Understanding how symptom domains relate to one another (e.g., whether generalized anxiety is more similar to depression than to panic) is central to psychiatric classification. We demonstrate a procedure for quantifying relative proximity, defined as whether one symptom domain is statistically closer to another compared to other domains. As a motivating application, we examine the structure of internalizing symptoms characterized by fear, distress, avoidance, and heightened arousal. Using a network approach, we analyzed data from six questionnaires assessing depression, generalized anxiety disorder (GAD), social anxiety disorder, panic disorder, posttraumatic stress disorder (PTSD), and obsessive-compulsive disorder (OCD) symptoms. In a community sample of young adults (n = 2051; ages 17-23), we estimated a symptom-level Gaussian graphical model, used community detection to characterize the network's modular structure, and derived shortest path length to quantify the relative proximity of predefined symptom domains. We then used permutation testing to determine whether distress-related symptom domains (depression, GAD, and PTSD) showed greater empirical proximity to one another compared to fear-related domains (social anxiety, panic, and OCD). Results indicated reciprocal proximity between the depressive and GAD symptom domains compared to other internalizing domains. PTSD showed its greatest relative proximity to depression and GAD. Panic, social anxiety, and OCD did not form a cohesive fear community and showed variable relative proximity to both distress- and fear-related domains. Overall, these findings lend support for a distress-based internalizing dimension encompassing depression, GAD, and possibly PTSD, while providing limited evidence for a fear-based dimension including social anxiety, panic, and OCD.

BACKGROUND: Depression, pain amplification, and functional impairment are central features of fibromyalgia (FM) and contribute to disability across chronic rheumatic diseases. However, cross-condition differences and shared mechanisms remain unclear. OBJECTIVES: To evaluate depression, pain, central sensitization, and functional impairment across FM, rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and healthy controls (HC), and to examine whether pain mediates the association between depressive symptoms and functional impairment. METHODS: We analyzed 876 adults (FM n = 591; RA n = 130; SLE n = 94; HC n = 61). Measures included the Beck Depression Inventory (BDI), McGill Pain Questionnaire (MPQ), Revised Fibromyalgia Impact Questionnaire (FIQR), Symptom Impact Questionnaire (SIQR), Central Sensitization Inventory (CSI), and SF-36 subdomains. Group differences were assessed using ANOVA/ANCOVA adjusting for age, sex, and BMI. Mediation (BDI → MPQ → FIQR) was evaluated using bootstrapped structural equation modeling (2000 draws), adjusting for covariates. RESULTS: FM exhibited the highest levels of depression, pain, central sensitization, and functional impairment (all p < 0.001), with RA and SLE intermediate and HC lowest. Depressive symptoms were associated with pain severity (β = 3.17, p < 0.001), and pain with functional impairment (β = 1.05, p < 0.001). The indirect effect was significant (β_indirect = 3.34; 95% CI [2.65, 4.02]), indicating partial mediation. CONCLUSIONS: Depressive symptoms, pain severity, and functional impairment are strongly associated across rheumatic conditions, with partial mediation through pain. Elevated central sensitization in RA and SLE suggests shared amplification pathways, supporting integrated treatment approaches targeting mood, pain, and function.

Secondary Restless Legs Syndrome (RLS) has repeatedly been associated with psychopharmacotherapy, especially antidepressants (ADs) and antipsychotics (APs). However, existing evidence is conflicting in terms of the magnitude of the association as well as the significance of substance classes or individual compounds. The objective of the present study was to evaluate secondary RLS linked to psychotropic medication in real-world, inpatient clinical routine treatment settings. For this purpose, a large dataset from a multinational pharmacovigilance program in German-speaking countries (AMSP) from January 2001 to December 2016 was retrospectively analyzed. In a total of 340 099 monitored inpatients, 67 cases of newly diagnosed and severe RLS related to psychotropic drug treatment were recorded equivalent to a relative frequency of 0.02%. Over 80% of the cases were attributable to two compounds: the AD mirtazapine and the AP quetiapine. Mirtazapine was found in 39 patients, while quetiapine was found in 16 patients with secondary RLS. For both substances drug dosages were generally low at onset of secondary RLS. Most cases exhibited an onset within 1 or 2 days after dosage start or change. Histamine neurotransmission may represent a crucial common denominator in terms of secondary RLS in association with psychopharmacotherapeutics, as both substances exhibit antihistamingeric effects at lower dosages.

