Biology subjects

Malpas, C.

Publications and source records attributed to Malpas, C..

5 recordsLinked to original sources

bioRxiv2023

Plasma neurofilament light protein provides evidence of accelerated brain ageing in treatment-resistant schizophrenia

BackgroundAccelerated brain aging has been observed across multiple psychiatric disorders. Blood markers of neuronal injury such as Neurofilament Light (NfL) protein may therefore represent biomarkers of accelerated brain aging in these disorders. The current study aimed to examine whether relationships between age and plasma NfL were increased in individuals with primary psychiatric disorders compared to healthy individuals. MethodsPlasma NfL was analysed in major depressive disorder (MDD, n = 42), bipolar affective disorder (BPAD, n = 121), treatment-resistant schizophrenia (TRS, n = 82), a large reference normative healthy control (HC) group (n= 1,926) and a locally-acquired HC sample (n = 59). A general linear model (GLM) was used to examine diagnosis by age interactions on NfL z-scores using the large normative HC sample as a reference group. Significant results were then validated using the locally-acquired HC sample. Resultsa GLM identified a significant age by diagnosis interaction for TRS vs HCs and BPAD vs HCs. Post hoc analyses revealed a positive correlation between NfL levels and age among individuals with TRS, whereas a negative correlation was found among individuals with BPAD. However, only the TRS findings were replicated using the locally-acquired HC sample. Post hoc analyses revealed that individuals with TRS aged <40 had lower NfL levels compared to same-age HCs, whereas individuals with TRS aged >40 had higher NfL levels compared to same-age HCs. ConclusionsThese findings add to the growing literature supporting the notion of accelerated brain ageing in schizophrenia-spectrum disorders.

neuroscience↗

bioRxiv2019

Immunotherapy prevents long-term disability in relapsing multiple sclerosis over 15 years

ObjectiveWhether immunotherapy improves long-term disability in multiple sclerosis has not been satisfactorily demonstrated. This study examined the effect of immunotherapy on long-term disability outcomes in relapsing-remitting multiple sclerosis.\n\nMethodsWe studied patients from MSBase followed for [≥]1 year, with [≥]3 visits, [≥]1 visit per year and exposed to a multiple sclerosis therapy, and a subset of patients with [≥]15-year follow-up. Marginal structural models were used to compare the hazard of 12-month confirmed increase and decrease in disability, EDSS step 6 and the incidence of relapses between treated and untreated periods. Marginal structural models were continuously re-adjusted for patient age, sex, pregnancy, date, disease course, time from first symptom, prior relapse history, disability and MRI activity.\n\nResults14,717 patients were studied. During the treated periods, patients were less likely to experience relapses (hazard ratio 0.60, 95% confidence interval 0.43-0.82, p=0.0016), worsening of disability (0.56, 0.38-0.82, p=0.0026) and progress to EDSS step 6 (0.33, 0.19-0.59, p=0.00019). Among 1085 patients with [≥]15-year follow-up, the treated patients were less likely to experience relapses (0.59, 0.50-0.70, p=10-9) and worsening of disability (0.81, 0.67-0.99, p=0.043).\n\nConclusionsContinued treatment with multiple sclerosis immunotherapies reduces disability accrual (by 19-44%), the risk of need of a walking aid by 67% and the frequency of relapses (by 40-41%) over 15 years. A proof of long-term effect of immunomodulation on disability outcomes is the key to establishing its disease modifying properties.

neuroscience↗

bioRxiv2019

Longitudinal white matter development in children is associated with puberty, attentional difficulties, and mental health

