scholarly journals Electrophysiological markers of genetic risk for attention deficit hyperactivity disorder

Author(s):  
Charlotte Tye ◽  
Gráinne McLoughlin ◽  
Jonna Kuntsi ◽  
Philip Asherson

Attention deficit hyperactivity disorder (ADHD) is a highly heritable neurodevelopmental disorder with complex genetic aetiology. The identification of candidate intermediate phenotypes may facilitate the detection of susceptibility genes and neurobiological mechanisms underlying the disorder. Electroencephalography (EEG) is an ideal neuroscientific approach, providing a direct measurement of neural activity that demonstrates reliability, developmental stability and high heritability. This systematic review evaluates the utility of a subset of electrophysiological measures as potential intermediate phenotypes for ADHD: quantitative EEG indices of arousal and intraindividual variability, and functional investigations of attention, inhibition and performance monitoring using the event-related potential (ERP) technique. Each measure demonstrates consistent and meaningful associations with ADHD, a degree of genetic overlap with ADHD and potential links to specific genetic variants. Investigations of the genetic and environmental contributions to EEG/ERP and shared genetic overlap with ADHD might enhance molecular genetic studies and provide novel insights into aetiology. Such research will aid in the precise characterisation of the clinical deficits seen in ADHD and guide the development of novel intervention and prevention strategies for those at risk.

2021 ◽  
Author(s):  
Veera Rajagopal ◽  
Jinjie Duan ◽  
Laura Vilar Ribó ◽  
Jakob Grove ◽  
Tetyana Zayats ◽  
...  

Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder, with onset in childhood ("childhood ADHD"), and around two thirds of affected individuals will continue to have ADHD symptoms in adulthood ("persistent ADHD"). Age at first diagnosis can vary, and sometimes ADHD is first diagnosed in adulthood ("late-diagnosed ADHD"). In this study, we analyzed a large Danish population-based case-cohort generated by iPSYCH in order to identify common genetic risk loci and perform in-depth characterization of the polygenic architecture of childhood (N=14,878), persistent (N=1,473) and late-diagnosed ADHD (N=6,961) alongside 38,303 controls. Additionally, the burden of rare protein truncating variants in the three groups were evaluated in whole-exome sequencing data from a subset of the individuals (7,650 ADHD cases and 8,649 controls). We identified genome-wide significant loci associated with childhood ADHD (four loci) and late-diagnosed ADHD (one locus). In analyses of the polygenic architecture, we found higher polygenic score (PGS) of ADHD risk variants in persistent ADHD (mean PGS=0.41) compared to childhood (mean PGS=0.26) and late-diagnosed ADHD (mean PGS=0.27), and we found a significant decreased genetic correlation of late-diagnosed ADHD with inattention (rg=0.57) compared to childhood ADHD (rg=0.86). These results suggest that a higher ADHD polygenic risk burden is associated with persistence of symptoms, and that a later diagnosis of ADHD could be due in part to genetic factors. Additionally, childhood ADHD demonstrated both a significantly increased genetic overlap with autism compared to late-diagnosed ADHD as well as the highest burden of rare protein-truncating variants in highly constrained genes among ADHD subgroups (compared to controls: beta=0.13, P=2.41x10-11). Late-diagnosed ADHD demonstrated significantly larger genetic overlap with depression than childhood ADHD and no increased burden in rare protein-truncating variants (compared to controls: beta=0.06). Overall, our study finds genetic heterogeneity among ADHD subgroups and suggests that genetic factors influence time of first ADHD diagnosis, persistence of ADHD and comorbidity patterns in the sub-groups.