INTRODUCTION: Service members and veterans may have been particularly vulnerable to the stressors of the COVID-19 pandemic because of the unique challenges tied to military service. Understanding the pandemic's impact on the health and well-being of these populations is critical for maintaining military readiness and preparing for future crises. MATERIALS AND METHODS: The study sample included 80,974 US military personnel and veterans from the Millennium Cohort Study who completed the 2019-2021 survey. Participants who responded between October 23, 2019, and March 10, 2020, were classified as pre-pandemic responders (63%), while those who responded between March 11, 2020, and August 31, 2021, were classified as peri-pandemic responders (37%). Associations between pre- or peri-pandemic response group and mental, behavioral, and physical health, and stress and resilience factors were estimated using modified Poisson regression with inverse probability of treatment weighting to account for differences in sociodemographic, military, behavioral, and prior health factors. This study was approved by the Naval Health Research Center Institutional Review Board. RESULTS: Compared with pre-pandemic responders, peri-pandemic responders had higher adjusted prevalences of mental health conditions, including problematic anger (adjusted prevalence ratio [aPR = 1.05, 95% confidence interval, [95% CI, 1.01, 1.09]), anxiety (aPR = 1.13, 95% CI, 1.09, 1.17), depression (aPR = 1.07, 95% CI, 1.02, 1.11), and post-traumatic stress disorder (aPR = 1.10, 95% CI, 1.06, 1.14). Peri-pandemic responders were also more likely to report poor health (aPR = 1.05, 95% CI, 1.02, 1.08) and express concern about stable housing (aPR = 1.19, 95% CI, 1.11, 1.27). Associations between pandemic response group and physical and behavioral health outcomes (insomnia, somatic symptoms, and tobacco use) varied by military service status. CONCLUSIONS: Findings suggest a higher burden of adverse health outcomes among service members and veterans during the COVID-19 pandemic. Tailored support strategies may be needed to address the specific needs of military and veteran populations during times of crisis. However, differences were modest in magnitude, which may reflect the underlying resilience of military communities.

Modern psychiatric treatment often necessitates polypharmacy, yet combination regimens carry significant risks of metabolic burden and drug-drug interactions. There is growing interest in and clinical acceptance of rational, mechanism-based drug combinations that are designed around desirable pharmacological properties rather than trial and error. The repurposing of D-cycloserine (DCS) is an example of this shift. An analog of d-alanine, DCS was originally developed as an antibiotic but failed to gain widespread use due to its propensity to induce psychotic symptoms such as hallucinations. More recently, DCS has emerged as a pharmaceutical with multifunctional actions including bimodal N-methyl-D-aspartate (NMDA) receptor modulation. At low doses (50-100 mg), it functions as a partial agonist that can enhance synaptic plasticity, whereas at higher doses (> 500 mg), it acts as a functional antagonist. NRX-101, a fixed-dose combination of high-dose DCS and the second-generation antipsychotic lurasidone, is currently being evaluated in clinical trials for bipolar depression with acute suicidality. In this combination, lurasidone offsets the psychotic effects of DCS, supporting its potential reconsideration for multidrug-resistant urinary tract infections. NRX-101 thus represents a case of rational polypharmacy in which complementary pharmacologic properties expand therapeutic possibilities for seemingly unrelated indications. More broadly, mechanism-based rational polypharmacy may continue to revive previously abandoned compounds for difficult-to-treat psychiatric and medical conditions.

PURPOSE: This study aims to describe time trends in dual diagnosis occurrence among adolescents and young adults (ages 12-25) treated in mental health services throughout Denmark between 2010 and 2022. It also aims to describe how incident cases are distributed by age, sex, diagnoses, educational attainment, and enrollment in substance use treatment services. MATERIALS AND METHODS: The study used diagnostic data on every admission to public mental health services in Denmark linked with data from other national social service- and educational registers. RESULTS: Our analyses show a substantial increase in dual diagnosis occurrence in 2010-17, followed by a declining trend. When distributed by sex, age and diagnoses, dual diagnosis was most frequently occurring among males; young adults (ages 22-25); adolescents and young adults with schizophrenia, schizotypal and delusional disorders; neurotic, stress-related and somatoform disorders; as well as cannabis related disorders across the study period. Our analyses also show an increase in the proportion who were enrolled in substance use treatment at the time of their first dual diagnosis contact with mental health services, but a decreasing trend in the proportion who enrolled within a year after their first dual diagnosis contact. Finally, our analyses show a slight increase in the number of adolescents and young adults with dual diagnosis above 16 years of age who had completed primary school (9 grade) during the study period.

PURPOSE: Self-harm is a frequent feature of borderline personality disorder. In severe conditions comorbidity across mental disorders is common. Intellectual developmental disorder (IDD) may be an underlying condition with high frequent self-harming behavior. Based on extensively hospitalized severe self-harm patients, we aimed to 1) explore associations between possible IDD (identified by Hayes Ability Screening Index, HASI), and mental health disorders, and 2) investigate the ability to identify possible IDD with a low-effort HASI subscale. We hypothesized that possible IDD was significantly associated with greater mental health comorbidity. METHOD: The study included 42 adults admitted to psychiatric hospitals for severe self-harm. Assessments included diagnostic interviews and IDD screening (HASI) by clinicians, and childhood trauma (patient self-report). Data were analyzed using Poisson regression. Validation of the HASI subscale background information was conducted using ROC analysis and exploratory data analysis. RESULTS: Possible IDD was significantly associated with higher incidence of mental disorders, even after adjusting for BPD, SUD, autism, and childhood trauma. Possible IDD and childhood trauma were independently associated with the number of mental disorders. The HASI background subscale demonstrated good predictive properties for identifying possible IDD. CONCLUSIONS: Results highlight the importance of assessing IDD among severe self-harm inpatients. A diagnosis of IDD may open the door to a broader range of treatment adaptations specifically addressing the needs of individuals with complex developmental and psychological challenges. Given the small sample size, these findings should be viewed as preliminary and hypothesis-generating. Replication in larger samples is required for further confirmation.

