Background: Depression is a pervasive global mental health issue, yet access to trained professionals remains severely limited. With the rapid advancement of artificial intelligence (AI), digital tools are increasingly seen as a viable way to address this shortage. However, questions remain about how digital platforms for mental health care can be effectively designed. Objective: This study aimed to investigate, from an end user’s (patient’s) perspective, the potential use scenarios, desired features, and perceived risks of AI psychotherapists in depression treatment, providing design guidelines for their development. Methods: A grounded theory approach was applied to analyze qualitative responses from 452 individuals recruited via Amazon Mechanical Turk. Data were collected through a scenario-based online survey on AI-assisted depression treatment administered between March 2023 and May 2023. Participants responded to 3 open-ended questions regarding the potential use of AI in treating depression, the characteristics expected from an AI psychotherapist, and the associated perceived risks, along with demographic, control, and contextual measures. The open-ended responses were inductively coded into themes, with intercoder reliability established (Cohen κ=0.80). In addition, variations in themes were further examined across participant profiles, including social stigma, current depression severity, trust in an AI psychotherapist, and privacy awareness. Results: Participants envisioned AI psychotherapists across 5 primary scenarios: diagnosis, treatment, consultation, self-management, and companionship. Key desired features include professionalism, warmth, precision care, empathy, remote services, active listener, personalization, flexible treatment options, patience, trustworthiness, and basic treatment alternative, while critical concerns include diagnostic inaccuracy, treatment errors, privacy breach, lack of human interaction, technical malfunctions, and lack of emotional engagement. Based on these findings, a general MoSCoW (must have, should have, could have, and won’t have) prioritization framework was proposed to serve as a conceptual starting point for future AI system design and empirical validation in mental health care. Notably, feature prioritization varied across user profiles: individuals with higher stigma placed greater emphasis on privacy protection, those with more severe depression prioritized precision care and timely access, low-trust users de-emphasized remote services, and privacy-sensitive individuals showed reduced preference for features requiring extensive data disclosure. These patterns highlight the need for context-sensitive design. Conclusions: This study provides a patient-centered framework for designing AI psychotherapists and complements the existing literature by highlighting the importance of balancing clinical effectiveness with relational considerations. The findings offer actionable guidelines for designing AI mental health care tools that are aligned with user expectations and sensitive to individual differences.
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OTX-202 Smartphone App to Reduce Suicidal Ideation Among High-Risk Transition-Age Youth: Open-Label, Single-Arm, Phase 1 Clinical Trial
<strong>Background:</strong> The transition from adolescence to adulthood (18 to 25 years) is associated with an increased risk of suicidal ideation and behaviors. Suicide-focused cognitive behavioral therapies (CBTs) have been shown to significantly reduce suicidal ideation and behaviors but are not widely available to high-risk individuals. Digital therapeutics could improve access to these treatments. <strong>Objective:</strong> This study aimed to evaluate the acceptability, safety, and potential efficacy of OTX-202 among transition-age youth (18 to 25 years) receiving mental health care outside an inpatient hospital setting. <strong>Methods:</strong> In this phase 1 single-arm clinical trial, 59 transition-age youth with recent suicidal ideation or suicide attempts used OTX-202, a smartphone app designed to deliver suicide-focused CBT, concurrently with usual outpatient mental health care. After baseline, eligible patients completed 12 weekly assessments of suicidal ideation, depression, and anxiety. <strong>Results:</strong> From baseline to week 12, participants reported statistically significant, large reductions in suicidal ideation (mean difference –5.1, 95% CI –6.5 to –3.7; <i>d</i>=0.95). In total, 3 (5.1%; 95% CI 0%-11.2%) participants reported suicide attempts. Reductions in suicidal ideation and suicide attempt rates were consistent with results from previously published randomized clinical trials of suicide-focused CBTs. Participants rated OTX-202 in the 97th percentile of usability and completed a mean of 9.0 (SD 3.5) of 12 app modules, supporting the app’s acceptability. There were no patient deaths, device-related events, or severe adverse events, supporting the app’s safety. <strong>Conclusions:</strong> Results support the safety, acceptability, and potential efficacy of OTX-202 for reducing suicide risk among transition-age youth. <strong>Trial Registration:</strong> ClinicalTrials.gov NCT06008132; https://clinicaltrials.gov/study/NCT06008132
