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.

The Hierarchical Taxonomy of Psychopathology (HiTOP) and Research Domain Criteria (RDoC) frameworks emphasize transdiagnostic and mechanistic aspects of psychopathology. We used a multi-omics approach to examine how HiTOP’s psychopathology spectra (externalizing [EXT], internalizing [INT], and shared EXT + INT) map onto RDoC’s units of analysis.

We conducted analyses across five RDoC units of analysis: genes, molecules, cells, circuits, and physiology. Using genome-wide association studies from the companion Part I article, we identified genes and tissue-specific expression patterns. We used drug repurposing analyses that integrate gene annotations to identify potential therapeutic targets and single-cell RNA sequencing data to implicate brain cell types. We then used magnetic resonance imaging data to examine brain regions and circuits associated with psychopathology. Finally, we tested causal relationships between each spectrum and physical health conditions.

Using five gene identification methods, EXT was associated with 1,759 genes, INT with 454 genes, and EXT + INT with 1,138 genes. Drug repurposing analyses identified potential therapeutic targets, including those that affect dopamine and serotonin pathways. Expression of EXT genes was enriched in GABAergic, cortical, and hippocampal neurons, while INT genes were more narrowly linked to GABAergic neurons. EXT + INT liability was associated with reduced gray matter volume in the amygdala and subcallosal cortex. INT genetic liability showed stronger causal effects on physical health – including chronic pain and cardiovascular diseases – than EXT.

Our findings revealed shared and distinct pathways underlying psychopathology. Integrating genomic insights with the RDoC and HiTOP frameworks advanced our understanding of mechanisms that underlie EXT and INT psychopathology.

There is considerable comorbidity between externalizing (EXT) and internalizing (INT) psychopathology. Understanding the shared genetic underpinnings of these spectra is crucial for advancing knowledge of their biological bases and informing empirical models like the Research Domain Criteria (RDoC) and Hierarchical Taxonomy of Psychopathology (HiTOP).

We applied genomic structural equation modeling to summary statistics from 16 EXT and INT traits in individuals genetically similar to European reference panels (EUR-like; n = 16,400 to 1,074,629). Traits included clinical (e.g. major depressive disorder, alcohol use disorder) and subclinical measures (e.g. risk tolerance, irritability). We tested five confirmatory factor models to identify the best fitting and most parsimonious genetic architecture and then conducted multivariate genome-wide association studies (GWAS) of the resulting latent factors.

A two-factor correlated model, representing EXT and INT spectra, provided the best fit to the data. There was a moderate genetic correlation between EXT and INT (r = 0.37, SE = 0.02), with bivariate causal mixture models showing extensive overlap in causal variants across the two spectra (94.64%, SE = 3.27). Multivariate GWAS identified 409 lead genetic variants for EXT, 85 for INT, and 256 for the shared traits.

The shared genetic liabilities for EXT and INT identified here help to characterize the genetic architecture underlying these frequently comorbid forms of psychopathology. The findings provide a framework for future research aimed at understanding the shared and distinct biological mechanisms underlying psychopathology, which will help to refine psychiatric classification systems and potentially inform treatment approaches.

Racial and ethnic variations in antibiotic utilization are well-reported in outpatient settings but little is known about inpatient settings. Our objective was to describe national inpatient antibiotic utilization among children by race and ethnicity.

This study included hospital visit data from the Pediatric Health Information System between 01/01/2022 and 12/31/2022 for patients <20 years. Primary outcomes were the percentage of hospitalization encounters that received an antibiotic and antibiotic days of therapy (DOT) per 1000 patient days. Mixed-effect regression models were used to determine the association of race-ethnicity with outcomes, adjusting for covariates.

There were 846,530 hospitalizations. 45.2% of children were Non-Hispanic (NH) White, 27.1% were Hispanic, 19.2% were NH Black, 4.5% were NH Other, 3.5% were NH Asian, 0.3% were NH Native Hawaiian/Other Pacific Islander (NHPI) and 0.2% were NH American Indian. Adjusting for covariates, NH Black children had lower odds of receiving antibiotics compared to NH White children (aOR 0.96, 95%CI 0.94–0.97), while NH NHPI had higher odds of receiving antibiotics (aOR 1.16, 95%CI 1.05–1.29). Children who were Hispanic, NH Asian, NH American Indian, and children who were NH Other received antibiotic DOT compared to NH White children, while NH NHPI children received more antibiotic DOT.

