Molecular Autism最新文献

{"title":"Reduced inter-subject functional connectivity during movies in autism: replicability across cross-national fMRI datasets.","authors":"Feng Lin, Laura Albantakis, Tuomo Noppari, Severi Santavirta, Marie-Luise Brandi, Lihua Sun, Lasse Lukkarinen, Pekka Tani, Juha Salmi, Lauri Nummenmaa, Juergen Dukart, Leonhard Schilbach, Juha M Lahnakoski","doi":"10.1186/s13229-026-00707-2","DOIUrl":"10.1186/s13229-026-00707-2","url":null,"abstract":"<p><p>BACKGROUND: Autism is a neurodevelopmental disorder characterized by repetitive behaviors and difficulties in social communication and interaction. Previous research has shown that these symptoms are linked to idiosyncratic behavioral and brain activity patterns while viewing natural social events in movies. This study aimed to investigate the replicability of brain activity idiosyncrasy in adult autistic individuals by comparing their inter-subject functional connectivity (ISFC) with that of neurotypical individuals. METHODS: We tested for ISFC differences between adult autistic and neurotypical groups using functional magnetic resonance imaging (fMRI) data from two independent datasets from Germany (Nneurotypical = 25, 7 Males, 18 Females; Nautism = 22, 12 Males, 10 Females) and Finland (Nneurotypical = 19, Nautism = 18; All males). Participants watched short movie stimuli, and pairwise ISFCs were computed across 273 brain regions. Group differences were evaluated using subject-wise permutation tests for each dataset. RESULTS: In both datasets, the autistic group showed lower ISFCs compared to the neurotypical group, specifically between visual regions (e.g., occipital gyrus, cuneus) and parietal regions (e.g., superior and inferior parietal lobules), as well as between visual regions and frontal regions (e.g., inferior frontal gyrus, precentral gyrus). ISFC was higher in the Finnish autistic group in temporal regions associated with sound and speech processing. LIMITATIONS: Larger multi-site datasets using diverse analysis pipelines are needed to evaluate the robustness and replicability of current findings. They are also essential for evaluating the reliability of the subject-wise permutation method without explicit correction for multiple comparisons. CONCLUSIONS: The study confirmed the replicability of reduced ISFCs in adult autistic individuals during naturalistic movie-watching, especially between visual and parietal/frontal brain regions. These findings reinforce the utility of ISFC and naturalistic movie-watching paradigm in studying neural connectivity alterations in autism.</p>","PeriodicalId":18733,"journal":{"name":"Molecular Autism","volume":" ","pages":"11"},"PeriodicalIF":5.7,"publicationDate":"2026-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12922298/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146213061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cholecystokinin upregulation in mPFC leads to social defeat-induced anxiety susceptibility in neuroligin 3 R451C knockin mice.","authors":"Yuzhen Fu, Yuke Xu, Huiyi Li, Kaipeng Jiang, Qun Yang, Zhiyuan Li, Jialin Chen, Yingwei Ju, Keying Xu, Hangtian Yan, Jiali Ge, Sien Li, Kexian Yan, Wenjie Dou, Xintai Wang, Jianhong Luo, Baoming Li, Wei Cao","doi":"10.1186/s13229-026-00708-1","DOIUrl":"10.1186/s13229-026-00708-1","url":null,"abstract":"<p><p>BACKGROUND: Anxiety is a prevalent and clinically debilitating comorbidity in autism spectrum disorder (ASD), yet its underlying neurobiological mechanisms remain incompletely elucidated. This study aimed to investigate the role of dysregulated cholecystokinin (CCK) signaling within the medial prefrontal cortex (mPFC) in mediating stress-induced anxiety susceptibility in ASD. METHODS: Using Neuroligin 3 R451C knockin (KI) mice, a genetically validated ASD model, we examined the developmental trajectory of CCK-expressing neurons in the mPFC through immunohistochemistry. Elevated plus maze tests were conducted to assess baseline anxiety and susceptibility to social defeat stress (SDS) across developmental stages. In vivo fiber photometry was employed to monitor SDS-induced mPFC CCK secretion dynamics. Functional manipulations included targeted knockdown and overexpression of Cck in mPFC excitatory neurons via viral-mediated gene transfer. RESULTS: We demonstrate a developmental perturbation in CCK-expressing excitatory neurons within the mPFC: their density increases sharply in early postnatal life, stabilizes during adolescence, and typically declines in adulthood in wild-type (WT) mice, yet