEDLINE, EMBASE, PsycINFO, Econlit, PEDE, NHS EED and HTA. Full economic evaluations of any types of early intervention for children with autism prior to school entry will be included. Two reviewers will screen the studies, extract the data and assess the study quality using established checklists. The risk of bias will be assessed using the extended CHEC-list for all studies and, additionally, the Philips checklist for modelled studies. Quality of reporting will be assessed using the CHEERS checklist. A narrative synthesis will be completed to collate the findings, describe the methods used and identify which interventions have been researched from an economic perspective. DISCUSSION: This review will provide researchers, policymakers and service providers with current information about the economic evidence for early interventions for young children with autism and point to priorities for further research. It will inform future economic evaluations by highlighting the gaps or inconsistencies in the methods used to date. Limitations of the review will be acknowledged and discussed. SYSTEMATIC REVIEW REGISTRATION: Open Science Framework: https://osf.io/sj7kt.

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11. Skrimpa V, Spanou V, Bongartz C, Peristeri E, Andreou M, Papadopoulou D. Bilingualism effects in pronoun comprehension: Evidence from children with autism. Autism research : official journal of the International Society for Autism Research. 2022; 15(2): 270-83.

The prevalence of autism worldwide has risen steadily in the last two decades, while bilingualism is also becoming increasingly prevalent in today’s rapidly globalizing world. The current study aimed to investigate bilingualism effects in the pronoun resolution skills of children with autism in comparison to age-matched monolingual children with autism, as well as monolingual and bilingual children of typical development (Ν = 20 participants per group). Results showed that autistic children had general difficulty anchoring ambiguous pronouns to entities that were linguistically expressed in discourse, yet, the bilingual children with autism were more sensitive to the topicality of the entities in syntactic subject position and more prone to identify them as suitable referents of ambiguous null pronouns as compared to their monolingual peers. The findings suggest that bilingualism is not detrimental to autistic children’s pronoun resolution skills. The current study aimed at determining how bilingualism influences ambiguous pronoun comprehension in children with autism as compared to bilingual and monolingual children of typical development. The findings show that bilingualism was not detrimental to the autistic children’s pronoun resolution skills, further suggesting that having acquired more than one language does not exacerbate autistic children’s deficits in the comprehension of pronouns.

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12. Taylor JL. Removing people with intellectual disabilities and autism from the England and Wales Mental Health Act. The lancet Psychiatry. 2022; 9(3): 188-90.

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13. Thomas RP, Milan S, Naigles L, Robins DL, Barton ML, Adamson LB, Fein DA. Symptoms of autism spectrum disorder and developmental delay in children with low mental age. The Clinical neuropsychologist. 2021: 1-21.

Objective: Autism spectrum disorder (ASD) in very young children with significant cognitive impairment is difficult to diagnose, depriving them of the earliest opportunities for autism-specific intervention. This study delineated specific symptoms in this group, compared to symptoms in children with Global Developmental Delay (GDD) and in ASD with milder developmental delays.Method: Autism Diagnostic Observation Schedule, 2nd Edition, Toddler Module revealed symptoms in three groups of toddlers, with mean ages of 17-20 months: (1) ASD and cognitive/language functioning below the 12-month level (ASD-MA < 12 mos; n = 28), (2) GDD (n = 27), and (3) ASD and cognitive/language functioning at or above the 12-month level (ASD-MA ≥ 12 mos; n = 29). Logistic regression models were fit to control for developmental level. Results: Items in all domains (social interaction, communication, repetitive movements) discriminated ASD-MA < 12 mos from GDD. The two ASD groups, matched for age but differing on developmental level, showed strikingly similar ASD symptomatology. Conclusion: ADOS-2 symptoms differentiated ASD-MA < 12 mos from GDD, after controlling for cognitive impairment. Symptoms in the two ASD groups were minimally related to developmental level. The ADOS-2 Toddler Module successfully captured ASD symptomatology even in children whose developmental level was below the recommended ADOS-2 cutoff of 12 months, which may increase their access to early ASD-specific intervention.

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14. van Leeuwen TM, Wilsson L, Norrman HN, Dingemanse M, Bölte S, Neufeld J. Perceptual processing links autism and synesthesia: A co-twin control study. Cortex; a journal devoted to the study of the nervous system and behavior. 2021; 145: 236-49.

Synesthesia occurs more commonly in individuals fulfilling criteria for an autism spectrum diagnosis than in the general population. It is associated with autistic traits and autism-related perceptual processing characteristics, including a more detail-focused attentional style and altered sensory sensitivity. In addition, these characteristics correlate with the degree of grapheme-color synesthesia (consistency of grapheme-color associations) in non-synesthetes. We investigated a predominantly non-synesthetic twin sample, including individuals fulfilling criteria for an autism spectrum diagnosis or other neurodevelopmental disorders (n = 65, 14-34 years, 60% female). We modelled linear relationships between the degree of grapheme-color synesthesia and autistic traits, sensory sensitivity, and visual perception, both within-twin pairs (22 pairs) where all factors shared by twins are implicitly controlled (including 50-100% genetics), and across the entire cohort. We found that the degree of grapheme-color synesthesia was associated with autistic traits within the domain of Attention to Details and with sensory hyper-, but not hypo-sensitivity. These associations were stronger within-twin pairs than across the sample. Further, twins with a higher degree of grapheme-color synesthesia were better than their co-twins at identifying fragmented images (Fragmented Pictures Test). This is the first twin study on the association between synesthesia and autism-related perceptual features and traits. The results suggest that investigating these associations within-twin pairs, implicitly adjusting for potential confounding factors shared by twins, is more sensitive than doing so in non-related individuals. Consistent with previous findings, the results suggest an association between the degree of grapheme-color synesthesia and autism-related perceptual features, while utilizing a different measure for sensory sensitivity. The novel finding of enhanced fragmented picture integration in twins with a higher degree of grapheme-color synesthesia challenges the view of a generally more detail-focused attentional style in synesthesia and might be related to enhanced memory or mental imagery in more synesthetic individuals.

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