1. Al-Enezi E, Alghamdi M, Al-Enezi K, AlBalwi M, Davies W, Eyaid W. Helsmoortel-Van der Aa syndrome in a 13-year-old girl with autistic spectrum disorder, dysmorphism, a right solitary kidney, and polycystic ovaries: a case report. J Med Case Rep;2024 (Sep 5);18(1):422.

BACKGROUND: Helsmoortel-Van der Aa syndrome was officially documented in 2014. Helsmoortel-Van der Aa syndrome is an extremely rare complex neurodegenerative disorder characterized by reduced intellectual capacity, motor dysfunction, facial dysmorphism, impaired development, and an increased predisposition to autism spectrum disorder. In addition, many patients also present with neuropsychiatric disorders, including attention deficit hyperactivity disorder, anxiety disorders, and various behavioral abnormalities. Helsmoortel-Van der Aa syndrome is challenging to identify solely on the basis of symptoms, and genetic investigations, including exome sequencing, may facilitate diagnosis. CASE PRESENTATION: We report a case of 13-year-old Saudi patient who presented with dysmorphic features as illustrated in Fig. 1, severe mental retardation, autism spectrum disorder, and attention deficit hyperactivity disorder. Initial genetic testing was unremarkable; thus, a clinical exome analysis was performed to identify the genetic basis of the condition. CONCLUSIONS: Clinical exome analysis indicated an autosomal dominant Helsmoortel-Van der Aa syndrome with a likely pathogenic de novo variant within the activity-dependent neuroprotector homeobox (ADNP) gene not previously reported in Helsmoortel-Van der Aa syndrome. The patient had a right-sided solitary kidney and polycystic ovaries, conditions that were not previously associated with HVDAS.

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2. Bahrami F, Taghizadeh M, Shayegh F. Investigation of Electrical Signals in the Brain of People with Autism Using Effective Connectivity Network. J Med Signals Sens;2024;14:24.

Unlike other functional integration methods that examine the relationship and correlation between two channels, effective connection reports the direct effect of one channel on another and expresses their causal relationship. In this article, we investigate and classify electroencephalographic (EEG) signals based on effective connectivity. In this study, we leverage the Granger causality (GC) relationship, a method for measuring effective connectivity, to analyze EEG signals from both healthy individuals and those with autism. The EEG signals examined in this article were recorded during the presentation of abstract images. Given the nonstationary nature of EEG signals, a vector autoregression model has been employed to model the relationships between signals across different channels. GC is then used to quantify the influence of these channels on one another. Selecting regions of interest (ROI) is a critical step, as the quality of the time periods under consideration significantly impacts the outcomes of the connectivity analysis among the electrodes. By comparing these effects in the ROI and various areas, we have distinguished healthy subjects from those suffering from autism. Furthermore, through statistical analysis, we have compared the results between healthy individuals and those with autism. It has been observed that the causal relationship between these two hemispheres is significantly weaker in healthy individuals compared to those with autism.

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3. Bose R, Posada-Pérez M, Karvela E, Skandik M, Keane L, Falk A, Spulber S, Joseph B, Ceccatelli S. Bi-allelic NRXN1α deletion in microglia derived from iPSC of an autistic patient increases interleukin-6 production and impairs supporting function on neuronal networking. Brain Behav Immun;2024 (Sep 5);123:28-42.

