1. Aspragkathou DD, Spilioti M, Gkampeta A, Dalpa E, Holeva V, Papadopoulou MT, Serdari A, Dafoulis V, Zafeiriou D, Evangeliou AE. Branched-Chain Amino Acids as Adjunctive-alternative Treatment in Patients with Autism: a pilot study. The British journal of nutrition. 2023: 1-22.

The Branched Chain Amino Acids (BCAAs) is a group of essential amino acids that are involved in maintaining the energy balance of a human being as well as the homeostasis of GABAergic, glutamatergic, serotonergic and dopaminergic systems. Disruption of these systems has been associated with the pathophysiology of autism while low levels of these amino acids have been discovered in patients with autism.A pilot open-label, prospective, follow-up study of the use of branched-chain amino acids (BCAAs) in children with autistic behavior was carried out.55 children between the ages of 6 and 18 participated in the study from May 2015 to May 2018. We used a carbohydrate-free branched-chain amino acid powdered mixture containing 45.5 g of leucine, 30 g of isoleucine, and 24.5 g of valine in a daily dose of 0,4gr/Kg of body weight which was administered every morning. Following the initiation of BCAA administration, children were submitted to a monthly psychological examination.Beyond the 4-week mark, BCAAs were given to 32 people (58.18%). Six of them (10.9%) discontinued after four to ten weeks owing to lack of improvement.The remaining 26 children (47.27%) who took BCAAs for longer than 10 weeks displayed improved social behavior and interactions, as well as improvements in their speech, cooperation, stereotypy, and principally, their hyperactivity. There were no adverse reactions reported during the course of the treatment.Although these data are very preliminary, there is some evidence that BCAAs could be used as adjunctive treatment to conventional therapeutic methods for the management of autistic children.

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2. Chen B, Yin B, Ke H. Interpretation of deep non-linear factorization for autism. Frontiers in psychiatry. 2023; 14: 1199113.

Autism, a neurodevelopmental disorder, presents significant challenges for diagnosis and classification. Despite the widespread use of neural networks in autism classification, the interpretability of their models remains a crucial issue. This study aims to address this concern by investigating the interpretability of neural networks in autism classification using the deep symbolic regression and brain network interpretative methods. Specifically, we analyze publicly available autism fMRI data using our previously developed Deep Factor Learning model on a Hibert Basis tensor (HB-DFL) method and extend the interpretative Deep Symbolic Regression method to identify dynamic features from factor matrices, construct brain networks from generated reference tensors, and facilitate the accurate diagnosis of abnormal brain network activity in autism patients by clinicians. Our experimental results show that our interpretative method effectively enhances the interpretability of neural networks and identifies crucial features for autism classification.

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3. Dibble KE, Lutz TM, Connor AE, Bruder MB. Breast and Ovarian Cancer Among Women with Intellectual and Developmental Disabilities: An Agenda for Improving Research and Care. Women’s health issues : official publication of the Jacobs Institute of Women’s Health. 2023.

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4. Ette EI, Fadiran EO, Missling C, Hammond E. The New Big Is Small: Leveraging Knowledge from Small Trials for Rare Disease Drug Development – Blarcamesine for Rett Syndrome. British journal of clinical pharmacology. 2023.

Big data in drug development may not satisfactorily address the demands of precision medicine in a rare disease population, making the use of smaller clinical trials necessary. Consequently, the use of innovative design and analysis of these clinical trials using model-informed approaches have become indispensable. This requires informative exposure-outcome analysis, together with formal statistical analysis, which should include the strength of evidence for a study outcome. We demonstrate how knowledge can be gained, with supporting strength of evidence, from a small (data) clinical trial with a low dose of blarcamesine in the treatment of Rett syndrome (RTT). Based on a small data paradigm, pharmacometrics item response theory modeling and Bayes factor analysis were used to show that blarcamesine is efficacious in RTT.

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5. Liu CH, Chen YL, Chen PJ, Ni HC, Lai MC. Exploring camouflaging by the Chinese version Camouflaging Autistic Traits Questionnaire in Taiwanese autistic and non-autistic adolescents: An initial development. Autism : the international journal of research and practice. 2023: 13623613231181732.

