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The magnetic resonance imaging (MRI) Core has been operating since Alzheimer's Disease Neuroimaging Initiative's (ADNI) inception, providing 20 years of data including reliable, multi-platform standardized protocols, carefully curated image data, and quantitative measures provided by expert investigators. The overarching purposes of the MRI Core include: (1) optimizing and standardizing MRI acquisition methods, which have been adopted by many multicenter studies and trials worldwide and (2) providing curated images and numeric summary values from relevant MRI sequences/contrasts to the scientific community. Over time, ADNI MRI has become increasingly complex. To remain technically current, the ADNI MRI protocol has changed substantially over the past two decades. The ADNI 4 protocol contains nine different imaging types (e.g., three dimensional [3D] T1-weighted and fluid-attenuated inversion recovery [FLAIR]). Our view is that the ADNI MRI data are a greatly underutilized resource. The purpose of this paper is to educate the scientific community on ADNI MRI methods and content to promote greater awareness, accessibility, and use. HIGHLIGHTS: The MRI Core provides multi-platform standardized protocols, carefully curated image data, and quantitative analysis by expert groups. The ADNI MRI protocol has undergone major changes over the past two decades to remain technically current. As of April 25, 2024, the following numbers of image series are available: 17,141 3D T1w; 6877 FLAIR; 3140 T2/PD; 6623 GRE; 3237 dMRI; 2846 ASL; 2968 TF-fMRI; and 2861 HighResHippo (see Table 1 for abbreviations). As of April 25, 2024, the following numbers of quantitative analyses are available: FreeSurfer 10,997; BSI 6120; tensor based morphometry (TBM) and TBM-SYN 12,019; WMH 9944; dMRI 1913; ASL 925; TF-fMRI NFQ 2992; and medial temporal subregion volumes 2726 (see Table 4 for abbreviations). ADNI MRI is an underutilized resource that could be more useful to the research community.

Structural neuroimaging data have been used to compute an estimate of the biological age of the brain (brain-age) which has been associated with other biologically and behaviorally meaningful measures of brain development and aging. The ongoing research interest in brain-age has highlighted the need for robust and publicly available brain-age models pre-trained on data from large samples of healthy individuals. To address this need we have previously released a developmental brain-age model. Here we expand this work to develop, empirically validate, and disseminate a pre-trained brain-age model to cover most of the human lifespan. To achieve this, we selected the best-performing model after systematically examining the impact of seven site harmonization strategies, age range, and sample size on brain-age prediction in a discovery sample of brain morphometric measures from 35,683 healthy individuals (age range: 5-90 years; 53.59% female). The pre-trained models were tested for cross-dataset generalizability in an independent sample comprising 2101 healthy individuals (age range: 8-80 years; 55.35% female) and for longitudinal consistency in a further sample comprising 377 healthy individuals (age range: 9-25 years; 49.87% female). This empirical examination yielded the following findings: (1) the accuracy of age prediction from morphometry data was higher when no site harmonization was applied; (2) dividing the discovery sample into two age-bins (5-40 and 40-90 years) provided a better balance between model accuracy and explained age variance than other alternatives; (3) model accuracy for brain-age prediction plateaued at a sample size exceeding 1600 participants. These findings have been incorporated into CentileBrain (https://centilebrain.org/#/brainAGE2), an open-science, web-based platform for individualized neuroimaging metrics.

Chitin is an abundant biopolymer and pathogen-associated molecular pattern that stimulates a host innate immune response. Mammals express chitin-binding and chitin-degrading proteins to remove chitin from the body. One of these proteins, Acidic Mammalian Chitinase (AMCase), is an enzyme known for its ability to function under acidic conditions in the stomach but is also active in tissues with more neutral pHs, such as the lung. Here, we used a combination of biochemical, structural, and computational modeling approaches to examine how the mouse homolog (mAMCase) can act in both acidic and neutral environments. We measured kinetic properties of mAMCase activity across a broad pH range, quantifying its unusual dual activity optima at pH 2 and 7. We also solved high-resolution crystal structures of mAMCase in complex with oligomeric GlcNAcn, the building block of chitin, where we identified extensive conformational ligand heterogeneity. Leveraging these data, we conducted molecular dynamics simulations that suggest how a key catalytic residue could be protonated via distinct mechanisms in each of the two environmental pH ranges. These results integrate structural, biochemical, and computational approaches to deliver a more complete understanding of the catalytic mechanism governing mAMCase activity at different pH. Engineering proteins with tunable pH optima may provide new opportunities to develop improved enzyme variants, including AMCase, for therapeutic purposes in chitin degradation.

