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Accurate diagnosis of bipolar disorder (BPD) is difficult in clinical practice, with an average delay between symptom onset and diagnosis of about 7 years. A depressive episode often precedes the first manic episode, making it difficult to distinguish BPD from unipolar major depressive disorder (MDD).
Aims
We use genome-wide association analyses (GWAS) to identify differential genetic factors and to develop predictors based on polygenic risk scores (PRS) that may aid early differential diagnosis.
Method
Based on individual genotypes from case–control cohorts of BPD and MDD shared through the Psychiatric Genomics Consortium, we compile case–case–control cohorts, applying a careful quality control procedure. In a resulting cohort of 51 149 individuals (15 532 BPD patients, 12 920 MDD patients and 22 697 controls), we perform a variety of GWAS and PRS analyses.
Results
Although our GWAS is not well powered to identify genome-wide significant loci, we find significant chip heritability and demonstrate the ability of the resulting PRS to distinguish BPD from MDD, including BPD cases with depressive onset (BPD-D). We replicate our PRS findings in an independent Danish cohort (iPSYCH 2015, N = 25 966). We observe strong genetic correlation between our case–case GWAS and that of case–control BPD.
Conclusions
We find that MDD and BPD, including BPD-D are genetically distinct. Our findings support that controls, MDD and BPD patients primarily lie on a continuum of genetic risk. Future studies with larger and richer samples will likely yield a better understanding of these findings and enable the development of better genetic predictors distinguishing BPD and, importantly, BPD-D from MDD.
The majority of studies of mental health interventions for young adolescents have only evaluated short-term benefits. This study evaluated the longer-term effectiveness of a non-specialist delivered group-based intervention (Early Adolescent Skills for Emotions; EASE) to improve young adolescents’ mental health.
Methods
In this single-blind, parallel, controlled trial, Syrian refugees aged 10-14 years in Jordan who screened positive for psychological distress were randomised to receive either EASE or enhanced usual care (EUC). Primary outcomes were scores on the Paediatric Symptom Checklist (PSC) assessed at Week 0, 8-weeks, 3-months, and 12 months after treatment. Secondary outcomes were disability, posttraumatic stress, school belongingness, wellbeing, and caregivers’ reports of distress, parenting behaviour, and their perceived children’s mental health.
Results
Between June, 2019 and January, 2020, 185 adolescents were assigned to EASE and 286 to EUC, and 149 (80.5%) and 225 (78.7%) were retained at 12 months, respectively. At 12 months there were no significant differences between treatment conditions, except that EASE was associated with less reduction in depression (estimated mean difference -1.6, 95% CI –3.2 to -0.1; p=.03; effect size, -0.3), and a greater sense of school belonging (estimated mean difference -0.3, 95% CI –5.7 to -0.2; p=.03; effect size, 5.0).
Conclusions
Although EASE led to significant reductions in internalising problems, caregiver distress, and harsh disciplinary parenting at 3-months, these improvements were not maintained at 12 months relative to EUC. Scalable psychological interventions for young adolescents need to consider their ongoing mental health needs. Prospectively registered: ACTRN12619000341123.
This proof-of-concept study evaluated an optimization strategy for the Community Case Detection Tool (CCDT) aimed at improving community-level mental health detection and help-seeking among children aged 6–18 years. The optimization strategy, CCDT+, combined data-driven supervision with motivational interviewing techniques and behavioural nudges for community gatekeepers using the CCDT. This mixed-methods study was conducted from January to May 2023 in Palorinya refugee settlement in Uganda. We evaluated (1) the added value of the CCDT+ in improving the accuracy of detection and mental health service utilization compared to standard CCDT, and (2) implementation outcomes of the CCDT+. Of the 1026 children detected, 801 (78%) sought help, with 656 needing mental health care (PPV = 0.82; 95% CI: 0.79, 0.84). The CCDT+ significantly increased detection accuracy, with 2.34 times higher odds compared to standard CCDT (95% CI: 1.41, 3.83). Additionally, areas using the CCDT+ had a 2.05-fold increase in mental health service utilization (95% CI: 1.09, 3.83). The CCDT+ shows promise as an embedded quality-optimization process for the detection of mental health problems among children and enhance help-seeking, potentially leading to more efficient use of mental health care resources.
