1. Bauer CK, Kortüm F, Möllring A, Grinstein L, Denecke J, Alawi M, Bähring R, Harms FL. Loss-of-function variant in KCNH3 is associated with global developmental delay, autistic behavior, insomnia, and nocturnal seizures. Seizure;2025 (Mar 20);129:14-21.

INTRODUCTION: The KCNH gene family encodes voltage-gated potassium (Kv) channels of the EAG subtype covering three subfamilies (Kv10-12). EAG channels are involved in the control of cardiac and neuronal excitation, and pathogenic variants in KCNH genes encoding Kv10 (eag) and Kv11 (erg) subfamily members cause a broad clinical spectrum ranging from cardiac arrhythmia to neurodevelopmental syndromes. However, no pathogenic variants have been hitherto reported for KCNH genes encoding Kv12 (elk) subfamily members. METHODS: Clinical, genomic, and functional studies were performed, including voltage-clamp experiments using heterologous channel expression in Xenopus oocytes. RESULTS: We examined an eight-year-old girl presenting with global developmental delay, intellectual disability, autistic and aggressive behavior, hyperactivity, insomnia, and nocturnal seizures. Focal seizures were successfully treated with sulthiame, which reduced the occurrence of temporo-parietal spike-wave paroxysms. Trio exome sequencing revealed a heterozygous de novo missense variant, NM_012284.3:c.1112C>T; p.(Ala371Val), in KCNH3, which encodes the Kv channel α-subunit Kv12.2. The amino acid substitution associated with the KCNH3 variant identified in the patient is located at a site highly conserved in EAG channels. The analogous variant in KCNH2 causes long-QT-syndrome 2, and has also been associated with epilepsy. Electrophysiological characterization of the KCNH3 p.(Ala371Val) variant demonstrated loss-of-function of the mutant Kv12.2 channels and strongly reduced current amplitudes upon co-expression of wildtype and mutant channel subunits in a dominant-negative manner. CONCLUSION: Our results propose KCNH3, which is primarily expressed in the nervous system, as a new disease gene associated with a neurodevelopmental phenotype including seizures.

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2. Deri E, Kumar Ojha S, Kartawy M, Khaliulin I, Amal H. Multi-omics study reveals differential expression and phosphorylation of autophagy-related proteins in autism spectrum disorder. Sci Rep;2025 (Mar 29);15(1):10878.

Our multi-omics study investigated the molecular mechanisms underlying autism spectrum disorder (ASD) using Shank3(Δ4-22) and Cntnap2(-/-) mouse models. Through global- and phospho- proteomics of the mouse cortex, we focused on shared molecular changes and found that autophagy was particularly affected in both models. Global proteomics identified a small number of differentially expressed proteins that significantly impact postsynaptic components and synaptic function, including key pathways such as mTOR signaling. Phosphoproteomics revealed unique phosphorylation sites in autophagy-related proteins such as ULK2, RB1CC1, ATG16L1, and ATG9, suggesting that altered phosphorylation patterns contribute to impaired autophagic flux in ASD. SH-SY5Y cells with SHANK3 gene deletion showed elevated LC3-II and p62 levels, indicating autophagosome accumulation and autophagy initiation, while the reduced level of the lysosomal activity marker LAMP1 suggested impaired autophagosome-lysosome fusion. The study highlights the involvement of reactive nitrogen species and nitric oxide (NO) on autophagy disruption. Importantly, inhibition of neuronal NO synthase (nNOS) by 7-NI normalized autophagy markers levels in the SH-SY5Y cells and primary cultured neurons. We have previously shown that nNOS inhibition improved synaptic and behavioral phenotypes in Shank3(Δ4-22) and Cntnap2(-/-) mouse models. Our multi-omics study reveals differential expression and phosphorylation of autophagy-related proteins in ASD but further investigation is needed to prove the full involvement of autophagy in ASD. Our study underscores the need for further examination into the functional consequences of the identified phosphorylation sites, which may offer potential novel therapeutic autophagy-related targets for ASD treatment.

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3. Gumusoglu SB, Schickling BM, Santillan DA, Teesch LM, Santillan MK. Disrupted fetal carbohydrate metabolism in children with autism spectrum disorder. J Neurodev Disord;2025 (Mar 29);17(1):16.

