BACKGROUND: Anorexia nervosa (AN) is a severe psychiatric disorder frequently associated with affective disturbances, particularly depression, and marked deficits in emotional awareness. Alexithymia has been identified as a core vulnerability factor in AN, however, its relationship with eating disorder symptomatology appears complex and may be influenced by depressive mood. Despite growing interest in transdiagnostic emotional processes, the mediating role of depression in the association between alexithymia and eating symptoms remains insufficiently explored, especially in young women and using comprehensive psychopathological assessment tools. OBJECTIVES: The present study aimed to examine differences in alexithymia, emotion regulation, mood, personality-related psychopathology, and eating disorder symptoms between young women with and without restrictive AN; to investigate associations among these dimensions within each group; and to test the mediating role of depression in the relationship between alexithymia and eating disorder symptomatology. METHODS: The sample consisted of 47 young women with restrictive AN and 48 non-clinical controls aged 16-30 years. Participants completed the Toronto Alexithymia Scale (TAS-20), Profile of Mood States (POMS), Emotion Regulation Questionnaire (ERQ), Minnesota Multiphasic Personality Inventory-2 (MMPI-2) and Eating Disorder Inventory-3 (EDI-3). Group comparisons were performed between the clinical and control groups. Correlational analyses and mediation models were conducted separately within each group. RESULTS: Compared to controls, patients with AN showed significantly higher levels of psychopathology, depressive mood, alexithymia, and expressive suppression. Correlational analyses revealed partially different patterns across groups. Mediation analyses indicated that, in the clinical group, the association between alexithymia and eating disorder symptoms was fully accounted for by depressive symptoms, whereas in the control group both direct and indirect associations remained statistically significant. CONCLUSIONS: These findings suggest that depressive symptoms may partially account for the observed association between alexithymia and eating disorder symptoms in AN. However, the cross-sectional design precludes causal inferences. Nevertheless, the results highlight the clinical relevance of assessing emotional awareness and depressive symptoms in young women with AN.

A growing number of studies point to a key role of the amygdala in Autism Spectrum Disorders (ASD). The amygdala is involved in several processes in ASD including emotional valence, facial recognition, regulation of social learning, empathy, and anxiety. Brain imaging and postmortem studies demonstrate altered amygdala development in children with ASD, associated with impairment in social behavior and anxiety. There is limited information regarding the molecular pathology of the amygdala in children with ASD. We conducted RNAseq profiling on postmortem amygdala samples from male children (4-14 years old) with ASD (n = 8) and normotypic male children (n = 6). Furthermore, we conducted drug repurposing analysis to identify compounds predicted to reverse the transcriptomic signatures identified in order to identify potential therapeutic targets for development of early intervention treatments. Full transcriptome gene expression profiling implicated molecular pathways involved in neuroimmune signaling, glycogen and carbohydrate metabolism, matrix metalloproteases, neurodevelopment, estrogen receptor signaling, and synaptic signaling. Targeted pathway analysis of the top 10% of genes ranked by log fold change implicated pathways involved in extracellular matrix organization (ECM), immune signaling, and synaptic signaling. Our drug repurposing analysis identified sleep modifying compounds and anti-inflammatory compounds including COX2 and GSK3 inhibitors amongst the top predicted therapeutic compounds. PDGF receptor tyrosine kinase inhibitors were identified as a top potential therapeutic mechanism of action. Collectively, we identified alterations in immune signaling, ECM, and synaptic signaling in the amygdala of children with ASD. Furthermore, our findings highlight a number of potential therapeutic drug targets for development of early intervention strategies.

PURPOSE: To describe the humanistic and economic burden among informal caregivers of individuals with transfusion-dependent β-thalassemia (TDT) across the US and Europe. METHODS: A mixed-methods study was conducted with qualitative interviews in the US and UK and an online survey in the US, UK, France, Italy, and the Netherlands. The survey included CarerQoL-7D, ZBI-12, and WPAI: CG and captured time spent providing informal care and out-of-pocket (OOP) expenses. Interviews were analyzed using the Framework Method, and survey data with descriptive analyses. Monetary values were standardized to US dollars (2025 USD). RESULTS: Interviews with 10 caregivers revealed five key themes: (1) Need for a strong support network; (2) Burden of disease management and constant care; (3) Barriers and facilitators to optimal care; (4) Impact on caregivers' daily life, work, and aspirations; and (5) Emotional distress and impacts on well-being. Seventy caregivers completed the survey. The CarerQoL-7D indicated adverse impacts on quality of life (QoL), with > 60% reporting mental health, daily activity, and physical health problems. On average, US and European caregivers spent 34.7 and 40.5 h per week performing caregiving activities, respectively. WPAI: CG results indicated overall work impairment of 33 and 43% among US and European caregivers, respectively. Average annual OOP expenses were $6000 in the US and $3348 in Europe. CONCLUSION: Caregivers of people with TDT experience negative impacts on QoL and work productivity. There is a need for healthcare policies to address caregiver's distinct challenges. Improving access to emerging therapies may ease caregiver and patient burden.

