Molecular Autism最新文献

Background: Humans form almost instantaneous impressions of everyone they encounter. These impressions set the first tone for how they approach and interact with others. Research on impression formation unveiled that impressions formed by autistic and non-autistic people are often less favourable when rating an autistic person. This effect is partly explainable by differences in motion dynamics.

Methods: In this preregistered study, we systematically assessed impressions formed by 27 autistic and 36 non-autistic comparison observers when watching videos showing silent interactions between either two non-autistic or between an autistic and a non-autistic person. We used an eye tracker to capture their gaze patterns while observing these interactions. Of each dyadic interaction, video vignettes with high and vignettes with low interpersonal synchrony of movement (IPS_mov) were extracted using Motion Energy Analysis so that we could investigate the effects of interpersonal synchrony and diagnosis, respectively.

Results: Interactions were rated less favourably when the observed dyad included an autistic adult. Additionally, interactions showing low IPS_mov were rated less favourably than interactions showing high IPS_mov, regardless of dyad type. Both autistic and comparison observers rated interactions of non-autistic dyads and high IPS_mov interactions more favourably. Gaze patterns revealed differences between autistic and comparison observers, but no differences due to IPS_mov or dyad type. Furthermore, dwell times to hands predicted ratings.

Limitations: In this study, we investigated specific influences on impression formation, specifically interpersonal synchrony of movement and autism. There are many more potentially interesting aspects of individuals that impact impression formation, such as facial expressiveness, gaze behaviour and linguistic content of conversations, which should be investigated systematically and in a controlled fashion in future research.

Conclusions: Extending research on autism and impression formation to dyadic interactions, this study reveals that motion dynamics play a role in how pleasant interactions are perceived. Autistic-involved interactions were rated lower, despite observers being unaware of the dyad type and only watching people's outlines. Future research should identify conversational aspects driving lower ratings of mixed dyads, potentially considering the effect of hand dwell times on ratings. Autistic and comparison observers showed different gaze patterns despite similar ratings, confirming distinct social information processing.

Background: Autism and attention deficit hyperactivity disorder (ADHD) are two highly heterogeneous neurodevelopmental conditions with variable underlying neurobiology. Imaging studies have yielded varied results, and it is now clear that there is unlikely to be one characteristic neuroanatomical profile of either condition. Parsing this heterogeneity could allow us to identify more homogeneous subgroups, either within or across conditions, which may be more clinically informative. This has been a pivotal goal for neurodevelopmental research using both clinical and neuroanatomical features, though results thus far have again been inconsistent with regards to the number and characteristics of subgroups.

Methods: Here, we use population modelling to cluster a multi-site dataset based on global and regional centile scores of cortical thickness, surface area and grey matter volume. We use HYDRA, a novel semi-supervised machine learning algorithm which clusters based on differences to controls and compare its performance to a traditional clustering approach.

Results: We identified distinct subgroups within autism and ADHD, as well as across diagnosis, often with opposite neuroanatomical alterations relatively to controls. These subgroups were characterised by different combinations of increased or decreased patterns of morphometrics. We did not find significant clinical differences across subgroups.

Limitations: Crucially, however, the number of subgroups and their membership differed vastly depending on chosen features and the algorithm used, highlighting the impact and importance of careful method selection.

Conclusions: We highlight the importance of examining heterogeneity in autism and ADHD and demonstrate that population modelling is a useful tool to study subgrouping in autism and ADHD. We identified subgroups with distinct patterns of alterations relative to controls but note that these results rely heavily on the algorithm used and encourage detailed reporting of methods and features used in future studies.

Background: The prevalence of autism spectrum disorder (ASD), a common developmental disorder, has surged in recent years. Accordingly, the identification and early management of possible risk factors can diminish ASD incidence.

Aim: To determine the prevalence and severity of idiopathic ASD in Egyptian children aged 12 months to 12 years, and to identify the epidemiological, sociodemographic, and environmental risk factors contributing to this disorder.

Methods: This study comprised 41,640 children from the main eight geographic areas in Egypt. It was conducted through four phases: household screening, facility-based screening for high-risk children, diagnosis confirmation, and risk factor assessment.

Results: The prevalence of ASD as confirmed by the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) and the Childhood Autism Rating Scale (CARS) was 1.1% (455 out of 41,640), with significant geographic variability. Urban areas had a significantly higher prevalence than rural areas. Children aged 3-6 years showed the highest prevalence at 1.5%. Boys were four times more affected than girls, with prevalence rates of 1.7% and 0.4%, respectively. Significant risk factors included: a history of convulsions (AOR = 4.7; 95% CI: 3.3-6.79), low birth weight (AOR = 2.08; 95% CI: 1.54-2.79), prolonged stays in neonatal intensive care unit (NICU) longer than two days (AOR = 1.91; 95% CI: 1.46-2.49) and maternal health problems during pregnancy (AOR = 1.66; 95% CI:1.36-1.95). Regarding severity, 45% of diagnosed children had moderate ASD, 39% had severe ASD, and 16% had mild ASD. Female gender and older age were significant predictors of greater ASD severity.