remains persistently elevated in adult KI counterparts. In line with this anomaly, adult WT mice exhibit greater resilience to social defeat stress (SDS) than their adolescent counterparts, whereas KI mice sustain heightened anxiety susceptibility throughout adulthood—despite showing no baseline anxiety. Remarkably, SDS elicits a rapid and exaggerated surge in mPFC CCK secretion in adult KI mice, whereas WT controls exhibit a delayed and blunted response. Targeted knockdown of Cck in mPFC excitatory neurons significantly ameliorates SDS-induced anxiety-like behaviors in adult KI mice, whereas Cck overexpression in adult WT animals recapitulates the anxiogenic phenotype. LIMITATIONS: All experiments were conducted in male mice. Given the well-documented sex differences in the prevalence of ASD and anxiety disorders, further studies are warranted to determine whether similar effects occur in females. CONCLUSIONS: These findings implicate dysregulated CCK signaling within the mPFC as a mechanistic substrate for stress-induced anxiety in ASD, and provide a neurobiological framework for understanding the heightened affective vulnerability associated with this condition.</p>","PeriodicalId":18733,"journal":{"name":"Molecular Autism","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12961789/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146207356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cerebellar purkinje cell dysfunction contributes to gait impairments in Shank3-mutant mice.","authors":"Haiying Liu, Xin Huang, Guaiguai Ma, Xin Zhao, Ruixin Xia, Zimeng Li, Baolin Guo, Shengxi Wu, Wenting Wang","doi":"10.1186/s13229-026-00704-5","DOIUrl":"10.1186/s13229-026-00704-5","url":null,"abstract":"<p><p>BACKGROUND: Complex motor dysfunction is a common comorbidity of autism spectrum disorder (ASD) and may be attributed to the perturbation of cerebellar function. Purkinje cells (PCs), which serve as the primary output neurons of the cerebellum, are integral to various aspects of cerebellar motor function, such as gait control. However, the specific contribution of PCs to ASD has not been fully characterized. METHODS: In this study, we utilized adult male homozygous Shank3-knockout (Δ13–16, KO) mice, a well-established autism mouse model, to investigate the relationship between structural and functional deficits in PCs and impaired motor performance. Digital gait analysis was used to examine gait abnormalities. Changes in dendritic arborization and cell body area were measured using sparse labeling technology. In vitro electrophysiology was used to evaluate alterations in PC firing patterns in Shank3-KO mice. RESULTS: Shank3-KO mice displayed autistic-like behaviors (stereotyped grooming behavior and social disorders) and motor impairments. Gait impairment was obvious in Shank3-KO mice and was mainly spatiotemporal and anatomical in nature. The stand duration and swing duration decreased, the body speed and swing speed clearly increased, and the print position parameters changed. PCs, the sole output neurons of the cerebellar cortex, exhibited reduced line density in different lobules and decreased cell body area in Shank3-KO mice, accompanied by cellular hypoactivity. Notably, the optogenetic inhibition of PCs in wild-type (WT) mice induced gait impairments, whereas the excitation of PCs in Shank3-KO mice rescued gait abnormalities. LIMITATIONS: Although cerebellar dysfunction, particularly in PCs, is implicated in gait abnormalities, the contributions of other regions, such as the basal ganglia and cerebral cortex, remain to be fully elucidated. Similarly, within the cerebellar circuitry, other cell types, including granule cells and interneurons, are also likely involved. An important limitation of our study is its restriction to male mice, leaving potential sex-dependent differences unexplored. Future studies are therefore necessary to delineate the roles of these various brain regions and cell types and to examine their interactions in both sexes. CONCLUSIONS: In this study, we found that Shank3-KO mice exhibit deficits in motor performance and gait, which are also observed in ASD patients. These motor dysfunctions were strongly linked to cerebellar pathology, and we established that PC dysfunction underlies the disrupted gait patterns in this ASD model.