Neural predictors underlying variability in depression outcomes are poorly understood. Functional MRI measures of subgenual cortex connectivity, self-blaming and negative perceptual biases have shown prognostic potential in treatment-naïve, medication-free and fully remitting forms of major depressive disorder (MDD). However, their role in more chronic, difficult-to-treat forms of MDD is unknown.

Forty-five participants (n = 38 meeting minimum data quality thresholds) fulfilled criteria for difficult-to-treat MDD. Clinical outcome was determined by computing percentage change at follow-up from baseline (four months) on the self-reported Quick Inventory of Depressive Symptomatology (16-item). Baseline measures included self-blame-selective connectivity of the right superior anterior temporal lobe with an a priori Brodmann Area 25 region-of-interest, blood-oxygen-level-dependent a priori bilateral amygdala activation for subliminal sad vs happy faces, and resting-state connectivity of the subgenual cortex with an a priori defined ventrolateral prefrontal cortex/insula region-of-interest.

A linear regression model showed that baseline severity of depressive symptoms explained 3% of the variance in outcomes at follow-up (F[3,34] = .33, p = .81). In contrast, our three pre-registered neural measures combined, explained 32% of the variance in clinical outcomes (F[4,33] = 3.86, p = .01).

These findings corroborate the pathophysiological relevance of neural signatures of emotional biases and their potential as predictors of outcomes in difficult-to-treat depression.

Although preventable through established infection control practices, catheter-associated urinary tract infections (CAUTIs) remain prevalent in acute-care settings. Our goal was to improve the CAUTI rates through multiple hospitals through implementing sustainable practices, including enhancing communication, provider engagement, accountability, and transparency in reporting to achieve long-term improvements.

Quality improvement with multiple levels of interventions

A health system in northern Ohio with 21 affiliated hospitals across 16 counties.

Adult patients admitted to the hospital between June 2020 and June 2023.

A broad set of quality improvement (QI) strategies was developed by an interdisciplinary team and guided by the Fractal Management System framework to ensure accountability, communication, and alignment across teams and facilities. Key drivers were indwelling urinary catheter (IUC) alternatives, insertion, maintenance, removal, and smart diagnostics. The main outcome measures were standardized infection ratios (SIR) and standardized utilization ratio (SUR), comparing period 1 (P1, June 2020 to December 2021) and period 2 (P2, January 2022 to June 2023).

Enhanced communication and management played crucial roles in minimizing IUC placement. Updated policies and protocols, coupled with clear guidelines and decision support tools, facilitated effective urinary management. Performance tracking and visual management boards provided real-time insights, while collaborative efforts, including staff huddles and multidisciplinary teamwork, ensured consistent adherence to best practices.

A systemwide QI initiative focused on enhanced communication, management, and collaboration contributed to improved SIR and reduced CAUTI rates across multiple hospitals, highlighting the impact of strong communication and proactive management in healthcare settings.

Major Depressive Disorder (MDD) is a complex mental health condition characterized by a wide spectrum of symptoms. According to the Diagnostic Statistical Manual 5 (DSM-5) criteria, patients can present with up to 1,497 different symptom combinations, yet all receive the same MDD diagnosis. This diversity in symptom presentation poses a significant challenge to understanding the disorder in the wider population. Subtyping offers a way to unpick this phenotypic diversity and enable improved characterization of the disorder. According to reviews, MDD subtyping work to date has lacked consistency in results due to inadequate statistics, non-transparent reporting, or inappropriate sample choice. By addressing these limitations, the current study aims to extend past phenotypic subtyping studies in MDD.

(1) To investigate phenotypic subtypes at baseline in a sample of people with MDD;

(2) To determine if subtypes are consistent between baseline 6- and 12-month follow-ups; and

(3) To examine how participants move between subtypes over time.

This was a secondary analysis of a one-year longitudinal observational cohort study. We collected data from individuals with a history of recurrent MDD in the United Kingdom, the Netherlands and Spain (N=619). The presence or absence of symptoms was tracked at three-month intervals through the Inventory of Depressive Symptomatology: Self-Report (IDS-SR) assessment. We used latent class and three-step latent transition analysis to identify subtypes at baseline, determined their consistency at 6- and 12-month follow-ups, and examined participants’ transitions over time.

