1. Davies M, Brown A, Hearps SJC, Langdon MC, Collins B, Beauchamp MH, Anderson VA. Social information processing in autism: The role of cognitive empathy in moral responding. J Neuropsychol;2026 (May 25)

Autistic individuals experience challenges in social functioning and have demonstrated atypical patterns of social cognition. However, limitations exist regarding the ecological validity of measures used to assess social cognition in autism, and the relationships between socio-cognitive processes are unclear. The current study aimed to investigate social cognition in autistic children using a novel assessment tool, comparing their social interpretation, perspective-taking abilities (i.e. cognitive empathy) and moral reasoning to that of neurotypical controls. The relationships between these socio-cognitive processes were explored in the context of socio-moral processing. Thirty-six participants were included in the autism group (86% male, aged 8-17 years-old) and 36 participants formed an age- and sex-matched neurotypical control group (86% male, aged 8-15 years-old). The autism group scored significantly lower than the neurotypical group in cognitive empathy only, t(69.37) = 5.95, p < .001. Higher levels of cognitive empathy, but not social interpretation, were significantly positively associated with moral responding, only in the autism group, R(2) = .11, F(1, 32) = 5.24, p = .029. Findings indicate the importance of perspective-taking abilities to social cognition difficulties in autism.

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2. Di X, Biswal BB. Context-Specific Decoupling and Competing Phenotypes: Transdiagnostic Eye-Tracking Biomarkers of ASD and ADHD During Naturalistic Viewing in a Large Pediatric Cohort. bioRxiv;2026 (May 15)

Autism Spectrum Disorder (ASD) and Attention-Deficit/Hyperactivity Disorder (ADHD) show considerable clinical overlap, yet categorical diagnostic boundaries can obscure shared physiological vulnerabilities. To characterize these traits dimensionally and categorically, we analyzed multimodal eye-tracking synchrony in a large-scale transdiagnostic pediatric cohort from the Healthy Brain Network during naturalistic viewing ( N = 2,036). Using a novel two-dimensional framework that simultaneously captures the strength and spatial geometry of gaze alignment across subjects – alongside a measure of shared pupillary responses – we quantified how closely children’s visual attention and physiological arousal matched those of their typically developing peers across four distinct media contexts. When autistic and ADHD traits were modeled concurrently, their effects on physiological alignment proved context-specific: autistic traits were uniquely associated with reductions in visual attention and arousal synchrony during a complex social narrative, whereas ADHD traits independently predicted reduced synchrony during fast-paced, visually demanding media. Examining the spatial direction of gaze misalignment further revealed that each child tended to scan the scene along a distinct spatial axis, inconsistent with a uniform group-level processing shift. Categorical models additionally revealed a non-additive interaction in comorbidity: rather than compounding physiological deficits, the attentional flexibility characteristic of ADHD appeared to partially offset the restricted spatial attention associated with isolated ASD, resulting in comparatively less severe gaze decoupling in the comorbid group. These findings support the utility of a Research Domain Criteria (RDoC) framework, positioning model-free physiological synchrony as a candidate transdiagnostic biomarker and suggesting that comorbid ASD and ADHD reflect competing rather than simply additive neurocognitive strategies.

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3. Graça NNJ, Duarte ML, Fernández-Cascardi M. Angelman syndrome with atypical presentation mimicking cerebral palsy: diagnosis and treatment challenges. Bol Med Hosp Infant Mex;2026;83(2):125-129.

