RARE DISEASE
Atypical autism
Atypical autism
Atypical autism
Drug discovery
1
drug
With orphan designation
Overview
Atypical Autism Overview
Atypical autism (PDD-NOS/DSM-IV term, now classified under ASD per DSM-5) presents with social-communication deficits and restricted/repetitive behaviors but does not meet full criteria for classic autism. Symptoms may emerge later or show atypical patterns, such as milder social challenges or isolated sensory sensitivities. Early diagnosis and personalized interventions (e.g., behavioral, speech, and occupational therapies) are critical for improving functional outcomes [1][3][6][11].
Therapies
Behavioral: Applied Behavior Analysis (ABA) for skill development and behavior modification [1][8][13].
Multidisciplinary: Speech therapy (language deficits), occupational therapy (sensory/motor skills), and social skills training [3][6][8].
Adjunctive: Limited pharmacotherapy (e.g., SSRIs for anxiety; risperidone for aggression) [1][3][18].
Categories: rare genetic diseases, rare neurological diseases
Research Papers
748 drug discovery papers about Atypical autism, with 2 first-in-class and 5 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
748 drug discovery papers about Atypical autism, with 2 first-in-class and 5 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
proteins
2026-08-12 | Pain Expectation in Individuals With High Autistic Traits: Decision-Evaluation Processes and Oxytocin Modulation.
Pain reflects both sensory input and predictive processes shaped by expectations. Individuals with high autistic traits (HATs) often exhibit atypical pain responses, potentially due to alterations in anticipatory processing. This study investigated pain anticipation in HAT individuals and examined the modulatory effects of oxytocin using behavioral, computational, and pharmacological approaches. In experiment 1, HAT and low autistic trait (LAT) individuals completed a cue-based pain anticipation task. Anticipatory processing was characterized through two components: decision-related processes and evaluative responses. HAT individuals showed altered decision-making, characterized by greater caution under uncertainty and reduced processing efficiency under certain high-pain conditions. They also exhibited more negative evaluative responses, which were associated with poorer psychological health. In experiment 2, HAT participants received intranasal oxytocin or placebo. Oxytocin selectively influenced decision-related processes under uncertainty, increasing evidence accumulation and reducing nondecision time while also increasing the tendency to choose high-pain outcomes under ambiguous conditions. In contrast, oxytocin showed limited effects on evaluative measures. These findings suggest that pain anticipation in HAT individuals involves partially distinct decision-related and evaluative components and that oxytocin exerts process-specific effects on anticipatory processing.
2026-04-18 | Ceruloplasmin deficiency drives a fusiform-centric lipid-myelin pathology underlying a visual subtype in autism.
Atypical visual processing (AVP) commonly occurs in autism spectrum disorder (ASD) and contributes to social impairments, yet its neurobiological basis remains poorly characterized. To investigate potential lipid and myelin mechanisms, this study integrated multimodal MRI, quantifying lipid (proton density fat fraction) and myelin content (synthetic MRI) of 74 nuclei or brain regions, with serum profiling of iron, lead, and ceruloplasmin in 288 children, including 90 ASD with atypical visual processing (ASD‑AVP), 89 ASD without atypical visual processing (ASD‑AVP), and 109 typically developing (TD). The ASD-AVP subgroup exhibited a distinct co-pathology of elevated lipid and myelin centered on the fusiform gyrus (FG), accompanied by a unique positive lipid-myelin correlation (left: r = 0.47, right: r = 0.41). Serum analyses revealed decreased iron and ceruloplasmin and increased lead in ASD-AVP, and mediation analysis indicated that ceruloplasmin deficiency influences FG myelination via lipid pathways (35%-55%). Crucially, BTBR AVP-like mice recapitulated this phenotype with disorganized hypermyelination, whereas nAVP-like mice showed hypomyelination. A combined FG lipid-myelin signature strongly distinguished ASD-AVP from TD (AUC = 0.93) and ASD-nAVP (AUC = 0.87). Preliminary longitudinal follow-up in a subset of patients revealed that improvement in serum ceruloplasmin was associated with a reduction in FG lipid content and stabilization of myelin, paralleling clinical improvement. These findings identify a ceruloplasmin-driven, FG-centric lipid-myelin co-pathology, representing a maladaptive "inflammatory pseudo-compensation" mechanism specific to a visual ASD subtype, and offer novel biomarkers for biological subtyping and targeted interventions.
2026-03-25 | The role of the oxytocinergic system in oral microbiome composition in children with autism: evidence from a randomized controlled trial of intranasal oxytocin.
Atypical oxytocinergic functioning and altered microbiome compositions have both been implicated in autism, with growing evidence of interactions between these systems. However, how exogenous oxytocin influences the oral microbiome remains largely unexplored. This exploratory study examined for the first time how oral microbiome alterations link to oxytocinergic signalling in school-aged autistic (n = 80) and non-autistic children (n = 40). Additionally, we investigated the effect of four-weeks of intranasal oxytocin administration in autistic children on oral microbiome compositions immediately post-treatment (T1) and at four-weeks follow-up (T2). At baseline, lower endogenous salivary oxytocin levels were linked to greater microbial evenness and diversity, with twelve genera showing significant associations with oxytocin levels. In autistic children, four weeks of oxytocin administration was associated with significant increases in the abundances of Centipeda immediately post-treatment (T0-T1), alongside decreases in Moraxella (T0-T1), and subsequent reductions in Rothia observed at the four-week follow-up (T1-T2). Particularly, the genus Moraxella emerged as relevant, as lower baseline abundance was associated with higher endogenous oxytocin levels, and a stronger oxytocin-induced downregulation of its abundance correlated with greater increases in endogenous oxytocin levels, accompanied by hypomethylation of the oxytocin receptor gene. All results persisted after adjusting for nutrition and dental care. This exploratory study provides initial evidence for a role of the oxytocinergic system in shaping the oral microbiome in autistic children. These results may facilitate the integration of oral microbiome profiling into autism diagnostic criteria and stimulate future studies on the use of oxytocin as a therapeutic option targeting oral microbiome alterations.
2026-02-27 | Preliminary Data Regarding the Potential of Oxytocin to Modulate Aggressive Behaviour in a VPA-Based Animal Model of Autism Spectrum Disorder.
Background/Objectives: Aggressive behaviour is commonly associated with neurodevelopmental disorders, such as autism spectrum disorder (ASD), and could be understood as a response to daily stress routines, which negatively impacts patients' quality of life. Oxytocin (OT), a neuropeptide involved in social bonding and socio-affective regulation, has emerged as a promising candidate to enrich, rather than replace, current pharmacological approaches in managing ASD-associated aggressive behaviour. In this study, we examined the potential of OT to modulate aggressive behaviour frequency in a VPA-based animal model of ASD. Methods: Sixty adult zebrafish (1:1 sex ratio) were divided into six groups (n = 10/group) and received the following treatment for 7 consecutive days: CTR-control (no treatment); VPA (28.8 mg/L valproic acid); OT (33.2 ng/mL oxytocin); RIS (170 μg/L risperidone); VPA + OT (28.8 mg/L valproic acid and 33.2 ng/mL oxytocin); and VPA + RIS (28.8 mg/L valproic acid and 170 μg/L risperidone). The locomotor performance, and socio-affective and aggressive behaviours, were measured in the Novel Tank and Mirror Biting tests at the end of the treatments. Results: We observed that the VPA treatment led to locomotion and socio-affective impairments, as well as aggressive behaviour. Also, we found that OT and RIS had comparable potential to modulate the frequency of aggressive and anxiety-like behaviours. Conclusions: Our preliminary data showed that OT has the potential to modulate the frequency of anxiety-like and aggressive behaviours, similarly to the atypical antipsychotic, RIS, in our VPA zebrafish model. However, further studies are needed to investigate the mechanisms of action and their potential synergistic effects.
2025-12-13 | Physiological mechanisms of social odor perception and their implications for Autism Spectrum Disorders.
Olfactory social communication shapes emotional bonding, social cognition, and survival behaviors across mammals. In humans, body-odor-based social chemosignals contribute uniquely to interpersonal recognition and affective communication. However, atypical processing of social odors may disrupt early attachment formation and oxytocin-mediated socio-emotional development. Here, we review behavioral and neurophysiological mechanisms underlying social odor perception with a specific focus on maternal-infant bonding and its modulation by oxytocin pathways. Integrating evidence from humans and animal models, we propose that early disruptions in social chemosignaling may contribute to atypical developmental trajectories relevant to Autism Spectrum Disorders (ASD). We also outline a mechanistic framework and future research directions aimed at leveraging social odor processing for translational advances in ASD.
small molecules
2026-08-11 | Exploring atypical spatial-functional coupling in adolescent autism spectrum disorder: insights from neurodevelopment and transcriptomic architecture.
Autism Spectrum Disorder (ASD) is associated with atypical large-scale brain network organization, yet how spatial-functional dependencies relate to clinical features and molecular reference maps remains incompletely understood. To quantify spatial functional heterogeneity (Sill) and coherence persistence (Range), we analyzed resting-state fMRI data from 162 ASD and 175 TD adolescents, all aged 12-18. Compared with TD, adolescents with ASD exhibited significantly increased Sill within higher-order association networks, including the left Language and right Posterior Multimodal networks, whereas no group differences in Range survived multiple-comparison correction. Within the ASD group, elevated Sill was selectively associated with greater social-affective symptom severity but not restricted and repetitive behaviors. To explore potential biological correlates, we integrated cortical gene expression reference data and identified transcriptomic patterns associated with regional Sill differences. These genes showed enrichment for synaptic signaling, mitochondrial processes, and glial-related functions, highlighting multiscale correspondence between spatial-functional organization and molecular reference maps. Together, these results demonstrate statistical associations among altered spatial-functional properties, clinical severity, and transcriptomic profiles related to synaptic signaling, mitochondrial processes, and glial-related functions in ASD, providing a complementary spatial perspective on large-scale functional organization.
2026-07-17 | Cortical Network Overconnectivity Relates to Sensory, Cognitive, and Social Dimensions in Young Children With Autism Spectrum Disorder.