The accumulation of pathogenic tau protein is linked to cognitive decline and neuronal loss in Alzheimer's disease (AD), with tau oligomers identified as particularly neurotoxic. The 51 kDa FK506-binding protein (FKBP51) stabilizes these toxic tau oligomers and has been identified as a risk factor for several neurodegenerative diseases. FKBP51 levels increase with age and are especially high in AD brains, suggesting its involvement in disease progression. The development of the selective FKBP51 inhibitor, SAFit2, which can cross the blood-brain barrier, has shown promise in reducing stress hormones, improving stress responses, and mitigating protein-related pathologies in other neurodegenerative models. However, the effects of SAFit2 on tauopathies, such as those seen in AD, have not yet been investigated. Here, the effects of the FKBP51-selective inhibitor, SAFit2, were evaluated in PS19 tau transgenic mice. Mice received a 28-day regimen of SAFit2, followed by comprehensive behavioral, neuropathological, and proteomic analyses. SAFit2 demonstrated effective brain penetrance, with sex-dependent pharmacokinetics. Treatment slowed cognitive decline and depressive-like behavior, with pronounced benefits in male PS19 mice, including improved spatial memory and reduced tau oligomer burden. In females, SAFit2 promoted clearance of AT8-positive tau multimers with some benefit to recognition memory. Proteomic profiling revealed distinct molecular signatures underlying these sex-specific responses: males exhibited upregulation of RNA processing and ribosomal proteins, while females showed restoration of calcium signaling and synaptic drivers. Notably, behavioral recovery occurred independently of widespread neuroinflammation reversal. These findings provide the first in vivo evidence that FKBP51 inhibition by SAFit2 induces sex-specific remodeling of the brain proteome. This study also provides further evidence for the therapeutic benefits of targeting FKBP51 for tauopathies.

BACKGROUND: The objective of this study was to examine the association between generalized anxiety disorder (GAD) and health-related quality of life (HRQOL) in the general Korean population, and whether this relationship differed by multimorbidity profiles and household income. METHODS: We included 5,542 participants aged 19 years or older from the data of the 2021 Korean National Health and Nutrition Examination Survey. The GAD was assessed using the Generalized Anxiety Disorder 7-item scale (GAD-7). Participants with a GAD-7 score ≥ 10 were classified as having GAD. HRQOL was measured using the Health-related Quality of Life Instrument with 8 Items (HINT-8). Multimorbidity profiles were derived using latent class analysis. Survey-weighted regression models were used to evaluate associations and interaction effects. RESULTS: The weighted prevalence of GAD was 4.23%, with a mean GAD-7 score of 1.99. The mean HINT-8 index was 0.80. Higher GAD-7 scores and the presence of GAD were consistently associated with lower HINT-8 index values. GAD was associated with increased odds of problems across all HINT-8 domains, with particularly strong associations for depression (odds ratio [OR] = 34.43) and moderate associations for memory (OR = 4.88) and sleep (OR = 4.68). Three multimorbidity profiles (Healthy, Geriatric Disease, and Cardiometabolic Disease groups) were identified, and the association between GAD-7 scores and HRQOL differed by multimorbidity profile and household income, with similar patterns observed for GAD status. CONCLUSIONS: Higher GAD-7 scores and GAD were associated with substantially poorer HRQOL across both physical and psychological domains. The strength of this relationship varied according to multimorbidity profile and socioeconomic context.

BACKGROUND: While most adolescent self-harm (SH) is transient, a substantial minority of adolescents repeat and continue it, requiring intensive care. Although social environmental factors play an important role in adolescent psychological development, little is known about their role in the persistence of SH. Moreover, few studies have focused specifically on early adolescence, when SH often begins, hospital presentations after SH increase sharply, and many preventive programs typically commence. We aimed to identify social environmental risk factors at age 12 that predict the persistence of SH through ages 14 and 16 in a population-based cohort. METHODS: We used data from the Tokyo Teen Cohort study (N = 1501). The experience of SH was self-reported at three timepoints (12, 14 and 16 years of age), and categorized as none, transient (one timepoint), or persistent (≥ 2 timepoints). Potential risk factors were assessed at age 12, including family related factors, school and peer related factors, sociodemographic and developmental characteristics, and psychopathological experiences. Multivariable and multinomial logistic regression analyses were conducted to examine the associations of potential risk factors with transient and persistent SH. RESULTS: Of the 1501 participants 195 (13.0%) experienced transient SH and 53 (3.5%) experienced persistent SH. In fully adjusted models, maternal depressive/anxious symptoms and female sex predicted persistent SH (maternal depressive/anxious symptoms: OR 1.47, 95% CI 1.13-1.92, female: OR 4.74, 95% CI 2.18-10.29), whereas companionship with mother predicted lower likelihood (OR 0.50, 95% CI 0.28-0.89). Depressive symptoms and psychotic experiences (PEs) predicted both transient (depressive symptoms: OR 1.77, 95% CI 1.50-2.10, PEs: OR 1.57, 95% CI 1.36-1.82) and persistent SH (depressive symptoms: OR 2.03, 95% CI 1.55-2.66, PEs: OR 1.89, 95% CI 1.48-2.41). CONCLUSIONS: Maternal depressive/anxious symptoms were the risk factor of persistent SH and companionship with mother was protective against persistence even after adjustment for other factors. Care for maternal depressive/anxious symptoms and support for mother-child relationships would be required to prevent the persistence of SH, in addition to the care for children's depressive symptoms and PEs.

