Functional impairment in daily activities, such as work and socializing, is part of the diagnostic criteria for major depressive disorder and most anxiety disorders. Despite evidence that symptom severity and functional impairment are partially distinct, functional impairment is often overlooked. To assess whether functional impairment captures diagnostically relevant genetic liability beyond that of symptoms, we aimed to estimate the heritability of, and genetic correlations between, key measures of current depression symptoms, anxiety symptoms, and functional impairment.

In 17,130 individuals with lifetime depression or anxiety from the Genetic Links to Anxiety and Depression (GLAD) Study, we analyzed total scores from the Patient Health Questionnaire-9 (depression symptoms), Generalized Anxiety Disorder-7 (anxiety symptoms), and Work and Social Adjustment Scale (functional impairment). Genome-wide association analyses were performed with REGENIE. Heritability was estimated using GCTA-GREML and genetic correlations with bivariate-GREML.

The phenotypic correlations were moderate across the three measures (Pearson’s r = 0.50–0.69). All three scales were found to be under low but significant genetic influence (single-nucleotide polymorphism-based heritability [h2SNP] = 0.11–0.19) with high genetic correlations between them (rg = 0.79–0.87).

Among individuals with lifetime depression or anxiety from the GLAD Study, the genetic variants that underlie symptom severity largely overlap with those influencing functional impairment. This suggests that self-reported functional impairment, while clinically relevant for diagnosis and treatment outcomes, does not reflect substantial additional genetic liability beyond that captured by symptom-based measures of depression or anxiety.

Patients with posttraumatic stress disorder (PTSD) exhibit smaller regional brain volumes in commonly reported regions including the amygdala and hippocampus, regions associated with fear and memory processing. In the current study, we have conducted a voxel-based morphometry (VBM) meta-analysis using whole-brain statistical maps with neuroimaging data from the ENIGMA-PGC PTSD working group.

T1-weighted structural neuroimaging scans from 36 cohorts (PTSD n = 1309; controls n = 2198) were processed using a standardized VBM pipeline (ENIGMA-VBM tool). We meta-analyzed the resulting statistical maps for voxel-wise differences in gray matter (GM) and white matter (WM) volumes between PTSD patients and controls, performed subgroup analyses considering the trauma exposure of the controls, and examined associations between regional brain volumes and clinical variables including PTSD (CAPS-4/5, PCL-5) and depression severity (BDI-II, PHQ-9).

PTSD patients exhibited smaller GM volumes across the frontal and temporal lobes, and cerebellum, with the most significant effect in the left cerebellum (Hedges’ g = 0.22, pcorrected = .001), and smaller cerebellar WM volume (peak Hedges’ g = 0.14, pcorrected = .008). We observed similar regional differences when comparing patients to trauma-exposed controls, suggesting these structural abnormalities may be specific to PTSD. Regression analyses revealed PTSD severity was negatively associated with GM volumes within the cerebellum (pcorrected = .003), while depression severity was negatively associated with GM volumes within the cerebellum and superior frontal gyrus in patients (pcorrected = .001).

PTSD patients exhibited widespread, regional differences in brain volumes where greater regional deficits appeared to reflect more severe symptoms. Our findings add to the growing literature implicating the cerebellum in PTSD psychopathology.

The COVID-19 pandemic and associated restrictive measures affected the mental health and well-being of individuals globally. We assessed non-modifiable and modifiable factors associated with the change in well-being and mental health from pre- to during the COVID-19 pandemic in South Africa.

A cross-sectional online survey was conducted from 26-April-2020 to 22-April-2021. Paired samples t-tests were conducted to assess change in well-being (measured on The World Health Organization-Five Well-Being Index (WHO-5)) and mental health (a validated composite psychopathology p-score). Sociodemographic, environmental, clinical and behavioral factors associated with change in outcomes were examined.

The sample comprised of 1866 adults (M age=44.26±17.36 years, female=78.9%). Results indicated a significant decrease in well-being (p<0.001) and increase in p-score (p<0.001) from pre- to during the pandemic. Having a prior mental health condition was associated with a worsening well-being score, while being female was associated with a worsening p-score. Being of Black African descent was associated with improved p-score and higher socioeconomic status (SES) was associated with improved well-being. Factors associated with worsening of both well-being and the p-score included adulthood adversity, financial loss since COVID-19, and placing greater importance on direct contact/interactions and substance use as coping strategies. Higher education level and endorsing studying/learning something new as a very important coping strategy were associated with improved well-being and p-score.