The heterogeneity in both the neurobiological mechanisms and the phenotypic presentations of autism spectrum disorder (ASD) poses a major challenge to clinical and translational research. Alterations in functional connectivity (FC) have been associated with ASD, yet it remains unclear whether and how divergent brain network properties may account for individual differences across ASD-related symptomatology and behaviors. We applied source-level reconstruction to rest-like non-task-related high-density EEG data in a cohort of 104 young children (38 with ASD) to identify global and local alterations of cortical network connectivity. We subsequently used regularized canonical correlation analysis (rCCA) to characterize specific FC patterns linked to variation in cognitive, social and sensory dimensions derived from standard clinical instruments. We found increased low-frequency FC in frontotemporal cross-hemispheric networks and lateral-occipital regions of young ASD children versus healthy peers. RCCA revealed three distinct FC patterns in recurrent ASD-related networks, each contributing to predict individual differences in cognitive, social and sensory features. These linked FC-behavior dimensions may shed light on atypical brain network topology associated with specific phenotypic manifestations of ASD, which might implicate unique underlying neurobiological mechanisms.
2026-06-15 | Unstable or Stable? Prosodic Features and Voice Quality in Autism Spectrum Disorder: A Systematic Review and Meta-analysis.
Speech prosody is fundamental to human spoken communication, and it is frequently characterized by atypical patterns, alongside voice quality, in individuals with autism spectrum disorder (ASD). However, findings across studies regarding these acoustic features in ASD remain inconsistent. Literature searches across four databases identified eligible studies comparing prosodic or voice quality acoustic parameters between individuals with ASD and matched TD individuals. A total of 40 studies involving 1023 individuals with ASD and 929 TD individuals were included. Subgroup and meta-regression analyses were conducted to assess potential moderators. The meta-analyses revealed a significantly higher mean pitch (Hedges' g = 0.43), broader pitch range (g = 0.29), and higher pitch standard deviation (g = 0.22) in the ASD group. For voice quality, significantly reduced shimmer (g = -0.44) and a trend toward reduced jitter (g = -0.26) indicated heightened stability of vocal fold vibrations in ASD. Our findings reveal a seemingly paradoxical acoustic profile in ASD: while individuals with ASD exhibit suprasegmental instability, they also demonstrate voicing hyper-stability. Moderators identified after subgroup and meta-regression analyses, including language background, IQ status, age span, mean age, and task type, may further moderate the prosodic features.
2026-06-01 | Medical treatment of autism spectrum disorder in children: Current evidence, controversies, and clinical challenges.
Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition associated with debilitating comorbidities [e.g., aggression, irritability, gastrointestinal (GI) issues]. Medical management primarily targets these symptoms, as no drug is Food and Drug Administration-approved for core social-communication deficits. To synthesize the efficacy and safety of five major pharmacological classes and evaluate the emerging evidence for biomarker-driven (precision medicine) interventions in pediatric ASD. Following PRISMA guidelines, we systematically reviewed randomized controlled trials (RCTs) for five classes: Atypical antipsychotics, stimulants, selective serotonin reuptake inhibitors, metabolic/nutritional, and microbiota-gut-brain axis agents. Quantitative meta-analysis for antipsychotics (n = 5 RCTs pooled) used the random-effects model, reporting I 2 to quantify heterogeneity. Atypical antipsychotics are the only drugs with robust, established efficacy for severe irritability: Pooled analysis for risperidone (n = 3 RCTs) showed a significant mean difference of approximately -11.0 on Aberrant Behavior Checklist-Irritability subscale (I 2 approximately 72%). Risperidone carries a greater metabolic burden (e.g., weight gain) than aripiprazole. Stimulants and selective serotonin reuptake inhibitors, respectively. Emerging therapies demonstrate targeted potential: Microbiota transfer therapy significantly improved GI and behavioral symptoms in cohorts with GI disease. Similarly, the efficacy of High-dose folinic acid was concentrated in the subgroup with folate receptor-α autoantibodies. The management of ASD demands a shift to a precision medicine model, as the efficacy of interventions is highly variable and concentrated in specific patient subgroups. Future research must prioritize the validation of biological biomarkers (metabolic, genetic, neurophysiological) to reliably predict treatment response, guiding the selection of targeted therapies, and addressing current evidence gaps.
2026-05-28 | Microglia, cerebellar inflammation, and autism spectrum disorders: Developmental mechanisms and therapeutic perspectives.
Autism spectrum disorders (ASD) are neurodevelopmental conditions characterized by deficits in social interaction and communication, as well as restricted and repetitive behaviors. These conditions often co-occur with medical issues linked to synaptic alterations, which compromise synaptic integrity and are associated with brain circuit dysfunction. Both human and animal studies have identified cerebellar structural and functional alterations in subsets of ASD cases, with evidence of abnormal morphology and disrupted connectivity correlating with symptom severity. Numerous studies further suggest that neuroinflammation and microglia dysfunction may contribute to atypical cerebellar development during critical postnatal windows and may be associated with ASD-like phenotypes. However, the timing and mechanisms underlying the onset of these processes remain unclear, and a primary causal role in human ASD has not been established. This review synthesizes current knowledge on microglia in early stages of cerebellar development and discusses how cerebellar inflammation could be linked to ASD-related phenotypes. A better understanding of these pathological processes and their behavioral correlates may reveal opportunities for early-life intervention strategies.
gene therapies
2026-07-23 | CRISPR/Cas9-Engineered HEK293T Cellular Model Harboring the Pathogenic CDKL5 c.172A>T Variant Recapitulates Core Molecular Phenotypes of CDKL5 Deficiency Disorder.
Mutations in the CDKL5 gene are strongly associated with severe neurodevelopmental disorders, including atypical Rett syndrome and autism spectrum disorder (ASD). This study aimed to establish a cell model carrying a targeted CDKL5 mutation using the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system and to evaluate the phenotypic and molecular consequences. A single-guide RNA (sgRNA) targeting exon 2 of CDKL5 was designed using in silico tools to minimize off-target activity. The sgRNA and Cas9 nuclease were cloned into the pSpCas9(BB)-2A-green fluorescent protein (GFP) (PX458) vector and transfected into human embryonic kidney 293T (HEK293T) cells. Following fluorescence-activated cell sorting (FACS), genome-editing efficiency was quantified using a T7 endonuclease I (T7E1) assay and Sanger sequencing. Homology-directed repair (HDR) mediated by single-stranded oligodeoxynucleotide (ssODN) templates was used to introduce a specific missense mutation (c.172A>T; p.Lys58Met). Edited clones were evaluated for CDKL5 expression using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and cell survival and apoptosis were assessed using Annexin V/propidium iodide (PI) staining and caspase-3 activity assays. The CRISPR/Cas9 construct achieved a mean on-target editing efficiency of 41.6 ± 3.2%, as determined by T7E1 digestion, and sequencing confirmed a heterozygous insertion in 28% of sorted clones. HDR-mediated precise editing was detected in 12% of clones. RT-qPCR analysis showed a 55% reduction in CDKL5 mRNA levels (P < 0.01) in edited cells, whereas Western blotting demonstrated a corresponding 48% decrease in protein expression. Functionally, mutant cells exhibited 25% lower viability (P < 0.05) and 2.3-fold higher apoptosis rates (P < 0.01) than wild-type controls. No significant off-target mutations were detected at the top five predicted loci. We successfully generated a human cell line model of CDKL5-related ASD using CRISPR/Cas9 technology. The mutation induced marked reductions in CDKL5 expression and cell survival. Although this HEK293T-based model provides a useful platform for mechanistic and screening studies, its non-neuronal origin limits its ability to fully recapitulate the neuronal context of CDKL5 deficiency disorder (CDD). This study establishes a novel, precisely engineered human cellular model using advanced CRISPR/Cas9 technology to mechanistically dissect the consequences of CDKL5 deficiency. By introducing a defined missense mutation (c.172A>T; p.Lys58Met) into HEK293T cells, this study provides a robust platform for investigating the role of CDKL5 in neurodevelopmental disorders and supports future therapeutic development.
2026-03-30 | Autism Spectrum Disorder in the Genomic Era: A Comprehensive Review of Etiology, Precision Diagnostics, Clinical Outcomes, and Emerging Gene-Editing Therapies.
Autism spectrum disorder (ASD) is a heterogeneous, lifelong neurodevelopmental condition characterized by deficits in social communication and restricted, repetitive behaviors. Over recent decades, diagnostic expansion and methodological advances have led to increased prevalence estimates and a deeper appreciation of phenotypic, etiological, and outcome heterogeneity. This review synthesizes evidence from 2015-2024 across epidemiology, clinical diagnosis, neurobiology, genetics, environmental risk factors, mortality, and treatment. We summarize robust genetic contributions, including polygenic risk from common variants and high-impact rare or de novo mutations converging on synaptic function, chromatin regulation, and neurodevelopmental pathways. Prenatal and perinatal environmental exposures such as maternal immune activation, air pollution, and selected teratogens interact with genetic susceptibility through inflammatory, oxidative, and epigenetic mechanisms to influence ASD risk. Neuroimaging and multimodal studies reveal altered cortical developmental trajectories and atypical large-scale network connectivity associated with core symptoms and common comorbidities. Mortality studies demonstrate increased all-cause and cause-specific mortality, particularly related to epilepsy, medical comorbidities, and injury, with highest risk observed in individuals with intellectual disability. Current treatments remain primarily symptomatic, with early, intensive, and individualized behavioral interventions providing the greatest functional benefit, while pharmacotherapy targets associated behavioral challenges. Emerging genomic technologies, including CRISPR-based approaches, offer powerful experimental models and potential precision therapies for selected monogenic or high-impact copy number variant-associated ASD, although substantial safety, delivery, and ethical challenges remain. We conclude by highlighting priorities for integrative longitudinal studies, mechanistic links between molecular and circuit-level dysfunction, and responsible translational pathways toward precision therapeutics.