BACKGROUND: Smartphone use has become deeply embedded in daily life, particularly among university students, who may adopt it as a coping mechanism for psychological distress. Excessive or maladaptive use may lead to smartphone addiction, a growing public health concern linked to adverse mental health outcomes. This study aimed to determine the prevalence of smartphone addiction and examine its association with depression, anxiety, and loneliness among public university students in Malaysia. METHODS: A cross-sectional online survey was conducted between July 2022 and January 2024 among 7,278 students from 20 Malaysian public universities. Data were collected using validated instruments, including the Smartphone Addiction Scale-Short Version (SAS-SV), Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), and the De Jong Gierveld Loneliness Scale (DJGLS-6). Descriptive statistics were used to estimate prevalence, and multivariable logistic regression was performed to identify associated factors of smartphone addiction. RESULTS: The prevalence of smartphone addiction was 30.1%. Depression (42.6%), anxiety (41.9%), and loneliness (83.8%) were also highly prevalent. After adjustment, factors associated with smartphone addiction included female gender (AOR 1.148; 95% CI 1.021-1.291), Bumiputera Sabah or Sarawak ethnicity (AOR 1.235; 95% CI 1.031-1.479), higher academic year, and daily smartphone use exceeding 10 h (AOR 5.277; 95% CI 3.514-7.925). Depression (AOR 1.968; 95% CI 1.745-2.218), anxiety (AOR 2.060; 95% CI 1.789-2.372), and loneliness (AOR 1.438; 95% CI 1.207-1.714) were independently associated with smartphone addiction. CONCLUSION: Smartphone addiction is common among Malaysian university students and is strongly associated with demographic factors, psychological distress, and excessive smartphone use. Interventions addressing mental well-being and promoting healthier digital behaviors are essential to reduce addiction risk in this population.

BACKGROUND: Depression and anxiety are prevalent mental disorders that contribute significantly to global disability. While the MIND diet has demonstrated benefits in preventing Alzheimer's disease, its potential impact on mental health outcomes remains unclear. This study systematically reviews evidence on the association between adherence to the MIND diet and symptoms of depression, anxiety, and stress. METHODS: We conducted a systematic search of PubMed, Web of Science, Scopus, and Google Scholar databases up to August 2025 to identify observational and interventional studies examining the relationship between the MIND diet and depression, anxiety, or stress. Twenty one eligible studies-including eleven cross-sectional designs-were included. RESULTS: Of the 21 studies, twelve reported a significant inverse association between adherence to the MIND diet and depression symptoms, seven found similar associations with anxiety, and three with stress. However, findings were inconsistent, likely due to heterogeneity in study design, assessment tools, and populations. CONCLUSION: Current evidence suggests that greater adherence to the MIND diet may be associated with lower levels of depression and anxiety, but the overall quality and consistency of the evidence are limited. Well-designed longitudinal and clinical trials are needed to confirm these potential benefits.

BACKGROUND: South Korea has the highest suicide rate among member countries of the Organisation for Economic Co-operation and Development, reaching 29.1 per 100,000 people in 2024, alongside a concurrent increase in the prevalence of adolescent non-suicidal self-injury (NSSI), estimated at 21.2%-24%, substantially exceeding the global average. Despite this public health crisis, evidence-based clinical practice guidelines specifically addressing adolescent suicidal behavior and NSSI in the Korean context remain lacking. This umbrella review synthesizes evidence on therapeutic interventions to inform the development of clinical practice guidelines. METHODS: A systematic search was conducted across five databases (PubMed, Embase, CINAHL, Cochrane CENTRAL, Scopus) for systematic reviews published between January 2015 and December 2024. Eligibility was assessed using a predefined Population, Intervention, Comparison, Outcome framework targeting adolescents and young adults aged 10-24 years. Methodological quality was appraised using A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR-2), and the certainty of evidence was graded using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. Both quantitative and narrative systematic reviews were included. RESULTS: Six systematic reviews (published between 2018 and 2022) encompassing 178 unique primary studies met the eligibility criteria. AMSTAR-2 ratings identified one review as high quality, three as moderate quality, and two as critically low quality. High-certainty evidence supported combination therapy (fluoxetine plus cognitive behavioral therapy (CBT)) over fluoxetine monotherapy, demonstrating significantly improved treatment response rates (RR = 1.12) and reduced one-year recurrence rates (RR = 0.27). For psychotherapy as a stand-alone intervention, high-certainty evidence demonstrated a small effect on self-harm reduction (d = 0.13), and moderate-certainty evidence supported a reduction in suicidal ideation (d = 0.31). However, evidence for widely adopted models-including dialectical behavior therapy for adolescents, mentalization-based treatment for adolescents, attachment-based family therapy, and multisystemic therapy-was uniformly rated as very low certainty, revealing a substantial evidence-practice gap. A substantial proportion of the included reviews did not distinguish between NSSI and suicidal behavior in outcome reporting, limiting differential conclusions. CONCLUSIONS: This umbrella review identified high-certainty evidence supporting fluoxetine plus CBT combination therapy as a first-line recommendation for adolescents with comorbid depression and suicidal risk. The evidence-practice gap for specific psychotherapy models underscores the need for methodologically rigorous primary research. Culturally adapted guidelines incorporating Korea-specific risk factors-including academic pressure, Confucian family values, and cyberbullying-are urgently needed to address the unique epidemiological and sociocultural context of Korean adolescents. This review was prospectively registered in INPLASY(registration number: INPLASY202630082, doi: https://doi.org/10.37766/inplasy2026.3.0082). CLINICAL TRIAL NUMBER: Not applicable.