BACKGROUND: Angelman syndrome (AS) is a rare genetic disorder caused by the lack of expression of the UBE3A gene, inherited maternally, and is associated with an abnormal chromosome 15q11-q13. Affects 1 in 12,000-20,000 individuals and is more commonly diagnosed in childhood, although some cases are missed in adulthood. This condition, which affects both genders equally, often is undiagnosed due to errors or underreporting. This case involves a patient with AS, initially misdiagnosed as cerebral palsy, presenting with severe developmental delay, autistic behaviors, hypotonia, and epilepsy. CLINICAL CASE: We describe the case of a 3-year and 10-month-old male patient with a family history of autism spectrum disorder and attention deficit hyperactivity presented with motor delay, severe hypotonia, brachycephaly, absence of trunk control, difficult-to-control epilepsy, and severe developmental delay (unable to walk or speak). Initial observations revealed he could not sit or crawl and had difficulty swallowing. He was prescribed risperidone and had follow-ups for ongoing issues. In 2022, he experienced a tonic-clonic seizure and was diagnosed with chronic non-progressive encephalopathy and epilepsy, leading to valproic acid treatment. Subsequent seizures led to adjustments in his medication regimen, including adding clonazepam, phenobarbital, and levetiracetam. Genetic testing confirmed a deletion in the Prader-Willi/AS critical region on chromosome 15. The patient is currently stable. CONCLUSIONS: AS is characterized by developmental delays, speech impairment, ataxia, and seizures, along with characteristic behaviors such as inappropriate laughter. The comorbidities associated with AS, such as seizures and ataxia, significantly increase the risk of injuries and accidents, leading to higher morbidity and mortality in patients.

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4. Haddon JE, Hall JH, Hall J, Owen MJ, van den Bree MBM. Family functioning and psychiatric outcomes in children and young people with intellectual and developmental disabilities caused by rare genetic mutations. medRxiv;2026 (May 13)

BACKGROUND: A range of rare chromosomal micro-deletions or -duplications (Copy Number Variants – CNVs) are associated with high risk of neurodevelopmental and mental health conditions (ND-CNVs). There is great individual variability in outcomes, but we lack insights into the contributing social factors, including family functioning. METHODS: Caregivers of 598 children and young people (CYP) with a range of 16 ND-CNVs and 222 siblings without ND-CNVs (controls) completed questionnaires on overall family climate (cohesion and conflict) as well as caregiver-CYP relationship warmth and hostility and took part in a research diagnostic interview about CYPs’ psychiatric symptoms. CYPs’ intelligence quotient (IQ) was also measured. RESULTS: Comparisons with published data from neurotypical families indicated that families affected by ND-CNVs are characterised by higher family cohesion and conflict as well as lower caregiver-CYP warmth and hostility. Symptoms of oppositional defiant disorder reduced more steeply in CYP with ND-CNVs compared to controls with increasing family cohesion (interaction effect: β = -0.14, p = 4.65 × 10⁻²). In contrast, they rose more steeply with increasing family conflict (interaction effect: β = 0.18, p = 1.05 × 10⁻²). Furthermore, symptoms of mood disorder increased more steeply with increased caregiver-CYP hostility in CYP with ND-CNVs (interaction effect: β = 0.15, p = 4.55 × 10⁻²). CONCLUSIONS: Raising a CYP with a rare genetic condition is challenging. Timely access to interventions that support caregivers in fostering a positive family environment may reduce behavioural difficulties in CYP, with subsequent benefits for family functioning.

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5. Hampson E, Waxman SE, Nicolson R. Demasculinized digit ratios in a sample of boys with childhood autism. Horm Behav;2026 (May 25);182:105950.

Some theories have proposed that children with autism spectrum disorder (ASD) may be exposed to increased levels of androgens during prenatal development, resulting in greater androgenization of testosterone-dependent traits including both peripheral (bodily) and central (brain-related) traits. Empirical support for this hypothesis is scant and inconsistent. In the present work, we studied an ostensible anatomical marker of testosterone exposure (sexually differentiated finger lengths) which develops during the first trimester or early second trimester of gestation. Participants were 25 boys with classic autism, recruited from the clinical practice of a local physician specializing in childhood autism, who met the standardized DSM (Diagnostic and Statistical Manual) criteria for ASD, and 57 normally-developing age- and sex-matched male and female controls (32 males, 25 females); N = 82; M(age) = 7.30 yrs., SD = 4.18. Finger length was measured to the nearest 0.5 mm from digital images of the ventral surface of the hands using a validated measurement protocol. Consistent with past reports from adult samples, several of the finger length ratios were confirmed to display sex differences among control children, but the group of boys with ASD showed a female-like finger growth pattern, not the hypermasculine pattern predicted, and were found to differ statistically from the male controls. Boys with ASD thus showed a demasculinized pattern of finger differentiation. Our data do not support theories which suggest that greater fetal testosterone exposure occurs in boys with autism.

