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.

Tenecteplase has been shown to be non-inferior to alteplase for the treatment of acute ischemic stroke within 4.5 hours of stroke onset. While not formally approved by regulatory authorities, many jurisdictions have transitioned to using tenecteplase for routine stroke treatment because it is simpler to use and has cost advantages.

We report a three-phase time-series analysis over 2.5 years and the process for transition from use of alteplase to tenecteplase for the routine treatment of acute ischemic stroke from a system-wide perspective involving an entire province. The transition was planned and implemented centrally. Data were collected in clinical routine, arising from both administrative sources and a prospective stroke registry, and represent real-world outcome data. Data are reported using standard descriptive statistics.

A total of 1211 patients were treated with intravenous thrombolysis (477 pre-transition using alteplase, 180 transition period using both drugs, 554 post-transition using tenecteplase). Baseline characteristics, adverse events and outcomes were similar between epochs. There were four dosing errors with tenecteplase, including providing the cardiac dose to two patients. There were no instances of major hemorrhage associated with dosing errors.

The transition to using intravenous tenecteplase for stroke treatment was seamless and resulted in identical outcomes to intravenous alteplase.

In major depressive disorder (MDD), only ~35% achieve remission after first-line antidepressant therapy. Using UK Biobank data, we identify sociodemographic, clinical, and genetic predictors of antidepressant response through self-reported outcomes, aiming to inform personalized treatment strategies.

In UK Biobank Mental Health Questionnaire 2, participants with MDD reported whether specific antidepressants helped them. We tested whether retrospective lifetime response to four selective serotonin reuptake inhibitors (SSRIs) (N = 19,516) – citalopram (N = 8335), fluoxetine (N = 8476), paroxetine (N = 2297) and sertraline (N = 5883) – was associated with sociodemographic (e.g. age, gender) and clinical factors (e.g. episode duration). Genetic analyses evaluated the association between CYP2C19 variation and self-reported response, while polygenic score (PGS) analysis assessed whether genetic predisposition to psychiatric disorders and antidepressant response predicted self-reported SSRI outcomes.

71%–77% of participants reported positive responses to SSRIs. Non-response was significantly associated with alcohol and illicit drug use (OR = 1.59, p = 2.23 × 10−20), male gender (OR = 1.25, p = 8.29 × 10−08), and lower-income (OR = 1.35, p = 4.22 × 10−07). The worst episode lasting over 2 years (OR = 1.93, p = 3.87 × 10−16) and no mood improvement from positive events (OR = 1.35, p = 2.37 × 10−07) were also associated with non-response. CYP2C19 poor metabolizers had nominally higher non-response rates (OR = 1.31, p = 1.77 × 10−02). Higher PGS for depression (OR = 1.08, p = 3.37 × 10−05) predicted negative SSRI outcomes after multiple testing corrections.

Self-reported antidepressant response in the UK Biobank is influenced by sociodemographic, clinical, and genetic factors, mirroring clinical response measures. While positive outcomes are more frequent than remission reported in clinical trials, these self-reports replicate known treatment associations, suggesting they capture meaningful aspects of antidepressant effectiveness from the patient’s perspective.

Peripheral inflammatory markers, including serum interleukin 6 (IL-6), are associated with depression, but less is known about how these markers associate with depression at different stages of the life course.

We examined the associations between serum IL-6 levels at baseline and subsequent depression symptom trajectories in two longitudinal cohorts: ALSPAC (age 10–28 years; N = 4,835) and UK Biobank (39–86 years; N = 39,613) using multilevel growth curve modeling. Models were adjusted for sex, BMI, and socioeconomic factors. Depressive symptoms were measured using the Short Moods and Feelings Questionnaire in ALSPAC (max time points = 11) and the Patient Health Questionnaire-2 in UK Biobank (max time points = 8).

