1. Correction: Creating a diagnostic assessment model for autism spectrum disorder by differentiating lexicogrammatical choices through machine learning. PLoS One. 2025; 20(4): e0320613.

[This corrects the article DOI: 10.1371/journal.pone.0311209.].

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2. Aikat V, Carpenter KLH, Babu PRK, Di Martino JM, Espinosa S, Compton S, Davis N, Franz L, Spanos M, Sapiro G, Dawson G. Autism Digital Phenotyping in Preschool- and School-Age Children. Autism Res. 2025.

There is a critical need for scalable and objective tools for autism screening and outcome monitoring, which can be used alongside traditional caregiver and clinical measures. To address this need, we developed SenseToKnow, a tablet- or smartphone-based digital phenotyping application (app), which uses computer vision and touch data to measure several autism-related behavioral features, such as social attention, facial and head movements, and visual-motor skills. Our previous work demonstrated that the SenseToKnow app can accurately detect and quantify behavioral signs of autism in 18-40-month-old toddlers. In the present study, we administered the SenseToKnow app on an iPad to 149 preschool- and school-age children (45 neurotypical and 104 autistic) between 3 and 8 years of age. Results revealed significant group differences between autistic and neurotypical children in terms of several behavioral features, which remained after controlling for sex and age. Repeat administration with a subgroup demonstrated stability in the individual digital phenotypes. Examining correlations between the Vineland Adaptive Behavior Scales and individual digital phenotypes, we found that autistic children with higher levels of communication, daily living, socialization, motor, and adaptive skills exhibited higher levels of social attention and coordinated gaze with speech, less frequent head movements, higher complexity of facial movements, higher overall attention, lower blink rates, and higher visual motor skills, demonstrating convergent validity between app features and clinical measures. App features were also significantly correlated with ratings on the Social Responsiveness Scale. These results suggest that the SenseToKnow app can be used as an accessible, scalable, and objective digital tool to measure autism-related behaviors in preschool- and school-age children.

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3. Al-Haddad BJS, Olson E, Reardon E, Bonney E. Neurodevelopmental screening for neonates less than 44 weeks gestation in low-income and middle-income countries: a systematic review. BMJ Glob Health. 2025; 10(4).

INTRODUCTION: With global improvements in neonatal survival, more small and sick newborns in low-income and middle-income countries (LMICs) are at increased risk of neurodevelopmental disability and delay. While there is increased recognition of the importance of early identification of neurodevelopmental differences and timely initiation of therapy, little is known about standardised neonatal neurodevelopmental screening tools in these settings. METHODS: We performed a systematic review to determine what standardised neurodevelopmental assessments had been used in LMICs for neonates before 44 weeks corrected gestational age and published in the literature. We excluded short-term clinical assessments designed for specific pathologies. We performed the search across seven databases, screened studies for eligibility and inclusion and extracted bibliographic data, country, patient characteristics, assessments and study aims. Results were summarised in tabular and graphical presentation. RESULTS: There were 2477 records screened, yielding 67 studies for inclusion. Studies in Asian countries made up 65.7%, while Latin America and Africa made up 19.4% and 16.4%, respectively. Physicians and paramedical staff performed the screening assessments in only 16.4% of studies, and 92.5% of studies used inpatient recruitment. The Neonatal Behavioural Neurological Assessment (25.4%) was the most frequently used screening tool followed by the General Movements Assessment (22.4%), the Hammersmith Neonatal Neurological Examination/Dubowitz (16.4%) and the Neonatal Behavioural Assessment Scale (10.4%). CONCLUSIONS: We did not identify any one neonatal neurodevelopmental screening assessment that is rapid, globally validated, identifies targets for intervention, has high predictive prognostic value and does not require neonatal or kinesiologic expertise or uncommon equipment. Such an assessment, in concert with evidence-based intervention, therapeutic delivery platforms, established referral pathways and trained personnel would improve functional outcomes for high-risk small and sick neonates in LMICs.

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4. Alabdali AN, Ben Bacha A, Alonazi M, Abuaish S, Almotairi A, Al-Ayadhi L, El-Ansary AK. Impact of GABA and nutritional supplements on neurochemical biomarkers in autism: a PPA rodent model study. Front Mol Neurosci. 2025; 18: 1553438.

