Predisposition Footprints in the Somatic Genome of Wilms tumour

Publication: Cancer Discovery

Approximately 10% of children with cancer harbor a mutation in a predisposition gene. In children with the kidney cancer Wilms tumor, the prevalence is as high as 30%. Certain predispositions are associated with defined histological and clinical features, suggesting differences in tumorigenesis. To investigate this, we assembled a cohort of 137 children with Wilms tumor, of whom 71 had a pathogenic germline or mosaic variant. We examined 237 neoplasms (including two secondary leukemias), utilizing whole-genome sequencing, RNA sequencing, and genome-wide methylation, validating our findings in an independent cohort. Tumor development differed in children harboring a predisposition, depending on the variant gene and its developmental timing. Differences pervaded the repertoire of driver events, including high-risk mutations, the clonal architecture of normal kidneys, and the relatedness of neoplasms from the same individual. Our findings indicate that predisposition may preordain Wilms tumorigenesis, suggesting a variant-specific approach to managing children merits consideration. Significance: Tumors that arise in children with a cancer predisposition may develop through the same mutational pathways as sporadic tumors. We examined this question in the childhood kidney cancer, Wilms tumor. We found that certain predispositions dictate the genetic development of tumors, with clinical implications for these children.

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Deconstructing delay discounting in human cocaine addiction using computational modelling and neuroimaging

Publication: Biological Psychiatry: Cognitive Neuroscience and Neuroimaging

Michal M Graczyk, Rudolf N Cardinal, Tsen Vei Lim, Salvatore Nigro, Elijah Mak, Karen D Ersche

A preference for sooner-smaller over later-larger rewards, known as delay discounting, is a candidate transdiagnostic marker of waiting impulsivity and a research domain criterion. While abnormal discounting rates have been associated with many psychiatric diagnoses and abnormal brain structure, the underlying neuropsychological processes remain largely unknown. Here, we deconstruct delay discounting into choice and rate processes by testing different computational models and investigate their associations with white matter tracts.

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How sleep in patients with serious mental illness is recorded and treated, and its impact on service engagement

Aviva Stafford, Sheri Oduola, Sarah Reeve

Published online 10 September 2024


Highlights

  • Sleep is minimally documented in severe mental illness (SMI) patient records.
  • Recommended sleep interventions (e.g., CBT-I) are rarely delivered in SMI settings.
  • Further work is needed to improve sleep assessment and intervention in SMI settings.
  • Targeting sleep in SMI patients could significantly improve symptoms and wellbeing.

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Temporal trends in population attributable fractions of modifiable risk factors for dementia: a time-series study of the English Longitudinal Study of Ageing (2004–2019).

Publication: BMC Medicine

Chen S, Underwood BR, Cardinal RN, Chen X, Chen S, Amin J, Jin H, Mueller C, Yan LL, Brayne C, Kuper H

26 June 2024

Summary

This was an analysis of pre-existing data from the English Longitudinal Study of Ageing, examining changes over time in risk factors for dementia that have the potential to be altered (such as hypertension, obesity, hearing loss, and social isolation).

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Associations between rural/urban status, duration of untreated psychosis and mode of onset of psychosis: a mental health electronic clinical records analysis in the East of England, UK.

Publication: Social Psychiatry and Psychiatric Epidemiology

Kaminska J, Hodgekins J, Lewis JR, Cardinal RN, Oduola S

09 September 2024

Summary

This study examined de-identified NHS data about people having a first episode of psychosis, and looked at how the psychosis began (abruptly or slowly), how long it went untreated, and factors including rural or urban residence. Among such people, some factors differed between rural and urban settings, e.g. employment and living with family. A slow onset of psychosis was associated with a longer time untreated, but rural/urban differences in “time untreated” were not found.

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Robust and interpretable AI-guided marker for early dementia prediction in real-world clinical settings

Publication: eClinicaMedicine

Liz Yuanxi Lee j, Delshad Vaghari j, Michael C. Burkhart, Peter Tino, Marcella Montagnese, Zhuoyu Li,
Katharina Zühlsdorff, Joseph Giorgio, Guy Williams, Eddie Chong, Christopher Chen, Benjamin R. Underwood, Timothy Rittman, Zoe Kourtzi

12 July 2024

Summary

Cambridge researchers have developed an artificially-intelligent tool capable of predicting in four cases out of five whether people with early signs of dementia will remain stable or develop Alzheimer’s disease. Read the full press release.

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Predicting patients with dementia most at risk of needing psychiatric inpatient or enhanced community care using routinely collected clinical data: retrospective multi-site cohort study.

Publication: BJPsych

London SR, Chen S, Sidhom E, Lewis JR, Wolverson E, Cardinal RN, Roalf D, Mueller C, Underwood BR

13 May 2024

Summary

People diagnosed with dementia are often diagnosed in memory clinics and then discharged back to their GP. Some later need intensive mental health support (e.g. crisis teams, or inpatient admission) but others do not. This study shows that it’s possible to predict who will and who won’t, with useful accuracy, based on information collected routinely at the time of initial diagnosis.

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The role of psychosis and clozapine load in excessive checking in treatment-resistant schizophrenia: longitudinal observational study.

Publication: BJPsych

Emilio Fernandez-Egea, Shanquan Chen, Estela Sangüesa, Patricia Gassó, Marjan Biria, James Plaistow, Isaac Jarratt-Barnham, Nuria Segarra, Sergi Mas, Maria-Pilar Ribate, Cristina B García, Naomi A Fineberg, Yulia Worbe, Rudolf N Cardinal, Trevor W Robbins

Summary

This study looked at a group of people treated with clozapine for schizophrenia, examining obsessive-compulsive symptoms (OCS). For some, genetic variants were examined. OCS were common in this group (37.9%). Analysis suggested that both psychosis and clozapine may drive aspects of OCS.

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Cortical gene expression architecture links healthy neurodevelopment to the imaging, transcriptomics and genetics of autism and schizophrenia

Publication: Nature Neuroscience

Richard Dear, Konrad Wagstyl, Jakob Seidlitz, Ross D. Markello, Aurina Arnatkevičiūtė, Kevin M. Anderson, Richard A. I. Bethlehem, Lifespan Brain Chart Consortium, Armin Raznahan, Edward T. Bullmore & Petra E. Vértes

22 April 2024

Summary

Human brain organization involves the coordinated expression of thousands of genes. For example, the first principal component (C1) of cortical transcription identifies a hierarchy from sensorimotor to association regions. In this study, optimized processing of the Allen Human Brain Atlas revealed two new components of cortical gene expression architecture, C2 and C3, which are distinctively enriched for neuronal, metabolic and immune processes, specific cell types and cytoarchitectonics, and genetic variants associated with intelligence. Using additional datasets (PsychENCODE, Allen Cell Atlas and BrainSpan), we found that C1–C3 represent generalizable transcriptional programs that are coordinated within cells and differentially phased during fetal and postnatal development.

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Childhood maltreatment influences adult brain structure through its effects on immune, metabolic, and psychosocial factors

Publication: PNAS

Sofia C. Orellana Richard A. I. Bethlehem, Ivan L. Simpson-Kent and Edward T. Bullmore

9 April 2024

Summary

A new study has found that childhood maltreatment can have an impact into adulthood because of how it effects an individual’s risk of poor physical health and traumatic experiences many years later

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