Findings inform the need for targeted interventions to reduce and prevent adverse well-being and mental health outcomes during a pandemic, especially among vulnerable groups.

Cardiac surgery-associated acute kidney injury (CS-AKI) and fluid overload (FO) are common among neonates who undergo cardiopulmonary bypass, and increase mortality risk. Current diagnostic criteria may delay diagnosis. Thus, there is a need to identify urine biomarkers that permit earlier and more accurate diagnosis.

This single-centre ancillary prospective cohort study describes age- and disease-specific ranges of 14 urine biomarkers at perioperative time points and explores associations with CS-AKI and FO. Neonates (≤28 days) undergoing cardiac surgery were included. Preterm neonates or those who had pre-operative acute kidney injury were excluded. Urine biomarkers were measured pre-operatively, at 0 to < 8 hours after surgery, and at 8 to 24 hours after surgery. Exploratory outcomes included CS-AKI, defined by the modified Kidney Disease Improving Global Outcomes criteria, and>10% FO, both measured at 48 hours after surgery.

Overall, α-glutathione S-transferase, β-2 microglobulin, albumin, cystatin C, neutrophil gelatinase-associated lipocalin, osteopontin, uromodulin, clusterin, and vascular endothelial growth factor concentrations peaked in the early post-operative period; over the sampling period, kidney injury molecule-1 increased and trefoil factor-3 decreased. In the early post-operative period, β-2 microglobulin and α-glutathione S-transferase were higher in neonates who developed CS-AKI; and clusterin, cystatin C, neutrophil gelatinase-associated lipocalin, osteopontin, and α-glutathione S-transferase were higher in neonates who developed FO.

In a small, single-centre cohort, age- and disease-specific urine biomarker concentrations are described. These data identify typical trends and will inform future studies.

Long-acting injectable antipsychotics (LAIs) have demonstrated better rates of adherence among patients with schizophrenia than oral antipsychotics (OAs). While LAIs often cost more than OAs, better adherence can lead to cost offsets in other areas.

The purpose of this LAI Cost-Offset Value Calculator (LCVC) model is to provide an evidence-based model that estimates total costs and total cost offsets for a hypothetical population of adult patients with schizophrenia treated with atypical LAIs relative to second-generation oral antipsychotics (SGOAs) in the United States.

The model was derived based on studies included in a recent meta-analysis of patients who relapsed while taking an SGOA and were either switched to an atypical LAI or continued an SGOA. User inputs to the model include population size and payer archetype. The model then estimates the difference in adherence rates, relapse rates, hospitalizations, hospital days, hospital costs, emergency department (ED) visits, ED costs, and pharmacy costs, as well as cost offsets overall and by source (ie, hospitalization, ED, pharmacy).

In the base case, representing a hypothetical cohort of 1000 adult patients with schizophrenia in the United States and a composite payer archetype, 1-year pharmacy costs were higher for patients who switched to an LAI relative to patients who continued taking an SGOA ($14,561,971 vs $7,203,142). However, cost offsets were observed for other dimensions of direct costs, including lower ED costs ($1,664,808 vs $2,241,483) and substantially lower hospital costs ($23,623,612 vs $44,195,100) due to fewer relapses (409 vs 508). For some payer archetypes (ie, Medicare and Veteran Affairs), the cost offsets completely covered the higher pharmacy costs for LAIs; for others (ie, Commercial and Medicaid), the cost offsets partially covered the higher pharmacy costs for LAIs, though sometimes substantially.

Despite potential higher pharmacy costs for LAIs, this model supports the conclusion that those costs could be mitigated by cost offsets in other areas, with varying results depending on payer archetype. The LCVC model, parameterized using real-world data extracted from a recent systematic review and meta-analysis, may be helpful for payers in understanding the potential cost offsets of switching patients with schizophrenia who have relapsed while taking OAs to LAIs. To our knowledge, there are no similar studies for schizophrenia that calculate cost offsets based solely on empirical evidence of patients who failed on OAs.