BACKGROUND: Despite the power and promise of early detection and treatment in autism spectrum disorder (ASD), early-life biomarkers are limited. An early-life risk biosignature would advance the field’s understanding of ASD pathogenies and targets for early diagnosis and intervention. We therefore sought to add to the growing ASD biomarker literature and evaluate whether fetal metabolomics are altered in idiopathic ASD. METHODS: Banked cord blood plasma samples (N = 36 control, 16 ASD) were analyzed via gas chromatography and mass spectrometry (GC-MS). Samples were from babies later diagnosed with idiopathic ASD (non-familial, non-syndromic) or matched, neurotypical controls. Metabolite set enrichment analysis (MSEA) and biomarker prediction were performed (MetaboAnalyst). RESULTS: We detected 76 metabolites in all samples. Of these, 20 metabolites differed significantly between groups: 10 increased and 10 decreased in ASD samples relative to neurotypical controls (p < 0.05). MSEA revealed significant changes in metabolic pathways related to carbohydrate metabolism and glycemic control. Untargeted principle components analysis of all metabolites did not reveal group differences, while targeted biomarker assessment (using only Fructose 6-phosphate, D-Mannose, and D-Fructose) by a Random Forest algorithm generated an area under the curve (AUC) = 0.766 (95% CI: 0.612-0.896) for ASD prediction. CONCLUSIONS: Despite a high and increasing prevalence, ASD has no definitive biomarkers or available treatments for its core symptoms. ASD's earliest developmental antecedents remain unclear. We find that fetal plasma metabolomics differ with child ASD status, in particular invoking altered carbohydrate metabolism. While prior clinical and preclinical work has linked carbohydrate metabolism to ASD, no prior fetal studies have reported these disruptions in neonates or fetuses who go on to be diagnosed with ASD. Future work will investigate concordance with maternal metabolomics to determine maternal-fetal mechanisms.

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4. Laroui A, Rojas D, Bouhour S, Proteau-Lemieux M, Galarneau L, Benachenhou S, Abolghasemi A, Plantefeve R, Mallet PL, Corbin F, Lepage JF, Çaku A. Associations between plasma 24(S)-Hydroxycholesterol and neuropsychological profile in Fragile X Syndrome. J Lipid Res;2025 (Mar 27):100787.

Fragile X Syndrome (FXS) is caused by mutations in the fragile X mental retardation 1 gene, characterized by low plasma cholesterol levels. Considering the essential role of brain cholesterol in signaling and synaptogenesis, it is important to screen for brain cholesterol abnormalities in FXS and explore their link with neuropsychological profiles. Brain cholesterol is synthesized in situ, and the excess is primarily converted to 24(S)-hydroxycholesterol (24(S)-OHC). 27-hydroxycholesterol (27-OHC) is the major cholesterol oxidation metabolite that crosses the blood-brain barrier from peripheral circulation into the brain Plasma levels of 24(S)-OHC and 27-OHC were quantified in FXS and control individuals. The FXS group underwent transcranial magnetic stimulation to evaluate corticospinal excitability and inhibition. The clinical profile was assessed using questionnaires evaluating specific symptoms related to autism, aberrant behaviors, and anxiety. Study results show a significant decrease in plasma levels of 24(S)-OHC in FXS as compared to controls (78.48 nM ± 20.90 vs 99.53 nM ± 32.30; p = 0.006). Moreover, a negative correlation was observed between plasma levels of 24(S)-OHC and Motor-Evoked Potential (r(s) = -0.57; p = 0.05) in FXS. Similarly, a negative correlation was also found between plasma levels of 24(S)-OHC and the total score of the Social Communication Questionnaire (r(s) = – 0.72; p = 0.002) and the Anxiety Depression and Mood Scale (r(s) = – 0.61; p = 0.02). The 24(S)-OHC is associated with specific neurophysiological and behavioral characteristics in individuals with FXS. Larger studies are warranted to confirm the potential of 24(S)-OHC as a reliable biomarker for FXS.