2025-02-11 | Interpersonal synchronization: An overlooked factor in development, social cognition, and psychopathology.
Intact social functioning relies on a combination of explicit and implicit behavioral, attentional, and interpersonal processes referred to as "social cognition". Characterizing these interpersonal processes forms a critical underpinning to understanding and treating psychopathology, particularly in disorders where deficits in social functioning do not emerge as a secondary symptom but rather as an essential feature of the disorder. Two of such disorders are autism spectrum disorders (ASD) and schizophrenia spectrum disorders (SZ). However, despite the substantial overlap in the features of social dysfunction between ASD and SZ, including social cognitive deficits in theory of mind, perspective-taking, and empathy, there is a limited understanding of the mechanisms underlying those shared deficits, and how to treat them. We suggest that disruptions of interpersonal functioning emerge over the course of development, and that interpersonal synchronization, a phenomenon in which behavioral and physiological cues align between interacting partners, forms a critical component of social cognition that underlies the disruption in social functioning in ASD and SZ. We present a conceptual review of typical and atypical development of social processes and highlight the role of interpersonal synchronization across the course of development. Then, we review the existing evidence suggesting impairments in both the intentional and spontaneous synchronization of interpersonal processes in ASD and SZ, as well as studies suggesting that interpersonal synchronization and clinical symptoms may be improved through body-oriented interventions within these disorders. Finally, we suggest potential mechanisms that may underpin typical and atypical development of interpersonal synchronization.
2024-12-14 | Short report on a distinct electroencephalogram endophenotype for MTHFR gene variation co-occurring in autism spectrum disorder.
Anecdotal reports link a distinct, bilateral, parieto-temporally generated 4.5-Hz rhythm on an electroencephalogram to a methylenetetrahydrofolate reductase gene variant co-occurring in autism spectrum disorder, but the validation of its precision is needed. The electroencephalograms of children with autism spectrum disorder showing the distinct bilateral parieto-temporally generated 4.5-Hz rhythm and their clinical chart report on polymerase chain reaction screening for methylenetetrahydrofolate reductase gene variants, 677C>T and 1298A>C, were retrieved from an outpatient clinic between February 2019 and April 2024. Twenty-five cases were identified. Patients were between 2 and 12 (7 ± 3) years old from Asian (n = 16, 64%), European (n = 5, 20%), African (n = 1, 4%) and mixed (n = 3, 12%) ethnicities. Twenty patients (80%) were positive for 677 C>Theterozygous (n = 3, 15%), 1298A>Cheterozygous (n = 8, 40%) or both (n = 9, 45%). The polymerase chain reaction testing detected neither variant in 5 (20%) patients. Therefore, the electroencephalogram-endophenotype showed 80% precision in identifying methylenetetrahydrofolate reductase gene variant within the sample. This preliminary data support the precision of the proposed distinct, bilateral, parieto-temporally generated 4.5-Hz rhythm in identifying methylenetetrahydrofolate reductase gene variants and its potential clinical applications as a valuable, non-invasive and objective measure within the population.Lay abstractMethylenetetrahydrofolate reductase mutations refer to genetic variations in the methylenetetrahydrofolate reductase enzyme, which plays an important role in folate metabolism. Folate is essential for neural development and signalling. Children with autism spectrum disorder have atypical neural signals compared with control. This study used a non-invasive method to identify a distinct neural signal that may be useful in future screening for methylenetetrahydrofolate reductase mutation in children with autism spectrum disorder. Given that the underlying causes of autism spectrum disorder have multiple genetic factors and often require subjective assessment, this study introduces a potential non-invasive screening method for methylenetetrahydrofolate reductase gene mutation. This method could provide valuable biomarkers for screening and personalised treatments, offering hope for improved risk stratification and bespoke nutritional support and supplements to mitigate the impact on affected individuals and their descendants.
2023-05-28 | SOX7: Novel Autistic Gene Identified by Analysis of Multi-Omics Data
ABSTRACT Background Genome-wide association studies and next generation sequencing data analyses based on DNA information have identified thousands of mutations associated with autism spectrum disorder (ASD). However, more than 99% of identified mutations are non-coding. Thus, it is unclear which of these mutations might be functional and thus potentially causal variants. Transcriptomic profiling using total RNA-sequencing has been one of the most utilized approaches to link protein levels to genetic information at the molecular level. The transcriptome captures molecular genomic complexity that the DNA sequence solely does not. Some mutations alter a gene’s DNA sequence but do not necessarily change expression and/or protein function. To date, few common variants reliably associated with the diagnosis status of ASD despite consistently high estimates of heritability. In addition, reliable biomarkers used to diagnose ASD or molecular mechanisms to define the severity of ASD do not exist. Objectives It is necessary to integrate DNA and RNA testing together to identify true causal genes and propose useful biomarkers for ASD. Methods We performed gene-based association studies with adaptive test using genome-wide association studies (GWAS) summary statistics with two large GWAS datasets (ASD 2019 data: 18,382 ASD cases and 27,969 controls [discovery data]; ASD 2017 data: 6,197 ASD cases and 7,377 controls [replication data]) which were obtained from the Psychiatric Genomics Consortium (PGC). In addition, we investigated differential expression for genes identified in gene-based GWAS with a RNA-seq dataset (GSE30573: 3 cases and 3 controls) using the DESeq2 package. Results We identified 5 genes significantly associated with ASD in ASD 2019 data (KIZ-AS1, p=8.67×10 −10 ; KIZ, p=1.16×10 −9 ; XRN2, p=7.73×10 −9 ; SOX7, p=2.22×10 −7 ; PINX1-DT, p=2.14×10 −6 ). Among these 5 genes, gene SOX7 (p=0.00087), LOC101929229 (p=0.009), and KIZ-AS1 (p=0.059) were replicated in ASD 2017 data. KIZ (p=0.06) was close to the boundary of replication in ASD 2017 data. Genes SOX7 (p=0.0017, adjusted p=0.0085), LOC101929229 (also known as PINX1-DT, p=5.83×10 −7 , adjusted p=1.18×10 −5 ), and KIZ (p=0.00099, adjusted p=0.0055) indicated significant expression differences between cases and controls in the RNA-seq data. SOX7 encodes a member of the SOX (SRY-related HMG-box) family of transcription factors pivotally contributing to determining of the cell fate and identity in many lineages. The encoded protein may act as a transcriptional regulator after forming a protein complex with other proteins leading to autism. Conclusion Gene SOX7 in the transcription factor family could be associated with ASD. This finding may provide new diagnostic and therapeutic strategies for ASD.
antibodies
2025-12-12 | Comprehensive multi-omics mapping of immune perturbations in autism spectrum disorder.
Autism spectrum disorder (ASD) is increasingly recognized as a neurodevelopmental condition with systemic immunological involvement, yet the underlying immune mechanisms remain incompletely defined. To delineate the peripheral immune landscape in ASD using integrated multi-omics profiling and to determine how immune and immunometabolic alterations relate to clinical severity. Circulating immune cells from individuals with ASD were profiled using multicolor flow cytometry, single-cell RNA sequencing, and bulk RNA sequencing. Plasma proteomic and metabolomic analyses were performed to identify immune-related and metabolic biomarkers. Immune features were evaluated for associations with clinical severity measures. Multi-omics profiling revealed marked immune dysregulation in ASD, with significant shifts in immune cell subsets and inflammatory signatures that correlated with clinical severity. T cell abnormalities included reduced frequencies and a skewed Th1/Th2 balance, consistent with a chronic inflammatory milieu. Natural killer (NK) cells showed increased activation but impaired cytotoxic capacity, accompanied by expansion of an atypical NK subset. Myeloid-derived suppressor cells (MDSCs) and hyperinflammatory CD56+ monocytes were elevated. Transcriptomic analyses corroborated broad immune activation, prominently implicating interferon-driven and antiviral signaling pathways. Plasma metabolomics and proteomics further indicated disruptions in purine metabolism and oxidative phosphorylation, alongside increased inflammatory markers, which were significantly associated with symptom severity. These findings support a systemic immunometabolic framework in ASD characterized by concurrent immune activation and altered myeloid/NK cell states, providing mechanistic context for peripheral biomarkers linked to clinical phenotype. Integrated multi-omics profiling identifies robust peripheral immune and metabolic disturbances in ASD. The dysregulated immune subsets, activated immune pathways, and plasma biomarker signatures highlight potential avenues for biomarker-driven stratification and immune-targeted therapeutic development in ASD. T cell dysregulation, NK cell impairment, and myeloid expansion indicate a chronic inflammatory state and immune exhaustion phenotype associated with ASD severity. Plasma metabolomic and proteomic alterations, including disrupted oxidative phosphorylation and elevated inflammatory markers, correlate with ASD severity and highlight potential biomarkers. Multi-omics profiling links peripheral immune dysregulation to neurodevelopmental abnormalities, providing a framework for immune-targeted ASD interventions.
2017-03-20 | Face perception and learning in autism spectrum disorders.
Autism Spectrum Disorder (ASD) is characterized by impairment in social communication and restricted and repetitive interests. While not included in the diagnostic characterization, aspects of face processing and learning have shown disruptions at all stages of development in ASD, although the exact nature and extent of the impairment vary by age and level of functioning of the ASD sample as well as by task demands. In this review, we examine the nature of face attention, perception, and learning in individuals with ASD focusing on three broad age ranges (early development, middle childhood, and adolescence/adulthood). We propose that early delays in basic face processing contribute to the atypical trajectory of social communicative skills in individuals with ASD and contribute to poor social learning throughout development. Face learning is a life-long necessity, as the social world of individual only broadens with age, and thus addressing both the source of the impairment in ASD as well as the trajectory of ability throughout the lifespan, through targeted treatments, may serve to positively impact the lives of individuals who struggle with social information and understanding.
2015-12-02 | Autism spectrum disorder in infancy: developmental considerations in treatment targets.
