Aggressive behaviors represent a common and clinically challenging comorbidity in individuals with autism spectrum disorder (ASD), yet the underlying neural mechanisms remain poorly understood. This study aimed to investigate the circuit-level pathology driving elevated aggression in Neuroligin-3 R451C knock-in mice (NL3R451C or KI mice). Aggressive behaviors in adult male mice were assessed using the resident-intruder and self-initiated aggression tests. Following the R-I test, c-Fos brain mapping was performed. Fiber photometry recording was used to capture neuronal activity in selected brain regions during attack bouts. Chemogenetic inhibition was applied to establish the causal role of specific neuronal subtypes or circuits in elevated aggression. Additive NL3 expression was used to examine the genetic contribution of distinct neuronal subpopulations to maladaptive aggression. NL3R451C mice exhibited heightened aggression and aggression-seeking behavior, accompanied by increased c-Fos expression in multiple brain regions, including the lateral hypothalamus (LH), prelimbic cortex (PrL), and ventral tegmental area (VTA). During attacks, KI mice showed enhanced calcium transients in LH GABAergic neurons and in PrL→LH glutamatergic neurons, but not in LH glutamatergic neurons. Critically, chemogenetic suppression of LH GABAergic neurons, or of LH neurons projecting to the VTA or periaqueductal gray (PAG), attenuated excessive aggression in KI mice, whereas inhibition of PrL→LH neurons had no effect. Moreover, additive NL3 expression specifically in LH GABAergic neurons, but not in PrL neurons, was sufficient to ameliorate the aggressive phenotype. First, the synaptic mechanisms underlying LH GABAergic dysregulation remain to be defined by direct electrophysiological characterization. Second, LH GABAergic neurons are heterogeneous, and our approach did not identify which specific subtype mediates excessive aggression. Third, our study used a male‑only design, reflecting the X‑linked clinical presentation of the NL3 R451C mutation. Future studies in female mutants could provide insights into sexual dimorphism and the underlying mechanisms. Fourth, NL3 rescue was achieved via viral‑mediated adult additive expression rather than developmental precisely genetic correcting. We conclude that hyperactive LH GABAergic neurons, caused by NL3 loss, is a core pathological mechanism underlying abnormal aggression in NL3R451C mouse model of ASD.
Autism early intervention meta-analyses have yielded important insights into questions such as ‘what works’ and ‘for what’ outcomes. However, because these studies primarily rely on study-level summary statistics, they may be limited with regard to more individualized insights. Mega-analyses utilizing individual participant data (IPD-MA) may be useful for these more individualized questions. We conducted an IPD-MA on the Autism Early Intervention Research (AEIR) consortium dataset, comprising n = 582 autistic children (n = 121 female) across 11 datasets collected in clinical and community settings in the USA, Switzerland, Italy, Israel, and Australia. Children received between 3 and 27 months of early intervention (age at start 13–60 months) of varying intensity. Of these datasets, one originates from a randomized controlled trial (RCT). Another 7 datasets are paired up into 5 separate controlled-group design studies, while the remaining 3 datasets come from uncontrolled pre–post design studies. Early Start Denver Model (ESDM; n = 281, 62 female) was compared against non-ESDM treatment-as-usual/community approaches (n = 301, 59 female) (e.g., speech and occupational therapy, applied behavioral analysis, pivotal response training). Outcome variables were Mullen Scales of Early Learning (MSEL) age-equivalent scores, Vineland Adaptive Behavior Scales (VABS) standardized scores, and Autism Diagnostic Observation Schedule (ADOS) calibrated severity scores. Predictors such as sex and cumulative intervention intensity were largely not associated with change in outcomes. Age at intervention start and pre-intervention developmental quotient (DQ) were strong moderators across all outcomes. Earlier age at intervention start predicted more positive outcomes, while higher pre-intervention DQ predicted accelerated growth on VABS motor and MSEL outcome measures. Interventions were similar in their effects on MSEL and VABS outcomes. However, for ADOS outcomes, ESDM resulted in significantly declining trajectories over time, with the sharpest decline for high pre-intervention DQ individuals. In contrast, ADOS trajectories in non-ESDM diverge in opposite directionalities (i.e. increases or decreases) depending on individual’s pre-intervention DQ. Data for the IDP-MA was contributed on a voluntary basis and only 1 study was contributed from an RCT. Therefore, the findings may be prone to self-selection bias that may limit generalizability. Inferences from the intervention type comparison (ESDM versus non-ESDM) may be limited due to the heterogeneous approaches lumped together in the non-ESDM category. Larger sample sizes are required for finer-grained comparisons of different intervention types. Age at intervention start and pre-intervention DQ are key individualized predictors and the latter can interact with intervention type to moderate early intervention response.
