Biology subjects

Anderson, V.

Publications and source records attributed to Anderson, V..

6 recordsLinked to original sources

bioRxiv2026

Genetic and environmental factors associated with DNA methylation across childhood and adolescence in individuals with and without attention-deficit/hyperactivity disorder

Background: Genetic and environmental factors both contribute risk to the development of childhood Attention-deficit/hyperactivity disorder (ADHD), yet the molecular mechanisms conferring this risk remain unclear. We investigated the genetic and environmental factors influencing DNA methylation (DNAm) at sites linked to ADHD symptom trajectories. Methods: We used two overlapping subsamples from a longitudinal paediatric cohort: (1) children with genetic and epigenetic data at first wave saliva sampling (Wave 3, n=113, 9.47-11.86 years) underwent methylation quantitative trait loci (meQTL) analysis; (2) children with environmental (Waves 1-3) and one or more waves of epigenetic data (n=126, 9.5-11.9 years) were analysed using LASSO regression to identify predictors of ADHD (Remitted ADHD/Persistent ADHD/Controls) and Wave 3 DNAm. In a subset with multiple DNAm timepoints (n=75), linear mixed models tested whether environmental predictors associated with longitudinal DNAm change, and whether ADHD moderated these associations. Analyses were conducted on 12 CpGs in which we previously identified change in DNAm according to the ADHD clinical outcome. Results: Nineteen meQTLs for 5 CpGs explained up to 40% of DNAm variance. We identified 17 environmental predictors of ADHD and wave 3 DNAm. Higher household income and school quality of life (QoL) were associated with reduced DNAm at cg02208776 (household) and cg11124426 (QoL) over time. Critically, higher income in Remitted ADHD showed greater DNAm declines than Controls, with opposite patterns in Persistent ADHD. Conclusion: DNAm patterns linked to ADHD outcomes were associated with genetic and environmental factors. Notably, household income and school functioning were associated with epigenetic change, with income effects varying by ADHD trajectories - characterising higher income as protective in remittent individuals.

genomics↗

bioRxiv2025

Linking Pain and Delirium via Microglial Activation: A Mouse Study Using BSEEG, Behavioral Assays, Immunohistochemistry, and RNA Sequencing

BackgroundThe rising incidence of delirium in surgical and critical care settings, especially in older patients, calls for improved preventative and management strategies. Chronic pain is increasingly recognized as a key risk factor for delirium, and microglial activation may be the central mediator linking these two conditions. MethodsWe used a spared nerve injury (SNI) model of persistent neuropathic pain in tandem with a postoperative delirium (POD) mouse model. Pain assessments, electroencephalography (EEG) recording, and immunofluorescence were performed to characterize pain and delirium-like states. Microglia were isolated for RNA-seq to elucidate gene expression changes comprehensively. ResultsSNI mice showed persistent mechanical hypersensitivity from Day 7 onwards and demonstrated disrupted sleep-wake patterns in EEG indices. Immunofluorescence revealed sustained microglial activation in both the hippocampus and cortex following SNI. RNA-seq analyses indicated the upregulation of pro-inflammatory pathways (e.g., interleukin-6 production, NF-{kappa}B signaling) in SNI mice that also underwent head-mount surgery. Notably, the coincidence of persistent pain and an acute delirium-like state further exacerbated neuroinflammation. ConclusionOur findings suggest that neuropathic pain-induced microglial activation primes the brain for exaggerated inflammatory responses under additional surgical stress, potentially worsening delirium. Further investigations into microglia-focused therapies may inform novel strategies for mitigating delirium in patients with neuropathic pain.

neuroscience↗

bioRxiv2024

Limbic System White Matter in Children and Adolescents with ADHD: A Longitudinal Diffusion MRI Analysis

Attention-deficit/hyperactivity disorder (ADHD) is increasingly recognized as a disorder linked to atypical white matter development across large-scale brain networks. However, current research predominantly focuses on cortical networks, leaving the developmental trajectories of many subcortical networks, including the limbic system, largely unexplored. The limbic system is crucial for emotion and cognition, making it a key area of interest in ADHD research. This study employed multi-shell high angular resolution diffusion magnetic resonance imaging to map the development of limbic system white matter in individuals with ADHD (n = 72) and controls (n = 97) across three time points between ages 9 and 14. Diffusion kurtosis imaging and graph theory metrics were used to characterize limbic system white matter, alongside assessments of emotional regulation and ADHD symptom severity. Compared to controls, individuals with ADHD exhibited significantly lower microstructural organization, particularly in kurtosis anisotropy, within the bilateral cingulum bundle from childhood to adolescence. Brain-behavior analyses further revealed that higher ADHD symptom severity was associated with a lower number of limbic system white matter connections, notably decreased routing efficiency and network density. These findings offer novel insights into the role of disrupted limbic system white matter in ADHD pathophysiology, broadening our understanding of the disorders neural mechanisms and opening promising avenues for future exploration of subcortical brain networks.