This review explores recent literature to prioritize aspects of development to be targeted by intervention for infants and toddlers with autism spectrum disorder (ASD). Recent investigation of early development in ASD, including prospective studies of infants at increased risk (i.e., those with an affected older sibling) identifies impairments in four key developmental domains that are predictive of ASD. These domains are early attentional control, emotion regulation, social orienting/approach, and communication development. Reciprocal relationships exist among these domains, both in ASD and in typical development. Thus, these domains represent key intervention targets, informing treatment models under investigation in recent clinical trials. By targeting the earliest and foundational manifestations of atypical development, we can capitalize on neural plasticity and build skills that are most likely to have scaffolding effects on development. The optimal timing and procedures of intervention remain empirical questions, but as the field moves toward earlier identification of risk, we are now poised to evaluate the impact of tailored approaches before the developmental cascade that leads to ASD is fully manifested. Consideration regarding community translation of ASD-specific interventions for infants and toddlers is also needed, with a focus on feasibility, cost-effectiveness, and sustainability.
2015-05-19 | Sex Differences in Autism Spectrum Disorders: Does Sex Moderate the Pathway from Clinical Symptoms to Adaptive Behavior?
Abstract We explored sex differences in diagnostic categories, clinical symptoms and adaptive behavior of persons with autism spectrum disorders, as well as sex-specific correlations of clinical and adaptive caracteristics. The study involved 108 patients (83 males, 6.73 ± 4.33 years old) diagnosed with autism spectrum disorders (ASD). Assessment included ADI-R and Vineland Adaptive Behavior Scale II. Males were more often diagnosed with typical autism. There were no sex differences in the autistic symptoms, while females showed better functioning in Daily living skills, without reaching statistically significant difference (p = 0.062). We have found different associations of autistic symptoms with different aspects of adaptive behavior in males and females. Social reciprocity in females correlated with social domain of adaptive behavior, in a positive direction. Our findings have shown that although there are no sex differences in autistic symptoms, females tend to be somewhat more functional and are also less frequently diagnosed with typical autism. Our results have also shown that sex might moderate the way clinical symptoms are expressed in adaptive behavior. Social reciprocity might be the core feature regarding sex differences in ASD. Our findings might have diagnostic and therapeutical implications, pointing out to the need for individualized, sex-specific treatment in this group of disorders.
2013-01-14 | Looking but not seeing: atypical visual scanning and recognition of faces in 2 and 4-year-old children with autism spectrum disorder.
This study used eye-tracking to examine visual scanning and recognition of faces by 2- and 4-year-old children with autism spectrum disorder (ASD) (N = 44) and typically developing (TD) controls (N = 30). TD toddlers at both age levels scanned and recognized faces similarly. Toddlers with ASD looked increasingly away from faces with age, atypically attended to key features of faces, and were impaired in face recognition. Deficits in recognition were associated with imbalanced attention between key facial features. This study illustrates that face processing in ASD may be affected early and become further compromised with age. We propose that deficits in face processing likely impact the effectiveness of toddlers with ASD as social partners and thus should be targeted for intervention.
other
2026-06-04 | Olfactory Valence-Processing Deficits and Aberrant Brain Network Connectivity Underlie Social Dysfunction in Shank3-/- ASD Model Mice.
Olfaction is crucial for rodent social behavior, and olfactory dysfunction has been observed in multiple autism spectrum disorder (ASD) models, but its phenotype in Shank3⁻/⁻ mice (a classic ASD model) remains unclear. We systematically assessed olfactory function in Shank3⁻/⁻ mice by using a modified olfactory three-chamber test and optimized ultrasonic vocalization (USV) detection in combination with resting-state functional magnetic resonance imaging (rs-fMRI), whole-brain c-Fos mapping, and three-dimensional (3D) behavioral analysis. Our results showed abnormal odor preference and hyperconnectivity in olfaction-associated brain networks. Upon exposure to neutral, appetitive, and social pheromone odors, Shank3⁻/⁻ mice displayed atypical whole-brain c-Fos activation patterns, which were coupled with synchronized locomotor suppression and stereotyped behaviors. This study maps the neural-behavioral responses to odors in Shank3-/- mice, linking olfactory deficits to autism-like behaviors, and highlights the olfactory system as a targetable pathway for sensory-based autism therapies.
2026-02-06 | Sex specific effects of adoptive Tregs transfer on the brain and periphery in maternal immune activation offspring rescuing immune dysregulation.
Autism spectrum disorder (ASD) is characterized by atypical communication, social interactions, and restricted interests. In ASD, there are dysfunctional immune regulatory control mechanisms that can lead to immune activation. Notably lower frequencies of regulatory T cells (Tregs) and reduced immunosuppressive cytokines are reported and associated with more impaired behaviors impacting both individuals with autism and their families. Therefore, therapeutic approaches that enhance immune regulation may offer substantial benefits. Using the maternal immune activation (MIA) model, we investigated whether adoptive transfer of wildtype Tregs into MIA offspring recipients could rescue immune activation, brain transcriptome changes and behaviors exhibited in adult MIA offspring. We also aimed to explore potential sex-differences in responses. In male but not female MIA offspring, Tregs transfer reduced the frequency of T helper (TH)-17 (RORγT+ CD4+) T cells in both the mesenteric lymph node (MLN) and spleen. Moreover, the frequency of CD25+Foxp3+ T cells was increased in the MLN and spleen of male but not female MIA offspring following Treg transfer. Splenocytes from male MIA offspring receiving Tregs showed reduced production of inflammatory cytokines (e.g., IL-6 and TNFα) following PMA/Ionomycin stimulations. In contrast, female MIA offspring that received Tregs exhibited different cytokine profiles characterized by increased production of cytokines, including GM-CSF, IFNγ, and IL-10. In the brain, bulk mRNA sequencing in the cerebellum, frontal cortex, and hippocampus revealed that Tregs-treated male MIA offspring had differentially expressed genes involved in neurodevelopmental disorders, synaptic function, and epigenetic regulation. Minimal gene expression differences were observed in female counterparts. There was significant improvement in self-grooming behaviors in males MIA offspring that received Tregs. In females, social novelty improved after Tregs treatment. In summary, adoptive Tregs transfer reduced systemic inflammation, brain transcription and behavior alterations in a sex dependent manner in the context of MIA. These findings suggest that adoptive Treg transfer may represent a viable therapeutic avenue for mitigating systemic inflammation and comorbidities associated with MIA and neurodevelopmental disorders such as ASD.
2025-07-07 | Stem Cell Therapy and Models for Autism Spectrum Disorder: Insights and Research.
Autism Spectrum Disorders (ASD) are complex neurodevelopmental conditions characterized by impaired social communication, repetitive behavior patterns, and atypical sensory perception. The Autism and Developmental Disabilities Monitoring Network reports that approximately 1 in 36 children are diagnosed with ASD, highlighting the increasing prevalence and the pressing need for innovative treatment approaches. Medications commonly used in ASD primarily aim to manage associated symptoms, as there are currently no FDA-approved medications specifically for treating ASD core symptoms. Stem cells have demonstrated significant potential in cell-based therapies for ASD and have been utilized in in vitro models to investigate the pathogenesis of the condition. This review focuses on the recent advancements in stem cell-based transplantation in animal models of ASD, aiming to explore the improvement of ASD symptoms and the underlying mechanisms involved. It also discussed the application of stem cell-based transplantation in pediatric and adolescent populations with ASD to evaluate treatment efficacy and potential preventive strategies. Furthermore, recent efforts are addressed in developing stem cell-based models for both syndromic and non-syndromic forms of ASD, emphasizing studies that utilize cerebral organoids for modeling ASD, which facilitate the exploration of disease mechanisms within a tissue-like environment.
2024-11-04 | Altered Functional Connectivity of Unimodal Sensory and Multisensory Integration Networks Is Related to Symptom Severity in Autism Spectrum Disorder.
Atypical sensory processing is a prevalent feature of autism spectrum disorder (ASD) and constitutes a core diagnostic criterion in DSM-5. However, the neurocognitive underpinnings of atypical unimodal and multimodal sensory processing and their relationships with autism symptoms remain unclear. In this study, we examined intrinsic functional connectivity (FC) patterns among 5 unimodal sensory and multisensory integration (MSI) networks in ASD using a large multisite dataset (N = 646) and investigated the relationships between altered FC, atypical sensory processing, social communicative deficits, and overall autism symptoms using correlation and mediation analyses. Compared with typically developing control participants, participants in the ASD group demonstrated increased FC of the olfactory network, decreased FC within the MSI network, and decreased FC of the MSI-unimodal sensory networks. Furthermore, altered FC was positively associated with autism symptom severity, and such associations were completely mediated by atypical sensory processing and social communicative deficits. ASD-specific olfactory overconnectivity and MSI-unimodal sensory underconnectivity lend support to the intense world theory and weak central coherence theory, suggesting olfactory hypersensitivity at the expense of MSI as a potential neural mechanism underlying atypical sensory processing in ASD. These atypical FC patterns suggest potential targets for psychological and neuromodulatory interventions.
2023-01-17 | An Early Enriched Experience Drives an Activated Microglial Profile at Site of Corrective Neuroplasticity in Ten-m3 Knock-Out Mice.
Environmental enrichment (EE) is beneficial for brain development and function, but our understanding of its capacity to drive circuit repair, the underlying mechanisms, and how this might vary with age remains limited. Ten-m3 knock-out (KO) mice exhibit a dramatic and stereotyped mistargeting of ipsilateral retinal inputs to the thalamus, resulting in visual deficits. We have recently shown a previously unexpected capacity for EE during early postnatal life (from birth for six weeks) to drive the partial elimination of miswired axonal projections, along with a recovery of visually mediated behavior, but the timeline of this repair was unclear. Here, we reveal that with just 3.5 weeks of EE from birth, Ten-m3 KOs exhibit a partial behavioral rescue, accompanied by pruning of the most profoundly miswired retinogeniculate terminals. Analysis suggests that the pruning is underway at this time point, providing an ideal opportunity to probe potential mechanisms. With the shorter EE-period, we found a localized increase in microglial density and activation profile within the identified geniculate region where corrective pruning was observed. No comparable response to EE was found in age-matched wild-type (WT) mice. These findings identify microglia as a potential mechanistic link through which EE drives the elimination of miswired neural circuits during early postnatal development. Activity driven, atypical recruitment of microglia to prune aberrant connectivity and restore function may have important therapeutic implications for neurodevelopmental disorders such as autistic spectrum disorder.
proteins
2026-08-12 | Pain Expectation in Individuals With High Autistic Traits: Decision-Evaluation Processes and Oxytocin Modulation.