Timing of exercise differentially modulates fear memory and hippocampal neurotransmitters in male rats
Exercise promotes neurogenesis and enhances memory consolidation while reducing the retention of aversive memories and anxiety-like behaviors. While our previous work found that acute exercise alters neurotransmitter concentrations, including dopamine and serotonin, in a time-of-day-dependent manner, the long-term effects of chronically timed exercise on neurotransmitter dynamics and behavioral phenotypes remain unclear. To examine whether the daily timing of a chronic exercise intervention modulates its impact on neurotransmitter profiles and fear responses, male rats were conditioned using a Pavlovian contextual fear approach, then assigned to a 4-week treadmill exercise intervention performed during the early (ZT14) or late (ZT22) active phase or a time-matched sham-exercise control group. One day after completing training, rats underwent a context retrieval test in the middle of active phase (ZT18), and hippocampal neurotransmitters were quantified using UPLC–MRM/MS. Rats subjected to sham-exercise at ZT22 exhibited higher freezing than sham-exercised rats at ZT14, whereas exercise interventions at ZT22 selectively attenuated freezing. Histamine, acetylcholine, and GABA exhibited significant exercise × time interactions. Direct neurotransmitter–freezing correlations were weak after false discovery rate control, consistent with a network-level reorganization rather than a single transmitter driver. These findings suggest that vulnerability to aversive memory expression can be buffered by exercise, if timed appropriately, and that exercise reshapes hippocampal neuromodulatory tone in a circadian–phase–dependent manner, supporting the potential of exercise timing as a chronotherapeutic strategy to enhance stress resilience and mental wellbeing.
Meta-analysis of the effects of exercise intervention on physical health in individuals undergoing compulsory isolation
BackgroundPhysical health is the basic indicator to evaluate the health of drug addicts after the process of drug rehabilitation. In order to better improve the deficiency degree of physical health of drug addicts, it is necessary to carry out a systematic review.ObjectiveTo explore the effects of exercise intervention on the physical health of individuals undergoing compulsory drug rehabilitation using Meta-Analysis, aiming to provide evidence-based support for improving their physical health.MethodsRandomized controlled trials (RCTs) published between 2019 and December 2024, examining the impact of exercise intervention on the physical health of compulsory detoxification individuals, were retrieved from databases including Web of Science, PubMed, Cochrane Library, Medline, China National Knowledge Infrastructure (CNKI), Wanfang Data, and VIP Chinese Journal Database. The quality of included studies was assessed using the Cochrane risk-of-bias assessment tool. RevMan 5.4 software was employed for heterogeneity testing, effect size synthesis (using mean difference [MD] and 95% confidence interval [CI]), and generation of forest plots, funnel plots, and quality assessment diagrams. Subgroup analyses were performed to evaluate sensitivity and heterogeneity of the included studies.ResultsExercise intervention effectively improved the physical health of compulsory drug rehabilitation individuals, particularly in physical fitness indicators: sit-and-reach test [MD = 3.92, 95%CI = (3.23, 4.62), P<0.001], single-leg standing with eyes closed [MD = 7.03, 95%CI = (6.05, 8.02), P<0.001], grip strength [MD = 1.23, 95%CI=(0.06, 2.39), P = 0.04], and choice reaction time [MD=-0.03, 95%CI=(-0.05, -0.01), P = 0.002]. Improvements in physical function were also observed; however, the increase in vital capacity [MD = 86.81, 95%CI=(-1.56, 175.17), P = 0.05] did not reach statistical significance.ConclusionThis meta-analysis provides evidence that exercise intervention significantly improves specific physical health deficits—namely flexibility (sit-and-reach), balance (single-leg stance), muscular strength (grip strength), cardiopulmonary function (vital capacity), and sensorimotor coordination (choice reaction time)—in individuals undergoing compulsory rehabilitation. It is recommended to adopt a combination of aerobic and traditional fitness exercises, with at least 3 sessions per week, each lasting no less than 40 minutes, and a duration of over 12 weeks, providing scientific evidence for drug rehabilitation practices. These indicators were selected because they directly reflect the multisystem damage (muscular, neural, and cardiorespiratory) caused by chronic substance use. However, this study acknowledges the limitation that psychological and neurocognitive outcomes (e.g., cravings, mood, executive function), which are crucial in addiction treatment, were not included in the eligibility criteria and systematic analysis. The follow-up research will combine physical and psychological indicators to conduct a comprehensive evaluation of the intervention effect of exercise on drug rehabilitation.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD420251029820.
