Compulsion is a defining feature of binge eating disorder (BED), yet the circuit basis sustaining compulsive binge eating remains unclear. Here, we identify tyrosine hydroxylase (TH)-BAC-Cre-labeled γ-aminobutyric acid (GABAergic) neurons in the anterior zona incerta (aZI^T neurons) as a key population driving compulsive binge eating. In a mouse BED model, intermittent high-fat-diet training increases aZI^T neuronal excitability, which is required for the development of compulsive intake. These neurons project to the ventral tegmental area (VTA), where they promote aversion-resistant food seeking and consumption. Mechanistically, BED training reduces inhibitory control from aZI^T neurons onto VTA dopamine neurons via both direct and indirect pathways, and this effect results in enhanced dopamine release in the nucleus accumbens. Single-cell RNA sequencing and behavioral profiling further identify neurensin 2 (Nrsn2) as a genetic marker for aZI binge neurons that functionally contribute to compulsive binge eating. Together, these findings define a cell-type-specific ZI-VTA circuit that engages mesolimbic dopamine signaling to drive compulsive binge eating.

This meta-analysis and systematic review updates and evaluates the efficacy and safety of non-invasive brain stimulation (NIBS) techniques for treating clinical symptoms of attention-deficit/hyperactivity disorder (ADHD), including original studies from China to improve the generalizability of the findings.

We searched for double-blind, parallel-group randomized controlled trials (RCTs) that assessed the effects of NIBS on clinical ADHD symptoms. Outcomes included clinical symptom improvement, dropout rates, and adverse events. The Hartung‑Knapp‑Sidik‑Jonkman (HKSJ) random‑effects model was used to calculate standardized mean differences (SMD) and 95% confidence intervals (CI), and was compared with the DerSimonian‑Laird (DL) method to control Type I error inflation from small samples and high heterogeneity.

We included 15 studies (17 comparisons, 746 participants). Overall, NIBS significantly improved ADHD symptoms (SMD=-1.12, 95% CI -2.05 to -0.19, p = 0.031), with high heterogeneity (I²=94%). Subgroup analysis suggested high-frequency repetitive transcranial magnetic stimulation (rTMS) with a figure‑8 coil over the right prefrontal cortex may be optimal; transcranial direct current stimulation (tDCS) and transcranial nerve stimulation (TNS) showed no significant efficacy. No significant differences in dropout rates or adverse events were found between the active stimulation and sham stimulation groups.

Meta-analyses of high-level evidence RCTs indicate that NIBS was generally well tolerated and safe. NIBS shows potential for ADHD, but current evidence remains insufficient to support its routine clinical use.

Radical cystectomy (RC) is associated with high perioperative morbidity, reflecting common preoperative vulnerability from frailty, sarcopenia, malnutrition, systemic inflammation, deconditioning (including during neoadjuvant chemotherapy), and psychological distress. Although prehabilitation is safe and feasible and has demonstrated improvements in functional capacity, quality of life, and select postoperative outcomes, real-world uptake remains low, in part due to uncertainty regarding appropriate patient selection and how to operationalize evidence-based interventions. We aimed to provide a pragmatic framework for identifying candidates for prehabilitation before RC and to summarize evidence-based prehabilitative interventions that can be implemented or referred from routine urologic oncology practice. A non-systematic, expert narrative review of contemporary literature was performed, evaluating prehabilitation in bladder cancer and RC populations, with emphasis on feasible clinic-based tools to identify physiologic and psychological vulnerability and on intervention components with demonstrated benefit. Multiple efficient screening approaches can identify candidates for prehabilitation, including frailty indices (e.g., Clinical Frailty Scale, modified frailty indices, claims- or chart-derived frailty tools), functional assessments (e.g., Short Physical Performance Battery, Timed Up & Go, sit-to-stand tests, grip strength, 6-minute walk test), and markers of nutritional risk and catabolism (e.g., albumin, unintentional weight loss, low body mass index (BMI), computed tomography (CT)-based sarcopenia measures, inflammatory markers). Psychological vulnerability (e.g., anxiety/depression, low mental health scores, limited social support) is also associated with worse postoperative recovery and can be screened using brief questionnaires. Evidence supports multimodal prehabilitation incorporating aerobic and resistance exercise, nutritional optimization (primarily targeted perioperative supplementation), and perioperative education (including stoma counseling), with emerging data for stress-management, smoking cessation, and cognitive prehabilitation. Establishing streamlined referral pathways to physical therapy/rehabilitation, nutrition, psychology/psychiatry, and social work improves feasibility. Prehabilitation prior to RC is an actionable, patient-centered strategy to improve functional reserve and recovery, though evidence to date demonstrates inconsistent effects on harder perioperative endpoints such as complications, length of stay, or readmissions. Routine vulnerability screening and standardized referral pathways can increase prehabilitation utilization and may reduce morbidity in this high-risk surgical population.

