This study investigates the synergistic antidepressant mechanisms of gastrodin (GAS) combined with repetitive transcranial magnetic stimulation (r-TMS) through the gut-brain axis and the endocannabinoid system. A depression model was established in male C57BL/6J mice using Chronic Unpredictable Mild Stress (CUMS). Following four weeks of modeling, animals were divided into five groups and received respective treatments for two weeks. A multi-modal approach was employed, encompassing behavioral tests, hematoxylin and eosin (HE) staining, 16S rRNA sequencing, liquid chromatography-mass spectrometry (LC-MS) metabolomics, Western blot analysis, and mediation analysis. Results demonstrated that the combined therapy significantly ameliorated depressive-like behaviors and cognitive deficits in CUMS mice, exhibiting superior efficacy compared to monotherapies. The treatment repaired hippocampal neuronal architecture and colonic mucosal integrity, upregulated the tight junction protein ZO-1, and reshaped the serum metabolic profile. Western blot analysis confirmed the activation of key proteins within the target pathway. Mediation analysis established a credible microbiota-metabolite-behavioral association, indicating that specific gut microbiota influence behavioral outcomes by modulating differential metabolites, with this relationship mediated through the endocannabinoid system. This study confirms that the combination of GAS and r-TMS exerts synergistic antidepressant effects by regulating gut-brain axis homeostasis and activating the target signaling pathway, providing a novel mechanistic foundation for combined depression treatment strategies.

Stress is a major precipitating factor for emotional disorders, including anxiety. To cope with stress, individuals frequently engage in hedonic behaviors, such as eating palatable food, which provide transient relief from psychological distress and may protect against the development of pathology. However, the neural mechanisms by which hedonic experience counteracts stress-induced anxiety remain poorly understood. Here, we identify a neural circuit functionally connecting the prefrontal cortex (PFC) to the paraventricular nucleus (PVN) of the hypothalamus that mediates stress mitigation through palatable food intake. Activation of this circuit suppresses stress-induced hyperactivity of PVN corticotropin-releasing factor (CRF) neurons and prevents the development of anxiety-like behaviors. This effect is driven by palatable-food-induced dopamine release in the PFC, which activates dopamine D1 receptor (D1R)-expressing neurons projecting to corticotropin-releasing factor receptor 1 (CRFR1)-expressing neurons in the PVN and peri-PVN. Notably, GABAergic CRFR1 neurons are enriched in the peri-PVN, with minimal presence within the PVN proper, suggesting that inhibition of PVN neurons is mediated indirectly via peri-PVN GABAergic inputs. These findings define a previously uncharacterized PFC→peri-PVN→PVN circuit through which hedonic experience modulates stress responses and reveal a neural substrate for behavioral resilience, providing a potential avenue for anxiety intervention.

INTRODUCTION: Feeling lonely defined as a subjective dissatisfaction with social relationships, is associated with an increased risk of functional and cognitive decline well-known factors for institutionalization. The objective was to evaluate the predictive role of feeling lonely on admission to nursing homes among elderly people hospitalized via emergency departments. METHODS: This was an observational, longitudinal, prospective, multicenter study. Participants were recruited over a period of ten months. Patients were eligible if they were aged 75 years or older and hospitalized in a medical ward of the same hospital as the emergency department (ED) where they were initially admitted. The assessment included the collection of sociodemographic data-age, sex, level of education, available support (particularly the presence of a primary caregiver), number of children, and living arrangements (home or institutional setting)-as well as clinical variables, including presence of dementia or delirium, mood disorders, comorbidities, nutritional status, dependence in activities of daily living (ADL), mobility, risk of falls, and risk of pressure ulcers. The assessment included the collection of sociodemographic (age, sex, level of education, available support (in particular the presence of a primary caregiver), number of children, living conditions (e.g., at home or in an institution) Loneliness was assessed using item 14 of the CES-D (Center for Epidemiologic Studies Depression) scale. Univariate and multivariate analyses were performed using a Cox model that took death into account as a competing risk, using a Fine & Gray model. RESULTS: The mean age was 84.4 ± 5.9 years, and 55% were women. In this population, 40% reported feeling lonely, 41% were at risk of depression, 78% had at least one child, 67% had at least one family caregiver, and 79% (n = 833) lived alone. Over the 36-month follow-up period, 31.46% of patients entered nursing homes. Independent risk factors for institutionalization included social determinants specifically feeling lonely, which was independently associated with an increased risk of placement at 12, 24, and 36 months. Individuals reporting loneliness showed an increased risk of functional and cognitive decline. CONCLUSION: This study regarding hospitalized elderly after admission to an Emergency Department shows that feeling lonely is not merely a marker of social vulnerability but is independently associated with of nursing home admission.

This study investigated the potential of Binaural Beats (BB) stimulations at Beta (20 Hz) and Gamma (40 Hz) frequencies to alter interoceptive accuracy (IAcc) and sensibility (ISen) in individuals with depressive symptoms. Fifty-two individuals (34 females, with mean age of 22.7 ± 5.06 years) were included. Following an initial assessment, participants underwent two periods of BB stimulation followed by Heartbeat Counting Tasks (HCT). The results demonstrated that acute BB stimulation at Beta and Gamma frequencies did not significantly alter IAcc and ISen in young adults with symptoms of depression. Despite slight reductions in heart rate (HR) during Beta (81.55 ± 13.54 bpm) and Gamma (81.11 ± 13.54 bpm) stimulation compared to the baseline resting moment (85.44 ± 13.89 bpm), the results suggest that the BB at these frequencies also did not change HR. This study indicates the need for further investigation to adapt stimulation techniques to meet the specific needs of patients with depressive symptoms.

