ObjectivesChildhood-onset schizophrenia (COS), defined by the onset of psychotic symptoms before the age of 13 years, is a rare and severe form of schizophrenia. Despite growing interest, little is known about how neurodevelopmental comorbidities shape its clinical presentation. This study aimed to examine whether COS with comorbid neurodevelopmental disorders differs in psychopathological profile from COS with psychiatric comorbidities and from COS without comorbidities.MethodsSixty-one children diagnosed with COS and evaluated at symptom onset in a specialized early psychosis service were included and classified into three subgroups: COS with neurodevelopmental comorbidities, COS with psychiatric comorbidities, and COS without comorbidities. Psychopathological dimensions were assessed using the Kiddie Schedule for Affective Disorders and Schizophrenia for School-Aged Children – Present and Lifetime Version and the Structured Interview for Psychosis-Risk Syndromes and the Scale of Prodromal Symptoms (SIPS/SOPS). Group differences were examined using MANOVA and mixed-design repeated-measures ANOVA, repeated with IQ as a covariate, with False Discovery Rate correction across all SIPS measures. A secondary analysis separated intellectual disability from autism spectrum disorder and/or attention-deficit/hyperactivity disorder.ResultsChildren with COS and neurodevelopmental comorbidities showed an earlier age at onset, lower IQ, greater bizarre thinking and less social anhedonia. In contrast, COS with psychiatric comorbidity and COS without comorbidities exhibited largely overlapping profiles, marked by greater severity of negative symptoms and more organized thought processes. Within the neurodevelopmental group, the symptom pattern did not appear to be driven by specific diagnoses.ConclusionsThese preliminary findings are consistent with variation in the configuration of psychopathological features within COS along a continuum, and highlight the relevance of neurodevelopmental trajectories in shaping symptom expression. Accounting for neurodevelopmental comorbidities may be crucial for improving early diagnostic characterization and informing targeted therapeutic strategies in pediatric schizophrenia.
The genetic orchestra of autism and its intersections with epilepsy, intellectual disability, and ADHD
Autism is a complex condition with marked phenotypic variability and a multifactorial etiology orchestrated by diverse genetic and environmental influences. In this review, we dissect what we refer to as autism’s “genetic orchestra”, spanning from the high-impact “soloists”, de novo and ultra-rare variants with large effect sizes, to the “polyphonic background” of common variants which individually exert modest effects but collectively have significant impact. We examine how this orchestra wires neural circuits, with convergent biological pathways modulating synaptic function and chromatin remodeling.
Ensemble of Domain-Specific Natural Language Processing and Large Language Models for Detecting Suicidal Ideation and Mental Health Conditions in Social Media Text: Development and Evaluation Study
<strong>Background:</strong> Mental illness contributes substantially to global disability, and public adoption of AI for mental health support is accelerating without commensurate safety evaluation. General-purpose large language models can fail to recognize naturalistic text expressing suicidal ideation, with immediate clinical consequences. Domain-specific natural language processing methods offer a contrasting approach, but ensembles integrating the two have not been formally characterized. <strong>Objective:</strong> We aimed to (1) benchmark 5 modeling approaches for classifying mental health–related social media text, (2) develop and optimize ensembles integrating a domain-specific natural language processing classifier with a fine-tuned large language model, and (3) derive a closed-form framework constraining ensemble weighting in safety-critical classification. <strong>Methods:</strong> We analyzed 60,889 publicly available Reddit and Twitter texts spanning 9 categories (anxiety, bipolar disorder, depression, a normal baseline, personality disorder, stress, suicidal ideation, attention-deficit/hyperactivity disorder, and autism spectrum disorder). Labels were derived from the originating subreddit or a self-stated condition and are not clinical diagnoses. Five architectures were compared: prompt-engineered base GPT-4o-mini; fine-tuned GPT-4o-mini; a domain-specific classifier (support vector machine over symptom-informed lexical features); and 2 ensembles of these models, hybrid probability–indicator fusion and soft probability fusion. Data were split into 70%, 10%, and 20% at the post level (n=42,622, n=6089, and n=12,178); weights were selected on the validation split and all reported performance comes from the held-out test split. Closed-form bounds on permissible language model weights were derived for both strategies. CIs are paired bootstrap intervals (n=10,000 replicates); accuracy differences were tested with exact McNemar tests. <strong>Results:</strong> The domain-specific classifier achieved 91.9% accuracy (95% CI 91.4%-92.4%), exceeding the base (58.7%) and fine-tuned (88.6%) large language models. Both ensembles outperformed either constituent model, reaching 93.9% (soft fusion; 95% CI 93.5%-94.3%) and 93.8% (hybrid fusion; 95% CI 93.4%-94.2%) at a weighting of 60% classifier to 40% fine-tuned model, selected on validation (<i>P</i><.001 for both against the classifier alone; the 2 ensembles did not differ from each other [<i>P</i>=.16]). The hybrid ensemble reduced the miss rate for the suicidal ideation category from 32.5% (650/2000) to 1.9% (37/2000), a 17.6-fold reduction relative to the base model, although its advantage over the classifier alone within that category was not significant (<i>P</i>=.68). Accuracy fell discontinuously above a 50% language model weight, where the hybrid ensemble reduced exactly to the fine-tuned model; the selected weight satisfies the derived instance-level bound of 44.0%. <strong>Conclusions:</strong> Domain-specific clinical grounding remained necessary for stable ensemble performance in this corpus, and probabilistic fusion outperformed both constituent models when language model weight was bounded by a derivable, model-agnostic constraint. Because labels were community-inferred and only one corpus was analyzed, these results are hypotheses requiring external validation on clinically characterized data before use in decision support.
