IntroductionThis study aimed to examine the association between loneliness and self-efficacy among adolescents and to investigate whether internet addiction mediated this association and whether sleep quality moderated the direct and indirect pathways. Although previous research has demonstrated significant associations between loneliness and both general and social self-efficacy, the behavioral mechanisms underlying these associations and the conditions under which their strength may vary remain insufficiently understood.MethodsA cross-sectional survey was conducted among 1,323 students in Grades 7–9 from two schools in Baotou, Inner Mongolia, China. Participants completed the UCLA Loneliness Scale, the General Self-Efficacy Scale, the Internet Addiction Diagnostic Questionnaire, and the Athens Insomnia Scale. A moderated mediation model was used to examine the mediating role of internet addiction and the moderating role of sleep quality in the association between loneliness and self-efficacy.ResultsLoneliness was negatively associated with self-efficacy. Internet addiction partially mediated the association between loneliness and self-efficacy. In addition, sleep quality moderated the direct association between loneliness and self-efficacy and the first stage of the indirect pathway from loneliness to internet addiction. Specifically, the associations of loneliness with self-efficacy and internet addiction varied across different levels of sleep quality.DiscussionThese findings provide a more comprehensive understanding of the mechanisms linking loneliness to adolescent self-efficacy by identifying internet addiction as an important behavioral mediator and sleep quality as a moderating factor. The findings highlight the importance of considering problematic Internet use and sleep quality when developing interventions aimed at promoting adolescents’ psychological adjustment, self-efficacy, and well-being.
Beyond dopamine: KarXT and emerging mechanism-based therapies in schizophrenia
KarXT (marketed as Cobenfy™), a fixed-dose combination of xanomeline and trospium chloride, represents the first new mechanism of action of an antipsychotic used for adult schizophrenia approved by the US Food and Drug Administration (FDA) in over 30 years. While mainstream drugs (e.g. haloperidol, chlorpromazine, risperidone, olanzapine, quetiapine, aripiprazole) mainly antagonize dopamine D2 or serotonin 5-HT2A receptors, KarXT acts through transient activation of muscarinic M1 and M4 receptors. M4 stimulation influences the functioning of mesolimbic dopaminergic pathways, providing an indirect means of regulating dopamine release that bypasses D2 blockade. Trospium, a peripherally acting muscarinic receptor antagonist, was used to reduce anticholinergic adverse effects (AEs). It does not cross the blood–brain barrier and therefore minimizes central adverse events. In a series of randomized placebo-controlled phase 2 and 3 studies, the KarXT significantly and clinically meaningfully reduced Positive and Negative Syndrome Scale (PANSS) total scores. The effect sizes were moderate to large with few extrapyramidal symptoms (EPS), minimal metabolic disturbances and no significant prolactin level increases. In this narrative review, we discuss in detail the pharmacological mechanism, basis of preclinical development, and clinical outcomes of KarXT. We also contextualize this drug within the development of a new wave of non-D2 antipsychotics, highlighting cholinergic dysfunction as one important mechanistic pathway within the broader multidimensional neurobiology of schizophrenia.
Maternal folate receptor alpha autoantibodies and folate levels during pregnancy in relation to autism spectrum disorder: a pilot case-control study
BackgroundFolate receptor alpha autoantibodies (FRAA) are reported to be associated with autism spectrum disorder (ASD) and are found more frequently in mothers of children with ASD. However, the relationship between maternal FRAA during pregnancy, folate status, and ASD risk in offspring remains unclear.ObjectiveIn this exploratory pilot study, we compared maternal serum binding FRAA measured during pregnancy between high-folate ASD cases and childbirth-time–matched mothers of typically developing children.MethodsFRAA were retrospectively analyzed in serum samples collected between gestational weeks 7 and 18 from women whose children were later diagnosed with ASD (case subgroup, n = 10) and mothers of neurotypical children (control subgroup, n = 10). Case samples were selected based on previously measured elevated folate levels, while controls were selected to minimize differences in biobank storage duration.ResultsFRAA were detected in 2 of 10 samples in each group, corresponding to a prevalence of 20%. Although based on limited statistical power, no significant difference in FRAA prevalence was observed.ConclusionIn this exploratory pilot study, no difference in binding FRAA prevalence was found between mothers of children with ASD, who were selected for elevated maternal folate levels, and mothers of neurotypical children. While this finding does not support a link between FRAA and elevated maternal folate levels, the small sample size and selection criteria limit interpretation.LimitationsThe study was limited by the small sample size, differences in subgroup selection, uncertainty in gestational age at sampling, and the inability to assess blocking FRAA.
