65 research outputs found
Neurexin-1 and Frontal Lobe White Matter: An Overlapping Intermediate Phenotype for Schizophrenia and Autism Spectrum Disorders
Background: Structural variation in the neurexin-1 (NRXN1) gene increases risk for both autism spectrum disorders (ASD) and schizophrenia. However, the manner in which NRXN1 gene variation may be related to brain morphology to confer risk for ASD or schizophrenia is unknown. Method/Principal Findings: 53 healthy individuals between 18–59 years of age were genotyped at 11 single nucleotide polymorphisms of the NRXN1 gene. All subjects received structural MRI scans, which were processed to determine cortical gray and white matter lobar volumes, and volumes of striatal and thalamic structures. Each subject’s sensorimotor function was also assessed. The general linear model was used to calculate the influence of genetic variation on neural and cognitive phenotypes. Finally, in silico analysis was conducted to assess potential functional relevance of any polymorphisms associated with brain measures. A polymorphism located in the 39 untranslated region of NRXN1 significantly influenced white matter volumes in whole brain and frontal lobes after correcting for total brain volume, age and multiple comparisons. Follow-up in silico analysis revealed that this SNP is a putative microRNA binding site that may be of functional significance in regulating NRXN1 expression. This variant also influenced sensorimotor performance, a neurocognitive function impaired in both ASD and schizophrenia. Conclusions: Our findings demonstrate that the NRXN1 gene, a vulnerability gene for SCZ and ASD, influences brai
Gender differences in coerced patients with schizophrenia
European Commission (Quality of life and
Management of Living Resources Programme, contract number QLG4-CT-
2002-01036), Czech Ministry of Education research grant MSM002160849,
and research grants PRVOUK–P26/LF1/4 and PRVOUK–P03/LF1/
Dyslexia in SNS: an Exploratory Study to Investigate Expressions of Identity and Multimodal Literacies
The paradigm of neurodiversity provides a theoretical scaffold to challenge the idea of dyslexia as a deficit, by considering how difficulties related to literacy may reflect possible cognitive strengths and opportunities for learning. In this paper we adopt this perspective which associates dyslexia with strengths in visual, oral and three-dimensional thinking. Our goal is to understand if and how the multimodal affordances of SNS mediate participation and new literacies for dyslexic youth, and how these affordances interact with identity work. Seven young people struggling with literacy were interviewed about their use of SNS. Our results show that the visual affordances of SNS enable new forms of participation and expression, furthering our understanding of visual literacies. Nonetheless, despite the pervasive use of visual affordances to perform identity work, we also find that young people's learning differences are not always obviated but re-constructed, or even confronted in SNS
Determinants of recovery from post-COVID-19 dyspnoea: analysis of UK prospective cohorts of hospitalised COVID-19 patients and community-based controls
Background The risk factors for recovery from COVID-19 dyspnoea are poorly understood. We investigated determinants of recovery from dyspnoea in adults with COVID-19 and compared these to determinants of recovery from non-COVID-19 dyspnoea. Methods We used data from two prospective cohort studies: PHOSP-COVID (patients hospitalised between March 2020 and April 2021 with COVID-19) and COVIDENCE UK (community cohort studied over the same time period). PHOSP-COVID data were collected during hospitalisation and at 5-month and 1-year follow-up visits. COVIDENCE UK data were obtained through baseline and monthly online questionnaires. Dyspnoea was measured in both cohorts with the Medical Research Council Dyspnoea Scale. We used multivariable logistic regression to identify determinants associated with a reduction in dyspnoea between 5-month and 1-year follow-up. Findings We included 990 PHOSP-COVID and 3309 COVIDENCE UK participants. We observed higher odds of improvement between 5-month and 1-year follow-up among PHOSP-COVID participants who were younger (odds ratio 1.02 per year, 95% CI 1.01–1.03), male (1.54, 1.16–2.04), neither obese nor severely obese (1.82, 1.06–3.13 and 4.19, 2.14–8.19, respectively), had no pre-existing anxiety or depression (1.56, 1.09–2.22) or cardiovascular disease (1.33, 1.00–1.79), and shorter hospital admission (1.01 per day, 1.00–1.02). Similar associations were found in those recovering from non-COVID-19 dyspnoea, excluding age (and length of hospital admission). Interpretation Factors associated with dyspnoea recovery at 1-year post-discharge among patients hospitalised with COVID-19 were similar to those among community controls without COVID-19. Funding PHOSP-COVID is supported by a grant from the MRC-UK Research and Innovation and the Department of Health and Social Care through the National Institute for Health Research (NIHR) rapid response panel to tackle COVID-19. The views expressed in the publication are those of the author(s) and not necessarily those of the National Health Service (NHS), the NIHR or the Department of Health and Social Care. COVIDENCE UK is supported by the UK Research and Innovation, the National Institute for Health Research, and Barts Charity. The views expressed are those of the authors and not necessarily those of the funders
Recommended from our members
Cognitive and psychiatric symptom trajectories 2–3 years after hospital admission for COVID-19: a longitudinal, prospective cohort study in the UK
Data sharing
