Publications by authors named "Lupton M"

Alzheimer's disease (AD) brain markers are needed to select people with early-stage AD for clinical trials and as quantitative endpoint measures in trials. Using 10 clinical cohorts (N = 9140) and the community volunteer UK Biobank (N = 37,664) we performed region of interest (ROI) and vertex-wise analyses of grey-matter structure (thickness, surface area and volume). We identified 94 trait-ROI significant associations, and 307 distinct cluster of vertex-associations, which partly overlap the ROI associations.

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Deficits in memory are seen as a canonical sign of aging and a prodrome to dementia in older adults. However, our understanding of age-related cognition and brain morphology occurring throughout a broader spectrum of adulthood remains limited. We quantified the relationship between cognitive function and brain morphology (sulcal width, SW) using three cross-sectional observational datasets (PISA, AIBL, ADNI) from mid-life to older adulthood, assessing the influence of age, sex, amyloid (Aβ) and genetic risk for dementia.

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Clinical identification of early neurodegenerative changes requires an accurate and accessible characterization of brain and cognition in healthy aging. We assessed whether a brief online cognitive assessment can provide insights into brain morphology comparable to a comprehensive neuropsychological battery. In 141 healthy mid-life and older adults, we compared Creyos, a relatively brief online cognitive battery, to a comprehensive in person cognitive assessment.

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Study Objectives: Evidence suggests that poor sleep impacts cognition, brain health, and dementia risk but the nature of the association is poorly understood. This study examined how self-reported sleep duration, napping, and subjective depression symptoms are associated with the brain-cognition relationship in older adults, using sulcal width as a measure of relative brain health.

Methods: A canonical partial least squares analysis was used to obtain two composite variables that relate cognition and sulcal width in a cross-sectional study of 137 adults aged 46-72.

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  • * A genome-wide association meta-analysis of nearly 122,000 ANX cases revealed 58 significant genetic variants and 66 related genes, with many of these findings replicated in a larger independent sample.
  • * The findings indicate a substantial genetic overlap between ANX and other conditions like depression, emphasizing GABAergic signaling as a key mechanism, thereby enhancing our understanding of the genetic basis of ANX for future research.
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  • PTSD genetics have been difficult to study compared to other psychiatric disorders, limiting our biological understanding of the condition.
  • A large-scale meta-analysis involving over 1.2 million individuals identified 95 genome-wide significant loci, with 80 being new discoveries related to PTSD.
  • Researchers identified 43 potential causal genes linked to neurotransmitter activity, developmental processes, synaptic function, and immune regulation, enhancing our knowledge of the neurobiological systems involved in PTSD.
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Background: Alzheimer's disease (AD) is an incurable neurodegenerative disorder with a rapidly increasing prevalence worldwide. Current approaches targeting hallmark pathological features of AD have had no consistent clinical benefit. Neuroinflammation is a major contributor to neurodegeneration and hence, microglia, the brain's resident immune cells, are an attractive target for potentially more effective therapeutic strategies.

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  • PTSD genetics are harder to study compared to other mental health disorders, resulting in limited biological insights from past research.
  • A large-scale analysis involving over 1.2 million individuals found 95 significant genetic loci related to PTSD, with 80 being new discoveries.
  • The study identified 43 potential causal genes linked to neurotransmitters, synaptic function, and immune responses, enhancing understanding of PTSD's biological mechanisms and suggesting new research directions.
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The recruitment of participants for research studies may be subject to bias. The Prospective Imaging Study of Ageing (PISA) aims to characterize the phenotype and natural history of healthy adult Australians at high future risk of Alzheimer's disease (AD). Participants approached to take part in PISA were selected from existing cohort studies with available genomewide genetic data for both successfully and unsuccessfully recruited participants, allowing us to investigate the genetic contribution to voluntary recruitment, including the genetic predisposition to AD.

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  • Primary open-angle glaucoma (POAG) is an optic nerve disease linked to vision loss and shows associations with major neurodegenerative disorders like Alzheimer's and Parkinson's, but their relationship is still unclear.
  • The study utilized genome-wide data to examine the genetic connections between POAG and these neurodegenerative diseases, discovering overlaps in genetic traits and brain morphology but lacking definitive causal links.
  • Findings suggest that while there are shared genetic factors between POAG and neurodegenerative conditions, these are likely part of independent neurodegenerative processes rather than direct causal relationships.
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  • The study aimed to assess knowledge attainment, enjoyment, and engagement among third-year medical students through three different online teaching methods: clinical case vignettes, patient-testimony videos, and mixed reality (MR) using Microsoft HoloLens 2.
  • 252 students participated, with performances in knowledge attainment being similar across all three methods, but case vignettes were reported as the most enjoyable and engaging.
  • The findings suggest that while MR is a feasible and effective teaching method, students preferred traditional case-based tutorials for their learning experience.
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Importance: Physical health and chronic medical comorbidities are underestimated, inadequately treated, and often overlooked in psychiatry. A multiorgan, systemwide characterization of brain and body health in neuropsychiatric disorders may enable systematic evaluation of brain-body health status in patients and potentially identify new therapeutic targets.

Objective: To evaluate the health status of the brain and 7 body systems across common neuropsychiatric disorders.

