With the widespread use of smartphones among adolescents, smartphone addiction has become a growing mental health concern. Adolescents' limited self-regulation makes them particularly vulnerable to using smartphones to escape real-life stress, heightening addiction risk. However, the heterogeneity of addictive behaviors and the dynamic role of experiential avoidance have been underexplored. This 6-month longitudinal study surveyed 547 Chinese primary and secondary students using the Smartphone Addiction Scale (SAS) and the Acceptance and Action Questionnaire-II (AAQ-II). Latent profile analysis (LPA) and latent transition analysis (LTA) were applied to identify subgroups and examine transitions between these subgroups. Cross-lagged panel network analysis (CLPN) revealed key symptom interactions between experiential avoidance and addiction. The study identified two addiction subgroups: a stable "low-risk group" (84.9 percent) and a "high-risk group," 51.4 percent of whom transitioned to low risk over time. Logistic regression showed that experiential avoidance significantly predicted high-risk membership (odds ratios [OR] = 1.083-1.102) and deterioration within the low-risk group (OR = 1.036). The CLPN identified "online intimacy" (SPA-3) and "hesitation and overcautious" (EA-7) as driver nodes, with "withdrawal symptoms" (SPA-2) serving as a central node. These findings emphasize the crucial role of experiential avoidance in adolescent smartphone addiction and suggest symptom-level targets for early intervention. The results support acceptance and commitment therapy (ACT) as a promising approach for reducing smartphone addiction among youth.

BACKGROUND: War, an intense and enduring source of stress, exerts wide-ranging impacts on psychological well-being, provoking significant stress and anxiety reactions even in individuals not directly exposed to combat. OBJECTIVE: To examine how ethnicity influences bruxism and temporomandibular disorders (TMD) during an armed conflict. METHODS: In a cross-sectional design, 895 subjects from two ethnic origins (595 Jews and 301 Arabs) were evaluated through an online survey. The assessment tools covered demographic data, TMD screening, subject-based sleep bruxism (SB), subject-based awake bruxism (AB) including grinding, clenching, teeth contact, and bracing behaviours, along with measures of psychological distress (Patient Health Questionnaire-4), perceived stress (Perceived Stress Scale), and resilient coping (Brief Resilient Coping Scale). RESULTS: Arab participants reported the greatest psychological distress and perceived stress, yet they also displayed the strongest resilient coping. Regression analyses identified a distinct pattern in the Arab group regarding TMD and bruxism. Compared with a Jewish reference group, Arabs had markedly higher odds of TMD (OR = 2.58) and higher odds of grinding (OR = 1.81). In contrast, they showed lower odds for sleep bruxism (OR = 0.55) and awake bruxism behaviours of teeth contact (OR = 0.44) and bracing (OR = 0.55). CONCLUSION: The elevated TMD risk among Arab participants (more than double that of Jewish participants) suggests combined effects of chronic psychosocial stress and potential barriers to accessing health care. These findings highlight the need for culturally informed approaches to diagnosing and treating TMD and bruxism, particularly during periods of widespread societal stress.

OBJECTIVES: The present study aims to analyze the impact of emotional intelligence and relaxation techniques on the mental health and quality of life of older adults. METHODS: A 12-week randomized controlled trial included 137 older adults: 68 in a control group (CG) and 69 in an experimental group (EG) who followed an emotional intelligence and relaxation program. Anxiety was assessed using the Hamilton Scale, depression with the Yesavage Scale, perceived stress with the Perceived Stress Scale (PSS), and quality of life with the SF-36. RESULTS: After a program of emotional intelligence and relaxation exercises, significant improvements were found in calmness, depression, stress and all dimensions of quality of life compared to a control group. CONCLUSIONS: Emotional intelligence and relaxation interventions improve mental health and quality of life in older adults, supporting their role as non-pharmacological strategies. CLINICAL IMPLICATIONS: These findings highlight the importance of integrating emotional education and relaxation techniques as essential non-pharmacological strategies to enhance mental health and quality of life in older adults.