Abstract Background Despite suicide’s public health significance and global mental health awareness, current suicide prevention efforts show limited impact, posing a challenge for low- and middle-income countries. This study aimed to develop a dynamic simulation model that could be used to examine the potential effectiveness of alternative interventions for reducing youth mental health problems and suicidal behavior in Bogotá, Colombia. Methods A system dynamics model was designed using a participatory approach involving three workshops conducted in 2021 and 2022. These workshops engaged 78 stakeholders from various health and social sectors to map key mental health outcomes and influential factors affecting them. A model was subsequently developed, tested, and presented to the participants for interactive feedback, guided by a moderator. Simulation analyses were conducted to compare projected mental health outcomes for a range of intervention scenarios with projections for a reference scenario corresponding to business-as-usual. Results A total of 6670 suicide attempts and 347 suicides are projected among 7 − 17-year-olds from January 1, 2023, to early 2031 under the business-as-usual scenario. Mental health issues among 12 − 17-year-olds are projected to increase from 18.9% (2023) to 27.8% (2031), and substance use issues from 2.29 to 2.49% over the same period. School-based suicide prevention and gatekeeper training are the most effective strategies, reducing total numbers of suicide attempts and suicides by more than 20% (i.e., compared to business-as-usual). However, discontinuous funding significantly hinders these effective suicide prevention efforts. Conclusions Systems modelling is an important tool for understanding where the best strategic financial and political investments lie for improving youth mental health in resource-constrained settings.

Abstract Background Emergency departments (EDs) are often the front door for urgent mental health care, especially when demand exceeds capacity. Long waits in EDs exert strain on hospital resources and worsen distress for individuals experiencing a mental health crisis. We used as a test case the Australian Capital Territory (ACT), with a population surge of over 27% across 2011–2021 and a lagging increase in mental health care capacity, to evaluate population-based approaches to reduce mental health-related ED presentations. Methods We developed a system dynamics model for the ACT region using a participatory approach involving local stakeholders, including health planners, health providers and young people with lived experience of mental health disorders. Outcomes were projected over 2023–2032 for youth (aged 15–24) and for the general population. Results Improving the overall mental health care system through strategies such as doubling the annual capacity growth rate of mental health services or leveraging digital technologies for triage and care coordination is projected to decrease youth mental health-related ED visits by 4.3% and 4.8% respectively. Implementation of mobile crisis response teams (consisting of a mental health nurse accompanying police or ambulance officers) is projected to reduce youth mental health-related ED visits by 10.2% by de-escalating some emergency situations and directly transferring selected individuals to community mental health centres. Other effective interventions include limiting re-presentations to ED by screening for suicide risk and following up with calls post-discharge (6.4% reduction), and limiting presentations of frequent users of ED by providing psychosocial education to families of people with schizophrenia (5.1% reduction). Finally, combining these five approaches is projected to reduce youth mental health-related ED presentations by 26.6% by the end of 2032. Conclusions Policies to decrease youth mental health-related ED presentations should not be limited to increasing mental health care capacity, but also include structural reforms.