The PHOSP-COVID protocol, consent form, definition and derivation of clinical characteristics and outcomes, training materials, regulatory documents, requests for data access, and other relevant study materials are available via the PHOSP-COVID website.Supplementary material is available online at: https://www.thelancet.com/cms/10.1016/S2215-0366(24)00214-1/attachment/7e690a57-1ab6-4295-8dd7-7cc2c44b2067/mmc1.pdf .Background: COVID-19 is known to be associated with increased risks of cognitive and psychiatric outcomes after the acute phase of disease. We aimed to assess whether these symptoms can emerge or persist more than 1 year after hospitalisation for COVID-19, to identify which early aspects of COVID-19 illness predict longer-term symptoms, and to establish how these symptoms relate to occupational functioning. Methods: The Post-hospitalisation COVID-19 study (PHOSP-COVID) is a prospective, longitudinal cohort study of adults (aged ≥18 years) who were hospitalised with a clinical diagnosis of COVID-19 at participating National Health Service hospitals across the UK. In the C-Fog study, a subset of PHOSP-COVID participants who consented to be recontacted for other research were invited to complete a computerised cognitive assessment and clinical scales between 2 years and 3 years after hospital admission. Participants completed eight cognitive tasks, covering eight cognitive domains, from the Cognitron battery, in addition to the 9-item Patient Health Questionnaire for depression, the Generalised Anxiety Disorder 7-item scale, the Functional Assessment of Chronic Illness Therapy Fatigue Scale, and the 20-item Cognitive Change Index (CCI-20) questionnaire to assess subjective cognitive decline. We evaluated how the absolute risks of symptoms evolved between follow-ups at 6 months, 12 months, and 2–3 years, and whether symptoms at 2–3 years were predicted by earlier aspects of COVID-19 illness. Participants completed an occupation change questionnaire to establish whether their occupation or working status had changed and, if so, why. We assessed which symptoms at 2–3 years were associated with occupation change. People with lived experience were involved in the study. Findings: 2469 PHOSP-COVID participants were invited to participate in the C-Fog study, and 475 participants (191 [40·2%] females and 284 [59·8%] males; mean age 58·26 [SD 11·13] years) who were discharged from one of 83 hospitals provided data at the 2–3-year follow-up. Participants had worse cognitive scores than would be expected on the basis of their sociodemographic characteristics across all cognitive domains tested (average score 0·71 SD below the mean [IQR 0·16–1·04]; p<0·0001). Most participants reported at least mild depression (263 [74·5%] of 353), anxiety (189 [53·5%] of 353), fatigue (220 [62·3%] of 353), or subjective cognitive decline (184 [52·1%] of 353), and more than a fifth reported severe depression (79 [22·4%] of 353), fatigue (87 [24·6%] of 353), or subjective cognitive decline (88 [24·9%] of 353). Depression, anxiety, and fatigue were worse at 2–3 years than at 6 months or 12 months, with evidence of both worsening of existing symptoms and emergence of new symptoms. Symptoms at 2–3 years were not predicted by the severity of acute COVID-19 illness, but were strongly predicted by the degree of recovery at 6 months (explaining 35·0–48·8% of the variance in anxiety, depression, fatigue, and subjective cognitive decline); by a biocognitive profile linking acutely raised D-dimer relative to C-reactive protein with subjective cognitive deficits at 6 months (explaining 7·0–17·2% of the variance in anxiety, depression, fatigue, and subjective cognitive decline); and by anxiety, depression, fatigue, and subjective cognitive deficit at 6 months. Objective cognitive deficits at 2–3 years were not predicted by any of the factors tested, except for cognitive deficits at 6 months, explaining 10·6% of their variance. 95 of 353 participants (26·9% [95% CI 22·6–31·8]) reported occupational change, with poor health being the most common reason for this change. Occupation change was strongly and specifically associated with objective cognitive deficits (odds ratio [OR] 1·51 [95% CI 1·04–2·22] for every SD decrease in overall cognitive score) and subjective cognitive decline (OR 1·54 [1·21–1·98] for every point increase in CCI-20). Interpretation: Psychiatric and cognitive symptoms appear to increase over the first 2–3 years post-hospitalisation due to both worsening of symptoms already present at 6 months and emergence of new symptoms. New symptoms occur mostly in people with other symptoms already present at 6 months. Early identification and management of symptoms might therefore be an effective strategy to prevent later onset of a complex syndrome. Occupation change is common and associated mainly with objective and subjective cognitive deficits. Interventions to promote cognitive recovery or to prevent cognitive decline are therefore needed to limit the functional and economic impacts of COVID-19. Funding: National Institute for Health and Care Research Oxford Health Biomedical Research Centre, Wolfson Foundation, MQ Mental Health Research, MRC-UK Research and Innovation, and National Institute for Health and Care Research.National Institute for Health and Care Research Oxford Health Biomedical Research Centre, Wolfson Foundation, MQ Mental Health Research, MRC-UK Research and Innovation, and National Institute for Health and Care Research
Effect of perinatal adversity on structural connectivity of the developing brain
Globally, preterm birth (defined as birth at <37 weeks of gestation) affects
around 11% of deliveries and it is closely associated with cerebral palsy,
cognitive impairments and neuropsychiatric diseases in later life.