Mindfulness-Based Intervention for Parents of Autistic Children in Pakistan
Conditions: Autism Spectrum Disorder; Parental Stress
Interventions: Behavioral: Stronger Together Mindfulness-Based Intervention; Behavioral: Psychoeducation Program
Sponsors: Northeast Normal University
Completed
Interventions: Behavioral: Stronger Together Mindfulness-Based Intervention; Behavioral: Psychoeducation Program
Sponsors: Northeast Normal University
Completed
Reliability of Childhood Autism Rating Scale, Second Edition, Assessments Using Telepsychiatry for Children With Neurodevelopmental Disorders and Their Caregivers: Randomized Feasibility Study
Background: The COVID-19 pandemic has increased the demand for telepsychiatry in neurodevelopmental assessment; however, few studies have examined the interrater reliability of clinician-rated autism scales, such as the Childhood Autism Rating Scale, Second Edition (CARS2), when used remotely. Although the feasibility and validity of telehealth assessments have been explored previously, the consistency between remote and in person CARS2 ratings by different clinicians remains underinvestigated. Objective: The objective of this study was to evaluate agreement between CARS2 total scores obtained by different evaluators using telepsychiatry and face-to-face assessments in children with autism spectrum disorder (ASD) and/or attention-deficit/hyperactivity disorder (ADHD). Methods: In this randomized feasibility study, 75 children aged 6 to 17 years with diagnoses of ASD, ADHD, or both were enrolled at 5 medical institutions in Japan; 73 of 75 were included in the final analysis. Each participant underwent 2 independent CARS2 evaluations, one face-to-face and the other via telepsychiatry, conducted by different evaluators who were blinded to each other’s ratings. Remote assessments were conducted using a secure video platform with caregiver facilitation. Agreement was assessed using intraclass correlation coefficients (ICCs) for the overall sample and subgroups defined by primary diagnosis, sex, and age. Results: The overall ICC for CARS2 total scores between face-to-face and telepsychiatry assessments was 0.582 (95% CI 0.407‐0.717), indicating moderate agreement. The ICC was 0.546 among participants with ASD as the primary diagnosis and 0.495 among those with ADHD as the primary diagnosis. Point estimates were higher among girls than boys (0.666 vs 0.495) and among children aged 11 years or older than among those aged 10 years or younger (0.676 vs 0.419). In a sensitivity analysis including all participants with an ASD diagnosis, the ICC was 0.580. Conclusions: CARS2 total scores obtained through telepsychiatry showed moderate agreement with scores obtained through face-to-face assessment when the assessments were conducted by different evaluators in different settings. Higher point estimates were observed among older children and girls, although these subgroup findings should be interpreted cautiously. Telepsychiatry-based CARS2 assessment may be considered a complementary approach rather than a replacement for comprehensive face-to-face evaluation. Larger studies using more standardized assessment protocols are needed.