BACKGROUND: Depression is common in healthcare students, severely affecting their academic performance and daily life. Problematic internet use and insomnia are related to depression, yet underlying mechanisms remain unclear in Macau, China. This study aims to explore associations among problematic internet use, insomnia, and depression, and to examine the mediating role of insomnia. METHODS: This cross-sectional study was implemented during January and February 2025. Two hundred and sixty-four healthcare students in Macau completed self-report questionnaires on sociodemographic variables, problematic internet use, insomnia, and depression using an online platform. Model 4 of the PROCESS macro was applied to explore the mediating effect. RESULTS: In this study, 40.2%, 18.6%, 6.4% and 3.4% of Macau healthcare students sustained mild, moderate, moderately severe, and severe depression, respectively. Problematic internet use was positively correlated with insomnia (r = 0.363, p < 0.001) and depression (r = 0.484, p < 0.001). Insomnia and depression were positively correlated (r = 0.666, p < 0.001). Insomnia served as a partial mediator between problematic internet use and depression, accounting for 35.6% of the total effect (95% Boot CI: 0.027-0.082). CONCLUSIONS: Depression is prevalent among Macau healthcare students. Improving sleep quality may reduce depression in students with problematic internet use. Clinical focus should shift toward assessing and treating insomnia as a core component of care for students with problematic internet use.

BACKGROUND: Emotional difficulties post-stroke are common, particularly among people from minoritised ethnic communities or with aphasia, an acquired communication disorder. However, there is a shortage of supportive evidence-based interventions, and of clinical psychologists to deliver them at scale. Wellbeing After Stroke-2 (WAterS-2) is a novel, online, group psychotherapy intervention based on Acceptance and Commitment Therapy. It was designed to support post-stroke psychological adjustment, delivered by a trained non-psychologist workforce to increase potential reach. To guide equitable implementation of such interventions into routine stroke care, this study explored barriers and facilitators from the perspectives of key stakeholders: healthcare commissioners, managers, and frontline clinicians. METHODS: Qualitative, semi-structured, individual interviews were conducted online with purposively recruited healthcare professionals involved in commissioning, managing, or delivering stroke care in England. The qualitative interview schedule was informed by both the Consolidated Framework for Implementation Research (CFIR) and Normalisation Process Theory (NPT), while the subsequent thematic template analysis was primarily guided by CFIR to explore contextual factors and practical strategies for equitable implementation. RESULTS: Fourteen interviews were conducted (Feb-April 2024), with commissioning managers (n = 8), service managers (n = 4), and clinicians (n = 2). Analyses suggested three themes around the barriers and facilitators likely to influence equitable implementation: (1) Quality of Care vs. Quality of Cash Flow - highlighting a tension between tailoring for inclusion and demonstrating clinical- and cost-effectiveness; (2) Time & Leadership - highlighting a need for leadership to prioritise time investment in equity efforts; (3) Postcode Lottery - highlighting existing variation in local infrastructure, with third-sector partnerships suggested as key enablers. CONCLUSION: Equitable implementation of online psychological support requires balancing the diverse needs of stroke survivors and the constraints of a publicly funded healthcare system. Recommended actions to enable equity provide useful insights for the development, implementation and commissioning of online mental health interventions for stroke survivors. Strategies such as embedding interventions within existing workflows, securing leadership support, and forming partnerships with community organisations may help translate online support like WAterS-2 into routine care.