Being married may protect late-life cognition. Less is known about living arrangement among unmarried adults and mechanisms such as brain health (BH) and cognitive reserve (CR) across race and ethnicity or sex/gender. The current study examines (1) associations between marital status, BH, and CR among diverse older adults and (2) whether one’s living arrangement is linked to BH and CR among unmarried adults.
Method:
Cross-sectional data come from the Washington Heights-Inwood Columbia Aging Project (N = 778, 41% Hispanic, 33% non-Hispanic Black, 25% non-Hispanic White; 64% women). Magnetic resonance imaging (MRI) markers of BH included cortical thickness in Alzheimer’s disease signature regions and hippocampal, gray matter, and white matter hyperintensity volumes. CR was residual variance in an episodic memory composite after partialing out MRI markers. Exploratory analyses stratified by race and ethnicity and sex/gender and included potential mediators.
Results:
Marital status was associated with CR, but not BH. Compared to married individuals, those who were previously married (i.e., divorced, widowed, and separated) had lower CR than their married counterparts in the full sample, among White and Hispanic subgroups, and among women. Never married women also had lower CR than married women. These findings were independent of age, education, physical health, and household income. Among never married individuals, living with others was negatively linked to BH.
Conclusions:
Marriage may protect late-life cognition via CR. Findings also highlight differential effects across race and ethnicity and sex/gender. Marital status could be considered when assessing the risk of cognitive impairment during routine screenings.
An array of information about the Antarctic ice sheet can be extracted from ice-sheet internal architecture imaged by airborne ice-penetrating radar surveys. We identify, trace and date three key internal reflection horizons (IRHs) across multiple radar surveys from South Pole to Dome A, East Antarctica. Ages of ~38 ± 2.2, ~90 ± 3.6 and ~162 ± 6.7 ka are assigned to the three IRHs, with verification of the upper IRH age from the South Pole ice core. The resultant englacial stratigraphy is used to identify the locations of the oldest ice, specifically in the upper Byrd Glacier catchment and the Gamburtsev Subglacial Mountains. The distinct glaciological conditions of the Gamburtsev Mountains, including slower ice flow, low geothermal heat flux and frozen base, make it the more likely to host the oldest ice. We also observe a distinct drawdown of IRH geometry around South Pole, indicative of melting from enhanced geothermal heat flux or the removal of deeper, older ice under a previous faster ice flow regime. Our traced IRHs underpin the wider objective to develop a continental-scale database of IRHs which will constrain and validate future ice-sheet modelling and the history of the Antarctic ice sheet.
Affective responses to the menstrual cycle vary widely. Some individuals experience severe symptoms like those with premenstrual dysphoric disorder, while others have minimal changes. The reasons for these differences are unclear, but prior studies suggest stressor exposure may play a role. However, research in at-risk psychiatric samples is lacking.
Methods
In a large clinical sample, we conducted a prospective study of how lifetime stressors relate to degree of affective change across the cycle. 114 outpatients with past-month suicidal ideation (SI) provided daily ratings (n = 6187) of negative affect and SI across 1–3 menstrual cycles. Participants completed the Stress and Adversity Inventory (STRAIN), which measures different stressor exposures (i.e. interpersonal loss, physical danger) throughout the life course, including before and after menarche. Multilevel polynomial growth models tested the relationship between menstrual cycle time and symptoms, moderated by stressor exposure.
Results
Greater lifetime stressor exposure predicted a more pronounced perimenstrual increase in active SI, along with marginally significant similar patterns for negative affect and passive SI. Additionally, pre-menarche stressors significantly increased the cyclicity of active SI compared to post-menarche stressors. Exposure to more interpersonal loss stressors predicted greater perimenstrual symptom change of negative affect, passive SI and active SI. Exploratory item-level analyses showed that lifetime stressors moderated a more severe perimenstrual symptom trajectory for mood swings, anger/irritability, rejection sensitivity, and interpersonal conflict.
Conclusion
These findings suggest that greater lifetime stressor exposure may lead to heightened emotional reactivity to ovarian hormone fluctuations, elevating the risk of psychopathology.