Camouflaging is a coping strategy used by some autistic and other neurodivergent people to fit in neurotypical social contexts. The self-reported Camouflaging Autistic Traits Questionnaire has been validated for use in research with adults in some Western societies, but not in non-Western cultural-ethnic groups. We translated Camouflaging Autistic Traits Questionnaire into traditional Chinese and examined the use of this measure in Taiwanese adolescents via both self-report and caregiver-report in 100 autistic and 105 non-autistic adolescents. Both self-reported and caregiver-reported Chinese version Camouflaging Autistic Traits Questionnaire were composed of two factors (i.e. a « compensation-masking » subscale and an « assimilation » subscale). Both adolescent self-reported and caregiver-reported Chinese version Camouflaging Autistic Traits Questionnaire total score and subscales were reliable in measurement, and they highly correlated with each other. Taiwanese autistic adolescents were more likely to camouflage than non-autistic adolescents, especially on assimilation. Female autistic adolescents showed higher assimilation than male autistic adolescents. Higher camouflaging, especially assimilation, was associated with higher stress in autistic and non-autistic adolescents alike. Both self-reported and caregiver-reported Chinese version Camouflaging Autistic Traits Questionnaire were reliable and offered meaningful information to help us understand the social coping experiences of autistic and non-autistic adolescents.

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6. Lockard BS, Dallara M, O’Malley C. A Short Report on the Impact of Judo on Behaviors and Social Skills of Children With Autism Spectrum Disorder. Cureus. 2023; 15(7): e41516.

INTRODUCTION: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by communication difficulty and social deficits. The current treatment employs the use of psychosocial therapy and medication as well as alternative treatments. This is a pilot study that assessed whether participation in judo improved behavior and social skills in children with ASD. METHODS: Twenty-four students from the Riverside Youth Judo Club were included in the study, after obtaining consent from their parents to participate. Inclusion criteria included participation in judo classes for more than one month and diagnosis of ASD and/or a developmental disability. Parent(s) of the children signed a consent form, filled out a study questionnaire and completed the Social Skills Improvement System Social-Emotional Learning Edition, Parent Form (SSIS-SEL). Parents also had the opportunity to volunteer their child’s baseline SSIS-SEL assessment. SSIS-SEL data was taken for four participants and compared to the baseline. RESULTS: In the study questionnaire, 62.5% of parents agreed that their children demonstrated improvement across all six categories. The category with the greatest improvement was ‘Behavior at home’, while the category with the least improvement was ‘Eye contact’. CONCLUSION: While the direct impact of judo on special needs children was difficult to assess due to variability in abilities and developmental milestones, we hope that improving awareness regarding the effectiveness of youth sports would impact the long-term quality of life for children with any developmental or mental disability and may help improve their social and behavioral skills in multiple environments.

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7. Maes P, Weyland M, Kissine M. Structure and acoustics of the speech of verbal autistic preschoolers. Journal of child language. 2023: 1-17.

In this study, we report an extensive investigation of the structural language and acoustical specificities of the spontaneous speech of ten three- to five-year-old verbal autistic children. The autistic children were compared to a group of ten typically developing children matched pairwise on chronological age, nonverbal IQ and socioeconomic status, and groupwise on verbal IQ and gender on various measures of structural language (phonetic inventory, lexical diversity and morpho-syntactic complexity) and a series of acoustical measures of speech (mean and range fundamental frequency, a formant dispersion index, syllable duration, jitter and shimmer). Results showed that, overall, the structure and acoustics of the verbal autistic children’s speech were highly similar to those of the TD children. Few remaining atypicalities in the speech of autistic children lay in a restricted use of different vocabulary items, a somewhat diminished morpho-syntactic complexity, and a slightly exaggerated syllable duration.

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8. Maloney SE, Sarafinovska S, Weichselbaum C, McCullough KB, Swift RG, Liu Y, Dougherty JD. A comprehensive assay of social motivation reveals sex-specific roles of autism-associated genes and oxytocin. Cell reports methods. 2023; 3(6): 100504.