BACKGROUND: Lung cancer surgery is associated with significant perioperative morbidity, including pulmonary complications and psychological distress. The effectiveness of comprehensive interdisciplinary care models in improving outcomes remains insufficiently studied. METHODS: This single-center randomized controlled trial enrolled 240 patients undergoing lung cancer surgery between March 2021 and December 2023. Patients were randomized 1:1 to receive either an interdisciplinary integrated care intervention (n = 120) or standard care (n = 120). The intervention included preoperative pulmonary rehabilitation, psychological support, nutritional optimization, and enhanced postoperative recovery protocols. The primary outcome was postoperative length of hospital stay (LOS). Secondary outcomes included postoperative pulmonary complications (PPCs), pain scores, functional recovery (6-min walk distance), psychological status (HADS), and quality of life (QLQ-C30). Intention-to-treat analysis was performed as the primary analysis. RESULTS: In the ITT analysis, the intervention group had significantly shorter LOS compared to control (7.43 ± 1.94 vs. 9.02 ± 2.30 days; mean difference 1.59 days, 95% CI: 1.07-2.12; p < 0.001; Cohen's d = 0.75). After adjusting for baseline FEV1 imbalance, the difference remained significant (adjusted mean difference 1.54 days, 95% CI: 1.02-2.06; p < 0.001). PPCs were significantly lower in the intervention group (12.0% vs. 26.1%; RR = 0.46, 95% CI: 0.26-0.81; p = 0.008). The intervention group demonstrated superior functional recovery, with 6-min walk distance differences of 57.77 m at 1 month and 61.97 m at 3 months, both exceeding the minimal clinically important difference of 22-42 m. Psychological outcomes (HADS-anxiety: 4.19 ± 2.55 vs. 6.48 ± 3.22; HADS-Depression: 3.57 ± 1.97 vs. 5.19 ± 2.89 at 3 months; both p < 0.001) and quality of life were significantly improved. CONCLUSIONS: An interdisciplinary integrated care model significantly reduces hospital stay, decreases pulmonary complications, and improves functional and psychological outcomes in patients undergoing lung cancer surgery. These findings support the implementation of comprehensive perioperative care programs.

PURPOSE: Psychological stress, here used as an umbrella term encompassing depression, anxiety, psychosocial stress, stressful life events, perceived stress, and job strain, is hypothesized to influence cancer development and prognosis, yet epidemiologic evidence is inconsistent. This umbrella review with secondary quantitative synthesis evaluated associations between stress-related exposures and cancer incidence and mortality. METHODS: PubMed was searched from inception to March 1, 2026, alongside Scopus, the Cochrane Library, citation tracking, and manual screening. Eligible studies included systematic reviews, meta-analyses, or pooled individual participant data analyses assessing depression, anxiety, psychosocial stress, stressful life events, perceived stress, or job strain in relation to cancer incidence or mortality, reporting adjusted HRs, RRs, or ORs. Random-effects models were used for secondary pooling. Overlap was assessed with corrected covered area, and evidence credibility with the Ioannidis framework. RESULTS: Fifteen publications met inclusion criteria; eight were quantitatively synthesized, representing over four million participants. Psychological stress was not significantly associated with overall cancer incidence (pooled RR/HR 1.06; 95% CI 0.99-1.14; I = 72.5%) or breast cancer incidence (RR/OR 1.13; 95% CI 0.95-1.34; I = 77.8%). In contrast, cancer mortality was consistently elevated across 4 analyses (RR/HR 1.23; 95% CI 1.19-1.27; I = 0%). Site-specific mortality risks ranged from HR 1.15 for lung cancer to HR 3.86 for leukemia. Review overlap was moderate (7.4%). Associations between depression/anxiety and cancer mortality reached Class I evidence. CONCLUSION: Psychological stress-related exposures were not significantly linked to cancer incidence in the available meta-analytic evidence, whereas depression, anxiety, and related distress were consistently associated with increased cancer mortality. These findings should be interpreted cautiously because residual confounding and measurement heterogeneity remain important limitations.

BACKGROUND: Academic pressure represents a primary source of stress for young people. While psychological capital, encompassing hope, efficacy, resilience, and optimism, benefits working populations, its significance in academic contexts remains less understood, particularly regarding student mental health. Drawing from the conservation of resources theory, it was hypothesized that academic PsyCap is prospectively associated with reduced anxiety and depressive symptoms through increased adaptive coping and decreased maladaptive coping strategies. METHODS: A two-wave prospective study was conducted on a sample of 507 undergraduate students in Hong Kong, China. Structured questionnaires were administered at the beginning (T1) and the end (T2) of the academic semester. The measures included academic PsyCap, coping strategies for academic stress, and anxiety and depressive symptoms. Structural equation modeling was conducted to test the hypothesized mediation model. RESULTS: The results indicated that academic PsyCap at T1 had a negative indirect effect on anxiety and depressive symptoms at T2 through reduced maladaptive coping strategies at T2. Conversely, adaptive coping strategies at T2 did not serve as an underlying mechanism for the effect of academic PsyCap at T1 on anxiety and depressive symptoms at T2. CONCLUSION: This study highlights the role of academic PsyCap as a valuable set of personal resources associated with reduced maladaptive navigation of academic stress and better mental health outcomes among university students. Working toward the development and evaluation of intervention programs designed to cultivate academic PsyCap may represent a potential avenue for supporting student well-being.