Autism spectrum disorder (ASD) is a set of heterogeneous neurodevelopmental conditions, with a highly diverse genetic hereditary component, including altered neuronal circuits, that has an impact on communication skills and behaviours of the affected individuals. Beside the recognised role of neuronal alterations, perturbations of microglia and the associated neuroinflammatory processes have emerged as credible contributors to aetiology and physiopathology of ASD. Mutations in NRXN1, a member of the neurexin family of cell-surface receptors that bind neuroligin, have been associated to ASD. NRXN1 is known to be expressed by neurons where it facilitates synaptic contacts, but it has also been identified in glial cells including microglia. Asserting the impact of ASD-related genes on neuronal versus microglia functions has been challenging. Here, we present an ASD subject-derived induced pluripotent stem cells (iPSC)-based in vitro system to characterise the effects of the ASD-associated NRXN1 gene deletion on neurons and microglia, as well as on the ability of microglia to support neuronal circuit formation and function. Using this approach, we demonstrated that NRXN1 deletion, impacting on the expression of the alpha isoform (NRXN1α), in microglia leads to microglial alterations and release of IL6, a pro-inflammatory interleukin associated with ASD. Moreover, microglia bearing the NRXN1α-deletion, lost the ability to support the formation of functional neuronal networks. The use of recombinant IL6 protein on control microglia-neuron co-cultures or neutralizing antibody to IL6 on their NRXN1α-deficient counterparts, supported a direct contribution of IL6 to the observed neuronal phenotype. Altogether, our data suggest that, in addition to neurons, microglia are also negatively affected by NRXN1α-deletion, and this significantly contributes to the observed neuronal circuit aberrations.

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4. Chen X, Fansler MM, Janjoš U, Ule J, Mayr C. The FXR1 network acts as a signaling scaffold for actomyosin remodeling. Cell;2024 (Sep 5);187(18):5048-5063.e5025.

It is currently not known whether mRNAs fulfill structural roles in the cytoplasm. Here, we report the fragile X-related protein 1 (FXR1) network, an mRNA-protein (mRNP) network present throughout the cytoplasm, formed by FXR1-mediated packaging of exceptionally long mRNAs. These mRNAs serve as an underlying condensate scaffold and concentrate FXR1 molecules. The FXR1 network contains multiple protein binding sites and functions as a signaling scaffold for interacting proteins. We show that it is necessary for RhoA signaling-induced actomyosin reorganization to provide spatial proximity between kinases and their substrates. Point mutations in FXR1, found in its homolog FMR1, where they cause fragile X syndrome, disrupt the network. FXR1 network disruption prevents actomyosin remodeling-an essential and ubiquitous process for the regulation of cell shape, migration, and synaptic function. Our findings uncover a structural role for cytoplasmic mRNA and show how the FXR1 RNA-binding protein as part of the FXR1 network acts as an organizer of signaling reactions.

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5. Elsayed LEO, AlHarbi NA, Alqarni AM, Eltayeb HHE, Mostafa NMM, Abdulrahim MM, Zaid HIB, Alanzi LM, Ababtain SA, Aldulaijan K, Aloyouni SY, Othman MAK, Alkheilewi MA, Binduraihem AM, Alrukban HA, Ahmed HY, AlRadini FA, Alahdal HM, Mushiba AM, Alzaher OA. Chromosome 16p11.2 microdeletion syndrome with microcephaly and Dandy-Walker malformation spectrum: expanding the known phenotype. Hum Genomics;2024 (Sep 4);18(1):95.

BACKGROUND: Chromosome 16p11.2 deletions and duplications were found to be the second most common copy number variation (CNV) reported in cases with clinical presentation suggestive of chromosomal syndromes. Chromosome 16p11.2 deletion syndrome shows remarkable phenotypic heterogeneity with a wide variability of presentation extending from normal development and cognition to severe phenotypes. The clinical spectrum ranges from neurocognitive and global developmental delay (GDD), intellectual disability, and language defects (dysarthria /apraxia) to neuropsychiatric and autism spectrum disorders. Other presentations include dysmorphic features, congenital malformations, insulin resistance, and a tendency for obesity. Our study aims to narrow the gap of knowledge in Saudi Arabia and the Middle Eastern and Northern African (MENA) region about genetic disorders, particularly CNV-associated disorders. Despite their rarity, genetic studies in the MENA region revealed high potential with remarkable genetic and phenotypic novelty. RESULTS: We identified a heterozygous de novo recurrent proximal chromosome 16p11.2 microdeletion by microarray (arr[GRCh38]16p11.2(29555974_30166595)x1) [(arr[GRCh37]16p11.2(29567295_30177916)x1)] and confirmed by whole exome sequencing (arr[GRCh37]16p11.2(29635211_30199850)x1). We report a Saudi girl with severe motor and cognitive disability, myoclonic epilepsy, deafness, and visual impairment carrying the above-described deletion. Our study broadens the known phenotypic spectrum associated with recurrent proximal 16p11.2 microdeletion syndrome to include developmental dysplasia of the hip, optic atrophy, and a flat retina. Notably, the patient exhibited a rare combination of microcephaly, features consistent with the Dandy-Walker spectrum, and a thin corpus callosum (TCC), which are extremely infrequent presentations in patients with the 16p11.2 microdeletion. Additionally, the patient displayed areas of skin and hair hypopigmentation, attributed to a homozygous hypomorphic allele in the TYR gene. CONCLUSION: This report expands on the clinical phenotype associated with proximal 16p11.2 microdeletion syndrome, highlighting the potential of genetic research in Saudi Arabia and the MENA region. It underscores the importance of similar future studies.