2021 ◽  
pp. 1-13
Author(s):  
Isabell Brikell ◽  
Christie Burton ◽  
Nina Roth Mota ◽  
Joanna Martin

Abstract Attention-deficit/hyperactivity disorder (ADHD) is a common and highly heritable neurodevelopmental disorder (NDD). In this narrative review, we summarize recent advances in quantitative and molecular genetic research from the past 5–10 years. Combined with large-scale international collaboration, these advances have resulted in fast-paced progress in understanding the etiology of ADHD and how genetic risk factors map on to clinical heterogeneity. Studies are converging on a number of key insights. First, ADHD is a highly polygenic NDD with a complex genetic architecture encompassing risk variants across the spectrum of allelic frequencies, which are implicated in neurobiological processes. Second, genetic studies strongly suggest that ADHD diagnosis shares a large proportion of genetic risks with continuously distributed traits of ADHD in the population, with shared genetic risks also seen across development and sex. Third, ADHD genetic risks are shared with those implicated in many other neurodevelopmental, psychiatric and somatic phenotypes. As sample sizes and the diversity of genetic studies continue to increase through international collaborative efforts, we anticipate further success with gene discovery, characterization of how the ADHD phenotype relates to other human traits and growing potential to use genomic risk factors for understanding clinical trajectories and for precision medicine approaches.


2020 ◽  
Vol 10 (2) ◽  
pp. 79 ◽  
Author(s):  
Yanni Liu ◽  
Gregory L. Hanna ◽  
Barbara S. Hanna ◽  
Haley E. Rough ◽  
Paul D. Arnold ◽  
...  

The pathophysiology of attention-deficit/hyperactivity disorder (ADHD) involves deficits in performance monitoring and adaptive adjustments. Yet, the developmental trajectory and underlying neural correlates of performance monitoring deficits in youth with ADHD remain poorly understood. To address the gap, this study recruited 77 children and adolescents with ADHD and 77 age- and gender-matched healthy controls (HC), ages 8–18 years, who performed an arrow flanker task during electroencephalogram recording. Compared to HC, participants with ADHD responded more slowly and showed larger reaction time variability (RTV) and reduced post-error slowing; they also exhibited reduced error-related negativity (ERN) and error positivity effects, and reduced N2 and P3 congruency effects. Age effects were observed across groups: with increasing age, participants responded faster, with less variability, and with increased post-error slowing. They also exhibited increased ERN effects and increased N2 and P3 congruency effects. Increased RTV and reduced P3 amplitude in incongruent trials were associated with increased ADHD Problems Scale scores on the Child Behavior Checklist across groups. The altered behavioral and ERP responses in ADHD are consistent with the pattern associated with younger age across groups. Further research with a longitudinal design may determine specific aspects of developmental alteration and deficits in ADHD during performance monitoring.


2020 ◽  
Vol 10 (01) ◽  
pp. e97-e103
Author(s):  
Irene Rethemiotaki

AbstractAttention-deficit hyperactivity disorder (ADHD) is an increasingly recognized chronic neurodevelopmental disorder. This work aims at studying the prevalence and clinical characteristics of children with ADHD in the United States in the period between 2009 and 2018. Data from the National Health Interview Survey were analyzed by univariate and multivariate statistics to assess the role of socioeconomic factors in the development of ADHD. It has been studied 615,608 children, 51.2% male and 48.7% female. The prevalence of ADHD was 9.13%, with males predominating over females. The number of children with ADHD increased from 2009 to 2018 by 14.8%. As specified by multiple logistic regression analysis, males (odds ratio [OR] 2.38) who have neither mother nor father (OR 1.76) are twice as likely to have ADHD compared with their peers. In addition, family income (OR 1.40) and parent's education (OR 1.12) were significantly associated with ADHD. It has been highlighted the significance of deprivation of both family and financial comfort as primary indicators for ADHD in children. Moreover, children with ADHD were more likely to be males in the age group of 12 to 17.


2010 ◽  
Vol 77 (3) ◽  
pp. 249-249
Author(s):  
Pál Czobor ◽  
Viktória Simon ◽  
László Tombor ◽  
Szilvia Papp ◽  
Sarolta Komlósi ◽  
...  

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