<img src="https://jmir-production.s3.us-east-2.amazonaws.com/thumbs/5ae732084c2741b52596b22d0df72157" />
Effectiveness of Interactive Techniques on Oral Hygiene Skills in a Group of Autistic Egyptian Children
Conditions: Autism Disorder; Autism Spectrum Disorder (ASD; Autism; Plaque Reduction; Plaque Induced Gingival Disease; Plaque Accumulation; Gingival Bleeding; Gingival Inflammation and Bleeding
Interventions: Procedure: Peer model; Procedure: Pre-recorded video of peer modeling; Other: Pedagogical method
Sponsors: Faculty of Dental Medicine for Girls
Not yet recruiting
Interventions: Procedure: Peer model; Procedure: Pre-recorded video of peer modeling; Other: Pedagogical method
Sponsors: Faculty of Dental Medicine for Girls
Not yet recruiting
Reduced contagious yawning in psychiatric disorders: a systematic review of potential social-cognitive mechanisms
IntroductionContagious yawning has been proposed to reflect multiple aspects of social cognition, including empathy, emotional contagion, self-processing, Theory of Mind (ToM), and action observation mechanisms such as the human mirror neuron system (hMNS). However, its underlying mechanisms remain debated, with evidence suggesting additional roles for social attention, gaze allocation, social motivation, and neurobiological factors. This systematic review examined evidence for reduced contagious yawning in Autism Spectrum Disorder (ASD), schizophrenia-spectrum disorders, and psychopathic traits, and evaluated potential underlying mechanisms.MethodsPubMed, PsycINFO, and Scopus were systematically searched for clinical and mechanistic studies of contagious yawning in psychiatric and healthy populations. Studies were screened using predefined eligibility criteria, and risk of bias was assessed using design-specific Joanna Briggs Institute (JBI) critical appraisal tools. Twenty-three studies met the inclusion criteria.ResultsReduced contagious yawning was reported in ASD, psychopathic traits, and schizophrenia-spectrum disorders, although findings varied across conditions. In ASD, reduced contagious yawning was associated with social attention, gaze allocation, oxytocin-related processes, and broader social-cognitive differences. In psychopathic traits, evidence more consistently implicated affective-interpersonal traits and reduced emotional responsiveness. Evidence for schizophrenia-spectrum disorders was more limited, with proposed mechanisms including impairments in social cognition, ToM, negative symptoms, and possible medication effects. Neuroimaging and electrophysiological findings implicate brain systems involved in social cognition, self-processing, and action observation, although the specific role of the hMNS remains uncertain.DiscussionReduced contagious yawning may reflect altered social-cognitive processing rather than empathy alone, with contributing mechanisms differing across psychiatric conditions. Interpretation is limited by small sample sizes, methodological heterogeneity, and variation in study design. Further well-powered studies are needed to clarify its neurobiological basis and clinical significance.
Development and Evaluation of a Parent-led Intervention Module for Early Autism Spectrum Disorder (PRIME-ASD) in Odisha, India: Protocol for a Multiphase Mixed-methods Study Including an Open-label Randomised Controlled Trial
Conditions: Autism Spectrum Disorder
Interventions: Behavioral: Behavioral: PRIME-ASD (Parent-led Intervention Module for Early Autism Spectrum Disorder); Behavioral: Behavioral: PRIME-ASD; Other: Treatment as usual
Sponsors: All India Institute of Medical Sciences, Bhubaneswar
Not yet recruiting
Interventions: Behavioral: Behavioral: PRIME-ASD (Parent-led Intervention Module for Early Autism Spectrum Disorder); Behavioral: Behavioral: PRIME-ASD; Other: Treatment as usual
Sponsors: All India Institute of Medical Sciences, Bhubaneswar
Not yet recruiting
Differences in autism features and adaptive functioning between adolescents with autism spectrum disorder and social communication disorder
IntroductionThis study aimed to characterize adolescents with social communication disorder (SCD) in comparison with those with autism spectrum disorder (ASD) across two dimensions: autism features and adaptive functioning. SCD shares social communication difficulties with ASD, resulting in unclear diagnostic boundaries and raising concerns about its clinical utility given that existing research and resources remain largely ASD-oriented.MethodsData from 76 adolescents with ASD and 44 with SCD (ages 10–18 years) were analyzed. Lifetime and current autism features were assessed using the Autism Diagnostic Interview–Revised (ADI-R) and Social Responsiveness Scale, Second Edition (SRS-2), respectively, and adaptive functioning using the Vineland Adaptive Behavior Scales, Second Edition. Propensity score matching was performed using age and Full-Scale Intelligence Quotient, and group differences were compared before and after matching. Exploratory interaction analyses additionally examined potential moderators of group differences.ResultsAfter matching, adolescents with SCD showed less severe lifetime autism features across the core ADI-R domains, with large effect sizes (ds = .98–1.34, all p <.001). Current autism features showed smaller group differences, which remained significant across all SRS-2 subscales except Social Motivation (ds = .46–.68, p = .004–.046). Adolescents with SCD showed better adaptive functioning than those with ASD, although group differences in Communication (p = .085) and Socialization (p = .144) were no longer statistically significant after matching. Psychiatric comorbidity moderated group differences in Communication, Socialization, and overall adaptive functioning, while attention-deficit/hyperactivity disorder showed a similar but less robust pattern for Communication, which did not remain significant after correction.DiscussionOverall, accounting for age and intellectual ability, the distinction between ASD and SCD remained evident at the symptom level, whereas functional differences were partly influenced by these factors. These findings suggest that diagnostic classification alone may not fully capture the functional needs of adolescents with ASD and SCD, highlighting the importance of a multidimensional approach that considers symptom profiles, adaptive functioning, developmental and intellectual factors, and psychiatric comorbidity.
