1. Dong HW, Weiss K, Dickerson JW, Meadows MJ, Zagol-Ikapitte I, Boutaud O, Rook JM, Neul JL, Niswender CM. Potentiation of group III metabotropic glutamate receptors positively affects neurophysiological features in a mouse model of Rett syndrome. J Pharmacol Exp Ther. 2025; 392(6): 103602.

Rett syndrome (RTT) is a neurodevelopmental disorder primarily caused by loss-of-function mutations in the X-linked methyl-CpG-binding protein 2 (MECP2) gene. Genetic restoration of MECP2 in mice can reverse phenotypes, providing hope for disease-modifying therapies in the disease. Studies in people with and mouse models of RTT have identified neurophysiological features, such as auditory event-related potentials (AEPs), that correlate with disease severity, suggesting potential as translatable biomarkers. We have identified reductions in the expression and function of the group III metabotropic glutamate receptor 7 (mGlu(7)), a G protein-coupled receptor regulating presynaptic neurotransmitter release, in both human and mouse RTT brains. Additionally, treatment of RTT mice with a positive allosteric modulator (PAM) of the group III mGlu receptors (VU0422288) improves behavioral phenotypes, most likely via mGlu(7) potentiation. To evaluate whether VU0422288 treatment modulates neurophysiological biomarkers, we acutely treated RTT mice with VU0422288 at 3,10, and 30 mg/kg and assessed neurophysiological features. VU0422288 treatment caused increases in AEP peak amplitudes in RTT mice but not in wild-type controls, with no effect on basal electroencephalogram power. Treatment with a different compound, ADX88178, a PAM that activates the mGlu(4, 6)(and 8) receptors, did not affect neurophysiological assessments, suggesting that the target of VU0422288 is likely mGlu(7). These findings suggest that neurophysiological features, like AEP, have potential as sensitive and quantitative biomarkers that may be useful in evaluating mGlu(7) PAMs and other pharmacological interventions as novel RTT treatment strategies. SIGNIFICANCE STATEMENT: Correlations between neurophysiological features and disease severity in Rett syndrome suggest their potential as translatable biomarkers sensitive to pharmacological modulation. This study demonstrates that potentiation of group III metabotropic glutamate receptors improves neurophysiological features in Rett syndrome mice.

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2. Earl M, Samyn M, Blackmore C, Brace M, Day J, Javed A, Begum-Ali J, Johnson MH, Jones EJH, Dhawan A, McAlonan GM. General and Autism-Related Neurodevelopmental Difficulties in Biliary Atresia. J Pediatr. 2025: 114673.

OBJECTIVE: To examine neurodevelopment in biliary atresia (BA) and the relationship of neurodevelopment to key disease-related factors STUDY DESIGN: In this single-center, observational study we deployed an anonymized survey of outcomes that was completed by 107 parents of children with BA less than age 12. A detailed assessment of general neurodevelopment (Mullens Scale of Early Learning [MSEL] and Vineland Adaptive Behavior Scale [VABS]) was carried out in 50 infants under 5 years old and emerging autistic traits [Autism Diagnostic Observation Schedule(ADOS-2)] were assessed in those eligible. Ninety-three age- and sex-matched infants, some with higher likelihood of neurodevelopmental conditions, was used as a reference. RESULTS: Neurodevelopmental concerns were raised by 37% of parents, and 47% of children required support from at least one service. In the under 5 years sample, children with BA had significantly lower adaptive and cognitive skills (ANCOVA:VABS,F=18·26,p<·001;MSEL,F=9·981,p<.001) when compared with both children with lower and higher likelihood of neurodevelopmental difficulties. A clinical or research diagnosis of autism was made in 30% of 35 children > 2 years old. Early surgical intervention and faster clearance of jaundice after surgery was associated with better general neurodevelopmental outcomes (F=2·428,p=·042) but not with the presence of emerging autistic traits. CONCLUSIONS: High levels of neurodevelopmental difficulties in children with BA reveal a need for greater awareness and enhanced surveillance. That early identification and treatment of BA is linked to better general neurodevelopmental outcome and encourages proactive management. However, the novel observation that BA is associated with autistic traits unrelated to disease management will need further investigation to establish clinical relevance and optimize clinical pathways.

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3. Fan XR, Zuo XN. Precision Neuromodulation on Amygdala-Cortical Circuits for Autism Spectrum Disorder Intervention. Biol Psychiatry. 2025; 97(12): 1108-10.

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4. Farhoomand F, Kaban T, Kecheliev V, Delaney KR. Impaired persistence of cortical sensory adaptation following repetitive tactile stimulation in the hindlimb somatosensory cortex of Rett syndrome mice. Neuroscience. 2025.