Tryptophan modulates the impact of prolactin on insomnia in perimenopausal women: a cross-sectional study
BackgroundInsomnia is highly prevalent among perimenopausal women and exerts detrimental effects on physical health, psychological well-being, and overall quality of life. However, its underlying mechanisms remain incompletely understood. This cross-sectional study aimed to identify factors associated with insomnia in perimenopausal women.MethodsA total of 187 perimenopausal women aged 45–55 years were enrolled. Insomnia, anxiety, and depression severity were assessed using the Insomnia Severity Index (ISI), Generalized Anxiety Disorder-7 (GAD-7), and Patient Health Questionnaire-9 (PHQ-9), respectively. Serum levels of relevant amino acids and hormones were measured. Spearman correlation and linear regression analyses were performed to examine the associations among prolactin levels, tryptophan levels, insomnia, anxiety, and depression. Moderation analysis was further conducted to evaluate the potential moderating role of tryptophan in these relationships.ResultsSerum prolactin levels were positively associated with scores of ISI, GAD-7, and PHQ-9. Furthermore, prolactin levels were positively correlated with the severity of sleep-onset difficulties, sleep maintenance problems, noticeability of impairment, and sleep-related distress. Of note, serum tryptophan levels significantly moderated the association between prolactin levels and ISI scores (β = 0.227, 95% CI = 0.04–0.41, p = 0.0148). To wit, he positive relationship between prolactin levels and insomnia severity was stronger in perimenopausal women with higher serum tryptophan levels compared with those with lower levels.ConclusionsThe moderating effect of serum tryptophan on the relationship between prolactin levels and insomnia in perimenopausal women helps us understand the neuroendocrine mechanisms underlying perimenopausal insomnia and may inform future research on targeted preventive and therapeutic strategies.
Research trends and knowledge mapping of transcranial direct current stimulation in depression: a bibliometric study based on web of science, Scopus, and PubMed (2000-2025)
BackgroundDepressive disorders are clinically heterogeneous and mechanistically complex psychiatric conditions. Transcranial direct current stimulation (tDCS), a key non-invasive neuromodulation technique, has expanded rapidly in both therapeutic application and mechanistic research. However, the field is marked by rapid publication growth, thematic diversity, and variability in evidence quality. A systematic quantitative synthesis is therefore needed to map the research landscape, identify hotspots, and inform future directions.MethodsA systematic search was conducted for English-language publications in the Web of Science Core Collection (WoSCC), Scopus, and PubMed using the terms (“Transcranial direct current stimulation” OR “tDCS”) AND (“depression” OR “major depressive disorder” OR “depressive disorder” OR “MDD”). Only articles and reviews were included. Records from 2026 and non-research publications, including conference abstracts, editorials, letters, news items, and errata, were excluded. Deduplication was performed using DOI-based matching followed by title-assisted matching. Bibliometrix (R), VOSviewer, and CiteSpace were used to analyze publication trends, contributions by countries/regions, institutions, authors, and journals, collaboration networks, keyword co-occurrence, thematic clustering, and burst terms. Citation analysis was based on WoSCC data only.ResultsResearch on tDCS for depression showed sustained growth, with marked acceleration after 2020 and a peak in 2024. The United States, Germany, and Brazil occupied central positions in both productivity and international collaboration, with the United States ranking first in publication volume. Major research hubs included the Universidade de São Paulo, the University of Toronto, and Harvard University, while Brain Stimulation, Journal of Affective Disorders, and Frontiers in Psychiatry were the leading publication venues. Highly cited studies mainly focused on neurophysiological mechanisms, pivotal randomized controlled trials, and evidence-based guidelines. Keyword analyses indicated a shift from early attention to cortical excitability, safety, and short-term efficacy toward a more integrated framework involving prefrontal-targeted stimulation, cognitive function, functional connectivity, treatment outcomes, and cross-disorder applications.ConclusiontDCS research in depression is entering a multidimensional and interdisciplinary phase, with increasing emphasis on network-level mechanisms and precision intervention. Functional connectivity is emerging as a potential biomarker for patient stratification and outcome prediction. Further progress depends on multicenter standardization, reproducible analytic pipelines, and high-quality comparative effectiveness research.
Case Report: Prism for PTSD in severe traumatic brain injury with psychiatric comorbidities: two cases
BackgroundTraumatic brain injury (TBI) with post-traumatic stress disorder (PTSD) is treatment-resistant, with conventional psychotherapy showing limited efficacy due to neurocognitive impairments.Case SummaryWe report two patients with severe TBI and psychiatric comorbidities treated with Prism neurofeedback.Case 144-year-old female, 35 years post-childhood TBI, with agoraphobia and hyperacusis, achieved 42% PTSD reduction and substantial functional gains (social reintegration, independent driving) sustained through 4-month follow-up.Case 240-year-old male, 3.5 years post-adult TBI with bipolar II disorder and severe PTSD (PCL-5 = 62), achieved 90% PTSD reduction with complete remission sustained at 1-month follow-up, enabling return to work and family system transformation. Both patients developed personalized regulatory strategies and maintained gains without relapse.ConclusionsPrism neurofeedback demonstrates clinically meaningful outcomes in severe TBI-PTSD where traditional psychotherapy shows limited efficacy. The intervention’s circumvention of cognitive processing demands may explain the favorable outcomes. Controlled trials are warranted.