Between 8-39% of people living with HIV (PLWH) in sub-Saharan Africa have a depressive disorder (DD). Despite considerable gains in the treatment of PLWH, DD is increasingly recognised as a threat to successful treatment and prevention. PLWH incur higher health-related costs than the general population due to chronic care management needs. We aimed to estimate the combined economic burden of DD and HIV amongst PLWH and explore their mechanisms of coping with high out of pocket (OOP) health expenditure. This was a cost of illness study nested in a cluster-randomised trial that assessed the effectiveness of integrating treatment of DD into routine HIV care in Uganda (HIV+D trial). The study used cross-sectional data collected from 1,115 PLWH across both trial arms at baseline, using the Patient Health Questionnaire (PHQ-9) to measure DD and a structured cost questionnaire. The mean monthly economic cost of HIV and DD amongst n=486 participants reporting at least one non-zero cost item was USD 11.72 (2022 prices), while the mean across the whole sample (including zeroes) was USD 5.05. Mean monthly OOP expenditure amongst participants reporting at least one non-zero item was USD 7.22, which is 4% of average monthly household income. It was USD 3.11 in the sample as a whole. Moderate DD symptoms (PHQ-9 between 15-19) and severe symptoms (PHQ-9 ≥ 20) were reported by 30% and 5% of respondents respectively, with the remainder experiencing mild symptoms. Social protection mechanisms combined with the integration of the management of DD into routine HIV care could help alleviate this burden.

BACKGROUND: Reference intervals for calculated free testosterone (cFT) in healthy, nonobese men have been released, but have not been validated in men with erectile dysfunction (ED). OBJECTIVES: To assess the clinical impact of new cFT reference intervals in men with new-onset ED. METHODS: Data from 410 healthy, nonobese men were analyzed (2015-2023). cFT was assessed using Vermeulen's formula and compared to Jasuja et al.'s (2022) reference values, using the 2.5th percentile as a pathological threshold. At baseline, all patients completed the International Index of Erectile Function (IIEF) and Beck Depression Inventory (BDI). Descriptive statistics and linear regression analyses were applied. RESULTS: Median (IQR) age and total testosterone at presentation were 48 (38-59) years and 4.7 (3.3-6.1) ng/mL. Median IIEF-EF score was 18 (8-23), with 134 patients (32.8%) reporting severe ED. Percentiles of cFT in ED men were: 2.5th = 10, 10th = 50, 50th = 90, 90th = 150, and 97.5th = 227.5 pg/mL, compared to 66, 91, 141, 240, and 309 pg/mL in healthy controls. Seventy-four had cFT between 10 and 66 pg/mL, normal for ED distribution but pathological by healthy reference. This group was older (p<0.01), had lower IIEF-EF (p<0.001), and higher BDI (p<0.01) versus those with cFT >66 pg/mL, though other parameters were similar. Severe ED rates were 72.7%, 44.6%, and 28.7% in men with cFT <10, 10-66, and >66 pg/mL (p<0.01). At multivariable regression, cFT >66 pg/mL was linked to higher IIEF-EF (p = 0.02), while cFT >66 pg/mL (p = 0.03) and younger age (p = 0.01) were associated with lower BDI scores. CONCLUSIONS: Reference thresholds for cFT derived from healthy men identify, among men with ED, a subgroup showing a less favorable erectile and psychometric profile. These findings suggest that healthy-derived cFT reference values may provide clinically useful information in the assessment of men presenting with ED.