Autism Target Discovered in Endothelial Cells in Genetic Deletion Mouse Model
Researchers at The Ottawa Hospital and at the University of Ottawa have been able to reverse certain behavioral symptoms in a mouse model of autism by fixing a problem in the endothelial cells (ECs) of brain blood vessels. Building on studies in a 16p11.2 deletion mouse model of ASD that identified brain endothelial cell abnormalities, the team linked 16p11.2 deletion with reduced levels of ATP in endothelial cells. They found that activating P2Y2 receptors rescued the 16p11.2-deletion-associated mouse behaviors.
The results present a promising new treatment target for autism spectrum disorder (ASD) symptoms. “The road from discovery to clinical trials is long, but we’re excited by the possibility that our findings might one day improve the daily lives of people with autism,” said Baptiste Lacoste, PhD, senior scientist at The Ottawa Hospital and professor at the University of Ottawa.
Baptiste is senior author of the team’s published paper in Neuron (“Purinergic receptor activation rectifies autism-associated endothelial dysfunction”), in which they concluded “These findings suggest that P2Y2 receptor activation represents a promising strategy to rescue brain EC dysfunction and, in turn, improve autism-related behaviors in the 16p11.2 deletion ASD syndrome.”
Autism is a neurodevelopmental condition with widely varying characteristics. Some of the behavioral symptoms can make life more challenging. While many people with autism have found ways to manage these symptoms, no drug treatment exists.
Lacoste’s team previously discovered that blood vessels in the brain don’t work properly in mouse models with a 16p11.2 deletion, one of the most common genetic mutations seen in autism. They were the first to look at what was happening in the blood vessels of the brain. “Recent evidence in a 16p11.2 deletion mouse model of autism spectrum disorder (ASD) revealed brain endothelial abnormalities postnatally, but the endothelial alterations eliciting these changes remain unknown,” they wrote.
Through their newly reported work the researchers have now found that the problem began in the endothelial cells lining the blood vessels. These cells make sure blood quickly gets to the parts of the brain that are active. This responsive blood supply is needed for proper brain function.
However, the endothelial cells in the 16p11.2 deletion mice don’t respond quickly enough. This happens early in brain development and causes behavioral symptoms later in life, including hyperactivity, repetitive movements, and motor learning impairment.
Headed by former PhD student, Julie Ouellette, PhD, the research team looked at what was wrong with these endothelial cells and whether it could be fixed. They discovered that the cells had half the normal level of ATP. “We demonstrate that 16p11.2 deletion induced EC dysfunction is caused by a bioenergetic failure with reduced intracellular ATP,” they explained. While ATP is usually considered an energy molecule, in this case the cell was missing its target, called a P2Y2 receptor, on its surface. “The identified energetic failure was restricted to ECs, emphasizing these cells as key contributors to ASD pathophysiology,” the investigators added.
By activating this P2Y2 receptor, the researchers were able to restore the cell’s function, increase blood flow in the brain, and reverse the behavioral symptoms in adult mice. This was achieved using a drug known to activate P2Y2 and which is currently approved for humans in Japan and South Korea to treat dry eye syndrome.
“Activation of ATP signaling via endothelial P2-class purinergic receptors, specifically P2Y2, rescued EC dysfunction, restoring angiogenic capacity in vitro, endothelium-dependent cerebrovascular reactivity ex vivo, and activity-dependent cerebral blood flow (CBF) in vivo,” the team stated. “A selective pharmacological P2Y2 agonist also rescued adult 16p11.2-deficient behavioral phenotypes.”
Lacoste said, “It’s as if these cells are asleep, and now we can wake them up. And we may only need to treat them once to wake them up permanently. We will test that further, but it’s an encouraging feature for a future treatment.”
In their paper the authors concluded, “Taken together, this study demonstrates that metabolic reprogramming of brain ECs via purinergic receptor engagement represents a promising therapeutic avenue for ASD.” They also point out that the study only looked at adult mice. This means targeting P2Y2 could reverse behavioral symptoms that were already well established.
Next, the team plans to treat mice earlier in life to see if early treatment has additional benefits. The team has also filed a patent application for using P2Y2 activation in the blood vessels to treat autism symptoms. They are interested in exploring drug development with the aim of eventual clinical trials.
The post Autism Target Discovered in Endothelial Cells in Genetic Deletion Mouse Model appeared first on GEN – Genetic Engineering and Biotechnology News.