BackgroundAdolescents with depressive disorders are at elevated risk for adverse mental health outcomes, and excessive Internet use has been increasingly linked to greater symptom severity. Therefore, this study aimed to examine the chain mediating roles of social anxiety and sleep quality in the association between excessive Internet use and depressive symptoms among adolescents with depressive disorders.MethodsA cross-sectional design was used. A total of 266 Chinese adolescents with clinically diagnosed depressive disorders (M = 15.79 years, SD = 1.85; 71.4% female) were assessed using the Internet Addiction Test, Zung Self-Rating Depression Scale, Social Anxiety Scale for Children, and Pittsburgh Sleep Quality Index. Correlation analyses and bootstrapping methods were conducted using SPSS and the PROCESS macro to examine the chain mediating effects of social anxiety and sleep quality.ResultsThe total indirect effect of excessive Internet use on depressive symptoms accounted for 65.66% of the total effect. Specifically, the indirect effects via social anxiety and sleep quality accounted for 24.10% and 26.51% of the total effect, respectively. In addition, the chain mediating effect of social anxiety and sleep quality was significant, accounting for 14.76% of the total effect.ConclusionExcessive Internet use was positively associated with more severe depressive symptoms among adolescents with depressive disorders, both directly and indirectly through the chain mediating effects of social anxiety and sleep quality. These findings highlight potential targets for preventing and intervening in excessive Internet use among this population.
Late-life difficult-to-treat depression and dementia subtypes: a naturalistic cohort study using electronic health records
IntroductionLate-life difficult-to-treat depression (LL-DTD) and dementia frequently coexist in later life, but it remains unclear whether clinical and sociodemographic characteristics, as well as medication exposure patterns, differ across dementia subtypes among older adults with both conditions.MethodsWe analysed anonymised electronic health records from a south London catchment area. We included patients aged ≥60 years at first recorded depression diagnosis with a dementia diagnosis. LL-DTD was defined as inadequate response to ≥2 antidepressant trials. Dementia diagnoses were classified as Alzheimer’s disease (AD), vascular dementia (VD), mixed AD/VD, dementia with Lewy bodies (DLB), or other/unspecified dementia. Around the index depressive episode, we captured sociodemographics, depressive symptoms, physical comorbidity, and medication indicators. We used multivariate logistic regression to examine cross-sectional correlates distinguishing dementia subtypes (with AD as reference) within the LL-DTD and dementia sample. We conducted stratified analyses comparing non-AD versus AD dementia by the temporal order of dementia and depression diagnoses.ResultsAmong 890 older adults with LL-DTD and dementia, AD was the most common subtype (33.9%), followed by mixed AD/VD (22.5%), VD (22.2%), other/unspecified dementia (15.2%), and DLB (6.2%). Depressive symptom profiles and psychotropic treatment history were broadly similar across subtypes. Compared with AD, VD was associated with greater functional impairment, while greater physical comorbidity burden was more evident in VD and mixed AD/VD.DiscussionSomatic multimorbidity and functional impairment provided the clearest clinical separation between subgroups, while depressive symptom patterns and medication exposure appeared largely non-specific across dementia subtypes. This underscores the importance of multimorbidity and physical health burden in understanding heterogeneity of dementia outcomes in LL-DTD.
Distinct sleep-disordered breathing phenotypes in elderly patients with depressive disorder: links to hypoxemia severity and inflammatory burden
ObjectiveTo identify sleep-disordered breathing phenotypes in older adults with depressive disorder and obstructive sleep apnea-hypopnea syndrome (OSAHS) and to evaluate their associations with systemic inflammation.MethodsElderly patients with depressive disorder and OSAHS were consecutively enrolled from January to December 2025. A Gower distance matrix was constructed and phenotypes were derived using partitioning around medoids (PAM; k-medoids), with k selected based on silhouette, elbow criteria, and clinical interpretability. Blood samples were collected the morning after PSG to measure serum high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α).ResultsAmong 198 participants, k = 2 was selected based on internal validity metrics (silhouette and elbow) and clinical interpretability. Compared with the lower-hypoxia/less-severe OSAHS phenotype (Cluster 1, n = 92), the high-hypoxia/severe OSAHS phenotype (Cluster 2, n = 106) had higher BMI, HAMD-17, and ESS, and more severe AHI/ODI/TS90 with a lower LSaO2. The high-hypoxia/severe OSAHS phenotype also showed higher hs-CRP, IL-6, IL-1β, TNF-α, WBC, neutrophils, and NLR. The inflammatory burden score was higher in the high-hypoxia/severe OSAHS phenotype (β = 1.10 SD unadjusted; β = 1.67 SD adjusted for age, sex, BMI, comorbidity, smoking, drinking, education, and MoCA; β = 1.45 SD further adjusted for HAMD-17 and ESS; all P < 0.001). In men (n = 135), PAM clustering similarly identified two phenotypes differentiated mainly by AHI/ODI, with selective elevations in IL-1β and neutrophil counts.ConclusionsThe high-hypoxia/severe OSAHS phenotype in older adults with depressive disorder is independently associated with a higher systemic inflammatory burden.
Applicable Scenarios, Desired Features, and Risks of AI Psychotherapists in Depression Treatment From the Patient’s Perspective: Exploratory Qualitative Study
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.
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.
Predictive Value of Early Peritraumatic Distress Screening for Childbirth-PTSD Following Unplanned Cesarean Delivery
Conditions: Post Traumatic Stress Disorder; Post Partum Depression; Acute Stress Symptoms
Interventions: Other: Postpartum Psychological Screening
Sponsors: University of British Columbia; Women’s Health Research Institute of British Columbia
Not yet recruiting
Interventions: Other: Postpartum Psychological Screening
Sponsors: University of British Columbia; Women’s Health Research Institute of British Columbia
Not yet recruiting
PB-18 Probiotic for Mild to Moderate Depression
Conditions: Depressive Disorder
Interventions: Dietary Supplement: Bifidobacterium; Other: Placebo
Sponsors: First Affiliated Hospital of Zhejiang University
Not yet recruiting
Interventions: Dietary Supplement: Bifidobacterium; Other: Placebo
Sponsors: First Affiliated Hospital of Zhejiang University
Not yet recruiting
Synaptic Mechanisms of Continuous Theta Burst Stimulation in Depression
Conditions: Major Depression
Interventions: Drug: D-Cycloserine (DCS); Device: Continuous theta-burst stimulation (cTBS); Device: Transcranial Magnetic Stimulation Sham; Drug: Memantine; Drug: Lorazepam (drug); Drug: Baclofen; Drug: Placebo
Sponsors: Mclean Hospital; National Institute of Mental Health (NIMH)
Recruiting
Interventions: Drug: D-Cycloserine (DCS); Device: Continuous theta-burst stimulation (cTBS); Device: Transcranial Magnetic Stimulation Sham; Drug: Memantine; Drug: Lorazepam (drug); Drug: Baclofen; Drug: Placebo
Sponsors: Mclean Hospital; National Institute of Mental Health (NIMH)
Recruiting