INTRODUCTION: Scars present repercussions beyond physical appearance, affecting emotional well-being and social interactions. Few studies have compared how different scar types, including keloids (K), hypertrophic scars (HS), and post-burn scars (BS), relate to psychosocial outcomes. OBJECTIVE: Assess body appreciation and screening indicators of anxiety and depression in patients with scars of different etiologies. METHODS: We conducted an exploratory cross-sectional study including 42 patients with scars allocated to three groups: K, HS, and BS. Body image perception was measured using the Body Appreciation Scale (BAS), and anxiety and depression were assessed using the Hospital Anxiety and Depression Scale (HADS). Mean BAS and HADS scores were compared across groups, and associations with clinical features were explored. RESULTS: The combined prevalence of anxiety and depression symptoms increased descriptively from HS (0%) to K (5.9%) to BS (20%) ( = 0.11). Higher odds of combined anxiety and depression symptoms were associated with facial involvement ( = 0.017; OR = 19.8, 95% CI 1.70-229.65), and functional impairment ( = 0.039; OR = 18.0, 95% CI 1.59-202.95) features more frequent among burn patients, although confidence intervals were wide. BAS scores did not differ significantly among groups ( = 0.78), indicating moderate-to-high body appreciation across scar types (mean BAS: 3.68 burns, 3.77 hypertrophic, 3.85 keloids). Anxiety ( = 0.57) and depression ( = 0.43) scores were similar. CONCLUSION: Different scar types were associated with broadly similar psychosocial outcomes. Emotional vulnerability among patients with burn scars appears more closely related to scar-related features, such as facial location and functional impairment, than to scar etiology alone. Findings should be interpreted cautiously and regarded as hypothesis-generating. LAY SUMMARY: This study examined how different types of scars, including burns, hypertrophic scars, and keloids, may affect emotional well-being and body image. Adults with these scars completed questionnaires assessing body appreciation, anxiety, and depression. Overall, levels of body appreciation were similar across groups, suggesting that many people can adapt to visible or symptomatic scars over time.Participants with burn scars showed a tendency toward higher levels of anxiety and depressive symptoms. However, these emotional difficulties were more strongly associated with features such as facial involvement and functional limitations than with the type of scar itself. This highlights the importance of considering the broader clinical and social context in which scars occur.As this was an initial study with a relatively small number of participants, the findings should be interpreted as exploratory rather than definitive conclusions. Overall, the results suggest that while many people adapt well to scars, those accompanied by greater visibility or functional impact may be linked to emotional vulnerability. Comprehensive scar management should therefore address not only physical and psychological support but also promote recovery that considers the person as a whole.

BACKGROUND: Underprivileged children from low socio-economic backgrounds lack access to the resources that promote cognitive, emotional and social development. Cognitive stimulation and psychological support enhance the neurobehavioural responses in underprivileged children. Interventions like Mindfulness-based Dance Movement Therapy (MBDMT) are inter-modal psychotherapy, enhancing mind and body integration, improving emotional regulation and alleviating mental health problems like loneliness and aggression. PURPOSE: The study aims to evaluate the effect of MBDMT on loneliness and aggression among underprivileged children of an NGO in Delhi-NCR, India. METHODS: A quasi-experimental pre-post design was adopted, with 100 participants (aged 10-16 years) divided into treatment and control groups. The intervention consisted of 15 sessions (60 min each, for 15 weeks). UCLA Loneliness Scale and Buss-Perry Aggression Questionnaire were administered pre- and post-intervention and at follow-up (3 months). Data was analysed through a paired samples -test using SPSS. RESULTS: The value of the treatment group was 17.890 at < .01, indicating a significant reduction in loneliness post-MBDMT. The aggression score of the treatment group has a value of 20.290, indicating a significant decrease in aggression post-intervention. The post-test scores of both treatment and control groups were analysed for loneliness and aggression; the values were -3.322 and -6.723, indicating a significant decrease in loneliness and aggression in the treatment group. The comparison of post-test and follow-up of loneliness had a value of -2.760. And the follow-up scores of aggression showed a significant value of 8.053. CONCLUSION: MBDMT is an effective community-based neurobehavioural intervention for reducing loneliness and aggression among underprivileged children. The results highlight the therapeutic value of mindfulness and movement-based expressive interventions in promoting emotional regulation and social connectedness in community settings. Although Indians have been known for practising classical dance forms, yoga and meditation for ages, schools should inculcate mindfulness and movement with the usual curriculum.

INTRODUCTION: Insomnia affects health, well-being, and productivity. Despite recommendations favoring Cognitive Behavioral Therapy for Insomnia (CBT-I) as first-line treatment, hypnotic medications remain widely used. OBJECTIVE: To examine the frequency and types of sleep medications used by individuals with insomnia symptoms seeking psychological treatment, as well as factors associated with hypnotic use. MATERIALS AND METHODS: The present cross-sectional study included 1,158 adults with insomnia symptoms recruited from a specialized service between 2021 and 2022. Participants completed online questionnaires assessing sociodemographic characteristics, medication use, and standardized measures of insomnia severity (Insomnia Severity Index), anxiety, and depression (Hospital Anxiety and Depression Scale). Descriptive analyses and multivariate logistic regression were performed. RESULTS: From the total (n = 1,158), 60% of participants reported current use of sleep medication. The most frequently used classes were Z-drugs and benzodiazepines, followed by sedative antidepressants. Greater insomnia severity was the primary factor associated with hypnotic use (odds ratio = 1.14;  < 0.001). White participants were also more likely to use hypnotics, regardless of insomnia severity. CONCLUSIONS: Pharmacological treatment remains predominant among individuals with insomnia symptoms, despite recommendations for CBT-I as the first-line treatment. These findings highlight the importance of expanding access to behavioral interventions and promoting the rational use of sleep medications in Brazil.

