1. Armingol E, Baghdassarian HM, Martino C, Perez-Lopez A, Aamodt C, Knight R, Lewis NE. Context-aware deconvolution of cell-cell communication with Tensor-cell2cell. Nat Commun;2022 (Jun 27);13(1):3665.

Cell interactions determine phenotypes, and intercellular communication is shaped by cellular contexts such as disease state, organismal life stage, and tissue microenvironment. Single-cell technologies measure the molecules mediating cell-cell communication, and emerging computational tools can exploit these data to decipher intercellular communication. However, current methods either disregard cellular context or rely on simple pairwise comparisons between samples, thus limiting the ability to decipher complex cell-cell communication across multiple time points, levels of disease severity, or spatial contexts. Here we present Tensor-cell2cell, an unsupervised method using tensor decomposition, which deciphers context-driven intercellular communication by simultaneously accounting for multiple stages, states, or locations of the cells. To do so, Tensor-cell2cell uncovers context-driven patterns of communication associated with different phenotypic states and determined by unique combinations of cell types and ligand-receptor pairs. As such, Tensor-cell2cell robustly improves upon and extends the analytical capabilities of existing tools. We show Tensor-cell2cell can identify multiple modules associated with distinct communication processes (e.g., participating cell-cell and ligand-receptor pairs) linked to severities of Coronavirus Disease 2019 and to Autism Spectrum Disorder. Thus, we introduce an effective and easy-to-use strategy for understanding complex communication patterns across diverse conditions.

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2. Belek B. ‘A Smaller Mask’: Freedom and Authenticity in Autistic Space. Cult Med Psychiatry;2022 (Jun 26):1-21.

Autscape is an autistic-led conference, organised annually in varying locations around England. Governed by a strict set of rules and regulations, Autscape is a social and spatial setup explicitly devised to accommodate the tendencies, sensitivities, and preferences of people on the autism spectrum. It is a design, in other words-as organisers and participants alike often profess-for an altogether autistic space. The uniqueness of the event, and consequently its value to anthropological theory, lies in the shared imagination of the setting by those who inhabit it as one in which neurotypical masks, otherwise worn daily in keeping with hegemonic society’s expectation of conformity, can finally be removed. I introduce the concept of un-festival as a means of depicting this event, similar to festival in its goals of defiance and inversion, but different from-and in important ways, opposite to-festival in its style and architecture, in the dispositions it encourages and mobilises, and in its potential implications. The un-festival offers a powerful comment on this moment in history, whereby masks are no longer seen as an item that affords freedom, but as one that stifles it. While Autscape participants remain doubtful as to the actual effect of this event on neurotypical society, they do nevertheless express a desire that this project will have some longstanding effects. That once a space has been designed for autistic people that considers their specific needs and tendencies, autism may then finally cease to be interpreted through a neuro-normative prism and freed to be understood in autistic people’s own terms.

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3. Charidza CA, Gillmeister H. Differential beta desynchronisation responses to dynamic emotional facial expressions are attenuated in higher trait anxiety and autism. Cogn Affect Behav Neurosci;2022 (Jun 27)

Daily life demands that we differentiate between a multitude of emotional facial expressions (EFEs). The mirror neuron system (MNS) is becoming increasingly implicated as a neural network involved with understanding emotional body expressions. However, the specificity of the MNS’s involvement in emotion recognition has remained largely unexplored. This study investigated whether six basic dynamic EFEs (anger, disgust, fear, happiness, sadness, and surprise) would be differentiated through event-related desynchronisation (ERD) of sensorimotor alpha and beta oscillatory activity, which indexes sensorimotor MNS activity. We found that beta ERD differentiated happy, fearful, and sad dynamic EFEs at the central region of interest, but not at occipital regions. Happy EFEs elicited significantly greater central beta ERD relative to fearful and sad EFEs within 800 – 2,000 ms after EFE onset. These differences were source-localised to the primary somatosensory cortex, which suggests they are likely to reflect differential sensorimotor simulation rather than differential attentional engagement. Furthermore, individuals with higher trait anxiety showed less beta ERD differentiation between happy and sad faces. Similarly, individuals with higher trait autism showed less beta ERD differentiation between happy and fearful faces. These findings suggest that the differential simulation of specific affective states is attenuated in individuals with higher trait anxiety and autism. In summary, the MNS appears to support the skills needed for emotion processing in daily life, which may be influenced by certain individual differences. This provides novel evidence for the notion that simulation-based emotional skills may underlie the emotional difficulties that accompany affective disorders, such as anxiety.