Care for a parent with dementia is often shared among multiple adult children, yet it is not always evenly distributed. Guided by the family stress process model, this study examined associations between perceptions of care equality, depressive symptoms, loneliness, and positive affect among 208 adult children caring for a parent with dementia within 110 families from the Siblings Caring for a Parent with Dementia Study (mean age = 58.36, = 9.38; 89% women), and mediating roles of caregiver burden and social support. When adult child caregivers perceived that they were contributing more to parental care than their sibling, they reported greater depressive symptoms than participants who reported equal care. Unequal care was linked to depressive symptoms, loneliness, and positive affect via caregiver burden but not social support. Perceptions of (un)equal divisions of care are associated with adult children's mental health, representing potential caregiving intervention targets.

BACKGROUND: This study examined specific mental health diagnoses groupings among patients admitted to specialty addiction treatment in the United States from 2006 to 2022. METHODS: Joinpoint regression was used to examine annual data from the publicly available Treatment Episode Data Set - Admissions. Sample selection criteria included having a primary substance listed and any of the following conditions: (a) anxiety disorders, (b) bipolar disorders, (c) depressive disorders, and (d) schizophrenia and other psychotic disorders. RESULTS: Prior to sample selection, across the full dataset of 31 152 649, cases with anxiety disorders accounted for 0.1%, bipolar disorders accounted for 0.3%, depressive disorders accounted for 0.4%, and schizophrenia and other psychotic disorders accounted for 0.1%. The total sample size was N = 224 051 with: (a) 13% for anxiety disorders (n = 29 111), (b) 30.3% for bipolar disorders (n = 67 926), (c) 43.4% for depressive disorders (n = 97 293), and (d) 13.3% for schizophrenia and other psychotic disorders (n = 29 721). Count data identified significant decreases including the following: 12.29% from 2008 to 2022 among the bipolar disorder group, 16.69% from 2019 to 2022 among the depressive disorder group, and 6.96% from 2006 to 2022 among the schizophrenia and other psychotic disorders group. CONCLUSION: This study has important implications for future research and clinical care related to co-occurring mental health and substance use disorders. Its findings demonstrate the need for further studies to examine how addiction treatment facilities are screening for and recording mental health disorder diagnoses. Future research is needed to clarify the prevalence of specific mental health diagnoses in the addiction treatment setting, including diagnoses such as anorexia nervosa and generalized anxiety disorder. This research would help determine specific treatment needs by using epidemiological data to provide a snapshot of the prevalence of these co-occurring conditions.

BACKGROUND: Mental health literacy (MHL) in Malawi is low. Mental illness is often attributed to substance abuse or spirit possession, resulting in stigma, maltreatment, and discrimination towards people with mental health problems. Inadequacies in Malawi's mental health services and workforce increase limited treatment access, knowledge, and negative attitudes, causing an epidemic of substance use and suicides. MHL is foundational for mental health promotion, prevention of mental illness, and stigma reduction. Educational settings are ideal for implementing mental health promotion activities. We want to deliver a MHL e-curriculum (MHLeC) to first-year university students in Malawi to improve their MHL. The project aims to assess the feasibility of implementing MHLeC in four Malawian universities within a cluster randomised trial. METHODS: In this pragmatic, cluster randomised feasibility trial, we will approach four to eight public and private tertiary institutions about study participation. Clusters will be participating universities allocated to the mandatory MHLeC or the voluntary MHLeC group using stratified randomisation on a 1:1 ratio. University type (e.g. public or private) will be used as the stratification factor for randomisation, with two levels ensuring two universities per stratum. This approach is appropriate for the four-cluster design. Specific feasibility objectives include (1) estimating likely participation rates of universities and students, (2) establishing potential attendance/retention rates during MHLeC delivery, (3) assessing acceptability of the MHLeC through qualitative feedback after intervention delivery, (4) assessing appropriateness of chosen questionnaires for measuring student outcomes. Data will be analysed descriptively. Outcomes from data collected will inform the feasibility of a future main trial including main trial design and recruitment strategies, sample size and power calculations for a full-scale cluster randomised trial. DISCUSSION: This trial will give us insights on how best to conduct the definitive trial. The intervention can be rolled out nationally within a full-scale trial in Malawi and tested in similar cohorts across Africa if positive results are obtained. More broadly, this research has the potential to significantly increase mental health awareness among young people in Malawi. TRIAL REGISTRATION: This study is registered on the Pan African Clinical Trials Registry (PACTR) website https://pactr.samrc.ac.za/ (PACTR202308849574524). Registered 31st August 2023.