Selective serotonin reuptake inhibitors (SSRIs) are widely used as first-line treatments for major depressive disorder (MDD) and anxiety disorders, with common adverse effects, including sexual dysfunction, anxiety, insomnia, and appetite changes, although seizures have also been reported, particularly in the presence of risk factors such as older age, family history of epilepsy, neurological comorbidities, and high antidepressant dosages. We describe two patients who developed generalized tonic-clonic seizures associated with SSRI therapy. The first case is a man with SSRI-resistant MDD and multiple medical comorbidities who experienced five generalized tonic-clonic seizures while receiving various antidepressants. The second case is a woman with generalized anxiety disorder (GAD) who developed two generalized tonic-clonic seizures temporally related to paroxetine use. In both cases, extensive investigations, including laboratory tests, electroencephalogram (EEG), CT, and MRI, yielded normal results, suggesting a potential drug-associated etiology. Both patients were subsequently switched to the atypical antidepressant agomelatine, which was followed by a complete cessation of seizures and marked improvement in mood and anxiety symptoms. These observations underscore the need to consider seizures as a potential adverse event of SSRIs and suggest that agomelatine could be considered an alternative pharmacological option for patients at risk of antidepressant-associated seizures.

BACKGROUND: Respiratory depression remains a major safety concern during propofol-based sedation for surgical abortion. Ciprofol is a novel intravenous sedative-hypnotic agent with pharmacological properties similar to propofol and a potentially improved safety profile. This randomized controlled trial aimed to compare the incidence of respiratory depression of ciprofol versus propofol, both combined with alfentanil, for procedural sedation in patients undergoing surgical abortion. METHODS: In this single-center, assessor-blinded, randomized controlled trial, 234 patients scheduled for surgical abortion under intravenous anesthesia were assessed for eligibility, and 226 were randomly assigned to receive either ciprofol (0.4 mg/kg; n=113) or propofol (2.0 mg/kg; n=113). Alfentanil (7.5 μg/kg) was administered intravenously as part of anesthesia induction in all patients. The primary outcome was the incidence of respiratory depression (SpO <90% requiring airway intervention) throughout the anesthesia and surgical procedure. Secondary outcomes included the overall incidence of perioperative adverse events as a composite safety endpoint defined as the occurrence of at least one prespecified adverse event from induction to discharge. Additional anesthesia-related variables, including induction characteristics, hemodynamic changes, depth of sedation, post-procedure pain scores, and patient satisfaction, were evaluated as exploratory outcomes. RESULTS: Under the same anesthesia depth, respiratory depression occurred less frequently with ciprofol than with propofol (9.7% vs 20.4%, =0.026). The overall incidence of perioperative adverse events was lower in the ciprofol group (28.3% vs 64.6%, < 0.001). Injection pain was observed in 34.5% of patients receiving propofol and in none receiving ciprofol. PONV, hemodynamic instability, procedure time, time to discharge, post-procedure pain scores and patient satisfaction were comparable between groups. No serious adverse events occurred. CONCLUSION: Ciprofol combined with alfentanil was associated with a lower incidence of respiratory depression and perioperative adverse events than propofol, while providing comparable procedural sedation efficacy in patients undergoing surgical abortion.

OBJECTIVE: Sepsis elicits neuroinflammation in the medullary visceral zone (MVZ), which disrupts the cholinergic anti-inflammatory pathway (CAP). However, the underlying mechanisms and translational therapeutic potential remain poorly defined. METHODS: Adult male Sprague-Dawley rats received either intracerebroventricular lipopolysaccharide (LPS; 25 μg/25 μL) to induce MVZ neuroinflammation model rats, or intraperitoneal LPS (6 mg/kg) to establish polymicrobial sepsis model rats. Anti-inflammation groups were involved with minocycline sucrose solution (120 mg/L) which was administered by drinking for 4 days prior to LPS challenge. CAP transection groups were undergone right cervical vagotomy 7 days before anti-inflammation interventions. Murine sepsis score (MSS), mortality rates, heart rate variability (HRV), cytokine levels in blood and medulla, systemic immunity level, and the expression levels of glial fibrillary acidic protein (GFAP), ionized calcium-binding adapter molecule 1 (IBA-1), CD22, tumor necrosis factor-α (TNF-α), Munc13-1, Synaptophysin (SYN), and postsynaptic density protein 95 (PSD-95) in the MVZ were measured and analyzed. RESULTS: Both sepsis and MVZ neuroinflammation model rats showed significantly increased mortality and MSS scores, depressed HRV parameters, and upregulated expressions of GFAP, IBA-1, CD22, and TNF-α, with downregulated expressions of Munc13-1, SYN, and PSD-95 in the MVZ. Synaptic structural damage including reduced synaptic vesicles, decreased RT1.D expression on lymphocytes, increased percentages of Th17 and Treg lymphocytes, and increased serum levels of TNF-α, IL-10, and INF-γ were observed. Anti-inflammatory intervention reversed these changes in both model rats, whereas CAP transection partially abolished the anti-inflammatory benefits, confirming CAP dependence. CONCLUSIONS: Sepsis-induced MVZ neuroinflammation dismantles synaptic integrity and CAP modulation, which intensifies peripheral cytokine storm. Early central anti-inflammation repairs MVZ synaptic plasticity and reinstates vagal immunomodulation, which may provide a translational strategy to limit septic escalation.