BACKGROUND: A subset of patients with schizophrenia do not respond sufficiently to conventional antipsychotic treatment and often have a more complex clinical course, including high rates of sleep disturbances, which can contribute to further worsening of symptoms. However, sleep disturbances are often overlooked in clinical psychiatric settings, and non-pharmacological treatment options are not initiated. Cognitive behavioral therapy for insomnia (CBT-I) has been shown to effectively ameliorate sleep disturbances in schizophrenia but is yet to be assessed in treatment-resistant schizophrenia. In the present study, we aim to investigate the efficacy of CBT-I versus standard cognitive behavioral therapy (CBT), an active control intervention. METHODS: Sixty patients diagnosed with treatment-resistant schizophrenia and comorbid sleep disturbance will be included in this randomized intervention study. Included patients will be randomized to 8-10 sessions of psychotherapy with either CBT-I (active intervention) or regular CBT (active control) following baseline. At baseline and 12-week follow-up, patients will be assessed with clinical interviews (Positive and Negative Syndrome Scale), self-reported measures (e.g., Insomnia Severity Index), and polysomnography. The 24-week follow-up will include the same assessments apart from polysomnography. The active intervention group will receive an individual course of treatment with CBT-I focused on the patients' sleep patterns, while the active control group will receive an individual course of treatment with standard cognitive behavioral therapy (CBT) focused on patients' psychopathology. It is hypothesized that while both groups will show improvements on central outcome measures, CBT-I will show greater improvements in sleep disturbances. Further, it is hypothesized that the improvement in sleep disturbances will correlate with an improvement in positive symptoms. Lastly, it is anticipated that the CBT-I group will show objective improvements in sleep architecture, such as sleep latency, wake after sleep onset, sleep efficiency, and total sleep time, compared to the CBT group. DISCUSSION: Should CBT-I prove efficacious in improving sleep disturbances in treatment-resistant schizophrenia, it would provide an avenue for a cost-beneficial, short-term, and implementable non-pharmacological treatment of a severe comorbidity in complex schizophrenia patients. Potential issues pertaining to the completion of the study are discussed. TRIAL REGISTRATION: ClinicalTrials.gov NCT06749444. Registered on December 27, 2024.

Moral injury (MI) spans biological, psychological, social, and spiritual domains, yet systematic bibliometric evaluation remains scarce. A bibliometric analysis of Scopus-indexed publications containing "moral injury" (1992-2025) was conducted using three search strategies (i) Title-Abstract-Keywords (TAK), (ii) Abstract-only (AO), and (iii) Title-only (TO). Publication types, annual trends, and the performance of authors, institutions, countries, sponsors, and journals were examined. A total of 2,081 documents were identified, including articles (1,491), reviews (164), book chapters (193), and editorials (75). TAK yielded 1,655 records, AO 1,400 records, and TO 879 records, demonstrating notable variation in dataset size. Output remained limited until 2017, followed by rapid growth from 2018, peaking in 2025. The USA led global production, followed by the UK, Canada, and Australia. TAK analysis identified the most prolific authors in this review by country: in the USA, Maguen, S. (36) and Koenig, H.G. (34); in the UK, Greenberg, N. (37) and Murphy, D. (36); in Canada, McKinnon, M.C. (23) and Nazarov, A. (21); and in Australia, Carey, L.B. (13) and Nickerson, A. (10). Other top contributors by country are also identified. Within this study, prolific institutions included VA Medical Center, King's College London, Western University, McMaster University, Duke University Medical Center, and the Boston University Chobanian and Avedisian School of Medicine. Prominent journals were 'Psychological Trauma: Theory, Research, Practice, and Policy', the 'European Journal of Psychotraumatology', 'Traumatology', 'Frontiers in Psychiatry', and the 'Journal of Religion and Health'. Title-based co-word analysis (AO and TO datasets) identified ten thematic clusters covering psychological outcomes, military and healthcare contexts, ethics, assessment, and interventions. Analysis of the top 100 most cited papers highlighted five foundational themes in conceptualization, measurement, mental health outcomes, and treatment approaches. MI research expanded rapidly after 2018, emphasizing the need for methodological transparency through a bibliometric study across multidisciplinary fields. While not all authors/coauthors or their respective institutions and nations have been acknowledged within this analysis of MI research, nevertheless the significant leaders have been identified, as have a number of key research and clinical themes. Search strategy selection however, substantially determines dataset size, contributor visibility, and thematic representation, hence a number of limitations regarding this analysis are noted.