BACKGROUND/OBJECTIVES: Autism spectrum disorder (ASD) is associated with excitatory-inhibitory imbalance and oxidative stress. GABA, an inhibitory neurotransmitter, and related nutritional therapies are promising in restoring these imbalances. GABAergic deficits and glutamate excitotoxicity are two essential signaling pathways that could be addressed to treat autism, thus medications targeting these pathways are critical for treating behavioral symptoms. In a rat model of autism produced by propionic acid (PPA), this study assessed the effects of GABA supplementation and combined nutritional therapy (probiotics, vitamin D3) and β-lactam as an activator of glutamate transporter. METHODS: Sixty rats were randomly assigned into six groups: Group I (Control), Group II (PPA-treated), Group III (Control-GABA), Group IV (Control-Combination), Group V (PPA-GABA), and Group VI (PPA-Combination). Social behavior was evaluated using the three-chamber test. Selected biochemical variables related to oxidative stress (GST, Catalase, Lipid peroxides, GSH and Vitamin C), GABA and glutamate signaling (EAAT2, KCC2, NKCC1, GABA, VD3, Glutamate and GABRA5) were measured in the brain homogenates of the six groups. The hippocampus was examined histopathologically to assess cellular integrity. RESULTS: The obtained data revealed that PPA treatment caused significant oxidative stress and neurotransmitter imbalances, characterized by reduced GABA and elevated glutamate levels. GABA supplementation alone produced moderate benefits in biochemical and behavioral markers, but combined therapy considerably restored GABA levels, reduced oxidative stress, and enhanced social interaction behaviors. Histopathology revealed that combination therapy mitigated neurodegenerative changes induced by PPA, preserving hippocampal cellular structure. CONCLUSION: This study demonstrated that combined therapy (GABA, probiotics, vitamin D3, and β-lactam) were more effective than GABA alone in enhancing neurochemical balance and lowering oxidative stress in a PPA-induced mouse model of autism, indicating promise for treating symptoms.

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5. AlSharari SD, Mahmood HM, Alasmari AF, AlDhalaan HM, Alasmari F, Khan MR, Ahmad SF, Aljasham AT, Damaj IM, Alshammari MA. Nicotine Attenuates Molecular Signalings in the BTBR T(+) Itpr3(tf)/J Mouse Model of Autism. Mol Neurobiol. 2025.

Accumulating evidence indicates that nicotinic receptor subtypes are altered in the brains of autistic individuals, and nicotinic acetylcholine receptors (nAChRs) play essential roles in autistic profiles in BTBR T(+) Itpr3(tf)/J mice. This study aimed to elucidate the roles of nicotine on systemic inflammatory cytokine levels and expression patterns of nicotinic receptor subtypes in the prefrontal cortex in BTBR T(+) Itpr3(tf)/J mice. This research project characterized the effect of chronic treatment with nicotine at a dose (100 mcg/ml; po) administrated orally in drinking water over a period of fourteen days in BTBR T(+) Itpr3(tf)/J mice, while C57BL/6 J mice were served as the controls. Following the nicotine treatment, the levels of tumor necrosis factor (TNF)-α, interferon (IFN)-γ interleukin (IL)-1β, and granulocyte-macrophage colony-stimulating factor (GM-CSF) were assessed in the serum; the levels of pro-inflammatory cytokines [interleukin (IL)-17 and interferon (IFN)-γ], on CD4(+) and CD8(+) T cells were evaluated in the blood. Moreover, the expression of α7, α4, and β2-nAChRs in the prefrontal cortex in BTBR T(+) Itpr3(tf)/J mice was examined. Biochemical analysis showed that nicotine had significantly decreased the concentration of inflammatory cytokines, including TNF-α, IFN-γ, IL-1β, and GM-CSF in the serum, and reduced the expression levels of intracellular pro-inflammatory cytokines (IL-17 & IFN-γ) on CD4(+) and CD8(+) T cells in the blood while mecamylamine reversed the effect of IL-17(+) CD4(+) T cells. Nicotine administration up-regulated the expressions of α7, α4, and β2 nAChRs in the prefrontal cortex in BTBR T(+) Itpr3(tf)/J mice. The current results indicate that nAChRs play a significant role, at least in part, in ASD and might serve as a crucial target for therapeutic interventions in ASD.

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6. Andari E, Gopinath K, O’Leary E, Caceres GA, Nishitani S, Smith AK, Ousley O, Rilling JK, Cubells JF, Young LJ. Random forest and Shapley Additive exPlanations predict oxytocin targeted effects on brain functional networks involved in salience and sensorimotor processing, in a randomized clinical trial in autism. Neuropsychopharmacology. 2025.