BACKGROUND: Antipsychotic-induced extrapyramidal symptoms (EPS), including drug-induced parkinsonism, akathisia, dystonia, and tardive dyskinesia, remain major limitations of long-term antipsychotic therapy and negatively affect treatment adherence and quality of life. Traditional Chinese Medicine (TCM) has increasingly been explored as an adjunctive strategy for EPS management; however, evidence regarding prescription patterns, clinical effectiveness, and mechanistic rationale remains fragmented. OBJECTIVE: To conduct an integrative review of TCM interventions for antipsychotic-induced EPS through synthesis of clinical evidence and quantitative analysis of prescription patterns. METHODS: A systematic search of English- and Chinese-language databases identified 31 eligible studies, including randomized controlled trials, non-randomized studies, and cohort investigations. Clinical characteristics, EPS subtypes, outcome measures, safety data, and herbal prescription components were extracted. Narrative evidence synthesis was combined with frequency analysis, association rule mining, clustering, and network mapping to identify recurrent herbal combinations and therapeutic structures. RESULTS: Included studies involved patients with schizophrenia-spectrum disorders receiving first- or second-generation antipsychotics. Drug-induced parkinsonism and tardive dyskinesia were the most frequently evaluated EPS subtypes. Frequently prescribed herbs included , , , and . Data mining identified reproducible prescription patterns centered on wind-extinguishing, blood-nourishing, and phlegm-resolving therapeutic principles. Across comparative studies, adjunctive TCM interventions were associated with reductions in EPS severity scores and generally mild adverse events. Mechanistic findings suggested potential roles in dopaminergic modulation, neuroprotection, anti-inflammatory activity, and oxidative stress reduction. However, methodological heterogeneity, inconsistent reporting standards, limited blinding, and short follow-up durations reduced certainty of evidence. CONCLUSION: Current evidence suggests that adjunctive TCM interventions may provide symptomatic benefit for antipsychotic-induced EPS, particularly drug-induced parkinsonism and tardive dyskinesia. Nevertheless, existing evidence remains preliminary and geographically concentrated, and higher-quality multicenter studies with standardized reporting and long-term safety evaluation are required before broader clinical implementation can be recommended.

This article examines the political abuse of psychiatry in Romania during the Ceaușescu era (1965-1989), analyzing how psychiatric institutions were systematically transformed into instruments of ideological control. Drawing on Securitate archives, victim testimonies, legal documents, and medical reports, this study demonstrates three interconnected dimensions of psychiatric repression: the operational mechanics through which political dissent was pathologized into psychiatric diagnosis; the deployment of medical authority to disguise political persecution as therapeutic intervention; and Romania's distinctive post-1989 failure of accountability, through which perpetrator structures survived regime change intact. The analysis reveals how complicit psychiatrists wielded diagnostic categories such as "paranoia" and "discordant syndrome" as political code, while institutions inflicted systematic violence masked as treatment. Unlike other post-communist transitions where lustration laws dismantled collaborator networks, Romania's psychiatric nomenclatura maintained uninterrupted control over professional structures, investigative commissions, and institutional memory. This article contributes to scholarship on medical ethics, state violence, and the weaponization of health care under authoritarian regimes, integrating operational, institutional, and transitional justice perspectives. In doing so, it demonstrates how the fusion of medical authority with security power produced a form of repression uniquely resistant to external scrutiny and post-communist accountability.

BACKGROUND: Falls and related injury are understudied among people aging with long-term physical disabilities (PAwLTPD). OBJECTIVES: This study examined the prevalence of falling and injury among PAwLTPD over three years and explored associations of disability-related symptoms with these outcomes. METHODS: A longitudinal survey (annual, three years: T0, T1, T2) was conducted among PAwLTPD (45-65 years). Participants were queried about whether they fell in the past year and fall-related injury. PROMIS measures were used to assess depression, fatigue, and pain. RESULTS: 323 PAwLTPD (69% women, 63% White, average age 56 years, average 19 years with disability) completed the three annual surveys. Over 65% fell in the past year at T0. Participants had lower odds of falling at T1 (odds ratio [OR] 0.55, 95% confidence interval [CI] 0.36-0.85) and at T2 (OR 0.55, CI 0.36-0.85). Approximately 40% fell in all three years. At T0, 15% fell with major injury. The odds of falling with major injury were lower at T1 (OR 0.15, CI 0.06-0.37) and T2 (OR 0.17, CI 0.07-0.40). In multivariable models, increasing fatigue T-score was associated with increased odds of falling (adjusted OR [aOR] 1.08, CI 1.05-1.12), falling all three years (aOR 1.12, CI 1.06-1.18), and minor injury (aOR 1.09, CI 1.05-1.13). CONCLUSION: Falls across multiple years and related injury are common among PAwLTPD and associated with disability symptoms. Regular screening and interventions to manage these conditions, including fatigue, should be researched as possible methods to decrease falls and injury among this understudied population.

Alcohol withdrawal syndrome (AWS) develops in patients with alcohol use disorder (AUD) and physical dependence after abrupt cessation or substantial reduction of sustained heavy alcohol use. It is common and potentially life-threatening in general medical practice. Characteristic features include tremor, autonomic activation, anxiety, insomnia, perceptual disturbances, seizures, and delirium tremens. This practical review aims to guide internists in early recognition, risk stratification, monitoring, pharmacological treatment, and transition to longitudinal AUD care. Most hospitalized patients can be managed effectively when physicians identify early high-risk features, select an appropriate level of monitoring, and use approved first-line therapy. Supportive care, including thiamine, hydration, electrolyte correction, and reassessment for differential diagnoses, is essential. Benzodiazepines remain the standard of care for moderate to severe withdrawal, but decisions should reflect withdrawal history, current severity, comorbidity, and symptom-scale limitations in medically complex patients. Benzodiazepine-based protocols include symptom-triggered therapy, fixed-dose therapy, and front loading; choosing among them should depend on the patient's risk profile, ability to participate in symptom scoring, and monitoring environment. Phenobarbital is increasingly used within standardized, closely monitored hospital protocols with appropriate expertise, whereas clomethiazole and sodium oxybate remain region-specific alternatives in some European countries. This review also emphasizes delirium tremens and refractory withdrawal, including when higher-acuity care and adjunctive sedatives should be considered. Hospitalization should be used to initiate treatment for AUD and reduce recurrent withdrawal, readmission, and mortality.

