Search Results (132)

Autistic traits—such as social communication deficits, cognitive rigidity, and repetitive behaviors—are increasingly recognized in individuals with schizophrenia, particularly in early-onset cases and subtypes with predominant negative symptoms. This overlap has prompted investigations into shared pathophysiological mechanisms. One emerging area of focus is the role of neuroinflammation in schizophrenia, which may contribute to the manifestation of autistic features. Immunological research indicates the presence of chronic low-grade inflammation, microglial activation, and disruption of the blood–brain barrier in schizophrenia. In particular, an imbalance in T-helper (Th) cell responses—specifically a shift toward Th2 dominance or concurrent Th1/Th2 activation—may lead to dysregulated cytokine production and disturbances in neural function. These findings highlight the importance of exploring immunological pathways as a basis for specific symptom profiles. Additionally, current efforts aim to identify reliable inflammatory biomarkers in schizophrenia that could support diagnosis, predict disease course, and guide treatment. Evaluating neuroinflammatory markers in patients with autistic features may provide novel insight into schizophrenia subtypes and help tailor immunomodulatory therapies. This review explores the expression of autistic traits in schizophrenia and examines the role of neuroinflammation and Th1/Th2 imbalance as potential mechanisms and biomarkers. Full article

Cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) is a severe X-linked neurodevelopmental condition characterized by early-onset, intractable epilepsy, motor and cognitive impairment, and autistic-like features. Although constitutive Cdkl5 knockout (KO) models have established the importance of CDKL5 during early brain development, CDKL5’s role in the mature brain remains poorly defined. Here, we employed an inducible, conditional KO model in which Cdkl5 is selectively deleted from forebrain glutamatergic neurons in adult mice to investigate the postdevelopmental functions of CDKL5. Using a total of 48 adult male mice, including Cdkl5^flox/Y(Cre⁺) (n = 30) and Cdkl5^flox/Y(Cre⁻) littermate controls (n = 18), we found that tamoxifen-induced Cdkl5 deletion led to prominent behavioral impairments, including deficits in motor coordination, reduced sociability, and impaired hippocampus-dependent spatial memory, while behavioral features such as hyperactivity and stereotypic jumping, typically present in germline KOs, were absent. Sensory functions, including olfaction and pain perception, were also preserved. At the cellular level, the loss of Cdkl5 resulted in a marked reduction in excitatory synapse density in the cortex and hippocampus, accompanied by increased numbers of immature dendritic spines and decreased mature spines. Neuronal loss in the hippocampal CA1 region and selective microglial activation in the cortex were also observed. These alterations closely resemble those seen in constitutive KO models, underscoring the ongoing requirement for CDKL5 expression in excitatory neurons for maintaining synaptic integrity and neuronal homeostasis in the adult brain. This study underscores the importance of temporally controlled models for investigating the mechanisms underlying CDD pathophysiology in the adult brain. Full article

Although prosodic differences in autistic individuals have been widely documented, little is known about their ability to perceive and interpret specific prosodic features, such as contrastive pitch accent—a prosodic signal that places emphasis and helps listeners distinguish between competing referents in discourse. This study addresses that gap by investigating the extent to which autistic children can (1) perceive contrastive pitch accent (i.e., discriminate contrastive pitch accent differences in speech); (2) interpret contrastive pitch accent (i.e., use prosodic cues to guide real-time language comprehension); and (3) the extent to which their ability to interpret contrastive pitch accent is associated with broader language and social communication skills, including receptive prosody, pragmatic language, social communication, and autism severity. Twenty-four autistic children and 24 neurotypical children aged 8 to 14 completed an AX same–different task and a visual-world paradigm task to assess their ability to perceive and interpret contrastive pitch accent. Autistic children demonstrated the ability to perceive and interpret contrastive pitch accent, as evidenced by comparable discrimination ability to neurotypical peers on the AX task and real-time revision of visual attention based on prosodic cues in the visual-world paradigm. However, autistic children showed significantly slower reaction time during the AX task, and a subgroup of autistic children with language impairment showed significantly slower processing of contrastive pitch accent during the visual-world paradigm task. Additionally, speed of contrastive pitch accent processing was significantly associated with pragmatic language skills and autism symptom severity in autistic children. Overall, these findings suggest that while autistic children as a group are able to discriminate prosodic forms and interpret the pragmatic function of contrastive pitch accent during spoken language comprehension, differences in prosody processing in autistic children may be reflected not in accuracy, but in speed of processing measures and in specific subgroups defined by language ability. Full article

