BackgroundThe use of electroencephalography (EEG) in automated screening of Attention-Deficit/Hyperactivity Disorder (ADHD) has created a large body of literature that suggests promising outcomes, with reported classification accuracies often above 90%. A major methodological issue suggests that a substantial part of these results are actually due to data leakage, whereby EEG epochs pertaining to the same subject end up in both training and testing sets, allowing classifiers to capitalize on features specific to the individual rather than on genuine disorder-related biomarkers.MethodsWe assessed the performance of three classical machine learning algorithms, namely, Logistic Regression (LR), Random Forest (RF), and Support Vector Machine (SVM), as well as three deep learning models: Long Short-Term Memory (LSTM), Convolutional Neural Network (CNN), and CNN-BiLSTM, on a standard pediatric EEG dataset containing 121 children and 4,173 epochs. The performance of each model was compared in terms of both segment-wise cross-validation (Protocol A) and subject-wise cross-validation (without any data leakage, Protocol B).To evaluate neurotopographic plausibility without making unsupported causal assertions, we applied Deep SHapley Additive exPlanations (SHAP) to the best-generalizing architecture.ResultsThe performance discrepancy was substantial. Under segment-wise evaluation, the SVM operating on power spectral density (PSD) features reached 90.0% accuracy (95% CI: [89.1%, 90.9%], AUC = 0.96). However, the same model dropped to 65.6% (95% CI: [62.1%, 69.1%], AUC = 0.72) under subject-wise evaluation—a statistically significant 24.4 percentage point collapse (p < 0.001, Wilcoxon signed-rank). In contrast, deep architectures learning directly from raw EEG were resilient: the stand-alone CNN lost only 2.5 percentage points, achieving 72.7% accuracy (95% CI: [66.0%, 79.4%], AUC = 0.72, recall = 88.0%) on completely unseen participants. Post-hoc SHAP attribution identified the highest relative contributions in frontal (F3, Fz, F4) and central (Cz) electrodes, aligning with established ADHD neurophysiology.ConclusionHand-engineered spectral features are highly vulnerable to identity leakage, whereas end-to-end convolutional models generalize across subjects with realistic, uninflated performance. Strict subject-wise validation is strongly recommended as standard practice for translational EEG research.
Psychologists’ knowledge, attitudes, and training experiences regarding mental illness in individuals with intellectual disabilities in Saudi Arabia: a cross-sectional study
IntroductionIntellectual disability (ID) impacts an estimated 1-3% of the population worldwide, with a higher incidence in regions with limited healthcare access. In Saudi Arabia, current prevalence data, especially for adults, are scarce. This cross-sectional study explores the systemic challenges psychologists perceived in the diagnosis and treatment of mental illnesses in individuals with intellectual disabilities.MethodsA standardized Arabic-language questionnaire was distributed to 144 licensed psychologists in Saudi Arabia to collect data on professional backgrounds, educational history, work experience, attitudes, and knowledge.ResultsData were analyzed using factorial ANOVA and Spearman’s correlation tests. The analysis revealed that years of professional experience significantly influenced attitudes (F = 5.024, p =.008, partial η² =.073), while training experience had a pronounced effect on knowledge of mental comorbidities in ID (F = 75.83, p <.001, partial η² =.367). A strong correlation was identified between training experience and knowledge (ρ =.811, p <.001), whereas no significant correlation was found for attitudes.
Clinical factors predicting tic persistence into adulthood
BackgroundDespite widespread patient and family interest in long-term outcome prediction at the time of Tourette syndrome (TS) diagnosis, there is limited data on factors associated with disease severity and impairment in adulthood. This study aimed to examine the relationship between childhood and adulthood worst-ever tics and identify predictors of adulthood tic severity and impairment, including the role of significant life events.MethodsIn a cross-sectional design, 258 adult participants with TS completed an online questionnaire assessing tic severity and impairment during their worst-ever tic periods in childhood and adulthood, co-occurring obsessive-compulsive disorder (OCD) and attention deficit hyperactivity disorder (ADHD) symptoms and clinical and demographic characteristics.ResultsWorst-ever childhood tic severity and impairment were significantly associated with greater worst-ever adulthood tic severity and impairment. Co-occurring OCD was also associated with greater tic severity and impairment in adulthood. Use of tic medication was a significant predictor of greater worst-ever adulthood tic impairment, but not severity. Overall, 153 (59.3%) participants reported experiencing a significant life event at the time of their worst-ever tics in adulthood, and the presence of a significant life event was associated with greater worst-ever adulthood tic impairment. There was a significant effect of negative and neutral life events, but not positive life events, on adult worst-ever tic severity and impairment, compared to those not reporting a significant life event.DiscussionThese findings provide insight into characteristics present either in childhood or in adulthood that may help predict the presence and severity of tic symptoms in adulthood.