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4. Chehbani F, Tomaiuolo P, Picinelli C, Baccarin M, Castronovo P, Scattoni ML, Gaddour N, Persico AM. Yield of array-CGH analysis in Tunisian children with autism spectrum disorder. Mol Genet Genomic Med;2022 (Jun 27):e1939.

BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with strong genetic underpinnings. Microarray-based comparative genomic hybridization (aCGH) technology has been proposed as a first-level test in the genetic diagnosis of ASD and of neurodevelopmental disorders in general. METHODS: We performed aCGH on 98 Tunisian children (83 boys and 15 girls) diagnosed with ASD according to DSM-IV criteria. RESULTS: « Pathogenic » or « likely pathogenic » copy number variants (CNVs) were detected in 11 (11.2%) patients, CNVs of « uncertain clinical significance » in 26 (26.5%), « likely benign » or « benign » CNVs were found in 37 (37.8%) and 24 (24.5%) patients, respectively. Gene set enrichment analysis involving genes spanning rare « pathogenic, » « likely pathogenic, » or « uncertain clinical significance » CNVs, as well as SFARI database « autism genes » in common CNVs, detected eight neuronal Gene Ontology classes among the top 10 most significant, including synapse, neuron differentiation, synaptic signaling, neurogenesis, and others. Similar results were obtained performing g: Profiler analysis. Neither transcriptional regulation nor immune pathways reached significance. CONCLUSIONS: aCGH confirms its sizable diagnostic yield in a novel sample of autistic children from North Africa. Recruitment of additional families is under way, to verify whether genetic contributions to ASD in the Tunisian population, differently from other ethnic groups, may involve primarily neuronal genes, more than transcriptional regulation and immune-related pathways.

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5. Chenausky KV, Norton AC, Tager-Flusberg H, Schlaug G. Auditory-motor mapping training: Testing an intonation-based spoken language treatment for minimally verbal children with autism spectrum disorder. Ann N Y Acad Sci;2022 (Jun 26)

We tested an intonation-based speech treatment for minimally verbal children with autism (auditory-motor mapping training, AMMT) against a nonintonation-based control treatment (speech repetition therapy, SRT). AMMT involves singing, rather than speaking, two-syllable words or phrases. In time with each sung syllable, therapist and child tap together on electronic drums tuned to the same pitches, thus coactivating shared auditory and motor neural representations of manual and vocal actions, and mimicking the « babbling and banging » stage of typical development. Fourteen children (three females), aged 5.0-10.8, with a mean Autism Diagnostic Observation Schedule-2 score of 22.9 (SD = 2.5) and a mean Kaufman Speech Praxis Test raw score of 12.9 (SD = 13.0) participated in this trial. The main outcome measure was percent syllables approximately correct. Four weeks post-treatment, AMMT resulted in a mean improvement of +12.1 (SE = 3.8) percentage points, compared to +2.8 (SE = 5.7) percentage points for SRT. This between-group difference was associated with a large effect size (Cohen’s d = 0.82). Results suggest that simultaneous intonation and bimanual movements presented in a socially engaging milieu are effective factors in AMMT and can create an individualized, interactive music-making environment for spoken-language learning in minimally verbal children with autism.