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6. Kobayashi A, Makino T, Mizuno Y, Kosaka H, Izuma K. Informational and Normative Influence on Conformity in Autism. Autism Res;2026 (May 25):e70284.

This preregistered study examined whether adults with autism spectrum disorder (ASD) show reduced social conformity and whether any such reduction depends on the type of social influence. Social conformity-the tendency to adjust one’s judgments to align with those of others-is typically driven by normative (acceptance-seeking) and informational (accuracy-seeking) motives. Thirty adults with ASD and 30 matched neurotypical (NT) adults completed two tasks: a preference rating task indexing normative influence, and a dot-counting task indexing informational influence with monetary rewards. Contrary to our predictions, adults with ASD conformed as much as NT adults in the preference rating task but showed significantly reduced conformity in the dot-counting task. Exploratory analyses indicated that this reduction was driven by a distinct subgroup of nine adults with ASD who never revised their initial estimates despite informative social cues, resulting in poorer accuracy and lower rewards. When this subgroup was excluded, group differences in conformity were no longer evident. These findings suggest that, overall, adults with ASD are as susceptible as NT adults to normative influence but less responsive to informational influence, highlighting the importance of distinguishing between types of social influence and considering individual differences when characterizing social behavior in ASD. This study examined how adults with and without autism change their answers after seeing other people’s opinions, both when rating what they like and when solving a numbers task with correct answers and rewards. Adults with autism adjusted their ratings as much as neurotypical adults when expressing preferences, but a subgroup of adults with autism almost never changed their answers in the numbers task, even when it meant earning fewer rewards. These findings suggest that social influence affects people with autism differently depending on the situation, highlighting the importance of support that respects this diversity in social decision‐making. eng

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7. Latrèche K, Godel M, Flò A, Journal F, Borghesani V, Schaer M. Early Trajectories of Resting-State EEG power in autistic children: a longitudinal study across language profiles. Transl Psychiatry;2026 (May 25)

Language development in autism spectrum disorder (ASD) is heterogeneous, ranging from subtle differences to significant delays. In previous work, we identified three autistic language profiles in early childhood: Language Unimpaired (LU), Language Impaired (LI), and Minimally-Verbal (MV). While these profiles show distinct vocabulary, grammar, and pragmatic development, understanding their underlying neural correlates is essential to predict outcomes and develop targeted interventions. Here, we examined whole-brain resting-state EEG power across five canonical frequency bands in a longitudinal sample comprising 66 typically developing (TD) children and 122 autistic children (ages 1.6-6.0 years), yielding 358 time points. Within the ASD group, 61 children belonged to the LU profile, 44 children to LI, and 17 children to MV. Compared to TD peers, autistic children showed increased power in low-frequency (delta, theta) and high-frequency bands (beta, gamma). Gamma power varied by autistic language profile, with the highest levels in MV children. Moreover, gamma power within ASD followed a quadratic trajectory in relation to word combination acquisition, peaking around the time of acquisition and decreasing afterward. This pattern suggests a dynamic, compensatory mechanism supporting the transition to phrase speech, which is a critical milestone toward functional speech that may predict language outcomes in ASD.