Heart rate variability biofeedback (HRVB) has been confirmed to enhance cardiovagal activation and alleviate depressive symptoms in patients with major depressive disorder (MDD). However, it remains unknown which dimensions of depression predict better treatment outcomes following HRVB. This study utilized a randomized controlled trial design. A total of 59 patients with depressive disorder were enrolled and randomly assigned to either the HRVB group or the relaxation training (RT) group. Both groups receive 60-min training sessions twice weekly for 10 sessions over five weeks. Psychological variables (depression and anxiety) and lead II electrocardiogram (ECG) were collected at pre-test and post-test. ECG data were converted into HRV indices. Two-way mixed-design analyses of variances were conducted to examine the Group (HRVB vs. RT) × Time (pre-test vs. post-test transfer) interaction effects on psychological outcomes and HRV indices. In addition, participants in the HRVB group were classified as responders (n = 10) or non-responders (n = 14) based on change in the root mean square of successive differences between normal heartbeats (RMSSD) following HRVB. Differences in demographic and psychological variables between these subgroups were further examined. (1) Both groups showed significant reductions in depression and anxiety over time; however, no significant differences between groups were observed. (2) At the transfer stage, the HRVB group demonstrated significant increases in HRV indices from pre-test rest stage to post-test transfer stage. (3) Within the HRVB group, responders exhibited significantly lower levels of depressive symptoms (including loss of pleasure, loss of interest, worthlessness, and loss of energy) and lower parasympathetic activity compared with non-responders. HRVB not only alleviated depression and anxiety symptoms but also enhanced autonomic nervous system activity. Moreover, patients who derived the greatest benefit from HRVB tended to exhibit more favorable psychological features at pre-test. These findings may inform the development of personalized and evidence-based psychological interventions for patients with depressive disorders.

INTRODUCTION: Neurofibromatosis type 1 with plexiform neurofibromas (NF1-PN) is a chronic condition associated with significant morbidity. While patient outcomes have been characterized, the burden on caregivers of adult patients with NF1-PN has not been well described. This study evaluated caregiver burden and health-related quality of life (HRQoL) among primary caregivers of adults with NF1-PN. METHODS: Primary caregivers of adult patients with NF1-PN in the United States participated in this cross-sectional survey study. Caregiver burden was measured using standardized tools including Zarit Burden Interview (ZBI), the Work Productivity and Activity Impairment Questionnaire for Caregivers (WPAI:CG), and EQ-5D-5L. RESULTS: One hundred caregivers completed the survey (mean age 49.0 years, 67.0% female). Caregivers were most frequently parents (25.0%) or spouses/partners (19.0%), and 41.0% had provided care for more than 10 years. Nearly all caregivers (93.0%) received additional caregiving support, with 69.0% receiving > 10 h per week of additional help. The mean ± standard deviation (SD) ZBI score was 36.6 ± 15.6, indicating comparable burden to caregivers of other severe chronic conditions. Most caregivers were not employed (37.0% homemakers, 24.0% retired). Among employed caregivers (18.0%), the mean ± SD overall work productivity loss was 47.5% ± 23.9, with 15.6% ± 27.7 work time missed and 41.7% ± 22.8 impairment while working. The mean ± SD activity impairment among all participants was 50.2% ± 20.5. Despite relatively preserved physical health (mean EQ-5D utility score 0.84 ± 0.18), 66.0% of caregivers reported anxiety or depression. CONCLUSIONS: Caregiving for adults with NF1-PN is associated with substantial burden, including reduced work productivity, restricted daily activities, pain, and psychological difficulties. Despite relatively preserved physical health among caregivers, psychological distress and activity limitations are common. These findings demonstrate that NF1-PN affects not only patients but also their caregivers, highlighting the need for caregiver-focused support alongside clinical management of patients.

INTRODUCTION: Water fasting involves completely abstaining from all caloric intake. Multiple studies have demonstrated that water fasting for up to 21 days is well-tolerated, but none focused on patients with severe obesity (body mass index ≥ 40) or utilized treatment with glucagon-like peptide-1 receptor agonists (GLP-1). METHODS: The patient was a 44-year-old male with severe morbid obesity, heart failure, oxygen-dependent obesity hypoventilation syndrome, uncontrolled hypertension, anemia, and depression. He underwent a 27 day inpatient fast with weekly tirzepatide, including 21 day water fast with structured refeeding. RESULTS: The patient lost 125 pounds during the fast. He regained independent ambulation and chronic oxygen supplementation was discontinued. Chronic anemia resolved and depression improved as measured by Patient Health Questionnaire. Systolic blood pressure improved despite discontinuation of his antihypertensives. His chronic leg wound resolved without antibiotics. Left ventricular mass decreased and fasting insulin normalized. Appetite remained tolerable, and the only complication was mild transaminitis. CONCLUSION: This case suggests prolonged medically-supervised water fasting with GLP-1 use is an effective short-term weight reduction strategy that allows for bridging to bariatric surgery with improvement in multiple chronic diseases. As the fast ended for surgery rather than intolerance, research into longer water fasts could be considered.