Low-burden speech-based screening of depressive symptoms using ultra-short speech samples
BackgroundSpeech holds promise for depressive symptom screening, but practical applications require clearer guidance on effective segmentation, optimal speech tasks, minimum duration, and feature-model matching.ObjectiveTo enable low-burden screening for depressive symptoms, this study aims to evaluate the effectiveness of short speech samples and systematically investigate how to identify the optimal practical combination of different speech tasks, time-window lengths, and the matching between features and models.MethodsUsing the HMU-DDAC-24 dataset of 143 participants aged 18–22 years, we evaluated 10 segmentation lengths (0.1–15 s), 5 models (Random Forest, Extreme Gradient Boosting (XGBoost), Long Short-Term Memory (LSTM), Transformer, Extended Long Short-Term Memory (xLSTM)), and 3 feature types (frame-level, statistical, fused). We also assessed 19 window lengths (1–35 s) across four speech tasks and their combinations. In addition, supplementary cross-dataset validation analysis was performed using the external Emotional Audio-Textual Depression (EATD) dataset.ResultsFrame-level features performed best with sequence models and short windows (0.1–2 s; Transformer accuracy: 0.731 at 2 s). Statistical features paired best with tree models and short windows (Random Forest accuracy: 0.698 at 1 s). Fused features improved tree models (Random Forest accuracy: 0.703 at 4 s) but introduced noise into sequence models. Task 4 (positive recall) achieved the best overall performance (Area Under the Receiver Operating Characteristic Curve (AUC) = 0.860), outperforming all single and combined tasks, showing no multi-task synergy. A 1-s segment performed comparably to full-length speech (3.14% relative performance loss). Kullback-Leibler divergence analysis showed short segments closely approximated the full recording’s distribution (Task 4 KL = 9.56 at 1 s).ConclusionsWhen combined with appropriate speech tasks and feature-model matching, short speech samples can facilitate low-burden screening for depressive symptoms. Supplementary analysis on the EATD dataset supported these trends, though absolute performance depended on feature representation. We recommend positive recall with 2-s truncation, frame-level features, and Transformer for accuracy-oriented settings; and 1-s truncation, statistical features, and Random Forest for resource-limited settings. These findings may inform rapid, remote speech-based screening for depressive symptoms, especially in resource-limited primary-care settings.
Opinion: Mentally ill women deserve more support to have children
A friend once told me approvingly that someone she knew had talked his schizophrenic adult son into having a vasectomy. Though I read “talked into” as “coerced,” I didn’t say anything.
Oh my god, I thought instead, maybe I shouldn’t be a mother. I’d had a break with reality after stopping my antipsychotic 10 years before, frustrated with weight gain. I had returned to taking medication and my mental health had stabilized long before this conversation. But I was now pursuing pregnancy.