We identified a 4-class solution based on model fit and interpretability, including (Class 1) severe with appetite increase, (Class 2), severe with appetite decrease, (Class 3) moderate, and (Class 4) low severity. The classes mainly differed in terms of severity (the varying likelihood of symptom endorsement) and, for the two more severe classes, the type of neurovegetative symptoms reported (Figure 1). The four classes were stable over time (measurement invariant) and participants tended to remain in the same class over baseline and follow-up (Figure 2).

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We identified four stable subtypes of depression, with individuals most likely to remain in their same class over 1-year follow-up. This suggests a chronic nature of depression, with (for example) individuals in severe classes more likely to remain in the same class throughout follow-up. Despite the vast heterogeneous symptom combinations possible in MDD, our results emphasize differences across severity rather than symptom type. This raises questions about the meaningfulness of these subtypes beyond established measures of depression severity. Implications of these findings and recommendations for future research are made.

C. Oetzmann Grant / Research support from: C.O. is supported by the UK Medical Research Council (MR/N013700/1) and King’s College London member of the MRC Doctoral Training Partnership in Biomedical Sciences., N. Cummins: None Declared, F. Lamers: None Declared, F. Matcham: None Declared, K. White: None Declared, J. Haro: None Declared, S. Siddi: None Declared, S. Vairavan Employee of: S.V is an employee of Janssen Research & Development, LLC and hold company stocks/stock options., B. Penninx : None Declared, V. Narayan: None Declared, M. Hotopf Grant / Research support from: M.H. is the principal investigator of the RADAR-CNS programme, a precompetitive public–private partnership funded by the Innovative Medicines Initiative and the European Federation of Pharmaceutical Industries and Associations. The programme received support from Janssen, Biogen, MSD, UCB and Lundbeck., E. Carr: None Declared

Functional connectivity of the default mode network (DMN) during rest has been shown to be different among adults with Mild Cognitive Impairment (MCI) relative to aged-matched individuals without MCI and is predictive of transition to dementia. Post-traumatic stress disorder (PTSD) is also associated with aberrant connectivity of the DMN. Prior work from this group has demonstrated a higher rate of MCI and PTSD among World Trade Center (WTC) responders relative to the general population. The current study sought to investigate the main and interactive effects of MCI and PTSD on DMN functioning. Based on prior work, we hypothesized that MCI, but not PTSD, would predict aberrant connectivity in the DMN.

99 WTC responders aged 44–65 stratified by MCI status (yes/no) and PTSD status (yes/no) and matched for age in years, sex (male vs. female), race (white, black, and other), and educational attainment (high school or less, some college / technical school, and university degree), and occupation on September 11, 2001 (law enforcement vs. other) underwent fMRI using a 3T Siemens Biograph MR scanner. A single 10-minute continuous functional MR sequence was acquired while participants were at rest with their eyes open. Group-level analyses were conducted using SPM-12, with correction for multiple comparisons using AFNI's 3dClustSim. Based on this threshold, the number of comparisons in our imaging volume, and the smoothness of our imaging data as measured by 3dFWHMx-acf, a minimum cluster size of 1134 voxels was required to have a corrected p . .05 with 2-sided thresholding. Spherical 3 mm seeds were placed in the dorsal (4, -50, 26) and ventral (4, -60, 46) posterior cingulate cortex (PCC).

Individuals with PTSD demonstrated significantly less connectivity of the dorsal posterior cingulate cortex (PCC) with medial insula (T = 5.21), subthalamic nucleus (T = 4.66), and postcentral gyrus (T = 3.81). There was no difference found in this study for connectivity between groups stratified by MCI status. There were no significant results for the ventral PCC seed.

Contrary to hypotheses that were driven by a study of cortical thickness in WTC responders, the impact of PTSD appears to outweigh the impact of MCI on dorsal DMN connectivity among WTC responders stratified by PTSD and MCI status. This study is limited by several issues, including low number of female and minority participants, relatively small group cell sizes (n = 23–27 per cell), a brief resting state sequence (10 minutes), and lack of a non-WTC control group. Importantly, responders are a unique population so generalizability to other populations may be limited. Individuals in the current study are now being followed longitudinally to relate baseline resting state functional connectivity with cognitive changes and changes in connectivity over a four-year period.