Pain reflects both sensory input and predictive processes shaped by expectations. Individuals with high autistic traits (HATs) often exhibit atypical pain responses, potentially due to alterations in anticipatory processing. This study investigated pain anticipation in HAT individuals and examined the modulatory effects of oxytocin using behavioral, computational, and pharmacological approaches. In experiment 1, HAT and low autistic trait (LAT) individuals completed a cue-based pain anticipation task. Anticipatory processing was characterized through two components: decision-related processes and evaluative responses. HAT individuals showed altered decision-making, characterized by greater caution under uncertainty and reduced processing efficiency under certain high-pain conditions. They also exhibited more negative evaluative responses, which were associated with poorer psychological health. In experiment 2, HAT participants received intranasal oxytocin or placebo. Oxytocin selectively influenced decision-related processes under uncertainty, increasing evidence accumulation and reducing nondecision time while also increasing the tendency to choose high-pain outcomes under ambiguous conditions. In contrast, oxytocin showed limited effects on evaluative measures. These findings suggest that pain anticipation in HAT individuals involves partially distinct decision-related and evaluative components and that oxytocin exerts process-specific effects on anticipatory processing.
2026-04-18 | Ceruloplasmin deficiency drives a fusiform-centric lipid-myelin pathology underlying a visual subtype in autism.
Atypical visual processing (AVP) commonly occurs in autism spectrum disorder (ASD) and contributes to social impairments, yet its neurobiological basis remains poorly characterized. To investigate potential lipid and myelin mechanisms, this study integrated multimodal MRI, quantifying lipid (proton density fat fraction) and myelin content (synthetic MRI) of 74 nuclei or brain regions, with serum profiling of iron, lead, and ceruloplasmin in 288 children, including 90 ASD with atypical visual processing (ASD‑AVP), 89 ASD without atypical visual processing (ASD‑AVP), and 109 typically developing (TD). The ASD-AVP subgroup exhibited a distinct co-pathology of elevated lipid and myelin centered on the fusiform gyrus (FG), accompanied by a unique positive lipid-myelin correlation (left: r = 0.47, right: r = 0.41). Serum analyses revealed decreased iron and ceruloplasmin and increased lead in ASD-AVP, and mediation analysis indicated that ceruloplasmin deficiency influences FG myelination via lipid pathways (35%-55%). Crucially, BTBR AVP-like mice recapitulated this phenotype with disorganized hypermyelination, whereas nAVP-like mice showed hypomyelination. A combined FG lipid-myelin signature strongly distinguished ASD-AVP from TD (AUC = 0.93) and ASD-nAVP (AUC = 0.87). Preliminary longitudinal follow-up in a subset of patients revealed that improvement in serum ceruloplasmin was associated with a reduction in FG lipid content and stabilization of myelin, paralleling clinical improvement. These findings identify a ceruloplasmin-driven, FG-centric lipid-myelin co-pathology, representing a maladaptive "inflammatory pseudo-compensation" mechanism specific to a visual ASD subtype, and offer novel biomarkers for biological subtyping and targeted interventions.
2026-03-25 | The role of the oxytocinergic system in oral microbiome composition in children with autism: evidence from a randomized controlled trial of intranasal oxytocin.
Atypical oxytocinergic functioning and altered microbiome compositions have both been implicated in autism, with growing evidence of interactions between these systems. However, how exogenous oxytocin influences the oral microbiome remains largely unexplored. This exploratory study examined for the first time how oral microbiome alterations link to oxytocinergic signalling in school-aged autistic (n = 80) and non-autistic children (n = 40). Additionally, we investigated the effect of four-weeks of intranasal oxytocin administration in autistic children on oral microbiome compositions immediately post-treatment (T1) and at four-weeks follow-up (T2). At baseline, lower endogenous salivary oxytocin levels were linked to greater microbial evenness and diversity, with twelve genera showing significant associations with oxytocin levels. In autistic children, four weeks of oxytocin administration was associated with significant increases in the abundances of Centipeda immediately post-treatment (T0-T1), alongside decreases in Moraxella (T0-T1), and subsequent reductions in Rothia observed at the four-week follow-up (T1-T2). Particularly, the genus Moraxella emerged as relevant, as lower baseline abundance was associated with higher endogenous oxytocin levels, and a stronger oxytocin-induced downregulation of its abundance correlated with greater increases in endogenous oxytocin levels, accompanied by hypomethylation of the oxytocin receptor gene. All results persisted after adjusting for nutrition and dental care. This exploratory study provides initial evidence for a role of the oxytocinergic system in shaping the oral microbiome in autistic children. These results may facilitate the integration of oral microbiome profiling into autism diagnostic criteria and stimulate future studies on the use of oxytocin as a therapeutic option targeting oral microbiome alterations.
2026-02-27 | Preliminary Data Regarding the Potential of Oxytocin to Modulate Aggressive Behaviour in a VPA-Based Animal Model of Autism Spectrum Disorder.
Background/Objectives: Aggressive behaviour is commonly associated with neurodevelopmental disorders, such as autism spectrum disorder (ASD), and could be understood as a response to daily stress routines, which negatively impacts patients' quality of life. Oxytocin (OT), a neuropeptide involved in social bonding and socio-affective regulation, has emerged as a promising candidate to enrich, rather than replace, current pharmacological approaches in managing ASD-associated aggressive behaviour. In this study, we examined the potential of OT to modulate aggressive behaviour frequency in a VPA-based animal model of ASD. Methods: Sixty adult zebrafish (1:1 sex ratio) were divided into six groups (n = 10/group) and received the following treatment for 7 consecutive days: CTR-control (no treatment); VPA (28.8 mg/L valproic acid); OT (33.2 ng/mL oxytocin); RIS (170 μg/L risperidone); VPA + OT (28.8 mg/L valproic acid and 33.2 ng/mL oxytocin); and VPA + RIS (28.8 mg/L valproic acid and 170 μg/L risperidone). The locomotor performance, and socio-affective and aggressive behaviours, were measured in the Novel Tank and Mirror Biting tests at the end of the treatments. Results: We observed that the VPA treatment led to locomotion and socio-affective impairments, as well as aggressive behaviour. Also, we found that OT and RIS had comparable potential to modulate the frequency of aggressive and anxiety-like behaviours. Conclusions: Our preliminary data showed that OT has the potential to modulate the frequency of anxiety-like and aggressive behaviours, similarly to the atypical antipsychotic, RIS, in our VPA zebrafish model. However, further studies are needed to investigate the mechanisms of action and their potential synergistic effects.
2025-12-13 | Physiological mechanisms of social odor perception and their implications for Autism Spectrum Disorders.
Olfactory social communication shapes emotional bonding, social cognition, and survival behaviors across mammals. In humans, body-odor-based social chemosignals contribute uniquely to interpersonal recognition and affective communication. However, atypical processing of social odors may disrupt early attachment formation and oxytocin-mediated socio-emotional development. Here, we review behavioral and neurophysiological mechanisms underlying social odor perception with a specific focus on maternal-infant bonding and its modulation by oxytocin pathways. Integrating evidence from humans and animal models, we propose that early disruptions in social chemosignaling may contribute to atypical developmental trajectories relevant to Autism Spectrum Disorders (ASD). We also outline a mechanistic framework and future research directions aimed at leveraging social odor processing for translational advances in ASD.
small molecules
2026-08-11 | Exploring atypical spatial-functional coupling in adolescent autism spectrum disorder: insights from neurodevelopment and transcriptomic architecture.
Autism Spectrum Disorder (ASD) is associated with atypical large-scale brain network organization, yet how spatial-functional dependencies relate to clinical features and molecular reference maps remains incompletely understood. To quantify spatial functional heterogeneity (Sill) and coherence persistence (Range), we analyzed resting-state fMRI data from 162 ASD and 175 TD adolescents, all aged 12-18. Compared with TD, adolescents with ASD exhibited significantly increased Sill within higher-order association networks, including the left Language and right Posterior Multimodal networks, whereas no group differences in Range survived multiple-comparison correction. Within the ASD group, elevated Sill was selectively associated with greater social-affective symptom severity but not restricted and repetitive behaviors. To explore potential biological correlates, we integrated cortical gene expression reference data and identified transcriptomic patterns associated with regional Sill differences. These genes showed enrichment for synaptic signaling, mitochondrial processes, and glial-related functions, highlighting multiscale correspondence between spatial-functional organization and molecular reference maps. Together, these results demonstrate statistical associations among altered spatial-functional properties, clinical severity, and transcriptomic profiles related to synaptic signaling, mitochondrial processes, and glial-related functions in ASD, providing a complementary spatial perspective on large-scale functional organization.
2026-07-17 | Cortical Network Overconnectivity Relates to Sensory, Cognitive, and Social Dimensions in Young Children With Autism Spectrum Disorder.
The heterogeneity in both the neurobiological mechanisms and the phenotypic presentations of autism spectrum disorder (ASD) poses a major challenge to clinical and translational research. Alterations in functional connectivity (FC) have been associated with ASD, yet it remains unclear whether and how divergent brain network properties may account for individual differences across ASD-related symptomatology and behaviors. We applied source-level reconstruction to rest-like non-task-related high-density EEG data in a cohort of 104 young children (38 with ASD) to identify global and local alterations of cortical network connectivity. We subsequently used regularized canonical correlation analysis (rCCA) to characterize specific FC patterns linked to variation in cognitive, social and sensory dimensions derived from standard clinical instruments. We found increased low-frequency FC in frontotemporal cross-hemispheric networks and lateral-occipital regions of young ASD children versus healthy peers. RCCA revealed three distinct FC patterns in recurrent ASD-related networks, each contributing to predict individual differences in cognitive, social and sensory features. These linked FC-behavior dimensions may shed light on atypical brain network topology associated with specific phenotypic manifestations of ASD, which might implicate unique underlying neurobiological mechanisms.