BACKGROUND: Obesity is a chronic disease that, beyond its physical and psychological repercussions, exposes adult individuals to stigma and negative social attitudes. These experiences may negatively affect self-esteem, mental health, and adherence to treatment regimens. The aim of this study is to evaluate multidimensional stigma perception among of stigma among adults diagnosed with obesity and examine the roles of mental health, social support, and treatment engagement in this context. METHODS: This descriptive cross-sectional study was conducted at a state hospital in the Southeastern Anatolia Region of Türkiye between January and April 2025. The study sample consisted of 139 patients who volunteered to participate in the study and met the inclusion criteria, as determined by a power analysis. Data were collected using a questionnaire and the Chronic Illness Anticipated Stigma Scale (CIASS). Total score of CIASS ranges from 12 to 60, with higher scores indicating greater perceived stigma. Data normality was assessed using the Kolmogorov-Smirnov test. Depending on distribution, Student's t-test, one-way ANOVA, Mann-Whitney U, and Kruskal-Wallis tests were used for group comparisons. Pearson correlation analysis and multiple linear regression analysis were performed. In the regression model, the CIASS total score was used as the dependent variable, and independent variables were selected based on the literature and univariate analysis results. Statistical significance was set at p < 0.05. Data were analysed using SPSS 23 software. RESULTS: Most of the participants (74.1%) reported being exposed to negative attitudes, mainly related to physical appearance (55.4%). In addition, 71.2% reported feeling stigmatised, and the majority of them reported receiving no support from family (69.1%) and society (85.6%). The total mean score of CIASS was 34.35 ± 8.02. Those who were exposed to negative attitudes and reported that stigma affected their treatment process had significantly higher CIASS total scores (p < 0.05). Furthermore, the participants who reported having mental health related to obesity had higher CIASS scores (p < 0.05). CONCLUSIONS: Consequently, it was determined that a great part of obese adults with obesity experienced stigma and had a lack of social support, resulting in a negative effect on psychological well-being and treatment processes. Interventions aimed at increasing awareness of obesity-related stigma and providing education and support for obese adults are recommended.

BACKGROUND: Cardiovascular-Kidney-Metabolic (CKM) syndrome is a newly recognized condition characterized by systemic inflammation, a process also implicated in depression. The Dietary Inflammatory Index (DII) quantifies the inflammatory potential of diet, yet its association with depression among individuals with CKM syndrome remains underexplored. METHODS: Utilizing data from 11,847 adults with CKM syndrome stages 0-3 enrolled in seven NHANES cycles (2005-2018), we examined the relationship between DII and depression. The DII was computed using 24-hour dietary recall data. Weighted logistic regression and restricted cubic spline (RCS) analyses were applied to evaluate linear and nonlinear associations. Subgroup and sensitivity analyses were also conducted to assess consistency and robustness. RESULTS: Elevated DII values were consistently associated with a greater likelihood of depression across all models. Participants in the highest DII quartile (Q4) exhibited significantly higher odds of depression than those in the lowest quartile (Q1). RCS models revealed a positive, nonlinear dose-response relationship. Additionally, a significant interaction was observed between DII and diabetes mellitus status. CONCLUSION: A pro-inflammatory dietary profile, reflected by higher DII scores, is positively associated with depression among individuals with CKM stages 0-3. These findings highlight the potential benefits of adopting anti-inflammatory dietary interventions to mitigate depression risk in this population.

BACKGROUND: Dental students face intense academic and clinical pressures, yet large-scale studies utilizing rigorous theoretical frameworks to evaluate their mental health remain limited in China. OBJECTIVE: This study aimed to investigate the prevalence of depression, anxiety, and stress among Chinese undergraduate dental students, identify key sociodemographic and experiential correlates, and evaluate the associations of coping styles with mental health outcomes using a Directed Acyclic Graph (DAG) framework. METHODS: Following STROBE guidelines, a national cross-sectional survey was conducted among 1,712 dental undergraduates from 34 universities across five geographic regions. Psychological distress was assessed via the DASS-21, and coping mechanisms via the SCSQ. Multivariable analyses were employed-specifically, multiple linear regression for continuous subscale scores and ordinal logistic regression for categorical severity levels-to identify factors independently associated with psychological morbidity. RESULTS: The prevalence of at-risk symptoms was 46.1% for anxiety, 36.0% for depression, and 24.4% for stress. Significant regional disparities were observed, with students in the Western region reporting the highest distress levels (Mean total score = 17.81 ± 10.59; p < 0.001). In multivariable models, suboptimal physical health emerged as the strongest factor independently associated with distress (β = 0.37; AOR = 3.71-4.44). While positive coping exhibited a significant inverse association with symptom severity (AOR = 0.87-0.92, p < 0.001), negative coping, poor college adaptation (β = -0.15), appearance dissatisfaction (β = -0.13), and excessive family interference were associated with significantly increased psychological burden. CONCLUSION: Chinese dental undergraduates experience a substantial burden of psychological distress, characterized primarily by anxiety and depression. This distress is disproportionately distributed, with students in Western China and those reporting suboptimal physical health emerging as particularly vulnerable. Positive coping strategies act as vital buffers associated with better mental health, whereas negative coping, body image dissatisfaction, and poor college adaptation are linked to increased psychological burden. Dental education institutions must implement targeted, evidence-based psychological support systems prioritizing these vulnerable cohorts.