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5. Logos K, Lim A, Brewer N, Young RL. The Behavioral Presentation of Autistic Adults in a Forensic Interview. J Autism Dev Disord;2025 (Mar 29)

Autism diagnostic criteria, and research primarily involving autistic children, highlight verbal and nonverbal behaviors likely to manifest during social interaction that may generate unfavorable impressions of interaction partners (e.g., poor credibility, incompetence). These behaviors are thought to bias evaluations of autistic individuals, particularly within high-stakes contexts (e.g., police or employment interviews). However, the prevalence of those behaviors in autistic adults is unclear. IQ-matched samples of autistic (n = 43) and non-autistic (n = 41) adults participated in a simulated chatroom, exposed to text-based conversations about illegal hacking. Participants were then interviewed about the chatroom in a one-on-one video-recorded online interview with the researcher. We measured the prevalence of 19 verbal and nonverbal behaviors, and memory report characteristics displayed by the interviewees, and investigated differences between the diagnostic groups. Diagnosis had a strong effect on overall behavioral displays but was only associated with minor differences in individual behaviors. Three significant effects indicated greater difficulty interpreting figurative language, longer speech hesitations, and greater verbal intonation for autistic than non-autistic adults. Inter-individual variability within groups and within-individual variability across behaviors highlighted that behaviors were neither ubiquitous nor consistently displayed in combination. There was also a suggestion of more noticeable differences in the behavior of male than female autistic adults. Although minor behavioral differences were detected based on diagnosis, they included behaviors that could lead to negative outcomes for autistic individuals during high-stakes interactions. Whether more pronounced behavioral differences are detected during face-to-face interactions warrants further research.

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6. Mou QH, Zhang Q, Chen L, Dai Y, Wei H, Jia FY, Hao Y, Li L, Zhang J, Wu LJ, Ke XY, Yi MJ, Hong Q, Chen JJ, Fang SF, Wang YC, Wang Q, Chen J, Li TY, Yang T. Gender specific influence of serotonin on core symptoms and neurodevelopment of autism spectrum disorders: A multicenter study in China. Child Adolesc Psychiatry Ment Health;2025 (Mar 29);19(1):35.

BACKGROUND: High serotonin (5-hydroxytryptamine [5-HT]) blood levels are the most reliable and frequently replicated biomarker for autism spectrum disorders (ASDs). However, their differential influence on core ASD symptoms in males and females remains unclear. This study aimed to investigate the changes in 5-HT levels in children with ASD to assess and compare its influence on the core symptoms and neurodevelopment of boys and girls. METHODS: Herein, 1,457 ASD children and 1,305 typically developing (TD) controls (age = 2-7 years) were enrolled from 13 cities across China. Social Responsiveness Scale (SRS) and Childhood Autism Rating Scale (CARS) were used to evaluate the ASD symptoms in children, and the revised Children Neuropsychological and Behavior Scale-Revision 2016 (CNBS-R2016) was used to evaluate their neurodevelopment. The 5-HT serum levels were measured by high-performance liquid chromatography-tandem mass spectrometry. RESULTS: In boys with ASD, increased serum 5-HT levels correlated with high scores on SRS and CARS and with communication warning behavior of CNBS-R2016. Conversely, concomitant decline was observed in the scores on the general, language, gross motor, adaptive behavior, and personal-social quotients. Notably, no differences were found in girls with ASD. CONCLUSIONS: Children with ASD, especially boys, presented higher serum 5-HT levels compared with TD children. Additionally, increased 5-HT content is considerably positively associated with core ASD symptoms and negatively associated with neurodevelopment in boys with ASD. Overall, this study highlights the gender bias in patients with ASD regarding 5-HT serum levels, underscoring its influence on ASD prevalence in a sex-specific manner. TRIAL REGISTRATION: This study has been approved by the Ethics Committee of the Children’s Hospital of Chongqing Medical University (approval number: (2018) IRB (STUDY) NO.121). Additionally, this study is registered with the China Clinical Trial Registry (Registration Number: ChiCTR2000031194).