Intranasal oxytocin (IN-OXT) has shown some promises in rescuing social deficits in autism spectrum disorder (ASD) as well as some inconsistencies in long-term trials. We conducted a target engagement study to study the precise effects of different doses of IN-OXT on brain resting-state functional connectivity (rsFC) in ASD. We examined the effects of varying doses of IN-OXT (0 IU, 8 IU, 24 IU, 48 IU) on rsFC in a double-blind, placebo-controlled, within-subject design in 30 male adults with ASD and 17 neurotypical controls (NT) receiving placebo. Random forest analysis was used to classify individuals as ASD or NT. Shapely Additive explanations values were calculated to rank brain functional networks by level of contribution to ASD deficits and to evaluate IN-OXT dose effects. The model predicted ASD diagnosis with an AUC of 94%. Hypoconnectivity between salience/empathy and visual networks, and hyperconnectivity between reward and sensorimotor networks and theory of mind networks were among the strongest predictors of ASD deficits. IN-OXT had a dose-dependent effect on rescuing both deficits described above. Overall, 48 IU dose was more effective, and 24 IU dose was more effective in those who have lower DNA OXT receptor methylation and lower severity of clinical symptoms. Higher doses of OXT might be necessary to enhance empathic responses, and ASD individuals with less support needs and with a preserved OXT system might benefit most from OXT treatment. Applying machine learning approaches in OXT research can provide data-driven unbiased results that can inform future clinical trials.

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7. Chmielewska A, Domellöf M. Iron deficiency in infants and children – the current research challenges. Curr Opin Clin Nutr Metab Care. 2025; 28(3): 284-8.

PURPOSE OF REVIEW: Iron deficiency (ID) affects one in five children before they reach preschool age. Existing evidence on ID contributing to suboptimal development and neurodevelopmental disorders come mostly from mechanistic and observational studies. Recommendations for screening and treatment are diverging, emphasizing the knowledge gap. The purpose of this review is to summarize recent evidence on ID in infants and children, its possible role in developmental disorders, and effects of iron supplementation. RECENT FINDINGS: Recent well powered randomized controlled trials showed no effect of early iron supplementation on psychomotor development in infants, neither in populations at high nor low risk of ID. Treatment of nonanemic ID in children 1-3 years did not improve their cognitive scores. Evidence from observational and imaging studies suggests association of brain ID and attention deficit hyperactivity disorder in children (ADHD). SUMMARY: Universal prophylactic iron supplementation in infants is not supported by current evidence. Whether non anemic ID needs to be treated is uncertain and so is the legitimacy and timing of screening for ID and anemia. The role of ID and iron availability for the brain in pathogenesis of neurodevelopmental conditions such as ADHD requires further studies.

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8. Ferguson BJ, Dovgan K, Hoffman M, Hogg M, Rose C, Beversdorf DQ. Pilot Trial on the Effects of Propranolol on Gastrointestinal Symptoms in Autism Spectrum Disorder and Heart Rate Variability as a Treatment Response Biomarker. J Child Adolesc Psychopharmacol. 2025.

Background: Many individuals with autism spectrum disorder (ASD) experience gastrointestinal (GI) symptoms, which can impact social interactions, exacerbate social communication deficits, and decrease the quality of life. GI symptoms have been shown to be correlated with the autonomic nervous system and endocrine response to stress in some people with ASD. Furthermore, propranolol, a central and peripheral beta-adrenergic antagonist that inhibits the stress response, has been shown to provide GI relief for some individuals with ASD, but not others. This pilot study examined whether baseline (i.e., resting) heart rate variability (HRV), a biomarker that is sensitive to the stress response, predicted the response to propranolol in decreasing GI symptoms. Methods: In this pilot study, a sample of 37 individuals with ASD participated in a 12-week open-label trial of propranolol. The Gastrointestinal Severity Index and HRV were collected at baseline (i.e., prior to taking propranolol) and again at the end of the 12-week trial period. Results: Higher HRV was associated with the greatest reduction in GI symptoms, with a strong effect size, but only for adolescents and young adults (15-24 years old). Baseline HRV and GI change scores were not significantly correlated for younger children (7-14 years old). Conclusions: The results from this open-label pilot trial suggest that autistic adolescents and young adults with higher baseline HRV, indicating greater parasympathetic tone, may respond better to propranolol and show the greatest reduction in GI symptoms. The data from this pilot should be interpreted with caution until larger, randomized, double-blinded, placebo-controlled trials of propranolol for GI symptoms in ASD are completed.

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9. Frenkel J, Kirst S, Naumann S, Simon M, Sessner J, Roesler E, Onnasch L, Dziobek I. Stakeholder acceptance of a robot-assisted social training scenario for autistic children compared to a tablet-computer-based approach. Sci Rep. 2025; 15(1): 11237.