Significant advances in the research of sport-related concussion (SRC) and repetitive head impacts (RHI) over the previous decade have translated to improved injury identification, diagnosis, and management. However, an objective gold standard for SRC/RHI treatment has remained elusive. SRC often result in heterogenous clinical outcomes, and the accumulation of RHI over time is associated with long-term declines in neurocognitive functioning. Medical management typically entails an amalgamation of outpatient medical treatment and psychiatric and/or behavioral interventions for specific symptoms rather than treatment of the underlying functional and/or structural brain injury. Transcranial photobiomodulation (tPBM), a form of light therapy, has been proposed as a non-invasive treatment for individuals with traumatic brain injuries (TBI), possibly including SRC/RHI. With the present proof-of-concept pilot study, we sought to address important gaps in the neurorehabilitation of former athletes with a history of SRC and RHI by examining the effects of tPBM on neurocognitive functioning.

The current study included 49 participants (45 male) with a history of SRC and/or RHI. Study inclusion criteria included: age 18-65 years and a self-reported history of SRC and/or RHI. Exclusion criteria included: a history of neurologic disease a history of psychiatric disorder, and MRI contraindication. We utilized a non-randomized proof-of-concept design of active treatment over the course of 8-10 weeks, and neurocognitive functioning was assessed at pre- and post-treatment. A Vielight Neuro Gamma at-home brain tPBM device was distributed to each participant following baseline assessment.

Participants completed standardized measures of neurocognitive functioning, including the California Verbal Learning Test (CVLT-3), Delis Kaplan Executive Function System (D-KEFS), Continuous Performance Test (CPT-3), and The NIH Toolbox Cognition Battery. Neurocognitive assessments were collected prior to and following tPBM treatment. Paired t-tests and Wilcoxon’s signed-rank tests were used to evaluate change in performance on measures of neurocognitive functioning for normal and nonnormal variables, respectively, and estimates of effect size were obtained.

Study participants’ ability for adapting to novel stimuli and task requirements (i.e., fluid cognition; t=5.96; p<.001; d=.90), verbal learning/encoding (t=3.20; p=.003; d=.48) and delayed recall (z=3.32; p=.002; d=.50), processing speed (t=3.13; p=.003; d=.47), sustained attention (t=-4.39; p<.001; d=-.71), working memory (t=3.61; p=.001; d=.54), and aspects of executive functioning improved significantly following tPBM treatment. No significant improvements in phonemic and semantic verbal fluencies, reading ability, and vocabulary were shown following tPBM treatment.

The results of this pilot study demonstrate that following 8-10 weeks of active tPBM treatment, retired athletes with a history of SRC and/or RHI experienced significant improvements in fluid cognition, learning and memory, processing speed, attention, working memory, and aspects of executive functioning. Importantly, the majority of effect sizes ranged from moderate to large, suggesting that tPBM has clinically meaningful improvements on neurocognitive functioning across various cognitive domains. These results offer support for future research employing more rigorous study designs on the potential neurorehabilitative effects of tPBM in athletes with SRC/RHI.

We identify a set of essential recent advances in climate change research with high policy relevance, across natural and social sciences: (1) looming inevitability and implications of overshooting the 1.5°C warming limit, (2) urgent need for a rapid and managed fossil fuel phase-out, (3) challenges for scaling carbon dioxide removal, (4) uncertainties regarding the future contribution of natural carbon sinks, (5) intertwinedness of the crises of biodiversity loss and climate change, (6) compound events, (7) mountain glacier loss, (8) human immobility in the face of climate risks, (9) adaptation justice, and (10) just transitions in food systems.

The Intergovernmental Panel on Climate Change Assessment Reports provides the scientific foundation for international climate negotiations and constitutes an unmatched resource for researchers. However, the assessment cycles take multiple years. As a contribution to cross- and interdisciplinary understanding of climate change across diverse research communities, we have streamlined an annual process to identify and synthesize significant research advances. We collected input from experts on various fields using an online questionnaire and prioritized a set of 10 key research insights with high policy relevance. This year, we focus on: (1) the looming overshoot of the 1.5°C warming limit, (2) the urgency of fossil fuel phase-out, (3) challenges to scale-up carbon dioxide removal, (4) uncertainties regarding future natural carbon sinks, (5) the need for joint governance of biodiversity loss and climate change, (6) advances in understanding compound events, (7) accelerated mountain glacier loss, (8) human immobility amidst climate risks, (9) adaptation justice, and (10) just transitions in food systems. We present a succinct account of these insights, reflect on their policy implications, and offer an integrated set of policy-relevant messages. This science synthesis and science communication effort is also the basis for a policy report contributing to elevate climate science every year in time for the United Nations Climate Change Conference.