BACKGROUND: Digital phenotyping - the moment-by-moment quantification of individual-level human behavior using data from personal digital devices - offers a novel approach to continuous, passive monitoring of psychiatric patients. Changes in behavioral digital phenotypes may serve as early warning signs of relapse or clinical deterioration, creating an opportunity for timely preventive intervention. METHODS: A systematic search of PubMed, PsycINFO, and IEEE Xplore was conducted for studies published up to January 2026. We included prospective and retrospective observational studies using passively collected smartphone or wearable data to predict relapse or clinical deterioration in individuals with diagnosed psychiatric disorders, with reported quantitative model performance metrics. Study quality was assessed using the modified Newcastle-Ottawa Scale [16] and the PROBAST [25, 26] tool. Data were synthesized narratively in accordance with the SWiM guideline. RESULTS: Fifty-two studies encompassing 4,814 participants met inclusion criteria. Disorders studied included schizophrenia spectrum disorders (35%), bipolar disorder (27%), and major depressive disorder (23%). Key predictive features included alterations in sleep patterns (83% of studies), physical activity (83%), GPS-derived mobility (75%), and social communication frequency (65%). Machine learning models reported AUC values ranging from 0.70 to 0.88 for predicting relapse one to four weeks in advance, although the majority of these estimates were derived from internal validation and are likely to overestimate real-world performance. Multi-modal data integration and individual-level modeling consistently outperformed single-modality and population-level approaches. High risk of bias was identified in 75% of studies, primarily attributable to inadequate analytic methodology and reliance on internal validation. CONCLUSIONS: Passive digital phenotyping demonstrates significant promise for predicting psychiatric relapse across diagnostic categories, with moderate-to-good predictive discrimination (AUC 0.70-0.88) achievable up to four weeks prior to confirmed relapse. However, substantial methodological limitations - including reliance on internal validation, heterogeneous outcome definitions, and limited demographic diversity - must be addressed. Standardized outcome definitions, prospective external validation in diverse cohorts, and closed-loop intervention trials are required before widespread clinical implementation can be responsibly pursued.

OBJECTIVE: This study aimed to construct a symptom network model of depression, anxiety, and NSSI using network analysis and to identify the most central and bridge symptoms within the depression-anxiety-NSSI symptom network. METHODS: A total of 200 adolescent patients with depression were recruited from hospitals and assessed using the Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder Scale-7 (GAD-7), and the Modified version of the Adolescent Self-Harm Scale (MASHS). The structural characteristics of depression, anxiety, and NSSI symptoms were characterized using "strength" and "bridge strength" as centrality indices within the symptom network. Network stability was examined using a case-dropping bootstrap procedure. RESULTS: The nodes GAD2 (uncontrollable worry), GAD3 (excessive worry), GAD5 (restlessness), and PHQ9 (suicidal ideation) were the most central symptoms in the network model. Furthermore, within this sample, the symptoms PHQ8 (psychomotor agitation/retardation) and GAD6 (irritability) served as bridge symptoms connecting the anxiety and depressive symptom clusters with the NSSI symptom cluster. CONCLUSION: The central symptoms (such as uncontrollable worry, excessive worry, restlessness, and suicidal ideation) and key bridge symptoms (such as psychomotor agitation/retardation and irritability) within the depression-anxiety-NSSI symptom network may serve as potential intervention targets for adolescent patients with depression.

BACKGROUND: Nursing students experience high prevalence of depression, anxiety, and stress, but traditional variable‑centered approaches may overlook distinct subgroups. This study aimed to identify homogeneous profiles of affective distress and examine their related factors. METHODS: Nursing students (n = 1184) from five medical colleges in Sichuan Province, China were recruited from March 3 to May 30, 2025. Participants were asked to complete questionnaires regarding depression, anxiety and stress, social emotional competency and alexithymia. Latent profile analysis (LPA) was used to identify depression, anxiety, and stress profiles. Chi-square tests and one-way analysis of variance (ANOVA) were used to examine differences in characteristics. Multivariate logistic regression analysis was conducted to explore related factors. RESULTS: The prevalence of depression, anxiety, and stress among nursing students were 38.52%, 46.12%, and 22.47%, respectively. LPA revealed three distinct profiles: "severe affective distress" (11.06%), "moderate affective distress" (35.14%), and "mild affective distress" (53.80%). Related factors for depression, anxiety, and stress included social emotional competency, alexithymia, gender, parenting style, monthly family income, professional identity, satisfaction with campus life, adverse childhood experiences, and campus bullying. CONCLUSIONS: To our knowledge, limited research has applied LPA to examine depression, anxiety, and stress among nursing students. This study identified three distinct latent profiles, revealing significant heterogeneity influenced by individual, family, academic, traumatic characteristics, while social emotional competency and alexithymia. The identified associated factors, including modifiable characteristics such as social emotional competency, alexithymia, campus environment, and bullying, may inform future targeted interventions. CLINICAL TRIAL NUMBER: Not applicable.

