1. Alagia M, Fecarotta S, Romano A, Parrini E, Auricchio G, Miano MG, Terrone G. A Novel Splicing SCN2A Mutation in an Adolescent With Low-Functioning Autism, Acute Dystonic Movement Disorder, and Late-Onset Generalized Epilepsy. Pediatric neurology. 2022; 138: 58-61.

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2. Deutsch SI, Burket JA. From Mouse to Man: N-Methyl-d-Aspartic Acid Receptor Activation as a Promising Pharmacotherapeutic Strategy for Autism Spectrum Disorders. The Medical clinics of North America. 2023; 107(1): 101-17.

The BALB/c mouse displays hypersensitivity to behavioral effects of MK-801 (dizocilpine), a noncompetitive N-methyl-d-aspartic acid (NMDA) receptor « open-channel » blocker, and shows both no preference for an enclosed stimulus mouse over an inanimate object and reduced social interaction with a freely behaving stimulus mouse. NMDA receptor agonist interventions improved measures of social preference and social interaction of the BALB/c mouse model of autism spectrum disorder (ASD). A « proof of principle/proof of concept » translational 10-week clinical trial with 8-week of active medication administration was conducted comparing 20 DSM-IV-TR-diagnosed older adolescent/young adult patients with ASD randomized to once-weekly pulsed administration (50 mg/d) versus daily administration of d-cycloserine (50 mg/d). The results showed that d-cycloserine, a partial glycine agonist, was well tolerated, the 2 dosing strategies did not differ, and improvement was noted on the « lethargy/social withdrawal » and « stereotypic behavior » subscales of the Aberrant Behavior Checklist. NMDA receptor activation contributes to the regulation of mTOR signaling, a pathologic point of convergence in several monogenic syndromic forms of ASD. Furthermore, both NMDA receptor hypofunction and imbalance between NMDA receptor activation mediated by GluN2B and GluN2A-containing NMDA receptors occur as « downstream » consequences of several genetically unrelated abnormalities associated with ASD. NMDA receptor-subtype selective « positive allosteric modulators (PAMs) » are particularly appealing medication candidates for future translational trials.

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3. Faustmann LL, Kretschmer-Trendowicz A, Altgassen M. Do emotionally salient cues improve prospective memory performance in children and adolescents with autism?. Research in developmental disabilities. 2022; 131: 104375.

BACKGROUND: Prospective memory (PM) describes the ability to initiate and perform a planned action after a delay. Previous studies suggest reduced PM in autism spectrum disorder (ASD); especially when tasks put high demands on executive control resources. Increasing cue salience by presenting emotional cues improves PM performance in non-autistic populations. AIMS: To explore whether children with ASD, whose processing of emotionally connoted information might differ from that of typically developing children, may also benefit from this type of salience in PM tasks. METHODS AND PROCEDURES: Twenty-five children with and 25 children without ASD completed a 1-back ongoing task into which an event-based PM task was embedded. Emotional salience of PM cues was varied. OUTCOMES AND RESULTS: Children with ASD performed as well as children without ASD on the PM task and equally benefited from emotionally salient cues. Specifically, negative cues increased PM performance compared to neutral cues in both groups CONCLUSIONS AND IMPLICATIONS: The findings are consistent with the multiprocess framework which postulates that salient PM cues increase performance by promoting automatic intention retrieval and reducing executive control demands. Children with ASD seem to show similar comprehension and accessibility to emotional cues as typically developing children.

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4. Gai J, Xing J, Wang Y, Lei J, Zhang C, Zhang J, Tang J. Exploration of potential targets and mechanisms of Naringenin in treating autism spectrum disorder via network pharmacology and molecular docking. Medicine. 2022; 101(46): e31787.