Teva Branded Pharmaceutical Products R&D, Inc.

Healthcare professionals (HCPs) face unique challenges when managing patients with schizophrenia. Educational initiatives targeting common clinical dilemmas encountered by clinicians, including partial or nonadherence, may alleviate knowledge gaps and clarify the role of long-acting injectable antipsychotic agents (LAIs) in treating this population.

4 experts in schizophrenia management used empirical evidence to identify 11 key clinical dilemmas where LAIs may be useful. These experts then developed a heuristic, educational tool (S.C.O.P.E.™: Schizophrenia Clinical Outcome Scenarios and Patient-Provider Engagement) based on empirical evidence and expert opinion for clinicians to use when encountering similar scenarios to optimize schizophrenia care.

S.C.O.P.E.™ is a freely-available resource comprising an interactive digital platform providing educational materials for HCPs involved in continued care for patients with schizophrenia. S.C.O.P.E.™ provides HCPs with considerations in common clinical scenarios met in inpatient and outpatient settings, as well as questions to consider when patients present to the emergency department. The potential usefulness of LAIs is explored in each scenario. Clinical education videos prepare nurse practitioners, social workers, and case managers to address patient concerns and communicate the benefits of LAI treatment. S.C.O.P.E.™ will not replace clinical judgment, guidelines, or continuing medical education, and is not a platform for recording patient-level data, nor intended for payer negotiations or access-related questions by HCPs.

S.C.O.P.E.™ is an educational tool for HCPs to use alongside standard psychiatric evaluations to improve understanding of how to manage common clinical dilemmas when treating patients with schizophrenia and the role of LAIs in schizophrenia management.

Teva Branded Pharmaceutical Products R&D, Inc.

Healthcare professionals (HCPs) face unique challenges when managing patients with schizophrenia. Educational initiatives targeting common clinical dilemmas encountered by clinicians, such as unfamiliarity with prescribing information for long-acting injectable antipsychotics (LAIs), may assist clinicians when treating patients with schizophrenia.

Four experts in schizophrenia management used empirical evidence to identify 11 key clinical dilemmas where LAIs may be useful. These experts then developed a heuristic, educational tool (S.C.O.P.E.™: Schizophrenia Clinical Outcome Scenarios and Patient-Provider Engagement) based on empirical evidence and expert opinion for clinicians to use when encountering similar scenarios to optimize schizophrenia care. S.C.O.P.E.™ also includes supportive elements such as an LAI selector.

S.C.O.P.E.™ is a freely available resource comprising an interactive digital platform providing educational materials for HCPs involved in continued care for patients with schizophrenia. To acquaint HCPs with characteristics of common LAIs used in schizophrenia treatment, S.C.O.P.E.™ offers a selector that filters LAIs by approved indication(s), initiation regimen, reconstitution, dosing strengths and frequency, injection volumes and routes, and supply and storage information based on approved product labels. The LAI selector does not provide LAI safety and efficacy data, so HCPs should visit individual product websites for this information. Therefore, S.C.O.P.E.™ will not replace clinical judgment, guidelines, or continuing medical education, and is not a platform for recording patient-level data, nor intended for payer negotiations or access-related questions by HCPs.

S.C.O.P.E.™ is an educational tool for HCPs to use alongside standard psychiatric evaluations to improve understanding of how to manage common clinical dilemmas when treating patients with schizophrenia, the role of LAIs in schizophrenia management, and the product characteristics of available LAIs.

Teva Branded Pharmaceutical Products R&D, Inc.

Early intervention in psychosis (EIP) services improve outcomes for young people, but approximately 30% disengage.

To test whether a new motivational engagement intervention would prolong engagement and whether it was cost-effective.

We conducted a multicentre, single-blind, parallel-group, cluster randomised controlled trial involving 20 EIP teams at five UK National Health Service (NHS) sites. Teams were randomised using permuted blocks stratified by NHS trust. Participants were all young people (aged 14–35 years) presenting with a first episode of psychosis between May 2019 and July 2020 (N = 1027). We compared the novel Early Youth Engagement (EYE-2) intervention plus standardised EIP (sEIP) with sEIP alone. The primary outcome was time to disengagement over 12–26 months. Economic outcomes were mental health costs, societal costs and socio-occupational outcomes over 12 months. Assessors were masked to treatment allocation for primary disengagement and cost-effectiveness outcomes. Analysis followed intention-to-treat principles. The trial was registered at ISRCTN51629746.

