Neurological and psychiatric disorders are a highly prevalent source of global disability. For the majority of these conditions, including autism spectrum disorder (ASD), disease-modifying treatments remain unavailable, and existing pharmacological interventions are largely palliative.
Psilocybin as a Novel Therapy for Residual Anhedonia
Conditions: Anhedonia; Emotional Blunting
Interventions: Drug: Psilocybin; Drug: Placebo
Sponsors: NYU Langone Health; National Institute of Mental Health (NIMH)
Not yet recruiting
Interventions: Drug: Psilocybin; Drug: Placebo
Sponsors: NYU Langone Health; National Institute of Mental Health (NIMH)
Not yet recruiting
Feasibility and Implementation of Early Referral in Perinatal Mental Health
Conditions: Perinatal Depression; Perinatal Anxiety
Interventions: Behavioral: The e-Perinatal intervention is a personalized mobile health (mHealth) program; Other: Standard routine maternal care
Sponsors: University of Seville; Andalusian Health Service; Junta de Andalucia
Not yet recruiting
Interventions: Behavioral: The e-Perinatal intervention is a personalized mobile health (mHealth) program; Other: Standard routine maternal care
Sponsors: University of Seville; Andalusian Health Service; Junta de Andalucia
Not yet recruiting
Helping Older Veterans Use Mental Health Apps: Qualitative Interviews and Development of a New Program
Background: Mobile mental health apps may provide an accessible, scalable, and private avenue for older veterans who may not otherwise seek or receive care to address their mental health concerns. However, older veterans may experience barriers to using these apps that need to be addressed to facilitate effective use. Such support could be effectively implemented within the US Veterans Health Administration to facilitate the use of the United States Department of Veterans Affairs’ established mental health apps and to benefit older veterans with mental health concerns. Objective: This study aimed to (1) assess older veterans’ interest in and barriers to using mental health apps to address problems such as difficulties with social connection, and (2) develop and pilot a coaching program to address barriers that older veterans experience in using mobile devices and apps. Methods: Rapid qualitative analysis of semistructured qualitative interviews with 12 older veterans identified themes regarding interest, barriers, and preferences for support for using mobile apps. These themes informed the development of a coaching program, which was piloted with 13 older veterans to assess acceptability, feasibility, and resultant signals of changes in mobile device proficiency. Results: Most veterans expressed interest in using mental health apps. One of the most common barriers was familiarity and proficiency with mobile devices and app technology. Other common barriers included usability or accessibility of the technology or app, motivation, and memory. Veterans reported interest in receiving coaching support. Though the majority of veterans expressed some preference for more individualized and in-person support, they identified both benefits and drawbacks to all potential coaching modalities (group vs one-on-one, in-person vs remote)—including issues of individualizable and guided assistance, feasibility and accessibility of the support, and group settings as potential avenues for social connection as well as potential susceptibility to challenging social dynamics and interactions. Mobile Device and App Learning (MoDAL)—a 2-session, interactive, remote educational group—was developed and piloted. Most veterans who participated found MoDAL helpful. Participants’ mobile device proficiency showed a statistically significant improvement on average pre- to post-MoDAL, although this effect was small, and the small sample size limits the strength of the conclusions. Conclusions: Older veterans do have some interest in using mobile mental health apps to address mental health–related issues. However, they experience critical barriers, including a lack of familiarity and proficiency with the technology. MoDAL may improve older veterans’ comfort and proficiency with mobile devices and apps, which could address one of the barriers that impacts downstream engagement in mental health apps and other virtual care modalities.
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Heart Attack Byproduct Linked to Brain Inflammation and Cognitive Decline
Researchers at the University of Ottawa has found that a heart attack may trigger neurological disorders and cognitive decline, and have identified the reactive molecule methylglyoxal as a potential driver of neuroinflammation after myocardial infarction. The research, published in the journal Advanced Science, adds to a growing body of evidence that injury to the heart can directly alter brain function through the “heart-brain axis.”
“Methylglyoxal has been widely studied for its role in metabolic diseases, including diabetes, but much less is known about its function in other diseases. In a previous study, we discovered that methylglyoxal was produced by dying heart tissue after a heart attack. Based on this evidence, we predicted that methylglyoxal in the blood would target other organs and tissues, including the brain—and this is what we did indeed observe,” said senior author Erik Suuronen, PhD, a professor in the department of surgery and director of the BEaTs research program at the University of Ottawa Heart Institute.
The researchers found that methylglyoxal-derived advanced glycation end products (MG-AGEs) accumulated in the brains of mice within hours after myocardial infarction and remained elevated seven days later. This accumulation resulted in neuroinflammation, activation of microglia and macrophages, increased inflammatory signaling, and disruption of the blood-brain barrier.
