OBJECTIVE: To evaluate whether sublingual immunotherapy (SLIT) for Japanese cedar pollinosis is associated with subsequent initiation of antidepressants, and to assess its clinical implications for mental health management in real-world clinical practice. METHODS: We conducted a retrospective real-world cohort study using a large nationwide administrative claims database in Japan from 2014 to 2021. Adult patients diagnosed with Japanese cedar pollinosis were identified and classified as SLIT users or non-users using a new-user design. Propensity score matching was performed to balance patients' baseline characteristics, including age, sex, insurance type, and medical history. The primary outcome was initiation of antidepressant prescriptions. Hazard ratios were estimated using matched cohorts. RESULTS: A total of 4,126 SLIT users and 88,455 non-users were identified, with 3,991 propensity-matched patients in each group. Before matching, mental disorders were more prevalent among SLIT users than among non-users, whereas allergic rhinitis severity was similar between groups. Crude initiation rates of antidepressants were 5.0 and 2.9 per 1,000 person-years among SLIT users and non-users, respectively. After matching, no statistically significant association was observed between SLIT use and antidepressant initiation (hazard ratio = 1.11, 95% confidence interval = 0.73-1.69). Kaplan-Meier analysis also showed no significant between-group differences. CONCLUSION: No statistically significant association was observed between SLIT for Japanese cedar pollinosis and antidepressant initiation. These findings suggest that mental health outcomes should continue to be monitored independently of immunotherapy use in routine clinical practice. Further adequately powered studies with longer follow-up periods are warranted to better characterize depressive outcomes in this population.

BACKGROUND: Pain, depressive and anxiety symptoms, sleep disturbance, and autonomic regulation may coexist in hospitalized patients with musculoskeletal pain. This study integrated item-level symptoms with resting-state photoplethysmography-derived heart rate variability (HRV) to characterize their regularized association structure. METHODS: This exploratory cross-sectional study retained 172 adults hospitalized with musculoskeletal pain-related conditions. Pain-duration information was available for all participants, and 169 complete cases entered the primary 58-node network. Regularized partial rank associations were estimated from Spearman correlations using EBICglasso (γ = 0.50) without additional thresholding. Sensitivity analyses examined participants with pain lasting at least 3 months and the influence of overlapping insomnia items. RESULTS: Median pain duration was 4.00 months (IQR, 0.57-24.33; range, 0.50-365.00), and 91 of 172 participants (52.9%) had pain lasting at least 3 months. The primary network retained 332 of 1653 possible edges. Prominent within- and cross-domain connections involved pain intensity and mood, gastrointestinal, cognitive, somatic, and insomnia symptoms. HRV indices formed a comparatively distinct physiological cluster; only 24 of 441 possible HRV-symptom edges were retained, all with absolute weights below 0.029. Strength and expected-influence estimates showed low bootstrap stability (CS coefficients = 0.000 and 0.207, respectively). In the ≥3-month subgroup, correlations with the primary network were 0.868 for edge weights, 0.552 for strength, 0.729 for expected influence, and 0.925 for bridge expected influence. Network structure and bridge patterns were partly preserved, but centrality rankings were more duration-sensitive. After overlapping insomnia items were removed, the global structure remained similar, but pain-related sleep interference fell from fourth to 27th in bridge expected influence. CONCLUSION: Item-level network analysis identified closely connected pain and psychological symptom patterns, whereas short-term PPG-derived HRV showed sparse and weak direct network connectivity with clinical symptoms. Sleep-related bridging was partly attributable to overlapping insomnia content. These exploratory findings support multidimensional inpatient assessment but require validation in larger longitudinal studies.

BACKGROUND: Antepartum depression is a common mental health issue. This study aimed to develop a tool to predict antepartum depression risk and contribute to improving the screening rate of antepartum depression. METHODS: This study used a prospective design, including a total of 1,701 mid-pregnancy women, who were followed up until late pregnancy. We comprehensively incorporate predictors from biological, psychological, demography, and obstetrics. Several machine learning algorithms (logistic regression, random forest, support vector machine and extreme gradient boosting) were used to predict antepartum depression. Predictive variables were screened using the least absolute shrinkage and selection operator (LASSO). The models were built based on 70% of the training set and evaluated on the remaining 30% test set using metrics such as accuracy, precision, sensitivity, specificity, F1 score, and area under the receiver operating characteristic curve (AUC). We also ranked the importance of the variables. RESULTS: LASSO was used to select the nine variables (out of a total of 42). The importance ranking of the nine variables is as follows: psychological resilience, rumination, stress, social support, body image satisfaction during pregnancy, preparation for neonatal parenting, low-density lipoprotein cholesterol, work status and relationship with parents. The logistic regression achieved 68% accuracy, 25.6% precision, 68.7% sensitivity, 68.4% specificity, 37.3% F1-score, and 76% AUC in the test set. The random forest achieved 66.1% accuracy, 24.1% precision, 68.5% sensitivity, 65.7% specificity, 35.6% F1-score, and 75.4% AUC in the test set. The support vector machine achieved 65.1% accuracy, 23% precision, 65.7% sensitivity, 65.1% specificity, 34.1% F1-score, and 70.1% AUC in the test set. The extreme gradient boosting achieved 86.8% accuracy, 57.8% precision, 15.7% sensitivity, 98.1% specificity, 24.7% F1-score, and 71.8% AUC in the test set. CONCLUSION: The antepartum depression risk prediction model developed in this study has moderate discriminative ability, which helps achieve early identification and classification management of risk, and provides a basis for targeted interventions.