BACKGROUND: Targeting methods for repetitive transcranial magnetic stimulation (rTMS) in patients with depression now include individual functional magnetic resonance imaging (fMRI) scans to target specific functional connectivity (FC) patterns. Potential biomarkers of rTMS response include target FC with the subgenual anterior cingulate cortex (SGC) or the causal depression circuit (CDC), each of which may be candidates for individualized functional targets (iFTs). We retrospectively assessed the relationship of these two approaches to outcomes in secondary analyses of two large rTMS clinical trials. METHODS: 501 subjects with moderate to severe depression underwent 4-6 weeks of daily rTMS to the left dorsolateral prefrontal cortex (DLPFC), targeted using neuronavigation to an optimized DLPFC-SGC-FC group-based functional target. Baseline resting-state scans were used to retrospectively compute iFTs using either SGC-DLPFC or CDC-DLPFC FC. Proximity (Euclidean distance) of the stimulated target to iFTs were correlated with outcomes. Electric field magnitude at iFTs was computed to capture non-linear stimulation propagation. RESULTS: Most iFTs were within 2cm of their group-target. Proximity to either an SGC- or CDC-iFT was not associated with better outcomes. Sensitivity analyses accounting for treatment target FC, methodology, data quality, or treatment parameters did not change results. Electric field-based measures were highly similar to Euclidean distance and likewise showed no association with outcomes. CONCLUSIONS: Under the specific fMRI acquisition parameters used, proximity to optimized DLPFC-SGC-iFTs was not associated with better outcomes in patients receiving neuronavigated rTMS to an optimized DLPFC-SGC group-target. Prospective randomized clinical trials definitively assessing the clinical utility of iFTs are warranted. .

OBJECTIVE: To identify barriers and facilitators to implementing guideline-recommended cognitive rehabilitation within the Veterans Health Administration (VHA) Polytrauma/Traumatic Brain Injury System of Care (PSC) and to systematically identify implementation strategies targeting these determinants. DESIGN: Qualitative study using semi-structured interviews informed by the Consolidated Framework for Implementation Research (CFIR), followed by CFIR-Expert Recommendations for Implementing Change (CFIR-ERIC) mapping to identify implementation strategies aligned with identified determinants. SETTING: VHA PSC. PARTICIPANTS: PSC providers involved in delivery of cognitive rehabilitation for Veterans with traumatic brain injury (TBI; n = 14), including referring providers and cognitive rehabilitation specialists. INTERVENTION: None. MAIN OUTCOME MEASURE(S): CFIR-based implementation determinants and implementation strategies aligned with identified determinants, identified using CFIR-ERIC query results. RESULTS: Barriers and facilitators to implementing guideline-recommended cognitive rehabilitation were identified across multiple CFIR domains. Key barriers included perceived misalignment between manualized treatments and individualized Veteran needs, intervention complexity, limited staffing and organizational prioritization, gaps in provider knowledge of evidence-based practices, and lack of systematic implementation planning and evaluation. Facilitators were primarily concentrated within the inner setting and included interdisciplinary collaboration, support for provider training, and leadership prioritization of cognitive rehabilitation. CFIR-ERIC mapping identified 23 discrete implementation strategies aligned with these determinants. The most aligned strategies included identifying and preparing champions, assessing readiness and barriers, developing an implementation blueprint, capturing and sharing local knowledge, and conducting local needs assessments. CONCLUSION AND RELEVANCE: Implementation of guideline-recommended cognitive rehabilitation within the PSC is shaped by multi-level determinants. Findings underscore the need for coordinated, multi-component implementation strategies that extend beyond training alone and are tailored to the organizational context of the PSC. This work provides a strong foundation for future implementation efforts capable of expanding access to evidence-based cognitive rehabilitation for Veterans with TBI.

OBJECTIVES: To systematically synthesize the evidence on the effect of positive psychology interventions (PPIs) on health and wellbeing outcomes in adults with spinal cord injury (SCI). DATA SOURCES: We performed a comprehensive search across six electronic databases: Medline, Embase, CINAHL, PsycInfo, SPORTDiscus, and CENTRAL (Cochrane Library). STUDY SELECTION: We included interventional studies published between 2000 and 2025. Studies were eligible for inclusion if they involved individuals with SCI and implemented PPIs aligned with Seligman's PERMA (Positive Emotion, Engagement, Relationships, Meaning, and Accomplishment) model. Studies with all health and wellbeing outcomes were included. The initial search retrieved 8288 studies, of which eight met the eligibility criteria for inclusion in the systematic review. DATA EXTRACTIONS: Two independent reviewers extracted data on study designs, intervention characteristics, outcome measures, and key findings using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline. Meta-analyses were performed for outcomes reported in at least three studies. DATA SYNTHESIS: The systematic review included eight studies, and the meta-analyses included seven of them. Of the eight studies, seven integrated one or more PPI components within their interventions, whereas only one study was fully grounded in a positive psychology framework. Results from the systematic review suggest the significant positive effects of PPIs on selected physical, emotional, and psychosocial outcomes. In meta-analyses conducted for self-efficacy, life satisfaction, anxiety, and depression outcomes, the standardized mean differences were statistically significant for self-efficacy, life satisfaction, and anxiety. However, evidence on the follow-up or long-term effects of PPIs remains limited or inconsistent. CONCLUSIONS: The PPIs or PPI-derived components exert beneficial effects on various health and wellbeing outcomes, particularly in emotional or psychological health. Nevertheless, further research using standardized, full-scale PPI and a larger sample is essential to establish these interventions as potential mainstream interventions within SCI rehabilitation.