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When asked to judge the duration of a face people typically overestimate the duration of angry compared with neutral faces. A novel feature of the current research was the inclusion of secondary manipulations designed to distort timing performance namely the effects of visual cues (Experiment 1) and action preparedness (Experiment 2). Furthermore, to establish whether the effects are multiplicative with duration, the effects were examined across two duration ranges (200-800 and 400-1,600 ms).

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The functional organization of the hippocampus mirrors that of the cortex, changing smoothly along connectivity gradients and abruptly at inter-areal boundaries. Hippocampal-dependent cognitive processes require flexible integration of these hippocampal gradients into functionally related cortical networks. To understand the cognitive relevance of this functional embedding, we acquired fMRI data while participants viewed brief news clips, either containing or lacking recently familiarized cues.

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Samples can be prone to ascertainment and attrition biases. The Australian Genetics of Depression Study is a large publicly recruited cohort (n = 20,689) established to increase the understanding of depression and antidepressant treatment response. This study investigates differences between participants who donated a saliva sample or agreed to linkage of their records compared to those who did not.

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Despite the substantial heritability of antisocial behavior (ASB), specific genetic variants robustly associated with the trait have not been identified. The present study by the Broad Antisocial Behavior Consortium (BroadABC) meta-analyzed data from 28 discovery samples (N = 85,359) and five independent replication samples (N = 8058) with genotypic data and broad measures of ASB. We identified the first significant genetic associations with broad ASB, involving common intronic variants in the forkhead box protein P2 (FOXP2) gene (lead SNP rs12536335, p = 6.

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  • - Alzheimer's disease is projected to impact 132 million individuals by 2050, highlighting a need to address lifestyle factors that may help prevent cases of dementia altogether.
  • - This study investigates the causal relationships between modifiable lifestyle risk factors, specifically educational attainment, intelligence, and household income, and their connection to Alzheimer's susceptibility using genetic data.
  • - The findings suggest that only intelligence, a component of educational attainment, has a distinct causal link to Alzheimer's, emphasizing the importance of cognitive factors in understanding and potentially mitigating AD risk.
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Background: Health professions education has undergone major changes with the advent and adoption of digital technologies worldwide.

Objective: This study aims to map the existing evidence and identify gaps and research priorities to enable robust and relevant research in digital health professions education.

Methods: We searched for systematic reviews on the digital education of practicing and student health care professionals.

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Background: Amyotrophic lateral sclerosis (ALS) is a multifactorial neurodegenerative disease characterised by the loss of upper and lower motor neurons. Increasing evidence indicates that neuroinflammation mediated by microglia contributes to ALS pathogenesis. This microglial activation is evident in post-mortem brain tissues and neuroimaging data from patients with ALS.

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  • * A genome-wide association study (GWAS) examined over 20,000 individuals and discovered 29 new genetic locations linked to acne, alongside confirming 14 previously recognized risk factors, raising the total to 46.
  • * The study also found connections between acne genetics and other health issues, such as hormone levels and psychiatric traits, and created a polygenic risk score that accounts for about 5.6% of acne risk in another group.
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We test whether genetic influences that explain individual differences in aggression in early life also explain individual differences across the life-course. In two cohorts from The Netherlands (N = 13,471) and Australia (N = 5628), polygenic scores (PGSs) were computed based on a genome-wide meta-analysis of childhood/adolescence aggression. In a novel analytic approach, we ran a mixed effects model for each age (Netherlands: 12-70 years, Australia: 16-73 years), with observations at the focus age weighted as 1, and decaying weights for ages further away.

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The bidirectional relationship between depression and chronic pain is well-recognized, but their clinical management remains challenging. Here we characterize the shared risk factors and outcomes for their comorbidity in the Australian Genetics of Depression cohort study ( = 13,839). Participants completed online questionnaires about chronic pain, psychiatric symptoms, comorbidities, treatment response and general health.

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  • Primary open-angle glaucoma (POAG) is a heritable eye condition leading to blindness and the study involved a large genetic analysis of over 34,000 patients and nearly 350,000 controls from different ethnic backgrounds.
  • Researchers identified 44 new genetic risk factors for POAG and confirmed 83 previously known ones, finding consistent impacts across various ancestries.
  • The study also suggests that certain genes could play significant roles in the disease's development, indicating potential new drug treatments targeting these genetic risk factors.
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Sarcastic speech is ubiquitous in most languages, though understanding sarcasm is highly dependent upon cultural and social contextual factors (Campbell & Katz, Discourse Processes, 2012, 49, 459). It is therefore surprising that little research has examined the ability of nonnative speakers to understand the sarcastic cues of a second language. In the current study, native English speakers and English as a second language (ESL) speakers were tested in each of four different conditions.

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This prospective cohort study, "Prospective Imaging Study of Ageing: Genes, Brain and Behaviour" (PISA) seeks to characterise the phenotype and natural history of healthy adult Australians at high future risk of Alzheimer's disease (AD). In particular, we are recruiting midlife and older Australians with high and low genetic risk of dementia to discover biological markers of early neuropathology, identify modifiable risk factors, and establish the very earliest phenotypic and neuronal signs of disease onset. PISA utilises genetic prediction to recruit and enrich a prospective cohort and follow them longitudinally.

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