Background/Objectives: Diagnosing ASD in adults presents unique challenges, and there are currently no specific biomarkers for this condition. Most existing studies on the gut microbiota in ASD are conducted in children; however, the composition of the gut microbiota in children differs significantly from that of adults. This study aimed to study the gut microbiota of young adults with high-functioning ASD. Methods: Using metagenomic sequencing, we evaluated the gut microbiota in 45 adults with high-functioning ASD and 45 matched healthy controls. Results: Adjusting for sociodemographic information, dietary habits, and clinical data, we observed a distinct microbiota profile of adults with ASD in comparison to controls, with the intensity of autistic traits strongly correlating to microbial diversity (correlation coefficient = −0.351, p-value < 0.001). Despite a similar dietary pattern, the ASD group exhibited more gastrointestinal symptoms than the healthy controls. An internally validated machine-learning predictive model that combines the Autism Spectrum Quotient questionnaire score of individuals with their microbial features could achieve an area under the receiver operating characteristic curve (AUC) of 0.955 in diagnosing ASD in adults. Conclusions: This study evaluates the gut microbiota in adult ASD and highlights its potential as a non-invasive biomarker to enhance the diagnosis of ASD in this population group. Full article

Background/Objectives: Recent lifestyle and dietary changes, driven by health awareness and ecological concerns, have led to the rise in numerous type of diets, which can promote well-being but may also contribute to Orthorexia Nervosa (ON), which have been suggested to be linked to autism spectrum disorder. This study aimed to explore the relationship between autistic traits, social camouflaging, and orthorexic tendencies in female university students, focusing on how these factors intersect with specific dietary habits. Methods: 554 female students were recruited via an online survey and assessed with the Adult Autism Subthreshold (AdAS) Spectrum, the Camouflaging Autistic Traits Questionnaire (CAT-Q), and the ORTO-R. Participants were categorized into four groups based on AdAS Spectrum and CAT-Q quartiles. Results: Vegans and vegetarians exhibited higher orthorexic tendencies and specific autistic traits. High scorers on the AdAS Spectrum and CAT-Q also showed higher ORTO-R scores, with both AdAS Spectrum and CAT-Q total scores, as well as certain domains, serving as significant positive predictors of higher ORTO-R scores. Notably, the AdAS Spectrum total score had a significant direct and indirect effect (through the CAT-Q) on the ORTO-R total score. Conclusions: The study found significant associations between autistic traits, social camouflaging behaviors, and orthorexic tendencies in female university students. These findings suggest that the strict dietary behaviors and rigid thinking characteristic of orthorexia may be influenced by underlying autistic features, highlighting the need for further research into the intersection of autism and eating disorders. Full article

Objectives: Hikikomori is a condition characterized by extreme social withdrawal, functional impairment, and mental distress, which has gained increasing recognition worldwide. While it can be associated with comorbid psychiatric disorders, hikikomori shares similarities with autism spectrum, prompting investigations into their relationship. Given that hikikomori commonly manifests in early adulthood, this study aimed to explore the relationship between autistic features and hikikomori tendencies among university students. Methods: A total of 2037 university students were recruited via an online survey and assessed with the Adult Autism Subthreshold (AdAS) Spectrum and the Hikikomori Questionnaire (HQ-25). Participants were categorized into four groups: healthy controls (HCs), subjects with hikikomori tendencies (HKs), subjects with significant autistic traits (ATs), and subjects with both significant ATs and hikikomori tendencies (AT-HKs). Results: Results showed significant effects of both hikikomori presence and significant ATs on AdAS Spectrum and HQ-25 scores, while a significant effect of their interaction was detected on AdAS Spectrum scores. The AT-HK group consistently scored higher on both AdAS Spectrum and HQ-25 compared to other groups, with the AT and HK groups outperforming HCs in specific domains. HQ-25 Socialization and Isolation domains predicted higher AdAS Spectrum scores in hikikomori subjects, while various AdAS Spectrum domains served as predictors of HQ-25 scores in AT subjects. Conclusions: This study highlights a significant relationship between ATs and hikikomori tendencies in university students, suggesting that their comorbidity may represent a more severe phenotype, where each condition may exacerbate the other. Full article