Despite increased advocacy and investments in mental health systems globally, there has been limited progress in reducing mental disorder prevalence. In this paper, we argue that meaningful advancements in population mental health necessitate addressing the fundamental sources of shared distress. Using a systems perspective, economic structures and policies are identified as the potential cause of causes of mental ill-health. Neoliberal ideologies, prioritizing economic optimization and continuous growth, contribute to the promotion of individualism, job insecurity, increasing demands on workers, parental stress, social disconnection and a broad range of manifestations well-recognized to erode mental health. We emphasize the need for mental health researchers and advocates to increasingly engage with the economic policy discourse to draw attention to mental health and well-being implications. We call for a shift towards a well-being economy to better align commercial interests with collective well-being and social prosperity. The involvement of individuals with lived mental ill-health experiences, practitioners and researchers is needed to mobilize communities for change and influence economic policies to safeguard well-being. Additionally, we call for the establishment of national mental wealth observatories to inform coordinated health, social and economic policies and realize the transition to a more sustainable well-being economy that offers promise for progress on population mental health outcomes. [phrase omitted] Malgre une meilleure sensibilisation et des investissements accrus dans A pesar del aumento de la promocion y las inversiones en sistemas de salud mental en todo el mundo, los avances en la reduccion de la prevalencia de los trastornos mentales han sido limitados. En este documento, sostenemos que para lograr avances significativos en la salud mental de la poblacion es necesario abordar las fuentes fundamentales de la angustia compartida. Mediante una perspectiva sistemica, las estructuras y politicas economicas se identifican como la posible causa de los problemas de salud mental. Las ideologias neoliberales, que priorizan la optimizacion economica y el crecimiento continuo, contribuyen al fomento del individualismo, la inseguridad laboral, el aumento de las exigencias a los trabajadores, el estres parental, la desconexion social y una gran variedad de manifestaciones bien reconocidas que perjudican la salud mental. Insistimos en la necesidad de que los investigadores y los defensores de la salud mental se impliquen cada vez mas en el discurso de la politica economica para atraer la atencion sobre las implicaciones para la salud mental y el bienestar. Pedimos un cambio hacia una economia del bienestar para alinear mejor los intereses comerciales con el bienestar colectivo y la prosperidad social. Para movilizar a las comunidades en favor del cambio e influir en las politicas economicas con el fin de salvaguardar el bienestar, es necesaria la participacion de personas que han padecido enfermedades mentales, profesionales e investigadores. Ademas, pedimos la creacion de observatorios nacionales de bienestar mental que sirvan de base a las politicas sanitarias, sociales y economicas coordinadas y permitan la transicion a una economia del bienestar mas sostenible, que ofrezca perspectivas de progreso en los resultados de salud mental de la poblacion. [phrase omitted] A pesar del aumento de la promocion y las inversiones en sistemas de salud mental en todo el mundo, los avances en la reduccion de la prevalencia de los trastornos mentales han sido limitados. En este documento, sostenemos que para lograr avances significativos en la salud mental de la poblacion es necesario abordar las fuentes fundamentales de la angustia compartida. Mediante una perspectiva sistemica, las estructuras y politicas economicas se identifican como la posible causa de los problemas de salud mental. Las ideologias neoliberales, que priorizan la optimizacion economica y el crecimiento continuo, contribuyen al fomento del individualismo, la inseguridad laboral, el aumento de las exigencias a los trabajadores, el estres parental, la desconexion social y una gran variedad de manifestaciones bien reconocidas que perjudican la salud mental. Insistimos en la necesidad de que los investigadores y los defensores de la salud mental se impliquen cada vez mas en el discurso de la politica economica para atraer la atencion sobre las implicaciones para la salud mental y el bienestar. Pedimos un cambio hacia una economia del bienestar para alinear mejor los intereses comerciales con el bienestar colectivo y la prosperidad social. Para movilizar a las comunidades en favor del cambio e influir en las politicas economicas con el fin de salvaguardar el bienestar, es necesaria la participacion de personas que han padecido enfermedades mentales, profesionales e investigadores. Ademas, pedimos la creacion de observatorios nacionales de bienestar mental que sirvan de base a las politicas sanitarias, sociales y economicas coordinadas y permitan la transicion a una economia del bienestar mas sostenible, que ofrezca perspectivas de progreso en los resultados de salud mental de la poblacion., Introduction Mental health systems are under-resourced, fragmented, inefficient and unable to meet the demands of the growing burden of mental and substance use disorders. Despite the intensive advocacy and action [...]

Abstract The kidney tubules constitute two-thirds of the cells of the kidney and account for the majority of the organ’s metabolic energy expenditure. Acute tubular injury (ATI) is observed across various types of kidney diseases and may significantly contribute to progression to kidney failure. Non-invasive biomarkers of ATI may allow for early detection and drug development. Using the SomaScan proteomics platform on 434 patients with biopsy-confirmed kidney disease, we here identify plasma biomarkers associated with ATI severity. We employ regional transcriptomics and proteomics, single-cell RNA sequencing, and pathway analysis to explore biomarker protein and gene expression and enriched biological pathways. Additionally, we examine ATI biomarker associations with acute kidney injury (AKI) in the Kidney Precision Medicine Project (KPMP) (n = 44), the Atherosclerosis Risk in Communities (ARIC) study (n = 4610), and the COVID-19 Host Response and Clinical Outcomes (CHROME) study (n = 268). Our findings indicate 156 plasma proteins significantly linked to ATI with osteopontin, macrophage mannose receptor 1, and tenascin C showing the strongest associations. Pathway analysis highlight immune regulation and organelle stress responses in ATI pathogenesis.