Conclusion: ASD prevalence in Egypt is comparable to other Middle Eastern countries. Policymakers should utilize these findings to design targeted public health interventions aimed at early detection, management, and prevention of ASD progression.

Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder defined by social communication deficits, repetitive behaviors and restricted interests. Studies have reported aberrant sensory responses, including altered experiences of social touch, in individuals with ASD. However, the relationship between atypical social touch and social networks in ASD remains poorly understood. Social touch is used to strengthen and manage social networks in many species. Studies in general populations across diverse cultures show that the extent of permissible touch is consistently linked to the strength of emotional bonds between the toucher and the touched individual. This study examined relationship-specific patterns of social touch and their association with emotional bonding in individuals with ASD.

Methods: Seventy adults with ASD and 70 typically developed (TD) adults rated their emotional bonds with different social network members (e.g., partners, fathers, strangers) and the pleasantness of being touched by each. Participants also identified body regions where they allowed touch. We hypothesized that patterns of interpersonal touch allowance and emotional bonding, and their relationship, would differ between ASD and TD adults.

Result: In all social network members except children and female friends, ASD adults allowed significantly less social touching than TD adults. Compared to TD adults, ASD adults also reported having significantly weaker emotional bonds with one social network member and experiencing significantly less pleasantness when touched by multiple members of their social network. In both groups, strength of emotional bond was significantly correlated with permissible touch area. Linear regression analyses showed that our ASD participants were more reliant on bodily touch allowance for emotional bonding than the TD controls.

Limitations: More participants are necessary to secure sufficient number of social network members in ASD.

Conclusions: Our results suggest that adults with ASD generally prefer less social touch from most social network members and show reduced emotional bonding with only a specific connection. In addition, touch allowance was more strongly associated with emotional bonding in ASD than TD adults. These findings highlight the influence of autistic traits on the relationship between social touch and emotional bonding within social networks.

Background: Accurately determining the sample size ("N") of a dataset is a key consideration for experimental design. Misidentification of sample size can lead to pseudoreplication, a process of artificially inflating the number of experimental replicates which systematically underestimates variability, overestimates effect sizes and invalidates statistical tests performed on the data. While many journals have adopted stringent requirements with regard to statistical reporting over the last decade, it remains unknown whether such efforts have had a meaningful impact on statistical rigour.

Methods: Here, we evaluated the prevalence of this type of statistical error among neuroscience studies involving animal models of Fragile-X Syndrome (FXS) and those using animal models of neurological disorders at large published between 2001 and 2024.

Results: We found that pseudoreplication was present in the majority of publication, increasing over time despite marked improvements in statistical reporting over the last decade. This trend generalised beyond the FXS literature to rodent studies of neurological disorders at large between 2012 and 2024, suggesting that pseudoreplication remains a widespread issue in the literature.

Limitations: The scope of this study was limited to rodent-model studies of neurological disorders which had the potential for being pseudoreplicated, by allowing repeat observations from individual animals. We did not consider reviews or articles whose experimental design could not allow for pseudoreplication, for example studies which reported only behavioural results, or studies which did not use inferential statistics.

Conclusions: These observations identify an urgent need for better standards in experimental design and increased vigilance for this type of error during peer review. While reporting standards have significantly improved over the past two decades, this alone has not been enough to curb the prevalence of pseudoreplication. We offer suggestions for how this can be remedied as well as quantifying the severity of this particular type of statistical error. Although the examined literature concerns a specific neuroscience-related area of research, the implications of pseudoreplication apply to all fields of empirical research.

Background: So-called 'mismatch accounts' propose that, rather than arising from a socio-cognitive deficit present in autistic people, mentalising difficulties are the product of a mismatch in neurotype between interaction partners. Although this idea has grown in popularity over recent years, there is currently only limited empirical evidence to support mismatch theories. Moreover, the social model of disability such theories are grounded in demands a culturally situated view of social interaction, yet research on mentalising and/or autism is largely biased towards Western countries, with little knowledge on how successful mentalising is defined differently, and how tools to assess socio-cognitive ability compare, across cultures.

Methods: Using a widely employed mentalising task-the animations task-, the current study investigated and compared the bi-directional mentalising performance of British and Japanese autistic and non-autistic adults and assessed observer-agent kinematic similarity as a potential dimension along which mismatches may occur between neurotypes. Participants were asked to depict various mental state- and action-based interactions by moving two triangles across a touch-screen device before viewing and interpreting stimuli generated by other participants.