Social motivation is critical to the development of typical social functioning. Social motivation, specifically one or more of its components (e.g., social reward seeking or social orienting), could be relevant for understanding phenotypes related to autism. We developed a social operant conditioning task to quantify effort to access a social partner and concurrent social orienting in mice. We established that mice will work for access to a social partner, identified sex differences, and observed high test-retest reliability. We then benchmarked the method with two test-case manipulations. Shank3B mutants exhibited reduced social orienting and failed to show social reward seeking. Oxytocin receptor antagonism decreased social motivation, consistent with its role in social reward circuitry. Overall, we believe that this method provides a valuable addition to the assessment of social phenotypes in rodent models of autism and the mapping of potentially sex-specific social motivation neural circuits.

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9. Morabito S, Reese F, Rahimzadeh N, Miyoshi E, Swarup V. hdWGCNA identifies co-expression networks in high-dimensional transcriptomics data. Cell reports methods. 2023; 3(6): 100498.

Biological systems are immensely complex, organized into a multi-scale hierarchy of functional units based on tightly regulated interactions between distinct molecules, cells, organs, and organisms. While experimental methods enable transcriptome-wide measurements across millions of cells, popular bioinformatic tools do not support systems-level analysis. Here we present hdWGCNA, a comprehensive framework for analyzing co-expression networks in high-dimensional transcriptomics data such as single-cell and spatial RNA sequencing (RNA-seq). hdWGCNA provides functions for network inference, gene module identification, gene enrichment analysis, statistical tests, and data visualization. Beyond conventional single-cell RNA-seq, hdWGCNA is capable of performing isoform-level network analysis using long-read single-cell data. We showcase hdWGCNA using data from autism spectrum disorder and Alzheimer’s disease brain samples, identifying disease-relevant co-expression network modules. hdWGCNA is directly compatible with Seurat, a widely used R package for single-cell and spatial transcriptomics analysis, and we demonstrate the scalability of hdWGCNA by analyzing a dataset containing nearly 1 million cells.

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10. Reichle J, Pustejovsky JE, Vannest KJ, Foster M, Pierson LM, Wattanawongwan S, Chen M, Fuller MC, Haas AN, Bhat BH, Sallese MR, Smith SD, Yllades V, Rodriguez D, Yoro A, Ganz JB. Systematic Review of Variables Related to Instruction in Augmentative and Alternative Communication Implementation: Group and Single-Case Design. American journal of speech-language pathology. 2023; 32(4): 1734-57.

PURPOSE: This article provides a systematic review and analysis of group and single-case studies addressing augmentative and alternative communication (AAC) intervention with school-aged persons having autism spectrum disorder (ASD) and/or intellectual/developmental disabilities resulting in complex communication needs (CCNs). Specifically, we examined participant characteristics in group-design studies reporting AAC intervention outcomes and how these compared to those reported in single-case experimental designs (SCEDs). In addition, we compared the status of intervention features reported in group and SCED studies with respect to instructional strategies utilized. PARTICIPANTS: Participants included school-aged individuals with CCNs who also experienced ASD or ASD with an intellectual delay who utilized aided or unaided AAC. METHOD: A systematic review using descriptive statistics and effect sizes was implemented. RESULTS: Findings revealed that participant features such as race, ethnicity, and home language continue to be underreported in both SCED and group-design studies. Participants in SCED investigations more frequently used multiple communication modes when compared to participants in group studies. The status of pivotal skills such as imitation was sparsely reported in both types of studies. With respect to instructional features, group-design studies were more apt to utilize clinical rather than educational or home settings when compared with SCED studies. In addition, SCED studies were more apt to utilize instructional methods that closely adhered to instructional features more typically characterized as being associated with behavioral approaches. CONCLUSION: The authors discuss future research needs, practice implications, and a more detailed specification of treatment intensity parameters for future research.

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11. Rivard M, Morin M, Rochefort C, Morin D, Mello C. Barriers and facilitators to accessibility, continuity, validity, flexibility, and provider-family relationship along the diagnostic pathway in developmental disabilities. Research in developmental disabilities. 2023; 139: 104570.