</p>","PeriodicalId":18733,"journal":{"name":"Molecular Autism","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12947416/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146097254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sub-groups of spoken language and broader communication skills in a large heterogenous cohort of minimally verbal school-age children: evidence of discrepant profiles.","authors":"Jo Saul, Mollie Cooke, Supipi Munaweera, Danielle Matthews","doi":"10.1186/s13229-026-00701-8","DOIUrl":"10.1186/s13229-026-00701-8","url":null,"abstract":"<p><p>BACKGROUND: Communication and language profiles in neurodevelopmental conditions are characterised by enormous phenotypic heterogeneity. We sought to identify subgroups of Minimally Verbal (MV) children in a school-age transdiagnostic sample. We hypothesised that a cluster with a discrepant profile (strong receptive but low speech production and expressive spoken language skills) would emerge. METHODS: We recruited MV children and their families (n = 193; mean age 7.6 years (sd: 2.5, range 4–13); 73% male). The sample varied in their adaptive skills and range of diagnoses (autism 77%, genetic syndrome 15%). Children took part in a play-based experimenter-child interaction designed to elicit communicative acts such as requesting or sharing attention. Parents completed questionnaires about their child’s developmental profile, communicative and adaptive skills. Additional in-person batteries probed children’s motor, imitative and receptive language skills. The multi-task, multi-informant communication-related variables were then entered into a pre-registered agglomerative hierarchical cluster analysis. RESULTS: Six distinct clusters emerged and were compared in relation to non-social autism symptoms, motor skills, adaptive skills and demographic measures. For four clusters, children’s receptive, expressive, adaptive and motor skills were fairly commensurate and could be described as very low-, low-, mid- or high-skill. Two further clusters described discrepant profiles of ability where speech and spoken language skills were disproportionately lower. Exploratory analyses revealed that children in different clusters differed in terms of their diagnostic profiles, use of Augmentative and Alternative Communication (AAC) and echolalia. LIMITATIONS: Whilst the inclusive, trait-based, transdiagnostic approach taken has high ecological validity, some measures employed were thus necessarily bespoke, adapted or non-normed and reported diagnoses did not undergo systematic validation. CONCLUSION: The hypothesised discrepant profile emerged whereby some MV children had stronger receptive than expressive skills, suggesting motor barriers to speech that necessitate tailored support.</p>","PeriodicalId":18733,"journal":{"name":"Molecular Autism","volume":" ","pages":"8"},"PeriodicalIF":5.7,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12874986/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146086402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum and cerebral folate are normal in Down Syndrome Regression Disorder.","authors":"Jonathan D Santoro, Mackenzie Silverman, Lilia Kazerooni, Samuel T Otey, Maeve C Lucas, Mariam M Yousuf, Mellad M Koshnood, Noemi A Spinazzi, Eileen A Quinn, Catherine Franklin, Taryn R Liu, Shafali S Jeste, Michael S Rafii","doi":"10.1186/s13229-026-00703-6","DOIUrl":"10.1186/s13229-026-00703-6","url":null,"abstract":"<p><p>BACKGROUND: Neuropsychiatric regression in individuals with Down syndrome (DS), termed Down Syndrome Regression Disorder (DSRD), has been reported to occur in the 2nd and 3rd decade of life. Symptoms of DSRD include acute onset of encephalopathy, catatonia, hallucinations, obsessive compulsive tendencies and “new autistic” features. To determine whether abnormalities in folate transport and/or metabolism may play a role in the pathogenesis of this disorder, studies explored whether abnormalities in serum, red blood cell (RBC), or cerebrospinal fluid (CSF) 5-methyltetrahydrofolate (5-MTHF) are associated with DSRD. METHODS: Prospective observational cohort study of individuals with possible or probable DSRD diagnosed between July 1, 2019, and June 30, 2025, were evaluated. Inclusion required standardized neurodiagnostic testing, including lumbar puncture. Serum folate and RBC folate and CSF 5-MTHF samples were analyzed using high-performance liquid chromatography. Associations between folate levels and clinical variables were assessed. RESULTS: Sixty-seven individuals were enrolled. Median serum folate was 14 ng/mL (IQR 10–19) and RBC folate 729 ng/mL (IQR 604–1113); all but one recording (1%) was within the reference range. Median CSF 5-MTHF was 72 mmol/L (IQR 57–84), with