PURPOSE: We aimed to identify factors associated with long-term suicide risk severity among youth who received treatment in a community mental health setting. METHOD: Participants were 100 adolescents who began outpatient behavioral health services between 2017 and 2019 (Initial Treatment) and completed a follow-up survey approximately five years later in 2023 (Survey). Suicide risk severity was measured by the Computerized Adaptive Test-Mental Health (CAT-MH) at time of Survey. Covariates included EHR-based sociocontextual, diagnostic, and service-related information at time of Initial Treatment, self-reports of social determinants of health and treatment experiences retrospective to time of Initial Treatment, and the frequency of behavioral health treatment sessions (≥4 vs <4 visits per 3-month quarter) during Initial Treatment. Exclusive LASSO and ordinary least square regressions identified covariates and estimated associations between covariates and suicide risk severity. We also tested interactions between treatment frequency and treatment experiences. RESULTS: Emergency department use had a significant association with longer-term suicide risk severity. DISCUSSION: Emergency department use, and its associated significant illness severity, may be associated with increased suicide severity risk for youth even multiple years later. Further research on the interaction between frequency of treatment and patient perceptions of care on future health outcomes would be valuable.

In high-risk occupational groups, current mental health status may be underreported because of stigma or concerns about disadvantage. Wearable data can capture short-term behavioral and physiological changes, but may be limited in capturing relatively stable biological characteristics. Structural brain magnetic resonance imaging (MRI) may reflect such individual differences and provide complementary information when combined with dynamic wearable signals. We evaluated whether a multimodal deep learning approach combining wearable-derived time-series data with structural brain MRI radiomics could help identify current depressive symptom status in firefighters and prosecution investigators. A total of 291 participants (184 firefighters and 107 prosecution investigators) were included, with a mean monitoring duration of 4.8 weeks. Elevated current depressive symptoms were defined as a Patient Health Questionnaire-9 (PHQ-9) score of 10 or higher at the final observation. Temporal deep learning models were evaluated under wearable-only and multimodal configurations. Multimodal models consistently outperformed wearable-only models, and the final multimodal LSTM model showed the best discriminative performance (AUROC = 0.867; 95% CI 0.814-0.914). In subgroup robustness analysis, performance was generally maintained across broader monitoring-duration categories and occupational groups. SHAP analysis identified the left paracentral lobule, right lateral ventricle, left amygdala, fragmented activity patterns, and minimum oxygen saturation during sleep as major contributors. These findings suggest that a multimodal approach integrating wearable-derived dynamic behavioral characteristics with relatively stable neuroanatomical information from structural brain MRI may serve as a supportive tool for more objectively identifying current depressive symptom status in high-risk occupational populations.

Major depressive disorder (MDD) involves cognitive impairment, altered affective states and dysregulation of neurotransmitter homeostasis. The Wistar Kyoto (WKY) rat is characterized by inherent depressive-like behaviour, anxiety, cognitive deficits and dysregulated monoaminergic/GABAergic neurotransmission. This study investigated strain-specific differences in learning and memory, affective states and neurochemical responses to Diazepam (DZP), a positive allosteric modulator of the GABA receptor, in Wistar and WKY rats. Learning and memory were assessed using the novel object recognition (NOR) paradigm, affective states through ultrasonic vocalizations (USVs) emitted, and monoaminergic levels in implicated brain areas using HPLC. DZPs significantly impaired NOR in Wistar, evidenced by reduced discrimination and recognition index (p < 0.05). DZP also increased contacts and approaches to familiar objects in Wistar (p < 0.05) and reduced approaches to novel objects in both Wistar (p < 0.01) and WKY (p < 0.001). DZP lowered bandwidth of 50-kHz USVs across both strains, though no DZP × strain interactions were observed on all acoustic and spectral parameters analyzed. WKYs displayed significantly lower baseline dopamine (DA) and serotonin (5-HT) in both PFC (DA: p < 0.001; 5-HT: p < 0.01) and hippocampus (DA: p < 0.01; 5-HT: p < 0.05). DZP reduced prefrontal (p < 0.001) and hippocampal DA (p < 0.001) levels in Wistar, with no effect in WKY, though DZP × strain interaction indicated differential effects on DA levels. Prefrontal 5-HT (p < 0.05) was also reduced in DZP-treated Wistars. Thus, strain-specific differences of the dopaminergic response to DZP and the finding that DZP's affected more cognitive measures in Wistar than in WKY underscores the importance of strain and individual variability in translational research.