BACKGROUND: Women with primary infertility experience elevated psychological distress, yet the interplay between individual symptoms and psychosocial factors remains unclear. This study aimed to identify central and bridge symptoms within a network of depression, anxiety, and psychosocial factors in Chinese women with primary infertility. METHODS: A total of 1,062 women with primary infertility were recruited from four reproductive medicine centers in China between February and December 2025. Depression (PHQ-9), anxiety (GAD-7), perceived stress (PSS-10), fertility-specific stress (COMPI-FPSS-SF), infertility stigma (ISS), social support (MSPSS), and resilience (CD-RISC-10) were assessed. Network analysis using regularized partial correlation networks was conducted to estimate network structure, centrality, bridge centrality, and predictability. RESULTS: Of the participants, 9.6% met clinical thresholds for depression and 5.3% for anxiety. Difficulty relaxing exhibited the highest centrality among symptoms. Public stigma showed the strongest centrality among psychosocial factors, with a robust connection to family stigma (edge weight = 0.538). Perceived stress emerged as the primary bridge linking psychosocial factors to symptoms (bridge expected influence = 0.297), followed by fertility-specific stress (bridge expected influence = 0.143). Guilt was the key bridge symptom (bridge expected influence = 0.086). Resilience showed the strongest negative association with perceived stress (edge weight = - 0.275). Network stability was excellent (CS-coefficient = 0.75). CONCLUSIONS: Difficulty relaxing, perceived stress, and guilt emerged as potentially important nodes that warrant further investigation as candidate intervention targets for psychological distress in women with primary infertility. Interventions targeting relaxation training, stress appraisal, and self-compassion, alongside resilience enhancement, warrant further investigation. CLINICAL TRIAL NUMBER: Not applicable.

BACKGROUND: Depression among older adults is increasingly emerging as a global public health concern. With the rapid advancement of digital information technology, digital smart devices have profoundly reshaped the lifestyle of older adults and may influence their mental health. However, the association between digital smart device use and depression in this population remains unclear, with existing studies reporting inconsistent findings. This study employed a three-level meta-analytic approach to systematically explore the association between digital smart device use and depression among older adults. METHODS: Systematic searches were conducted on six electronic databases including PubMed, Cochrane Library, Embase, Web of Science, MEDLINE, and PsycINFO from their inception to May 6, 2025. Original observational studies (cross-sectional or cohort) were included. Exclusion criteria comprised non-English publications, review articles, conference papers or abstracts, duplicate publications, and studies without available full text or required data. Two researchers independently performed literature screening, data extraction, and quality assessment. Three-level random-effects meta-analyses were conducted to estimate the pooled standardized beta coefficients (β) for continuous depression outcomes and odds ratios (OR) for binary depression outcomes. Risk of bias was assessed using the Newcastle-Ottawa Scale (NOS) for cohort studies and the AHRQ criteria for cross-sectional studies. Potential moderators were explored using three-level meta-regression, and potential publication bias was evaluated using funnel plots, modified Egger's test, and trim-and-fill analysis. RESULTS: A total of 28 articles (23 cross-sectional, 5 cohort) published between 2014 and 2025 were included in the systematic review, with 24 eligible for meta-analysis. All included studies were deemed high quality (mean NOS score: 7.60; mean AHRQ score: 7.57). For continuous outcomes, digital smart device use was significantly associated with lower depression scores (β = -0.201, 95% CI: -0.324, -0.079, p < 0.01). For binary outcomes, device use was associated with a decreased risk of depression (OR = 0.676, 95% CI: 0.613, 0.745, p < 0.001). Moderator analyses indicated that the association was not significantly modified by age, study design, sample size, region, measurement tools, or publication year (p > 0.05). CONCLUSIONS: This study has certain limitations, including publication bias (p < 0.001). However, trim-and-fill analyses confirmed that the results remained statistically significant after imputing missing studies. This three-level meta-analysis provides robust evidence that digital device use is inversely associated with depression among older adults, supporting their potential role in mental health promotion. TRIAL REGISTRATION: The study protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO) in 2024 (registration number: CRD42024616432).

BACKGROUND: Attention-Deficit/Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder characterized by inattention, hyperactivity, impulsivity, emotion dysregulation, and executive dysfunction. Current treatment guidelines recommend a multimodal approach. Cognitive Behavioral Therapy (CBT) has proven effective for alleviating core symptoms, improving executive functioning, and reducing emotional comorbidities, with benefits sustained for up to one year. Dialectical Behavior Therapy (DBT), an adaptation of CBT that integrates mindfulness and emotion regulation components, has also shown potential benefits in adult ADHD populations. However, no prior studies have directly compared CBT and DBT in Chinese adults with ADHD. This trial aimed to compare the efficacy of group DBT and group CBT in adults with ADHD across multiple dimensions, with follow-up assessments extending to six months post-treatment. METHODS: Ninety-eight adults with ADHD were randomly assigned to either the DBT (n = 49) or CBT (n = 49) group, and received 12 weeks of group-based intervention. Assessments were conducted at baseline (T0), weeks 4 (T1) and 8 (T2), post-treatment (T3), and at 3-month (T4) and 6-month (T5) follow-ups. Outcome measures included core symptoms (ADHD-RS), emotional symptoms (SAS and SDS), emotion regulation (DERS and ERQ), quality of life (WHOQOL-BREF), global functioning (GSES and SDS), and executive function assessed via both self-report (BRIEF-A) and laboratory-based tasks (TMT, SCWT, SST, and CPT-IP). Linear mixed models (LMM) were employed to examine group-by-time interaction effects. RESULTS: Both the DBT and CBT groups showed improvement over time in core ADHD symptoms and several secondary outcomes at post-treatment and follow-up. No significant group-by-time interactions were observed for core ADHD symptoms and the between-group effect sizes were small at post-treatment (d = 0.06, 95% CI [-0.33, 0.46]) and at 6-month follow-up (d = 0.17, 95% CI [-0.27, 0.61]). However, the confidence intervals were not fully contained within the prespecified non-inferiority margin (d = 0.40), and formal non-inferiority of DBT relative to CBT was therefore not established. Across secondary outcomes, most between-group differences were generally small, time-specific, and not consistently maintained over follow-up. For laboratory-based executive function measures, CBT showed a relative advantage on a spatial working memory task, whereas no stable between-group differences were observed for most other measures. CONCLUSION: This is the first randomized controlled trial in China to directly compare DBT and CBT for adults with ADHD. The findings indicate that both interventions were associated with improvement across multiple symptom and functional domains, with generally small between-group differences over 6 months of follow-up. DBT may represent a potentially useful psychotherapeutic option for adults with ADHD. However, formal non-inferiority relative to CBT was not established, and the present findings do not support a conclusion of equivalence between the two treatments. Further studies with larger and more diverse samples are needed to obtain more precise estimates of treatment effects and to evaluate the generalizability of the present findings. TRIAL REGISTRATION: ChiCTR2300072075, registered 2023.6.1.