Recent studies indicate the potential benefits of robot-assisted therapy (RAT) for children on the autism spectrum (AS), yet acceptance among stakeholders remains unclear due to methodological shortcomings in existing research. This study evaluates stakeholders’ acceptance of a RAT-scenario designed to train emotion recognition and regulation in AS children using Softbank Robotics Pepper, a humanoid robot with an integrated tablet screen, compared to a tablet-based therapy (TBT) control. An online survey of 123 stakeholders (caregivers, professionals, and autistic adults) assessed RAT and TBT using global acceptance, intention to use, and acceptance-related factors (ALMERE model), alongside stakeholders’ concerns. While a larger proportion of stakeholders (58%) showed high global acceptance of RAT, stakeholders preferred TBT across measures and groups (p < .001, Wilk's Λ = 0.595), potentially due to its established familiarity and easier usability. The intention to use RAT was predicted by perceived usefulness, and, to a smaller extent, perceived ease of use, and affinity for technology, independent of stakeholder group. Concerns mainly addressed the expected effort to implement RAT in therapeutic services. Overall, the results highlight stakeholder acceptance and underscore the need to enhance RAT's perceived usefulness and ease of implementation, suggesting a user-centered design approach for future deployments.

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10. Geier DA, Geier MR. Tooth decay prevention and neurodevelopmental disorder risk following childhood fluoride exposure. BMC Pediatr. 2025; 25(1): 265.

BACKGROUND: The Centers for Disease Control and Prevention (CDC) reports that water fluoridation is among the ten greatest public health achievements of the 20(th )Century. Tooth decay (TD) prevention and neurodevelopmental disorder (ND) risk were assessed in relation to childhood water fluoridation exposure. METHODS: This longitudinal cohort study examined the Independent Healthcare Research Database (IHRD) composed of prospectively collected healthcare data from the Florida Medicaid system for the period 1990-2012, using logistic and frequency statistical modeling (with adjustment for covariates). A cohort of 73,254 children continuously enrolled for their first 10 years of life was examined. The yearly percentage of persons in Florida receiving fluoridated water exposure from community water systems was examined by county. The number of children diagnosed with TD, autism spectrum disorder (ASD), attention deficit-hyperactivity disorder (ADHD), intellectual disability (ID), and specific delays in development (SDD) was evaluated. RESULTS: Fluoride exposure in the year of birth, statistically significantly and dose-dependently, slightly reduced the risk of TD, and, separately, slightly increased the risk of ASD, ADHD, ID, and SDD. During the first 10 years of life, children who were fluoride-exposed as compared to unexposed were at significantly lower risk for TD, and, separately, at significantly greater risk for ASD, ID, and SDD. CONCLUSIONS: Findings from the present study, coupled with previous studies, suggest new risk/benefit analyses of water fluoridation should be undertaken.

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11. Gerber AH, Naples A, Chawarska K, Dawson G, Kleinhans N, Jeste S, Faja S, Dziura J, Webb S, Sugar C, Shic F, Levin AR, McPartland JC. Longitudinal relationships between social anhedonia and internalizing symptoms in autistic children: results from the Autism Biomarkers Consortium for Clinical Trials. Psychol Med. 2025; 55: e104.

BACKGROUND: Social anhedonia, indicating reduced pleasure from social interaction, is heightened in autistic youth and associated with increased internalizing symptoms transdiagnostically. The stability of social anhedonia over time and its longitudinal impact on internalizing symptoms in autism have never been examined. METHODS: Participants were 276 autistic children (M(age) = 8.60, SD(age) = 1.65; 211 male) with IQ ≥ 60 (M(IQ) = 96.74, SD(IQ) = 18.19). Autism severity was measured using the Autism Diagnostic Observation Schedule, Second Edition. Caregivers completed the Child and Adolescent Symptom Inventory, Fifth Edition (CASI-5) at baseline, 6 weeks, and 6 months. The CASI-5 includes a social anhedonia subscale derived from relevant items across domains. ICC (Intraclass Correlation Coefficient) analysis assessed stability, while cross-lagged panel models examined associations among social anhedonia, depression, and social anxiety across time. RESULTS: At baseline, social anhedonia correlated with autism severity, as well as parent-reported social anxiety and depression. Social anhedonia showed relative stability (ICC = 0.763) over 6 months, with a significant decline between baseline and 6 weeks (β = -0.52, p < .001). Cross-lagged models revealed a bidirectional relationship between social anhedonia and depression over time, while social anxiety displayed concurrent, but not predictive, associations across time. CONCLUSIONS: Social anhedonia demonstrated stability over 6 months, suggesting that it may be a relatively stable characteristic in autistic children. Concurrent relationships were observed between social anhedonia and depression, as well as social anxiety and attention-deficit/hyperactivity disorder. Only depression demonstrated a bidirectional longitudinal association with social anhedonia. This bidirectional relationship aligns with developmental models linking early negative social experiences to subsequent internalizing symptoms in autistic children, underscoring the clinical significance of social anhedonia assessment in this population.