Antibiotic utilization in children’s hospitals differs by race and ethnicity. Hospitals should assess policies and practices that may contribute to disparities in treatment; antibiotic stewardship programs may play an important role in promoting inpatient pharmacoequity. Additional research is needed to examine individual diagnoses, clinical outcomes, and drivers of variation.

Attention-deficit/hyperactivity disorder (ADHD) is a highly prevalent psychiatric condition that frequently originates in early development and is associated with a variety of functional impairments. Despite a large functional neuroimaging literature on ADHD, our understanding of the neural basis of this disorder remains limited, and existing primary studies on the topic include somewhat divergent results.

The present meta-analysis aims to advance our understanding of the neural basis of ADHD by identifying the most statistically robust patterns of abnormal neural activation throughout the whole-brain in individuals diagnosed with ADHD compared to age-matched healthy controls.

We conducted a meta-analysis of task-based functional magnetic resonance imaging (fMRI) activation studies of ADHD. This included, according to PRISMA guidelines, a comprehensive PubMed search and predetermined inclusion criteria as well as two independent coding teams who evaluated studies and included all task-based, whole-brain, fMRI activation studies that compared participants diagnosed with ADHD to age-matched healthy controls. We then performed multilevel kernel density analysis (MKDA) a well-established, whole-brain, voxelwise approach that quantitatively combines existing primary fMRI studies, with ensemble thresholding (p<0.05-0.0001) and multiple comparisons correction.

Participants diagnosed with ADHD (N=1,550), relative to age-matched healthy controls (N=1,340), exhibited statistically significant (p<0.05-0.0001; FWE-corrected) patterns of abnormal activation in multiple brains of the cerebral cortex and basal ganglia across a variety of cognitive control tasks.

This study advances our understanding of the neural basis of ADHD and may aid in the development of new brain-based clinical interventions as well as diagnostic tools and treatment matching protocols for patients with ADHD. Future studies should also investigate the similarities and differences in neural signatures between ADHD and other highly comorbid psychiatric disorders.

None Declared

This quality improvement project assessed the outcomes of telephone consultations for ENT patients in order to identify areas where telephone consultations may be useful in the long term.

New ENT patient appointments in May 2019 and May 2020 were reviewed. Total outcomes as well as subspecialty-specific and presentation-specific outcomes were compared for telephone versus face-to-face consultations.

There were 638 consultations in total (465 in 2019 and 173 in 2020). Following telephone consultations, more patients were followed up and fewer patients were listed for surgery or discharged. Overall outcomes for subspecialties followed the general trend, albeit with a few variations.

Lack of clinical examination in telephone consultations likely affects confidence in making a diagnosis and therefore discharging or listing patients for surgery. Nevertheless, looking at specialty-specific and presentation-specific data, there may be a role for telephone consultations in selected patients.

Smell impairment affects 60–80 per cent of individuals aged over 80 years. This review aimed to identify any association between vitamin D deficiency and smell impairment, and determine the efficacy of vitamin D to treat smell impairment.

A literature search was conducted across four databases between the years 2000 and 2022. The literature screen was performed by two independent reviewers.

Seven articles were included in this review. Four studies examined the association between vitamin D deficiency and smell impairment, with three studies identifying a significant relationship. Three studies investigated the use of vitamin D as treatment for smell impairment, which found complete resolution or significant symptom improvement after vitamin D deficiency was treated.

This review identified limited studies on this topic. As vitamin D supplementation is relatively cost-efficient, further large-scale studies should be carried out to investigate the efficacy of vitamin D for treating anosmia.

We aimed to examine how public health policies influenced the dynamics of coronavirus disease 2019 (COVID-19) time-varying reproductive number (Rt) in South Carolina from February 26, 2020, to January 1, 2021.

COVID-19 case series (March 6, 2020, to January 10, 2021) were shifted by 9 d to approximate the infection date. We analyzed the effects of state and county policies on Rt using EpiEstim. We performed linear regression to evaluate if per-capita cumulative case count varies across counties with different population size.

Rt shifted from 2-3 in March to <1 during April and May. Rt rose over the summer and stayed between 1.4 and 0.7. The introduction of statewide mask mandates was associated with a decline in Rt (−15.3%; 95% CrI, −13.6%, −16.8%), and school re-opening, an increase by 12.3% (95% CrI, 10.1%, 14.4%). Less densely populated counties had higher attack rates (P < 0.0001).