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7. Pagán AF, Kenemore J, Ahlenius MM, Hernandez L, Armstrong S, Loveland KA, Acierno R. Launching! To Adulthood, A Culturally Adapted Treatment Program for Military-Dependent Autistic Young Adults and Their Military Parents: A Pilot Study. Mil Med;2025 (Mar 29)

INTRODUCTION: Military-dependent young adults (17-25 years old) with autism spectrum disorder (ASD) face significant barriers to accessing services during their transition to adulthood. Frequent relocations, disrupted care, and limited ASD-tailored interventions exacerbate the challenges for these families, with many young adults experiencing a « service cliff » as they age out of pediatric care and school-based services. Addressing these gaps is critical, particularly given the rising mental health challenges and executive dysfunction in this population. This study evaluates the preliminary efficacy of an adapted telehealth intervention, the Military-Launching! program, designed to support young adults with ASD and their military families. MATERIALS AND METHODS: A repeated measures design was used to evaluate changes in functioning, self-efficacy, and quality of life among 20 military-dependent young adults with ASD and 34 of their parents. Participants completed measures at baseline, mid-treatment, and post-treatment. Young adults met ASD diagnostic criteria and exclusion criteria included intellectual disability (IQ < 75) or severe mental health conditions. Recruitment was facilitated through military programs at bases in Texas. RESULTS: Significant improvements were observed in young adults' social cognition (η = 0.52, P = .016) and executive functioning (BRIEF-A GEC, η = 0.26, P = .016). Parents reported significant reductions in stress (BRIEF-A BRI, η = 0.28, P = .004) and enhanced quality of life in social relationships (WHOQOL-BREF, P = .047). While adaptive functioning improvements were limited to specific subscales, parent-perceived transition readiness showed a large effect size (η = 0.36). CONCLUSIONS: Preliminary findings suggest that the Military-Launching! program improves social cognition, executive functioning, and family outcomes for military-dependent young adults with ASD. Tailored, evidence-based interventions addressing co-occurring mental health and military-specific stressors are essential for fostering successful transitions to adulthood.

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8. Stefanyshyn V, Stetsyuk R, Hrebeniuk O, Ayoub G, Fishchuk L, Rossokha Z, Gorovenko N. Analysis of the Association Between the SLC19A1 Genetic Variant (rs1051266) and Autism Spectrum Disorders, Cerebral Folate Deficiency, and Clinical and Laboratory Parameters. J Mol Neurosci;2025 (Mar 29);75(2):42.

Autism spectrum disorders (ASD) are characterized by clinical heterogeneity and may be associated with cerebral folate deficiency (CFD). Among the causes, folate receptor alpha autoantibodies (FRAA) and variants of the SLC19A1 gene are commonly highlighted. The aim of this study was to analyze the rs1051266 variant of the SLC19A1 gene in patients with ASD and CFD and to determine its relationship with clinical and laboratory parameters. The study included 227 children with ASD, 156 of whom had CFD. FRAA detection, genotyping of the rs1051266 variant, and folate metabolism marker measurement (homocysteine, vitamins B9, B12, B6) were performed. FRAA binding was detected in 39.2% of ASD patients, blocking FRAA in 3.5%, and a specific soluble folate receptor in 13.2%. The 80GA genotype was the most common (46.3%), and homocysteine levels tended to be moderately elevated (upper quartile – 7.0). Significant correlations were found between homocysteine levels and vitamins B9, B12, and B6 (p < 0.05) and between verbal impairments and vitamin B12 (p = 0.043). In ASD and CFD patients, the 80GG genotype was more frequent (p = 0.03) and vitamin B12 levels were elevated (p = 0.021). In the ASD group, correlations were found between the 80AA genotype and demyelination (p = 0.020) and between homocysteine levels and demyelination (p = 0.042). In conclusion, the rs1051266 variant of the SLC19A1 gene modifies the clinical course of ASD. Patients with ASD and CFD exhibited high variability in folate metabolism markers. These findings underline the need for further research on folate transport genetics for personalized prevention and treatment strategies for ASD and CFD.