Flumioxazin and S-metolachlor are widely used in conventional sweetpotato production in North Carolina and other states; however, some growers have recently expressed concerns about potential effects of these herbicides on sweetpotato yield and quality. Previous research indicates that activated charcoal has the potential to reduce herbicide injury. Field studies were conducted in 2021 and 2022 to determine whether flumioxazin applied preplant and S-metolachlor applied before and after transplanting negatively affect sweetpotato yield and quality when activated charcoal is applied with transplant water. The studies evaluated five herbicide treatments and two activated charcoal treatments. Herbicide treatments included two flumioxazin rates, one S-metolachlor rate applied immediately before and immediately after transplanting, and no herbicide. Charcoal treatments consisted of activated charcoal applied at 9 kg ha−1, and no charcoal. No visual injury from herbicides or charcoal was observed. Likewise, no effect of herbicide or charcoal treatment on no. 1, marketable (sum of no. 1 and jumbo grades), or total yield (sum of canner, no. 1, and jumbo grades) was observed. Additionally, shape analysis conducted on calculated length-to-width ratio (LWR) for no. 1 sweetpotato roots found no effect from flumioxazin at either rate on sweetpotato root shape. However, both S-metolachlor treatments resulted in lower LWR of no. 1 sweetpotato roots in 2021. Results are consistent with prior research and indicate that flumioxazin and S-metolachlor are safe for continued use on sweetpotato at registered rates.
This paper analyses the institutional incentives and constraints of the Black Mouth Society – the traditional police of the pre-colonial Mandan and Hidatsa tribes – to understand how it successfully maintained social order without abusing power. The Black Mouth Society was a fraternal organization of middle-aged men that monitored and enforced rules created by the village council and chiefs. Two categories of institutions ensured reliable policing. First, on the front end, a long probationary period and system of unanimous consent facilitated the selection of reputable men who would wield policing power responsibly, reducing the chance of predation. However, individual Black Mouths occasionally abused their power. Therefore, on the back end, public communication created common knowledge, leading to social sanctions in the form of shame and restitution that punished abuses and limited further abuse. Thus, well-functioning self-governance, including reliable policing, is possible without a centralized state, as these tribes have demonstrated.
Major depressive disorder (MDD) is the leading cause of disability globally, with moderate heritability and well-established socio-environmental risk factors. Genetic studies have been mostly restricted to European settings, with polygenic scores (PGS) demonstrating low portability across diverse global populations.
Methods
This study examines genetic architecture, polygenic prediction, and socio-environmental correlates of MDD in a family-based sample of 10 032 individuals from Nepal with array genotyping data. We used genome-based restricted maximum likelihood to estimate heritability, applied S-LDXR to estimate the cross-ancestry genetic correlation between Nepalese and European samples, and modeled PGS trained on a GWAS meta-analysis of European and East Asian ancestry samples.
Results
We estimated the narrow-sense heritability of lifetime MDD in Nepal to be 0.26 (95% CI 0.18–0.34, p = 8.5 × 10−6). Our analysis was underpowered to estimate the cross-ancestry genetic correlation (rg = 0.26, 95% CI −0.29 to 0.81). MDD risk was associated with higher age (beta = 0.071, 95% CI 0.06–0.08), female sex (beta = 0.160, 95% CI 0.15–0.17), and childhood exposure to potentially traumatic events (beta = 0.050, 95% CI 0.03–0.07), while neither the depression PGS (beta = 0.004, 95% CI −0.004 to 0.01) or its interaction with childhood trauma (beta = 0.007, 95% CI −0.01 to 0.03) were strongly associated with MDD.
Conclusions
Estimates of lifetime MDD heritability in this Nepalese sample were similar to previous European ancestry samples, but PGS trained on European data did not predict MDD in this sample. This may be due to differences in ancestry-linked causal variants, differences in depression phenotyping between the training and target data, or setting-specific environmental factors that modulate genetic effects. Additional research among under-represented global populations will ensure equitable translation of genomic findings.