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12. Hu E, Kuang X, Zhaohui S, Wang S, Wang P, Zhou W, Ming Z, Cheng Y, Ye C, Yan K, Gong X, Wang T, Peng X. Data independent acquisition proteomics and machine learning reveals that proteins associated with immunity are potential molecular markers for early diagnosis of autism. Clin Chim Acta. 2025: 120238.

BACKGROUND: Early diagnosis of autism is critical to its treatment, but so far, there is no clear molecular marker for early diagnosis in children. METHODS: We used data independent acquisition (DIA) mass spectrometry to compare protein expression in serum from 99 Chinese children with autism spectrum disorders with 70 healthy children. RESULTS: We identified 347 downregulated and 394 upregulated proteins. Based on bioinformatics analysis, differential proteins were enriched in the immune system, immune disease, cell motility, and focal adhesion. Machine learning revealed a model with eight proteins (IGH c1898_heavy_IGHV3-33_IGHD3-9_IGHJ4, LYZ, IGL c1860_light_IGLV8-61_IGLJ2, SERPINA10, IG c1421_light_IGKV1-27_IGKJ4, rheumatoid factor RF-ET1, IGL c600_light_IGKV4-1_IGKJ4, and SELL) that were mostly associated with immunity, and accurate for diagnosis of autism. The protein family was verified by a logic-regression leave-one cross-validation method with bidirectional feature screening. The accuracy of this model was 0.9527, and the kappa coefficient was 0.9025. CONCLUSIONS: Our study showed that immunity is closely related to the onset of autism and can be used for early screening of patients. A model with eight proteins (IGH c1898_heavy_IGHV3-33_IGHD3-9_IGHJ4, LYZ, IGL c1860_light_IGLV8-61_IGLJ2, SERPINA10, IG c1421_light_IGKV1-27_IGKJ4, rheumatoid factor RF-ET1, IGL c600_light_IGKV4-1_IGKJ4, and SELL), which are mostly associated with immunity, is accurate for diagnosis of autism.

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13. Lin H, Zeng J, Zheng Q, Huang L, Liu G, Zhou X, Song M, Guo S. Effects of a WeChat-based parent-child creative art therapy for mothers of children with autism spectrum disorder: A pilot randomized controlled trial. J Pediatr Nurs. 2025.

PURPOSE: This study was conducted to evaluate the efficacy of a WeChat-based parent-child creative art therapy (PCCAT) program on child-parent relationships and psychological well-being in mothers of children with autism spectrum disorder (ASD). DESIGN AND METHODS: A two-arm randomized controlled trial was employed. Sixty-eight child-parent dyads were recruited and followed up in a special training school from August 2022 to March 2023. They were randomly assigned to either the intervention group (n = 34) receiving WeChat-based PCCAT plus online home visits or control group (n = 34) receiving online home visits alone. Outcomes were assessed using the Child-Parent Relationship Scale (C-PRS), Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale (SDS), and Posttraumatic Growth Inventory (PTGI) at baseline, 12-week (T1), and 24-week (T2) follow-ups. RESULTS: Sixty dyads completed the 24-week protocol. Linear mixed model analyses revealed significant group×time interaction effects for C-PRS, SAS, SDS, and PTGI scores (p < 0.001). Pairwise comparisons demonstrated significantly lower anxiety (SAS) and depression (SDS) scores, alongside higher parent-child relationship (C-PRS) and posttraumatic growth (PTGI) scores in the intervention group versus controls (all p < 0.05). Participant satisfaction data indicated 86.6 % of mothers reported extremely satisfaction with the program, with 93.3 % of dyads maintaining >90 % participation adherence. CONCLUSION: The WeChat-based PCCAT program effectively improved parent-child relationships, reduced maternal anxiety and depression, and enhanced posttraumatic growth. PRACTICE IMPLICATIONS: This nurse-led intervention demonstrates feasibility for integration into ASD family management protocols. The program’s digital delivery format suggests potential adaptability across comparable platforms, warranting implementation in broader clinical contexts. TRIAL REGISTRATION: Chinese Clinical Trials Registry, ChiCTR2200062598. Registration date: 13/08/2022.