We highlight recent and policy-relevant advances in climate change research – with input from more than 200 experts.

Caregivers of adult phase 1 oncology trial patients experience high levels of distress and face barriers to in-person supportive care. The Phase 1 Caregiver LifeLine (P1CaLL) pilot study assessed the feasibility, acceptability, and general impact of an individual telephone-based cognitive behavioral stress-management (CBSM) intervention for caregivers of phase I oncology trial patients.

The pilot study involved 4 weekly adapted CBSM sessions followed by participant randomization to 4 weekly cognitive behavioral therapy sessions or metta-meditation sessions. A mixed-methods design used quantitative data from 23 caregivers and qualitative data from 5 caregivers to examine the feasibility and acceptability outcomes. Feasibility was determined using recruitment, retention, and assessment completion rates. Acceptability was assessed with self-reported satisfaction with program content and participation barriers. Baseline to post-intervention changes in caregiver distress and other psychosocial outcomes were assessed for the 8-session intervention.

The enrollment rate was 45.3%, which demonstrated limited feasibility based on an a priori criterion enrollment rate of 50%. Participants completed an average of 4.9 sessions, with 9/25 (36%) completing all sessions and an 84% assessment completion rate. Intervention acceptability was high, and participants found the sessions helpful in managing stress related to the phase 1 oncology trial patient experience. Participants showed reductions in worry and isolation and stress.

The P1CaLL study demonstrated adequate acceptability and limited feasibility and provided data on the general impact of the intervention on caregiver distress and other psychosocial outcomes. Caregivers of phase 1 oncology trial patients would benefit from supportive care services; a telephone-based intervention may have more utilization and thus make a larger impact.

Persons discharged from inpatient psychiatric services are at greatly elevated risk of harming themselves or inflicting violence on others, but no studies have reported gender-specific absolute risks for these two outcomes across the spectrum of psychiatric diagnoses. We aimed to estimate absolute risks for self-harm and interpersonal violence post-discharge according to gender and diagnostic category.

Danish national registry data were utilized to investigate 62,922 discharged inpatients, born 1967–2000. An age and gender matched cohort study was conducted to examine risks for self-harm and interpersonal violence at 1 year and at 10 years post-discharge. Absolute risks were estimated as cumulative incidence percentage values.

Patients diagnosed with substance misuse disorders were at especially elevated risk, with the absolute risks for either self-harm or interpersonal violence being 15.6% (95% CI 14.9, 16.3%) of males and 16.8% (15.6, 18.1%) of females at 1 year post-discharge, rising to 45.7% (44.5, 46.8%) and 39.0% (37.1, 40.8%), respectively, within 10 years. Diagnoses of personality disorders and early onset behavioral and emotional disorders were also associated with particularly high absolute risks, whilst risks linked with schizophrenia and related disorders, mood disorders, and anxiety/somatoform disorders, were considerably lower.

Patients diagnosed with substance misuse disorders, personality disorders and early onset behavioral and emotional disorders are at especially high risk for internally and externally directed violence. It is crucial, however, that these already marginalized individuals are not further stigmatized. Enhanced care at discharge and during the challenging transition back to life in the community is needed.

There is substantial variation in patient symptoms following psychological therapy for depression and anxiety. However, reliance on endpoint outcomes ignores additional interindividual variation during therapy. Knowing a patient's likely symptom trajectories could guide clinical decisions. We aimed to identify latent classes of patients with similar symptom trajectories over the course of psychological therapy and explore associations between baseline variables and trajectory class.

Patients received high-intensity psychological treatment for common mental health problems at National Health Service Improving Access to Psychological Therapies services in South London (N = 16 258). To identify trajectories, we performed growth mixture modelling of depression and anxiety symptoms over 11 sessions. We then ran multinomial regressions to identify baseline variables associated with trajectory class membership.

Trajectories of depression and anxiety symptoms were highly similar and best modelled by four classes. Three classes started with moderate-severe symptoms and showed (1) no change, (2) gradual improvement, and (3) fast improvement. A final class (4) showed initially mild symptoms and minimal improvement. Within the moderate-severe baseline symptom classes, patients in the two showing improvement as opposed to no change tended not to be prescribed psychotropic medication or report a disability and were in employment. Patients showing fast improvement additionally reported lower baseline functional impairment on average.