BACKGROUND: Excessive time spent on social media and smartphones, as well as inappropriate use, has raised concerns about their potential impact on mental health. Many studies have shown that social media addiction and smartphone addiction are associated with poor sleep quality and increased risk of depression and anxiety. This study examined the mediating role of lifestyle on the relationship between social media and smartphone use addictions with poor sleep quality, anxiety, and depression. METHODS: A cross-sectional study was conducted among 1324 undergraduate and graduate students aged 20-40 years. Participants completed validated self-report measures assessing social media addiction, smartphone addiction, sleep quality, anxiety symptoms, depressive symptoms, and lifestyle behaviors, including smoking, alcohol consumption, eating behaviors, and physical activity. RESULTS: The mean scores for sleep quality, anxiety, and depressive symptoms were 6.9 ± 3.4, 6.7 ± 5.4, and 8.6 ± 5.8, respectively. In this cross-sectional study, mediation analysis indicated statistically significant indirect associations through lifestyle between social media addiction and poor sleep quality (the indirect effects: unstandardized coefficient [B] = 0.006, 95% confidence interval [CI] [0.002-0.014]), anxiety symptoms (B = 0.007, 95% CI [0.001-0.016]), and depressive symptoms (B = 0.013, 95% CI [0.006-0.025]). Similarly, lifestyle was observed to mediate the association between smartphone use addiction and poor sleep quality (the indirect effects: B = 0.005, 95% CI [0.002-0.010]), anxiety symptoms (B = 0.006, 95% CI [0.001-0.015]), and depressive symptoms (B = 0.012, 95% CI [0.005-0.020]). Although the indirect effects were statistically significant, their magnitude was small, indicating that lifestyle accounted for a limited proportion of the associations between technology-related addictions and sleep quality and mental health problems. CONCLUSION: Lifestyle behaviors statistically mediated the associations of social media or smartphone use addiction with poor sleep quality, anxiety, and depression. Although causal inferences cannot be made, these findings suggest that lifestyle practices may be important in understanding and addressing the mental health challenges associated with excessive technology use.

OBJECTIVE: To systematically evaluate the efficacy of various forest therapy interventions for alleviating depressive symptoms using network meta-analysis, identify the optimal intervention pattern, and provide evidence-based guidance for clinical application. ELIGIBILITY CRITERIA: Randomized controlled trials (RCTs) evaluating forest therapy for depressive symptoms were included. Studies were limited to English publications with extractable outcome data; non-forest interventions, simulated nature exposure, and studies with severe comorbidities or incomplete data were excluded. INFORMATION SOURCES: PubMed, Medline, Embase, Cochrane Library, and CINAHL were searched from inception to May 2026. STUDY APPRAISAL AND SYNTHESIS METHODS: Study quality was assessed using the Cochrane ROB 2.0 tool. Network meta-analysis was performed with a random-effects model; heterogeneity was quantified using . Subgroup analyses were conducted by population, intervention mode, and assessment scale. Publication bias was evaluated using funnel plots and the trim-and-fill method. RESULTS: Eighteen RCTs with 2169 participants were included. Random-effects meta-analysis showed forest therapy significantly reduced depressive symptoms: SMD = -1.009, 95% CI (-1.411, -0.608), < 0.0001. Severe inter-study heterogeneity existed ( = 90.1%, 95% CI [-2.765, 0.746], < 0.0001). Leave-one-out sensitivity analysis confirmed stable pooled SMD ranging from -1.083 to -0.880 after removing any single trial. Trim-and-fill test detected publication bias; after imputing seven missing studies, the therapeutic effect remained significant yet slightly weakened. Subgroup analyses found significant antidepressant effects in healthy people (SMD = -0.642, 95% CI [-0.981, -0.303], = 0.0002), chronic somatic disease patients (SMD = -1.431, 95% CI [-2.461, -0.400], = 0.0065) and depressed patients (SMD = -1.187, 95% CI [-1.662, -0.712], = 0.05), with no intergroup efficacy difference across populations ( = 0.1961). Both guided (SMD = -0.881, 95% CI [-1.344, -0.418], = 0.0002) and unguided forest therapy (SMD = -1.134, 95% CI [-1.786, -0.482], = 0.0007) worked comparably. CONCLUSION: Forest therapy is an effective non-pharmacological intervention for depressive symptoms. While forest therapy seems to offer benefits, the certainty of the evidence is constrained by significant heterogeneity, potential publication bias, a scarcity of direct comparisons among intervention models, and a lack of long-term follow-up studies. Future research should standardize protocols, conduct large-scale RCTs, incorporate long-term follow-up, and develop regionally adapted interventions. REGISTRATION: PROSPERO CRD420261402570.

