Shared genetic background between children and adults with attention deficit/hyperactivity disorder

Rovira, Paula; Demontis, Ditte; Sánchez-Mora, Cristina; Zayats, Tetyana; Klein, Marieke; Mota, Nina Roth; Weber, Heike; Garcia-Martínez, Iris; Pagerols, Mireia; Vilar, Laura; Arribas, Lorena; Richarte, Vanesa; Corrales, Montserrat; Fadeuilhe, Christian; Bosch, Rosa; Martín, Gemma Español; Álmos, P.Z.; Doyle, Alysa E.; Grevet, Eugênio H.; Grimm, O.; Halmøy, Anne; Hoogman, Martine; Hutz, Mara Helena; Jacob, Christian; Kittel‐Schneider, Sarah; Knappskog, Per M.; Lundervold, Astri J.; Rivero, Olga; Rovaris, Diego Luiz; Salatino-Oliveira, Angélica; Silva, Bruna Santos da; Svirin, Evgenij; Sprooten, Emma; Strekalova, Tatyana; Andreassen, Ole A.; Banaschewski, Tobias; Bellgrove, Mark A.; Biederman, Joseph; Burton, Christie L.; Crosbie, Jennifer; Dalsgaard, Søren; Elia, Josephine; Hákonarson, Hákon; Hartman, Catharina A.; Hawi, Ziarih; Hebebrand, Johannes; Hinney, Anke; Loo, Sandra K.; McGough, James J.; Neale, Benjamin M.; Oades, Robert D.; Reichborn‐Kjennerud, Ted; Rothenberger, Aribert; Schachar, Russell; Waldman, Irwin D.; Agee, Michelle; Alipanahi, Babak; Auton, Adam; Bell, Robert K.; Bryc, Katarzyna; Elson, Sarah L.; Fontanillas, Pierre; Furlotte, Nicholas A.; Hinds, David A.; Huber, Karen E.; Kleinman, Aaron; Litterman, Nadia K.; McCreight, Jennifer C.; McIntyre, Matthew H.; Mountain, Joanna L.; Noblin, Elizabeth S.; Northover, Carrie A. M.; Pitts, Steven J.; Sathirapongsasuti, J. Fah; Sazonova, Olga V.; Shelton, Janie F.; Shringarpure, Suyash; Tian, Chao; Tung, Joyce Y.; Vacic, Vladimir; Wang, Xin; Wilson, Catherine H.; Arias-Vásquez, Alejandro; Sonuga‐Barke, Edmund; Asherson, Philip; Bau, Claiton Henrique Dotto; Buitelaar, Jan K.; Cormand, Bru; Faraone, Stephen V.; Haavik, Jan; Johansson, Stefan; Kuntsi, Jonna; Larsson, Henrik; Lesch, Klaus‐Peter; Reif, Andreas; Rohde, Luís Augusto; Casas, Miquel; Børglum, Anders D.; Franke, Barbara; Ramos‐Quiroga, Josep Antoni; Artigas, María Soler; Ribasés, Marta

doi:10.1101/589614

Cited by 7 publications

(10 citation statements)

References 75 publications

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“…DSM-5 does acknowledge some developmental differences by (i) providing suggestions of how childhood symptoms may present in adolescence or adulthood (such as running or climbing about when it is inappropriate instead presenting as feeling restless ), and (ii) requiring fewer symptoms to meet diagnostic criteria in adulthood ( American Psychiatric Association, 2013 ). Genetic research also suggests that while there is considerable overlapping genetic liability (approximately 66% shared) between child and adult ADHD ( Rovira et al, 2019 ), there is also likely age-specific genetic liability. Both genetic and environmental factors likely contribute to developmental differences in the presentation of ADHD symptoms, for example exposure to stressful life events or different environmental demands.…”

Section: Discussionmentioning

confidence: 99%

Exploring ADHD Symptoms and Associated Impairment across Development

et al. 2021

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Objective ADHD symptoms typically decline with age, but less is known about whether the presentation of specific ADHD symptoms differs across development. This study aimed to examine the frequency and associated impairment of specific ADHD symptoms in childhood, adolescence, and young adulthood. Method A prospective, longitudinal cohort, the Avon Longitudinal Study of Parents and Children, was utilized ( N = 2,327). ADHD symptoms and impairment were assessed using the Development and Well Being Assessment at ages 7, 15, and 25. Results Specific ADHD symptom frequencies and their associated impairment varied across development for the majority of symptoms, although easily distracted was one of the most commonly reported symptoms at each age, and difficulty sustaining attention was consistently associated with high levels of impairment. Conclusion These findings suggest differences in the presentations of ADHD symptoms across development: current understanding of how ADHD presents in childhood/adolescence may not be generalizable to young adulthood.