Autism spectrum disorder (ASD) affects social interaction, communication and behavioural flexibility. Recent theories grounded in the Bayesian Brain Framework propose that autistic individuals process environmental uncertainty differently, overweighting volatility when updating predictions about the world. However, the robustness of these predictive processing differences and their relevance to core symptoms remains unclear. Lawson and colleagues (1) reported a tendency to overestimate environmental volatility in autistic adults based on belief states extracted using a Hierarchical Gaussian Filter. We extended their paradigm to a domain central to the autistic experience: rather than distinguishing houses from faces, participants detected valence in emotional facial expressions. Preregistered hypotheses were evaluated using Bayesian linear mixed models based on data of 22 autistic and 22 non-autistic participants. Despite using an identical computational model to extract belief states, we did not find robust differences between autistic and non-autistic adults, though autistic participants showed a non-credible trend towards increased processing of phasic volatility. Largely comparable probabilistic associative learning was also reflected in response times and pupil sizes. While participants reacted faster to expected than unexpected trials in the beginning, this effect decreased over the course of the experiment; thus, possibly indicating that the individual blocks of stable cue-outcome associations were too short. We were unable to find credible differences in environmental volatility and learning rate updates using a task designed to probe a key autistic difficulty, facial emotion recognition. The current results call into question the generalisability and clinical relevance of prior findings.
Adults presenting for autism-related clinical care often report a range of physical and mental health condition histories. This exploratory study examined whether reported conditions formed person-level profiles among adults with documented or self-reported autism seeking autism-affirming telehealth services. We conducted a retrospective chart review of 640 adults receiving care from a United States-based telehealth organization. Latent class analysis used 30 binary indicators: 28 physical health condition endorsements and two psychiatric diagnostic indicators, anxiety and mood disorder. Supporting analyses included bivariate correlations, logistic regression, class comparisons, covariate analyses, and sensitivity analyses for rare indicators, overlapping indicators, physical-only class structure, and ADHD. The retained three-class solution identified a Mental and Physical Health class (17.7
Autism spectrum disorder (ASD) is characterized by profound clinical and biological heterogeneity. The neurodynamic profiles associated with divergent developmental trajectories of executive function (EF) during the critical transition from late childhood to early adolescence remain poorly understood. This study aimed to determine whether heterogeneity in EF development is associated with distinct neurodynamic profiles. In a longitudinal study, 68 children with ASD (aged 6–9 years) and 50 age-matched typically developing (TD) controls underwent baseline resting-state fMRI. The ASD group was followed for approximately 4 years. EF was assessed using the Behavior Rating Inventory of Executive Function (BRIEF), alongside follow-up depression, anxiety, and sleep outcomes. Longitudinal EF trajectory clusters were identified to characterize developmental heterogeneity. In parallel, baseline neurofunctional subtypes were derived from ALFF using a normative-deviation framework, with fALFF used for sensitivity analysis. CAP analysis was then applied to examine brain-state dynamics across these complementary stratification approaches. EF declined longitudinally in the ASD group, particularly in behavioral regulation domains, and these changes were associated with depressive symptoms and sleep problems at follow-up. Three longitudinal EF trajectory clusters were identified, but baseline CAP dynamics showed minimal differences across these groups. In contrast, ALFF-derived neurofunctional subtypes exhibited distinct CAP dynamic profiles, with Subtype 1 showing greater engagement of visual-related states and Subtype 2 exhibiting enhanced transitions among DMN/FPN-related control states. fALFF-based analyses yielded similar subtype assignments, supporting the robustness of the neurofunctional stratification. Critically, similar EF deterioration was associated with distinct neurodynamic profiles, as reflected by subtype-specific state-transition patterns that showed opposite associations with EF changes. First, the TD group was not followed longitudinally, limiting precise quantification of deviation from normative developmental pathways. Second, the sample size and attrition during follow-up may affect the stability of subtype assignment. Finally, as inferences were based on resting-state fMRI, task-based or ecologically valid measures were not available to validate functional interpretations. These findings provide evidence for neurodynamic heterogeneity in ASD, suggesting that similar clinical outcomes may be associated with divergent brain-state profiles. This work supports the move toward neuro-subtype–informed precision stratification and targeted intervention strategies.