Antipsychotic medications remain the conventional treatment for treatment-resistant schizophrenia (TRS), yet some patients exhibit poor responses. Due to the limitations of pharmacological interventions, physical therapies are increasingly recognized as essential supplements in managing TRS. This article systematically examines the current clinical applications and research advances of physical therapeutic techniques for TRS. Existing evidence suggests that electroconvulsive therapy (ECT), particularly when administered as an adjunct to antipsychotic medication, may improve positive symptoms and overall clinical outcomes in a subset of patients with TRS. However, its potential cognitive adverse effects and related ethical considerations warrant careful evaluation. As a non-invasive neuromodulatory technique, transcranial magnetic stimulation (TMS) may exert therapeutic effects by modulating frontotemporal cortical excitability and activity within associated neural circuits, thereby contributing to improvements in auditory hallucinations, negative symptoms, and cognitive function. Transcranial electrical stimulation (tES), including transcranial direct current stimulation (tDCS), is characterized by procedural simplicity, favorable safety, and good tolerability. Its clinical effects may be mediated through modulation of cortical excitability, synaptic plasticity, and functional connectivity. However, current studies remain highly heterogeneous with respect to sample size, stimulation parameters, treatment duration, outcome measures, and follow-up periods. Moreover, no physical therapy has yet been approved by the US. Food and Drug Administration (FDA) for the treatment of TRS. This article aims to synthesize the therapeutic efficacy of various physical interventions for TRS and summarize the current clinical evidence, thereby broadening the range of potential treatment options for patients with TRS and promoting a more comprehensive clinical understanding and management of this condition.

OBJECTIVE: Older adults undergoing ERCP are particularly susceptible to sedation-related respiratory and circulatory adverse events. This trial compared the safety and efficacy of remimazolam-esketamine with propofol-fentanyl, with identical standardized nasopharyngeal airway-assisted respiratory management in both groups. PATIENTS AND METHODS: This single-center, prospective, randomized, parallel-group superiority trial enrolled 160 patients aged 60-80 years with American Society of Anesthesiologists physical status I-III who were scheduled for elective ERCP. Participants were randomly assigned 1:1 to remimazolam-esketamine (RE group; n=80) or propofol-fentanyl (PF group; n=80). Both groups received identical nasopharyngeal airway placement, oxygen delivery, capnography, and rescue algorithms; the randomized intervention was the anesthetic drug regimen. The primary outcome was composite sedation-related adverse events (SRAEs), comprising prespecified hypotension, bradycardia, hypoxemia, or respiratory depression from anesthesia induction to endoscope withdrawal. Analyses followed the intention-to-treat principle. RESULTS: Composite SRAEs occurred in 14 of 80 patients (17.5%) in the RE group and 28 of 80 patients (35.0%) in the PF group (RR, 0.50; 95% CI, 0.29-0.88; risk difference, -17.5 percentage points; 95% CI, -30.9 to -4.1; P=0.016). The adjusted RR was 0.49 (95% CI, 0.31-0.78; P=0.003). Anesthetic regimen success was similar between groups (97.5% vs 98.8%). Induction was modestly longer with RE, whereas eye-opening and modified Aldrete recovery time were slightly shorter. CONCLUSION: In this selected population of older patients undergoing ERCP, the remimazolam-esketamine regimen was associated with fewer composite SRAEs than propofol-fentanyl while achieving a similar anesthetic regimen success rate. Induction was modestly longer. Tachycardia, hypertension, and psychotomimetic symptoms were numerically more frequent with RE, but event counts were small and estimates were imprecise. Multicenter studies are required to confirm generalizability.

BACKGROUND: Pediatric anti-NMDAR encephalitis can cause severe disability and profound caregiver distress. Narrative medicine has been proposed as a humanistic intervention, but its impact across the complete caregiving triad of children, parents, and healthcare providers has not been systematically evaluated. This exploratory study aimed to assess the multidimensional impact of narrative medicine interventions in this setting. METHODS: This retrospective mixed-methods study included five children with severe anti-NMDAR encephalitis (admission mRS ≥4), their mothers, two physicians, and six nurses. Narrative medicine interventions included daily bedside narrative attention, parallel chart writing, family conferences, nurse-led narrative communication, and weekly sharing sessions. Quantitative outcomes included child mRS, parental anxiety (SAS), depression (SDS), caregiver burden (ZBI), and provider empathy (IRI), burnout (NBS), and meaningful work (WAMI). Qualitative data from parallel charts, reflective writings, and family interviews were analyzed thematically. RESULTS: All five children showed favourable neurological improvement (median mRS: 5→1 at 6 months; p=0.039); three returned to school. Parental outcomes showed substantial improvements: SAS (42.8→23.4, p<0.001, d=9.7), SDS (54.8→27.4, p<0.001, d=6.5), and ZBI (59.6→29.6, p<0.001, d=3.4). Nurses (n=6) showed increased empathy (IRI: 63.7→78.0, p=0.003, d=1.9) and reduced burnout (NBS: 73.0→56.3, p=0.002, d=2.1); physicians showed parallel improvements. Thematic analysis identified three potential mechanisms: clinical narrative signals, a window of narrative intervention (weeks 2-4), and bidirectional healing. CONCLUSION: In this small, exploratory retrospective case series, narrative medicine interventions were temporally associated with favourable trends in neurological outcomes, parental psychological states, and provider well-being. The proposed concepts of clinical narrative signals, a window of narrative intervention, and bidirectional healing offer a preliminary framework for integrating narrative practices into pediatric neurocritical care. These findings are hypothesis-generating and warrant prospective investigation in larger controlled studies.