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6. Jensen AR, Lane AL, Werner BA, McLees SE, Fletcher TS, Frye RE. Modern Biomarkers for Autism Spectrum Disorder: Future Directions. Mol Diagn Ther;2022 (Jun 27)

Autism spectrum disorder is an increasingly prevalent neurodevelopmental disorder in the world today, with an estimated 2% of the population being affected in the USA. A major complicating factor in diagnosing, treating, and understanding autism spectrum disorder is that defining the disorder is solely based on the observation of behavior. Thus, recent research has focused on identifying specific biological abnormalities in autism spectrum disorder that can provide clues to diagnosis and treatment. Biomarkers are an objective way to identify and measure biological abnormalities for diagnostic purposes as well as to measure changes resulting from treatment. This current opinion paper discusses the state of research of various biomarkers currently in development for autism spectrum disorder. The types of biomarkers identified include prenatal history, genetics, neurological including neuroimaging, neurophysiologic, and visual attention, metabolic including abnormalities in mitochondrial, folate, trans-methylation, and trans-sulfuration pathways, immune including autoantibodies and cytokine dysregulation, autonomic nervous system, and nutritional. Many of these biomarkers have promising preliminary evidence for prenatal and post-natal pre-symptomatic risk assessment, confirmation of diagnosis, subtyping, and treatment response. However, most biomarkers have not undergone validation studies and most studies do not investigate biomarkers with clinically relevant comparison groups. Although the field of biomarker research in autism spectrum disorder is promising, it appears that it is currently in the early stages of development.

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7. Lee JK, Andrews DS, Ozturk A, Solomon M, Rogers S, Amaral DG, Nordahl CW. Altered Development of Amygdala-Connected Brain Regions in Males and Females with Autism. J Neurosci;2022 (Jun 27)

Altered amygdala development is implicated in the neurobiology of autism, but little is known about the coordinated development of the brain regions directly connected with the amygdala. Here we investigated the volumetric development of an amygdala-connected network, defined as the set of brain regions with monosynaptic connections with the amygdala, in autism from early to middle childhood. Nine-hundred and fifty longitudinal structural MRI scans were acquired from 282 children (93 female) with autism and 128 children with typical development (61 female) at up to four timepoints (mean ages: 39, 52, 64, 137 months, respectively). Volumes from 32 amygdala-connected brain regions were examined using mixed effects multivariate distance matrix regression. The Social Responsiveness Scale-2 was administered to assess degree of autistic traits and social impairments. The amygdala-connected network exhibited persistent diagnostic differences (ps ≤ 0.03) that increased over time (ps ≤ 0.02). These differences were most prominent in autistics with more impacted social functioning at baseline. This pattern was not observed across regions without monosynaptic amygdala connection. We observed qualitative sex-differences. In males, the bilateral subgenual anterior cingulate cortices were most affected, while in females the left fusiform and superior temporal gyri were most affected. In conclusion, (a) autism is associated with widespread alterations to the development of brain-regions connected with the amygdala, which were associated with autistic social behaviors, and (b) autistic males and females exhibited different patterns of alterations, adding to a growing body of evidence of sex differences in the neurobiology of autism.SIGNIFICANCE STATEMENTGlobal patterns of development across brain regions with monosynaptic connection to the amygdala differentiate autism from typical development, and is modulated by social functioning in early childhood. Alterations to brain regions within the amygdala-connected network differed in males and females with autism. Results also indicate larger volumetric differences in regions having monosynaptic connection with the amygdala than in regions without monosynaptic connection.

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8. Moody CT, Factor RS, Gulsrud AC, Grantz CJ, Tsai K, Jolliffe M, Rosen NE, McCracken JT, Laugeson EA. A pilot study of PEERS® for Careers: A comprehensive employment-focused social skills intervention for autistic young adults in the United States. Res Dev Disabil;2022 (Jun 27);128:104287.