Positive and negative symptoms are considered core features of psychotic disorders. However, no study has identified joint trajectories of positive and negative symptoms in early psychosis with long-term follow-up.

We conducted 12-year follow-up of a randomized-controlled trial on extended early intervention for first-episode psychosis in order to identify joint positive and negative symptom trajectories over 12 years, their baseline predictors and associations with 12-year outcomes. Participants who completed Positive and Negative Syndrome Scale (PANSS) at three or more timepoints, including baseline, and 1-, 2-, 3- and 12-year follow-up, were included in the study. Premorbid adjustment, illness characteristics, symptom severity, functioning, and treatment profiles were assessed. Multivariate latent growth-mixture modelling was employed to derive joint symptom trajectories based on PANSS.

A total of 151 participants were included in this study, with 105 patients completed 12-year follow-up. Our results identified four distinct trajectories, including concordant-low (35.1%,n = 53), concordant-improved (11.3%,n = 17), worsening positive/improving negative symptoms (21.2%,n = 32) and persistently-high positive/improving negative symptoms (32.5%,n = 49) classes. Poorer insight, worse quality of life and potentially longer duration of untreated psychosis could predict poorer joint symptom trajectories. Patients in worsening positive/improving negative symptoms and persistently-high positive/improving negative symptoms classes exhibited worse functional and recovery outcomes at 12-year follow-up.

Our results indicate heterogeneous trajectory patterns of positive and negative symptoms. Concurrent improvement in both symptoms over the illness course is important for better long-term functional outcomes. Further longitudinal research is warranted to facilitate development of interventions to optimize concurrent improvement in both symptoms in early psychosis patients.

Negative symptoms (NS) are a core dimension of schizophrenia and a major determinant of real-life functioning. The National Institute of Mental Health-Measurement and Treatment Research to Improve Cognition in Schizophrenia (NIMH-MATRICS) initiative and the European Psychiatric Association (EPA) guidance have refined NS conceptualization and promoted the use of second-generation assessment instruments. However, the assessment and treatment of NS remain challenging due to the frequent use of first-generation rating scales, likely heterogeneous underlying mechanisms, longitudinal trajectories, and treatment responsiveness. Several constructs have been developed to address this complexity: primary versus secondary NS, Deficit Schizophrenia (DS), persistent negative symptoms (PNS), and predominant and prominent NS. These reflect different priorities, ranging from etiological specificity to operational feasibility. However, their inconsistent use has limited comparability across studies, complicating the interpretation of research evidence. This editorial provides a practice-oriented framework of the definitions, operationalization and implications of these constructs. The primary versus secondary NS distinction remains foundational despite its operational complexity. DS represents the most specific construct for identifying primary and enduring negative symptoms, but its feasibility is constrained by the need for longitudinal assessment and strict exclusion criteria. The PNS construct offers a pragmatic compromise and is supported by EPA recommendations for clinical trials. Predominant and prominent negative symptoms constructs facilitate recruitment but introduce heterogeneity due to their cross-sectional nature. Overall, NS constructs should be considered complementary rather than interchangeable. Greater conceptual alignment and standardized assessment strategies are essential to improve patient stratification, enhance comparability across studies, and support the development of effective treatments.