Monogenic conditions, such as neurofibromatosis type 1 (NF1), provide a unique opportunity to study autism within a known molecular pathway. This study estimated the prevalence of autism in a large international NF1 cohort and examined how autistic traits relate to cognitive, behavioral, and adaptive functioning. In this cross-sectional study, 202 children with NF1 and 106 typically developing controls (aged 3–15 years) completed standardized cognitive testing and parent-reported behavioral measures. NF1 participants scoring ≥ 60 on the Social Responsiveness Scale-2 were evaluated using the Autism Diagnostic Observation Schedule-2 and Autism Diagnostic Interview–Revised, with DSM-5-TR autism diagnoses established by multidisciplinary consensus. Neurodevelopmental profiles were compared across NF1 subgroups (autism, broader autistic traits, no-autistic-traits) and controls. Autistic traits were elevated and continuously distributed in NF1. An estimated 28
Background The diagnostic term, autism spectrum disorder, encompasses the full range of impairments associated with the autism spectrum, a significant change from earlier DSM definitions that identified various subtypes of autism. However, the majority of autism-related research and cultural representations in recent years has focused on autistic individuals with strong language and cognitive abilities. In 2021, the administrative term Profound Autism (PA) was proposed by a Lancet Commission to draw attention to autistic people whose impairments require lifelong, round-the-clock care. The initial definition of PA included a minimum age and requiring 24/7 access to an adult to ensure safety, and suggested considering IQ, and verbal ability when defining this group. However, researchers have subsequently utilized widely varying criteria in studies of this group, producing results that are difficult to compare and limit the potential for the identification of this group to advance knowledge about their strengths and needs.Methods To address the need for studies that use comparable samples and increase clarity in communication and interpretation of results, we carried out a systematic, multi-stage Delphi consensus study with over 70 participants who identified as researchers, caregivers, autistic individuals, and clinicians, to measure consensus on components of a research definition of PA. A series of questions was developed for the primary domains of interest.Results After two rounds of review and voting, 76% of the respondents agreed on a research definition of PA of: adaptive functioning well below age level, requiring adult supervision to ensure physical and mental health, safety and well-being, being at least 8 years old, diagnosed with ASD, and having severely impaired cognitive abilities (reflected by IQ score below 50) and/or not verbally communicating other than single words or fixed phrases used predominantly to have their basic needs met.Limitations Variations in access to measurement tools, as well as access to services across the world, limit the utility of this definition outside research practices, and a response rate of 58% yielded a final round sample size of 78 that may underrepresent portions of the stakeholder community and was overwhelmingly composed of respondents from the United States.Conclusions Based on these findings, a new working research definition of profound autism is proposed. Adoption of this definition could improve comparability across research studies, enhance the impact and generalizability of results, and better target interventions and supports for this high-needs group.