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8. Ma KK, Burn AM, Wong OW, Choi O, Chan SS. Healthcare professionals’ perspectives on the challenges faced by parents of children with autism and recommendations to address them: a qualitative study in Hong Kong. BMJ Paediatr Open;2026 (May 25);10(1)

OBJECTIVE: To explore healthcare professionals’ (HCPs) perspectives on the challenges and needs of parents caring for children with autism spectrum disorder (ASD). DESIGN: In-depth individual and group interviews were conducted with 16 HCPs with over 10 years’ experience working closely with children with autism and their families. HCPs interviewed provided tertiary specialist clinical services for ASD across a range of roles, including child psychiatrists, psychologists, psychiatric nurses, a social worker, an occupational therapist and a hospital-based teacher. Data was coded inductively and analysed using reflective thematic analysis. SETTING: A university-affiliated tertiary hospital in Hong Kong. RESULTS: Three themes were generated: (1) emotional strain and its negative impact on parenting practices, (2) misunderstanding about ASD and its management and (3) acknowledgement and acceptance of the ASD diagnosis. HCPs observed that challenges faced by parents and caregivers of children with ASD were often shaped by misinformation and misinterpretation of child behaviours and needs, as well as unrealistic expectations based on stereotypes and norms. HCPs provided recommendations for parents and caregivers, highlighting the need to strengthen relational skills to connect with their children, take their child’s perspective and show appreciation and affection for their child’s strengths. CONCLUSIONS: Findings from this study highlighted the need for psychoeducation and identified the potential target and timing for intervention to better support parents and caregivers of children with ASD in overcoming challenges and building stronger relationships with their children. This has important practical implications for mitigating bidirectional mutual perpetuation of parental stress and child behavioural and emotional problems.

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9. O’Brien AM, Perrachione TK, Gabrieli JDE, D’Mello AM. Neurodiversity in the brain: More variable localization of face regions in autism. bioRxiv;2026 (May 14)

A fundamental principle in human neuroscience is that the brain is organized into distinct functional regions specialized for particular processes. These functional regions develop early and are shaped by sensory experiences. Strikingly, the precise location of these functional regions is relatively consistent across individuals, with specific regions found in stereotyped locations with respect to the macroanatomy (e.g., particular sulci and gyri). An important question is how flexible this functional neuroanatomy is, particularly in neurodevelopmental disorders like autism which are characterized by atypical brain development and behavior. Here, we investigated this question by focusing on the organization of the face-processing network – a well-characterized system of regions that are reliably localized across neurotypical individuals, including, famously, the fusiform face area. Using precision fMRI, we identified subject-specific face-sensitive regions in the brains of autistic and neurotypical adults, and assessed their topographical alignment across individuals. Face regions in autism were globally and highly variably displaced – located farther from their expected locations in the brain relative to much more homogenous localization in neurotypical adults. Autistic individuals whose face regions were more displaced had greater sociocommunicative challenges. In contrast, the spatial organization of object-sensitive regions was not affected. These findings suggest that the spatial organization of the face network is atypical in autism, with behaviorally meaningful increased variability in the precise location of face-sensitive areas, and highlights the importance of individualized approaches in neuroimaging. SIGNIFICANCE STATEMENT: The human brain is organized into specialized functional regions positioned in remarkably consistent locations across individuals. It is unclear how altered neurodevelopment affects this organization. Using precision fMRI, we found that autism was characterized by globally and highly variably displaced face-sensitive functional brain regions. Atypical spatial organization of these regions was associated with greater sociocommunicative difficulties. In contrast, the spatial organization of object-sensitive regions did not differ in autism. These findings reveal that functional neuroanatomy in autism is altered in category-specific ways, with direct relevance to core sociocommunicative features of the condition. This work underscores the importance of individualized brain mapping in neuroimaging and may shed light on inconsistent findings in previous group-level neuroimaging studies.

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10. Pérez-Arzola AA, Crisanto-López IE, Hernández-Castañeda Y, Vera-Loaiza Á, Salazar-Bonilla W, Muñoz-Pérez MJ, Júarez-Melchor D. Factors associated to motor development in Down syndrome patients. Bol Med Hosp Infant Mex;2026;83(2):94-101.