Mood disorders including major depressive disorder and bipolar disorder are among the leading causes of disability worldwide, often emerging early in life and following chronic, relapsing courses. The development of these disorders is influenced by a range of familial, environmental, clinical, and genetic risk factors. In recent years, neuroimaging techniques have played a key role in identifying biomarkers of vulnerability among individuals at elevated risk, with the goal of improving early detection and preventive interventions. This systematic review aimed to consolidate neuroimaging findings in populations vulnerable to mood disorders, with a particular focus on resilience as a complementary framework to risk, the latter having historically received far more research attention. Following PRISMA 2020 guidelines, we searched PubMed, Embase, and Scopus, applying an independent duplicate screening process to identify relevant studies based on predefined inclusion and exclusion criteria. A total of 31 studies met the inclusion criteria, spanning structural MRI (sMRI), functional MRI (fMRI), and diffusion MRI (dMRI). Synthesis of these findings highlights neurobiological markers of resilience, including preserved task-related and resting-state fronto-limbic function, enhanced connectivity within neural circuits supporting emotion regulation, and structural integrity in prefrontal regions that may underlie adaptive functioning in individuals at high risk for mood disorders.

Cigarette smoking is a major contributor to chronic disease and multimorbidity, but less is known about how morbidity burden varies across contemporary nicotine-use profiles, particularly among people who use e-cigarettes with and without a history of smoking. This study examined associations between mutually exclusive nicotine-use groups and long-standing condition burden in a population-based sample of adults in England.

We analysed cross-sectional data from 7625 adults aged ≥16 years in the 2022 Health Survey for England. Participants were classified into six mutually exclusive groups: never users, exclusive cigarette smokers, former smokers, current e-cigarette users who had never smoked, current e-cigarette users who had ever smoked, and dual users. Outcomes included seven self-reported long-standing condition groups, a composite indicator of any condition, and ordinal multimorbidity, defined as 0, 1, 2, or ≥3 condition groups. Survey-weighted logistic and ordered logistic regression models accounted for sampling weight, clustering, and stratification. Adjusted models controlled for age group, sex, ethnicity, area-level deprivation, educational attainment, alcohol consumption, and physical activity.

Compared with never users, adjusted odds of reporting any of the seven long-standing conditions were higher among exclusive cigarette smokers (aOR 1.87, 95% CI 1.51-2.31), former smokers (aOR 1.44, 95% CI 1.27-1.65), current e-cigarette users who had ever smoked (aOR 2.13, 95% CI 1.61-2.82), and dual users (aOR 2.35, 95% CI 1.59-3.45). Current e-cigarette users who had never smoked did not show clear evidence of higher overall morbidity, but estimates were imprecise (aOR 1.24, 95% CI 0.58-2.63). Similar patterns were observed for ordinal multimorbidity, with higher adjusted odds among exclusive cigarette smokers (aOR 1.84, 95% CI 1.51-2.25), former smokers (aOR 1.48, 95% CI 1.31-1.68), current e-cigarette users who had ever smoked (aOR 2.14, 95% CI 1.67-2.75), and dual users (aOR 2.27, 95% CI 1.63-3.18), but not among current e-cigarette users who had never smoked (aOR 1.11, 95% CI 0.57-2.17). Mental health, respiratory, and musculoskeletal conditions showed the most robust disease-specific associations after false discovery rate correction. No disease-specific association involving current e-cigarette users who had never smoked remained significant after correction for multiple comparisons.