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6. Finkel E, Sah E, Spaulding M, Herrington JD, Tomczuk L, Masino A, Pang X, Bhattacharya A, Hedley D, Kushleyeva Y, Thomson P, Doppelt N, Tan J, Pennington J, Dissanayake C, Bonafide CP, Nuske HJ. Physiological and communicative emotional disconcordance in children on the autism spectrum. J Neurodev Disord;2024 (Sep 4);16(1):51.

BACKGROUND: Individuals on the autism spectrum commonly have differences from non-autistic people in expressing their emotions using communicative behaviors, such as facial expressions. However, it is not yet clear if this reduced expressivity stems from reduced physiological reactivity in emotional contexts or if individuals react internally, but do not show these reactions externally to others. We hypothesized that autism is characterized by a discordance between in-the-moment internal psychophysiological arousal and external communicative expressions of emotion. METHODS: Forty-one children on the autism spectrum and 39 non-autistic, typically developing (TD) children of two age groups (2-4 and 8-12 years) participated in a low-level stress task whilst wearing a wireless electrocardiogram. Children’s negative emotional expressions (facial, vocal, bodily) were coded following standardized protocols. Alexithymia traits were assessed using the Children’s Alexithymia Measure with school-aged children only. Data analyses involved ANOVAs, correlations, and sensitivity analyses. RESULTS: There were no group differences in physiological arousal (heart rate) or in communicative expressions of stress to the stress task. For TD preschoolers, physiological arousal during the stress task was associated with vocal expressions and for TD school-aged children, they were associated with facial and bodily expressions. By contrast, for children on the autism spectrum, physiological arousal during the stress tasks was not associated with communicative expressions across age groups. CONCLUSIONS: Our findings suggest that children on the autism spectrum might experience emotional disconcordance, in that their physiological arousal does not align with their communicative expressions. Therefore, the internally experienced stress of children on the autism spectrum may be inadvertently missed by teachers and caregivers and, consequently, learning opportunities for teaching emotional communication and regulation may be also missed. Our results support the use of wearable biosensors to facilitate such interventions in children on the autism spectrum.

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7. Haddad S, Jacobs E, Núñez Pereira S, Ruiz de Villa A, Pupak A, Barcheni M, Ramírez Valencia M, Pizones J, Kleinstück FS, Pérez Grueso FS, Alanay A, Obeid I, Pellisé F. Long-Term Loss of Alignment Following ASD Surgery in the Absence of Mechanical Complications: Aging Spine?. Spine (Phila Pa 1976);2024 (Sep 5)