INTRODUCCIÓN: El síndrome de Down (SD) se caracteriza por dismorfias, retraso psicomotor y afectaciones sistémicas. Su prevalencia es de 1:700 nacidos vivos. Aproximadamente el 80% de los recién nacidos con SD presentan hipotonía, que es la principal causa de retraso motor grueso. El desarrollo motor se considera atípico, dado que se retrasa en comparación con niños de la población general. El objetivo de este trabajo es describir los factores asociados al desarrollo motor en pacientes con SD. MÉTODOS: Se realizó un estudio observacional, analítico, transversal y ambispectivo en el Servicio de Genética Médica del Hospital General de Zona No. 20, Puebla. Se analizaron: edad, sexo, mecanismo citogenético, prematurez, lactancia materna, nivel socioeconómico, cardiopatía congénita, función tiroidea y rehabilitación para el desarrollo motor. Se realizó análisis estadístico descriptivo e inferencial (chi cuadrada) para identificar las variables asociadas al desarrollo motor de pacientes con SD. RESULTADOS: Se analizaron 40 pacientes con SD, 22 (55%) de sexo masculino y 18 (45%) femenino; la mediana de edad fue 32.5 meses; 22 individuos (55%) presentaron trisomía 21 libre y 18 (45%) en mosaico; en 37 individuos (92.5%) se retrasó el desarrollo motor y solo 3 (7.5%) alcanzaron los hitos. Se encontró una diferencia estadísticamente significativa entre el presentar o no hipotiroidismo y el logro de los hitos (p = 0.046). CONCLUSIONES: En este estudio se comprobó que los pacientes con SD presentan retraso del desarrollo motor y que existe una diferencia estadísticamente significativa entre el hipotiroidismo y los hitos motores, destacando que el hipotiroidismo no limitó el desarrollo motor en los pacientes con SD que alcanzaron sus hitos motores. BACKGROUND: Down syndrome (DS) is characterized by dysmorphia, psychomotor delay, and systemic conditions, with a prevalence of 1:700 live births. Around 80% of newborns with DS exhibit hypotonia, which is the main cause of gross motor delay. In these children, motor milestones are considered atypical because it is delayed compared to children in the general population. The aim is to describe factors associated to motor development in patients with DS. METHODS: An observational, analytical, cross-sectional, and ambispective study was conducted at the Medical Genetics Service of the General Hospital of Zone No. 20, Puebla. Age, sex, cytogenetic mechanism, prematurity, breastfeeding, socioeconomic level, congenital heart disease, thyroid function, and rehabilitation for motor development were analyzed. Descriptive and inferential statistical analysis was performed with the chi square test to identify variables associated with the motor development of patients with DS. RESULTS: Forty patients were analyzed, 22 (55%) male and 18 (45%) female, a median age of 32.5 months; 22 individuals (55%) had regular trisomy 21 and 18 (45%) mosaicism; 37 individuals (92.5%) presented developmental motor delay and 3 (7.5%) reached the milestones. A statistically significant difference was found between having or not having hypothyroidism and milestone achievement (p = 0.046). CONCLUSIONS: This study found that patients with DS have delayed motor development and that there is a statistically significant difference between hypothyroidism and motor milestones, highlighting that hypothyroidism did not limit motor development in patients with DS who reached their motor milestones.

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11. RameshRaju MK, Parambath SV, Srividhya D, Shankarappa B, Basappa RN, Murthy ASN. In silico Genotype-Phenotype Correlation Analysis of Inherited Variations in Autism Spectrum Disorder Families Identify an Interplay between Sensory Function and Repetitive-behaviour Genes. J Mol Neurosci;2026 (May 25);76(2)