Multiple trajectory classes of depression and anxiety symptoms were associated with baseline characteristics. Identifying the most likely trajectory for a patient at the start of treatment could inform decisions about the suitability and continuation of therapy, ultimately improving patient outcomes.

We summarize what we assess as the past year's most important findings within climate change research: limits to adaptation, vulnerability hotspots, new threats coming from the climate–health nexus, climate (im)mobility and security, sustainable practices for land use and finance, losses and damages, inclusive societal climate decisions and ways to overcome structural barriers to accelerate mitigation and limit global warming to below 2°C.

We synthesize 10 topics within climate research where there have been significant advances or emerging scientific consensus since January 2021. The selection of these insights was based on input from an international open call with broad disciplinary scope. Findings concern: (1) new aspects of soft and hard limits to adaptation; (2) the emergence of regional vulnerability hotspots from climate impacts and human vulnerability; (3) new threats on the climate–health horizon – some involving plants and animals; (4) climate (im)mobility and the need for anticipatory action; (5) security and climate; (6) sustainable land management as a prerequisite to land-based solutions; (7) sustainable finance practices in the private sector and the need for political guidance; (8) the urgent planetary imperative for addressing losses and damages; (9) inclusive societal choices for climate-resilient development and (10) how to overcome barriers to accelerate mitigation and limit global warming to below 2°C.

Science has evidence on barriers to mitigation and how to overcome them to avoid limits to adaptation across multiple fields.

No single environmental factor is a necessary or sufficient cause of mental disorder; multifactorial and transdiagnostic approaches are needed to understand the impact of the environment on the development of mental disorders across the life course.

Using linked multi-agency administrative data for 71 932 children from the New South Wales Child Developmental Study, using logistic regression, we examined associations between 16 environmental risk factors in early life (prenatal period to <6 years of age) and later diagnoses of mental disorder recorded in health service data (from age 6 to 13 years), both individually and summed as an environmental risk score (ERS).

The ERS was associated with all types of mental disorder diagnoses in a dose–response fashion, such that 2.8% of children with no exposure to any of the environmental factors (ERS = 0), compared to 18.3% of children with an ERS of 8 or more indicating exposure to 8 or more environmental factors (ERS ⩾ 8), had been diagnosed with any type of mental disorder up to age 13–14 years. Thirteen of the 16 environmental factors measured (including prenatal factors, neighbourhood characteristics and more proximal experiences of trauma or neglect) were positively associated with at least one category of mental disorder.

Exposure to cumulative environmental risk factors in early life is associated with an increased likelihood of presenting to health services in childhood for any kind of mental disorder. In many instances, these factors are preventable or capable of mitigation by appropriate public policy settings.

People diagnosed with a severe mental illness (SMI) are at elevated risk of dying prematurely compared to the general population. We aimed to understand the additional risk among people with SMI after discharge from inpatient psychiatric care, when many patients experience an acute phase of their illness.

In the Clinical Practice Research Datalink (CPRD) GOLD and Aurum datasets, adults aged 18 years and older who were discharged from psychiatric inpatient care in England between 2001 and 2018 with primary diagnoses of SMI (schizophrenia, bipolar disorder, other psychoses) were matched by age and gender with up to five individuals with SMI and without recent hospital stays. Using survival analysis approaches, cumulative incidence and adjusted hazard ratios were estimated for all-cause mortality, external and natural causes of death, and suicide. All analyses were stratified by younger, middle and older ages and also by gender.

In the year after their discharge, the risk of dying by all causes examined was higher than among individuals with SMI who had not received inpatient psychiatric care recently. Suicide risk was 11.6 times (95% CI 6.4–20.9) higher in the first 3 months and remained greater at 2–5 years after discharge (HR 2.3, 1.7–3.2). This risk elevation remained after adjustment for self-harm in the 6 months prior to the discharge date. The relative risk of dying by natural causes was raised in the first 3 months (HR 1.6, 1.3–1.9), with no evidence of elevation during the second year following discharge.

There is an additional risk of death by suicide and natural causes for people with SMI who have been recently discharged from inpatient care over and above the general risk among people with the same diagnosis who have not recently been treated as an inpatient. This mortality gap shows the importance of continued focus, following discharge, on individuals who require inpatient care.