Predicting the Outcome of ADHD in White Matter Injure Neonates With Multi-modality MRI
Conditions: White Matter Abnormalities, Nonspecific; ADHD; Neurodevelopment Outcome
Sponsors: First Affiliated Hospital Xi’an Jiaotong University
Completed
Sponsors: First Affiliated Hospital Xi’an Jiaotong University
Completed
Novel Approaches to Supporting Students With ADHD in Multi-Tiered Systems of Support
Conditions: Attention Deficit Hyerpactivity Disorder
Interventions: Behavioral: Academic Competency Enhancement (ACE) classroom; Behavioral: School as Usual Classroom Supports
Sponsors: Florida International University
Not yet recruiting
Interventions: Behavioral: Academic Competency Enhancement (ACE) classroom; Behavioral: School as Usual Classroom Supports
Sponsors: Florida International University
Not yet recruiting
Irreconcilable differences?: epistemic injustice and the integration of mental healthcare for LGBTQ+ young people
BackgroundIntegrated youth mental healthcare is an approach that has evolved in response to the global escalation of young people’s poor mental health, and the failure of current mental health systems and models to improve this situation. Lesbian, gay, bisexual, transgender, and queer/questioning (LGBTQ+) young people have disproportionately high rates of poor mental health compared with their cisgender, heterosexual peers, but there is a dearth of research examining how best to integrate mental healthcare for LGBTQ+ youth.AimTo identify differences in the discursive construction of LGBTQ+ identity, youth, and mental health between LGBTQ+-specific youth mental health services and mainstream services and how these differences may facilitate or limit the integration of mental healthcare.MethodsWe conducted a qualitative secondary analysis using Foucauldian discourse analysis, a method that centralises power and knowledge, to examine the discourses used to construct LGBTQ+ identity, youth, and mental health across four different mental health services. Using epistemic injustice as a theoretical framework, we analysed interviews with LGBTQ+ young people and staff (n = 30).ResultsMainstream discourses of LGBTQ+ youth mental health concentrate on risks, trauma, and harm, and reinforce a passive, pathologised, and patronised subject position for LGBTQ+ youth. In contrast, we identified three counter-discourses in LGBTQ+-specific mental health services: Knowing and telling, Resisting pathology, and Capability. These counter-discourses allowed for wider, transformative possibilities for LGBTQ+ youth subjectivities and mental wellbeing.DiscussionExisting models of integrated youth mental healthcare privilege a clinical, developmental, and universal approach that does not consider justice or the oppressive power systems implicated in LGBTQ+ young people’s mental healthcare. Without addressing in/justice, there will remain fundamental irreconcilable differences that will forfeit effective and inclusive systems of mental healthcare for LGBTQ+ young people.
In Vivo Characterization of Fatty Acid Amide Hydrolase in Posttraumatic Stress Disorder: A [11C]CURB Positron Emission Tomography Study
Posttraumatic stress disorder (PTSD) is associated with impaired fear extinction and dysfunction in amygdala-centered circuits, for which treatments remain insufficient. The endocannabinoid system, particularly anandamide signaling regulated by fatty acid amide hydrolase (FAAH), has been implicated in stress and fear regulation. Preclinical studies suggest increased FAAH is linked to heightened stress responsivity, but FAAH status in PTSD remains unclear. We used [11C]CURB positron emission tomography (PET) to characterize FAAH levels in the amygdala and in corticolimbic regions in PTSD and examine associations with clinical symptoms.
Effectiveness and Usability of Digital Slow Breathing and Detached Mindfulness Interventions in Late Adolescents: Mixed Methods Study
Background: Many adolescents experience elevated stress and anxiety; yet, access to effective psychological support is limited. Brief digital mental health interventions, such as slow breathing (SB) and detached mindfulness (DM), offer a potentially scalable approach to promoting emotion regulation in daily life. Objective: This study aimed to investigate whether 1 week of daily practice with a SB or DM intervention reduced stress, anxiety, and negative metacognitive beliefs in youth, and explored participants’ experiences to inform the development of accessible, youth-tailored digital interventions. Methods: A mixed method approach was used, including quantitative and qualitative data. A total of 147 university students between 16 and 19 years old were randomly allocated to the DM (n=49), SB (n=49), or passive control group (n=49). Participants who were allocated to DM or SB practiced the intervention for 1 week. Stress, anxiety, and negative metacognitive beliefs were assessed at pre- and postintervention using self-report questionnaires. The quantitative data were analyzed with linear mixed-effects models, and we explored daily changes in intervention effect. After posttest, participants were invited to focus groups to evaluate their experience with the interventions (n=37). The qualitative data were analyzed with a content analysis. Results: Our results showed that a week-long DM intervention significantly reduced stress compared with the control condition. No other differences emerged for the main outcomes on pre- and postmeasurements. However, in the SB group, higher perceived usability was associated with greater reductions in stress. Qualitative findings showed that both interventions were viewed as calming, easy to use, and acceptable, while also highlighting challenges such as maintaining motivation and integrating the exercises into daily routines. Conclusions: This study provides early formative evidence that brief digital interventions such as SB and DM are feasible and usable, with preliminary indication that DM intervention may support short-term stress reduction. Future research should focus on enhancing motivation and sustained engagement to maximize the effectiveness of digital mental health tools for late adolescents. Trial Registration: OSF Registries osf.io/vu56y; https://osf.io/vu56y/overview
<img src="https://jmir-production.s3.us-east-2.amazonaws.com/thumbs/0a38872547dbab297133778beef6238d" />