BACKGROUND: Major depressive disorder (MDD) has become one of the diseases that seriously affects the quality of life and social function of patients. Electroconvulsive therapy (ECT) is an important method for treating mental disorders. This study aims to conduct a comparison of symptomatic improvement in patients with MDD across different age groups following ECT, thereby providing more precise and personalized treatment plans. METHODS: PubMed, Cochrane Library, CNKI, Wanfang, and other databases were searched for related studies from self-built databases until February 2025. The retrieved studies were then subjected to a meta-analysis using R software. Based on the assessment of heterogeneity across studies, either a fixed-effect model or a random-effect model was selected for data synthesis. RESULTS: A total of 15 eligible articles were included in this meta-analysis, involving 1617 patients with MDD. The results indicated ECT could reduce the scores of the Hamilton Depression Rating Scale (HAMD), Montgomery-Åsberg Depression Rating Scale (MADRS), and Hamilton Anxiety Rating Scale (HAMA). Additionally, it could increase the scores of the Mini-Mental State Examination (MMSE). However, no statistical significance was observed on the subscales of the Wechsler Memory Scale (WMS). Subgroup analysis and meta-regression revealed that the older patients (>60 years old) may benefit more significantly in improving depressive symptoms (HAMD and MADRS) and WMS recognition memory. No significant age-related differences are observed in HAMA, MMSE, or other WMS subtests. CONCLUSIONS: ECT demonstrates therapeutic effects across all age groups of patients with MDD. The older group seemed to benefit more from this treatment modality compared to other age groups. These findings contribute to a better understanding of the differential effects of ECT in patients with MDD of different ages, which may guide clinical decision-making.

Insomnia is common among older adults receiving palliative care, yet the role of sleep hygiene in insomnia severity remains unclear. We conducted a cross-sectional study of 76 older veterans receiving outpatient palliative care (mean age, 75 years; 85.5% male). Participants completed the Sleep Hygiene Index, Insomnia Severity Index, Epworth Sleepiness Scale, and Geriatric Depression Scale. Nighttime pain was assessed using a 0-10 numeric rating scale. Multivariable linear regression examined the association between sleep hygiene and insomnia severity after adjusting for age, depressive symptoms, and nighttime pain. Poorer sleep hygiene was independently associated with greater insomnia severity (B = 0.382, 95% CI, 0.198-0.566; p < 0.001). Higher depressive symptoms (B = 1.063, 95% CI, 0.684-1.442; p < 0.001) and nighttime pain (B = 0.725, 95% CI, 0.331-1.119; p < 0.001) were also independently associated with greater insomnia severity. These findings support the potential value of addressing sleep hygiene alongside depressive symptoms and nighttime pain in palliative care. Prospective and interventional studies are needed to determine whether such approaches improve sleep outcomes.

BACKGROUND: Vaped nicotine use is associated with nicotine dependence, mental health symptoms, and physical health problems in adolescents, and peer nicotine use is a robust predictor of nicotine vaping in adolescents and young adults. OBJECTIVE: Examine associations between peer nicotine vaping and participant nicotine vaping cessation outcomes or nicotine dependence treatment adherence among adolescents and young adults enrolled in a vaping cessation trial. DESIGN: Exploratory secondary analysis of a 12-week randomized controlled trial with 3-month follow-up. METHODS: Participants completed a three arm, 12-week trial of varenicline and counseling, placebo and counseling, or enhanced treatment-as-usual. Participants (N=280; ages 16-25) indicated number of close friends in their broad peer network who use nicotine vapes, and a subset reported on frequency of nicotine vaping among their 10 closest friends as well as frequency of vaping by their best friend. Analyses evaluated the effect of peer vaping on biochemically-verified 7-day nicotine abstinence (end-of-treatment and follow-up) and treatment adherence. Multilevel mixed-effects models accounted for treatment condition. RESULTS: Participants reported a mean of 6.9 (=6.8) close peers in their broad peer network used vaped nicotine at baseline; more peers using nicotine vapes was inversely associated with end-of-treatment abstinence (β=-.11, =.03), and more frequent vaping among participants' top 10 closest peers and best friend vaping frequency were inversely associated with abstinence at end-of-treatment and follow-up (βs=-.25 to -.32, s≤.05). For every 1 SD increase in participants' best friend's vape frequency, participants were 76% less likely to maintain a vape quit at 3-month follow-up (β=-1.26, =.044; OR=0.24). Measures of peer vaping were also inversely associated with study medication adherence (βs>=-.52, s≤.007) and fewer counseling sessions attended (βs=-.49 to -.60, s≤.008). CONCLUSION: Peer vaping behavior may be associated with adolescents' capacity to quit vaped nicotine. Interventions that directly address peer network influences may enhance vaping cessation outcomes.