BACKGROUND: Relieving pre-operative anxiety in children is a major concern for anesthesiologists. Midazolam has been the most commonly used sedative agent due to its long history of efficacy. However, it has been associated with complications, such as agitation, cognitive impairment, amnesia, and respiratory depression. For these reasons, other drugs, such as dexmedetomidine, have been explored as safe and effective alternatives in children undergoing surgery. OBJECTIVE: To evaluate the efficacy and safety of intranasal dexmedetomidine as compared to intranasal or oral midazolam in reducing preoperative anxiety in pediatric surgical patients. METHODS: PubMed, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials (CENTRAL) were searched for relevant articles published from inception to January 2026. The search was limited to articles written in English and involved keywords and MeSH terms related to midazolam, dexmedetomidine, surgery, and children. RESULTS: Nineteen randomized controlled trials with 1475 pediatric surgical patients were included. The pooled analysis revealed that intranasal dexmedetomidine was associated with significantly lower anxiety scores at or before induction (SMD: -1.10; 95% CI: -1.68 to -0.53; p = 0.0002), parental separation anxiety (SMD: -0.56; 95% CI: -0.99 to -0.12; p = 0.01), and mean heart rate (HR) (MD: -6.60 beats/min; 95% CI: -10.56 to -2.64; p = 0.001) compared to intranasal midazolam. However, intranasal dexmedetomidine was comparable to oral midazolam in terms of anxiety at or before induction (MD: -7.70; 95% CI: -18.89 to 3.59; p = 0.18), parental separation anxiety (RR: 1.13; 95% CI: 0.44 to 2.88; p = 0.80), and postoperative emergence agitation (RR: 0.22; 95% CI: 0.02 to 2.94; p = 0.25). CONCLUSION: Intranasal dexmedetomidine is more effective than intranasal midazolam in reducing preoperative anxiety in children. No statistically significant difference was detected between intranasal dexmedetomidine and oral midazolam, but studies may have been underpowered to detect clinically important differences. SYSTEMATIC REVIEW PROTOCOL REGISTRATION: PROSPERO: CRD420251234972.

BACKGROUND: Dementia is a neurocognitive disorder that involves deterioration in cognitive and daily functioning, leading to loss of independence and reduced quality of life. While pharmacological treatments offer limited symptomatic relief, non-pharmacological approaches such as exercise have shown promise in improving cognitive and functional outcomes. However, evidence from community-based structured exercise interventions remains limited, particularly in low-resource settings. This trial aims to evaluate the effects of a community-based structured group exercise program on cognitive and physical function among older adults with dementia. METHODS: This assessor-blinded, community-based randomized controlled trial will be conducted from February to September 2026 in Bangladesh. A total of 120 older adults diagnosed with dementia will be randomly allocated (1:1) to either the experimental group (structured group exercise program with healthy lifestyle advice) or the control group (healthy lifestyle advice alone). The intervention will consist of supervised sessions three times a week for 12 weeks, followed by a 12-week follow-up period. The outcome will be measured on both cognitive and physical function bases. Cognitive function will be evaluated using the Mini-Mental State Examination (MMSE), Addenbrooke's Cognitive Examination Revised (ACE-R), Trail Making Test (TMT) A-B, and Digit Span Test (DST). Physical function will be measured using the Senior Fitness Test (SFT), Berg Balance Scale (BBS), Timed Up and Go (TUG) Test, and Instrumental Activities of Daily Living scale (IADLs). All outcomes will be measured at baseline, posttest (12 weeks), and follow-up period (12 weeks). Data will be analyzed using SPSS following the intention-to-treat principle. DISCUSSION: The findings are expected to support the integration of physiotherapist-led, community-based exercise into dementia care, offering a feasible, safe, and cost-effective approach for improving cognitive and physical function in older adults with dementia. Despite potential limitations in generalizability, the study's community implementation and follow-up design will contribute valuable insights into sustainable rehabilitation practices in resource-limited settings. TRIAL REGISTRATION: This trial is registered prospectively in the Clinical Trial Registry India; ID: CTRI/2025/10/096618; Registered on: 29/10/2025. Link: https://ctri.nic.in/Clinicaltrials/pmaindet2.php?EncHid=MTQ0NDg3&Enc=&userName=.