Naringenin (NR) is a kind of flavonoid which plays a great role in the treatment of autism spectrum disorder (ASD). However, the underlying mechanism of NR in treating ASD still remains unclear. This study used network pharmacology and molecular docking to examine the potential targets and pharmacological mechanism of NR on ASD. Targets related to NR were screened from Traditional Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP), Encyclopedia of Traditional Chinese Medicine Database (ETCM), Traditional Chinese Medicine Integrated Database (TCMID), PharmaMapper database, and targets related to ASD were screened from Online Mendelian Inheritance In Man (OMIM), Disgenet, GeneCards, Therapeutic Target Database (TTD), Drugbank, and ETCM. Screened of the intersected gene targets. Then, we used the protein-protein interaction (PPI) networks to construct a PPI network and used Network Analyzer plug-in to perform topological analysis to screen out the core target. We used Metascape platform to perform gene ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and used Chem draw, Pymol, AutoDock 1.5.6 software for molecular docking verification with core targets. A total of 149 targets of NR and 1594 potential targets of ASD were screened, and 43 intersected targets and 8 key targets were obtained and screened. A total of 176 GO items were obtained by GO enrichment analysis (P < .05), 153 entries on biological process (BP), 12 entries on BP and 11entries on cell composition (CC) were included. A total of 100 signaling pathways were obtained by KEGG pathway enrichment screening (P < .05).The pathways that are closely related to the pathogenesis of ASD are estrogen signaling, thyroid hormone signaling pathway, prolactin signaling pathway, and endocrine resistance pathway. Molecular docking results showed that NR had the best docking activity with the core target CASP3, and had good binding ability with AKT1, ESR1, ACTB and MAPK3. Taken together, our findings support that NR exerts therapeutic effects on ASD with multi-target, and multi-pathway characteristics, which provides a preliminary theoretical basis for clinical trials. The mechanism of anti-oxidative stress response, anti-apoptosis, regulation of cell growth and metabolism, anti-inflammatory, balance hormone levels may be important for the therapeutic effect.

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5. Hajdúk M, Straková A, Januška J, Ivančík V, Dančík D, Čavojská N, Valkučáková V, Heretik A, Pečeňák J, Abplanalp SJ, Green MF. Connections between and within extended psychosis and autistic phenotypes and social relationships in the general population. Journal of psychiatric research. 2022; 157: 36-42.

OBJECTIVES: Non – clinical individuals with higher levels of autistic traits and psychotic experiences also have problems in social relationships. Therefore, this study aimed to model complex associations between autistic and psychotic phenotypes and indicators of social relationships in the general population using a network approach. METHODS: The sample consisted of 649 participants with a mean age of M = 40.23 and SD = 13.09 sampled from the general population. The sample was representative for the 18-65 years old general population in the Slovak Republic. The following scales were administered: Community Assessment of Psychic Experiences, The Comprehensive Autistic Trait Inventory, and NIH Toolbox Adult Social Relationship Scales. Associations between variables and the presence of communities were identified using Exploratory Graph Analysis. RESULTS: Results revealed four highly stable and densely connected communities within the network: social relationships, autistic traits, positive symptoms, and the last one consisting of all negative symptoms, problems in social interactions, and depression. The most important variables in the network were difficulties in social interaction, perceived rejection, bizarre ideas, depression, and social withdrawal. CONCLUSIONS: The psychotic and autistic phenotypes in the general population showed a network of connections with characteristics of social relationships. Community detection revealed that autistic traits and psychotic-like experiences formed relatively independent communities. Further, there was substantial overlap between negative symptoms (e.g., social withdrawal), and core features of the autistic phenotype, especially social interaction difficulties.

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6. Hantman RM, Johnston EB, Tager-Flusberg H. Parental Perspectives: How Sensory Sensitivities Impact the Transition to Adulthood in Adolescents and Young Adults with Autism Spectrum Disorder. Journal of autism and developmental disorders. 2022: 1-19.

Sensory sensitivities are common in autism spectrum disorder (ASD) and impact daily life, but research has largely focused on children, neglecting older individuals. Likewise, while there is research regarding parental concerns for their autistic children’s transition to adulthood, little is known about the role of sensory sensitivities. To address this gap, 66 parents of autistic adolescents and young adults were interviewed and their responses were qualitatively analyzed. All parents believed their children’s sensory sensitivities impacted their transition to adulthood, primary developmentally/psychologically, interpersonally/socially, and managerially. These beliefs did not significantly differ by child characteristics, such as age and ASD severity. Parent perceptions were modality and context specific. Given these findings, transition planning should consider individual’s specific sensory sensitivities to optimize independence.

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7. Nic Ghiolla Phadraig A, Smyth S. Sleep mediates the relationship between having an autistic child and poor family functioning. Sleep medicine. 2022; 101: 190-6.

Sleep is an important biological necessity, a lack of which can have many cognitive, psychological, social, and physical impacts. Children with autism are known to present with sleep difficulties more frequently than their typically developing peers but despite this, there is relatively little research looking at the impact of sleep on the family. To investigate the effect of sleep on families of autistic and typically developing (TD) children, we conducted a study of sleep disturbances among children, sleep quality of their parents in association with their family function. In our study, 239 parents of autistic children and 227 parents of TD children participated. These parents completed a survey about their child’s sleep disturbances, their own sleep quality, and their family function, along with a series of demographic questions. Analyses indicated that autistic children experience more sleep difficulties than TD peers, that children’s sleep disturbances are associated with parental sleep quality and that parents of autistic children report decreased sleep quality compared to parents of TD children. Parental sleep quality, and child sleep quality were both found to partially mediate the relationship between autism diagnosis and family function.