BACKGROUND: Parents of children with developmental disabilities must navigate a complex network to obtain a diagnosis and interventions for their child. However, their subjective experience of this journey has yet to be analyzed through the lens of a theorical framework that could support research, organizational program evaluation, and facilitate providers’ reflection on how to enhance families’ diagnostic services trajectory. AIMS: This study sought to examine the diagnostic journey as experienced by 77 parents whose children were recently diagnosed with developmental disabilities (e.g., autism, intellectual disability) in the metropolitan area of Montréal, Québec (Canada). METHODS AND PROCEDURES: A mixed qualitative content analysis approach was used to describe their perspective on barriers and facilitators in reference to the five dimensions of the Evaluation of the Trajectory Autism for Parents (ETAP) model (Rivard et al., 2020): accessibility, continuity, validity, flexibility, and provider-family relationship. OUTCOMES AND RESULTS: The barriers and facilitators related to systemic factors identified by parents were consistent with the five dimensions outlined by the ETAP model. However, beyond these characteristics of the service delivery system, parents additionally identified their own, personal facilitators CONCLUSIONS AND IMPLICATIONS: This study supports the relevance of the ETAP framework to understanding the experience of families seeking a diagnosis. It also reinforces the potential contributions of this model to organize extant and future research as well as structure program evaluation and improvements.

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12. Rodnyy AY, Kondaurova EM, Tsybko AS, Popova NK, Kudlay DA, Naumenko VS. The brain serotonin system in autism. Reviews in the neurosciences. 2023.

Autism spectrum disorders (ASDs) are among the most common neurodevelopmental diseases. These disorders are characterized by lack of social interaction, by repetitive behavior, and often anxiety and learning disabilities. The brain serotonin (5-HT) system is known to be crucially implicated in a wide range of physiological functions and in the control of different kinds of normal and pathological behavior. A growing number of studies indicate the involvement of the brain 5-HT system in the mechanisms underlying both ASD development and ASD-related behavioral disorders. There are some review papers describing the role of separate key players of the 5-HT system in an ASD and/or autistic-like behavior. In this review, we summarize existing data on the participation of all members of the brain 5-HT system, namely, 5-HT transporter, tryptophan hydroxylase 2, MAOA, and 5-HT receptors, in autism in human and various animal models. Additionally, we describe the most recent studies involving modern techniques for in vivo regulation of gene expression that are aimed at identifying exact roles of 5-HT receptors, MAOA, and 5-HT transporter in the mechanisms underlying autistic-like behavior. Altogether, results of multiple research articles show that the brain 5-HT system intimately partakes in the control of some types of ASD-related behavior, and that specific changes in a function of a certain 5-HT receptor, transporter, and/or enzyme may normalize this aberrant behavior. These data give hope that some of clinically used 5-HT-related drugs have potential for ASD treatment.

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13. Rodrigues JVS, Poli MCF, Petrilli PH, Dornelles RCM, Turcio KH, Theodoro LH. Food selectivity and neophobia in children with autism spectrum disorder and neurotypical development: a systematic review. Nutrition reviews. 2023; 81(8): 1034-50.

CONTEXT: Individuals with autism spectrum disorder (ASD) have common eating problems, including food refusal, dietary restrictions, and behavioral problems during eating. OBJECTIVE: The aim of this systematic review was to find more clear evidence on the relationship between food selectivity or food neophobia (FN) and ASD in children up to age 14 years. The PECO-based question was: Are food selectivity and FN behaviors more prevalent in children with ASD than in children with neurotypical development (NTD)?, in which the P is children, E is ASD, C is children with NTD, and O is food selectivity and FN. DATA SOURCES: Clinical studies in the databases PubMed, Embase and Web of Science, comparing children with ASD and those with NTD, were reviewed from October 1966 to October 2021. STUDY SELECTION AND DATA EXTRACTION: A total of 122 studies were analyzed for summary reading, and only 17 of these were included in the descriptive qualitative analysis. In 9 studies, the analysis of food selectivity was performed via a questionnaire. RESULTS: The results showed that children with ASD are more selective than those with NTD. Four studies evaluated FN through scales; however, only 2 found higher levels of FN in the ASD group than in children with NTD. The sensory profile was measured using questionnaires in 9 studies, and we found that altered sensory processing is more common in children with ASD. CONCLUSION: Children with ASD present greater food selectivity than children with NTD. However, the occurrence of FN was higher in only 50% in which FN was investigated, which points to a need for studies that compare FN between siblings with ASD and those with NTD in the same family nucleus. In addition, atypical oral sensitivity seems to be a sensory characteristic most related to eating disorders. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42021247880.