Background: Borderline personality disorder (BPD) is a pervasive mental health condition characterized by a heightened risk of suicidal behavior. Emerging research has suggested a potential overlap between BPD and subthreshold autistic traits (ATs), raising the possibility that these traits may influence the development, course, and severity of BPD, particularly in relation to suicidal ideation and behaviors. This study aims to evaluate the relationship between suicidal ideation, suicidal behaviors, and ATs in individuals with BPD. Methods: We assessed 106 subjects with BPD using the mood spectrum self-report version (MOODS-SR) of the Adult Autism Subthreshold Spectrum (AdAS Spectrum) questionnaire. The sample was divided into three groups based on suicidal ideation and behaviors. Non-parametric tests compared AdAS Spectrum scores, while Spearman’s correlation assessed the relationships between AdAS Spectrum scores and suicidality. Logistic regression analyses were conducted to identify predictive AdAS Spectrum domains for suicidal ideation and behaviors. Results: Subjects with suicidal behaviors and suicidal ideation showed significantly more autistic features than non-suicidal subjects. Correlation analysis revealed that all AdAS Spectrum domains, except empathy, were significantly correlated with both suicidal ideation and behaviors, with stronger correlations for suicidal behaviors. Moreover, restricted interests, rumination, and sensory sensitivity emerged as significant predictors of suicidal ideation, while the lack of empathy was a significant predictor of suicidal behavior. Conclusions: Our results confirm a strong correlation between the presence of ATs and suicidality in subjects with BPD, in particular highlighting rumination, altered sensitivity, and empathic deficits as specific predictors of suicidal thoughts and behaviors. Full article

Background/Objectives: Electroencephalography (EEG) has been widely used to differentiate individuals with autism spectrum disorder (ASD) and co-occurring conditions, particularly epilepsy. However, the relationship between EEG abnormalities and core features of ASD remains unclear. This study reviews the potential impact of EEG findings on the development, behavior, sleep, and seizure occurrence in ASD patients. Additionally, it evaluates whether routine EEG testing is warranted for all ASD patients, particularly in the absence of clinical seizures. Methods: A systematic review was conducted that covered literature published between 2014 and 2024. The review focused on EEG abnormalities, both epileptiform and non-epileptiform, in individuals with ASD. Studies were selected based on predefined inclusion criteria, emphasizing the prevalence, type, and clinical relevance of EEG findings. The analysis also included a critical assessment of whether EEG abnormalities correlate with specific ASD symptoms, such as cognitive impairment, speech delay, or behavioral issues. Results: EEG abnormalities were reported in 23–80% of ASD patients, indicating a broad range of findings. Despite their frequent occurrence, the evidence linking these abnormalities to specific clinical symptoms remains inconclusive. Some studies suggest an association between epileptiform patterns and more severe ASD traits, while others do not confirm this. Furthermore, the effectiveness of anticonvulsant treatment in children with EEG abnormalities and no seizures remains uncertain, with limited supporting data. Conclusions: Given the uncertain relationship between EEG findings and ASD symptoms, routine EEG testing for all children with ASD appears unnecessary. EEG should be considered primarily when epilepsy is clinically suspected. Full article

Evidence suggests that carriers of FMR1 mutations (e.g., fragile X syndrome and the FMR1 premutation) may demonstrate specific phenotypic patterns shared with autism (AU), particularly in the domain of pragmatic language, which involves the use of language in social contexts. Such evidence may implicate FMR1, a high-confidence gene associated with AU, in components of the AU phenotype. Prosody (i.e., using intonation and rhythm in speech to express meaning) is a pragmatic feature widely impacted in AU. Prosodic differences have also been observed in unaffected relatives of autistic individuals and in those with fragile X syndrome, although prosody has not been extensively studied among FMR1 premutation carriers. This study investigated how FMR1 variability may specifically influence prosody by examining the prosodic characteristics and related neural processing of prosodic features in women carrying the FMR1 premutation (PM). In Study 1, acoustic measures of prosody (i.e., in intonation and rhythm) were examined in speech samples elicited from a semi-structured narrative task. Study 2 examined the neural frequency following response (FFR) as an index of speech prosodic processing. Findings revealed differences in the production of intonation and rhythm in PM carriers relative to controls, with patterns that parallel differences identified in parents of autistic individuals. No differences in neural processing of prosodic cues were found. Post hoc analyses further revealed associations between speech rhythm and FMR1 variation (number of CGG repeats) among PM carriers. Together, the results suggest that FMR1 may play a role in speech prosodic phenotypes, at least in speech production, contributing to a deeper understanding of AU-related speech and language phenotypes among FMR1 mutation carriers. Full article