The study examined five brain regions in female and male mice after they induced myocardial infarction. Brain tissue was collected at six hours and seven days after the cardiac event. Researchers measured levels of MG-H1, the major MG-derived advanced glycation end product, along with glyoxalase-1, inflammatory cytokines, receptors for AGEs, activated microglia, and macrophages.
The work builds on a multiple earlier research studies linking cardiovascular disease and neurological disorders. Prior clinical studies have found that myocardial infarction and heart failure are associated with increased risks of dementia, depression, anxiety, and cognitive impairment. Patients with depression after myocardial infarction also face a greater risk of future cardiovascular events.
The heart-brain axis is the bidirectional relationship between cardiac and neurological function similar to the gut-brain axis. Changes in heart function can influence the brain, while neurological disease can also affect cardiovascular health. While the biological factors relating to this interaction are still emerging, the new research indicates that methylglyoxal may be one factor contributing to this relationship.
MG is produced as a byproduct of glycolysis and can react with proteins, lipids, and DNA, contributing to cellular dysfunction. Conditions associated with myocardial infarction, such as ischemia, inflammation, oxidative stress, and metabolic shifts toward anaerobic glycolysis, promote MG production while limiting its detoxification.
The mouse studies showed that the brainstem had the highest accumulation of MG-H1 after myocardial infarction, followed by the cortex. These same regions also showed elevated expression of inflammatory markers and receptors associated with MG-mediated signaling. Male mice exhibited higher MG-AGE accumulation and greater neuroinflammation than females in several brain regions.
The team also documented increases in inflammatory markers including NF-κB, TNF-α, and activated microglia across multiple brain regions. The cortex and brainstem demonstrated the highest inflammatory responses. According to the authors, the findings suggest a “region-specific vulnerability to glycation-induced stress post-MI.”
The findings could have implications for better understanding how heart attacks contribute to long-term neurological disease risk, including dementia and Alzheimer’s disease. The researchers noted that MG-AGEs already have recognized roles in neurodegenerative disease and mental health disorders.
The researchers have already used the information from the study to develop a peptide designed to trap methylglyoxal and prevent cellular damage, as a potential new therapy. The peptide will be tested for its ability to protect the brain after myocardial infarction.
“Given the increased risk of subsequent heart attacks or death in heart attack patients who experience depression or anxiety, being able to alleviate these conditions could reduce subsequent major cardiac events and improve the lives of countless patients, filling an urgent unmet clinical need,” Suuronen says.
The researchers said future work will examine how MG-driven inflammation contributes to neuron death and behavioral changes after myocardial infarction. They also plan further research to better understand the glyoxalase detoxification system, including glyoxalase-1 activity and glutathione levels.
The post Heart Attack Byproduct Linked to Brain Inflammation and Cognitive Decline appeared first on Inside Precision Medicine.
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Text Messaging for Mental Health Promotion With Migrants Returning to Mexico: Content Development and Piloting With a Needs Assessment Approach
Background: Returning migrants face a variety of challenges that limit their ability to integrate and adapt to Mexico. This represents a break in their life trajectory, with effects on family dynamics, mid- and long-term projects, and uncertainty about short-term plans. Objective: This study describes the coproduction approach used to design and develop a WhatsApp-based psychoeducational program entitled “Here Again: Coping With Return,” which aims to promote the adoption of self-care behaviors to reduce the risk of mental health and substance use problems among returning migrants. Methods: The process included four phases: (1) a situational diagnosis of the needs of migrants in preventing mental health problems and reducing the risks associated with alcohol use, (2) the design and development of content, (3) evaluation by a group of experts in mental health and substance use, and (4) pilot testing. Results: The study identified 4 intervention pillars: emotional risk factors, coping strategies, barriers to care, and technological feasibility. Eighty WhatsApp messages were developed, focusing on mental health (n=52, 65%) and alcohol use (n=20, 25%) through a sequence of motivation, instruction, and reinforcement. Following an expert evaluation that simplified technical language, a pilot study with 14 migrants showed a 78.6% completion rate. Participants reported the successful application of emotional management tools and a preference for text-based messages over audiovisual content to conserve mobile data. Conclusions: This study describes the development of a psychoeducational program for returning migrants based on coproduction, integrating user needs and expert experience. The intervention addresses emotional management, self-care, and substance use prevention, using WhatsApp for its accessibility and low cost. The pilot results demonstrated high acceptability and a 78.6% retention rate over 16 weeks, highlighting that the culturally sensitive approach and accessible language enabled participants to apply mental health tools autonomously and effectively.