STUDY DESIGN: Retrospective analysis of a prospective multicenter Adult Spinal Deformity (ASD) registry. OBJECTIVE: Assess whether spinal alignment deteriorates post-surgery in absence of mechanical complications and evaluate the long-term outcomes of ASD surgery over a five-year period. SUMMARY OF BACKGROUND DATA: ASD is prevalent among older adults, leading to significant pain and disability. Surgical intervention, although increasingly popular, is associated with complications, high costs, and uncertain long-term outcomes beyond two years. Mechanical failure and alignment loss often necessitate revision surgeries, but the natural progression of spinal alignment post-surgery without complications remains unclear. METHODS: Clinical and radiological data were analyzed from surgical patients in a multicenter ASD registry who maintained alignment within the instrumented region and completed a 5-year follow-up. The study evaluated patient demographics, surgical details, radiological parameters, and quality of life (QoL) outcomes. Sub-analyses were conducted to compare patients with different initial postoperative alignments and fixation levels. RESULTS: The study included 79 patients (83.5% women, average age 61.9 years) with a mean of 10.7 fused levels. Of these, 29.1% underwent three-column osteotomies (3CO), and 88.6% had a posterior-only approach. While 65% showed favorable alignment at 6 weeks post-surgery, there was a progressive deterioration in global sagittal alignment (Global Tilt/RSA) and thoracic kyphosis over five years (P<0.05), along with increased pelvic compensation (PT SS/RPV). These changes did not correlate with worsening Health-Related Quality of Life outcomes (P>0.05). Older age was linked to greater progression in T2-T12 kyphosis, and osteoporosis was associated with increased SVA and RPV. Optimal immediate postoperative sagittal alignment did not prevent this « aging effect. » CONCLUSIONS: ASD surgery and achieving ideal postoperative alignment do not prevent the ongoing « aging » of the non-instrumented spine. Both thoracic and global sagittal alignments deteriorate over time. Although no functional decline has been observed, the implications of these changes for surgical planning remain uncertain.

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8. Jiang X, Xu C, Xu C, Liu Y, Li L, Li Q, Huang C, Hu J. 2-Ethylhexyl Diphenyl Phosphate Induces Autism Spectrum Disorder-Like Behaviors in Offspring Mice by Disrupting Postsynaptic Development. Environ Sci Technol;2024 (Sep 5)

As organophosphorus flame retardants (OPFRs) are constantly detected in human samples, the neurotoxicity of OPFRs is of concern. In this study, pregnant ICR mice were exposed to 2-ethylhexyl diphenyl phosphate (EHDPP) in drinking water from gestation to lactation to investigate its effects on autism spectrum disorder-like (ASD-like) behaviors in offspring. Serum EHDPP concentrations in dams in the 0.4, 2, and 10 mg/kg groups were 0.282 ± 0.051, 0.713 ± 0.115, and 0.974 ± 0.048 ng/mL, respectively, within the concentration range in humans. At the highest dose, EHDPP exposure induced ASD-like behaviors in both female and male offspring. Significant reductions in mature dendritic spines and structural damage to the postsynaptic density zone were noted in all but the lowest exposure groups, indicating postsynaptic membrane impairment. Mechanistically, EHDPP significantly downregulated disc large MAGUK scaffold protein 4 expression by inhibiting protein kinase B and type 1 insulin-like growth factor receptor phosphorylation. In the heterologous synapse formation assay in vivo, EHDPP significantly reduced the levels of postsynaptic density protein 95 expression in neurons at 1 μM. Overall, the study utilized in vitro and in vivo experiments to confirm that EHDPP damaged postsynaptic membrane formation and might increase the incidence of ASD in offspring.

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9. Kasahara S, Takahashi M, Takahashi K, Morita T, Matsudaira K, Sato N, Momose T, Niwa SI, Uchida K. Case Report: Methylphenidate and venlafaxine improved abdominal nociplastic pain in an adult patient with attention deficit hyperactivity disorder, autism spectrum disorder, and comorbid major depression. Front Pain Res (Lausanne);2024;5:1394131.