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14. Sideris G, Panagoulis E, Grigoropoulos C, Mermiri D, Nikolopoulos T, Delides A. Fiberoptic Endoscopic Evaluation of Swallowing Findings in Children With Rett Syndrome. Clinical pediatrics. 2023: 99228231184673.

Feeding abnormalities, swallowing dysfunction, and gastrointestinal issues cause poor weight gain, oral motor dysfunction, and air swallowing in children with Rett syndrome (RTT). Pneumonia is the leading cause of death. Our study describes fiberoptic endoscopic swallowing findings in 11 female RTT children. Each patient was evaluated using the 8-point Penetration/Aspiration Scale (PAS). The average age was 7 years. All patients had tongue dyskinesis and prolonged oral stage. Eight girls exhibited liquid entering the airway without coughing, whereas 6 did well with pureed meal. Three girls had pneumonia. Age was not correlated with pneumonia episodes (P = .18). Pureed material was related with pneumonia (P = .006), whereas liquids were not. Pureed PAS was positively correlated with Liquid PAS (P = .008) and age (P = .004). All aspiration/penetration incidents occurred before the pharyngeal phase. No patient under 7 years experienced pneumonia episodes. Silent aspiration can occur early in infancy, although pneumonia episodes can occur later.

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15. Sotgiu MA, Lo Jacono A, Barisano G, Saderi L, Cavassa V, Montella A, Crivelli P, Carta A, Sotgiu S. Brain perivascular spaces and autism: clinical and pathogenic implications from an innovative volumetric MRI study. Frontiers in neuroscience. 2023; 17: 1205489.

INTRODUCTION: Our single-center case-control study aimed to evaluate the unclear glymphatic system alteration in autism spectrum disorder (ASD) through an innovative neuroimaging tool which allows to segment and quantify perivascular spaces in the white matter (WM-PVS) with filtering of non-structured noise and increase of the contrast-ratio between perivascular spaces and the surrounding parenchyma. METHODS: Briefly, files of 65 ASD and 71 control patients were studied. We considered: ASD type, diagnosis and severity level and comorbidities (i.e., intellectual disability, attention-deficit hyperactivity disorder, epilepsy, sleep disturbances). We also examined diagnoses other than ASD and their associated comorbidities in the control group. RESULTS: When males and females with ASD are included together, WM-PVS grade and WM-PVS volume do not significantly differ between the ASD group and the control group overall. We found, instead, that WM-PVS volume is significantly associated with male sex: males had higher WM-PVS volume compared to females (p = 0.01). WM-PVS dilation is also non-significantly associated with ASD severity and younger age (< 4 years). In ASD patients, higher WM-PVS volume was related with insomnia whereas no relation was found with epilepsy or IQ. DISCUSSION: We concluded that WM-PVS dilation can be a neuroimaging feature of male ASD patients, particularly the youngest and most severe ones, which may rely on male-specific risk factors acting early during neurodevelopment, such as a transient excess of extra-axial CSF volume. Our findings can corroborate the well-known strong male epidemiological preponderance of autism worldwide.

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16. Vegni N, D’Ardia C, Di Filippo G, Melchiori FM. The impact of Lego® Therapy on cognitive skills in Autism Spectrum Disorders: a brief discussion. AIMS neuroscience. 2023; 10(2): 190-9.

Over the years, several interventions have been implemented, including Lego® Therapy, with the aim of supporting and implementing social and communication skills impairments in Autism Spectrum Disorders (ASD). Although recent studies have shown that the ability to learn implicitly is preserved in ASDs, no study related to Lego® Therapy has analyzed whether and how this training can also affect aspects not directly treated. In this study, we report a first attempt of assessment of Lego® Therapy’s effect on the specific area of cognitive skills in an ASD child. Over a period of 12 months, a child with ASD had weekly meetings with an expert operator of Lego® aiming to improve the child’s ability to communicate, reduce impulsiveness and hyper verbalism, and encourage pro-social behavior. The intervention resulted in positive outcomes that were assessed after 12 months.

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17. Wang F, Qi N, Gao Y, Wu D, Zhang M, Zhang Q, Yang K, Peng H, Lei X, Liao S. [Genetic analysis of two children with developmental delay and intellectual disability]. Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics. 2023; 40(7): 876-80.