The ability to remotely monitor cognitive skills is increasing with the ubiquity of smartphones. The Mobile Toolbox (MTB) is a new measurement system that includes measures assessing Executive Functioning (EF) and Processing Speed (PS): Arrow Matching, Shape-Color Sorting, and Number-Symbol Match. The purpose of this study was to assess their psychometric properties.
Method:
MTB measures were developed for smartphone administration based on constructs measured in the NIH Toolbox® (NIHTB). Psychometric properties of the resulting measures were evaluated in three studies with participants ages 18 to 90. In Study 1 (N = 92), participants completed MTB measures in the lab and were administered both equivalent NIH TB measures and other external measures of similar cognitive constructs. In Study 2 (N = 1,021), participants completed the equivalent NIHTB measures in the lab and then took the MTB measures on their own, remotely. In Study 3 (N = 168), participants completed MTB measures twice remotely, two weeks apart.
Results:
All three measures exhibited very high internal consistency and strong test-retest reliability, as well as moderately high correlations with comparable NIHTB tests and moderate correlations with external measures of similar constructs. Phone operating system (iOS vs. Android) had a significant impact on performance for Arrow Matching and Shape-Color Sorting, but no impact on either validity or reliability.
Conclusions:
Results support the reliability and convergent validity of MTB EF and PS measures for use across the adult lifespan in remote, self-administered designs.
We present radio observations of the galaxy cluster Abell S1136 at 888 MHz, using the Australian Square Kilometre Array Pathfinder radio telescope, as part of the Evolutionary Map of the Universe Early Science program. We compare these findings with data from the Murchison Widefield Array, XMM-Newton, the Wide-field Infrared Survey Explorer, the Digitised Sky Survey, and the Australia Telescope Compact Array. Our analysis shows the X-ray and radio emission in Abell S1136 are closely aligned and centered on the Brightest Cluster Galaxy, while the X-ray temperature profile shows a relaxed cluster with no evidence of a cool core. We find that the diffuse radio emission in the centre of the cluster shows more structure than seen in previous low-resolution observations of this source, which appeared formerly as an amorphous radio blob, similar in appearance to a radio halo; our observations show the diffuse emission in the Abell S1136 galaxy cluster contains three narrow filamentary structures visible at 888 MHz, between $\sim$80 and 140 kpc in length; however, the properties of the diffuse emission do not fully match that of a radio (mini-)halo or (fossil) tailed radio source.
Introducing soybean cultivars resistant to 2,4-D and dicamba allowed for postemergence applications of these herbicides. These herbicides pose a high risk for off-target movement, and the potential influence on crops such as hemp is unknown. Two studies were conducted from 2020 through 2022 in controlled environments to evaluate hemp response to rates simulating off-target events of 2,4-D and dicamba. The objectives of these studies were to (1) determine the effects of herbicide (2,4-D and dicamba) and rate (1× to 1/100,000× labeled rate) on visible injury, height, and branching, and (2) determine the effect of 2,4-D rate (1× to 1/100,000× labeled rate) on visible injury, height, branching, and reproductive parameters. Herbicides were applied in the early vegetative stage, and evaluations took place 14 and 28 d after treatment (DAT) and at trial termination (42 DAT in the greenhouse trial and at harvest in the growth chamber trial). In the greenhouse study, 2,4-D and dicamba at the 1× rate, and the 1/10× rate of dicamba, caused 68%, 78%, and 20% injury 28 DAT, respectively. At the time of trial termination 42 DAT, plants treated with 1× rates of 2,4-D and dicamba, or 1/10× dicamba, were 19, 25, and 9 cm shorter than the nontreated control, respectively. Simulated off-target rates of 2,4-D and dicamba did not influence branching or plant weight at trial termination. In the growth chamber study, the 1× and 1/10× rates of 2,4-D caused 82% and 2% injury 28 DAT, respectively. Plant height, fresh weight, and cannabidiol (CBD) levels of plants treated with simulated off-target rates of 2,4-D were not different from the nontreated control. These studies suggest that hemp grown for CBD exposed to off-target rates of 2,4-D or dicamba in early vegetative stages may not have distinguishable effects 42 DAT or at harvest.
To examine associations between three different plant-based diet quality indices, chronic kidney disease (CKD) prevalence and related risk factors in a nationally representative sample of the Australian population.