Abstract Preeclampsia, a pregnancy complication characterized by hypertension after 20 gestational weeks, is a major cause of maternal and neonatal morbidity and mortality. Mechanisms leading to preeclampsia are unclear; however, there is evidence of high heritability. We evaluated the association of polygenic scores (PGS) for blood pressure traits and preeclampsia to assess whether there is shared genetic architecture. Non-Hispanic Black and White reproductive age females with pregnancy indications and genotypes were obtained from Vanderbilt University’s BioVU, Electronic Medical Records and Genomics network, and Penn Medicine Biobank. Preeclampsia was defined by ICD codes. Summary statistics for diastolic blood pressure (DBP), systolic blood pressure (SBP), and pulse pressure (PP) PGS were acquired from Giri et al. Associations between preeclampsia and each PGS were evaluated separately by race and data source before subsequent meta-analysis. Ten-fold cross validation was used for prediction modeling. In 3504 Black and 5009 White included individuals, the rate of preeclampsia was 15.49%. In cross-ancestry meta-analysis, all PGSs were associated with preeclampsia (ORDBP = 1.10, 95% CI 1.02–1.17, p = 7.68 × 10−3; ORSBP = 1.16, 95% CI 1.09–1.23, p = 2.23 × 10−6; ORPP = 1.14, 95% CI 1.07–1.27, p = 9.86 × 10−5). Addition of PGSs to clinical prediction models did not improve predictive performance. Genetic factors contributing to blood pressure regulation in the general population also predispose to preeclampsia.

Abstract Mental fitness is a construct that goes beyond a simple focus on subjective emotional wellbeing to encompass more broadly our ability to think, feel, and act to achieve what we want in our daily lives. The measurement and monitoring of multiple (often interacting) domains is crucial to gain a holistic and complete insight into an individual’s mental fitness. We aimed to demonstrate the capability of a new mobile app to characterise the mental fitness of a general population of Australians and to quantify the interrelationships among different domains of mental fitness. Cross-sectional data were collected from 4901 adults from the general population of Australians engaged in work or education who used a mobile app (Innowell) between September 2021 and November 2022. Individuals completed a baseline questionnaire comprised of 26 questions across seven domains of mental fitness (i.e., physical activity, sleep and circadian rhythms, nutrition, substance use, daily activities, social connection, psychological distress). Network analysis was applied at both a domain-level (e.g., 7 nodes representing each cluster of items) and an individual item-level (i.e., 26 nodes representing all questionnaire items). Only 612 people (12%) were functioning well across all domains. One quarter (n = 1204, 25%) had only one problem domain and most (n = 3085, 63%) had multiple problem domains. The two most problematic domains were physical activity (n = 2631, 54%) and social connection (n = 2151, 44%), followed closely by daily activity (n = 1914, 39%). At the domain-level, the strongest association emerged between psychological distress and daily activity (r = 0.301). Psychological distress was the most central node in the network (as measured by strength and expected influence), followed closely by daily activity, sleep and circadian rhythms and then social connection. The item-level network revealed that the nodes with the highest centrality in the network were: hopelessness, depression, functional impairment, effortfulness, subjective energy, worthlessness, and social connectedness. Social connection, sleep and circadian rhythms, and daily activities may be critical targets for intervention due to their widespread associations in the overall network. While psychological distress was not among the most common problems, its centrality may indicate its importance for indicated prevention and early intervention. We showcase the capability of a new mobile app to monitor mental fitness and identify the interrelationships among multiple domains, which may help people develop more personalised insights and approaches.

Abstract There has recently been an increase in ongoing patient-report routine outcome monitoring for individuals within clinical care, which has corresponded to increased longitudinal information about an individual. However, many models that are aimed at clinical practice have difficulty fully incorporating this information. This is in part due to the difficulty in dealing with the irregularly time-spaced observations that are common in clinical data. Consequently, we built individual-level continuous-time trajectory models of suicidal ideation for a clinical population (N = 585) with data collected via a digital platform. We demonstrate how such models predict an individual’s level and variability of future suicide ideation, with implications for the frequency that individuals may need to be observed. These individual-level predictions provide a more personalised understanding than other predictive methods and have implications for enhanced measurement-based care.