STAT+: OxyContin maker Purdue Pharma set to dissolve after judge approves its criminal sentence
NEWARK, N.J. — OxyContin maker Purdue Pharma is set to be dissolved and replaced by a company focused on the public good by the week’s end, as a massive legal settlement resolving thousands of lawsuits takes effect.
A federal judge on Tuesday delivered a criminal sentence to the company to resolve a Department of Justice probe — a last necessary step to clear the way for the settlement.
U.S. District Judge Madeline Cox Arleo made her decision after listening to hours of impact statements from people who lost loved ones or struggled with addiction themselves and requested she reject the negotiated sentence. While she didn’t go that far, she said she sympathized with people who bore the brunt of an epidemic linked to more than 900,000 deaths in the U.S. since 1999.
Implications of Glucagon-Like Peptide-1 Receptor Agonists (GLP-1 RAs) for Mood Disorders and Suicide Risk
A strategic imperative in mood disorders is to identify innovative mechanisms that translate into improved therapeutics when compared to the extant options. More specifically, there is a need for treatments with greater efficacy, shorter time-to-peak efficacy, greater durability of effect as well as improved tolerability profiles. Moreover, priority has also shifted towards identifying mood disorder therapeutics capable of targeting domains of psychopathology that are most pervasive, debilitating and inadequately treated by conventional pharmacology (e.g., anhedonia, cognitive impairment).
Current Landscape of Mental Health Conversational Agents From a Trauma-Informed Care Lens: Scoping Review
Background: Conversational agents (CAs) are increasingly used in mental health care to enhance access and engagement. However, their safe, ethical, and user-sensitive design remains a challenge. Despite growing attention to trauma-informed approaches in human-computer interaction, there is limited work on how the trauma-informed care (TIC) framework could be applied in the design of mental health CAs and no comprehensive synthesis to date. Objective: Guided by the Substance Abuse and Mental Health Services Administration’s TIC framework, this scoping review explored how TIC principles (safety; trustworthiness and transparency; collaboration and mutuality; empowerment, voice, and choice; peer support; and cultural, historical, and gender issues) are currently represented in the design and evaluation of mental health conversational agents (MHCAs) and identified gaps and opportunities to promote more trauma-informed design practices. Methods: Online databases, as well as a secondary survey of citation lists from an initial search, were used to identify English-language journal articles and conference proceedings from 2000 to 2024 that empirically evaluated an independent, web- or app-based, unassisted CA used for mental health and included concepts from TIC. Results: Our analysis included 38 publications (n=28, 73.7%, published in 2020 or later) covering 28 distinct MHCAs. Most studies used experimental methods (n=23, 60.6%) or user studies (n=11, 28.9%), with samples skewed toward female (men: mean 34.92%, SD 18.64%), young in age (mean 32.52, SD 14.6 y), and predominantly nonclinical (n=29, 76.3%). MHCAs were largely rule-based prototypes. No studies explicitly referenced the TIC framework as a guiding lens for MHCA design or evaluation. A total of 26 studies referenced terminology from TIC core principles but rarely defined them, while all 38 included language that could be linked to one or more principles. Overall, TIC-related concepts appeared most often within intervention design descriptions, qualitative assessments, or as items embedded in questionnaires evaluating broader constructs. Trustworthiness and transparency, safety, empowerment, voice and choice, and collaboration and mutuality were comparatively well addressed, while peer support and cultural, historical, and gender issues were largely absent. Design recommendations, where present, were relatively broad and emphasized secure, customizable, reliable, human-like, and context-sensitive MHCAs that offered multimodal interaction, goal setting and tracking, and transparency. Conclusions: Studies did not self-identify as using Substance Abuse and Mental Health Services Administration’s framework for TIC, making it more difficult to identify its elements. The fragmented terms, disciplines, and metrics used make it difficult to draw more systematic conclusions about the current research landscape related to TIC, but our analysis indicates TIC to be a descriptive and potentially unifying framework and provides a starting point for the explicit trauma-informed MHCA research and design.
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