Social communication difficulties in autism were traditionally attributed to deficits in empathy, that is, understanding others’ mental states and responding to these with a similar or appropriate emotion, within autistic individuals. The double empathy problem theory proposes that difficulties with cross-neurotype empathy are bidirectional. This study examines predictions from the double empathy problem theory, mainly whether autistic and non-autistic individuals differ in their empathy towards autistic versus non-autistic social targets, using an empathic accuracy paradigm alongside self-report measures of empathy and empathic interest. A novel empathic accuracy stimulus featuring video-recorded autobiographical stories from five autistic and five non-autistic adult storytellers was used. Participants [141 autistic, 94 non-autistic; mean age: 49.09 years (SD = 16.41)] were recruited through the Cambridge Autism Research Database. Each participant viewed two stories (one autistic, one non-autistic storyteller) in a randomized design, continuously rated storytellers’ emotional valence, and globally rated the degree to which they believed the storytellers felt each of 12 discrete emotions. Accuracy was computed as concordance with storytellers’ own ratings. Participants also self-reported empathy and empathic interest toward the storyteller in the target videos. Mixed linear models examined the effects of rater neurotype, target neurotype, and their interaction. Participants’ text responses were qualitatively analyzed using an inductive, data-driven approach to identify patterns within the data, which converged into subthemes and themes. No significant main effects emerged for rater or target neurotype on continuous valence or specific emotions’ empathic accuracy. A trend-level interaction (p=.059, d = 0.13) suggested that autistic raters showed relatively higher continuous valence empathic accuracy toward autistic targets than non-autistic raters. Non-autistic raters reported significantly higher self-reported empathy (p<.001, d=-0.67) and empathic interest (p<.001, d=-0.43) regardless of target neurotype. Qualitative analysis revealed that autistic participants described difficulties in identifying emotions and in performing the EA task, and engaged in metacognitive introspection, while non-autistic participants focused more on task design feedback. The use of video-based experimental design may not fully capture the complexity of spontaneous social encounters. The self-selected sample of autistic participants may not represent the full autism spectrum or include individuals requiring greater support, potentially affecting generalizability. Findings suggest partial support for the double empathy problem theory and potential underestimation of autistic participants of their own empathic abilities. Individual variability patterns caution against treating neurotypes as homogeneous categories that alone determine double empathy processes. Future research should examine real-world interactions and include measures of autistic traits across participants.
BACKGROUND:Dysregulated stress responses are increasingly implicated in the pathophysiology of autism spectrum disorder (ASD). Astrocytes, which are highly vulnerable to stress, critically support neuronal survival; however, their specific role in ASD remains poorly defined. METHODS:We analyzed single nucleus RNA sequencing data from postmortem cortices of ASD and control donors. Our analysis included enrichment analysis of astrocyte subpopulations and integrated pySCENIC-based GRN reconstruction, TF profiling, regulon-DEG analysis, and cell-cell communication. Mechanistic studies involved human iPSC-derived astrocytes-neurons co-culture and astrocyte-specific JUND overexpression in mice. Functional and behavioral assessments were performed to evaluate neuronal viability and ASD-relevant phenotypes. RESULTS:A subpopulation of stress-responsive astrocytes (SRAs) was identified as specifically enriched in ASD, displaying early transcriptional activation and increased abundance. These SRAs showed marked upregulation of both stress-response pathways and distinct reactive signatures. JUND was established as the core transcriptional orchestrator, controlling 23.8% of the dysregulated transcriptome that defines the core stress-responsive signature, including multiple ASD risk genes. JUND overexpression in astrocytes recapitulated the SRAs molecular profile, while astrocyte-specific JUND activation in mouse cortex elicited core ASD-like behaviors. Mechanistically, JUND upregulated the gap junction gene GJA1, enhancing astrocyte-neuron communication and promoting neuronal apoptosis. This pathogenic cascade was rescued by the gap junction inhibitor GAP27. LIMITATIONS:This study is focused solely on specific brain regions, the generalizability of the JUND-GJA1-GAP axis across diverse ASD subtypes remains to be validated, and the complete activation pathway of JUND signaling within SRAs as well as their interaction mechanisms with other glial cells are not well understood. CONCLUSIONS:Our findings demonstrate that a specialized astrocyte subpopulation mediates stress-induced dysfunction in ASD via a JUND-GJA1-GAP apoptotic signaling axis, providing a translational anchor for targeting astrocyte-specific pathways in ASD therapy.