2026-06-15 | Unstable or Stable? Prosodic Features and Voice Quality in Autism Spectrum Disorder: A Systematic Review and Meta-analysis.
Speech prosody is fundamental to human spoken communication, and it is frequently characterized by atypical patterns, alongside voice quality, in individuals with autism spectrum disorder (ASD). However, findings across studies regarding these acoustic features in ASD remain inconsistent. Literature searches across four databases identified eligible studies comparing prosodic or voice quality acoustic parameters between individuals with ASD and matched TD individuals. A total of 40 studies involving 1023 individuals with ASD and 929 TD individuals were included. Subgroup and meta-regression analyses were conducted to assess potential moderators. The meta-analyses revealed a significantly higher mean pitch (Hedges' g = 0.43), broader pitch range (g = 0.29), and higher pitch standard deviation (g = 0.22) in the ASD group. For voice quality, significantly reduced shimmer (g = -0.44) and a trend toward reduced jitter (g = -0.26) indicated heightened stability of vocal fold vibrations in ASD. Our findings reveal a seemingly paradoxical acoustic profile in ASD: while individuals with ASD exhibit suprasegmental instability, they also demonstrate voicing hyper-stability. Moderators identified after subgroup and meta-regression analyses, including language background, IQ status, age span, mean age, and task type, may further moderate the prosodic features.
2026-06-01 | Medical treatment of autism spectrum disorder in children: Current evidence, controversies, and clinical challenges.
Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition associated with debilitating comorbidities [e.g., aggression, irritability, gastrointestinal (GI) issues]. Medical management primarily targets these symptoms, as no drug is Food and Drug Administration-approved for core social-communication deficits. To synthesize the efficacy and safety of five major pharmacological classes and evaluate the emerging evidence for biomarker-driven (precision medicine) interventions in pediatric ASD. Following PRISMA guidelines, we systematically reviewed randomized controlled trials (RCTs) for five classes: Atypical antipsychotics, stimulants, selective serotonin reuptake inhibitors, metabolic/nutritional, and microbiota-gut-brain axis agents. Quantitative meta-analysis for antipsychotics (n = 5 RCTs pooled) used the random-effects model, reporting I 2 to quantify heterogeneity. Atypical antipsychotics are the only drugs with robust, established efficacy for severe irritability: Pooled analysis for risperidone (n = 3 RCTs) showed a significant mean difference of approximately -11.0 on Aberrant Behavior Checklist-Irritability subscale (I 2 approximately 72%). Risperidone carries a greater metabolic burden (e.g., weight gain) than aripiprazole. Stimulants and selective serotonin reuptake inhibitors, respectively. Emerging therapies demonstrate targeted potential: Microbiota transfer therapy significantly improved GI and behavioral symptoms in cohorts with GI disease. Similarly, the efficacy of High-dose folinic acid was concentrated in the subgroup with folate receptor-α autoantibodies. The management of ASD demands a shift to a precision medicine model, as the efficacy of interventions is highly variable and concentrated in specific patient subgroups. Future research must prioritize the validation of biological biomarkers (metabolic, genetic, neurophysiological) to reliably predict treatment response, guiding the selection of targeted therapies, and addressing current evidence gaps.
2026-05-28 | Microglia, cerebellar inflammation, and autism spectrum disorders: Developmental mechanisms and therapeutic perspectives.
Autism spectrum disorders (ASD) are neurodevelopmental conditions characterized by deficits in social interaction and communication, as well as restricted and repetitive behaviors. These conditions often co-occur with medical issues linked to synaptic alterations, which compromise synaptic integrity and are associated with brain circuit dysfunction. Both human and animal studies have identified cerebellar structural and functional alterations in subsets of ASD cases, with evidence of abnormal morphology and disrupted connectivity correlating with symptom severity. Numerous studies further suggest that neuroinflammation and microglia dysfunction may contribute to atypical cerebellar development during critical postnatal windows and may be associated with ASD-like phenotypes. However, the timing and mechanisms underlying the onset of these processes remain unclear, and a primary causal role in human ASD has not been established. This review synthesizes current knowledge on microglia in early stages of cerebellar development and discusses how cerebellar inflammation could be linked to ASD-related phenotypes. A better understanding of these pathological processes and their behavioral correlates may reveal opportunities for early-life intervention strategies.
gene therapies
2026-07-23 | CRISPR/Cas9-Engineered HEK293T Cellular Model Harboring the Pathogenic CDKL5 c.172A>T Variant Recapitulates Core Molecular Phenotypes of CDKL5 Deficiency Disorder.
Mutations in the CDKL5 gene are strongly associated with severe neurodevelopmental disorders, including atypical Rett syndrome and autism spectrum disorder (ASD). This study aimed to establish a cell model carrying a targeted CDKL5 mutation using the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system and to evaluate the phenotypic and molecular consequences. A single-guide RNA (sgRNA) targeting exon 2 of CDKL5 was designed using in silico tools to minimize off-target activity. The sgRNA and Cas9 nuclease were cloned into the pSpCas9(BB)-2A-green fluorescent protein (GFP) (PX458) vector and transfected into human embryonic kidney 293T (HEK293T) cells. Following fluorescence-activated cell sorting (FACS), genome-editing efficiency was quantified using a T7 endonuclease I (T7E1) assay and Sanger sequencing. Homology-directed repair (HDR) mediated by single-stranded oligodeoxynucleotide (ssODN) templates was used to introduce a specific missense mutation (c.172A>T; p.Lys58Met). Edited clones were evaluated for CDKL5 expression using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and cell survival and apoptosis were assessed using Annexin V/propidium iodide (PI) staining and caspase-3 activity assays. The CRISPR/Cas9 construct achieved a mean on-target editing efficiency of 41.6 ± 3.2%, as determined by T7E1 digestion, and sequencing confirmed a heterozygous insertion in 28% of sorted clones. HDR-mediated precise editing was detected in 12% of clones. RT-qPCR analysis showed a 55% reduction in CDKL5 mRNA levels (P < 0.01) in edited cells, whereas Western blotting demonstrated a corresponding 48% decrease in protein expression. Functionally, mutant cells exhibited 25% lower viability (P < 0.05) and 2.3-fold higher apoptosis rates (P < 0.01) than wild-type controls. No significant off-target mutations were detected at the top five predicted loci. We successfully generated a human cell line model of CDKL5-related ASD using CRISPR/Cas9 technology. The mutation induced marked reductions in CDKL5 expression and cell survival. Although this HEK293T-based model provides a useful platform for mechanistic and screening studies, its non-neuronal origin limits its ability to fully recapitulate the neuronal context of CDKL5 deficiency disorder (CDD). This study establishes a novel, precisely engineered human cellular model using advanced CRISPR/Cas9 technology to mechanistically dissect the consequences of CDKL5 deficiency. By introducing a defined missense mutation (c.172A>T; p.Lys58Met) into HEK293T cells, this study provides a robust platform for investigating the role of CDKL5 in neurodevelopmental disorders and supports future therapeutic development.
2026-03-30 | Autism Spectrum Disorder in the Genomic Era: A Comprehensive Review of Etiology, Precision Diagnostics, Clinical Outcomes, and Emerging Gene-Editing Therapies.
Autism spectrum disorder (ASD) is a heterogeneous, lifelong neurodevelopmental condition characterized by deficits in social communication and restricted, repetitive behaviors. Over recent decades, diagnostic expansion and methodological advances have led to increased prevalence estimates and a deeper appreciation of phenotypic, etiological, and outcome heterogeneity. This review synthesizes evidence from 2015-2024 across epidemiology, clinical diagnosis, neurobiology, genetics, environmental risk factors, mortality, and treatment. We summarize robust genetic contributions, including polygenic risk from common variants and high-impact rare or de novo mutations converging on synaptic function, chromatin regulation, and neurodevelopmental pathways. Prenatal and perinatal environmental exposures such as maternal immune activation, air pollution, and selected teratogens interact with genetic susceptibility through inflammatory, oxidative, and epigenetic mechanisms to influence ASD risk. Neuroimaging and multimodal studies reveal altered cortical developmental trajectories and atypical large-scale network connectivity associated with core symptoms and common comorbidities. Mortality studies demonstrate increased all-cause and cause-specific mortality, particularly related to epilepsy, medical comorbidities, and injury, with highest risk observed in individuals with intellectual disability. Current treatments remain primarily symptomatic, with early, intensive, and individualized behavioral interventions providing the greatest functional benefit, while pharmacotherapy targets associated behavioral challenges. Emerging genomic technologies, including CRISPR-based approaches, offer powerful experimental models and potential precision therapies for selected monogenic or high-impact copy number variant-associated ASD, although substantial safety, delivery, and ethical challenges remain. We conclude by highlighting priorities for integrative longitudinal studies, mechanistic links between molecular and circuit-level dysfunction, and responsible translational pathways toward precision therapeutics.
2025-02-11 | Interpersonal synchronization: An overlooked factor in development, social cognition, and psychopathology.
Intact social functioning relies on a combination of explicit and implicit behavioral, attentional, and interpersonal processes referred to as "social cognition". Characterizing these interpersonal processes forms a critical underpinning to understanding and treating psychopathology, particularly in disorders where deficits in social functioning do not emerge as a secondary symptom but rather as an essential feature of the disorder. Two of such disorders are autism spectrum disorders (ASD) and schizophrenia spectrum disorders (SZ). However, despite the substantial overlap in the features of social dysfunction between ASD and SZ, including social cognitive deficits in theory of mind, perspective-taking, and empathy, there is a limited understanding of the mechanisms underlying those shared deficits, and how to treat them. We suggest that disruptions of interpersonal functioning emerge over the course of development, and that interpersonal synchronization, a phenomenon in which behavioral and physiological cues align between interacting partners, forms a critical component of social cognition that underlies the disruption in social functioning in ASD and SZ. We present a conceptual review of typical and atypical development of social processes and highlight the role of interpersonal synchronization across the course of development. Then, we review the existing evidence suggesting impairments in both the intentional and spontaneous synchronization of interpersonal processes in ASD and SZ, as well as studies suggesting that interpersonal synchronization and clinical symptoms may be improved through body-oriented interventions within these disorders. Finally, we suggest potential mechanisms that may underpin typical and atypical development of interpersonal synchronization.