BACKGROUND: Autistic young adults are at elevated risk for poor employment/internship outcomes, despite having many strengths relevant to the workplace. Currently, very few employment interventions for this population comprehensively promote skills development and success across the various stages of employment. AIMS: To address this gap, the current study aimed to test the feasibility, acceptability, and efficacy of a novel college to career intervention program, PEERS® for Careers. METHODS AND PROCEDURES: Twelve autistic young adults (19-30 years old) were enrolled and matched to a career coach. The pilot program consisted of 90-minute sessions delivered twice per week, for 10 weeks, covering content relevant to obtaining, maintaining, and thriving in employment/internship settings. OUTCOMES AND RESULTS: Results indicated that young adults showed a significant improvement in employment-related social skills knowledge, p < .001. Participants also reported significant improvements in their feelings of preparedness for employment over the course of the study, p = .009, with all young adults self-identifying as "somewhat prepared" or "very prepared" post-intervention. Additionally, in only a brief 10-week intervention, a slight increase in participants who secured or maintained internship/employment-related activities was observed. Overall, lesson content and coaching were perceived as helpful. No significant changes were observed in self-reported autism symptomatology. CONCLUSIONS AND IMPLICATIONS: In sum, the PEERS® for Careers program shows promise as a college to career intervention program for autistic young adults. WHAT THIS PAPER ADDS: There is a dearth of evidence-based interventions for autistic young adults, despite significant need for supports to bolster vocational and relational success. This paper is the first to evaluate the PEERS® for Careers intervention in a pilot study by exploring feasibility, acceptability, and efficacy of this novel college to career intervention program, which teaches ecologically valid employment-related skills using a strengths-based approach. Results suggest PEERS® for Careers shows significant potential as a comprehensive intervention to address the multi-faceted needs of autistic individuals in the workplace through didactic lessons, behavioral rehearsals to practice skills, and out of group assignments. Autistic young adult participants reported a high level of satisfaction with the program and lessons surrounding employment-related social skills. They also endorsed increased feelings of internship/employment readiness and increased knowledge of workplace etiquette, with most participants maintaining or securing employment. This study supports PEERS® for Careers as a feasible intervention that likely benefits autistic individuals' vocational outcomes, which emerge as a strong correlate of well-being in adulthood. This work is essential to furthering the development and provision of effective services to meet needs of the autism community.

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9. Okay K, Varış P, Miral S, Pavlopoulou A, Oktay Y, Karakülah G. Whole Genome Analysis of Dizygotic Twins With Autism Reveals Prevalent Transposon Insertion Within Neuronal Regulatory Elements: Potential Implications for Disease Etiology and Clinical Assessment. J Autism Dev Disord;2022 (Jun 27)

Transposable elements (TEs) have been implicated in autism spectrum disorder (ASD). However, our understanding of their roles is far from complete. Herein, we explored de novo TE insertions (dnTEIs) and de novo variants (DNVs) across the genomes of dizygotic twins with ASD and their parents. The neuronal regulatory elements had a tendency to harbor dnTEIs that were shared between twins, but ASD-risk genes had dnTEIs that were unique to each twin. The dnTEIs were 4.6-fold enriched in enhancers that are active in embryonic stem cell (ESC)-neurons (p < 0.001), but DNVs were 1.5-fold enriched in active enhancers of astrocytes (p = 0.0051). Our findings suggest that dnTEIs and DNVs play a role in ASD etiology by disrupting enhancers of neurons and astrocytes.

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10. Oti-Boadi M, Osei-Tutu A, Mate-Kole CC. Challenges and support needs of parents of children with developmental disabilities (DD) in Accra, Ghana. Res Dev Disabil;2022 (Jun 23);128:104274.

BACKGROUND: Parents of children with developmental disabilities (DD) have diverse challenges and needs. If met, these parents are able to provide adequate care for their children. Unfulfilled needs like information about their child’s diagnosis, counselling, and poor access to informal and formal supports increase parental stress and hinder their potential to provide optimal care for their children and themselves. AIMS: This study explores the unique challenges and needs of parents caring for children with DD in the Accra metropolis. This is the first study exploring the needs of parents in a Lower-middle income (LMIC) country like Ghana. METHODS AND PROCEDURES: A qualitative research design was adopted for this study. Data was collected using semi-structured interviews from 9 parents of children with DD. RESULTS: Findings from thematic analysis revealed five themes including; Emotional needs; Informational needs; Financial needs; Informal Support, and Formalized Support. Parents indicated their great need for information on their children’s condition, support from family, religious groups, and other formalized institutions and how to provide better care. CONCLUSIONS AND IMPLICATIONS: Parents have several expectations and needs which must be addressed. Findings have the potential of influencing the design and development of appropriate interventions to meet the needs and improve the quality of life of parents of children with DD in the Ghanaian context.

