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Aging-Dependent Genetic Effects Associated to ADHD Predict Longitudinal Changes of Ventricular Volumes in Adulthood.

ABSTRACT: Background:Attention-Deficit/Hyperactivity Disorder (ADHD) is a childhood-onset disorder that can persist into adult life. Most genetic studies have focused on investigating biological mechanisms of ADHD during childhood. However, little is known about whether genetic variants associated with ADHD influence structural brain changes throughout adulthood. Methods:Participant of the study were drawn from a population-based sample of 3,220 healthy individuals drawn from the Rotterdam Study, with at least two magnetic resonance imaging (MRI)-scans (8,468 scans) obtained every 3-4 years. We investigate associations of genetic single nucleotide polymorphisms (SNPs) that have previously been identified in genome-wide association studies for ADHD, and trajectories of global and subcortical brain structures in an adult population (aged 50 years and older), acquired through MRI. We also evaluated the existence of age-dependent effects of these genetic variants on trajectories of brain structures. These analyses were reproduced among individuals 70 years of age or older to further explore aging-dependent mechanisms. We additionally tested baseline associations using the first MRI-scan of the 3,220 individuals. Results:We observed significant age-dependent effects on the rs212178 in trajectories of ventricular size (lateral ventricles, P= 4E-05; inferior lateral ventricles, P=3.8E-03; third ventricle, P=2.5E-03; fourth ventricle, P=5.5E-03). Specifically, carriers of the G allele, which was reported as protective for ADHD, had a smaller increase of ventricular size compared with homozygotes for the A allele in elder stages. Post hoc analysis on the subset of individuals older than 70 years of age reinforced these results (lateral ventricles, P=7.3E-05). In addition, the rs4916723, and the rs281324 displayed nominal significant age-dependent effects in trajectories of the amygdala volume (P=1.4E-03), and caudate volume (P=1.8E-03), respectively. Conclusions:To the best of our knowledge, this is the first study suggesting the involvement of protective genetic variants for ADHD on prevention of brain atrophy during adulthood.

SUBMITTER: Vilor-Tejedor N

PROVIDER: S-EPMC7344235 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Aging-Dependent Genetic Effects Associated to ADHD Predict Longitudinal Changes of Ventricular Volumes in Adulthood.

Vilor-Tejedor Natalia N Ikram Mohammad Arfan MA Roshchupkin Gennady G Vinke Elisabeth J EJ Vernooij Meike W MW Adams Hieab H H HHH

Frontiers in psychiatry 20200629

<h4>Background</h4>Attention-Deficit/Hyperactivity Disorder (ADHD) is a childhood-onset disorder that can persist into adult life. Most genetic studies have focused on investigating biological mechanisms of ADHD during childhood. However, little is known about whether genetic variants associated with ADHD influence structural brain changes throughout adulthood.<h4>Methods</h4>Participant of the study were drawn from a population-based sample of 3,220 healthy individuals drawn from the Rotterdam ...[more]

PMID: 32714213

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Project description:BACKGROUND AND PURPOSE:We hypothesize that reversal in diffusion-weighted imaging (DWI) volume at 24 hours predicts favorable clinical outcome only if accompanied by immediate reperfusion. Our aim was to quantify the immediate DWI and mean transit time changes at 2 and 24 hours after intravenous tissue-type plasminogen activator to evaluate the effect of reperfusion and DWI change on outcome. METHODS:Patients were selected from the Lesion Evolution in Stroke and Ischemia On Neuroimaging Project if they had an acute MRI with evaluable DWI and perfusion-weighted imaging, were treated with standard intravenous tissue-type plasminogen activator, had post-thrombolysis MRI with evaluable DWI and perfusion-weighted imaging at 2 and 24 hours and had follow-up fluid attenuated inversion recovery MRI at discharge through 90 days. A reader measured the DWI, mean transit time, and fluid attenuated inversion recovery volumes using a validated technique. A vascular neurologist scored the National Institutes of Health Stroke Scale at admit, 2, and 24 hours and the modified Rankin Scale at discharge, 5, 30, and 90 days. Favorable clinical outcome was defined as modified Rankin Scale of 0 or 1. RESULTS:Seventy-one patients met the study criteria with mean (±SD) age of 71.6 (±16.4) years, 58% women, median admit National Institutes of Health Stroke Scale 9 (interquartile range, 4-18), median onset to triage 45 minutes (30-65), and median first MRI to intravenous tissue-type plasminogen activator 47 minutes (39-59). In binary multiple logistic regression analysis, younger age (odds ratio, 1.165; P=0.014; 95% confidence interval [CI], 1.031-1.316), lower admit National Institutes of Health Stroke Scale (odds ratio, 1.221; P=0.012; 95% confidence interval, 1.045-1.427), decrease in mean transit time volume at 2 hours (odds ratio, 1.021; P=0.031; 95% confidence interval, 1.002-1.040), and decrease in DWI volume at 24 hours (odds ratio, 1.173; P=0.027; 95% confidence interval, 1.018-1.351) were significant predictors of favorable clinical outcome. CONCLUSIONS:Reversal of the DWI volume at 24 hours because of immediate reperfusion in patients post thrombolysis is predictive of favorable clinical outcome.

Dataset Information

Aging-Dependent Genetic Effects Associated to ADHD Predict Longitudinal Changes of Ventricular Volumes in Adulthood.

Publications

Aging-Dependent Genetic Effects Associated to ADHD Predict Longitudinal Changes of Ventricular Volumes in Adulthood.

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