AbstractDespite the efficacy of digital mental health technologies (DMHTs) in clinical trials, low uptake and poor engagement are common in real-world settings. Accordingly, digital technology experts or “digital navigators” are increasingly being used to enhance engagement and shared decision-making between health professionals and clients. However, this area is relatively underexplored and there is a lack of data from naturalistic settings. In this paper, we report observational findings from the implementation of a digital navigator in a multidisciplinary mental health clinic in Sydney, Australia. The digital navigator supported clients and health professionals to use a measurement-based DMHT (the Innowell platform) for improved multidimensional outcome assessment and to guide personalized decision-making. Observational data are reported from implementation logs, platform usage statistics, and response rates to digital navigator emails and phone calls. Ultimately, support from the digital navigator led to improved data collection and clearer communications about goals for using the DMHT to track client outcomes; however, this required strong partnerships between health professionals, the digital navigator, and clients. The digital navigator helped to facilitate the integration of DMHT into care, rather than providing a stand-alone service. Thus, collaborations between health professionals and digital navigators are mutually beneficial and empower clients to be more engaged in their own care.

Given the rapid development of digital mental health technologies and a focus on connecting with youth, there is an urgent need to enhance the engagement of young people with lived expertise in research. Even so, youth with lived experience of accessing mental health services are particularly affected by power imbalances and may receive limited compensation in academic settings. Therefore, an emphasis on how research engagement not only improves the work but can benefit young people themselves is required. Here, 5 young people with lived expertise report on their experience of being employed as researchers at the University of Sydney’s Brain and Mind Centre. As such, this team is uniquely placed to offer reflections from their work across multiple stages of research. This led to four key insights, including (1) creating accepting work cultures, (2) providing diverse opportunities for involvement, (3) giving young people agency and flexibility around sharing lived experiences, and (4) creating accommodating work environments for all researchers. We suggest that these insights can support more diverse ways of engaging young people and maximizing the value of participation for both researchers and young people themselves.

Background The COVID-19 pandemic, while a major stressor, increased flexibility in sleep–wake schedules.Objectives To investigate the impact of the pandemic on sleep patterns in people with a history of depression and identify sociodemographic, clinical or genetic predictors of those impacts.Methods 6453 adults from the Australian Genetics of Depression Study (45±15 years; 75% women) completed surveys before (2016–2018) and during the pandemic (2020–2021). Participants were assigned to ‘short sleep’ (8 hours). We focused on those having prepandemic ‘optimal sleep’.Findings Pre pandemic, the majority (70%, n=4514) reported optimal sleep, decreasing to 49% (n=3189) during the pandemic. Of these, 57% maintained optimal sleep, while 16% (n=725) shifted to ‘short sleep’ and 27% (n=1225) to ‘long sleep’. In group comparisons ‘optimal-to-short sleep’ group had worse prepandemic mental health and increased insomnia (p’s

Introduction: Esketamine has been approved in Australia and New Zealand as a third-line antidepressant treatment for treatment resistant depression. This study describes changes in quality of life, depressive symptoms and productivity in participants treated with esketamine in real-world settings. Methods: Participants were recruited from an esketamine early access program and had not responded to two or more different antidepressants and not received neurostimulation for their current depressive episode. Participants received esketamine for 16 weeks or longer. Data collected included Assessment of Quality-of-Life scale (AQoL-8D), Hamilton Depression Rating Scale (HAM-D) and Work Productivity Activity Index (WPAI). Results: Participants (n = 105) had a mean age of 38.7 years (standard deviation (SD) = 14.6) and were predominantly female (59.0%). The mean duration of major depressive disorder was 7.2 years (SD = 4.2) and almost half of participants had been treated with 3–5 prior therapies. After 16-weeks on esketamine, participants showed improvement of greater than 10% across all dimensions of AQoL-8D, HAM-D scores decreased 8.0 points, and activity impairment decreased 20.4% as measured by WPAI. Limitations: This was a non-randomized and unblinded study and may have selection and reporting bias. The population was not necessarily representative of the broader Australian and New Zealand population. It is not possible to determine if the results will be sustained or changed if participants received treatment for longer. Conclusions: Esketamine early access program participants, who were a real-world cohort with extensive prior treatment, showed clinically significant improvements in quality of life, depression severity and productivity after 16-weeks on treatment.