all values within the normal range. In univariate, unadjusted, analyses, CSF 5-MTHF was associated with developmental regression (p = 0.04) and CSF abnormalities including elevated IgG index and oligoclonal bands (each p < 0.001), elevated total protein (p = 0.01), and pleocytosis (p = 0.03); all CSF 5-MTHF values remained within the reference range. After Benjamini–Hochberg FDR correction, associations with elevated IgG index, oligoclonal bands, and any abnormal LP finding remained significant (each q = 0.01). LIMITATIONS: This study is limited by its single center design and homogenous cohort of individuals with DSRD. In addition, this study did not have a control group of individuals with autism spectrum disorder or DS alone. CONCLUSIONS: Serum, RBC, and CSF folate concentrations are normal in individuals with DSRD, suggesting that systemic folate deficiency, and cerebral folate deficiency in particular, are not contributors to its pathogenesis. The authors advise that expanded testing for disorders of cerebral folate metabolism should not be performed in possible cases of DSRD in the absence of clinical symptoms consistent with these conditions.</p>","PeriodicalId":18733,"journal":{"name":"Molecular Autism","volume":"17 1","pages":"9"},"PeriodicalIF":5.7,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12922418/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146227156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing the psychometric properties of the Autism Diagnostic Observation Schedule - Generic (ADOS-G) in a clinical setting in the Chinese mainland.","authors":"Wuxia Enid Bai, Elinda Ai Lim Lee, Bahareh Afsharnejad, HuiJun Chih, Richard Parsons, Xiaobing Zou, Hongzhu Deng, Huilin Zhu, Sven Bölte, Sonya Girdler","doi":"10.1186/s13229-026-00702-7","DOIUrl":"10.1186/s13229-026-00702-7","url":null,"abstract":"<p><p>BACKGROUND: The awareness of autism spectrum condition (ASC) and the estimated prevalence rate are lower in the context of the Chinese mainland, compared to western countries. The Chinese adaptation of the Autism Diagnostic Observation Schedule – Generic (ADOS-G) has been widely used in the diagnostic process of ASC for many years despite its psychometric properties not having been established in a large clinical sample. Thus, the purpose of this study was to evaluate the metrics of the ADOS-G in a well characterized sample from a renowned child developmental-behavioural centre that provides clinical services to a nationwide reach of people in China. METHODS: The present study analysed a large retrospective record review of individuals who visited the centre’s outpatient clinic between January of 2018 and August of 2021. Participants in this study were divided into ASC (n = 2330) and non-ASC (n = 473) groups according to their clinical diagnosis. All participants completed the ADOS-G Chinese version, with 1333 administered Module 1, 867 Module 2 and 603 Module 3. Psychometric properties of the ADOS-G Chinese version were evaluated in terms of item characteristics, internal consistency, concurrent validity, and convergent validity. RESULTS: The ADOS-G Chinese version demonstrated different levels of internal consistency reliability for different domains, with low Cronbach alpha values for Communication domains (0.40-0.60), but higher for the Communication and Social Interaction combined domains (above 0.75). Evaluation of validity yielded good sensitivity (> 90%) and positive predictive values (> 0.85), but low specificity (0.15-0.60) and negative predictive values (around 0.60). Agreement between ADOS-G diagnosis and clinician’s diagnosis was fair (Cohen’s kappa ranging from 0.20 to 0.35 for different modules), but low between the ADOS-G and ADI-R (< 0.15). Almost all items of the ADOS-G differentiated between ASC and non-ASC. LIMITATIONS: Sample sizes were unevenly distributed between ADOS-G Modules 1 to 3, with Module 1 having the largest sample and none for Module 4. Retest reliability could not be assessed with the retrospective chart data. CONCLUSIONS: This study is the first to examine the ADOS-G Chinese adapted version in a large clinical sample in the Chinese mainland. The ADOS-G contributes valuable information to support the clinical diagnosis of ASC, though additional research into its psychometric properties and cultural adaptation in the Chinese mainland context may be necessary. This study highlights the importance of cultural validation and the considerations required when interpreting ADOS results in non-Western settings.