neuroscience↗

bioRxiv2020

A longitudinal analysis of puberty-related cortical development

The brain undergoes extensive structural changes during adolescence, concurrent to puberty-related physical and hormonal changes. While animal research suggests these biological processes are related to one another, our knowledge of brain development in humans is largely based on age-related processes. Thus, the current study characterized puberty-related changes in human brain structure, by combining data from two longitudinal neuroimaging cohorts. Beyond normative changes in cortical thickness, we examined whether individual differences in the rate of pubertal maturation (or "pubertal tempo") was associated with variations in cortical trajectories. Participants (N = 192; scans = 366) completed up to three waves of MRI assessments between 8.5 and 14.5 years of age, as well as questionnaire assessments of pubertal stage at each wave. Generalized additive mixture models were used to characterize trajectories of cortical development. Results revealed widespread linear puberty-related changes across much of the cortex. Many of these changes, particularly within the frontal and parietal cortices, were independent of age-related development. Males exhibiting faster pubertal tempo demonstrated greater thinning in the precuneus and frontal cortices than same-aged and -sex peers. Findings suggest that the unique influence of puberty on cortical development may be more extensive than previously identified, and also emphasize important individual differences in the coupling of these developmental processes.

neuroscience↗

bioRxiv2019

Tracing Autism Traits in Large Multiplex Families to Identify Endophenotypes of the Broader Autism Phenotype

Families comprising many individuals with Autism Spectrum Disorder (ASD) may carry a dominant predisposing mutation. Our aim was to use rigorous phenotyping of the Broader Autism Phenotype (BAP) in large multiplex ASD families to identify endophenotypes of the BAP for future genetic studies. We evaluated ASD/BAP features using standardised tests and a semi-structured interview to assess social, intellectual, executive and adaptive functioning in 109 individuals, including two large multiplex families (Family A: 30; Family B: 34) and an independent sample of small families (n=45). Our protocol identified four psychological endophenotypes of the BAP that were evident in both samples, and showed high sensitivity (97%) and specificity (82%) for individuals classified with the BAP. The patterns of inheritance of these endophenotypes varied in the two large families, supporting their utility for identifying genes in autism.

neuroscience↗

bioRxiv2018

Development of white matter fibre density and morphology over childhood: a longitudinal fixel-based analysis

PurposeWhite matter fibre development in childhood involves dynamic changes to microstructural organisation driven by increasing axon diameter, density, and myelination. However, there is a lack of longitudinal studies that have quantified advanced diffusion metrics to identify regions of accelerated fibre maturation, particularly across the early pubertal period. We applied a novel longitudinal fixel-based analysis (FBA) framework, in order to estimate microscopic and macroscopic white matter changes over time.\n\nMethodsDiffusion-weighted imaging (DWI) data were acquired for 59 typically developing children (27 female) aged 9 - 13 years at two time-points approximately 16 months apart (time-point 1: 10.4 {+/-} 0.4 years, time-point 2: 11.7 {+/-} 0.5 years). Whole brain FBA was performed using the connectivity-based fixel enhancement method, to assess longitudinal changes in fibre microscopic density and macroscopic morphological measures, and how these changes are affected by sex, pubertal stage, and pubertal progression. Follow-up analyses were performed in sub-regions of the corpus callosum to confirm the main findings using a Bayesian repeated measures approach.\n\nResultsThere was a statistically significant increase in fibre density over time localised to medial and posterior commissural and association fibres, including the forceps major and bilateral superior longitudinal fasciculus. Increases in fibre cross-section were substantially more widespread. The rate of fibre development was not associated with age or sex. In addition, there was no significant relationship between pubertal stage or progression and longitudinal fibre development over time. Follow-up Bayesian analyses were performed to confirm the findings, which supported the null effect of the longitudinal pubertal comparison.\n\nConclusionUsing a novel longitudinal fixel-based analysis framework, we demonstrate that white matter fibre density and fibre cross-section increased within a 16-month scan rescan period in specific regions. The observed increases might reflect increasing axonal diameter or axon count. Pubertal stage or progression did not influence the rate of fibre development in the early stages of puberty. Future work should focus on quantifying these measures across a wider age range to capture the full spectrum of fibre development across the pubertal period.

neuroscience↗