INTRODUCTION: Major depressive disorder is a leading cause of disability, with a significant rate of patients responding inadequately to antidepressants, and residual symptoms, including insomnia, worsening overall outcomes. Current adjunctive options display partial efficacy and tolerability, motivating the search for different strategies. Beyond regulating the sleep-wake cycle, orexin systems are implicated in reward and cognition, and have emerged as new targets for depressive disorders. AREAS COVERED: This Drug Profile summarizes the published peer-reviewed evidence on seltorexant (JNJ-42847922; MIN-202), a selective orexin-2 receptor antagonist, for adjunctive treatment of MDD, covering its pharmacological, preclinical, and clinical profile, efficacy, safety and tolerability, head-to-head comparisons with current adjunctive treatments, regulatory status, and competitive landscape. Relevant literature was identified through structured searches of PubMed/MEDLINE and ClinicalTrials.gov (from database inception to April 2026), complemented by Google Scholar employed solely to identify conference proceedings, using combinations of terms related to seltorexant and depression. EXPERT OPINION: Seltorexant 20 mg has shown a promising antidepressant effect, particularly in patients with clinically significant insomnia, and a favorable tolerability profile. The mixed phase-3 results, the modest effect sizes, and gaps on core symptoms of depression, including anhedonia and suicidality, and on long-term safety warrant a measured positive view, pending confirmatory data.

BACKGROUND: Mental health problems in older adults are often underrecognized despite their substantial impact on health and well-being. Brief, valid screening tools with age-specific normative data are needed for this growing population. This study examined the psychometric properties of the Patient Health Questionnaire-4 (PHQ-4) and established age- and gender-specific normative values for adults aged 60 years and older in Germany. METHODS: Data were drawn from four nationally representative face-to-face household surveys conducted in Germany between 2021 and 2024. Four of the total 3,212 participants were excluded due to missing PHQ-4 responses, resulting in a final sample of N = 3,208. The psychometric properties of the Generalized Anxiety Disorder-2 (GAD-2), the Patient Health Questionnaire-2 (PHQ-2), and the Patient Health Questionnaire-4 (PHQ-4) were evaluated. RESULTS: The PHQ-4 showed excellent internal consistency. The correlated two-factor model, distinguishing depression and anxiety symptoms, demonstrated excellent fit. Measurement invariance was supported across gender and age groups. Women reported higher overall psychological distress than men, mainly due to higher anxiety symptoms, and PHQ-4 scores were highest in the oldest age group. Convergent validity was supported by moderate to strong negative correlations with quality of life, resilience, sense of coherence, and well-being. Age- and gender-specific normative values were provided for the PHQ-2, GAD-2, and PHQ-4. CONCLUSIONS: The PHQ-4 is a reliable and valid ultra-brief screening instrument for psychological distress. The age- and gender-specific normative values provided here may improve score interpretation for community-dwelling older adults in Germany and help identify individuals who may require further clinical assessment.

BACKGROUND: Adolescent mental ill health is increasing globally and in Sweden, with rising levels of stress, anxiety, depression, and sleep problems. Many adolescents do not seek help due to stigma, fear of judgement, and limited mental health literacy. School nurses play a key role in early identification and preventive support. Digital tools may complement relational nursing practices and lower thresholds for help-seeking, but little is known about what features school nurses consider feasible and useful in their daily practice. OBJECTIVE: To explore school nurses' perspectives on key features and content of a mobile app intended to support early identification and management of mental health problems among high school students. METHODS: An exploratory qualitative study was conducted using semi-structured interviews with ten school nurses working in upper secondary schools. Interviews were held via Zoom, transcribed verbatim, and analysed using reflexive thematic analysis (RTA). COREQ guidelines informed the study's design and reporting. RESULTS: Two overarching themes emerged. First, Fostering mental wellbeing: the school nurse as a trusted ally in a complex world highlighted how early identification often relies on relational continuity, trust, and interpretation of indirect indicators such as somatic complaints or behavioural changes. Second, Nurturing minds: the digital dance of support and solitude reflected nurses' belief that a mobile app could support time management, self-regulation, psychoeducation, and accessible communication. Feasibility, however, depended on safeguarding confidentiality, maintaining professional boundaries, preventing workload escalation, and managing the "anonymity paradox," in which anonymity can both facilitate disclosure and hinder safe escalation. CONCLUSIONS: School nurses perceive that a mobile app could complement face-to-face care by supporting early identification and self-management among adolescents. Successful implementation requires aligning digital features with relational nursing practice, ensuring ethical governance, and integrating clear escalation pathways. Thoughtfully designed mHealth solutions have potential to strengthen preventive mental health support within school health services. CLINICAL TRIAL NUMBER: Not applicable.