</p>","PeriodicalId":18733,"journal":{"name":"Molecular Autism","volume":" ","pages":"6"},"PeriodicalIF":5.7,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12849687/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146018949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risk of hospitalization and death among autistic young people in England during the Covid-19 pandemic.","authors":"Brigid Saoirse Kennedy, Elizabeth Weir, Matthew C Fysh, Alex Tsompanidis, Rupert A Payne, Carrie Allison, Fiona E Matthews, Simon Baron-Cohen","doi":"10.1186/s13229-025-00698-6","DOIUrl":"10.1186/s13229-025-00698-6","url":null,"abstract":"&lt;p&gt;&lt;p&gt;BACKGROUND: Autistic people experience increased health vulnerability and risk of premature mortality; the Covid-19 pandemic posed a serious health risk globally. The present study estimated risks of (i) first hospitalization, (ii) first hospitalization with a positive Covid-19 test, (iii) all-cause death, and (iv) Covid-19 associated death from 1 January 2020–31 March 2021 among autistic people compared to matched peers in England. METHODS: We leveraged National Health Service records from 45,756 individuals, including 15,252 autistic individuals, via the Clinical Practice Research Datalink. Participants were matched 1:2 on birth year (± 2 years), gender, and general practitioner practice to 30,504 non-autistic people. The sample primarily comprised males and younger individuals, with a median age of 19.0 years (IQR = 12.0 years), which was expected based on the demographics of clinically diagnosed autistic people. For all outcomes, cox proportional hazards regression models were performed, accounting for matching criteria of gender, birth year, and clustering across GP practices. Additional models adjusting for matching criteria, as well as socioeconomic status, intellectual disability, obesity, alcohol misuse, and smoking were performed to assess risks of all-cause and Covid-19 related hospitalizations. However, due to perfect separation, it was not possible to conduct analyses for mortality that were adjusted for additional covariates (beyond matching factors), and Covid-19 related mortality modelling only assessed risk for male individuals. RESULTS: Autistic individuals had increased likelihood of all-cause hospitalization (HR: 1.32, 95% CI: 1.22–1.42, p &lt; .001) compared to matched peers, even after adjusting for intellectual disability, obesity, alcohol misuse, smoking, socioeconomic status, and matching factors. Autistic individuals had increased risk of Covid-19 related hospitalizations compared to matched non-autistic individuals when only accounting for matching factors; however, after adjusting for additional covariates of interest, autism did not remain a significant predictor of Covid-19 related hospitalization. In addition, while only models adjusting for matching factors could be performed, the results provide some evidence of heightened all-cause mortality risk for autistic individuals compared to matched non-autistic individuals during the covid period (HR = 2.47, 95% CI: 1.31–4.66, p = .005) and was inconclusive for Covid-19 associated deaths due to sparse events (HR = 1.26, 95% CI: 0.15–4.14, p = .79). LIMITATIONS: The study included a relatively young sample; thus, these results may be less applicable to older individuals and may underestimate effects for older individuals, as increasing age is a well-established risk factor for severe disease due to Covid-19 infection. In addition, due to low counts, analyses for mortality could only be adjusted for matching factors and the Covid-19 mortality analysis could only be cond","PeriodicalId":18733,"journal":{"name":"Molecular Autism","volume":" ","pages":"5"},"PeriodicalIF":5.7,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12849145/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145959757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Resting state aperiodic and periodic EEG activity in preschool-aged autistic children: differences from neurotypical peers and links to language skills.","authors":"Yanru Chen, Meagan Tsou, Charles A Nelson, Helen Tager-Flusberg, Carol L Wilkinson","doi":"10.1186/s13229-025-00700-1","DOIUrl":"10.1186/s13229-025-00700-1","url":null,"abstract":"<p><p>BACKGROUND: The neural mechanisms underpinning language development in autism spectrum disorder remain unclear. While prior studies have identified associations between resting-state EEG absolute power and language skills in autistic children, none have examined the distinct roles of