Higher baseline IL-6 was associated with worse depression symptom trajectories in both cohorts (largest effect size: 0.046 [ALSPAC, age 16 years]). These associations were stronger in the younger ALSPAC cohort, where additionally higher IL-6 levels at age 9 years was associated with worse depression symptoms trajectories in females compared to males. Weaker sex differences were observed in the older cohort, UK Biobank. However, statistically significant associations (pFDR <0.05) were of smaller effect sizes, typical of large cohort studies.

These findings suggest that systemic inflammation may influence the severity and course of depressive symptoms across the life course, which is apparent regardless of age and differences in measures and number of time points between these large, population-based cohorts.

History of prior mental disorder, particularly post-traumatic stress disorder (PTSD), increases risk for PTSD following subsequent trauma exposure. However, limited research has examined differences associated with specific prior mental disorders among people with PTSD.

The current study examined whether different prior mental disorders were associated with meaningful differences among individuals presenting to a specialist service for severe earthquake-related distress following the Canterbury earthquakes (N = 177).

Two sets of comparisons were made: between participants with no history of prior disorder and participants with history of any prior disorder; and between participants with history of prior PTSD and those with history of other prior disorders. Comparisons were made in relation to sociodemographic factors, earthquake exposure, peri-traumatic distress, life events and current psychological functioning.

Participants with any prior mental disorder had more current disorders than those with no prior disorder. Among participants with history of any prior disorder, those with prior PTSD reported more life events in the past 5 years than those with other prior disorders.

Findings suggest a history of any prior mental disorder contributes to increased clinical complexity, but not increased PTSD severity, among people with PTSD seeking treatment. Although post-disaster screening efforts should include those with prior mental disorders, it should also be recognised that those with no prior disorders are also at risk of developing equally severe PTSD.

Diagnostic criteria for major depressive disorder allow for heterogeneous symptom profiles but genetic analysis of major depressive symptoms has the potential to identify clinical and etiological subtypes. There are several challenges to integrating symptom data from genetically informative cohorts, such as sample size differences between clinical and community cohorts and various patterns of missing data.

We conducted genome-wide association studies of major depressive symptoms in three cohorts that were enriched for participants with a diagnosis of depression (Psychiatric Genomics Consortium, Australian Genetics of Depression Study, Generation Scotland) and three community cohorts who were not recruited on the basis of diagnosis (Avon Longitudinal Study of Parents and Children, Estonian Biobank, and UK Biobank). We fit a series of confirmatory factor models with factors that accounted for how symptom data was sampled and then compared alternative models with different symptom factors.

The best fitting model had a distinct factor for Appetite/Weight symptoms and an additional measurement factor that accounted for the skip-structure in community cohorts (use of Depression and Anhedonia as gating symptoms).

The results show the importance of assessing the directionality of symptoms (such as hypersomnia versus insomnia) and of accounting for study and measurement design when meta-analyzing genetic association data.

Community health workers and promotoras (CHW/Ps) increasingly support research conducted in communities but receive variable or no training. We developed a culturally and linguistically tailored research best practices course for CHW/Ps that can be taken independently or in facilitated groups. The purpose of this study was to evaluate the facilitated training.

CHW/Ps were recruited from communities and partners affiliated with study sites in Michigan, Florida, and California. They participated in virtual or in-person training facilitated by a peer in English or Spanish and then completed a survey about their abilities (i.e., knowledge and skills for participating in research-related work) and perceptions of the training. Linear regression analyses were used to examine differences in training experience across several factors.

A total of 394 CHW/Ps, mean age 41.6 ± 13.8 years, completed the training and survey (n = 275 English; 119 Spanish). Most CHW/Ps were female (80%), and 50% identified as Hispanic, Latino, or Spanish. Over 95% of CHW/Ps rated their abilities as improved after training; 98% agreed the course was relevant to their work and felt the training was useful. Small differences were observed between training sites.

Most CHW/Ps rated the training positively and noted improved knowledge and skills for engaging in research-related work. Despite slight site differences, the training was well received, and CHW/Ps appreciated having a facilitator with experience working in community-based settings. This course offers a standard and scalable approach to training the CHW/P workforce. Future studies can examine its uptake and effect on research quality.