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8. Oudet S, Howard K, Durrleman S. Early years autism and bilingualism: An interpretative phenomenological analysis of parent perceptions during lockdown. Autism & developmental language impairments. 2022; 7: 23969415221138704.

AIM: This study explores how bilingual parents of autistic children made language decisions for their families, how the event of the SARS-CoV-2 pandemic and subsequent lockdown impacted the communication environment of their households, and whether these experiences affected their language habits. METHOD: Semi-structured interviews were conducted with five bilingual parents of autistic children who lived through lockdown in France. Data were analysed using interpretative phenomenological analysis. Demographic and background information was collected using an adapted version of the Questionnaire for Parents of Bilingual Children. RESULTS: Participants reported conflicting advice given by a range of practitioners. Parents expressed differing beliefs about the impact of language choices on their children. Parents described active engagement with their children’s home-learning as generally positive. Parents identified an increase in children’s exposure to their first language during the lockdown. Parents reported an increase in children’s overall communication abilities. CONCLUSION: Parents believed that their children’s positive communication development during lockdown was related to increased exposure to their first language(s), and direct involvement in their children’s learning programs.

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9. Pijuan I, Balducci E, Soto-Sánchez C, Fernández E, Barallobre MJ, Arbonés ML. Impaired macroglial development and axonal conductivity contributes to the neuropathology of DYRK1A-related intellectual disability syndrome. Scientific reports. 2022; 12(1): 19912.

The correct development and activity of neurons and glial cells is necessary to establish proper brain connectivity. DYRK1A encodes a protein kinase involved in the neuropathology associated with Down syndrome that influences neurogenesis and the morphological differentiation of neurons. DYRK1A loss-of-function mutations in heterozygosity cause a well-recognizable syndrome of intellectual disability and autism spectrum disorder. In this study, we analysed the developmental trajectories of macroglial cells and the properties of the corpus callosum, the major white matter tract of the brain, in Dyrk1a(+/-) mice, a mouse model that recapitulates the main neurological features of DYRK1A syndrome. We found that Dyrk1a(+/-) haploinsufficient mutants present an increase in astrogliogenesis in the neocortex and a delay in the production of cortical oligodendrocyte progenitor cells and their progression along the oligodendroglial lineage. There were fewer myelinated axons in the corpus callosum of Dyrk1a(+/-) mice, axons that are thinner and with abnormal nodes of Ranvier. Moreover, action potential propagation along myelinated and unmyelinated callosal axons was slower in Dyrk1a(+/-) mutants. All these alterations are likely to affect neuronal circuit development and alter network synchronicity, influencing higher brain functions. These alterations highlight the relevance of glial cell abnormalities in neurodevelopmental disorders.

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10. Ravaei A, Rubini M. Folate in maternal rheumatoid arthritis-filial autism spectrum disorder continuum. Reproductive toxicology (Elmsford, NY). 2022; 115: 29-35.

Rheumatoid Arthritis (RA) is an inflammatory autoimmune disease that affects women three times more than men. Epidemiological studies found that the incidence of Autism Spectrum Disorder (ASD), a neurological and developmental disorder, in children born to mothers suffering from RA is higher compared with the control population. Considering that the pathogenesis of ASD could be traced back to pregnancy and in uterine conditions, and the evidence of reduced folate levels in the brain of ASD-affected children, we aimed to study the role of folate, as an important nutritional factor during pregnancy, in associating maternal RA to ASD development in the offspring. Folate balance during RA could be influenced twice, initially during the immune activation associated with disease onset, and later during the treatment with anti-folate drugs, with a potential consequence of folate deficiency. Maternal folate deficiency during pregnancy could increase homocysteine levels, oxidative stress, and global DNA hypomethylation, all known risk factors in ASD pathogenesis. These effects could be intensified by genetic polymorphisms in the folate system, which were also found as genetic risk factors for both RA and ASD. The available evidence suggests that folate level as an important factor during RA, pregnancy and ASD could have pathological and therapeutical significance and should be carefully monitored and investigated in the RA-pregnancy-ASD axis.

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