Magnetic Resonance Imaging (MRI) has utility for measuring different
properties of the brain during the lifespan. Specially, diffusion MRI has been
used in the neonatal period to quantify the effect of preterm birth on white
matter structure, which enables inference about brain development and
injury.
By combining information from both structural and diffusion MRI, is it possible
to calculate structural connectivity of the brain. This involves calculating a
model of the brain as a network to extract features of interest. The process
starts by defining a series of nodes (anatomical regions) and edges
(connections between two anatomical regions). Once the network is created,
different types of analysis can be performed to find features of interest,
thereby allowing group wise comparisons.
The main frameworks/tools designed to construct the brain connectome have
been developed and tested in the adult human brain. There are several
differences between the adult and the neonatal brain: marked variation in
head size and shape, maturational processes leading to changes in signal
intensity profiles, relatively lower spatial resolution, and lower contrast
between tissue classes in the T1 weighted image. All of these issues make
the standard processes to construct the brain connectome very challenging
to apply in the neonatal population. Several groups have studied the neonatal
structural connectivity proposing several alternatives to overcome these
limitations.
The aim of this thesis was to optimise the different steps involved in
connectome analysis for neonatal data. First, to provide accurate parcellation
of the cortex a new atlas was created based on a control population of term
infants; this was achieved by propagating the atlas from an adult atlas
through intermediate childhood spatio-temporal atlases using image
registration. After this the advanced anatomically-constrained tractography
framework was adapted for the neonatal population, refined using software
tools for skull-stripping, tissue segmentation and parcellation specially
designed and tested for the neonatal brain. Finally, the method was used to
test the effect of early nutrition, specifically breast milk exposure, on
structural connectivity in preterm infants. We found that infants with higher
exposure to breastmilk in the weeks after preterm birth had improved
structural connectivity of developing networks and greater fractional
anisotropy in major white matter fasciculi. These data also show that the
benefits are dose dependent with higher exposure correlating with increased
white matter connectivity.
In conclusion, structural connectivity is a robust method to investigate the
developing human brain. We propose an optimised framework for the
neonatal brain, designed for our data and using tools developed for the
neonatal brain, and apply it to test the effect of breastmilk exposure on
preterm infants
Post-acute COVID-19 neuropsychiatric symptoms are not associated with ongoing nervous system injury
A proportion of patients infected with severe acute respiratory syndrome coronavirus 2 experience a range of neuropsychiatric symptoms months after infection, including cognitive deficits, depression and anxiety. The mechanisms underpinning such symptoms remain elusive. Recent research has demonstrated that nervous system injury can occur during COVID-19. Whether ongoing neural injury in the months after COVID-19 accounts for the ongoing or emergent neuropsychiatric symptoms is unclear. Within a large prospective cohort study of adult survivors who were hospitalized for severe acute respiratory syndrome coronavirus 2 infection, we analysed plasma markers of nervous system injury and astrocytic activation, measured 6 months post-infection: neurofilament light, glial fibrillary acidic protein and total tau protein. We assessed whether these markers were associated with the severity of the acute COVID-19 illness and with post-acute neuropsychiatric symptoms (as measured by the Patient Health Questionnaire for depression, the General Anxiety Disorder assessment for anxiety, the Montreal Cognitive Assessment for objective cognitive deficit and the cognitive items of the Patient Symptom Questionnaire for subjective cognitive deficit) at 6 months and 1 year post-hospital discharge from COVID-19. No robust associations were found between markers of nervous system injury and severity of acute COVID-19 (except for an association of small effect size between duration of admission and neurofilament light) nor with post-acute neuropsychiatric symptoms. These results suggest that ongoing neuropsychiatric symptoms are not due to ongoing neural injury
- …