The brain can be represented as a network, with nodes as brain regions and edges as region-to-region connections. Nodes with the most connections (hubs) are central to efficient brain function. Current findings on structural differences in Major Depressive Disorder (MDD) identified using network approaches remain inconsistent, potentially due to small sample sizes. It is still uncertain at what level of the connectome hierarchy differences may exist, and whether they are concentrated in hubs, disrupting fundamental brain connectivity.

We utilized two large cohorts, UK Biobank (UKB, N = 5104) and Generation Scotland (GS, N = 725), to investigate MDD case–control differences in brain network properties. Network analysis was done across four hierarchical levels: (1) global, (2) tier (nodes grouped into four tiers based on degree) and rich club (between-hub connections), (3) nodal, and (4) connection.

In UKB, reductions in network efficiency were observed in MDD cases globally (d = −0.076, pFDR = 0.033), across all tiers (d = −0.069 to −0.079, pFDR = 0.020), and in hubs (d = −0.080 to −0.113, pFDR = 0.013–0.035). No differences in rich club organization and region-to-region connections were identified. The effect sizes and direction for these associations were generally consistent in GS, albeit not significant in our lower-N replication sample.

Our results suggest that the brain's fundamental rich club structure is similar in MDD cases and controls, but subtle topological differences exist across the brain. Consistent with recent large-scale neuroimaging findings, our findings offer a connectomic perspective on a similar scale and support the idea that minimal differences exist between MDD cases and controls.

Although COVID-19 is known to have cardiac effects in children, seen primarily in severe disease, more information is needed about the cardiac effects following COVID-19 in non-hospitalised children and adolescents during recovery. This study aims to compare echocardiographic markers of cardiac size and function of children following acute COVID-19 with those of healthy controls.

This single-centre retrospective case–control study compared 71 cases seen in cardiology clinic following acute COVID-19 with 33 healthy controls. Apical left ventricle, apical right ventricle, and parasternal short axis at the level of the papillary muscles were analysed to measure ventricular size and systolic function. Strain was analysed on vendor-independent software. Statistical analysis was performed using t-test, chi-square, Wilcoxon rank sum, and regression modelling as appropriate (p < 0.05 significant).

Compared to controls, COVID-19 cases had slightly higher left ventricular volumes and lower left ventricular ejection fraction and right ventricular fractional area change that remained within normal range. There were no differences in right or left ventricular longitudinal strain between the two groups. Neither initial severity nor persistence of symptoms after diagnosis predicted these differences.

Echocardiographic findings in children and adolescents 6 weeks to 3 months following acute COVID-19 not requiring hospitalisation were overall reassuring. Compared to healthy controls, the COVID-19 group demonstrated mildly larger left ventricular size and lower conventional measures of biventricular systolic function that remained within the normal range, with no differences in biventricular longitudinal strain. Future studies focusing on longitudinal echocardiographic assessment of patients following acute COVID-19 are needed to better understand these subtle differences in ventricular size and function.

Globally, burns are responsible for around 11 million injuries and 180 000 burn-related deaths yearly. Unfortunately, 9 of 10 burn injuries and deaths happen in low-and-middle-income countries (LMICs) such as Pakistan. One in three people admitted to hospitals with burn injuries die within three weeks, and survivors face serious lifelong physical, emotional and psychosocial problems. This may result in anxiety, depression, post-traumatic stress disorder, increased mortality and social disintegration. This study aims to evaluate if implementation of a culturally adapted multidisciplinary rehabilitation programme for burn survivors is clinically and cost-effective, sustainable and scalable across Pakistan.