The pubertal period involves dynamic white matter development. This period also corresponds with rapid gains in higher cognitive functions including attention, as well as increased risk of developing mental health difficulties. This longitudinal study comprised children aged 9-13 years (n=130). Diffusion magnetic resonance imaging (dMRI) data were acquired (b=2800 s/mm2, 60 directions) at two time-points. We derived measures of fibre density and morphology using the fixel-based analysis framework and performed a tract-based mixed-effects modelling analysis to understand patterns of white matter development with respect to age, pubertal stage, attentional difficulties, and internalising and externalising problems. We observed significant increases in apparent fibre density across a large number of white matter pathways, including major association and commissural pathways. We observed a linear relationship between fibre density and morphology with pubertal stage, in the right superior longitudinal fasciculus and in the right inferior longitudinal fasciculus. In terms of symptom severity, fibre density was positively associated with attentional dysfunction in the right uncinate fasciculus. Overall, white matter development across ages 9-13 years involved the expansion of major white matter fibre pathways, with key right-lateralised association pathways linked with pubertal development and attentional difficulties.

neuroscience↗

bioRxiv2017

Age, sex, and puberty related development of the corpus callosum: a multi-technique diffusion MRI study

PurposeThe corpus callosum is integral to the central nervous system, and continually develops with age by virtue of increasing axon diameter and ongoing myelination. Magnetic resonance imaging (MRI) techniques offer a means to disentangle these two aspects of white matter development. We investigate the profile of microstructural metrics across the corpus callosum, and assess the impact of age, sex and pubertal development on these processes.\n\nMethodsThis study made use of two independent paediatric populations. Multi-shell diffusion MRI data were analysed to produce a suite of diffusion tensor imaging (DTI), neurite orientation density and dispersion imaging (NODDI), and apparent fibre density (AFD) metrics. A multivariate profile analysis was performed for each diffusion metric across 10 subdivisions of the corpus callosum.\n\nResultsAll diffusion metrics significantly varied across the length of the corpus callosum. AFD exhibited a strong relationship with age across the corpus callosum (partial{eta} 2 = .65), particularly in the posterior body of the corpus callosum (partial{eta} 2 = .72). In addition, females had significantly higher AFD compared with males, most markedly in the anterior splenium (partial{eta} 2 = .14) and posterior genu (partial{eta} 2 = .13). Age-matched pubertal group differences were localised to the splenium.\n\nConclusionWe present evidence of a strong relationship between apparent fibre density and age, sex, and puberty during development. These results are consistent with ex vivo studies of fibre morphology, providing insights into the dynamics of axonal development in childhood and adolescence using diffusion MRI.\n\nTarget journalsBrain Structure & Function; HBM; NeuroImage; Developmental Cognitive Neuroscience

neuroscience↗

bioRxiv2017

Different Brain Networks Underlying Intelligence In Autism Spectrum Disorders And Typically Developing Children

BackgroundThere has been sustained clinical and cognitive neuroscience research interest in how network correlates of brain-behaviour relationships might be altered in Autism Spectrum Disorders (ASD) and other neurodevelopmental disorders. As previous work has mostly focused on adults, the nature of whole-brain connectivity networks underlying intelligence in pediatric cohorts with abnormal neurodevelopment requires further investigation.\n\nMethodsWe used network-based statistics (NBS) to examine the association between resting-state functional Magnetic Resonance Imaging (fMRI) connectivity and fluid intelligence ability in male children (n=50) with Autism Spectrum Disorders (ASD; M=10.45, SD=1.58 years and in controls (M=10.38, SD=0.96 years) matched on fluid intelligence performance, age and sex. Repeat analyses were performed in independent sites for validation and replication.\n\nResultsDespite being equivalent on fluid intelligence ability to strictly matched neurotypical controls, boys with ASD displayed a subnetwork of significantly increased associations between functional connectivity and fluid intelligence. Between-group differences remained significant at higher edge thresholding, and results were validated in independent-site replication analyses in an equivalent age and sex-matched cohort with ASD. Regions consistently implicated in atypical connectivity correlates of fluid intelligence in ASD were the angular gyrus, posterior middle temporal gyrus, occipital and temporo-occipital regions.\n\nConclusionDevelopment of fluid intelligence neural correlates in young ASD males is aberrant, with an increased strength in intrinsic connectivity association during childhood. Alterations in whole-brain network correlates of fluid intelligence in ASD may be a compensatory mechanism that allows equal task performance to neurotypical peers.

neuroscience↗