The gut-brain axis plays a critical role in anxiety disorders, yet the underlying mechanisms remain incompletely understood. Using a mouse model of radiofrequency radiation (RFR)-induced anxiety-like behaviors, we employed gut microbiota intervention, regulation of tryptophan metabolites, and other methods to investigate the impact of the gut-brain axis on brain function changes. It was found that gut microbiota dysbiosis disrupts tryptophan metabolism, leading to reduced serotonin (5-HT) levels and NLRP3 inflammasome-mediated neuronal pyroptosis in the medial prefrontal cortex (mPFC). Probiotic intervention restored microbial homeostasis, normalized central 5-HT metabolism, suppressed neuronal pyroptosis, and partially alleviated anxiety-like behaviors. Similarly, treatment with the selective serotonin reuptake inhibitor (SSRI) paroxetine increased brain 5-HT, attenuated NLRP3 activation and pyroptosis, and improved behavioral outcomes. These findings reveal that perturbations in gut-brain tryptophan metabolism are strongly correlated with anxiety-like behaviors via neuroinflammatory pyroptotic pathways, offering new mechanistic insights and potential therapeutic targets for anxiety disorders.

Cannabis withdrawal in cannabis use disorder (CUD) increase the risk of relapse and lacks effective treatments. The endocannabinoid enzyme fatty acid amide hydrolase (FAAH) may influence cannabis use and withdrawal, but the relationship between FAAH levels and withdrawal symptoms remains unclear. This study aims to investigate changes in FAAH levels during short-term abstinence from cannabis and their relationship with withdrawal symptoms. FAAH levels were measured in whole-brain regions of interest using positron emission tomography (PET) with the FAAH-specific probe [C]CURB. An irreversible two-tissue compartment model determined [C]CURB binding. Participants with CUD were scanned once after overnight abstinence (T1) and ~3-7 days after monitored last use (T2). FAAH polymorphism (rs324420) was determined from blood samples, and mood, cognition, withdrawal symptoms, and craving were assessed. In a sample of 14 participants (N = 17 prior to attrition) who completed both scans, FAAH binding in whole-brain increased between T1 and T2 (n = 14; %ΔFAAH = 10%; p = 0.003), with the largest change in the ventral striatum (11%, p = 0.026). Increases in FAAH (%ΔFAAH whole-brain) were significantly associated with longer cannabis abstinence, greater baseline depression severity, and tendency to act without thinking (p < 0.001). Short-term cannabis abstinence is associated with increases in brain FAAH levels. These changes are linked to traits and symptoms associated with relapse vulnerability, including negative mood and impulsivity. These preliminary findings suggest that FAAH may play a key role in the neurobiological response to short-term abstinence and could represent a potential target for interventions.

Maternal mental health is associated with fetal neurodevelopment. Identifying effective treatments for maternal psychiatric conditions is a public health priority. SRIs (SSRIs and SNRIs) are commonly prescribed for prenatal mental health conditions; however, their impact on fetal brain development remains understudied. In this observational cohort study, we compared fetal brain and placental structures between SRI-exposed and unexposed pregnancies divided by categories of maternal depressive symptom severity from the Edinburgh Postnatal Depression Scale (EPDS). Pregnant women treated with SRIs and controls without mental illness or antidepressant exposure underwent fetal MRI studies between 20-40 weeks' gestation. Fetal brain motion correction and 3D reconstructions were performed using slice-to-volume registration. Fetal brain volumes (cortical gray matter, white matter, deep gray matter, cerebellum, brainstem, and hippocampi) were quantified using deep learning-based segmentation with manual correction. Cerebral cortical folding measures included local gyrification index, sulcal depth, curvedness, and surface area. Placental volume and microstructure were assessed with T2-weighted and diffusion-weighted MRI, respectively. EPDS scores were categorized as low ( ≤ 4), moderate (5-9), and high ( ≥ 10). A total of 182 pregnant women were included [62 SRI-exposed (59 SSRIs, 3 SNRIs); 120 controls]. Notably, 29% of SRI-exposed women continued to report elevated depression. SRI-exposed fetuses had smaller hippocampal volumes and reduced cortical gyrification, curvedness, and surface area. Subgroup analysis of stratification by EPDS scores revealed that SRI-exposed fetuses had reduced hippocampal volumes compared to unexposed fetuses with low and moderate, but not high, EPDS scores, and reduced cortical curvedness compared to unexposed subgroups. Among unexposed subgroups, fetuses exposed to high maternal EPDS scores had smaller hippocampal volumes compared to those with low scores. Placenta volume and microstructural diffusion were increased in the SRI-exposed compared to the unexposed group. Larger placental volume was associated with larger total fetal brain volume, and higher placental diffusion was associated with larger fetal white matter and cerebellar volumes in the SRI-exposed group. These findings suggest that prenatal SRI exposure may be associated with altered fetal hippocampal volumes, cerebral cortical maturation, and placental volume and microstructural diffusion. The clinical significance and long-term neurodevelopmental consequences of these structural alterations remain unknown and are currently under study.

Adolescents and young adults (AYAs) with cancer show a strong interest in digital health interventions (DHIs); however, limited pooled evidence from randomized controlled trials (RCTs) exists regarding their quantitative benefits in this population. This systematic review and meta-analysis (PROSPERO: CRD42024593656) screened a total of 9949 records from six databases, registers and other sources up to January 5, 2025, and included 31 articles from 25 studies examining DHIs targeting psychological outcomes among AYAs. Most DHIs were conducted via websites (n = 13), mobile applications (n = 5), wearable devices (n = 6), or videoconferencing/telephone (n = 6), and interventions were multicomponent and promoted self-management. Meta-analysis showed a significant effect of DHIs on quality of life, anxiety, psychological distress, and social support. Meta-regression revealed that the mode of delivery (instructor-based vs. self-guided) moderated the effects of DHIs on anxiety and depressive symptoms, with instructor-based DHIs producing significantly stronger effects. Future RCTs evaluating the impact of DHIs on cognitive impairment and cost-effectiveness are needed.