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14. Qin Q, Li M, Fan L, Zeng X, Zheng D, Wang H, Jiang Y, Ma X, Xing L, Wu L, Liang S. RVG engineered extracellular vesicles-transmitted miR-137 improves autism by modulating glucose metabolism and neuroinflammation. Mol Psychiatry. 2025.

Autism spectrum disorder (ASD) is a prevalent neurodevelopmental disorder. The microglia activation is a hallmark of ASD, which involves increased glycolysis. Elevated glycolysis regardless of oxygen availability, known as « Warburg effect », is crucial to pathogenesis in neuropsychiatric disorders. Psychiatric risk gene MIR137 plays an important role in neurogenesis and neuronal maturation, but the impact on neuroinflammation and glucose metabolism remains obscure. Extracellular vesicles (EVs) can delivery miR-137 crossing the blood-brain barrier. Meanwhile, EVs can help miR-137 avoid being rapidly degraded by endogenous nucleases. Here, after first detecting miR-137 decreased both in the peripheral blood of individuals with ASD and the serum and cerebellum of BTBR mice, we demonstrated that microglia activation, the level of lactate and key enzymes (HK2, PKM2 and LDHA) involved in glycolysis were increased significantly in BTBR mice. Of particular note, EVs engineered by rabies virus glycoprotein (RVG) could promote the miR-137 (RVG-miR137-EVs) targeted to the brain accurately, and alleviated autism-like behaviors. Pro-inflammatory activation of BTBR mice was considerably inhibited by RVG-miR137-EVs via tail vein administration, accompanied by decreased lactate production. Mechanically, these effects were attributed to TLR4, the key target gene, which was regulated by miR-137. The TLR4/NF-κB pathway was inhibited, subsequently reducing HIF-1α and repressing the transcription of HK2, PKM2 and LDHA involved in glycolysis. Pharmacological inhibition of glycolysis and TLR4 attenuated microglial activation and lactate production, ultimately improved autism-like behaviors of BTBR mice. In conclusion, our results indicated that miR-137 could alleviate autism-like behaviors by HIF-1α-mediated adaptive metabolic changes in glycolysis and neuroinflammation.

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15. Ross PD, Gadalla KKE, Thomson SR, Selfridge J, Bahey NG, Benito J, Burstein SR, McMinn R, Bolon B, Hector RD, Cobb SR. Self-regulating gene therapy ameliorates phenotypes and overcomes gene dosage sensitivity in a mouse model of Rett syndrome. Sci Transl Med. 2025; 17(792): eadq3614.

Conventional methods of gene transfer lead to inconsistent transgene expression within cells. This variability can be problematic, particularly in conditions like Rett syndrome (RTT), a neurological disorder caused by mutations in the MECP2 (methyl-CpG binding protein 2) gene, because overexpression of MECP2 can also cause adverse effects. To address these challenges, we devised a gene regulation system called Expression Attenuation via Construct Tuning (EXACT), which uses a self-contained, microRNA-based feed-forward loop that not only ensures more consistent transgene expression but also protects against excessive expression. Through cell-based screening assays, we demonstrated the ability of the EXACT circuit to modulate the expression of full-length human MeCP2. Compared with a conventional construct, an EXACT-MECP2 construct exhibited a narrower range of cellular protein abundance. Furthermore, the degree of regulation by the EXACT circuit increased with higher transgene doses in vitro and in wild-type mice and mice modeling RTT. On the basis of cellular and in vivo testing, we identified an optimal configuration for the adeno-associated virus serotype 9 (AAV9) construct for self-regulated MECP2 gene therapy, designated NGN-401. Delivery of NGN-401 to neonatal male Mecp2(-/y) hemizygous mice via intracerebroventricular injection resulted in prolonged survival and amelioration of RTT-like phenotypes compared with vehicle-treated animals. NGN-401 was also well tolerated by female Mecp2(+/-) mice and healthy juvenile nonhuman primates, in contrast with a conventional construct, which caused toxicity. The results from these studies underpin a first-in-human pediatric trial of NGN-401 in RTT (ClinicalTrials.gov, NCT05898620).

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16. Schinaia C. Catastrophism and catastrophic images: Ferenczi’s identification with the aggressor and Ogden’s autistic-contiguous position as defence mechanisms. Am J Psychoanal. 2025.