IMPORTANCE: Health care workers (HCWs), particularly those identifying as female or Black, face disproportionate mental health strain. Digital mental health platforms have grown in popularity and, for health systems, may offer scalable solutions, but their differential impact across demographic groups remains understudied. DESIGN, SETTING, AND PARTICIPANTS: This secondary analysis of a randomized controlled trial enrolled 1275 HCWs from an urban academic health system between January and May 2022. Participants were randomized to usual care or proactive digital engagement via the Cobalt platform. Female and Black HCWs were oversampled to assess subgroup effects. INTERVENTION: Monthly digital outreach, including mental health symptom screening and linkage to resources via the Cobalt platform, compared with usual care. MAIN OUTCOMES AND MEASURES: Primary outcomes were changes in depression (PHQ-9) and anxiety (GAD-7) scores at 6 and 9 months. Secondary outcomes included well-being (WHO-5, WBI-9) and work productivity (LEAPS). Generalized linear models assessed HTE by gender and race. RESULTS: Of 1275 randomized participants (mean age 38.6 years; 83.4% female; 25.1% Black), both intervention and control groups showed significant reductions in anxiety and depression scores over time. No significant HTE was observed by gender or race for primary outcomes. Female HCWs receiving the intervention reported significantly greater improvement in work productivity at 6 months (LEAPS score difference: 1.70; p = 0.03). Black HCWs in the intervention arm showed a sustained improvement in depression scores at 9 months (- 2.21; p < 0.001), though adjusted models did not confirm statistical significance. CONCLUSIONS AND RELEVANCE: A proactive digital mental health strategy coupled with a well-being platform improved mental health outcomes across HCWs, with modest differential effects in productivity and depression among female and Black participants. These findings support the scalability of digital interventions and highlight the need for culturally tailored approaches to enhance equity and impact.

IMPORTANCE: The COVID-19 pandemic disrupted traditional substance use disorder (SUD) treatment modalities, prompting innovative telemedicine solutions. OBJECTIVE: To evaluate the association between state-level telemedicine policies and SUD treatment during the COVID-19 pandemic. DESIGN: An augmented synthetic control analysis comparing changes in SUD treatment before and after the implementation of telemedicine policies in states that adopted these policies to changes in SUD treatment in comparison states without these policies from 2018 to 2022. SETTING: This study utilized a comprehensive policy database merged with de-identified patient claims data from the OptumLabs® Data Warehouse. PARTICIPANTS: Individuals aged 18 in only fully insured commercial, private plans subject to state insurance policies between January 2018 and December 2022. EXPOSURE: Combined implementation of three state telemedicine policies during the early months of the COVID-19 pandemic (March-July 2020), including telemedicine coverage parity, telemedicine payment parity, and in-person relationship waivers. MAIN OUTCOMES: SUD treatment initiation and continuation, measured at the patient-month level and aggregated to the state-month level for analyses, with subgroup analyses for opioid use disorder (OUD) and alcohol use disorder (AUD) treatment. RESULTS: Implementation of the three policies was associated with average effects of less than 0.006 percentage points in the proportion of adults initiating SUD, AUD, or OUD treatment between March/April 2020 and December 2022, with confidence intervals not exceeding a 0.02 percentage point increase or decrease (p > 0.05). Among adults receiving treatment prior to the COVID-19 pandemic, these policies were associated with an estimated average change of less than 1.5 percentage points in the proportion of adults receiving SUD, AUD, or OUD treatment, with confidence intervals not exceeding a 4.5 percentage point increase or decrease (p > 0.05). CONCLUSIONS AND RELEVANCE: Our study did not identify impacts of state telemedicine coverage parity, payment parity, and in-person relationship waiver policies on SUD treatment during the COVID-19 pandemic.