• - To understand lived experiences of burn survivors, families, and other stakeholders including the experience of care and impact of burns To work together with key stakeholders (such as burn survivors, family members) to adapt a culturally appropriate affordable burn rehabilitation programme

• - To undertake social media campaigns to promote burn prevention and risk assessment at communities, workplaces/industries/households; improve first aid; and address burn related stigma

• - To work with policy makers/parliamentarians to develop national guidelines for burns care and prevention in Pakistan

There are 6 work-packages (WPs). WP1 is to co-adapt a culturally appropriate burn care and rehabilitation programme. WP2 will develop and implement national burn registry on WHO’s initiative. WP3 is a cluster randomised controlled trial to determine clinical and cost-effectiveness in Pakistan. WP4 will evaluate social media campaigns for burn prevention and reduce stigma. WP5 involves working with key-stakeholders for burns-related care and policy and WP6 offers sustainable capacity and capability for burns treatment and rehabilitation.

A clinical and cost-effective burn care quality and rehabilitation programme may have a huge potential to save lives and contribute health and socio-economic benefits for patients, families, and the healthcare system in Pakistan. The nation-wide implementation and involvement of burn centres across all provinces offer an excellent opportunity to overcome the problem of burn care access experienced in LMICs.

To date, burns prevention, care and rehabilitation have not received sufficient attention in policy initiatives in Pakistan and other LMICs. This study is an excellent opportunity to evaluate culturally adapted burn care and rehabilitation programmes that can be implemented across LMICs. We will disseminate our findings widely, using a variety of approaches, supported by our stakeholder and patient advisory groups.

None Declared

Childhood trauma and adversity are common across societies and have strong associations with physical and psychiatric morbidity throughout the life-course. One possible mechanism through which childhood trauma may predispose individuals to poor psychiatric outcomes is via associations with brain structure. This study aimed to elucidate the associations between childhood trauma and brain structure across two large, independent community cohorts.

The two samples comprised (i) a subsample of Generation Scotland (n=1,024); and (ii) individuals from UK Biobank (n=27,202). This comprised n=28,226 for mega-analysis. MRI scans were processed using Free Surfer, providing cortical, subcortical, and global brain metrics. Regression models were used to determine associations between childhood trauma measures and brain metrics and psychiatric phenotypes.

Childhood trauma associated with lifetime depression across cohorts (OR 1.06 GS, 1.23 UKB), and related to early onset and recurrent course within both samples. There was evidence for associations between childhood trauma and structural brain metrics. This included reduced global brain volume, and reduced cortical surface area with highest effects in the frontal (β=−0.0385, SE=0.0048, p(FDR)=5.43x10−15) and parietal lobes (β=−0.0387, SE=0.005, p(FDR)=1.56x10−14). At a regional level the ventral diencephalon (VDc) displayed significant associations with childhood trauma measures across both cohorts and at mega-analysis (β=−0.0232, SE=0.0039, p(FDR)=2.91x10−8). There were also associations with reduced hippocampus, thalamus, and nucleus accumbens volumes.

Associations between childhood trauma and reduced global and regional brain volumes were found, across two independent UK cohorts, and at mega-analysis. This provides robust evidence for a lasting effect of childhood adversity on brain structure.

The COVID-19 pandemic may disproportionately affect the mental health of healthcare professionals (HCPs), especially patient-facing HCPs.

To longitudinally examine mental health in HCPs versus non-HCPs, and patient-facing HCPs versus non-patient-facing HCPs.

Online surveys were distributed to a cohort at three phases (baseline, July to September 2020; phase 2, 6 weeks post-baseline; phase 3, 4 months post-baseline). Each survey contained validated assessments for depression, anxiety, insomnia, burnout and well-being. For each outcome, we conducted mixed-effects logistic regression models (adjusted for a priori confounders) comparing the risk in different groups at each phase.