Ferenczi’s concept, the confusion of tongues between the child’s language of tenderness and the adult’s language of passion, explains that the child feels physically and psychically helpless and alone in the presence of an aggressor who disavows the traumatic acts, creating confusion for the child whether the traumatic experience happened at all. Fully dependent on the adults, the child adopts by introjecting the guilt and hate of the aggressor, in order to maintain the relationship with the adults. The confusion of tongues situation is linked to Ferenczi’s complex construct, the identification with the aggressor, in understanding external traumas. With the concept of « autistic-contiguous position, » Ogden identifies an area of pre-symbolic experience of a sensory nature, mainly centered on the surface of the skin as the starting point of mental life. These two concepts may permit us to be in touch with attitudes and beliefs in the exploration of individual and group defense mechanisms against climate change and environmental disasters. Using psychoanalytical knowledge, we can try to help people who are reluctant to fully acknowledge the seriousness of climate change, and so to change damaging behaviors in our relationship with the nonhuman world. The author critiques the repeated terrifying and bombarding images on TV and the Internet which would intend to inform about crises and disasters in the world, instead, those images paralyze psychic functioning. He describes how climate terrorism promotes the emergence of persecutory and primitive anxieties, even the activation of psychotic defenses. They foster the difficulties of getting in touch with deep-seated anxieties and remove a sense of responsibility and awareness of one’s own participation in the creation of the damage.

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17. Selvanayagam T, Hoang N, Sarikaya E, Howe J, Russell C, Iaboni A, Quirbach M, Marshall CR, Szatmari P, Anagnostou E, Vorstman J, Hartley DM, Scherer SW. Clinical utility of genome sequencing in autism: illustrative examples from a genomic research study. J Med Genet. 2025.

BACKGROUND: Genetics is an important contributor to autism spectrum disorder (ASD). Clinical guidelines endorse genetic testing in the medical workup of ASD, particularly tests that use whole genome sequencing (WGS) technology. While the clinical utility of genetic testing in ASD is demonstrated, the breadth of impact of results can depend on the variant and/or gene being reported. METHODS: We reviewed research results returned to families enrolled in our ASD WGS study between 2012 and 2023. For significant results, we grouped the outcome of each genetic finding into three outcome categories: (1) genetic diagnosis, (2) counselling benefits and (3) support to family. RESULTS: Out of 202 families who received genome sequencing results, 100 had at least one clinically relevant finding related to ASD. With detailed examples, we show that all significant results led to a genetic diagnosis and counselling benefits. CONCLUSION: Our findings show the relevance of genome sequencing in ASD and provide illustrative examples of how the information can be used.

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18. Wainer AL, Edmunds SR, Carter AS, Stone WL, Sheldrick RC, Broder-Fingert S, Stern YS, Harrington E, L VI, Ingersoll B. A hybrid type I randomized effectiveness-implementation trial of a Naturalistic Developmental Behavioral Intervention in the Part C early intervention system: study protocol. BMC Pediatr. 2025; 25(1): 263.

BACKGROUND: Participation in Naturalistic Developmental Behavioral Interventions (NDBI) is associated with significant improvements in functioning for toddlers with, and showing early signs of, autism spectrum disorder. The Part C Early Intervention (EI) system, which is publicly funded and available in all U.S. states, offers an optimal infrastructure through which toddlers can receive NDBIs. This study seeks to assess the effectiveness and fit of one NDBI, Caregiver Implemented Reciprocal Imitation Teaching (CI-RIT), within the Part C EI system. METHODS: This hybrid type 1 effectiveness/implementation trial uses a multi-site randomized control design to simultaneously test effectiveness and collect implementation data on CI-RIT in the Part C EI system across four states: Illinois, Massachusetts, Michigan and Washington. Participants include EI providers (target n = 160) who are randomized to either CI-RIT or treatment as usual (TAU), and child/caregiver dyads on their caseloads (target n = 440). Primary effectiveness outcomes focus on (1) child social communication, joint attention, motor imitation; and (2) caregiver responsivity, implementation fidelity of RIT, and self-efficacy, which are all measured at baseline and then 4-months and 9-months after baseline. Implementation outcomes include CI-RIT modifications, treatment acceptability, fidelity of CI-RIT coaching, and RIT session completion. DISCUSSION: This study represents a critical effort to transport an evidence-based NDBI, CI-RIT, into a national service delivery setting, the Part C EI system. The large, multi-site nature of the trial provides the opportunity to address critical questions about training and intervention effectiveness, which will, in turn, optimize and support CI-RIT implementation at scale. TRIAL REGISTRATION: The trial protocol is registered at ClinicalTrials.gov (NCT05114538; Registration date: 10/28/2021).