2024-12-14 | Short report on a distinct electroencephalogram endophenotype for MTHFR gene variation co-occurring in autism spectrum disorder.
Anecdotal reports link a distinct, bilateral, parieto-temporally generated 4.5-Hz rhythm on an electroencephalogram to a methylenetetrahydrofolate reductase gene variant co-occurring in autism spectrum disorder, but the validation of its precision is needed. The electroencephalograms of children with autism spectrum disorder showing the distinct bilateral parieto-temporally generated 4.5-Hz rhythm and their clinical chart report on polymerase chain reaction screening for methylenetetrahydrofolate reductase gene variants, 677C>T and 1298A>C, were retrieved from an outpatient clinic between February 2019 and April 2024. Twenty-five cases were identified. Patients were between 2 and 12 (7 ± 3) years old from Asian (n = 16, 64%), European (n = 5, 20%), African (n = 1, 4%) and mixed (n = 3, 12%) ethnicities. Twenty patients (80%) were positive for 677 C>Theterozygous (n = 3, 15%), 1298A>Cheterozygous (n = 8, 40%) or both (n = 9, 45%). The polymerase chain reaction testing detected neither variant in 5 (20%) patients. Therefore, the electroencephalogram-endophenotype showed 80% precision in identifying methylenetetrahydrofolate reductase gene variant within the sample. This preliminary data support the precision of the proposed distinct, bilateral, parieto-temporally generated 4.5-Hz rhythm in identifying methylenetetrahydrofolate reductase gene variants and its potential clinical applications as a valuable, non-invasive and objective measure within the population.Lay abstractMethylenetetrahydrofolate reductase mutations refer to genetic variations in the methylenetetrahydrofolate reductase enzyme, which plays an important role in folate metabolism. Folate is essential for neural development and signalling. Children with autism spectrum disorder have atypical neural signals compared with control. This study used a non-invasive method to identify a distinct neural signal that may be useful in future screening for methylenetetrahydrofolate reductase mutation in children with autism spectrum disorder. Given that the underlying causes of autism spectrum disorder have multiple genetic factors and often require subjective assessment, this study introduces a potential non-invasive screening method for methylenetetrahydrofolate reductase gene mutation. This method could provide valuable biomarkers for screening and personalised treatments, offering hope for improved risk stratification and bespoke nutritional support and supplements to mitigate the impact on affected individuals and their descendants.
2023-05-28 | SOX7: Novel Autistic Gene Identified by Analysis of Multi-Omics Data
ABSTRACT Background Genome-wide association studies and next generation sequencing data analyses based on DNA information have identified thousands of mutations associated with autism spectrum disorder (ASD). However, more than 99% of identified mutations are non-coding. Thus, it is unclear which of these mutations might be functional and thus potentially causal variants. Transcriptomic profiling using total RNA-sequencing has been one of the most utilized approaches to link protein levels to genetic information at the molecular level. The transcriptome captures molecular genomic complexity that the DNA sequence solely does not. Some mutations alter a gene’s DNA sequence but do not necessarily change expression and/or protein function. To date, few common variants reliably associated with the diagnosis status of ASD despite consistently high estimates of heritability. In addition, reliable biomarkers used to diagnose ASD or molecular mechanisms to define the severity of ASD do not exist. Objectives It is necessary to integrate DNA and RNA testing together to identify true causal genes and propose useful biomarkers for ASD. Methods We performed gene-based association studies with adaptive test using genome-wide association studies (GWAS) summary statistics with two large GWAS datasets (ASD 2019 data: 18,382 ASD cases and 27,969 controls [discovery data]; ASD 2017 data: 6,197 ASD cases and 7,377 controls [replication data]) which were obtained from the Psychiatric Genomics Consortium (PGC). In addition, we investigated differential expression for genes identified in gene-based GWAS with a RNA-seq dataset (GSE30573: 3 cases and 3 controls) using the DESeq2 package. Results We identified 5 genes significantly associated with ASD in ASD 2019 data (KIZ-AS1, p=8.67×10 −10 ; KIZ, p=1.16×10 −9 ; XRN2, p=7.73×10 −9 ; SOX7, p=2.22×10 −7 ; PINX1-DT, p=2.14×10 −6 ). Among these 5 genes, gene SOX7 (p=0.00087), LOC101929229 (p=0.009), and KIZ-AS1 (p=0.059) were replicated in ASD 2017 data. KIZ (p=0.06) was close to the boundary of replication in ASD 2017 data. Genes SOX7 (p=0.0017, adjusted p=0.0085), LOC101929229 (also known as PINX1-DT, p=5.83×10 −7 , adjusted p=1.18×10 −5 ), and KIZ (p=0.00099, adjusted p=0.0055) indicated significant expression differences between cases and controls in the RNA-seq data. SOX7 encodes a member of the SOX (SRY-related HMG-box) family of transcription factors pivotally contributing to determining of the cell fate and identity in many lineages. The encoded protein may act as a transcriptional regulator after forming a protein complex with other proteins leading to autism. Conclusion Gene SOX7 in the transcription factor family could be associated with ASD. This finding may provide new diagnostic and therapeutic strategies for ASD.
antibodies
2025-12-12 | Comprehensive multi-omics mapping of immune perturbations in autism spectrum disorder.
Autism spectrum disorder (ASD) is increasingly recognized as a neurodevelopmental condition with systemic immunological involvement, yet the underlying immune mechanisms remain incompletely defined. To delineate the peripheral immune landscape in ASD using integrated multi-omics profiling and to determine how immune and immunometabolic alterations relate to clinical severity. Circulating immune cells from individuals with ASD were profiled using multicolor flow cytometry, single-cell RNA sequencing, and bulk RNA sequencing. Plasma proteomic and metabolomic analyses were performed to identify immune-related and metabolic biomarkers. Immune features were evaluated for associations with clinical severity measures. Multi-omics profiling revealed marked immune dysregulation in ASD, with significant shifts in immune cell subsets and inflammatory signatures that correlated with clinical severity. T cell abnormalities included reduced frequencies and a skewed Th1/Th2 balance, consistent with a chronic inflammatory milieu. Natural killer (NK) cells showed increased activation but impaired cytotoxic capacity, accompanied by expansion of an atypical NK subset. Myeloid-derived suppressor cells (MDSCs) and hyperinflammatory CD56+ monocytes were elevated. Transcriptomic analyses corroborated broad immune activation, prominently implicating interferon-driven and antiviral signaling pathways. Plasma metabolomics and proteomics further indicated disruptions in purine metabolism and oxidative phosphorylation, alongside increased inflammatory markers, which were significantly associated with symptom severity. These findings support a systemic immunometabolic framework in ASD characterized by concurrent immune activation and altered myeloid/NK cell states, providing mechanistic context for peripheral biomarkers linked to clinical phenotype. Integrated multi-omics profiling identifies robust peripheral immune and metabolic disturbances in ASD. The dysregulated immune subsets, activated immune pathways, and plasma biomarker signatures highlight potential avenues for biomarker-driven stratification and immune-targeted therapeutic development in ASD. T cell dysregulation, NK cell impairment, and myeloid expansion indicate a chronic inflammatory state and immune exhaustion phenotype associated with ASD severity. Plasma metabolomic and proteomic alterations, including disrupted oxidative phosphorylation and elevated inflammatory markers, correlate with ASD severity and highlight potential biomarkers. Multi-omics profiling links peripheral immune dysregulation to neurodevelopmental abnormalities, providing a framework for immune-targeted ASD interventions.
2017-03-20 | Face perception and learning in autism spectrum disorders.
Autism Spectrum Disorder (ASD) is characterized by impairment in social communication and restricted and repetitive interests. While not included in the diagnostic characterization, aspects of face processing and learning have shown disruptions at all stages of development in ASD, although the exact nature and extent of the impairment vary by age and level of functioning of the ASD sample as well as by task demands. In this review, we examine the nature of face attention, perception, and learning in individuals with ASD focusing on three broad age ranges (early development, middle childhood, and adolescence/adulthood). We propose that early delays in basic face processing contribute to the atypical trajectory of social communicative skills in individuals with ASD and contribute to poor social learning throughout development. Face learning is a life-long necessity, as the social world of individual only broadens with age, and thus addressing both the source of the impairment in ASD as well as the trajectory of ability throughout the lifespan, through targeted treatments, may serve to positively impact the lives of individuals who struggle with social information and understanding.
2015-12-02 | Autism spectrum disorder in infancy: developmental considerations in treatment targets.
This review explores recent literature to prioritize aspects of development to be targeted by intervention for infants and toddlers with autism spectrum disorder (ASD). Recent investigation of early development in ASD, including prospective studies of infants at increased risk (i.e., those with an affected older sibling) identifies impairments in four key developmental domains that are predictive of ASD. These domains are early attentional control, emotion regulation, social orienting/approach, and communication development. Reciprocal relationships exist among these domains, both in ASD and in typical development. Thus, these domains represent key intervention targets, informing treatment models under investigation in recent clinical trials. By targeting the earliest and foundational manifestations of atypical development, we can capitalize on neural plasticity and build skills that are most likely to have scaffolding effects on development. The optimal timing and procedures of intervention remain empirical questions, but as the field moves toward earlier identification of risk, we are now poised to evaluate the impact of tailored approaches before the developmental cascade that leads to ASD is fully manifested. Consideration regarding community translation of ASD-specific interventions for infants and toddlers is also needed, with a focus on feasibility, cost-effectiveness, and sustainability.
2015-05-19 | Sex Differences in Autism Spectrum Disorders: Does Sex Moderate the Pathway from Clinical Symptoms to Adaptive Behavior?