Brain iron homeostasis is indispensable for sustaining central nervous system development, neural circuit stability, and core neurobiological processes including neurotransmission, mitochondrial energetics, and synaptic plasticity. Compelling clinical and preclinical evidence has established that iron dyshomeostasis represents a pervasive, convergent pathological driver of multiple psychiatric disorders, spanning anxiety, depression, schizophrenia, and neurodevelopmental and affective spectrum conditions. Nevertheless, current literature remains fragmented by disease-specific investigation, with persistent unresolved contradictions regarding regional iron deficiency versus overload in disease pathogenesis. Moreover, the cell-type- and circuit-specific mechanisms linking iron imbalance to psychiatric phenotypes, lacks systematic integration-hindering mechanistic consensus and translational advancement. In this comprehensive review, we synthesize multimodal evidence from human neuroimaging, post-mortem tissue analysis, clinical cohorts, and preclinical animal studies to delineate the distinct regulatory logics governing peripheral and cerebral iron metabolism. We systematically dissect how disrupted iron homeostasis triggers a cascade of neurobiological impairments, encompassing oxidative stress, ferroptosis, neuroinflammation, myelination defects, neurotransmitter dysfunction, and maladaptive synaptic remodeling. Synthesizing these findings, we construct a unified mechanistic framework illustrating how diverse etiological factors-genetic predisposition, chronic psychosocial stress, neuroinflammatory insult, and developmental influences-converge to drive region- and cell-specific iron perturbations and subsequent circuit dysfunction. We further summarize the translational potential and inherent limitations of existing iron-targeted intervention strategies. Collectively, this synthesis positions brain iron dyshomeostasis as a core convergent node in the pathophysiological network of psychiatric disorders, bridges basic iron neurobiology with translational neuroscience, and provides a conceptual framework and practical roadmap for biomarker discovery, mechanistic dissection, and next-generation therapeutic development in psychiatry.

In the context of medication shortages, the creation of a list of essential medications (EML) is becoming necessary in France, as it is in other industrialized countries newly affected by this issue. This approach differs from the World Health Organization's EML and is thought of as an extension of the definition of medications (and therapeutic classes) of major therapeutic importance as outlined in the public health code. The principle behind this list is to maintain a high standard of care. The first EML for French psychiatry was formalized by the French Association of Biological Psychiatry and Neuropsychopharmacology (AFPBN) in June 2023. It was initially compiled by a steering committee of five mental health practioners and proposed to a panel of 31 experts who were asked to rate their degree of approval for each medication (Delphi method) along with the level of criticality in the event of a shortage. Based on 163 medications, the AFPBN selected 98, after validation by its expert group. (June 2023). The Directorate General of Health later removed 18 medications from this list, including molecules with no medical benefit, mainly substances under compassionate use authorization, or those with an insufficient, low, or moderate medical benefit. This first EML for French psychiatry can obviously be improved but is proposed as a working basis for future modifications.

OBJECTIVES: Mental health disorders and suicidal behaviors are a major public health issue worsened by the COVID-19 pandemic. Social prescribing initiatives such as Art on Prescription aim to integrate artistic activities into healthcare to promote well-being and reduce depressive symptoms. This pilot study aimed to assess the impact of an Art on Prescription program on individuals at risk of suicide. METHODS: An AoP program was implemented in Montpellier coordinated by the Department of Emergency Psychiatry and Acute Care at Montpellier University Hospital, in partnership with MO.CO. (Montpellier Contemporain). Fifty-one adults, referred after an emergency visit for suicidal ideation or a suicide attempt, were enrolled between 2022 and 2024. The program was delivered through five successive cycles. Each participant was enrolled in one cycle only, led by an artist, and included one museum visit followed by five weekly creative sessions. Depressive symptoms (PHQ-9, Patient Health Questionnaire-9) and well-being (WEMWBS, Warwick-Edinburgh Mental Wellbeing Scale) were assessed at the end of each of the five creative sessions. Wilcoxon tests and Generalized Estimating Equations (GEE) were used for analysis. RESULTS: Among the 29 participants with complete data from the first to the fifth creative sessions, a significant improvement in well-being was observed (mean WEMWBS increase: +2.24; P=0.02), whereas the decrease in depressive symptoms was not statistically significant (PHQ-9: -0.79; P=0.12). In the full sample (n=51), the comparison between the first and third creative sessions showed a significant decrease in depressive symptoms (-0.65; P=0.05), but a non-significant increase in well-being (+1.22; P=0.11). GEE models confirmed a significant negative association between PHQ-9 and WEMWBS scores (β=-1.1; P<0.001), with no significant effect of time or interaction. CONCLUSIONS: The Art on Prescription program appears to have a positive impact on well-being and depressive symptoms in individuals at risk of suicide. These findings support the potential value of innovative, non-pharmacological interventions as a complement to traditional psychiatric care, aligned with recovery-oriented approaches.