BACKGROUND: Functional impairment remains a central yet insufficiently addressed challenge in mental health care, as many systems continue to prioritise symptom containment over sustained participation in daily life. This study aimed to identify and prioritise strategies that support optimal functioning among individuals living with mental illness by integrating psychosocial, community-based, and digital approaches within recovery-oriented and biopsychosocial frameworks. METHODS: A modified Delphi design was employed with 18 experts from clinical, counselling, and academic settings. In Round 1, participants generated strategy statements that were synthesised through thematic analysis, supported by AI-assisted coding and subsequent human review, into eight dimensions of functional support. In Round 2, 16 experts ranked these dimensions by perceived importance, and Kendall's coefficient of concordance was used to assess consensus. RESULTS: The final framework comprised: Medical and Professional Support; Social and Family Support; Physical Health and Wellness; Emotional and Cognitive Coping; Mindfulness and Spiritual Practice; Structured Daily Living; Self-Directed Support and Autonomy; and Functional Adaptation and Masking. Experts prioritised formal clinical care, relational support, and physical health as foundational, with everyday self-regulation and structured routines occupying mid-level importance, and masking-based or high-effort compensatory strategies ranked lowest. Kendall's W indicated statistically significant but modest agreement, consistent with the expert's heterogeneity. CONCLUSIONS: The findings recast functional recovery as an emergent property of treatment access, social ecology, lifestyle stability, and self-regulation, while highlighting the ethical limits of placing responsibility for functioning primarily on individuals. The framework offers a practice-oriented scaffold for clinicians, service planners, and policymakers seeking to reorient mental health systems toward cultivating meaningful, sustainable everyday living. CLINICAL TRIAL NUMBER: Not applicable.

Green spaces and their biodiversity seem to improve the urban life quality. However, a wide range of descriptors were associated with multiple health outcomes, which limits the comparability of existing evidence. The objective of this systematic review was to organise this knowledge, investigating the relationship between biodiversity in urban green spaces and health outcomes in adults. Following PRISMA guidelines and a registered protocol (PROSPERO: CRD42025636281), a search of PubMed, Scopus, Web of Science identified studies published between January 2014 and July 2025. The search strategy ("biodiversity" AND "human health" AND "urban green space") yielded 147 eligible studies. Most were published between 2017 and 2020 (57%) and predominantly relied on medium-sized cohorts of 101-10,000 participants (55%). Health outcomes fell into four categories: (i) general health, mental health, and well-being; (ii) drug prescriptions; (iii) chronic diseases (cardiovascular disease, T2 diabetes, obesity); and (iv) birth outcomes. Green exposure was primarily assessed through vegetation-based indicators: 66.1% of studies used green-exposure metrics (tree canopy or vegetation cover), 34.0% NDVI, and 22.4% percentage green area. Only a minority incorporated composite ecological indices or fauna-based metrics (bird or insect richness). Across all health domains, findings were predominantly favourable. Between 70% and 90% of studies on general health, mental health, and well-being reported beneficial associations with green exposure, including improved self-rated health, reduced depressive and anxiety symptoms, lower stress, and increased life satisfaction. All studies using drug prescription data found inverse associations between green exposure and antidepressant or anxiolytic prescriptions. Evidence for chronic diseases consistently indicated protective associations: reduced cardiovascular and respiratory disease risk, prevalence of T2 diabetes, and all-cause mortality. Birth outcomes demonstrated more variability, with half of the studies reporting positive associations, largely influenced by socioeconomic and contextual factors. Socioeconomic status frequently modified associations, with stronger positive effects observed among lower-SES populations. The overall evidence indicates that richness of urban green spaces is associated with health benefits. However, the role of biodiversity remains unclear and understudied, mostly due to inconsistent measurements and ambiguous associations with health outcomes. Integrating ecological quality into urban planning may therefore represent an important strategy for promoting healthier and more equitable urban environments.

BACKGROUND: Many individuals with bipolar disorders (BD) value creativity, and some consider it a strength associated with BD. Existing literature supports a link between creativity and BD. This photovoice study represents the first of its kind, offering novel insights into the complex relationships among mood, creativity, and the lived experiences of individuals with BD in a non-Western cultural setting. METHODS: Our research team recruited 10 Chinese individuals in recovery from BD. They participated in either painting or expressive writing. Participants used a photovoice methodology over a nine-month period to document their creative processes and recovery, culminating in a public art exhibition and "human library" event, sharing their experiences and reducing stigma. RESULTS: The study revealed that mood had a significant influence on participants' creativity over time. During hypomanic episodes, some participants described heightened creativity, characterized by bursts of inspiration and increased output. Some participants reported an enhanced sense of perception during depressive episodes. Participants also reported that their ambitions and ability to execute their plans for achieving their goals seemed to play a significant role in explaining the relationship between mood episodes and creativity levels. Through activities such as drawing and writing, the participants gained a deeper understanding of themselves, exploring and making sense of their thoughts, emotions, and experiences. The sharing of creative work on social media during the study period emerged as a catalyst for fostering community, motivation, and self-confidence. Limitations include all‑female participants with high school or higher education levels, and variability in attendance and artistic output. CONCLUSIONS: This investigation offers insights into strengths-based approaches to supporting those with BD through the transformative power of the creative arts. The participants in this study emphasized the importance of finding meaning in their creative goals and cultivating determination by connecting their aspirations to personal values and intrinsic strengths. The present findings add to studies exploring the talents and skills of Chinese individuals with BD and to reducing stigma toward this population.