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When AI Colludes: Clinical Reliability of Training and Preference Data as a Trustworthy-AI Criterion
Research on artificial intelligence (AI) and mental health has focused largely on harms at deployment, including chatbot safety, sycophancy, and AI-associated delusions. Less attention has been paid to a prior question: whether the human-generated text and preference judgments that shape large language models are themselves clinically reliable, particularly when self-report may be distorted. This Viewpoint aims to develop the clinical psychiatric construct of collusion—the uncritical acceptance of an unreliable account—as an analytic lens for AI training and deployment, and to argue that the clinical reliability of training and preference data should be treated as an explicit trustworthy-AI criterion in mental-health–relevant systems. A conceptual synthesis of psychiatry, clinical psychology, and AI safety literature was undertaken. The analysis distinguishes three pipeline layers: pretraining corpora, preference data and posttraining methods, and deployment-time interaction. It maps the clinical construct of collusion against adjacent technical concepts, including sycophancy, reward overoptimization, grounding, refusal training, red-teaming, and live monitoring. The synthesis suggests that collusion-like dynamics are least applicable at the pretraining layer and most applicable at the preference-data and deployment layers, where unassessed user or labeler input can be reinforced without corroboration. Existing mitigations, including data curation, Constitutional AI, reward-model evaluation, grounded generation, refusal training, red-teaming, and postdeployment monitoring, address parts of this problem. However, these approaches are not yet organized around a clinically informed account of when self-report is unreliable. The central novelty is therefore not a generic claim about bias, but the proposal that clinical self-report reliability should be assessed as a distinct data-quality and governance dimension. Trustworthy-AI frameworks for mental-health–relevant applications should incorporate clinical expertise in self-report reliability into preference-data design, red-teaming, and postmarket surveillance. Adding the clinical reliability of training and preference data as an explicit criterion could complement existing technical safeguards while leaving empirical evaluation of clinician involvement as an open research agenda.
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Progenitor diversity during formation of the mammalian neocortex
Mammalian neocortical development follows a precise spatiotemporal sequence to generate the organized structure responsible for higher-order cognition and behavior. Increasing evidence suggests that diversification of neural stem and progenitor cells during prenatal development is a key step in the emergence of the intricate circuitry and functional architecture of the cerebral cortex. This review discusses novel findings with an emphasis on mechanisms and consequences of cell lineage variation during normal and altered brain development, including focus on neurodevelopmental disorders such as autism spectrum disorders and Down syndrome.
Aggression and emotional distress in adolescents: a cross-sectional chain mediation model of internet addiction and somatization
BackgroundAdolescent depression and anxiety are major public health concerns. Aggression is frequently associated with internalizing symptoms, but the behavioral and body related mechanisms underlying this association remain insufficiently clarified. This study examined a theoretically proposed chain mediation model linking aggression with depressive and anxiety symptoms through internet addiction and somatization.MethodsA cross-sectional survey was conducted among 5,307 high school students in Chongqing, China. Participants filled in the Buss and Perry Aggression Questionnaire (BPAQ), Internet Addiction Test (IAT), Patient Health Questionnaire – 15 (PHQ – 15), Patient Health Questionnaire – 9 (PHQ – 9) and Generalized Anxiety Disorder Scale – 7 (GAD – 7). Regression based chain mediation analyses with 5,000 bootstrap samples were performed using PROCESS Model 6, with gender and age controlled as covariates.ResultsThe results showed that aggression was positively correlated with depressive symptoms (β = 0.256, p < 0.001) and anxiety symptoms (β = 0.275, p < 0.001). Chain mediation analysis showed that aggression was indirectly associated with mental health through three distinct pathways: 1. the independent mediating effect of internet addiction; 2. the independent mediating effect of somatization; 3. the sequential chain mediating effect from internet addiction to somatization. The model explained more variance in depressive symptoms (R² = 58.2%) than in anxiety symptoms (R² = 53.5%). Furthermore, the association between somatization and depressive symptoms (β = 0.457) was stronger than that between somatization and anxiety symptoms (β = 0.428).ConclusionThis study supports a statistically significant chain mediation pattern in which aggression is associated with depressive and anxiety symptoms through internet addiction and somatization. The findings suggest that somatization may represent an important body related correlate in the association between maladaptive digital behavior and emotional distress, with a slightly stronger association observed for depressive symptoms than for anxiety symptoms. These findings highlight the importance of integrated school based interventions that address digital behavior regulation, somatic symptom monitoring, and emotional distress among adolescents with higher aggressive tendencies.