Major depressive disorder remains a leading cause of disability worldwide, and current antidepressant treatments are limited by a delayed onset of action, modest remission rates, and residual symptoms. Emerging evidence suggests that selective targeting of specific serotonergic receptors may offer faster and more precise therapeutic strategies. Among these targets, the serotonin type 4 (5-HT) receptor has gained increasing attention due to its involvement in corticolimbic circuits regulating mood, cognition, and stress responses. Preclinical studies demonstrate that 5-HT receptor agonists produce rapid antidepressant- and anxiolytic-like effects, accompanied by early neuroplastic adaptations. Prucalopride, a highly selective 5-HT receptor agonist approved for chronic idiopathic constipation, has recently emerged as a promising candidate for drug repurposing in psychiatry. Converging evidence from animal models, experimental human studies, and epidemiological analyses suggest that prucalopride may modulate mood-related neural circuits and cognitive processes. This perspective discusses the translational potential of 5-HT receptor agonism as a novel therapeutic avenue for mood disorders.

Major depressive disorder remains unsatisfactorily addressed by monoaminergic antidepressants, and the search for mechanistically novel targets has converged on the immune system. Among these, the complement system offers a defined molecular route through which locally synthesized complement proteins may tag synapses for microglial engulfment. Preclinical studies implicate the C1q-C3-CR3 pruning axis and the anaphylatoxin receptors C3aR and C5aR in linking immune activation to region-dependent synaptic and neuroinflammatory changes, but causal evidence in patients remains absent. This review synthesizes genetic and pharmacological studies of C3, C3aR, and C1q in stress- and inflammation-based animal models; critically appraises the heterogeneous human biomarker and large-scale proteomic literature; and organizes candidate pharmacology into natural products and small molecules, established drugs with secondary complement-related actions, and clinical-stage complement inhibitors developed for other indications. We emphasize that no randomized controlled trial has tested deliberate complement inhibition in depression and that physiological complement functions, infectious risk, CNS delivery, regional heterogeneity, sex, and patient selection remain major barriers. Complement therefore represents a testable, biomarker-linked therapeutic hypothesis rather than an established treatment mechanism, requiring stratified trials with direct pharmacodynamic evidence.

Numerous commonly used antibacterial agents frequently induce acute anorexia as a clinical side effect, yet the underlying mechanism remains poorly understood. Here, we investigated the role of gut bacteria-derived hydrogen sulfide (HS) signaling in the regulation of feeding behavior and its involvement in antibiotic-associated anorexia. Using methylene blue colorimetric and fluorescent probe-based detection, we found that 24-h fasting elevated HS levels in rat feces and serum, which robustly stimulated feeding behavior. 16S rRNA sequencing revealed that fasting reshaped the gut microbiota and enriched certain HS-producing bacterial taxa. Through fecal microbiota transplantation and pharmacological manipulations, our findings suggest a contribution of microbiota-derived HS to fasting-induced feeding behavior. Mechanistically, fasting-induced HS promoted feeding by activating AMP-activated protein kinase (AMPK) in the hypothalamic arcuate nucleus, a key center for feeding regulation, via an S-sulfhydration-dependent mechanism, which in turn enhanced the activity of neuropeptide Y-positive neurons. Furthermore, we showed that impaired gut bacterial HS signaling contributed to metronidazole-induced acute anorexia, a common adverse clinical effect. Given that HS-producing taxa, especially Desulfovibrio, are sensitive to a broad range of antibacterial agents, our findings suggest an important role for gut bacterial HS signaling in gut-brain communication and appetite control, and point to a microbiota-host feedback mechanism underlying antibacterial-induced acute anorexia.

Psychological distress, encompassing PTSD, depression, and anxiety-is highly prevalent among Veterans receiving care in Veterans Health Administration (VHA) primary care settings, yet it frequently goes untreated or undertreated. Traditional psychotherapies and psychiatric medications are often misaligned with Veterans' preferences for self-reliance, low-stigma formats, and skill-based approaches. Primary Care Brief Mindfulness Training (PCBMT) was developed as a brief, transdiagnostic, group-based mindfulness intervention co-facilitated by licensed mental health providers and Veteran peer specialists in VHA primary care. Two preliminary randomized controlled trials (RCTs) demonstrated reductions in PTSD and depression severity relative to control conditions. An ongoing study extends this work through a Hybrid Type I effectiveness-implementation trial at three geographically and demographically diverse VHA sites (Phoenix, San Diego, St. Louis). Three hundred primary care patients with clinically significant psychological distress are being randomized 1:1 to PCBMT or Moving Forward (MF), a transdiagnostic problem-solving group that serves as an active comparison condition. The primary outcome is change in total psychological distress as measured by the Depression Anxiety and Stress Scale (DASS-21) from baseline to post-intervention (8 weeks). Secondary aims will test transdiagnostic mediators (mindfulness, emotion regulation, psychological flexibility, thought suppression) and explore social determinants of health (SDOH) as potential moderators of initiation, completion, and clinical benefit. A qualitative implementation aim, guided by the Consolidated Framework for Implementation Research (CFIR), will characterize barriers and facilitators to support future scale-up. This protocol describes participant selection criteria, intervention conditions, facilitator training, outcome measurement, and analytic strategy. Trial Registration:ClinicalTrials.gov Identifier: NCT-06162741.