Autism Spectrum Disorder (ASD) is a neurodevelopmental condition with a strong genetic basis. Most genetic studies on ASD emphasize de novo mutations, while inherited rare variants remain understudied. We hypothesize that subtle, inherited ASD-related traits accumulate across generations and clinically manifest as ASD in offspring. To investigate this, we extracted inherited variations from trio-based Whole Exome Sequences (WES) of 23 simplex ASD families (accession number PRJNA1071313 and PRJNA1072259). Data was processed in BWA, GATK and VarScan. Variants were annotated, filtered for functional impact, and scored using a ‘weighted scoring’ approach based on intolerance to genetic alterations. Overall 751 ‘weighted-genes’ with evolutionary and neuronal functions hosting deleterious inherited variations were functionally annotated for ASD-linked behaviours and comorbidities. We found 149 (20%) genes enriched for core ASD-behaviours like social-interaction and restrictive repetitive behaviours (RRB), 200 genes (26.6%) for associated-behaviours like hyperactivity, communication, intelligence and mood and 225 genes displayed neuronal-functions (p = 3.799E-20). Importantly, 62% of RRB genes displayed sensory functions and 71.43% of genes associated to social interaction deficits were also linked to seizures. Brain tissue expression analysis of all 751 genes revealed 95 prenatally and 195 postnatally upregulated genes were enriched with neurodevelopmental and neurotransmission functions, respectively; protein-protein-interactions suggested genes BUB1, HMGA2, HDAC2, KALRN, SORL1, IGF2, FASN, WFS1 as promising new-candidates for ASD. In our ASD cohort, inherited variations in genes regulating sensory function and neurodevelopment were also RRB producing genes- supporting a multigenic, subdued but additive genetic load being passed down from unrelated parents to their offsprings- promising an underexplored avenue for autism genetic research.

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12. Stewart ME, Bertilsdotter Rosqvist H, Day A, Long J, Grant A, Hersh M, Michael C, Doherty M, Ingard C, Lawson W. Priorities for Research on Autism and Ageing: A Roundtable Discussion. Autism Adulthood;2026 (Apr);8(2):149-158.

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13. Wang X, Li Y, Young DM, Ljungdahl A, Dema C, Rohani N, Nowakowski T, Roeder K, Sanders SJ. Spatiotemporal analysis of autism gene enrichment implicates cortex, thalamus, and hypothalamus. bioRxiv;2026 (May 14)

Autism spectrum disorder (ASD) is a highly heritable neurodevelopmental disorder. Sequencing analyses have identified 185 ASD-associated genes, which implicate neurons, but the specific brain regions through which these neurons influence neurodevelopment remain unclear. Here, we integrate over one million single-cell RNA sequencing profiles from 20 regions of the developing human brain (4-23 post-conceptual weeks) using a new framework, STARMAPS (Sparse Task-specific Analysis for Revealing Molecular Associations in Particular Single-cell datasets). STARMAPS accounts for coordinated regional and developmental perturbations in gene expression, enabling robust cross-region comparison. We replicate prior findings that ASD-associated genes are enriched in excitatory neurons during mid-fetal development, and we extend these results to reveal distinct spatial signatures. Across 26 excitatory neuron subtypes, six clusters showed significant enrichment for ASD-associated genes. These clusters localize to both cortical and subcortical regions, including the motor, temporal, and visual cortex, as well as the thalamus and hypothalamus. Our findings support a major role for excitatory neurons across distributed brain circuits, implicating previously underappreciated subcortical structures in ASD etiology. By providing a statistically rigorous framework for spatiotemporal integration of single-cell data, STARMAPS enables refined mapping of molecular vulnerability across the developing human brain.

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14. Xie F, Wang X, Pascual E, Mazzaggio G. Formula Production and its Relation to General Language Ability in Mandarin-Speaking Autistic Children. J Psycholinguist Res;2026 (May 25);55(3)

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15. Xu L, Zhang F, Li X. Barriers to and facilitation of long-term physical exercise participation among Chinese adolescents with autism spectrum disorder: a parental perspective. Front Psychol;2026;17:1797823.

From a parental perspective, this study explores the main barriers and facilitation strategies associated with long-term participation in physical exercise among Chinese adolescents with autism spectrum disorder (ASD). A qualitative research design was adopted, involving semi-structured interviews with parents of 19 adolescents with ASD who had participated in physical exercise for more than 3 years. Interview data were analyzed using reflexive thematic analysis. The findings indicate that adolescents with ASD encounter five major categories of barriers during sustained physical exercise participation: physical, cognitive, social communication, rule-related, and psychological adaptation barriers. In response to these challenges, five facilitation strategies were identified, including: improving rule design, adjusting instructional content and task difficulty, strengthening post-session tasks, refining training methods, and optimizing instructional delivery. Together, these findings provide practical insights for enhancing the effectiveness and sustainability of long-term physical exercise participation among adolescents with ASD.

