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European Archives of Psychiatry and Clinical Neuroscience

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Open Access 28-06-2023 | Original Paper

Shared genetic etiology between ADHD, task-related behavioral measures and brain activation during response inhibition in a youth ADHD case–control study

Authors: Gülhan Saraçaydın, I. Hyun Ruisch, Daan van Rooij, Emma Sprooten, Barbara Franke, Jan K. Buitelaar, Andrea Dietrich, Pieter J. Hoekstra

Published in: European Archives of Psychiatry and Clinical Neuroscience | Issue 1/2024

Abstract

Impaired response inhibition is commonly present in individuals with attention-deficit/hyperactivity disorder (ADHD) and their unaffected relatives, suggesting impaired response inhibition as a candidate endophenotype in ADHD. Therefore, we explored whether behavioral and neural correlates of response inhibition are related to polygenic risk scores for ADHD (PRS-ADHD). We obtained functional magnetic resonance imaging of neural activity and behavioral measures during a stop-signal task in the NeuroIMAGE cohort, where inattention and hyperactivity-impulsivity symptoms were assessed with the Conners Parent Rating Scales. Our sample consisted of 178 ADHD cases, 103 unaffected siblings, and 173 controls (total N = 454; 8–29 years), for whom genome-wide genotyping was available. PRS-ADHD was constructed using the PRSice-2 software. We found PRS-ADHD to be associated with ADHD symptom severity, a slower and more variable response to Go-stimuli, and altered brain activation during response inhibition in several regions of the bilateral fronto-striatal network. Mean reaction time and intra-individual reaction time variability mediated the association of PRS-ADHD with ADHD symptoms (total, inattention, hyperactivity-impulsivity), and activity in the left temporal pole and anterior parahippocampal gyrus during failed inhibition mediated the relationship of PRS-ADHD with hyperactivity-impulsivity. Our findings indicate that PRS-ADHD are related to ADHD severity on a spectrum of clinical, sub-threshold, and normal levels; more importantly, we show a shared genetic etiology of ADHD and behavioral and neural correlates of response inhibition. Given the modest sample size of our study, future studies with higher power are warranted to explore mediation effects, suggesting that genetic liability to ADHD may adversely affect attention regulation on the behavioral level and point to a possible response inhibition-related mechanistic pathway from PRS-ADHD to hyperactivity-impulsivity.

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Title: Shared genetic etiology between ADHD, task-related behavioral measures and brain activation during response inhibition in a youth ADHD case–control study
Authors: Gülhan Saraçaydın
I. Hyun Ruisch
Daan van Rooij
Emma Sprooten
Barbara Franke
Jan K. Buitelaar
Andrea Dietrich
Pieter J. Hoekstra
Publication date: 28-06-2023
Publisher: Springer Berlin Heidelberg
Published in: European Archives of Psychiatry and Clinical Neuroscience / Issue 1/2024
Print ISSN: 0940-1334
Electronic ISSN: 1433-8491
DOI: https://doi.org/10.1007/s00406-023-01632-8

At a glance: The STEP trials

Springer Medicine

Shared genetic etiology between ADHD, task-related behavioral measures and brain activation during response inhibition in a youth ADHD case–control study

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

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