A total of 1574 HCPs and 147 non-HCPs completed the baseline survey. Although there were generally higher rates of various probable mental health issues among HCPs versus non-HCPs at each phase, there was no significant difference, except that HCPs had 2.5-fold increased risk of burnout at phase 2 (emotional exhaustion: odds ratio 2.50, 95% CI 1.15–5.46, P = 0.021), which increased at phase 3 (emotional exhaustion: odds ratio 3.32, 95% CI 1.40–7.87, P = 0.006; depersonalisation: odds ratio 3.29, 95% CI 1.12–9.71, P = 0.031). At baseline, patient-facing HCPs (versus non-patient-facing HCPs) had a five-fold increased risk of depersonalisation (odds ratio 5.02, 95% CI 1.65–15.26, P = 0.004), with no significant difference in the risk for other outcomes. The difference in depersonalisation reduced over time, but patient-facing HCPs still had a 2.7-fold increased risk of emotional exhaustion (odds ratio 2.74, 95% CI 1.28–5.85, P = 0.009) by phase 3.

The COVID-19 pandemic had a huge impact on the mental health and well-being of both HCPs and non-HCPs, but there is disproportionately higher burnout among HCPs, particularly patient-facing HCPs.

Major depressive disorder (MDD) was previously associated with negative affective biases. Evidence from larger population-based studies, however, is lacking, including whether biases normalise with remission. We investigated associations between affective bias measures and depressive symptom severity across a large community-based sample, followed by examining differences between remitted individuals and controls.

Participants from Generation Scotland (N = 1109) completed the: (i) Bristol Emotion Recognition Task (BERT), (ii) Face Affective Go/No-go (FAGN), and (iii) Cambridge Gambling Task (CGT). Individuals were classified as MDD-current (n = 43), MDD-remitted (n = 282), or controls (n = 784). Analyses included using affective bias summary measures (primary analyses), followed by detailed emotion/condition analyses of BERT and FAGN (secondary analyses).

For summary measures, the only significant finding was an association between greater symptoms and lower risk adjustment for CGT across the sample (individuals with greater symptoms were less likely to bet more, despite increasingly favourable conditions). This was no longer significant when controlling for non-affective cognition. No differences were found for remitted-MDD v. controls. Detailed analysis of BERT and FAGN indicated subtle negative biases across multiple measures of affective cognition with increasing symptom severity, that were independent of non-effective cognition [e.g. greater tendency to rate faces as angry (BERT), and lower accuracy for happy/neutral conditions (FAGN)]. Results for remitted-MDD were inconsistent.

This suggests the presence of subtle negative affective biases at the level of emotion/condition in association with depressive symptoms across the sample, over and above those accounted for by non-affective cognition, with no evidence for affective biases in remitted individuals.

Major depressive disorder (MDD) is a polygenic disorder associated with brain alterations but until recently, there have been no brain-based metrics to quantify individual-level variation in brain morphology. Here, we evaluated and compared the performance of a new brain-based ‘Regional Vulnerability Index’ (RVI) with polygenic risk scores (PRS), in the context of MDD. We assessed associations with syndromal MDD in an adult sample (N = 702, age = 59 ± 10) and with subclinical depressive symptoms in a longitudinal adolescent sample (baseline N = 3,825, age = 10 ± 1; 2-year follow-up N = 2,081, age = 12 ± 1).

MDD-RVIs quantify the correlation of the individual’s corresponding brain metric with the expected pattern for MDD derived in an independent sample. Using the same methodology across samples, subject-specific MDD-PRS and six MDD-RVIs based on different brain modalities (subcortical volume, cortical thickness, cortical surface area, mean diffusivity, fractional anisotropy, and multimodal) were computed.

In adults, MDD-RVIs (based on white matter and multimodal measures) were more strongly associated with MDD (β = 0.099–0.281, PFDR = 0.001–0.043) than MDD-PRS (β = 0.056–0.152, PFDR = 0.140–0.140). In adolescents, depressive symptoms were associated with MDD-PRS at baseline and follow-up (β = 0.084–0.086, p = 1.38 × 10−4−4.77 × 10−4) but not with any MDD-RVIs (β < 0.05, p > 0.05).

Our results potentially indicate the ability of brain-based risk scores to capture a broader range of risk exposures than genetic risk scores in adults and are also useful in helping us to understand the temporal origins of depression-related brain features. Longitudinal data, specific to the developmental period and on white matter measures, will be useful in informing risk for subsequent psychiatric illness.