The Rt dynamics over time indicated that public health interventions substantially slowed COVID-19 transmission in South Carolina, while their relaxation may have promoted further transmission. Policies encouraging people to stay home, such as closing nonessential businesses, were associated with Rt reduction, while policies that encouraged more movement, such as re-opening schools, were associated with Rt increase.

To describe the development and implementation of a novel tool designed to enhance nurse–patient communication in a major academic cancer center, which nurses can learn quickly, incorporate into their primary palliative care practice, and broadly disseminate in order to improve the patient experience.

An evidence-based empathic communication tool and educational program were designed to provide essential skills to oncology nurses in having discussions with patients about their personal values. Evaluation included nurse focus groups, pre- and post-course evaluations and interviews, and patient questionnaires.

Nurses were satisfied with the educational program and found the communication tool effective in a variety of clinical situations including discussions about personal values. Patients reported increased occurrences of these discussions when nurses utilized the framework (97% vs. 58%, p < 0.0001) and a higher quality of clinician communication (mean [SD] from 0 = very worst to 10 = very best: 7.18 [2.3] vs. 5.04 [2.9], p = 0.001).

Skilled, empathic communication is an essential component of high-quality primary palliative care. Oncology nurses are well suited to lead communication and provide this care as part of an interprofessional team. The training and tool described here are targeted and efficient, and prepare nurses to respond skillfully to emotion while facilitating important discussions about patient values.

Mood disorders are characterised by pronounced symptom heterogeneity, which presents a substantial challenge both to clinical practice and research. Identification of subgroups of individuals with homogeneous symptom profiles that cut across current diagnostic categories could provide insights in to the transdiagnostic relevance of individual symptoms, which current categorical diagnostic systems cannot impart.

To identify groups of people with homogeneous clinical characteristics, using symptoms of manic and/or irritable mood, and explore differences between groups in diagnoses, functional outcomes and genetic liability.

We used latent class analysis on eight binary self-reported symptoms of manic and irritable mood in the UK Biobank and PROTECT studies, to investigate how individuals formed latent subgroups. We tested associations between the latent classes and diagnoses of psychiatric disorders, sociodemographic characteristics and polygenic risk scores.

Five latent classes were derived in UK Biobank (N = 42 183) and were replicated in the independent PROTECT cohort (N = 4445), including ‘minimally affected’, ‘inactive restless’, active restless’, ‘focused creative’ and ‘extensively affected’ individuals. These classes differed in disorder risk, polygenic risk score and functional outcomes. One class that experienced disruptive episodes of mostly irritable mood largely comprised cases of depression/anxiety, and a class of individuals with increased confidence/creativity reported comparatively lower disruptiveness and functional impairment.

Findings suggest that data-driven investigations of psychopathological symptoms that include sub-diagnostic threshold conditions can complement research of clinical diagnoses. Improved classification systems of psychopathology could investigate a weighted approach to symptoms, toward a more dimensional classification of mood disorders.

Anxiety and depressive disorders can be chronic and disabling. Although there are effective treatments, only a fraction of those impaired receive treatment. Predictors of treatment-seeking and treatment receipt could be informative for initiatives aiming to tackle the burden of untreated anxiety and depression.

To investigate sociodemographic characteristics associated with treatment-seeking and treatment receipt.

Two binary retrospective reports of lifetime treatment-seeking (n = 44 810) and treatment receipt (n = 37 346) were regressed on sociodemographic factors (age, gender, UK ethnic minority background, educational attainment, household income, neighbourhood deprivation and social isolation) and alternative coping strategies (self-medication with alcohol/drugs and self-help) in UK Biobank participants with lifetime generalised anxiety or major depressive disorder. Analyses were also stratified by gender.

Treatment access was more likely in those who reported use of self-help strategies, with university-level education and those from less economically advantaged circumstances (household income <£30 000 and greater neighbourhood deprivation). Treatment access was less likely in those who were male, from a UK ethnic minority background and with high household incomes (>£100 000). Men who self-medicated and/or had a vocational qualification were also less likely to seek treatment.

This work on retrospective reports of treatment-seeking and treatment receipt at any time of life replicates known associations with treatment-seeking and treatment receipt during time of treatment need. More work is required to understand whether improving rates of treatment-seeking improves prognostic outcomes for individuals with anxiety or depression.