BACKGROUND: Obesity and depression are independently associated with liver disease, yet to our knowledge, no prior study has specifically examined their joint longitudinal trajectories or the mediating role of frailty in this association. OBJECTIVES: To identify joint trajectories of body mass index and depressive symptoms, examine their associations with incident liver disease, and evaluate frailty as a potential mediator. METHODS: This multicohort prospective study included 17,582 participants aged 45 years or more from the China Health and Retirement Longitudinal Study (2011-2015; n = 10,487) and the Korean Longitudinal Study of Aging (2014-2018; n = 7095). Joint body mass index-depressive symptom trajectories were identified using group-based multi-trajectory modeling in the Chinese cohort and replicated in the Korean cohort via trajectory mean squared error matching. Associations with incident liver disease were estimated using Cox proportional hazards models with progressive covariate adjustment. Mediation analysis assessed the mediating role of mid-wave frailty index with 1000 bootstrap iterations. RESULTS: Four joint trajectory groups were identified: Normal Weight-Low Depression (25.3%), Overweight-Low Depression (31.8%), Normal Weight-High Depression (22.3%), and Obese-Moderate Depression (20.6%). During follow-up, 925 incident liver disease events occurred (5.3%). In fully adjusted models, compared with Normal Weight-Low Depression, hazard ratios for Obese-Moderate Depression were 3.53 (95% confidence interval 2.59-4.79; p < 0.001) in the Chinese cohort and 3.14 (95% confidence interval 2.21-4.47; p < 0.001) in the Korean cohort. Normal Weight-High Depression was associated with hazard ratios of 2.45 (95% confidence interval 1.80-3.35; p < 0.001) and 2.33 (95% confidence interval 1.62-3.33; p < 0.001), respectively. Frailty index mediated 8.5%-15.3% of these associations in the Chinese cohort and 6.8%-12.7% in the Korean cohort. Results remained robust across subgroup and sensitivity analyses, although marginal attenuation was observed for the Overweight-Low Depression group in the Korean cohort. CONCLUSIONS: Joint body mass index-depressive symptom trajectories are differentially associated with incident self-reported physician-diagnosed liver disease, partially mediated through frailty accumulation. Integrated metabolic, psychological, and frailty assessment may inform liver disease risk stratification, although further research with objective outcome ascertainment is needed.

Dancing can be an alternative to traditional intervention programs for caregivers. This study aims to examine the effects of the Brazilian Circle Dance Program (CircleCare) on the physical and mental health of family caregivers of older adults with Alzheimer's disease (AD). Twenty-five caregivers over the age of 50 were randomized into an Intervention Group (IG, n = 13, CircleCare, 60 min, 2x/week for 12 weeks) and a Control Group (CG, n = 12, without intervention). Physical health was assessed using measures of functional mobility, walking speed, and lower limb strength. Mental health was assessed using measures of cognition, caregiver burden, perceived stress, depressive symptoms, and quality of life. Frailty was assessed using the frailty phenotype. The Statistical analysis was performed using two-way repeated-measures ANOVA (significance level 5%). Only the IG shows improvements in functional mobility (p < 0.001), burden (p = 0.001), stress level (p = 0.045) and contribution to a transition from pre-frail to non-frail. However, CircleCare was not sufficient to induce applied responses concerning walking speed, lower limb strength, cognition and quality of life. CircleCare can be considered as an intervention option for caregivers of older people with AD, especially middle-aged and older women, as it was effective in improving functional mobility, burden, stress level and contributed to the transition from pre-frailty to non-frailty. TRIAL REGISTRATION: ClinicalTrials.gov Number NCT03081533. Registered 2 March 2017, https://clinicaltrials.gov/study/NCT03081533.

Psychiatric disability in schizophrenia may reflect the combined effects of clinical symptoms, cognitive impairment, individual resources, and environmental support rather than the influence of a single risk factor. This study used fuzzy-set qualitative comparative analysis to identify configurations associated with higher and lower psychiatric disability states among patients with stable-phase schizophrenia. A cross-sectional study was conducted among 482 patients with stable-phase schizophrenia. Psychiatric disability was assessed using the World Health Organization Disability Assessment Schedule 2.0. Seven conditions were examined: negative symptoms, depressive symptoms, neurocognition, social cognition, psychological resilience, family functioning, and social support. Necessary condition analysis showed that no single condition reached the necessity consistency threshold. Sufficiency analysis identified five configurations associated with higher psychiatric disability and five configurations associated with lower psychiatric disability. For higher psychiatric disability, the overall solution consistency was 0.935 and coverage was 0.724; for lower psychiatric disability, the overall solution consistency was 0.932 and coverage was 0.695. Low social cognitive functioning appeared in all higher-disability configurations, whereas the absence of negative symptoms and the presence of social cognitive ability appeared in all lower-disability configurations. These findings indicate equifinality and configurational asymmetry, suggesting that psychiatric disability in schizophrenia should be assessed and addressed through combined consideration of symptoms, cognition, especially social cognition, and resource conditions.