Sonogenetics combines genetic tools and low-intensity ultrasound to non-invasively modulate specific neuronal populations and circuits, exhibiting potential for treating brain diseases. This study examines sonogenetics' potential in a mouse depression model, targeting excitatory medial prefrontal cortex (mPFC) neurons projecting to the dorsal raphe nucleus (DRN). Projecting neurons were induced to express a mechanosensitive ion channel (MscL-G22S), and alterations in patterns of neuronal activation and despair-like behaviors upon sonication were evaluated. Sonogenetics selectively activated targeted excitatory mPFC neurons projecting to the DRN, enhancing real-time DRN neuronal activity and serotonin release, with no observed tissue damage or astrocytic/microglial activation. Tail suspension and forced swim tests revealed that sonogenetically activating this pathway rapidly reversed despair-like behaviors in stressed mice, whereas effects observed upon mPFC sonication were abrogated by functionally silencing downstream DRN neurons, and this effect is fully recapitulated by selective inhibition of DRN serotonergic neurons alone. Collectively, this study constitutes the first demonstration of the potential for a circuit-targeted sonogenetic therapeutic approach for relieving despair behaviors.

Smartphone-delivered interventions offer a scalable solution for university students experiencing depression, yet outcomes remain inconsistent. This study examined predictors of depression remission and response in the AI-enhanced Vibe Up adaptive trial of brief smartphone-based interventions in 1282 Australian university students (mean age 23.52 years; 78.39% women) with elevated distress (Kessler-10 ≥ 20). After a two-week monitoring period, participants were randomised to two-week self-guided smartphone-based interventions targeting sleep hygiene, mindfulness, physical activity, or an ecological momentary assessment control intervention. Predictors of depression remission (DASS-21 in normal range) and response (≥50% reduction) were examined using hierarchical logistic regression. At post-intervention, 40.87% achieved remission and 29.88% showed response. Baseline depression severity, quality of life, general practitioner visits, and pre-intervention credibility predicted remission and/or response across all intervention arms. Higher baseline anxiety specifically predicted poorer remission in the sleep hygiene arm. Individual factors modestly predicted outcomes. Trajectory-based predictors may be needed to improve outcome prediction.

Social anxiety and sleep are both crucial to young people's development, yet the nature of their association remains unclear and has not been systematically examined. This meta-analysis aimed to examine the relationship between social anxiety and several sleep indicators (e.g., sleep quality, sleep disorders, and sleep duration) in young people, and to explore potential moderators of this relationship. We searched six databases (PubMed, Embase, Web of Science, the Cochrane Library, WANFANG, CNKI) on March 22, 2025. In total, thirty-six studies were included in the analysis. We found a moderate positive correlation between social anxiety and poor sleep quality in young people (r = 0.25). The moderating variables included ages (university and middle school students) and measurement tools for social anxiety. Social anxiety was positively correlated with insomnia (r = 0.42), daytime sleepiness (r = 0.54), and general sleep problems (r = 0.24), and negatively associated with sleep duration (r = - 0.27) in young people. This research suggests that promoting young people's coordinated psychological and physical health requires equal attention on social anxiety and sleep, with targeted, comprehensive interventions for overall well-being.