Disengagement was low at 15.9% overall in standardised stand-alone services. The adjusted hazard ratio for EYE-2 + sEIP (n = 652) versus sEIP alone (n = 375) was 1.07 (95% CI 0.76–1.49; P = 0.713). The health economic evaluation indicated lower mental healthcare costs linked to reductions in unplanned mental healthcare with no compromise of clinical outcomes, as well as some evidence for lower societal costs and more days in education, training, employment and stable accommodation in the EYE-2 group.

We found no evidence that EYE-2 increased time to disengagement, but there was some evidence for its cost-effectiveness. This is the largest study to date reporting positive engagement, health and cost outcomes in a total EIP population sample. Limitations included high loss to follow-up for secondary outcomes and low completion of societal and socio-occupational data. COVID-19 affected fidelity and implementation. Future engagement research should target engagement to those in greatest need, including in-patients and those with socio-occupational goals.

Motor neuron disease (MND) is a progressive, fatal, neurodegenerative condition that affects motor neurons in the brain and spinal cord, resulting in loss of the ability to move, speak, swallow and breathe. Acceptance and commitment therapy (ACT) is an acceptance-based behavioural therapy that may be particularly beneficial for people living with MND (plwMND). This qualitative study aimed to explore plwMND’s experiences of receiving adapted ACT, tailored to their specific needs, and therapists’ experiences of delivering it.

Semi-structured qualitative interviews were conducted with plwMND who had received up to eight 1:1 sessions of adapted ACT and therapists who had delivered it within an uncontrolled feasibility study. Interviews explored experiences of ACT and how it could be optimised for plwMND. Interviews were audio recorded, transcribed and analysed using framework analysis.

Participants were 14 plwMND and 11 therapists. Data were coded into four over-arching themes: (i) an appropriate tool to navigate the disease course; (ii) the value of therapy outweighing the challenges; (iii) relevance to the individual; and (iv) involving others. These themes highlighted that ACT was perceived to be acceptable by plwMND and therapists, and many participants reported or anticipated beneficial outcomes in the future, despite some therapeutic challenges. They also highlighted how individual factors can influence experiences of ACT, and the potential benefit of involving others in therapy.

Qualitative data supported the acceptability of ACT for plwMND. Future research and clinical practice should address expectations and personal relevance of ACT to optimise its delivery to plwMND.

1. (1) To understand the views of people living with motor neuron disease (plwMND) and therapists on acceptance and commitment therapy (ACT) for people living with this condition.

2. (2) To understand the facilitators of and barriers to ACT for plwMND.

3. (3) To learn whether ACT that has been tailored to meet the specific needs of plwMND needs to be further adapted to potentially increase its acceptability to this population.

This study explores the transformative effects of the Community Plunge, an educational program at the Wake Forest University School of Medicine (WFUSOM), on healthcare delivery, community engagement, and trainee perspectives. It addresses the broader context of health outcomes, where clinical care only accounts for 20%, emphasizing the critical role of social determinants of health (SDOH) and individual behaviors in the remaining 80%.

WFUSOM’s Community Plunge, established in 2002, involves a guided tour of the community, discussions with residents, and debriefing sessions. Qualitative interviews with 20 clinicians were conducted to extract key themes and insights.

The study identified several key outcomes. First, participants gained crucial insights into the community’s history, structural challenges, and prevalent SDOH, enhancing their understanding of the diverse patient populations they serve. Second, the program positively influenced clinician attitudes, fostering empathy, reducing paternalism, and promoting holistic patient care. Third, participants expressed a desire for increased community involvement and reported career trajectory changes toward advocacy and volunteerism. However, challenges such as time constraints were acknowledged.

The study advocates for collaborative efforts to enhance the program’s impact, including proactive measures to ensure respectful engagement during community tours. It positions the Community Plunge as an innovative, scalable, and transformative strategy for experiential SDOH exposure, crucial for the evolving social consciousness of healthcare learners.