Discrepancies of polygenic effects on symptom dimensions between adolescents and adults with ADHD

Jiang, Wenhao; Rootes-Murdy, Kelly; Duan, Kuaikuai; Schoenmacker, Gido; Hoekstra, Pieter J.; Hartman, Catharina A.; Oosterlaan, Jaap; Heslenfeld, Dirk J.; Franke, Barbara; Sprooten, Emma; Buitelaar, Jan K.; Arias-Vásquez, Alejandro; Liu, Jingyu; Turner, Jessica A.

doi:10.1016/j.pscychresns.2021.111282

Cited by 3 publications

(2 citation statements)

References 35 publications

(36 reference statements)

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“…In contrast, polygenic risk score (PRS)-based analyses allow evaluations of the relationship between the overall genetic risk of disease and altered brain patterns. Recently, we examined the associations between PRS of ADHD and brain alterations in frontal and cerebellum regions that related to working memory performance and inattention in adults with ADHD [53]. We did not find any linear relationships between PRS and these brain alterations, although the ADHD-PRS was associated with hyperactivity symptoms, indicating that the lumpsum risk from the whole genome may not have the specificity to link to ADHDrelated brain alterations.…”

Section: Introductionmentioning

confidence: 74%

Genomic patterns linked to gray matter alterations underlying working memory deficits in adults and adolescents with attention-deficit/hyperactivity disorder

et al. 2023

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Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable neurodevelopmental disorder, with onset in childhood and a considerable likelihood to persist into adulthood. Our previous work has identified that across adults and adolescents with ADHD, gray matter volume (GMV) alteration in the frontal cortex was consistently associated with working memory underperformance, and GMV alteration in the cerebellum was associated with inattention. Recent knowledge regarding ADHD genetic risk loci makes it feasible to investigate genomic factors underlying these persistent GMV alterations, potentially illuminating the pathology of ADHD persistence. Based on this, we applied a sparsity-constrained multivariate data fusion approach, sparse parallel independent component analysis, to GMV variations in the frontal and cerebellum regions and candidate risk single nucleotide polymorphisms (SNPs) data from 341 unrelated adult participants, including 167 individuals with ADHD, 47 unaffected siblings, and 127 healthy controls. We identified one SNP component significantly associated with one GMV component in superior/middle frontal regions and replicated this association in 317 adolescents from ADHD families. The association was stronger in individuals with ADHD than in controls, and stronger in adults and older adolescents than in younger ones. The SNP component highlights 93 SNPs in long non-coding RNAs mainly in chromosome 5 and 21 protein-coding genes that are significantly enriched in human neuron cells. Eighteen identified SNPs have regulation effects on gene expression, transcript expression, isoform percentage, or methylation level in frontal regions. Identified genes highlight MEF2C, CADM2, and CADPS2, which are relevant for modulating neuronal substrates underlying high-level cognition in ADHD, and their causality effects on ADHD persistence await further investigations. Overall, through a multivariate analysis, we have revealed a genomic pattern underpinning the frontal gray matter variation related to working memory deficit in ADHD.

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Section: Introductionmentioning

confidence: 74%

Genomic patterns linked to gray matter alterations underlying working memory deficits in adults and adolescents with attention-deficit/hyperactivity disorder

et al. 2023

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“…This difference could be explained by the fact that adults have developed adaptive control strategies, particularly because participants were all high-functioning university students. Another possibility could be that structures involved in reactive control could mature more slowly in children with ADHD than in TD children (Cortese et al, 2012;Jiang et al, 2021), and maturation would be reached only in adulthood.…”

Section: Adhd Affects Reactive Inhibitory Controlmentioning

confidence: 99%

Two sides of the same coin: ADHD affects reactive but not proactive inhibition in children

Suarez

Aragón

Grandjean

et al. 2021

Cognitive Neuropsychology

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Children with attention-deficit/hyperactivity disorder (ADHD) present a deficit in inhibitory control. Still, it remains unclear whether it comes from a deficit in reactive inhibition (ability to stop the action in progress), proactive inhibition (ability to exert preparatory control), or both.We compared the performance of 39 children with ADHD and 42 typically developing children performing a Simon choice reaction time task. The Simon task is a conflict task that is well-adapted to dissociate proactive and reactive inhibition. Beyond classical global measures (mean reaction time, accuracy rate, and interference effect), we used more sophisticated dynamic analyses of the interference effect and accuracy rate to investigate reactive inhibition. We studied proactive inhibition through the congruency sequence effect (CSE).Our results showed that children with ADHD had impaired reactive but not proactive inhibition. Moreover, the deficit found in reactive inhibition seems to be due to both a stronger impulse capture and more difficulties in inhibiting impulsive responses. These findings contribute to a better understanding of how ADHD affects inhibitory control in children.

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Examining the impact of ADHD polygenic risk scores on ADHD and associated outcomes: A systematic review and meta-analysis

Green¹,

Baroud²,

DiSalvo³

et al. 2022

Journal of Psychiatric Research

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Discrepancies of polygenic effects on symptom dimensions between adolescents and adults with ADHD

Cited by 3 publications

References 35 publications

Genomic patterns linked to gray matter alterations underlying working memory deficits in adults and adolescents with attention-deficit/hyperactivity disorder

Genomic patterns linked to gray matter alterations underlying working memory deficits in adults and adolescents with attention-deficit/hyperactivity disorder

Two sides of the same coin: ADHD affects reactive but not proactive inhibition in children

Examining the impact of ADHD polygenic risk scores on ADHD and associated outcomes: A systematic review and meta-analysis

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