Abstract Background Autism spectrum disorder (ASD) is a neurodevelopmental disorder with a strong genetic component, and over a thousand associated genes have been identified, including CNTNAP2 and SHANK3. Our previous work using Cntnap2 -/- and Shank3 Δ4–22 ASD mouse models implicated dysregulated nitric oxide (NO) signaling in ASD-related behaviors, which were improved by inhibition of neuronal nitric oxide synthase (nNOS) with 7-Nitroindazole (7-NI). However, the molecular mechanisms linking NO signaling to ASD pathology remain poorly defined. Methods We performed mass spectrometry-based global proteomic profiling of cortical tissue from both mouse models under baseline conditions and following 7-NI treatment. Systems biology and bioinformatics analyses were used to identify differentially expressed proteins, enriched pathways, and treatment-responsive networks. Cross-model comparisons were performed to assess molecular convergence and overlap with human ASD-risk genes. Behavioral and biochemical assessments were reanalyzed to evaluate ASD-like phenotypes and treatment effects. Results Treatment with 7-NI improved ASD-like behavioral deficits in Cntnap2 and Shank3 mutant mice, including increased sociability and reduced anxiety-like behavior. 7-NI was also associated with attenuation of cortical protein alterations across synaptic, neuronal, and metabolic pathways, shifting subsets of dysregulated proteins toward wild-type expression levels. Despite distinct genetic mutations, the two models converged at the protein and pathway levels, including treatment-responsive proteins encoded by high-confidence human ASD risk genes. Limitations Analyses were restricted to cortical tissue; additional brain regions may reveal complementary mechanisms. Mass spectrometry may underrepresent low-abundance proteins; larger sample sizes could improve statistical power. Potential off-target effects of 7-NI should also be considered. Conclusions These findings show that nNOS inhibition improves ASD-like behaviors and is associated with partial normalization of altered cortical proteins across two genetically distinct ASD mouse models that display convergent molecular changes, including proteins encoded by high-confidence ASD risk genes.
Background Some autistic people "camouflage" by modifying autistic characteristics in social situations. Operationalizations of camouflaging remain limited and inconsistent. Quantitative studies primarily use retrospective self-report questionnaires, constraining ecological precision and conceptual scope. Methodological limitations obscure knowledge about (1) how multi-faceted camouflaging behaviors and experiences, as part of general impression management (IM), differ between autistic and non-autistic people; and (2) how episodic IM vary by social demands and individual traits. Methods We developed a context-discrepancy assessment of camouflaging, conceptualized as a form of IM, in autistic and non-autistic adults. Forty-eight adults (23 autistic, 25 non-autistic) recorded video responses to two hypothetical scenarios with discrepant social evaluative pressure (i.e., job interview vs. video call with trusted other). Immediately after filming, participants rated facets of their IM experiences, including felt inauthenticity, behavioral monitoring extent, effort, and anxiety, and identified behavioral aspects that they particularly monitored. We analyzed IM experiential facet ratings using a 2 (diagnosis) by 2 (social demand) mixed-factorial ANOVA and open-ended data using summative content analysis. Pooled elastic-net regression explored associations between self-reported individual traits (including social coping, cognitive skills, expressivity, gender identity, and neurodivergent traits) and context-dependent discrepancies in IM experiential facet ratings. Results IM felt more effortful for all participants when social demands increased, but autistic adults experienced greater inauthenticity and behavioral monitoring extent when social demands elevated. Increased social demands also disproportionately heightened anxiety for autistic compared to non-autistic adults. Both groups monitored more behavioral aspects under higher social demands, but autistic adults especially increased their monitoring of nonverbal and idiosyncratic behaviors. Context-discrepancies in IM experiential facet ratings showed distinct associations with trait-level camouflaging use versus subjective self-monitoring and executive functioning abilities, as well as with autistic versus ADHD traits. Limitations The video-mediated design may not capture the spontaneity of real-life IM. Findings warrant replication with larger, more diverse cohorts, with counter-balanced or randomized designs. Future research is needed for the current findings to generalize to autistic individuals across sexes and genders, communication and intellectual abilities, as well as ethnicities and cultures. Conclusions This novel context-discrepancy assessment suggests that increased social-evaluative demands exacerbate the psychological tolls of IM for autistic compared to non-autistic adults. Autistic relative to non-autistic adults may particularly monitor nonverbal behaviors in such circumstances. Individual trait associations further delineate IM facets and implicate cognitive and neurodivergent characteristics as potential sources of heterogeneous IM experiences. These insights shed new light into how autistic and non-autistic adults similarly and differently coordinate and experience social coping in context-dependent ways.