BACKGROUND: Perioperative neurocognitive disorder (PND) is a frequent postoperative complication in older individuals and is commonly linked to microglial activation. Endoplasmic reticulum (ER) stress has been implicated in neuroinflammation and postoperative cognitive decline; however, whether hippocampal ER stress acts upstream to bias microglia toward a pro-inflammatory M1 phenotype, rather than serving only as a trigger of cytokine cascades, remains insufficiently defined in PND. To determine whether hippocampal ER stress promotes an M1-like microglial shift and amplifies neuroinflammation after anesthesia and surgery. METHODS: Eighteen-month-old male C57BL/6 mice underwent aseptic tibial fracture surgery under isoflurane anesthesia. Tauroursodeoxycholic acid（TUDCA）, a pharmacological ER stress suppressor, was delivered bilaterally into dorsal hippocampal CA1 as a perioperative mechanistic probe. ER ultrastructure in hippocampal cells was examined using transmission electron microscopy (TEM). ER stress related proteins (GRP78, p-PERK, p-eIF2ɑ, p-IRE1ɑ, ATF4, and ATF6) in hippocampus were quantified by Western blotting. Microglial phenotypic signatures were assessed by Western blotting (CD86, iNOS, CD206, ARG-1) and double immunofluorescence (CD86/Iba-1 and CD206/Iba-1). Open-field testing was performed to control for locomotion/anxiety, followed by memory assessments using novel object recognition and Morris water maze starting on postoperative day 3. RESULTS: Anesthesia and surgery induced postoperative cognitive deficits, accompanied by heightened hippocampal inflammatory signaling and a shift toward a pro-inflammatory microglial signature characterized by increased CD86 and iNOS with concomitant reductions in CD206 and ARG-1. In parallel, hippocampal ER stress activation was evident, including ER ultrastructural disruption and increased GRP78 with engagement of PERK/eIF2ɑ/ATF4-, IRE1ɑ-, and ATF6-related pathways. hippocampus-targeted delivery of TUDCA attenuated ER stress activation, mitigated the pro-inflammatory microglial shift (decreasing CD86/iNOS and restoring CD206/ARG-1), reduced inflammatory readouts, and improved postoperative memory performance. CONCLUSIONS: These findings support a mechanistic link between hippocampal ER stress and the pro-inflammatory microglia bias linked to postoperative neuroinflammation and cognitive impairment in aged mice.

Adolescent binge drinking is a strong predictor of alcohol use disorder and related mental health outcomes in adulthood, which may be due to disruptions in myelination during this dynamic period of brain development. White matter expansion in frontal regions during adolescence is essential for mature decision-making and stress regulation, yet the cellular mechanisms by which alcohol impairs myelination remain poorly understood. Multi-label immunofluorescence and confocal microscopy were used to visualize proteins in oligodendrocyte lineage cells and myelin ensheathment of axons in the anterior cingulate cortex (Cg1) and corpus callosum (CC) of male and female C57BL/6NJ mice following four weeks of episodic voluntary binge drinking during adolescent development using the Drinking-in-the-Dark model. Contrary to our hypothesis, alcohol targeted mature oligodendrocytes rather than early-stage oligodendrocyte precursor cells (OPCs). Binge drinking reduced oligodendrocytes expressing aspartoacylase (ASPA) in the Cg1 and CC. This enzyme is essential for lipid biosynthesis and myelin production, and cellular loss was accompanied by hypomyelination of axons. Notably, males appear especially sensitive to adolescent alcohol, as ASPA+ oligodendrocytes and myelin were not reduced in binge-drinking females. Differential vulnerability could carry important implications for adult neurodevelopmental outcomes. Altogether the findings advance our mechanistic understanding of myelin deficits after alcohol, identifying late-stage oligodendroglial development and ASPA as possible targets for therapeutic intervention in the treatment of alcohol use disorder and demyelinating diseases.

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by deficits in social behavior and cognition. Increasing evidence suggests that alterations in dopaminergic neurotransmission, including changes in dopamine transporter (DAT) function, may contribute to ASD-related behavioral abnormalities. This study investigated whether selective DAT inhibition during early postnatal development influences behavioral and molecular alterations in a rat model of ASD induced by prenatal exposure to sodium valproate (NaVP). Pregnant Wistar rats received NaVP (600mg/kg, i.p.) on gestational day 12.5. Male offspring were treated with the selective DAT inhibitor CE-123 (10mg/kg, i.p.) once daily from postnatal day (PND) 10 to 23. Behavioral assessments during adolescence (PND25-42) evaluated social interaction, recognition memory, spatial preference, anxiety-like behavior, locomotor activity, and aversive memory. DAT, dopamine D2 receptor, brain-derived neurotrophic factor (BDNF), and interleukin-1β (IL-1β) protein expression were assessed in selected brain regions. Prenatal NaVP exposure impaired social novelty discrimination, declarative, spatial, and aversive memory, reduced locomotor activity, and increased anxiety-like behavior. These behavioral alterations were accompanied by elevated DAT and dopamine D2 receptor expression. Early postnatal CE-123 treatment attenuated several ASD-like behavioral abnormalities, normalized DAT and dopamine D2 receptor expression, increased BDNF levels in the prefrontal cortex (PFC), and increased IL-1β expression, without inducing non-specific locomotor stimulation. Together, these findings demonstrate that early postnatal CE-123 treatment was associated with long-lasting behavioral improvements accompanied by alterations in dopaminergic markers and BDNF expression. Although these findings support a role for dopaminergic regulation and neuroplasticity in the observed behavioral effects, the underlying mechanisms require further investigation.