Sleep and Drug Use: Neuroimaging Evidence for a Multidimensional Brain Framework
Sleep plays a critical role in the initiation and maintenance of drug use, as well as recovery among individuals with substance use disorders. Sleep is a multidimensional construct, and a growing body of research has demonstrated the relative independence of various components. Specific sleep characteristics including insomnia (self-reported sleep disturbances), short sleep duration, late sleep timing and sleep irregularity have each been associated with increased risks of drug use. However, it remains unclear whether these sleep components contribute to substance use through shared neurobiological pathways.
Anti-Inflammatory Drug Target for Alzheimer’s, TBI, and Neurodegenerative Disease Identified
The results of research headed by a team at the University of Birmingham suggest that inflammatory conditions in the brain, including traumatic brain injury (TBI) and degenerative diseases such as Alzheimer’s disease and Parkinson’s disease, could be targeted with an existing developmental drug.
Using live cultures of human brain cells and slices of brain tissue obtained during neurosurgery, the researchers, headed by Nicholas Barnes, PhD, professor at the University of Birmingham College of Medicine and Health, investigated the role of the P2X7 receptor, which is responsible for triggering inflammatory signaling. Their findings revealed that these P2X7 receptors drive the release of cytokines involved in controlling inflammation. By blocking this receptor with a specific antagonist, the team was able to significantly reduce the inflammatory response in human brain tissue.
The team suggests that their results could open the door to treating a wide spectrum of chronic neurological conditions, including TBI, neurodegenerative diseases, and even psychiatric disorders such as depression and psychosis, which are increasingly understood to have a neuroinflammatory component.
Barnes said, “This exciting discovery marks a major step toward repurposing existing therapeutics to combat neuroinflammation at its source. The identification of this receptor could have far-reaching implications for some of the most debilitating and widespread brain disorders such as Alzheimer’s disease, Parkinson’s, and multiple sclerosis, or inflammation-linked psychiatric conditions like schizophrenia and depression.”
Barnes is senior and corresponding author of the team’s published paper in Brain, titled “P2X7 receptor-mediated IL-1β release by human brain tissue: the impact of CNS-penetrant potential therapeutics,” in which they concluded “Our findings provide direct relevant evidence for the use of P2X7R antagonism to inhibit human microglia-mediated inflammation, with arising potential benefits for patients with TBI and other neuroinflammatory diseases.”
TBI is a major cause of death globally, and there are currently there are no approved therapeutic drugs to improve clinical outcomes, “… emphasizing the clear unmet substantial clinical need,” the authors wrote.
The mechanical damage associated with TBI drives a neuroinflammatory response. “The purinergic P2X7 receptor (P2X7R) is a key driver of neuroinflammation in a range of animal models of traumatic brain injury,” the team continued. P2X7R is expressed by microglia, the resident immune cells in the CNS that are involved in many developmental, homeostatic and pathological roles. “It is well recognized that microglial activation and the hostile neuroinflammatory response arising after the initial insult provide a therapeutic window for pharmacological intervention,” the investigators further stated.
For their reported study investigating how brain cells respond to and manage inflammation, the team developed a way of turning a type of white blood cell into microglia, replicating a normal cellular transformation that has recently been identified to occur in the brain as a natural part of human aging. These microglia are the central coordinators of the immune system in the brain.
Using readily accessible human peripheral monocytes taken from blood samples, the researchers converted them into microglia-like cells—human monocyte-derived microglia (hMDM)—that were used to see how microglia are likely to respond to the inflammation signals. “This enabled us to demonstrate the ability of clinically relevant P2X7R antagonists, including brain-penetrant molecules, to curtail pro-inflammatory cytokine release,” they wrote.
