Biology subjects

Chirokoff, V.

Publications and source records attributed to Chirokoff, V..

4 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↗

bioRxiv2026

Epigenetic and brain age across development: Performance and associations in the MIND consortium

Understanding how biological age measures perform across development lays the groundwork for investigations into lifespan trajectories of healthy aging. We provide the most comprehensive assessment of epigenetic and brain age models across development (birth to 24 years; [≤]20,917 observations across 15 cohorts), evaluating how these models associate with chronological age and with each other, and how these associations change across development. Chronological age-prediction accuracy of epigenetic and brain age models was modest and varied substantially. Accuracy improved with age and stabilized by middle childhood. Few brain and fewer epigenetic clocks performed stably and well across all developmental stages. Performance was better when age range and tissue corresponded between training and testing data. Associations between epigenetic-brain age residuals were small, and changed little across development, tissues or clock generation. Given this developmentally dynamic system of epigenetic-brain age performances and associations, we give key recommendations to improve developmental research in this field.

neuroscience↗

bioRxiv2025

Longitudinal DNA methylation dynamics distinguish Persistent and Remitted ADHD in childhood and adolescence

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder, with symptoms that remit or persist over time. Biological mechanisms underlying symptom change remain poorly understood, though epigenetic processes, like DNA methylation (DNAm), may serve as dynamic biomarkers of clinical outcomes. We examined change in DNAm in children and adolescents with and without ADHD, including differences between remitted and persistent ADHD. MethodsWe analyzed 219 saliva samples from 94 participants (aged 9.5-14.5 years) attending 2 to 3 waves of NICAP. DNAm was profiled using the Infinium MethylationEPIC BeadChip. Linear mixed models adjusted for age, sex, medication, batch and cell-proportion assessed longitudinal change. Comparisons included (1) all ADHD cases versus controls, (2) persistent or remitted ADHD versus controls, and (3) persistent versus remitted ADHD. False discovery rate correction controlled for multiple testing (FDR p<0.05). ResultsNo CpGs were statistically different between ADHD and controls, after correction. Compared to controls, the average DNAm at 5 sites was statistically different in persistent or remitted ADHD, and methylation of 3 additional CpGs differentially changed over time in persistent ADHD. Remitted differed from persistent ADHD at four CpGs, including cg21443143 (ZFAT), which showed a unique decline over time. Gene enrichment links findings to brain structures and function, though these did not survive multiple testing. ConclusionOur study identified several epigenetic differences between remitted and persistent ADHD outcomes from typical development, and from each other. Given the early stage of this research, our findings warrant further prospective epigenome-wide studies into these diagnostic trajectories.

genomics↗

bioRxiv2020

Static and Dynamic Aspects of Cerebro-Cerebellar Functional Connectivity are Associated with Self-reported Measures of Impulsivity: A Resting-State fMRI Study

Converging evidence from human and animal studies predict a possible role of the cerebellum in impulsivity. However, this hypothesis has not been thoroughly investigated within the framework of functional connectivity (FC). To address this issue, we employed resting-state fMRI data and two self-reports of impulsivity (UPPS-P and BIS/BAS) from a large group of healthy young individuals (N=134). We identified cerebral and cerebellar resting-state networks, and evaluated the association of static (strength) and dynamic (temporal variability) aspects of cerebro-cerebellar FC with different elements of self-reported impulsivity. Our results revealed that the behavioral inhibition and approach systems (BIS/BAS) were inversely associated with basal ganglia-cerebellar and fronto-cerebellar FC strength, respectively. In addition, we found that lack of premeditation was inversely associated with the temporal variability of FC between the cerebellum and top-down control networks that included sub-regions of the prefrontal cortex, precuneus, and posterior cingulate cortex. Moreover, we found that sensation seeking was associated with the temporal variability of FC between the cerebellum and networks that included cortical control regions and sub-cortical reward regions: the basal ganglia and the thalamus. Together, these findings indicate that the cerebellum may contribute to different forms of impulsivity through its connections to large-scale control and reward networks.

neuroscience↗