BACKGROUND: Orthopedic trauma patients frequently struggle with pain control, prolonged opioid use, and psychiatric co-morbidities, including depression and post-traumatic stress disorder (PTSD). Current treatment strategies inadequately address both pain and psychological recovery. Ketamine, an NMDA receptor antagonist with analgesic and psychotropic properties, has shown promise in surgical and psychiatric populations but has not been evaluated in polytraumatized orthopedic patients. OBJECTIVES: This study evaluates ketamine's effectiveness on postoperative pain measured by the Visual Analog Scale (VAS), opioid consumption converted to morphine milligram equivalents (MME), and psychological recovery assessed with the Patient Health Questionnaire-9 (PHQ-9) and PTSD Checklist for DSM-5 (PCL-5). METHODS: In this prospective, randomized, single-blind, active comparator study, 90 adults aged 18-65 undergoing operative fixation for orthopedic injuries at a Level I Trauma Center will receive either ketamine (0.5 mg/kg IV bolus) or standard general anesthesia without ketamine. Participants remain blinded to treatment, while surgical, anesthesia, and postoperative clinical care teams are unblinded. Outcomes will be measured at 1-7 days, 2-3 weeks, 6 weeks, 3 months, and 6 months postoperatively. DISCUSSION: This is the first randomized controlled trial to evaluate intraoperative ketamine for both physical and psychological recovery in orthopedic trauma patients, addressing a critical gap in perioperative trauma care. CLINICAL TRIAL REGISTRATION: The www.clinicaltrials.gov identifier is NCT06903819.

BACKGROUND: Autism and attention deficit hyperactivity disorder (ADHD) are common neurodevelopmental conditions that have both consistently been linked to internalising problems like anxiety and depression. However, the mechanisms that underpin these associations are unclear, especially in adults. To fill this research gap, we used a trait approach to investigate two theoretically relevant dispositional characteristics that may explain these relationships: intolerance of uncertainty (IU) and negative problem orientation (NPO). METHODS: We recruited a large (N = 504), nationally representative sample of adults from the United Kingdom using Prolific. Participants provided basic demographic information and completed self-report measures of ADHD traits, autistic traits, internalising (depression and anxiety) symptoms, IU and NPO. Using parallel mediation analyses, we examined the roles of IU and NPO in the associations of ADHD and autistic traits with internalising symptoms. RESULTS: We found that, together, IU and NPO fully mediated the association between autistic traits and internalising symptoms whilst accounting for participants' ADHD traits, age, sex and education level (standardised indirect effects: IU = 0.100, NPO = 0.139). Interestingly, these two dispositional characteristics only partially mediated the link between ADHD traits and internalising symptoms (standardised indirect effects: IU = 0.049, NPO = 0.128), suggesting that additional factors not captured by the mediation model may contribute to this positive relationship. CONCLUSIONS: We conclude that a person's perception of their capacity to tolerate uncertain or ambiguous situations and their views on their (in)ability to effectively solve problems in their day-to-day lives may underpin the strong association between autism and internalising problems and, to a lesser extent, between ADHD and internalising problems.

BACKGROUND: Depression is a clinically important comorbidity of trigeminal pain disorders, including trigeminal neuralgia, yet the neural circuits linking persistent trigeminal nerve injury to negative affect remain incompletely understood. The present study aimed to investigate the involvement of the ventrolateral periaqueductal gray (vlPAG)-lateral habenula (LHb) pathway in depression-like behavioral measures in a young adult male mouse model of trigeminal neuropathic pain. METHODS: A mouse model of trigeminal neuropathic pain was established in young adult male mice using infraorbital nerve chronic constriction injury (IoN-CCI). Spontaneous facial pain-related behavior and depression-like behavioral measures were assessed using facial grooming analysis, the sucrose preference test, the open field test, and the tail suspension test. c-Fos mapping, cell-type analysis, viral tracing, and chemogenetic manipulation of vlPAG glutamatergic neurons and the vlPAG-LHb pathway were performed to examine neuronal recruitment, anatomical connectivity, and behavioral relevance. RESULTS: In young adult male mice, IoN-CCI induced persistent facial grooming behavior as an index of spontaneous facial pain-related behavior and, by 4 weeks after surgery, was associated with depression-like behavioral changes without detectable alterations in body weight, general locomotor activity, or hindpaw mechanical and thermal sensitivity. c-Fos mapping and cell-type analyses showed a progressive increase in c-Fos expression in vlPAG neurons following IoN-CCI, with most labeled neurons identified as glutamatergic, suggesting recruitment of vlPAG glutamatergic neurons in this model. Chemogenetic inhibition of vlPAG glutamatergic neurons decreased depression-like behavioral measures, whereas chemogenetic activation increased these measures, without significantly altering facial grooming behavior used as an index of spontaneous facial pain-related behavior. Viral tracing provided anatomical evidence for a projection from the vlPAG to the LHb, and c-Fos expression in LHb neurons increased following IoN-CCI. Chemogenetic inhibition of the vlPAG-LHb pathway decreased depression-like behavioral measures, whereas chemogenetic activation increased these measures in IoN-CCI mice and was associated with similar behavioral changes in naive mice. CONCLUSION: These findings suggest that the vlPAG-LHb pathway is functionally associated with behavioral measures related to negative affect in a young adult male mouse model of trigeminal neuropathic pain, providing a circuit-level framework for understanding pain-associated affective disturbances. CLINICAL TRIAL NUMBER: Not applicable.