Activity-dependent neuroprotective protein (ADNP) is a critical regulator of neurodevelopment, and most pathogenic variants reported in Helsmoortel–Van der Aa syndrome (HVDAS) are truncating variants. In contrast, the functional consequences of ADNP missense variants remain largely unclear. We integrated an ADNP variant cohort in China with variants recorded in the NCBI ClinVar database, revealing a major gap in the interpretation of ADNP missense variants. We investigated a rare de novo ADNP missense variant, p.C687R, predicted to disrupt the ninth zinc finger domain. In vitro, p.C687R was overexpressed in HEK293T cells to assess subnuclear localization by immunofluorescence and chromatin binding patterns using CUT Tag, with chromatin interactions inferred from published Hi-C datasets. CRISPR/Cas9-mediated ADNP knockout was performed for comparison. In vivo, wild-type ADNP or p.C687R was introduced into the embryonic mouse cortex at E14.5 via in utero electroporation (IUE) and neuronal development was evaluated at E18.5 and P14. Patient-derived induced pluripotent stem cells (iPSCs) from a de novo p.C687R carrier were differentiated into neural progenitor cells (NPCs) and analyzed by multi-omic profiling (RNA-seq, ChIP-seq, ATAC-seq), with lineage-specific markers examined by immunofluorescence. p.C687R displays altered subnuclear localization and redistributes wild-type ADNP when overexpressed in HEK293T. IUE in the mouse cortical plate revealed impaired neuronal migration and abnormal cortical arborization. Genome-wide profiling in HEK293T demonstrated a p.C687R-specific chromatin occupancy pattern, preferentially targeting histone modification-related genes. Knockout of ADNP led to upregulation of neuronal genes, including GABAergic lineage-associated genes. In patient-derived iPSCs, a distinct set of neurodevelopmental genes, including key regulators of GABAergic differentiation, showed increased bivalent histone marks (H3K4me3/H3K27me3). Although their promoters remained in an open chromatin state, these genes were transcriptionally silent in pluripotent cells but became more activated upon GABAergic differentiation. This study is based on a single patient-derived line in combination with complementary experimental models. In the heterozygous endogenous context, distinguishing increased functional activity from dosage-related effects requires further investigation. Replication in additional patient-derived or engineered lines is required to determine the generalizability. Our results suggest that p.C687R may exert gain-of-function-like effects in experimental systems and underscore chromatin-mediated regulation of GABAergic lineage genes in HVDAS.
Social learning is the process of acquiring social skills, new information, or associating negative or positive valence to a context through the observation of others and through direct social interaction with others. Neurodevelopmental disorders such as autism spectrum disorder show deficits in social salience and reciprocal affective responses. Social learning implicates the basolateral amygdala (BLA), anterior cingulate cortex (ACC), and anterior insula (AI). The lateral habenula (LHb), a brain area renowned for its role in negative reinforcement learning, has not been yet extensively studied in the domain of social learning. We developed a fear conditioning by proxy paradigm called ‘social transmission of negative valence’ (STNV) and tested prairie voles on the task. Observers experienced negative social conditioning through a proxy cage mate that served as the demonstrator during retrieval of a cued fear memory. Observers went through a social memory recall session 24 h after observation. We measured observers’ freezing time, self-grooming, rearing, and ultrasonic vocalizations emitted as signs of distress. We also quantified immediate early gene translation as a proxy for neural activity using c-Fos immunochemistry 80 min after observing demonstrators going through memory recall. Socially-conditioned observers that were exposed to the fear-conditioned demonstrators displayed increased freezing time, self-grooming, and rearing during social recall sessions compared to control observers. They also displayed higher ultrasonic vocalization frequency compared to controls. Socially-conditioned observers showed increased c-Fos expression in the LHb, BLA, ACC and AI compared to controls. The c-Fos findings are correlational and additional experiments involving chemo- or optogenetic inhibition or excitation of LHb neurons in observers are necessary for causality confirmation. We found that the LHb is co-activated with other key areas during social learning in prairie voles. These findings extend the traditional view of the LHb as an area involved in negative reinforcement learning and position it as a critical area for social affect. This offers a fresh perspective on the neural mechanisms of social affect and opens a new line of inquiry into brain dysfunction of social salience in neurodevelopmental disorders.