INTRODUCTION: Nociplastic pain (NP), classified as a third type of pain alongside nociceptive and neuropathic pain, is chronic pain arising from the amplification of nociceptive stimuli through central sensitization, despite the absence of tissue damage, sensory nerve damage, or disease. An important clinical feature of NP is that it is not only associated with pain but also with sensory hypersensitivity to sound and light and cognitive dysfunction, including mood and attention disorders. Recent studies have suggested that depression and developmental disorders, such as attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), coexist with NP at high frequency. Additionally, cognitive impairment in individuals with NP may be associated with these psychiatric comorbidities. However, to our knowledge, there are no reports on (1) multidimensional evaluation and diagnostic details of abdominal NP in adults with ADHD/ASD; (2) how ADHD drugs and antidepressants are administered when ADHD and depression coexist with NP; and (3) how central sensitization, brain function, and family relationship problems underlying NP are altered by treatments of ADHD and depression. CASE PRESENTATION: Herein, we present the case of a 51-year-old woman with abdominal NP. She developed severe right lower abdominal pain and underwent a thorough medical examination; however, the physical, medical cause remained unknown, making treatment challenging. Additionally, she took time off work as she began to complain of insomnia and anxiety. She was referred to our pain center, where a diagnosis of depression, ADHD, and ASD was confirmed, and treatment with ADHD medication was initiated. While ADHD medications alone did not yield sufficient improvement, a combination of methylphenidate and the antidepressant venlafaxine eventually led to improvements in abdominal NP, depression, ADHD symptoms, central sensitization, and family relationship issues. During treatment, cerebral blood flow in the anterior cingulate, prefrontal, and parietal cortices also improved. CONCLUSION: The treatment of comorbid depression is important while treating NP, and venlafaxine may be effective, especially in cases of comorbid ADHD/ASD. Screening for developmental disorders and depression is required in patients with abdominal NP.

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10. Lin F. Acquisition Time for Resting-State HbO/Hb Coupling Measured by Functional Near-Infrared Spectroscopy in Assessing Autism. J Biophotonics;2024 (Sep 4):e202400150.

Functional near-infrared spectroscopy was used to record spontaneous hemodynamic fluctuations form the bilateral temporal lobes in 25 children with autism spectrum disorder (ASD) and 22 typically developing (TD) children. The coupling between oxygenated hemoglobin (HbO) and deoxygenated hemoglobin (Hb) was calculated by Pearson correlation coefficient, showing significant difference between ASD and TD, thus the coupling could be a characteristic feature for ASD. To evaluate the discrimination ability of the feature obtained in different acquisition times, the receiver operating characteristic curve (ROC) was constructed and the area under curve (AUC) was calculated. The results showed AUC > 0.8 when the time duration was longer than 1.5 min, but longer than 4 min, AUC value (~0.87) hardly varied, implying the maximal discrimination ability reached. This study demonstrated the coupling could be one of characteristic features for ASD even acquired in a short measurement time.

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11. Liu X, Hasan MR, Gedeon T, Hossain MZ. MADE-for-ASD: A multi-atlas deep ensemble network for diagnosing Autism Spectrum Disorder. Comput Biol Med;2024 (Sep 3);182:109083.

In response to the global need for efficient early diagnosis of Autism Spectrum Disorder (ASD), this paper bridges the gap between traditional, time-consuming diagnostic methods and potential automated solutions. We propose a multi-atlas deep ensemble network, MADE-for-ASD, that integrates multiple atlases of the brain’s functional magnetic resonance imaging (fMRI) data through a weighted deep ensemble network. Our approach integrates demographic information into the prediction workflow, which enhances ASD diagnosis performance and offers a more holistic perspective on patient profiling. We experiment with the well-known publicly available ABIDE (Autism Brain Imaging Data Exchange) I dataset, consisting of resting state fMRI data from 17 different laboratories around the globe. Our proposed system achieves 75.20% accuracy on the entire dataset and 96.40% on a specific subset – both surpassing reported ASD diagnosis accuracy in ABIDE I fMRI studies. Specifically, our model improves by 4.4 percentage points over prior works on the same amount of data. The model exhibits a sensitivity of 82.90% and a specificity of 69.70% on the entire dataset, and 91.00% and 99.50%, respectively, on the specific subset. We leverage the F-score to pinpoint the top 10 ROI in ASD diagnosis, such as precuneus and anterior cingulate/ventromedial. The proposed system can potentially pave the way for more cost-effective, efficient and scalable strategies in ASD diagnosis. Codes and evaluations are publicly available at https://github.com/hasan-rakibul/MADE-for-ASD.