Design:
Cross-sectional analysis. Three plant-based diet scores were calculated using data from two 24-h recalls: an overall plant-based diet index (PDI), a healthy PDI (hPDI) and an unhealthy PDI (uPDI). Consumption of plant and animal ingredients from ‘core’ and ‘discretionary’ products was also differentiated. Associations between the three PDI scores and CKD prevalence, BMI, waist circumference (WC), blood pressure (BP) measures, blood cholesterol, apo B, fasting TAG, blood glucose levels (BGL) and HbA1c were examined.
Setting:
Australian Health Survey 2011–2013.
Participants:
n 2060 adults aged ≥ 18 years (males: n 928; females: n 1132).
Results:
A higher uPDI score was associated with a 3·7 % higher odds of moderate-severe CKD (OR: 1·037 (1·0057–1·0697); P = 0·021)). A higher uPDI score was also associated with increased TAG (P = 0·032) and BGL (P < 0·001), but lower total- and LDL-cholesterol (P = 0·035 and P = 0·009, respectively). In contrast, a higher overall PDI score was inversely associated with WC (P < 0·001) and systolic BP (P = 0·044), while higher scores for both the overall PDI and hPDI were inversely associated with BMI (P < 0·001 and P = 0·019, respectively).
Conclusions:
A higher uPDI score reflecting greater intakes of refined grains, salty plant-based foods and added sugars were associated with increased CKD prevalence, TAG and BGL. In the Australian population, attention to diet quality remains paramount, even in those with higher intakes of plant foods and who wish to reduce the risk of CKD.
Greenhouse trials were conducted to determine the response of stevia to reduced-risk synthetic and nonsynthetic herbicides applied over-the-top post-transplant. In addition, field trials were conducted with stevia grown in a polyethylene mulch production system to determine crop response and weed control in planting holes to reduced-risk synthetic and nonsynthetic herbicides applied post-transplant directed. Treatments included caprylic acid plus capric acid, clove oil plus cinnamon oil, d-limonene, acetic acid (200 grain), citric acid, pelargonic acid, eugenol, ammonium nonanoate, and ammoniated soap of fatty acids. Stevia yield (dry aboveground biomass) in the greenhouse was reduced by all herbicide treatments. Citric acid and clove oil plus cinnamon oil were the least injurious, reducing yield by 16% to 20%, respectively. In field studies, d-limonene, pelargonic acid, ammonium nonanoate, and ammoniated soap of fatty acids controlled Palmer amaranth (>90% 1 wk after treatment (WAT). In field studies caprylic acid plus capric acid, pelargonic acid, and ammonium nonanoate caused >30% injury to stevia plants at 2 WAT, and d-limonene, citric acid, acetic acid, and ammoniated soap of fatty acids caused 18% to 25% injury 2 WAT. Clove oil plus cinnamon oil and eugenol caused <10% injury. Despite being injurious, herbicides applied in the field did not reduce yield compared to the nontreated check. Based upon yield data, these herbicides have potential for use in stevia; however, these products could delay harvest if applied to established stevia. In particular, clove oil plus cinnamon oil has potential for use for early-season weed management for organic production systems. The application of clove oil plus cinnamon oil over-the-top resulted in <10% injury 28 d after treatment (DAT) in the greenhouse and 3% injury 6 WAT postemergence-directed in the field. In addition, this treatment provided 95% control of Palmer amaranth 4 WAT.