aperiodic and periodic activity decomposed from the absolute power spectra on language development in autistic children. METHODS: At the group level, we examined resting-state power spectra differences between 64 neurotypical and 64 age-matched autistic children from 2 to 6 years old, as well as within the autistic group based on language impairment status. At the individual level, we examined whether aperiodic and periodic EEG features were associated with concurrent language skills measured by natural language samples and a standardized language assessment in participants with autism spectrum disorder. RESULTS: Autistic children exhibited higher aperiodic offset, but not aperiodic slope, compared to their neurotypical peers. While we did not find significant differences in peak alpha frequency and alpha peak amplitude between neurotypical and autistic children, after separating the autistic group by language impairment status, we found that autistic children with language impairment had significantly lower alpha peak amplitude compared to autistic children without language impairment and their age-matched neurotypical peers. Regarding the brain-language association, autistic children with lower aperiodic offset demonstrated better concurrent expressive and receptive language skills, but not nonverbal developmental quotient. Autistic children with higher alpha peak amplitude demonstrated better concurrent language and nonverbal developmental skills. LIMITATIONS: Findings were based on cross-sectional data from children with relatively higher socioeconomic backgrounds. Future studies are needed to explore the longitudinal relation between resting-state EEG aperiodic and periodic features and language development in autistic children, while accounting for potential confounding effects of demographic variability and data quality. CONCLUSIONS: The characteristic features of resting-state power differences vary when comparing autistic children to neurotypical peers versus comparing within the autistic subgroup based on language phenotypes. These findings underscore the importance of considering the heterogeneity of the autism spectrum when investigating the neural mechanisms underlying language development in autistic children.</p>","PeriodicalId":18733,"journal":{"name":"Molecular Autism","volume":" ","pages":"7"},"PeriodicalIF":5.7,"publicationDate":"2026-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12849409/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145948413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Loss of the Mecp2 gene in parvalbumin interneurons leads to an inhibitory deficit in the amygdala and affects its functional connectivity.","authors":"Maj Liiwand, Joni Haikonen, Bojana Kokinovic, Svetlana M Molchanova, Teemu Aitta-Aho, Sari E Lauri, Maria Ryazantseva","doi":"10.1186/s13229-025-00699-5","DOIUrl":"10.1186/s13229-025-00699-5","url":null,"abstract":"<p><strong>Background: </strong>The MECP2 gene is located on the X chromosome and encodes a methyl-CpG-binding protein 2 involved in transcriptional regulation. Loss-of-function mutations in the MECP2 gene lead to Rett syndrome, a severe neurodevelopmental disorder. The clinical picture of Rett syndrome includes, among other symptoms, social deficits, learning impairment, and heightened anxiety. The amygdala is a brain region responsible for emotional learning and is involved in the regulation of social behaviour as well as fear and anxiety. Parvalbumin interneurons tightly control the excitability, oscillation and synchronisation of the amygdala network, which are relevant to its functions. Here, we investigated the effects of Mecp2 gene ablation in parvalbumin interneurons on the microcircuit and functional connectivity of the mouse amygdala.</p><p><strong>Methods: </strong>Male mice with conditional knockout of the Mecp2 gene in parvalbumin interneurons were used as a genetic mouse model. Littermates with an intact gene were used as controls. Ex vivo brain slice electrophysiology, combined with pharmacology and optogenetics, was utilised to characterise microcircuits within the lateral amygdala. In vivo functional ultrasound imaging was used to visualise the connectivity within the amygdala-ventral hippocampus-prefrontal cortex network triad.</p><p><strong>Results: </strong>Loss of Mecp2 in parvalbumin interneurons significantly attenuated GABAergic synaptic input to principal neurons in the lateral amygdala. The deficit in inhibition was accompanied by higher excitability of local principal neurons in adult animals. A deficient in vivo functional connectivity of the amygdala with the ventral hippocampus and prefrontal cortex was observed in conditional knockouts.