(1) Background: Autism, as an important global problem that affects many phenotypically different individuals, is associated with electroencephalographic (EEG) abnormalities and adaptability impairment. (2) Materials and Methods: In this retrospective study of a group of 101 autistic children, we aimed to evaluate the presence of EEG abnormalities, adaptive features, and clinical phenotypes via EEG, the Adaptive Behavior Assessment System II (ABAS II) scale, and neurological examination. (3) Results: Our results showed statistically significant associations between the level of adaptability obtained through the ABAS II scale and neurological deficit, specifically in terms of coordination impairment. There were also statistically significant differences between the level of adaptability and clinical phenotypes between autism type groups. (4) Conclusions: This study shows that children with autism are likely to exhibit neurological and adaptive abnormalities. Non-invasive assessment tools, such as EEG recordings, the ABAS II scale, and neurological examination offer valuable support for improved diagnosis and management. Full article

Background/Objectives: The literature highlights the importance of parental involvement in autism treatment. However, much research has predominantly focused on child outcomes and cognitive dimensions. This study explores the impact of an early intensive intervention with parental involvement, focusing on changes in parents’ affective exchanges. Notably, given the paucity of studies on fathers in the intervention context, this study examines the comparative trajectory of change considering both caregivers. Methods: Twenty autistic preschoolers were monitored for one year during a parental-based intervention. Child–mother and child–father play interactions were coded with the Emotional Availability Scales at baseline and at 12 months. Repeated measures linear mixed-effect models were employed to investigate time and caregiver effects and their interaction. Results: Results highlighted both similarities and differences in change trajectories between caregivers. Parental sensitivity, structuring, and non-intrusiveness significantly increased for both parents with fathers showing more prominent gains in structuring the interaction while being non-intrusive. Child responsiveness and involvement significantly increased, showing similar trajectories with both caregivers. Children were generally more involved while interacting with their fathers. Conclusion: Parent–child interactions with caregivers evolved toward more adaptive exchanges regarding emotional availability for children’s and parents’ dimensions. Fathers appeared to be particularly receptive regarding acquiring structuring abilities and non-intrusive behaviors. Our results underscore the importance of investigating parental features as well as the importance of actively involving caregivers to support distal outcomes and generalization. Full article

Background: Intellectual developmental disorder with autism and speech delay (IDDAS) is a rare and complex neurological disorder characterized by the presence of both intellectual and speech impairment and features of autism spectrum disorder (ASD). The prevalence of IDDAS is unknown but genetically, it is caused by heterozygous variants in the TBR1 gene. Methods: A 7-year-old female with autistic features and delayed speech development was presented with unaffected parents. Trio-joint analysis was conducted on whole-genome sequencing (WGS) data from the proband and unaffected parents. A phenotype-driven analysis was conducted to investigate variants related to the patient’s clinical presentation. A zygosity-focused analysis was performed to investigate de novo and compound heterozygote variants related to the etiology. Results: The joint-genome analysis identified a novel NM_006593.4(TBR1):c.1303C>T p.Gln435* nonsense variant in the proband. The de novo analysis confirmed the absence of the variant in the parents. No additional causative variants were identified in genes associated with the proband’s phenotype. Conclusions: This is the first report of the NM_006593.4(TBR1):c.1303C>T variant in a patient with IDDAS. This study presents the clinical features of the patient and highlights details of trio-WGS analysis in the molecular diagnosis of this complex disease. Sharing these details is important, as they contribute to the understanding of the spectrum of this rare syndrome. Full article