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11. Walker R, Swain J, Pellicano E. « It’s about sharing a moment »: Parents’ views and experiences of home reading with their autistic children with moderate-to-severe intellectual disabilities. Res Dev Disabil;2022 (Jun 24);128:104289.

BACKGROUND: The home literacy environment plays a critical role in the development of children’s literacy and language development. Little is known, however, about the home literacy environment of autistic children, especially those with moderate-to-severe intellectual disabilities. AIMS: The current study used a sequential mixed-methods design to understand how parents attempt to engage their autistic children in reading activities and support them in learning to read. METHODS AND PROCEDURE: First, 63 parents (53 mothers) whose autistic children attended an autism-specific special school completed a bespoke questionnaire about the home literacy environments for their children (n = 69, age range = 3-11 years, 61 boys, 8 girls). Second, a subsample of parents (n = 19, 15 mothers) participated in focus groups to understand in-depth their views and experiences of home reading with their children (n = 20, age range = 3-11 years, 19 boys, 1 girl). We used reflexive thematic analysis to analyse the focus group data. OUTCOMES AND RESULTS: Across questionnaire and focus group methods, parents were united in considering reading to be an important life skill, a sentiment that was reflected both by their often literacy-rich homes and the ingenuity in their efforts to engage their children in shared home-reading activities – even when such engagement could be challenging. They also emphasised, however, the importance of valuing these activities as an opportunity to « catch a moment » with their child. CONCLUSIONS AND IMPLICATIONS: Parents and teachers should work together to identify ways to enhance autistic children’s engagement in shared home-reading activities, listening to and learning from each other’s experiences and expertise, and to show what is possible within each learning context.

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12. Yankowitz LD, Petrulla V, Plate S, Tunc B, Guthrie W, Meera SS, Tena K, Pandey J, Swanson MR, Pruett JR, Jr., Cola M, Russell A, Marrus N, Hazlett HC, Botteron K, Constantino JN, Dager SR, Estes A, Zwaigenbaum L, Piven J, Schultz RT, Parish-Morris J. Infants later diagnosed with autism have lower canonical babbling ratios in the first year of life. Mol Autism;2022 (Jun 27);13(1):28.

BACKGROUND: Canonical babbling-producing syllables with a mature consonant, full vowel, and smooth transition-is an important developmental milestone that typically occurs in the first year of life. Some studies indicate delayed or reduced canonical babbling in infants at high familial likelihood for autism spectrum disorder (ASD) or who later receive an ASD diagnosis, but evidence is mixed. More refined characterization of babbling in the first year of life in infants with high likelihood for ASD is needed. METHODS: Vocalizations produced at 6 and 12 months by infants (n = 267) taking part in a longitudinal study were coded for canonical and non-canonical syllables. Infants were categorized as low familial likelihood (LL), high familial likelihood diagnosed with ASD at 24 months (HL-ASD) or not diagnosed (HL-Neg). Language delay was assessed based on 24-month expressive and receptive language scores. Canonical babble ratio (CBR) was calculated by dividing the number of canonical syllables by the number of total syllables. Generalized linear (mixed) models were used to assess the relationship between group membership and CBR, controlling for site, sex, and maternal education. Logistic regression was used to assess whether canonical babbling ratios at 6 and 12 months predict 24-month diagnostic outcome. RESULTS: No diagnostic group differences in CBR were detected at 6 months, but HL-ASD infants produced significantly lower CBR than both the HL-Neg and LL groups at 12 months. HL-Neg infants with language delay also showed reduced CBR at 12 months. Neither 6- nor 12-month CBR was significant predictors of 24-month diagnostic outcome (ASD versus no ASD) in logistic regression. LIMITATIONS: Small numbers of vocalizations produced by infants at 6 months may limit the reliability of CBR estimates. It is not known if results generalize to infants who are not at high familial likelihood, or infants from more diverse racial and socioeconomic backgrounds. CONCLUSIONS: Lower canonical babbling ratios are apparent by the end of the first year of life in ASD regardless of later language delay, but are also observed for infants with later language delay without ASD. Canonical babbling may lack specificity as an early marker when used on its own.

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