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9. Thota NR, Kosaraju K, Rudrapogu JS, Nevali KP, Kondaveeti TR. Safety and One-year Follow-Up Analysis of Percutaneous ASD Closure at a Tertiary Care Hospital. Indian Heart J;2025 (Mar 27)

AIM: This study was designed to evaluate the safety and effectiveness of the Cocoon Septal Occluder device (Vascular Innovations Co. Nonthaburi, Thailand) for transcatheter closure of isolated secundum type atrial septal defect (ASD) in Indian patients METHODS: This was a single-center, retrospective, observational study which included patients who underwent transcatheter closure of isolated secundum ASD using the Cocoon Septal Occluder between April 2014 and May 2023. Follow-up assessments up to one-year were conducted through review of hospital medical records, clinic visits, or via telephonic communication with primary care physicians. RESULTS: A total of 400 patients were included in the study, consisting of 28 paediatric (aged ≤15 years, 8.14±4.41 years) and 372 adult patients (40.83±13.23 years). The mean defect diameter and device size were 16.75±5.85 mm and 20.43±6.24 mm for paediatric patients, and 21.62±6.87 mm and 24.94±7.28 mm for adult patients, respectively. The device was successfully implanted in all paediatric patients, achieving 100% closure of the defect with no complications, which persisted through one-year follow-up. In the adult cohort, complete ASD closure was achieved in 99.2% of patients, with two cases of device embolization and one case of device withdrawal. At one-year follow-up, adult patients experienced 0.3% late device embolization, 0.8% pericardial effusion/cardiac tamponade, 0.5% atrioventricular block, and 0.5% atrial flutter/fibrillation. No cases of endocarditis, haemolysis, nickel allergy, stroke/transient ischemic attack, or migraine were reported in either paediatric or adult patients. CONCLUSION: The results demonstrate that Cocoon Septal Occluder is safe and effective in closing isolated secundum ASD during one-year follow-up.

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10. Tsukui N, Nomura Y, Newcorn JH, Takahashi N, Ishikawa-Omori Y, Nakayasu C, Okumura A, Iwabuchi T, Harada T, Rahman MS, Nishimura T, Tsuchiya KJ. Temperament Profiles at Age 18 Months as Distinctive Predictors of Elevated ASD- and ADHD-Trait Scores and Their Co-Occurrence at Age 8-9: HBC Study. Res Child Adolesc Psychopathol;2025 (Mar 29)

Autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) can be traced back to specific early childhood temperament patterns. However, no unique pattern has been identified for their co-occurrence. Given that children with both traits often require more clinical attention, this study aimed to discover such patterns by examining three temperament domains measured during early childhood-Surgency/Extraversion (SE), Negative Affectivity (NA), and Effortful Control (EC)-and their association with group membership defined as being above the cut-off points for either ASD- or ADHD-trait scores or their co-occurrence at school age. We enrolled 814 children from a birth cohort, assessing temperament at 18 months using the Early Childhood Behavior Questionnaire, and ASD- and ADHD-trait scores at ages 8-9 using the Social Responsiveness Scale-2 and ADHD-Rating Scale. Group membership was determined by clinically significant symptoms, defined as + 1 SD after standardizing scores by age and sex. Multinomial regression analyses examined associations between temperament domain scores and group membership (ASD-dominant, ADHD-dominant, co-occurring, neither-ASD-nor-ADHD). The co-occurring group showed a unique temperament profile, with higher scores in both NA and EC (OR in NA = 1.48, 95% confidence interval (CI): 1.11 to 1.96 and OR in EC = 1.61, 95% CI: 1.18 to 2.20), distinct from the patterns shown by the ASD-dominant and ADHD-dominant groups. The combination of high NA and EC scores uniquely characterizes the co-occurring group, highlighting the need for early temperament assessments to identify children potentially requiring clinical attention for both ASD and ADHD traits.

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11. Xing C, Yu X. Oxytocin and autism: Insights from clinical trials and animal models. Curr Opin Neurobiol;2025 (Mar 28);92:103015.

Autism spectrum disorder is a highly heritable and heterogeneous neurodevelopmental disorder, characterized by impaired social interactions and repetitive behaviors. Despite its complex etiology, increasing evidence has linked autism to the oxytocin system. The oxytocin peptide has long been known as the « social hormone, » and has been shown to increase attention to social cues, elevate salience of socially relevant stimuli, and increase learning and reward in social situations. Reduced oxytocin levels and mutations in the oxytocin system have been reported in autism patients, while exogenously delivered oxytocin has been shown to alleviate social interaction deficits in both patients and animal models. Here, we summarize the results of recent clinical trials using oxytocin nasal spray to treat individuals with autism, as well as studies of autism animal models with oxytocin system deficits, and the rescue of their social behavior deficits by oxytocin. Finally, we discuss factors influencing clinical outcomes and reflect on future directions.

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