The team showed that administering a P2X7 receptor antagonist interrupted the triggers that these microglia give off as they are damaged and die. Barnes said, “Studying human microglia has long been a major challenge: once removed from their native brain environment, they rapidly lose their defining characteristics, likely due to the absence of critical regulatory signals. Our approach involved the use of monocyte-derived microglia which provide a powerful, scalable, and virtually unlimited platform for studying human microglial biology with unprecedented precision.”
The team confirmed their results using adult human precision-cut brain slices that had been generated subsequent to neurosurgical resections. “Having identified the response in the human monocyte-derived microglia, this provided the impetus to translate these findings with human brain obtained following neurosurgical procedures, Barnes continued. “This successful translation means the next stage for this research is the development of clinical trials in patients with neurodegenerative conditions and patients with TBI where there are no effective pharmacological treatments to reduce the neuroinflammation and arising damage.”
In their paper the authors concluded, “The present study provides direct translational evidence from human cellular and brain tissue models to support the clinical use of P2X7R antagonists to limit secondary ATP-driven neuroinflammatory events, such as those that occur in TBI, and thus might improve the clinical outcomes for patients.”
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Depression and musculoskeletal diseases: a framework of systemic mechanisms
Musculoskeletal disorders (MSDs) encompass a broad spectrum of conditions affecting bones, joints, and muscles, characterized by significant pain and functional impairment, and have become a major global health burden. In recent years, accumulating evidence has revealed complex bidirectional interactions between depression and musculoskeletal health. This review focuses on depression and delineates how it may influence the pathological progression of MSDs through multiple pathways, including neuroendocrine dysregulation, aberrant inflammatory responses, epigenetic modifications, dysregulated extracellular vesicle-mediated communication, abnormal neural activity along the brain–joint axis, and gut microbiota ecological imbalance. Collectively, depression is associated with an increased risk of MSDs and engages intricate interactions across multiple biological systems. Our study underscores that musculoskeletal disorders are by no means confined to isolated joints or local tissues, but rather represent complex diseases with prominent systemic features. Integrated management strategies combining psychosocial interventions, appropriate physical exercise, and dietary modification hold promise as potential multitargeted approaches for the comprehensive treatment of MSDs.
EEG signature in psychiatrist’s subjective experience: a pilot study
IntroductionThe Assessment of Clinician’s Subjective Experience (ACSE) is a self-report questionnaire developed to evaluate clinicians’ subjective experiences during patient interactions. While its psychometric properties and clinical validity have been supported, its neurobiological correlates have not yet been investigated.MethodsIn this pilot study, two clinicians and ten patients participated in a three-phase protocol comprising: (1) a first clinical interview, (2) ACSE administration, and (3) listening to the audio recording of the first clinical interview. EEG activity was recorded from clinicians during both the first clinical interview and questionnaire administration. Neural data were analyzed in terms of relative power spectral density, node strength, and global efficiency computed from imaginary coherence.ResultsClinicians were psychiatrists, one male and one female. Seven patients were diagnosed with mixed anxiety and depressive disorder, and three with unspecified anxiety disorders. ACSE scores were highest for the Difficulty in attunement and Engagement dimensions, consistent with previous literature. EEG findings revealed dimension-specific and topographically distinct oscillatory patterns for only two ACSE dimensions: Difficulty in Attunement and Engagement. More limited evidence emerged for Disconfirmation. Functional connectivity analyses indicated different network profiles, characterized by differences in global efficiency patterns. Correlational analyses further identified significant associations between ACSE dimensions and EEG-derived features.DiscussionThese preliminary findings provide initial evidence that clinicians’ subjective experiences during clinical encounters could be associated with measurable neural signatures, offering a novel perspective on the neurobiological basis of intersubjective processes in clinical settings.
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
Inhibitory control and error processing in Obsessive-Compulsive Disorder: A mega-analysis of task-based fMRI data by the ENIGMA-OCD consortium
Obsessive-compulsive disorder (OCD) is a chronic condition in which impaired inhibitory control and excessive error monitoring may contribute to maintenance of obsessions and compulsions. This mega-analysis investigates neural activation during response inhibition and error processing using adult (OCD=563; control=348) and child (OCD=83, control=114) data from the ENIGMA-OCD consortium and the ABCD study (probable OCD=343; control=361).