Background: Currently, there is a need for approaches to understand and manage the multidimensional autism spectrum and quantify its heterogeneity. The diagnosis is based on behaviors observed in two key dimensions, social communication and repetitive, restricted behaviors, alongside the identification of required support levels. However, it is now recognized that additional modifiers, such as language abilities, IQ, and comorbidities, are essential for a more comprehensive assessment of the complex clinical presentations and clinical trajectories in autistic individuals. Different approaches have been used to identify autism subgroups based on the genetic and clinical heterogeneity, recognizing the importance of autistic behaviors and the assessment of modifiers. While valuable, these methods are limited in their ability to evaluate a specific individual in relation to a normative reference sample of autistic individuals. A quantitative score based on axes of phenotypic variability could be useful to compare individuals, evaluate the homogeneity of subgroups, and follow trajectories of an individual or a specific group. Here we propose an approach by (i) combining measures of phenotype variability that contribute to clinical presentation and could impact different trajectories in autistic persons and (ii) using it with normative modeling to assess the clinical heterogeneity of a specific individual. Methods: Using phenotypic data available in a comprehensive reference sample, the Simons Simplex Collection (n = 2744 individuals), we performed principal component analysis (PCA) to find components of phenotypic variability. Features that contribute to clinical heterogeneity and could impact trajectories in autistic people were assessed by the Autism Diagnostic Interview-Revised (ADI-R), Vineland Adaptive Behavior Scales (VABS) and the Child Behavior Checklist (CBCL). Cognitive assessment was estimated by the Total Intelligence Quotient (IQ). Results: Three PCs embedded 72% of the normative sample variance. PCA-projected dimensions supported normative modeling where a multivariate normal distribution was used to calculate percentiles. A Multidimensional General Functionality Score (MGFS) to evaluate new prospective single subjects was developed based on percentiles. Conclusions: Our approach proposes a basis for comparing individuals, or one individual at two or more times and evaluating homogeneity in phenotypic clinical presentation and possibly guides research sample selection for clinical trials. Full article

Computer vision using deep learning algorithms has served numerous human activity identification applications, particularly those linked to safety and security. However, even though autistic children are frequently exposed to danger as a result of their activities, many computer vision experts have shown little interest in their safety. Several autistic children show severe challenging behaviors such as the Meltdown Crisis which is characterized by hostile behaviors and loss of control. This study aims to introduce a monitoring system capable of predicting the Meltdown Crisis condition early and alerting the children’s parents or caregivers before entering more difficult settings. For this endeavor, the suggested system was constructed using a combination of a pre-trained Vision Transformer (ViT) model (Swin-3D-b) and a Residual Network (ResNet) architecture to extract robust features from video sequences to extract and learn the spatial and temporal features of the Stereotyped Motor Movements (SMMs) made by autistic children at the beginning of the Meltdown Crisis state, which is referred to as the Pre-Meltdown Crisis state. The evaluation was conducted using the MeltdownCrisis dataset, which contains realistic scenarios of autistic children’s behaviors in the Pre-Meltdown Crisis state, with data from the Normal state serving as the negative class. Our proposed model achieved great classification accuracy, at 92%. Full article

Background: The link between autism spectrum disorder (ASD) and obsessive–compulsive disorder (OCD) and the complexity of their differential diagnosis has been vastly investigated. Growing attention has been paid to the presence of problematic Internet use (PIU) in autistic individuals. Studies assessing OCD traits in autistic individuals are scarce and even less take into account the role that this overlap may have on the development and maintenance of PIU. We aimed to investigate OCD features in ASD individuals and their association with autism severity and the prevalence of PIU, and the potential dimensions associated with a greater probability of PIU. Methods: a total of 46 participants with ASD and 53 controls were assessed with the Adult Autism Subthreshold Spectrum questionnaire and the Obsessive–Compulsive Spectrum—Short Version. Results: There were significantly higher OCD features in ASD participants along with important correlations between OCD and ASD dimensions and a higher prevalence of PIU in the ASD group. Participants with putative PIU reported greater scores on some ASD and OCD dimensions, the with Doubt and Non-verbal communication domains emerging as significant predictors of the presence of putative PIU. Conclusions: These results support the three-way link between ASD, OCD, and PIU, contributing to the hypothesis of a neurodevelopmental basis for those conditions. Full article