OBJECTIVE: To explore the genetic etiology of two patients with developmental delay and intellectual disability. METHODS: Two children who were respectively admitted to Henan Provincial People’s Hospital on August 29, 2021 and August 5, 2019 were selected as the study subjects. Clinical data were collected, and array comparative genomic hybridization (aCGH) was carried out on the children and their parents for the detection of chromosomal microduplication/microdeletions. RESULTS: Patient 1 was a 2-year-and-10-month female and patient 2 was a 3-year-old female. Both children had featured developmental delay, intellectual disability, and abnormal findings on cranial MRI. aCGH revealed that patient 1 has harbored arr[hg19] 6q14.2q15(84621837_90815662)×1, a 6.19 Mb deletion at 6q14.2q15, which encompassed ZNF292, the pathogenic gene for Autosomal dominant intellectual developmental disorder 64. Patient 2 has harbored arr[hg19] 22q13.31q13.33(46294326_51178264)×1, a 4.88 Mb deletion at 22q13.31q13.33 encompassing the SHANK3 gene, haploinsufficiency of which can lead to Phelan-McDermid syndrome. Both deletions were classified as pathogenic CNVs based on the guidelines of American College of Medical Genetics and Genomics (ACMG) and were not found in their parents. CONCLUSION: The 6q14.2q15 deletion and 22q13-31q13.33 deletion probably underlay the developmental delay and intellectual disability in the two children, respectively. Haploinsufficiency of the ZNF292 gene may account for the key clinical features of the 6q14.2q15 deletion.

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18. Xia QQ, Walker AK, Song C, Wang J, Singh A, Mobley JA, Xuan ZX, Singer JD, Powell CM. Effects of heterozygous deletion of autism-related gene Cullin-3 in mice. PloS one. 2023; 18(7): e0283299.

Autism Spectrum Disorder (ASD) is a developmental disorder in which children display repetitive behavior, restricted range of interests, and atypical social interaction and communication. CUL3, coding for a Cullin family scaffold protein mediating assembly of ubiquitin ligase complexes through BTB domain substrate-recruiting adaptors, has been identified as a high-risk gene for autism. Although complete knockout of Cul3 results in embryonic lethality, Cul3 heterozygous mice have reduced CUL3 protein, demonstrate comparable body weight, and display minimal behavioral differences including decreased spatial object recognition memory. In measures of reciprocal social interaction, Cul3 heterozygous mice behaved similarly to their wild-type littermates. In area CA1 of hippocampus, reduction of Cul3 significantly increased mEPSC frequency but not amplitude nor baseline evoked synaptic transmission or paired-pulse ratio. Sholl and spine analysis data suggest there is a small yet significant difference in CA1 pyramidal neuron dendritic branching and stubby spine density. Unbiased proteomic analysis of Cul3 heterozygous brain tissue revealed dysregulation of various cytoskeletal organization proteins, among others. Overall, our results suggest that Cul3 heterozygous deletion impairs spatial object recognition memory, alters cytoskeletal organization proteins, but does not cause major hippocampal neuronal morphology, functional, or behavioral abnormalities in adult global Cul3 heterozygous mice.

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19. Yozevitch R, Dahan A, Seada T, Appel D, Gvirts H. Classifying interpersonal synchronization states using a data-driven approach: implications for social interaction understanding. Scientific reports. 2023; 13(1): 11150.

This study presents a data-driven approach to identifying interpersonal motor synchrony states by analyzing hand movements captured from a 3D depth camera. Utilizing a single frame from the experiment, an XGBoost machine learning model was employed to differentiate between spontaneous and intentional synchrony modes with nearly [Formula: see text] accuracy. Our findings demonstrate a consistent pattern across subjects, revealing that movement velocity tends to be slower in synchrony modes. These insights support the notion that the relationship between velocity and synchrony is influenced by the cognitive load required for the task, with slower movements leading to higher synchrony in tasks demanding higher cognitive load. This work not only contributes to the limited literature on algorithms for identifying interpersonal synchrony but also has potential implications for developing new metrics to assess real-time human social interactions, understanding social interaction, and diagnosing and developing treatment strategies for social deficits associated with conditions such as Autism Spectrum Disorder.

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