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12. M GB, Vesey O, Chavarro JE, Hart JE, Tabb LP, Weisskopf MG, Croen LA, Fallin D, Hertz-Picciotto I, Newschaffer C, Schmidt RJ, Volk H, Lyall K. Characterizing self-reported physical activity before and during a subsequent pregnancy among parents in a familial autism cohort. Autism;2024 (Sep 5):13623613241273034.

Parents of autistic children may have limited time and resources to participate in physical activity, a key aspect of health. Previous studies have been small and included mostly mothers, rather than fathers. No studies have examined physical activity in these parents during another pregnancy, when physical activity is especially important for maternal and fetal health. We aimed to fill this gap by examining physical activity levels among mothers and fathers caring for an autistic child before and during a subsequent pregnancy. We used data from a study which followed pregnant individuals who already had a child with autism. We asked mothers and fathers to report their levels of moderate and vigorous physical activity. We found that mothers and fathers of autistic children reported lower physical activity levels than the national average and were unlikely to meet Physical Activity Guidelines for Americans. Pregnant mothers were the least likely to participate in physical activity, particularly if their autistic child scored highly on a measure of autistic traits. Given that parental physical activity has benefits for parents and children, family-based interventions may be needed to help support parents’ physical activity levels.

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13. Maltman N, Sterling A, Santos E, Hagerman R. Language use predicts symptoms of fragile X-associated tremor/ataxia syndrome in men and women with the FMR1 premutation. Sci Rep;2024 (Sep 5);14(1):20707.

Fragile X-associated tremor/ataxia syndrome (FXTAS) is an age-related neurodegenerative disorder caused by a premutation of the FMR1 gene on the X chromosome. Despite the pervasive physical and cognitive effects of FXTAS, no studies have examined language in symptomatic males and females, limiting utility as an outcome measure in clinical trials of FXTAS. The goal of this work is to determine (a) the extent to which male and female FMR1 premutation carriers with FXTAS symptoms differ in their language use and (b) whether language production predicts FXTAS symptoms. Thirty-one individuals with the FMR1 premutation (21M, 10F), ages 58-85 years with some symptoms of FXTAS, were recruited from a larger cross-sectional study. Participants completed a five-minute monologic language sample. Language transcripts were assessed for rate of dysfluencies, lexical-semantics, syntax, and speech rate. Multivariable linear and ordinal regressions were used to predict FXTAS-associated symptoms, cognitive functioning, and executive functioning. Males and females did not differ in their language use. Language production predicted FXTAS symptom severity, cognitive functioning, and executive functioning. Language production difficulties may co-occur with FXTAS-associated symptoms and may be a viable outcome measure in future clinical trials, with future research needed.

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14. Marín Soro M, Gisbert Gustemps L, Boix Alonso H, Martínez-Maldonado S, Coronado Contreras R. Longitudinal study for the early detection of autism in children with very preterm birth. Brain Dev;2024 (Sep 5)

INTRODUCTION: Very preterm birth is an important risk factor for autism spectrum disorder (ASD). The aim of this study is the early detection of ASD risk, using a follow-up protocol, in children weighing less than 1500 g at birth or born before 32 weeks of gestation. METHODS: This is a prospective longitudinal study in which a total of 133 very premature babies were monitored to the age of 2 years with the M-CHAT autism screening test and, in the event of a positive result, the Autism Diagnostic Observation Schedule (ADOS-2). RESULTS: 53 cases (4 out of 10) screened positive, and the rest negative. Among the positives, the ADOS-2 was administered in 50 cases, of which 24 scored above the ASD cutoff point. The average age of detection was 25.39 months. The results suggest an estimated prevalence of ASD in the very premature population of 18.46 %. CONCLUSIONS: The application of the follow-up protocol in the very premature population is effective for early detection of ASD.