Reduced response to repeated stimulation (RS) is a signature feature of sensory systems. In this study we examined cortical sensory responses to brief tactile stimulation of the foot/ankle before, during and after periods of RS in young male, young and old female mice. We compared cortical activity in wild-type (WT) mice to mice with mutation in Mecp2 that causes the neurodevelopmental disorder Rett syndrome (RTT). Intrinsic optical signal imaging (IOS) and intracortical local field potential (LFP) measurements revealed reduced cortical responses to test stimuli on the order of 40-50% after 15-min periods of RS. The time-course and magnitude of reduced IOS and LFP to tactile test-stimuli were similar in WT and RTT mice before and during application of RS. However, after cessation of RS cortical responses remained persistently below pre-stimulation in WT mice while RTT mice had significantly more rapid and in some cases complete recovery with an hour of rest. LFP responses to each stimulus in a 7-stimulus test-train characteristically decline. Examining the buildup of this adaptation during test-trains revealed that while the response to the first stimulus in the test-train was generally consistent, responses to successive stimuli in the test-train declined more rapidly after application of RS. This increased adaptation during test-trains persisted in WT mice and reversed more rapidly in RTT mice suggesting that persistent cortical sensory adaptation results from enhancement of processes responsible for short-term adaptation. The lack of persistent cortical sensory adaptation in RTT mice may reflect reduced long-term plasticity within central somatosensory processing circuits.

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5. Griborio-Guzman AG, Ducas RA. Autism and its correlation with increased cardiovascular mortality and diseases. Can J Cardiol. 2025.

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6. Knudsen LV, Sheldrick-Michel AJ, Vafaee MS, Michel TM. Dissimilarities in volume and function of social brain regions in autism. J Neural Transm (Vienna). 2025.

Despite growing awareness, diagnosing Autism Spectrum Condition (ASC) in adulthood remains challenging due to a limited range of diagnostic tools beyond psychological assessments. Although recent neuroimaging advancements have identified social brain regions (SBR) associated with sociability, research on these areas in ASC, particularly within the largely understudied adult ASC population, remains scarce. Explore functional and volumetric differences in the SBR between autistic and neurotypical individuals. We conducted a volumetric and functional assessment of SBRs using open-source MRI data from the Autism Brain Imaging Data Exchange (ABIDE). The sample included 44 adult ASC (37 male, mean age 25.86 ± 6.58) and 64 adult neurotypical individuals (51 male, mean age 25.36 ± 4.05). Autistic adult individuals demonstrated lower left nucleus accumbens volume. The amplitude of low frequency fluctuations was enhanced in the orbitofrontal cortex and temporoparietal junction, and decreased in the caudate, hippocampus, thalamus, and ventral tegmental area in the autistic group. Additionally, a widespread increase in functional connectivity within the SBR was demonstrated in the ASC group. Structural and functional measures allowed classification of autistic and neurotypical individuals with 76% accuracy using a support vector machine model. The results demonstrate significant SBR differences between adult autistic and neurotypical individuals, highlighting the SBR as potentially essential in ASC etiology, we demonstrate its ability to classify autistic and neurotypical individuals. However, further exploration of the SBR using advanced imaging techniques is required.

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7. Oğur Ç, Olçay S. The Effectiveness of Video Visual Scene Display-Assisted Behavioral Skills Training in the Instruction of Skills to Prevent Online Sexual Abuse Among Adults with Autism Spectrum Disorder. Arch Sex Behav. 2025.

The present study aimed to determine the effectiveness of the video visual scene display-assisted behavioral skills training in skills to prevent online sexual abuse among adults with autism spectrum disorder (ASD). The study was conducted with three 21-23-year-old male individuals with ASD, and the multiple probe model across participants, a single-subject research model. The study findings demonstrated that all individuals acquired the skills to prevent online sexual abuse, generalized the acquired skills to different individuals, and maintained these skills for 2-4 weeks after the instruction. Furthermore, social validity data were collected from the participants, their parents, and teachers with the subjective analysis approach, and it was observed that participants, their parents, and teachers reported positive views about the instruction of the skills, the intervention, and the outcomes.

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8. Oner E, Kurutas EB, Altun H. Evaluation of Erythropoietin and Erythropoietin Receptor Levels in Children with Autistic Spectrum Disorder: Cross-sectional Study. Clin Psychopharmacol Neurosci. 2025; 23(2): 212-8.

OBJECTIVE: Autistic spectrum disorders (ASD) are a heterogeneous collection of neurodevelopmental disorders with an unknown etiology. Erythropoietin is a versatile growth factor that plays a crucial role in the nervous system, exhibiting high expression in various regions of the brain, including neurons, glial cells and endothelial cells. Recent animal studies have demonstrated that Epo exerts neuroprotective and neurotrophic effects. The objective of this study was to examine the levels of erythropoietin-(Epo) and its receptor-(EpoR) in children with ASD and to elucidate the potential effects of Epo in the disorder. METHODS: The study involved 50 children diagnosed with ASD based on the 5th Edition of the Diagnostic and Statistical Manual of Mental Disorders criteria, with ASD severity assessed using the Childhood Autism Rating Scale. Additionally, a control group of 50 healthy children was included. Serum samples were collected from both groups, and levels of Epo and its EpoR. RESULTS: There were no statistically significant differences between the age and sex distributions of the ASD and control groups (p > 0.05). However, analysis of the serum samples revealed a statistically significant reduction in Epo levels in the ASD cohort compared to the control. CONCLUSION: The results of our study indicate that Epo may have potential as an adjunctive therapy for children with ASD. The observed decrease in Epo levels and increase in EpoR levels in children with ASD suggest a dysregulation in the Epo-EpoR axis that may contribute to the pathophysiology of ASD. Further research is required to investigate the therapeutic effects of modulating Epo levels in ASD and to elucidate the mechanisms underlying these changes.

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