BACKGROUND: Despite significant advances in understanding facial emotion recognition (FER) in autistic adults in recent decades, the mechanisms underlying FER difficulties in individuals with autism remain unclear, with inconsistent findings across studies. A key limitation may be the reliance on aggregate accuracy scores, which overlook item- and subject-level variability. Here, we investigated the effects of task adaptation and stimulus properties on FER performance in autistic and non-autistic adults using mixed-effects modelling. METHODS: A total of 120 autistic and 116 non-autistic participants completed the Berlin Emotion Recognition Test 2. Performance was analyzed on a trial-by-trial basis, considering trial number, stimulus properties—derived from automated facial analysis—and their interactions with diagnostic group. Response times were analyzed using mixed-effects linear regression models, while accuracy was analyzed using mixed-effects logistic regression models. RESULTS: Compared with non-autistic participants, autistic participants demonstrated lower overall accuracy and slower responses, accompanied by significantly reduced task adaptation. Contextual ambiguity of stimulus faces moderated group differences in FER accuracy, with non-autistic subjects showing greater use of contextual information. Social-cognitive traits further moderated the effect of contextual ambiguity in autistic subjects. LIMITATIONS: Our findings are specific to the design and stimulus material of the Berlin Emotion Recognition Test 2 and may not generalize to other FER tasks. Furthermore, our sample did not include individuals with intellectual disabilities, limiting generalizability across the autism spectrum. Lastly, the reliability of stimulus property estimates derived from automated facial analysis may require validation on a larger sample of stimulus faces. CONCLUSIONS: Our findings reveal that differences in task adaptation and contextual cue processing underlie FER performance differences in individuals with autism, emphasizing the importance of participant- and item-level analysis. These results may inform future study designs and highlight the advantages of integrating automated FER with mixed-effects modeling in autism research.
Abstract Background Interpersonal coordination is a fundamental social behavior that has been shown to be reduced in autism, though less is known about other psychiatric conditions. An automated quantitative measure of interpersonal coordination would enhance assessment, diagnosis, and monitoring of treatment-related change in autism and other psychiatric conditions. We introduce and apply a novel AI-based measure (’concurrence’) to quantify and compare nonverbal interpersonal coordination during naturalistic conversation in individuals with and without various psychiatric presentations. Methods The primary analysis included 380 12–18-year-olds with neurotypical development (NT), autism (AUT), or other psychiatric conditions (PSY), recorded during videoconference get-to-know-you conversations with a research staff member (‘partner’). Replication analyses included 72 12–18-year-olds with NT or AUT, recorded during face-to-face conversations. A self-supervised AI method (concurrence) was applied to time series data representing facial expressions and head movements of participants and their conversation partners. This yielded interpersonal coordination scores for all participant-partner dyads, which were then compared transdiagnostically. Convergent and discriminant validity were assessed using annotated subsamples from a combined sample of 609 5–52-year-olds. Convergent validity was assessed with measures of social gaze, motor imitation ability, and conversation quality; discriminant validity was assessed with IQ scores. Results In the videoconference sample, AUT demonstrated significantly lower interpersonal coordination than PSY (unadjusted Cohen’s d = 0.46, p < 0.001) and NT (d = 1.03, p < 0.001), with PSY also lower than NT (d = 0.50, p < 0.001). The AUT < NT effect was replicated in the face-to-face sample (d = 0.73, p < 0.05). The group-by-context interaction was nonsignificant (p = 0.33), suggesting group differences are robust to recording context. Convergent and discriminant validity was demonstrated through positive associations between interpersonal coordination and mutual social gaze (r(108) = 0.46, p < 0.0001), gross motor imitation ability (r(35) = 0.41, p < 0.05), and conversation quality ratings (r(364) = 0.34, p < 0.0001), but not IQ (r(367) = 0.03, p = 0.55). Limitations Generalizability is limited by sample characteristics including cognitive and verbal ability, age, and sex. Conclusions The study demonstrates reduced interpersonal coordination in adolescents with autism and other psychiatric conditions (AUT
Autism stigma significantly impacts the quality of life for autistic individuals and their families. Methods to measure stigma, such as self-report scales, may be influenced by social desirability biases and fail to uncover the psychological mechanisms underlying stigma formation. The present study used the reverse-correlation image classification (RCIC) technique to investigate whether the mental faces of autistic children were represented more negatively than non-autistic children, and to examine potential associations between these biases and behavioral characteristics or diagnostic labels of autism. In Study 1, participants selected between two faces (with random visual noise) that best matched their mental image of an autistic child. The selected and unselected faces were averaged to generate mental face representations, which were then rated on attractiveness, felt disgust, and behavioral avoidance. Studies 2 and 3 further examined the impact of behavioral characteristics and diagnostic labels on these mental representations by presenting participants with target persons paired with autistic behaviors or autism labels versus typical behaviors or non-autism labels. Study 1 found that, compared to mental representations of non-autistic children, participants rated mental representations of autistic children as less attractive, reported increased felt disgust toward them, and indicated a greater likelihood of avoiding them. Parents of autistic children similarly exhibited negative representations. Studies 2 3 revealed that arbitrary pairing of faces with autistic behaviors (vs. typical) or autism labels (vs. non-autism) led to less attractive mental images. The stimuli were limited to male children’s faces with neutral expressions, restricting generalizability across gender, age, and emotion. The design could not determine whether negative representations reflect autism‑specific stigma or a broader social bias triggered by perceived difference. The study did not explore individual differences or incorporate autistic perspectives in stimulus design. Negative mental face representations of autism exist independently of physical traits, shaped by behavioral cues and diagnostic labels. These findings highlight a possible mechanism underlying stigma: the formation of negative mental face representations contributes to biased evaluations of autistic children. Future research could explore whether modifying such representations might offer a new pathway for supporting strategies.