Results: In the UK sample, our results replicate a seminal prior study in showing poorer mentalising abilities in non-autistic adults for animations generated by the autistic group. Crucially, the same pattern did not emerge in the Japanese sample, where there were no mentalising differences between the two groups.

Limitations: Limitations of the current study include that efforts to match all samples within and across cultures in terms of IQ, gender, and age were not successful in all comparisons, but control analyses suggest this did not affect our results. Furthermore, any performance differences were found for both the mental state- and action-based conditions, mirroring prior work and raising questions about the domain-specificity of the employed task.

Conclusions: Our results add support for a paradigm shift in the autism literature, moving beyond deficit-based models and towards acknowledging the inherently relational nature of social interaction. We further discuss how our findings suggest limited cultural transferability of common socio-cognitive measures rather than superior mentalising abilities in Japanese autistic adults, underscoring the need for more cross-cultural research and the development of culturally sensitive scientific and diagnostic tools.

Background: Behavioral endocrinology examines associations between hormone expression, such as testosterone and cortisol, and behavior; both of which have been implicated in autism spectrum disorder (ASD). The overarching aim of the study was to examine the intersection of sex-based (Male, Female), hormonal (testosterone, cortisol), diagnostic (ASD, typically developing, (TD)) and developmental (age, puberty) patterns over four years of a longitudinal study in a well-characterized sample of youth (spanning 10 to 17 years).

Methods: In year 1 (Y1), participants included 140 autistic youth (36 females, 104 males) and 105 TD youth (46 females, 59 males.). For Y4, participants included 83 ASD and 77 TD youth. Immediate waking morning salivary samples were collected for hormone assay. Mixed effects and ordinary linear regression models were used, as well as mediation effects of hormones on behavior.

Results: For cortisol, there was a significant diagnosis by sex by age interaction (X² = 15.62, df = 3, p = 0.0014, S = 0.2446) showing that autistic females evidence higher morning cortisol that increased over developmental progression compared to TD females. Moreover, ASD males had stunted testosterone growth compared to TD males (Est = 0.1530, p = 0.0130). Regarding biobehavioral associations in year 1, diagnosis (X² = 80.72, df = 1, p < 0.0001, S = 0.5704) and cortisol (X² = 14.42, df = 3, p = 0.0024, S = 0.2159) were associated with social problems; however, there were no effects for testosterone on diagnosis or a mediation effect on social problems. There was a significant effect of diagnosis on CBCL Aggression score (X² = 34.39, df = 1, p < 0.0001, S = 0.3692) independent of hormonal measurements.

Limitations: Despite the large sample, it was not fully representative based on race, ethnicity or intellectual profile. Attrition of the sample is also acknowledged especially between portions of Y2 and Y3 due to the COVID-19 pandemic. Finally, only the immediate morning salivary samples were used due to lower and undetectable concentration levels of testosterone in younger and female children.

Conclusions: Collectively, these findings underscore the need to elucidate the biobehavioral patterns that emerge during the complex adolescent transition for autistic youth to determine how they impact clinical and long-term outcomes. The unique hormonal trajectories may be related to differences in advanced pubertal progression and affective states found in autistic females.

Background: The key pathological mechanisms underlying autism spectrum disorder (ASD) remain relatively undetermined, potentially due to the heterogenous nature of the condition. Targeted studies of a series of monogenic ASDs have revealed postsynaptic dysfunction as a central conserved mechanism. Presynaptic dysfunction is emerging as an additional disease locus in neurodevelopmental disorders; however, it is unclear whether this dysfunction drives ASD or is an adaptation to the altered brain microenvironment.

Methods: To differentiate between these two competing scenarios, we performed a high content analysis of key stages of the synaptic vesicle lifecycle in primary neuronal cultures derived from a series of preclinical rat models of monogenic ASD. These five independent models (Nrxn1^+/-, Nlgn3^-/y, Syngap^+/-, Syngap^+/Δ-GAP, Pten^+/-) were specifically selected to have perturbations in a diverse palette of genes that were expressed either at the pre- or post-synapse. Synaptic vesicle exocytosis and cargo trafficking were triggered via two discrete trains of activity and monitored using the genetically-encoded reporter synaptophysin-pHluorin. Activity-dependent bulk endocytosis was assessed during intense neuronal activity using the fluid phase marker tetramethylrhodamine-dextran.

Results: Both synaptic vesicle fusion events and cargo trafficking were unaffected in all models investigated under all stimulation protocols. However, a key convergent phenotype across neurons derived from all five models was revealed, a depression in activity-dependent bulk endocytosis.

Limitations: The study is exclusively conducted in primary cultures of hippocampal neurons; therefore, the impact on neurons from other brain regions or altered brain microcircuitry was not assessed. No molecular mechanism has been identified for this depression.

Conclusion: This suggests that depression of activity-dependent bulk endocytosis is a presynaptic homeostatic mechanism to correct for intrinsic dysfunction in ASD neurons.