Morbidity burden was unevenly distributed across nicotine-use groups and was most consistently elevated among adults with current or previous combustible cigarette exposure, including former smokers, dual users, and current e-cigarette users with a smoking history. Current e-cigarette users who had never smoked did not show clear evidence of higher morbidity, but this subgroup was small and estimates were imprecise. Distinguishing smoking history is essential when interpreting the health profiles of people who use e-cigarettes. Longitudinal studies with larger samples of never-smoker e-cigarette users and more detailed exposure histories are needed.

Nursing homes (NHs) are an important setting of care for individuals with complex mental health conditions, including schizophrenia, bipolar disorder, and other (nonschizophrenia) psychoses [ie, serious mental illness (SMI)]. The federally mandated Preadmission Screening and Resident Review (PASRR) program is in place to help ensure that individuals identified as having SMI, among other conditions, are appropriately admitted to an NH rather than a less restrictive community setting. However, it is unclear the extent to which the PASRR SMI flag aligns with diagnoses recorded by clinicians in claims/encounter data.

Cross-sectional study design.

One hundred percent of 2022 Minimum Data Set admission assessments linked to Medicare (including traditional Medicare and Medicare Advantage) and Medicaid inpatient and outpatient administrative claims to examine the overlap between PASRR priority categories and SMI as derived from complementary resident claims/encounter diagnoses.

Descriptive (χ², analysis of variance).

Of roughly 1.9 million new admissions in 2022, 2.4% had a PASRR SMI flag, whereas 12.3% had an administratively data-derived SMI diagnosis. Among the 234,519 admissions with a claims/encounter-derived SMI diagnosis, 11.3% had a PASRR:SMI flag.

Federally mandated PASRR screening assessments appropriately identify roughly 1 in every 10 admissions with a claims/encounter-derived SMI diagnosis, raising substantial concerns over whether the program can effectively facilitate appropriate NH placement, as originally intended. Forty years after the Omnibus Budget Reconciliation Act of 1987, our findings raise questions about the continued utility of this federal screening program and suggest that more substantive revisions may be necessary to meet the needs of the increasingly complex and multifaceted population of patients who enter NHs.

The death of a spouse in late life is associated with a sense of social disconnection, lack of engagement in pleasant activities, and disruptions in daily routines. Bereaved spouses are more likely to die by suicide than non-bereaved spouses yet there are no behavioral interventions designed to reduce suicide risk in this population. We describe the rationale and methodology of the NIMH-funded RISE Study (Rhythms after loss for Improving Suicide risk in bereaved Elders), a single arm clinical trial examining risk and resilience to late-life suicide following spousal bereavement by investigating the extent to which social connectedness and circadian rhythms influence suicide risk.

We will enroll 169 recently bereaved (≤12 mo post-death) adults aged 60 years and older who currently have at least subthreshold symptoms of depression or have a history of depression and/or suicide attempt. All participants will complete repeated assessments over 12 months of multiple dimensions of social connectedness, clinical assessments of depression and suicidal ideation, and actigraphic assessments of 24-hour rest/activity rhythms. Participants also complete a 3-month behavioral probe, designed to directly target and increase social activity and more regular sleep-wake cycles in older bereaved adults.

RISE findings will inform the development of scalable technology-based suicide prevention programs by determining the extent to which social connectedness and behavioral rhythms are modifiable and if doing so reduces depression severity and suicide risk in older bereaved adults.

NCT06191484.

We studied the dynamics of peripheral inflammatory mediators (LPS, LPS-binding protein, and proinflammatory cytokines TNFα and IL‑8) in the blood serum of men with alcohol dependence at the stages of withdrawal syndrome: on days 2‑3 of alcohol withdrawal, after standard 14‑17-day therapy, and during remission several months after hospital discharge, with assessment of patient's clinical status. A significant increase in the levels of inflammatory markers compared to the control group (apparently healthy men) was observed during the withdrawal syndrome followed by a decrease in these parameters (except for chemokine IL‑8) after therapy and during remission. Correlations between the levels of inflammatory mediators and alcohol craving scores (measured using the Pennsylvania Alcohol Craving Scale) were found during therapy and in remission.