Sickle cell hemoglobinopathy is not merely a genetic disorder but a deeply embedded socio-cultural phenomenon in the remote regions of Odisha. Drawing on long-term ethnographic fieldwork in Koraput and surrounding districts, this study explores the lived experiences of individuals with sickle cell trait (SCT) and sickle cell disease (SCD), focusing on social discrimination, medical uncertainty, and healthcare accessibility. The findings reveal reluctance toward screening, particularly among unmarried women, due to fears of marital exclusion and family stigma. Misconceptions about SCT, including beliefs that it can appear or disappear over time, further reinforce social anxiety and misinformation. Inconsistencies in diagnosis, limited genetic counselling, geographic isolation, and economic insecurity exacerbate these challenges. The study also examines women's caregiving roles, therapeutic pluralism involving traditional healers, and youth perspectives on reproductive futures. By foregrounding the social consequences of carrier status alongside disease, the article challenges assumptions that SCT is negligible. These findings highlight the need for culturally sensitive genetic education, decentralized health services, and community-based interventions, contributing to a holistic understanding of sickle cell hemoglobinopathy within medical anthropology.

Cognitive impairment (CI) is a significant non-motor symptom of Parkinson's disease (PD), necessitating effective assessment tools to evaluate treatment efficacy. Minimal Clinically Important Difference (MCID) thresholds provide critical benchmarks for interpreting cognitive intervention outcomes. This study establishes MCID values for PD Cognitive Rating Scale (PD-CRS), Scales for Outcomes in PD-Cognition (SCOPA-COG), and Montreal Cognitive Assessment (MoCA) in PD-CI. A total of 110 patients with PD-CI were recruited; 105 (mean age 71.96 ± 2.40 years) completed the 12-week Dual-Task Training (DTT) program and were included in the final analyses. Cognitive function was assessed using PD-CRS, SCOPA-COG, and MoCA at baseline and post-intervention, with the Global Rating of Change (GRoC) questionnaire serving as an anchor. The MCID value was determined using anchor-based and distribution-based approaches. Receiver Operating Characteristic (ROC) analysis was employed to evaluate these thresholds. Significant improvements were observed across all cognitive measures post-intervention. The anchor-based MCID values were 7.70 points for PD-CRS, 3.11 points for SCOPA-COG, and 2.05 points for MoCA, respectively. Additionally, ROC curve analysis further determined that MCID cut-off points were > 3 points for the PD-CRS, > 2 points for the SCOPA-COG, and > 1 point for the MoCA. The distribution-based MCID values ranged from 1.48 to 4.10 points for PD-CRS, 1.37 to 5.95 points for SCOPA-COG, and 0.54 to 3.71 points for MoCA. This study established MCID thresholds for PD-CRS, SCOPA-COG, and MoCA in PD-CI, providing essential tools for clinicians and researchers to assess clinically meaningful changes after cognitive intervention.

Traumatic brain injury (TBI) continues to be one of the world's top causes of mortality and long-term disability. It is a severe and frequently fatal disorder. Patients with traumatic brain injury (TBI) not only sustain neurological impairment but also undergo significant metabolic changes and psychological stress, which may affect their ability to recover. The purpose of this study was to investigate the nutritional determinants and epidemiological trends linked to outcomes in traumatic brain injury patients. This prospective cohort study was carried out at the Imam Reza Hospital's Trauma Department in Tabriz, Iran. Over the course of six months, 520 patients with moderate-to-severe traumatic brain injury were consecutively enrolled, and they were monitored for one month following their release from the hospital. Clinical findings, radiographic results, laboratory data, therapies, outcomes, mechanisms of injury, and demographics were all methodically documented. BMI and serum albumin levels were used at discharge and one-month follow-up to evaluate nutritional status. The Impact of Event Scale (IES) and the Hospital Anxiety and Depression Scale (HADS) were used to assess psychological status. Descriptive techniques, correlation analyses, paired comparisons, and receiver operating characteristic (ROC) curve analysis were among the statistical techniques used to evaluate the standalone discriminatory ability of psychological and nutritional variables. The mean age of the patients was 32.49 ± 13.78 years, and 71.7% were male. Nearly 75% of injuries were caused by falls, making them the most frequent cause. In total, 51.2% of patients passed away while in the hospital, whereas 48.8% of patients survived discharge. Discharge and one-month Glasgow Coma Scale (GCS) scores demonstrated a substantial correlation with outcome (p < 0.001), and neurological severity was strongly associated with survival. Survival, neurological improvement, and psychological distress did not significantly correlate with either discharge or follow-up BMI. Additionally, there was no significant correlation between serum albumin levels and survival, anxiety, depression, or symptoms of post-traumatic stress disorder. BMI, HADS, and IES all showed poor outcome discrimination, and ROC analyses supported their limited standalone discriminatory ability. In this cohort of patients with moderate-to-severe TBI, BMI and serum albumin were not associated with survival or psychological distress and showed limited standalone discriminatory ability for short-term outcomes. These findings suggest that recovery after TBI cannot be adequately characterized by simple nutritional indices alone and support the use of more comprehensive, multidimensional approaches to nutritional and prognostic assessment in TBI survivors.