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19. Wu X, Liang C, Bustillo J, Kochunov P, Wen X, Sui J, Jiang R, Yang X, Fu Z, Zhang D, Calhoun VD, Qi S. The Impact of Atlas Parcellation on Functional Connectivity Analysis Across Six Psychiatric Disorders. Hum Brain Mapp. 2025; 46(5): e70206.

Neuropsychiatric disorders are associated with altered functional connectivity (FC); however, the reported regional patterns of functional alterations suffered from low replicability and high variability. This is partly because of differences in the atlas and delineation techniques used to measure FC-related deficits within/across disorders. We systematically investigated the impact of the brain parcellation approach on the FC-based brain network analysis. We focused on identifying the replicable FCs using three structural brain atlases, including Automated Anatomical Labeling (AAL), Brainnetome atlas (BNA) and HCP_MMP_1.0, and four functional brain parcellation approaches: Yeo-Networks (Yeo), Gordon parcel (Gordon) and two Schaefer parcelletions, among correlation, group difference, and classification tasks in six neuropsychiatric disorders: attention deficit and hyperactivity disorder (ADHD, n = 340), autism spectrum disorder (ASD, n = 513), schizophrenia (SZ, n = 200), schizoaffective disorder (SAD, n = 142), bipolar disorder (BP, n = 172), and major depression disorder (MDD, n = 282). Our cross-atlas/disorder analyses demonstrated that frontal-related FC deficits were reproducible in all disorders, independent of the atlasing approach; however, replicable FC extraction in other areas and the classification accuracy were affected by the parcellation schema. Overall, functional atlases with finer granularity performed better in classification tasks. Specifically, the Schaefer atlases generated the most repeatable FC deficit patterns across six illnesses. These results indicate that frontal-related FCs may serve as potential common and robust neuro-abnormalities across 6 psychiatric disorders. Furthermore, in order to improve the replicability of rsfMRI-based FC analyses, this study suggests the use of functional templates at larger granularity.

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20. Yuan S, Pang C, Wu L, Yi L, Guo K, Jiang YH, Zhang YQ, Han S. Autism-like atypical face processing in Shank3 mutant dogs. Sci Adv. 2025; 11(14): eadu3793.

Atypical face processing is a neurocognitive basis of social deficits in autism spectrum disorder (ASD) and a candidate cognitive marker for the disease. Although hundreds of risk genes have been identified in ASD, it remains unclear whether mutations in a specific gene may cause ASD-like atypical face processing. Dogs have acquired exquisite face processing abilities during domestication and may serve as an effective animal model for studying genetic associations of ASD-like atypical face processing. Here, we showed that dogs with Shank3 mutations exhibited behavioral and attentional avoidance of faces, contrasting with wild-type controls. Moreover, neural responses specific to faces (versus objects) recorded from the electrodes over the temporal cortex were significantly decreased and delayed in Shank3 mutants compared to wild-type controls. Cortical responses in the frontal/parietal region underlying categorization of faces by species/breeds were reduced in Shank3 mutants. Our findings of atypical face processing in dogs with Shank3 mutations provide a useful animal model for studying ASD mechanisms and treatments.

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21. Yuill N, Elphick C, Marshall J, Jones WD, Waite J, Viner H. Behavioral profiles and social relationships in Wiedemann-Steiner syndrome: parent reports on 25 cases. Orphanet J Rare Dis. 2025; 20(1): 154.

BACKGROUND: Wiedemann-Steiner syndrome (WSS) is a rare, variable neurodevelopmental condition associated with developmental delay, intellectual disability and congenital abnormalities. There are few investigations into behavioral characteristics. Importantly, parental perspectives are particularly lacking. This study investigated commonalities in the behavioral characteristics through the perspectives of parents’ lived experiences. METHOD: We conducted in-depth interviews with 25 parents of children with WSS in the United States and United Kingdom, tapping lived experience and specific examples of behavior, relationships and communication. Responses were analysed using reflexive thematic analysis. RESULTS: We report three main themes: intense sociability (confirming questionnaire-based research), intense relationships and executive dysregulation (novel findings). We also found previously unreported sensory sensitivities and cognitive patterns of uneven memory and poor comprehension. CONCLUSIONS: These data direct from parent experience reveal novel commonalities in behavior and relationships in this group. Findings should inform clinical assessment and diagnosis, new research questions and choice of patient-focused outcome measures for clinical interventions. The findings also contribute to improved practice in providing care and support for people with WSS and their families and to guidelines for more tailored education and improved healthcare.

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