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15. Mottolese N, Coiffard O, Ferraguto C, Manolis A, Ciani E, Pietropaolo S. Autistic-relevant behavioral phenotypes of a mouse model of cyclin-dependent kinase-like 5 deficiency disorder. Autism Res;2024 (Sep 5)

Cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) is a neurodevelopmental disease caused by mutations in the X-linked CDKL5 gene and characterized by early-onset epilepsy, intellectual disability, and autistic features. To date, the etiological mechanisms underlying CDD are largely unknown and no effective therapies are available. The Cdkl5 knock-out (KO) mouse has been broadly employed in preclinical studies on CDD; Cdkl5-KO mice display neurobehavioral abnormalities recapitulating most CDD symptoms, including alterations in motor, sensory, cognitive, and social abilities. However, most available preclinical studies have been carried out on adult Cdkl5-KO mice, so little is known about the phenotypic characteristics of this model earlier during development. Furthermore, major autistic-relevant phenotypes, for example, social and communication deficits, have been poorly investigated and mostly in male mutants. Here, we assessed the autistic-relevant behavioral phenotypes of Cdkl5-KO mice during the first three post-natal weeks and in adulthood. Males and females were tested, the latter including both heterozygous and homozygous mutants. Cdkl5 mutant pups showed qualitative and quantitative alterations in ultrasonic communication, detected first at 2 weeks of age and confirmed later in adulthood. Increased levels of anxiety-like behaviors were observed in mutants at 3 weeks and in adulthood, when stereotypies, reduced social interaction and memory deficits were also observed. These behavioral effects of the mutation were evident in both sexes, being more marked and varied in homozygous than heterozygous females. These findings provide novel evidence for the autistic-relevant behavioral profile of the Cdkl5 mouse model, thus supporting its use in future preclinical studies investigating CDD pathology and autism spectrum disorders.

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16. Paixão I, de Moura FS, de Oliveira LP, Garcia LF. Portuguese-language content about autism spectrum disorder on YouTube: a cross-sectional study. Trends Psychiatry Psychother;2024 (Sep 5)

AIM: This study evaluated the quality and reliability of information about autism spectrum disorder (ASD) available in Portuguese on YouTube, based on the growing demand for accessible information about ASD and the relevance of digital platforms as sources of health information. METHODS: Using a cross-sectional observational study design, videos published in the last 5 years with more than 50,000 views were selected. The analysis consisted of two stages: characterization of the profile of the selected videos and assessment of information quality with the DISCERN Questionnaire. RESULTS: A total of 48 videos, predominantly produced by healthcare providers and educators, were analyzed. The content of videos made by professionals was of higher quality and reliability compared to videos posted by laypersons and news reports. These findings highlight expertise in the field as a critical determinant of content quality, stressing the importance of relying on expert sources when disseminating information about ASD. The ICD-10 and DSM-V were rarely mentioned, especially in videos by non-professionals, which is indicative of challenges in conveying diagnostic information. CONCLUSIONS: The findings of this study demonstrate the significant potential of YouTube as an educational tool to raise ASD awareness, but also highlight the need for a collaborative approach between content creators, healthcare providers, educators, and policymakers to ensure that the information made available is reliable, accurate, and of high quality. Therefore, we recommend the development of specific guidelines for content creators and the implementation of verification mechanisms for YouTube channels run by subject matter experts.

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17. Romanovsky E, Choudhary A, Peles D, Abu-Akel A, Stern S. Uncovering convergence and divergence between autism and schizophrenia using genomic tools and patients’ neurons. Mol Psychiatry;2024 (Sep 5)