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Section: Discussionmentioning

confidence: 99%

Exploring ADHD Symptoms and Associated Impairment across Development

et al. 2021

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“…This suggests that the differences we observed between participants with persistent and remittent ADHD might be genomic effects. Moreover, 8.1% of the measured meQTL SNPs-more than one would expect by chance (X = 5.008, p = 0.025)-were associated (unadjusted p-value < 0.05) with adult, persistent ADHD in a recent GWAS meta-analysis (Rovira et al, 2019), but none of the findings survived correction for multiple testing.…”

Section: Differential Methylation Observations In Persistent Adhd Migmentioning

confidence: 95%

Genome-Wide DNA Methylation Patterns in Persistent Attention-Deficit/Hyperactivity Disorder and in Association With Impulsive and Callous Traits

et al. 2020

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Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder that often persists into adulthood. ADHD and related personality traits, such as impulsivity and callousness, are caused by genetic and environmental factors and their interplay. Epigenetic modifications of DNA, including methylation, are thought to mediate between such factors and behavior and may behave as biomarkers for disorders. Here, we set out to study DNA methylation in persistent ADHD and related traits. We performed epigenome-wide association studies (EWASs) on peripheral whole blood from participants in the NeuroIMAGE study (age range 12-23 years). We compared participants with persistent ADHD (n = 35) with healthy controls (n = 19) and with participants with remittent ADHD (n = 19). Additionally, we performed EWASs of impulsive and callous traits derived from the Conners Parent Rating Scale and the Callous-Unemotional Inventory, respectively, across all participants. For every EWAS, the linear regression model analyzed included covariates for age, sex, smoking scores, and surrogate variables reflecting blood cell type composition and genetic background. We observed no epigenome-wide significant differences in single CpG site methylation between participants with persistent ADHD and healthy controls or participants with remittent ADHD. However, epigenome-wide analysis of differentially methylated regions provided significant findings showing that hypermethylated regions in the APOB and LPAR5 genes were associated with ADHD persistence compared to ADHD remittance (p = 1.68 * 10 −24 and p = 9.06 * 10 −7 , respectively); both genes are involved in cholesterol signaling. Both findings appeared to be linked to genetic variation in cis. We found neither significant epigenome-wide single CpG sites nor regions associated with impulsive and callous traits; the top-hits from these analyses were annotated to genes involved in neurotransmitter release and the regulation of the biological clock. No link to genetic variation was observed for these findings, which thus might reflect environmental influences. In conclusion, in this pilot study with a small sample size, we observed several DNA-methylation-disorder/trait associations of potential significance for ADHD and the related behavioral traits. Although we do not wish to draw conclusions before replication in larger, independent samples, cholesterol signaling and metabolism may be of relevance for the onset and/or persistence of ADHD.

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“…These findings overall suggest that the genetic contribution to childhood ADHD also contribute to its persistence in adult life. More recently, independent genome-wide association studies of adult ADHD and child ADHD also showed strong genetic correlation between adult ADHD and child ADHD [45]; again suggesting that while ADHD symptoms might show developmental change, the genetic correlates do not appear to be very different.…”

Section: Adhd: What Happens Over Timementioning

confidence: 97%

The importance of a developmental perspective in Psychiatry: what do recent genetic-epidemiological findings show?

Thapar

Riglin

2020

Mol Psychiatry

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There is growing appreciation that a developmental perspective is helpful in Psychiatry. However, clinical practice and research, especially in an era of very large sample sizes, often ignore the developmental context. In this perspective piece, we discuss why a developmental view is important in Psychiatry and how recent genetic-epidemiological findings further highlight this. DSM-5 childhood neurodevelopmental disorders such as ADHD, typically onset in early childhood but can persist into adult life; the same ADHD genetic loading appears to contribute across the life course. However, recent longitudinal studies have observed that ADHD symptoms may emerge later during adolescence and adult life in some individuals although the etiology of this late-onset group is unclear. The epidemiology and genetics of depression do not appear to be the same in childhood, adolescence, and adult life. Recent genetic findings further highlight this. Autistic type problems and irritability also appear to show developmental variation in their genetic etiology. These findings raise the question of whether social communication and irritability have the same meaning at different ages. Schizophrenia typically onsets after adolescence. However, it is commonly preceded by childhood antecedents that do not resemble schizophrenia itself but do appear to index schizophrenia genetic liability. We conclude that there is a need for clinicians and scientists to adopt a developmental perspective in clinical practice and research by considering age-at-onset and changes over time as well as different developmental periods when interpreting clinical symptoms.

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Shared genetic background between children and adults with attention deficit/hyperactivity disorder

Cited by 7 publications

References 75 publications

Exploring ADHD Symptoms and Associated Impairment across Development

Exploring ADHD Symptoms and Associated Impairment across Development

Genome-Wide DNA Methylation Patterns in Persistent Attention-Deficit/Hyperactivity Disorder and in Association With Impulsive and Callous Traits

The importance of a developmental perspective in Psychiatry: what do recent genetic-epidemiological findings show?

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