</p><p><strong>Limitations: </strong>This study used only male mice. Mecp2 knockout males exhibit shorter latency to symptom onset and lower phenotypic variability, making them suitable for mechanistic studies. Since previous studies in the field used males, we aimed to advance the existing body of research using the same approach. Finally, the link between the effects observed and possible behavioural alterations needs further investigation.</p><p><strong>Conclusions: </strong>Our study characterised the consequences of Mecp2 loss in parvalbumin interneurons on amygdala microcircuit function and connectivity within the prefrontal cortex‒amygdala‒hippocampus triad. It also provided evidence that supports and complements previous findings on the role of interneurons in the functional deficits observed in Mecp2 knockout animal models.</p>","PeriodicalId":18733,"journal":{"name":"Molecular Autism","volume":" ","pages":"4"},"PeriodicalIF":5.5,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12829049/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145906329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early developmental trajectory phenotypes for risk stratification of autism spectrum disorder in very preterm infants: a machine learning approach.","authors":"Li-Wen Chen, Yi-Tien Li, Chi-Hsiang Chu, Chin-Chin Wu, Ching-Lin Chu, Lan-Wan Wang, Han-Yi Tsai, Chung-Hsin Chiang, Chao-Ching Huang","doi":"10.1186/s13229-025-00692-y","DOIUrl":"10.1186/s13229-025-00692-y","url":null,"abstract":"<p><p>BACKGROUND: Very preterm infants are at elevated risk for autism spectrum disorder (ASD), though early identification is challenging due to overlapping neurodevelopmental disorders. While the Bayley Scales of Infant and Toddler Development (BSID) is widely used for follow-up, it remains unclear whether domain-specific developmental trajectories—such as cognition, receptive and expressive communication, and fine and gross motor function assessed by the BSID, Third Edition (BSID-III)—can support the development of a prediction model for ASD risk by preschool age in this population. METHODS: This population-based multicenter cohort study included infants born < 32 weeks’ gestation in 2011–2018. Neurodevelopment was assessed at 6, 12, and 24 months using domain-specific BSID-III scaled scores. ASD diagnosis was determined at age 5 years using the Autism Diagnostic Observation Schedule and the Autism Diagnostic Interview–Revised. Infants with congenital anomalies or severe sensorimotor impairments were excluded. Developmental trajectories were analyzed using locally estimated scatterplot smoothing. Six machine learning algorithms were used to evaluate ASD prediction based on neonatal risks and longitudinal domain-specific scaled score data. RESULTS: Of 583 very-preterm infants, 75 (12.9%) were diagnosed with ASD at preschool age. Infants later diagnosed with ASD exhibited persistently lower cognitive scores across the first two years of life (p < 0.05) and significantly slower development in receptive and expressive communication and fine motor skills during the second year (p < 0.0001 by 24 months) than infants without ASD. Gross motor trajectories did not differ significantly between groups. Integrating neurodevelopmental trajectories up to 24 months with neonatal risk factors improved prediction performance. The Support Vector Machine model yielded 71.8% accuracy (Area Under the Curve 0.69), with sensitivity of 64.2%, specificity of 72.9%, positive predictive value of 24.7%, and negative predictive value of 93.6%. LIMITATIONS: Although the model shows promise in identifying infants at low likelihood of ASD, its overall predictive performance remains modest. The model was developed in a single regional cohort, potentially limiting generalizability. CONCLUSIONS: Preterm infants later diagnosed with ASD exhibit distinct, domain-specific developmental trajectories. The model’s high negative predictive value suggests that developmental trajectory phenotypes may support early risk stratification by identifying infants at low likelihood of ASD.</p>","PeriodicalId":18733,"journal":{"name":"Molecular Autism","volume":" ","pages":"3"},"PeriodicalIF":5.7,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12805792/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145843899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}