Background Social camouflaging refers to strategies to hide or compensate for social difficulties, often at significant mental health costs, and is particularly prevalent in autism. The large-scale neural network associated with this adaptation remains poorly understood. This study aimed to identify these neural network patterns and their link to potential mental health issues. Methods Using a dimensional approach, we recruited 110 healthy young adults who completed self-report questionnaires measuring autistic traits and camouflaging as well as depression and anxiety, and underwent resting-state fMRI scans. The interaction between camouflaging and autistic traits on brain network connectivity was examined using the 300-node Seitzman atlas, encompassing 13 functional networks. Results Among individuals with higher autistic traits, greater camouflaging was associated with increased connectivity between the Default Mode Network (DMN) and the Cingulo-Opercular Network (CON), as well as within the CON. Crucially, DMN-CON hyperconnectivity statistically mediated the relationship between camouflaging and potential mental health costs (i.e., depression and anxiety scores) but only in individuals with higher autistic traits. Limitations: Our study was limited by its predominantly non-clinical sample, the cross-sectional design, and the use of resting-state rather than task-based fMRI. Conclusions These findings reveal specific compensatory neural network patterns associated with camouflaging in those high in autistic traits, involving interoception, self-referential, and executive control systems, and provide a neurobiological explanation for its potential mental health burden, highlighting the need for societal changes that reduce the pressure for such adaptations.
Despite rising rates of autism prevalence, there remains a pressing need to enhance the quality of life for autistic people in Europe and around the world. We conducted the 10 Points for Change survey to identify the 10 most important areas that require improvement for autistic people across the region. Data from 1,709 autistic people, parents/carers and members of autism-related organisations residing within the European Union (EU) and the United Kingdom (UK) were analysed, together with autism-related differences (autistic vs. non-autistic; formal vs. no formal autism diagnosis) and gender differences (male vs. female) in results. Across groups, areas that require the most urgent changes are education, public awareness and understanding of autism, employment, and government funding for autism-specific services. Differences in results between groups reflect their specific needs and experiences. Discrimination is a crucial area for change according to autistic people with formal diagnosis of autism, whereas autistic people without formal diagnosis indicate diagnostic services as a priority for change. According to parents/carers and members of autism-related organisations, changes are also needed to improve social inclusion of autistic people. Other areas of priority for change across all groups include mental healthcare (within top 10 for autistic participants and parents/carers), support with daily living, and post-diagnostic services (the latter two within top 10 for parents/carers and members of autism-related organisations). For some areas, their identification and importance as priorities for change significantly varied with whether participants were autistic or formally diagnosed and autistic participants’ gender. Comparisons across countries with the greatest representation in the survey – Germany, the UK, France, Spain and Poland – revealed consistent priorities. Consideration should be given to issues related to methodology and data availability such as how representative the sample is of countries across the EU and the UK. Autistic people with high support needs might have also been unable to participate directly and responses from carers representing them might not fully reflect their views or provide representative data. Change through concerted legislative actions within and across countries in Europe is needed to address the priority areas for change for autistic people.