OBJECTIVES/GOALS: Irritability, a proneness to anger and frustration, is a transdiagnostic symptom associated with poor mental health outcomes. Levels of irritability vary across development and high-risk trajectories have been observed. This study aims to use machine learning to predict irritability trajectories across the transition to adolescence. METHODS/STUDY POPULATION: Data were from the Adolescent Brain Cognitive Development (ABCD) Study, which is a 10-year longitudinal study that tracks the brain development, cognitive skills, physical health, and psychosocial functioning of a large, national sample starting from preadolescence. The baseline sample consisted of 11,861 9-10-year-old preadolescent youth. Irritability was parent-rated at baseline, 1-year, 2-year, 3-year, and 4-year follow-ups on the Child Behavior Checklist (CBCL) irritability index. Latent class growth analysis (LCGA) was used to determine developmental trajectories of irritability. Two machine learning approaches were applied to develop predictive models of youth irritability developmental trajectories. We used baseline (preadolescent) variables that spanned a wide range of domains. RESULTS/ANTICIPATED RESULTS: Preliminary results fromthe LCGA indicated best support for a four-class model that differentiated growth trajectories in irritability across the transition to adolescence: 1) persistent low irritability (n = 8691, 73.27%), 2) moderate irritability and decreasing (n = 1257, 10.60%), 3) low to moderate irritability and increasing (n = 1295, 10.92%), and 4) chronic high irritability (n = 618, 5.21%). We expect the machine learning analyses to generate predictive models with acceptable accuracy. We hypothesize that the most important predictors in the models will originate from the youth mental health domain, including baseline youth irritability, externalizing symptoms, internalizing symptoms, and oppositional behaviors, and the parent psychopathology domain, particularly parent irritability. DISCUSSION/SIGNIFICANCE: The present study elucidates unique developmental trajectories of irritability and generates predictive models to classify high-risk irritability trajectories using machine learning approaches. Clinicians can use these predictive models to identify at-risk youth and provide early intervention to preadolescents at high risk.
OBJECTIVES/GOALS: To introduce the new Team Science Community Toolkit, co-created by community and academic partners, and showcase its potential to empower Community Organizations (COs) in achieving equity in community-engaged research (CER). METHODS/STUDY POPULATION: In response to the challenges faced by COs in CER collaborations, qualitative interviews were conducted with CO staff from historically marginalized communities. These interviews informed the development of the Team Science Community Toolkit, a collaborative effort involving a Community Advisory Board (CAB) and Team Science experts from Northwestern University. The toolkit, designed using a community-based participatory research approach, incorporates the Science of Team Science and User-Centered Design principles. Integrated into the NIH-sponsored COALESCE website, it includes templates, checklists, and interactive tools, along with a real-world simulation, to support COs in all stages of the research process. RESULTS/ANTICIPATED RESULTS: Focus groups and usability testing involving external community experts validated the toolkit’s content and usability. Participants expressed enthusiasm and a sense of empowerment, indicating that the toolkit allows them to actively shape research processes and infuse their specific voices and needs into their partnerships. The toolkit is designed to support breaking down barriers like jargon and cultural adaptability to improve accessibility and open conversation. The impact of this Team Science focused toolkit is under evaluation. This presentation will showcase the toolkit, detail its collaborative development, and explore potential applications, ultimately offering a path to more equitable and valuable community-based research. DISCUSSION/SIGNIFICANCE: By providing COs with the resources and knowledge to participate as equal partners in research collaborations, it enhances self-advocacy, transparency, and equity. The toolkit has the potential to utilize Team Science to foster productive communication in community-academic research partnerships.
Let $X$ be a smooth geometrically connected projective curve over the field of fractions of a discrete valuation ring $R$, and $\mathfrak {m}$ a modulus on $X$, given by a closed subscheme of $X$ which is geometrically reduced. The generalized Jacobian $J_\mathfrak {m}$ of $X$ with respect to $\mathfrak {m}$ is then an extension of the Jacobian of $X$ by a torus. We describe its Néron model, together with the character and component groups of the special fibre, in terms of a regular model of $X$ over $R$. This generalizes Raynaud's well-known description for the usual Jacobian. We also give some computations for generalized Jacobians of modular curves $X_0(N)$ with moduli supported on the cusps.
There are two kinds of time bias: near bias and future bias. While philosophers typically hold that near bias is rationally impermissible, many hold that future bias is rationally permissible. Call this normative hybridism. According to arbitrariness objections, certain patterns of preference are rationally impermissible because they are arbitrary. While arbitrariness objections have been leveled against both near bias and future bias, the kind of arbitrariness in question has been different. In this article we investigate whether there are forms of arbitrariness that are common to both kinds of preferences and, hence, whether there are versions of the arbitrariness objection that are objections to both near bias and future bias. If there are, then this might go some way toward undermining normative hybridism and to defending thoroughgoing time-neutralism.