Autism spectrum disorders (ASDs) are highly heritable and result in abnormal repetitive behaviors and impairment in communication and cognitive skills. Previous studies have focused on the genetic correlation between ASDs and other neuropsychiatric disorders, but an in-depth understanding of the correlation to other disorders is required. We conducted an extensive meta-analysis of common variants identified in ASDs by genome-wide association studies (GWAS) and compared it to the consensus genes and single nucleotide polymorphisms (SNPs) of Schizophrenia (SCZ). We found approximately 75% of the GWAS genes that are associated with ASD are also associated with SCZ. We further investigated the cellular phenotypes of neurons derived from induced pluripotent stem cell (iPSC) models in ASD and SCZ. Our findings revealed that ASD and SCZ neurons initially follow divergent developmental trajectories compared to control neurons. However, despite these early diametrical differences, both ASD and SCZ neurons ultimately display similar deficits in synaptic activity as they mature. This significant genetic overlap between ASD and SCZ, coupled with the convergence towards similar synaptic deficits, highlights the intricate interplay of genetic and developmental factors in shaping the shared underlying mechanisms of these complex neurodevelopmental and neuropsychiatric disorders.

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18. Seymour M, Pecora L, McMahon G, Wood CE, Feinberg M, Hock R, Giallo R. Trajectories of psychological distress for Australian fathers parenting a child on the autism spectrum: Evidence from early childhood to adolescence. Autism;2024 (Sep 5):13623613241272005.

This study explores the mental health journey of fathers with children on the autism spectrum. Little is known about mental health over time for these fathers. This research spans six-timepoints from when children were aged 4 to 14 years, to track fathers’ mental health. This study had three aims: (1) report estimates of fathers’ psychological distress across 10 years of child development; (2) identify separate courses of psychological distress over time; and (3) identify early risk factors associated with these courses. This study used data from 281 fathers of children on the autism spectrum who took part in the Longitudinal Study of Australian Children. Using a statistical method to group fathers based on their psychological distress scores over 10 years of child development, the results showed that two groups best explained the data; this included a group of fathers who experienced low levels of psychological distress over the 10 years of child development (84%), and another group of fathers who experienced heightened psychological distress across this time (16%). Further analysis showed that fathers who had an ongoing medical condition and higher levels of interparental conflict with their partners were more likely to be in the heightened psychological distress group. These findings show that almost one in six fathers deal with persistent psychological distress throughout their child’s early childhood and into early adolescence. This study advocates for interventions focusing on improving fathers’ physical health and the couple relationship as ways to positively impact fathers’ mental health in the long run.

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19. Straiton D, Pomales-Ramos A, Broder-Fingert S. Health Equity and Rising Autism Prevalence: Future Research Priorities. Pediatrics;2024 (Sep 5)

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20. Tomasello DL, Barrasa MI, Mankus D, Alarcon KI, Lytton-Jean AKR, Liu XS, Jaenisch R. Mitochondrial dysfunction and increased reactive oxygen species production in MECP2 mutant astrocytes and their impact on neurons. Sci Rep;2024 (Sep 4);14(1):20565.

Studies on MECP2 function and its implications in Rett Syndrome (RTT) have traditionally centered on neurons. Here, using human embryonic stem cell (hESC) lines, we modeled MECP2 loss-of-function to explore its effects on astrocyte (AST) development and dysfunction in the brain. Ultrastructural analysis of RTT hESC-derived cerebral organoids revealed significantly smaller mitochondria compared to controls (CTRs), particularly pronounced in glia versus neurons. Employing a multiomics approach, we observed increased gene expression and accessibility of a subset of nuclear-encoded mitochondrial genes upon mutation of MECP2 in ASTs compared to neurons. Analysis of hESC-derived ASTs showed reduced mitochondrial respiration and altered key proteins in the tricarboxylic acid cycle and electron transport chain in RTT versus CTRs. Additionally, RTT ASTs exhibited increased cytosolic amino acids under basal conditions, which were depleted upon increased energy demands. Notably, mitochondria isolated from RTT ASTs exhibited increased reactive oxygen species and influenced neuronal activity when transferred to cortical neurons. These findings underscore MECP2 mutation’s differential impact on mitochondrial and metabolic pathways in ASTs versus neurons, suggesting that dysfunctional AST mitochondria may contribute to RTT pathophysiology by affecting neuronal health.

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