PURPOSE: Cancer often affects not only the patients but also their relatives, as diagnosis and prognosis, treatment, and side effects can have a significant psychosocial impact. We aimed to investigate unmet information and support needs and quality of life in a German cohort of relatives of metastatic breast cancer (mBC) patients. METHODS: Between July 2022 and August 2023, adults with mBC were included in the BRE-BY-MED "Breast Cancer Care in Bavaria for Patients with Metastatic Disease" cohort study (DRKS00026601) at the University Hospital Würzburg. Relatives of these patients completed a questionnaire on unmet support and information needs at the 3-month follow-up. RESULTS: 75.8% (n = 25) of the relatives had at least one unmet support need, mostly observed in the categories "medical information about the relative's illness" (54.5%) and "contact person who coordinates the treatment/aftercare" (42.4%). 45.5% (n = 15) of the relatives had at least one information need, with the highest needs in the categories "the likely course of the disease in the relative" (39.4%) and "how to deal with the treatment side effects" (36.4%). In 72.7% and 88.0% of the relatives, respectively, there was evidence for severe depressive or anxiety symptoms. CONCLUSION: Dedicated support programmes for relatives of patients with mBC should be developed, targeting their unmet support and information needs regarding the disease, treatments, side effects, prognosis, and aftercare. Furthermore, physicians should be aware of actively involving mBC patients' relatives in the disease and treatment process.

Neuroleptic malignant syndrome (NMS) is a potentially life-threatening condition associated with dopamine antagonist medications. Although the classical presentation includes hyperthermia, generalized rigidity, autonomic instability, and altered mental status, atypical forms lacking these features may occur and complicate diagnosis. We report a case most consistent with atypical NMS in a 76-year-old patient who developed acute delirium and intermittent paratonia without fever or sustained rigidity following antipsychotic exposure. The clinical course was characterized by marked autonomic instability and a transient elevation of creatine kinase, peaking early and subsequently normalizing. A temporal relationship between antipsychotic exposure, symptom onset, and laboratory findings supported the diagnostic consideration. Although clinical improvement was observed following dopaminergic therapy, this finding was interpreted cautiously given potential confounding factors. This case highlights that NMS may occur without fulfilling classical diagnostic criteria and underscores the importance of integrating clinical, laboratory, and temporal features, particularly in critically ill patients.

Cholestatic liver diseases (CLD), including PBC and PSC, are frequently associated with debilitating sickness‑behavior symptoms such as fatigue, cognitive impairment, and anxiety/depression, which have poorly defined etiology and limited treatment options, substantially reducing quality of life. Across immune‑mediated diseases, thalamic changes have been well documented and found to correlate with a number of theses symptoms. Changes in thalamic structure and neural connectivity have been previously identified in PBC patients by us and other groups. These changes include findings indicating reduced tissue neuronal density and myelination, decreased thalamic size, and changes in functional neural connectivity between the thalamus and basal ganglia and cortical behavior-regulating areas that correlated with symptom severity. These observations implicate altered thalamic structure and function in the genesis of CLD-related sickness‑behavior symptoms. Therefore, we used a well characterized mouse model of CLD due to bile duct ligation (BDL) to mechanistically examine how CLD impacts thalamic structure and function. BDL mice showed reduced thalamic volume compared to sham-ligated controls, as determined by MRI, and an altered thalamic RNA-seq transcriptomic signature with predicted molecular activity consistent with inhibition of cellular growth, proliferation, neurite formation, neural function, and myelination, as well as enhanced apoptosis. Additionally, BDL was associated with changes in gene expression for key thalamic nervous system signaling pathways that regulate neurotransmission and behavior. We have previously demonstrated that systemic TNF is a key regulator of liver-to-brain communication and the development of adverse behavioral symptoms in BDL mice. Therefore, we administered anti-TNF antibody to neutralize systemic TNF in BDL mice and determined the impact on thalamic transcriptomic changes. TNF neutralization attenuated BDL-associated thalamic transcriptomic changes and enhanced gene expression in pathways regulating neurotransmission, cell proliferation, and those associated with neuron survival, although myelination pathways remained unaltered. We show that reduced thalamic volume in BDL mice is associated with transcriptomic alterations suggesting inhibition of structural machinery and dysfunction of neural signaling; findings that are significantly attenuated after systemic TNF neutralization. Our findings suggest that TNF inhibition may represent a potential novel approach to attenuate thalamic changes in CLD.