Abstract We explored sex differences in diagnostic categories, clinical symptoms and adaptive behavior of persons with autism spectrum disorders, as well as sex-specific correlations of clinical and adaptive caracteristics. The study involved 108 patients (83 males, 6.73 ± 4.33 years old) diagnosed with autism spectrum disorders (ASD). Assessment included ADI-R and Vineland Adaptive Behavior Scale II. Males were more often diagnosed with typical autism. There were no sex differences in the autistic symptoms, while females showed better functioning in Daily living skills, without reaching statistically significant difference (p = 0.062). We have found different associations of autistic symptoms with different aspects of adaptive behavior in males and females. Social reciprocity in females correlated with social domain of adaptive behavior, in a positive direction. Our findings have shown that although there are no sex differences in autistic symptoms, females tend to be somewhat more functional and are also less frequently diagnosed with typical autism. Our results have also shown that sex might moderate the way clinical symptoms are expressed in adaptive behavior. Social reciprocity might be the core feature regarding sex differences in ASD. Our findings might have diagnostic and therapeutical implications, pointing out to the need for individualized, sex-specific treatment in this group of disorders.
2013-01-14 | Looking but not seeing: atypical visual scanning and recognition of faces in 2 and 4-year-old children with autism spectrum disorder.
This study used eye-tracking to examine visual scanning and recognition of faces by 2- and 4-year-old children with autism spectrum disorder (ASD) (N = 44) and typically developing (TD) controls (N = 30). TD toddlers at both age levels scanned and recognized faces similarly. Toddlers with ASD looked increasingly away from faces with age, atypically attended to key features of faces, and were impaired in face recognition. Deficits in recognition were associated with imbalanced attention between key facial features. This study illustrates that face processing in ASD may be affected early and become further compromised with age. We propose that deficits in face processing likely impact the effectiveness of toddlers with ASD as social partners and thus should be targeted for intervention.
other
2026-06-04 | Olfactory Valence-Processing Deficits and Aberrant Brain Network Connectivity Underlie Social Dysfunction in Shank3-/- ASD Model Mice.
Olfaction is crucial for rodent social behavior, and olfactory dysfunction has been observed in multiple autism spectrum disorder (ASD) models, but its phenotype in Shank3⁻/⁻ mice (a classic ASD model) remains unclear. We systematically assessed olfactory function in Shank3⁻/⁻ mice by using a modified olfactory three-chamber test and optimized ultrasonic vocalization (USV) detection in combination with resting-state functional magnetic resonance imaging (rs-fMRI), whole-brain c-Fos mapping, and three-dimensional (3D) behavioral analysis. Our results showed abnormal odor preference and hyperconnectivity in olfaction-associated brain networks. Upon exposure to neutral, appetitive, and social pheromone odors, Shank3⁻/⁻ mice displayed atypical whole-brain c-Fos activation patterns, which were coupled with synchronized locomotor suppression and stereotyped behaviors. This study maps the neural-behavioral responses to odors in Shank3-/- mice, linking olfactory deficits to autism-like behaviors, and highlights the olfactory system as a targetable pathway for sensory-based autism therapies.
2026-02-06 | Sex specific effects of adoptive Tregs transfer on the brain and periphery in maternal immune activation offspring rescuing immune dysregulation.
Autism spectrum disorder (ASD) is characterized by atypical communication, social interactions, and restricted interests. In ASD, there are dysfunctional immune regulatory control mechanisms that can lead to immune activation. Notably lower frequencies of regulatory T cells (Tregs) and reduced immunosuppressive cytokines are reported and associated with more impaired behaviors impacting both individuals with autism and their families. Therefore, therapeutic approaches that enhance immune regulation may offer substantial benefits. Using the maternal immune activation (MIA) model, we investigated whether adoptive transfer of wildtype Tregs into MIA offspring recipients could rescue immune activation, brain transcriptome changes and behaviors exhibited in adult MIA offspring. We also aimed to explore potential sex-differences in responses. In male but not female MIA offspring, Tregs transfer reduced the frequency of T helper (TH)-17 (RORγT+ CD4+) T cells in both the mesenteric lymph node (MLN) and spleen. Moreover, the frequency of CD25+Foxp3+ T cells was increased in the MLN and spleen of male but not female MIA offspring following Treg transfer. Splenocytes from male MIA offspring receiving Tregs showed reduced production of inflammatory cytokines (e.g., IL-6 and TNFα) following PMA/Ionomycin stimulations. In contrast, female MIA offspring that received Tregs exhibited different cytokine profiles characterized by increased production of cytokines, including GM-CSF, IFNγ, and IL-10. In the brain, bulk mRNA sequencing in the cerebellum, frontal cortex, and hippocampus revealed that Tregs-treated male MIA offspring had differentially expressed genes involved in neurodevelopmental disorders, synaptic function, and epigenetic regulation. Minimal gene expression differences were observed in female counterparts. There was significant improvement in self-grooming behaviors in males MIA offspring that received Tregs. In females, social novelty improved after Tregs treatment. In summary, adoptive Tregs transfer reduced systemic inflammation, brain transcription and behavior alterations in a sex dependent manner in the context of MIA. These findings suggest that adoptive Treg transfer may represent a viable therapeutic avenue for mitigating systemic inflammation and comorbidities associated with MIA and neurodevelopmental disorders such as ASD.
2025-07-07 | Stem Cell Therapy and Models for Autism Spectrum Disorder: Insights and Research.
Autism Spectrum Disorders (ASD) are complex neurodevelopmental conditions characterized by impaired social communication, repetitive behavior patterns, and atypical sensory perception. The Autism and Developmental Disabilities Monitoring Network reports that approximately 1 in 36 children are diagnosed with ASD, highlighting the increasing prevalence and the pressing need for innovative treatment approaches. Medications commonly used in ASD primarily aim to manage associated symptoms, as there are currently no FDA-approved medications specifically for treating ASD core symptoms. Stem cells have demonstrated significant potential in cell-based therapies for ASD and have been utilized in in vitro models to investigate the pathogenesis of the condition. This review focuses on the recent advancements in stem cell-based transplantation in animal models of ASD, aiming to explore the improvement of ASD symptoms and the underlying mechanisms involved. It also discussed the application of stem cell-based transplantation in pediatric and adolescent populations with ASD to evaluate treatment efficacy and potential preventive strategies. Furthermore, recent efforts are addressed in developing stem cell-based models for both syndromic and non-syndromic forms of ASD, emphasizing studies that utilize cerebral organoids for modeling ASD, which facilitate the exploration of disease mechanisms within a tissue-like environment.
2024-11-04 | Altered Functional Connectivity of Unimodal Sensory and Multisensory Integration Networks Is Related to Symptom Severity in Autism Spectrum Disorder.
Atypical sensory processing is a prevalent feature of autism spectrum disorder (ASD) and constitutes a core diagnostic criterion in DSM-5. However, the neurocognitive underpinnings of atypical unimodal and multimodal sensory processing and their relationships with autism symptoms remain unclear. In this study, we examined intrinsic functional connectivity (FC) patterns among 5 unimodal sensory and multisensory integration (MSI) networks in ASD using a large multisite dataset (N = 646) and investigated the relationships between altered FC, atypical sensory processing, social communicative deficits, and overall autism symptoms using correlation and mediation analyses. Compared with typically developing control participants, participants in the ASD group demonstrated increased FC of the olfactory network, decreased FC within the MSI network, and decreased FC of the MSI-unimodal sensory networks. Furthermore, altered FC was positively associated with autism symptom severity, and such associations were completely mediated by atypical sensory processing and social communicative deficits. ASD-specific olfactory overconnectivity and MSI-unimodal sensory underconnectivity lend support to the intense world theory and weak central coherence theory, suggesting olfactory hypersensitivity at the expense of MSI as a potential neural mechanism underlying atypical sensory processing in ASD. These atypical FC patterns suggest potential targets for psychological and neuromodulatory interventions.
2023-01-17 | An Early Enriched Experience Drives an Activated Microglial Profile at Site of Corrective Neuroplasticity in Ten-m3 Knock-Out Mice.
Environmental enrichment (EE) is beneficial for brain development and function, but our understanding of its capacity to drive circuit repair, the underlying mechanisms, and how this might vary with age remains limited. Ten-m3 knock-out (KO) mice exhibit a dramatic and stereotyped mistargeting of ipsilateral retinal inputs to the thalamus, resulting in visual deficits. We have recently shown a previously unexpected capacity for EE during early postnatal life (from birth for six weeks) to drive the partial elimination of miswired axonal projections, along with a recovery of visually mediated behavior, but the timeline of this repair was unclear. Here, we reveal that with just 3.5 weeks of EE from birth, Ten-m3 KOs exhibit a partial behavioral rescue, accompanied by pruning of the most profoundly miswired retinogeniculate terminals. Analysis suggests that the pruning is underway at this time point, providing an ideal opportunity to probe potential mechanisms. With the shorter EE-period, we found a localized increase in microglial density and activation profile within the identified geniculate region where corrective pruning was observed. No comparable response to EE was found in age-matched wild-type (WT) mice. These findings identify microglia as a potential mechanistic link through which EE drives the elimination of miswired neural circuits during early postnatal development. Activity driven, atypical recruitment of microglia to prune aberrant connectivity and restore function may have important therapeutic implications for neurodevelopmental disorders such as autistic spectrum disorder.
Access all drug discovery papers and probability of success in trials forecasts:
Access all drug discovery papers and probability of success in trials forecasts:
Drug Discovery Landscape
1 orphan drug designation for Atypical autism.
1 orphan drug designation for Atypical autism.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
Fluoxetine | small molecules | FDA | 1999-04-30 | — | Neuropharm, Ltd. |
Let's accelerate rare disease drug discovery
Let's accelerate drug discovery
Get access to Explority AI’s forecasts to outperform average preclinical success rates. Whether you’re expanding your R&D pipeline, evaluating a partnership, or simply have a question — we’d love to hear from you.