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16. Yin Y, Wang A, Dong Q, Zhang Z, Bu Q, Wang R, Chang Q. A high-throughput screening platform to facilitate treatment development in Rett syndrome. Front Neurol;2026;17:1759410.

Rett syndrome (RTT) is a rare X-linked progressive neurodevelopmental disorder affecting predominantly females with no cure and a prevalence of ~1 in 10,000 female birth worldwide. Before mutations in the methyl-CpG binding protein 2 (MECP2) gene were identified to cause classic RTT, there were suggestions that RTT is a mitochondrial disease. Being an essential organelle for all eukaryotic cells, the mitochondria produce energy, buffer calcium, and regulate the generation of reactive oxygen species. Indeed, accumulated reports documented mitochondrial abnormalities in RTT patient biopsies, and animal models and human stem cell models of RTT, including reduced ATP production, altered mitochondrial structure, increased systemic oxidative stress, abnormal calcium activity, mtDNA copy number, and deficiencies in mitochondrial enzyme activity. While it remains unclear how loss of MECP2 function leads to wide-ranging mitochondrial deficits, improving mitochondrial function could still bring benefits to RTT patients. After defining the mitochondrial membrane potential deficit in astrocytes differentiated from RTT patient-specific induced pluripotent stem cells (iPSC), we established a novel high-throughput screening (HTS) platform based on the JC-10 mitochondrial membrane potential (MMP) assay, which served as a rapid primary readout. All primary hits were subsequently validated by independent functional assays to confirm their effects on mitochondrial health. Using this system, we performed a small-molecule screening of 1,134 selected US Food and Drug Administration (FDA)-approved drugs and a small interfering RNA (siRNA) screening of 336 genes upregulated in RTT astrocytes and identified candidate drugs and candidate genes that reversed the MMP deficits in RTT astrocytes. Among the candidate drug hits, isradipine, a dihydropyridine calcium-channel blocker, provided preliminary evidence of neuroprotective effects both in vitro and in vivo. Among the candidate gene hits, LRRC17, a gene encoding a secreted protein, emerged as a strong candidate mediator whose elevated levels are strongly associated with and likely contribute to various observed cellular deficits. siRNA knockdown of LRRC17 not only rescued mitochondrial dysfunction in RTT astrocytes but also reversed deficits in neurons cultured in astrocyte-conditioned media. Our study provides new insights into mitochondrial dysfunction in RTT and establishes an HTS platform for the initial identification of novel therapeutic targets for follow-up studies.

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17. Young DM, Sharma R, Rohani N, Dema C, Liang L, Devlin B, Manoli DS, Sanders SJ. Spatial transcriptomics implicates the thalamus and cortex in autism and schizophrenia. bioRxiv;2026 (May 15)

The past decade has seen tremendous progress in the identification of genes associated with complex neuropsychiatric disorders, including autism spectrum disorder (ASD) and schizophrenia. Expression patterns of these genes in single cell data strongly implicate excitatory and inhibitory neurons; however, there are limited data on the brain regions involved – a critical question for neurobiology. Spatial transcriptomics provide an opportunity to perform systematic multi-regional analyses to provide insights into this question. Here, we have generated a spatial transcriptomics dataset encompassing the diverse anatomical territories of the adult mouse brain sagittal midsection. We compare neuropsychiatric gene enrichment by applying Gene Fraction Enrichment Score (GFES), a novel statistic method that controls for differing neuronal proportions across regions. ASD-associated genes identified by exome sequencing were most enriched in the thalamus followed by the cortex. Schizophrenia genes from genome-wide association studies were also enriched in the thalamus, along with the hippocampus and cortex. These findings add to the evidence that the thalamus plays a major role in neuropsychiatric disorders whilst supporting roles for the cortex and hippocampus. The results highlight shared and distinct patterns for pleiotropic brain disorders that could elucidate common underlying mechanisms and circuitry.

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