To analyze the prevalence of frailty in community-dwelling older adults with knee osteoarthritis (KOA) and explore its independent association with fall risk. A cross-sectional study was conducted among older adults with KOA in Zunyi, China, from October 2022 to September 2023 using convenience sampling. Data were collected on sociodemographic characteristics, instrumental activities of daily living (IADL), depression, anxiety, sleep quality, frailty, and fall risk. Propensity score matching (PSM) was performed to match frail and non-frail participants at a 1:1 ratio using nearest-neighbor matching with a caliper of 0.05, based on sociodemographic and lifestyle variables. Conditional logistic regression analysis was then employed to adjust for other potential confounders and determine the strength of the association between frailty and fall risk. A total of 986 community-dwelling elderly patients with KOA were enrolled. The prevalence of frailty was 25.25%, and the proportion of individuals at high fall risk was 51.72%. After PSM, 470 matched participants were obtained (235 in each group). Conditional logistic regression analysis showed that frailty was significantly associated with high fall risk (P < 0.001), with frail individuals having a 5.21-fold higher likelihood of being at high fall risk than non-frail individuals (OR = 5.21, 95%CI 2.66-10.17). Additionally, poor self-rated health (OR = 7.38, 95%CI 1.20-45.46, P = 0.031) and IADL impairment (OR = 4.74, 95%CI 1.37-16.43, P = 0.014) were also significantly associated with increased fall risk. Frailty is independently associated with an increased fall risk in community-dwelling older adults with KOA. Routine frailty screening could be integrated into primary care for this population to support fall risk monitoring and stratified assessment.

Anxiety is a common mental health disorder marked by heightened stress responses and impaired emotional regulation. While the hippocampus and the hypothalamic-pituitary-adrenal (HPA) axis play key roles in regulating anxiety, the molecular mechanisms remain incompletely understood. In this study, we identified a strong link between ARHGAP39 function and anxiety using brain-specific Arhgap39 conditional knockout (cKO) mice. ARHGAP39 is a brain-enriched Rho GTPase-activating protein implicated in neurodevelopment and synaptic regulation. Arhgap39 cKO mice exhibited ectopic progenitor cells in the hilus of the hippocampus during early postnatal development, along with impaired adult neurogenesis in dentate gyrus (DG). Behaviorally, adult cKO mice demonstrated pronounced anxiety-like phenotypes without cognitive impairments, whereas aged cKO mice exhibited persistent anxiety accompanied by learning and memory deficits. Molecular profiling revealed that cKO mice exhibited significantly elevated RNA expression levels of glutamatergic and glucocorticoid receptor-related genes in the hippocampus. In addition, cKO mice exhibited more stress-activated neurons in the DG. Mechanistically, Arhgap39 deficiency disrupted Rho GTPase-related actin pathways, leading to elevated Cofilin-1 and Arp3 expression and reduced PSD-95 levels, suggesting disruption of synaptic organization. Finally, hippocampal overexpression of Arhgap39 in C57BL/6 mice did not affect baseline behavior but alleviated chronic stress-induced anxiety in light-dark box test. In conclusion, our findings demonstrate that ARHGAP39 plays a critical role in modulating anxiety, hippocampal neurogenesis, and synaptic stability, highlighting it as a promising target for developing anxiolytic therapies.

Attention-deficit/hyperactivity disorder (ADHD) is a heterogeneous neurodevelopmental disorder marked by inattention, impulsivity, and hyperactivity. Although the spontaneously hypertensive rat (SHR) is widely used to model ADHD, intra-strain behavioral heterogeneity and its neurobiological relevance remain insufficiently defined. We conducted a comprehensive multidomain behavioral assessment of male adolescent SHR and Wistar-Kyoto (WKY) rats spanning locomotion/exploration, anxiety- and risk-related behavior, compulsive-like activity, cognition, and sensorimotor gating. Across tasks, SHR rats exhibited increased impulsive and repetitive exploratory behaviors, context-dependent alterations in anxiety-related measures, reduced spontaneous alternation, and impaired prepulse inhibition. Exploratory factor analysis of 26 behavioral variables identified five interpretable latent dimensions, including exploratory-attentional engagement and impulsivity/disinhibition, and revealed substantial heterogeneity within the SHR population. Using WKY-referenced factor-score deviation, SHR were stratified into normative-range and combined-deviant subtypes. The combined-deviant subtype exhibited convergent circuit-level alterations, including reduced parvalbumin (PV)/glutamate decarboxylase 67 (GAD67)-associated inhibitory features and decreased synaptic marker signals in prelimbic and infralimbic medial prefrontal cortex, together with increased dopamine transporter expression (DAT) in the striatum without changes in tyrosine hydroxylase (TH). Complementary principal axis factoring, bootstrap resampling, and split-sample analyses supported the robustness of the factor structure. These findings link multidimensional behavioral subtypes in SHR to distinct prefrontal-striatal signatures, strengthening the translational utility of SHR-based ADHD research.