BACKGROUND: Obsessive-compulsive disorder (OCD) is a chronic and debilitating mental health condition that significantly impairs the quality of life. Although cognitive-behavioral therapy (CBT), particularly exposure and response prevention (ERP), is considered the gold standard, many patients remain symptomatic or find these approaches challenging due to emotional and cognitive barriers. Distress tolerance techniques (DTT), a component of dialectical behavior therapy (DBT), have demonstrated efficacy in various conditions, including substance dependence, binge eating, and depression, by managing negative emotional states and enhancing coping mechanisms beyond their original focus on borderline personality disorder. However, the application of DTT in the treatment of patients with OCD has not been extensively explored. This study aims to evaluate the efficacy of DTT in reducing OCD severity and improving psychological outcomes. METHODS: This prospective, single-center, open-label randomized controlled trial will recruit 80 adults (18-40 years) diagnosed with OCD (ICD-10 criteria, Y-BOCS score ≥ 16) from the Department of Psychiatry, All India Institute of Medical Sciences, Bhopal. Participants will be randomized 1:1 using a random number table to either the intervention or active control group. Participants in the intervention group will engage in a 12-week structured DTT program specifically tailored for obsessive-compulsive disorder (OCD), whereas those in the active control group will undergo standard treatment of exposure and response prevention (ERP). The primary outcome will be OCD severity, measured using the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). Secondary outcomes included distress tolerance (measured using the Distress Tolerance Scale), depressive symptoms (measured using the Beck Depression Inventory), coping strategies (measured using the Dialectical Behavior Therapy-Ways of Coping Checklist), mindfulness (measured using the Kentucky Inventory of Mindfulness Skills), and acceptance (measured using the Acceptance and Action Questionnaire-II). Outcomes for the treatment groups will be evaluated before randomization (baseline, T1) and 12 weeks (end of treatment, T2). The protocol was approved by the Institute Ethical Committee (approval number) and was performed in strict adherence to the Declaration of Helsinki formulated by the World Medical Association. DISCUSSION: This trial will explore the efficacy of distress tolerance techniques in patients with OCD. This study will provide evidence for a therapeutic approach that addresses the limitations of traditional CBT and improves outcomes for patients with OCD. TRIAL REGISTRATION: Central Trial Register of India CTRI/2024/09/073672. Registered on 21 December 2024.

BACKGROUND: Uniformed service personnel are routinely exposed to occupational trauma in their roles which contribute to elevated rates of mental health conditions. A wide range of mental health and wellbeing interventions may help uniformed service personnel manage their psychological responses to challenging incidents at work. Previous reviews of those interventions have focused on single groups of professionals or intervention types, limiting cross-sector insights. This review uses a mixed methods approach to synthesise evidence associated with mental health and wellbeing interventions across uniformed services. METHODS: The protocol was registered with PROSPERO (CRD42024605877). A mixed methods systematic review was conducted using the Joanna Briggs Institute (JBI) convergent segregated approach. Searches were conducted in Medline, CINAHL, Web of Science and PsycINFO (Dec 2024). Screening and quality appraisal (Mixed Methods Appraisal Tool) were performed independently by two reviewers. Due to heterogeneity, findings were narratively synthesised. Quantitative and qualitative results were integrated following the JBI approach. RESULTS: Eighty-six primary studies from 22 countries were included, covering a range of professions and intervention types. Synthesis of quantitative data from 82 studies showed that mindfulness-based training, resilience coaching, cognitive behavioural therapies and supported lifestyle activities demonstrated reduced symptoms of PTSD, anxiety and depression. However, interventions such as Critical Incident Stress Debriefing (CISD) and peer support yielded mixed results. Qualitative data from 9 studies were grouped into 5 categories: enhanced emotional insight, improved interpersonal relationships, perceived effectiveness, barriers to engagement and delivery challenges. Participants valued interventions that fostered self-awareness and support but cited stigma, guilt and logistical constraints as significant barriers. Integration of quantitative and qualitative findings revealed alignment in outcomes for several interventions, while highlighting evidence gaps, such as the lack of qualitative data for many interventions and limited exploration of cultural and organisational barriers. CONCLUSIONS: Mental health interventions for uniformed service personnel show promise but are influenced by delivery format, occupational culture and contextual factors. This review underscores the need for delivering interventions informed by ecological models, standardised outcome sets and deeper qualitative exploration into stigma and engagement barriers.