Support for an independent familial segregation of executive and intelligence endophenotypes in ADHD families

Rommelse, Nanda; Altink, Marieke E.; Oosterlaan, Jaap; Buschgens, Cathelijne J. M.; Buitelaar, Jan K.; Sergeant, Joseph A.

doi:10.1017/s0033291708002869

Cited by 102 publications

(122 citation statements)

References 67 publications

Supporting

Mentioning

105

Contrasting

Unclassified

Order By: Relevance

“…Working memory Bipolar disorder 41 , schizophrenia 33 , ADHD 42 0.49 43 COWA 44 The subject was given 60 s to think of words beginning with a certain letter. The phenotype was total number of correct words across three letters.…”

Section: Association Analysismentioning

confidence: 99%

Common genetic variation and performance on standardized cognitive tests

et al. 2010

View full text Add to dashboard Cite

One surprising feature of the recently completed waves of genome-wide association studies is the limited impact of common genetic variation in individually detectable polymorphisms on many human traits. This has been particularly pronounced for studies on psychiatric conditions, which have failed to produce clear, replicable associations for common variants. One popular explanation for these negative findings is that many of these traits may be genetically heterogeneous, leading to the idea that relevant endophenotypes may be more genetically tractable. Aspects of cognition may be the most important endophenotypes for psychiatric conditions such as schizophrenia, leading many researchers to pursue large-scale studies on the genetic contributors of cognitive performance in the normal population as a surrogate for aspects of liability to disease. Here, we perform a genomewide association study with two tests of executive function, Digit Symbol and Stroop Color-Word, in 1086 healthy volunteers and with an expanded cognitive battery in 514 of these volunteers. We show that, consistent with published studies of the psychiatric conditions themselves, no single common variant has a large effect (explaining 44-8% of the population variation) on the performance of healthy individuals on standardized cognitive tests. Given that these are important endophenotypes, our work is consistent with the idea that identifying rare genetic causes of psychiatric conditions may be more important for future research than identifying genetically homogenous endophenotypes.

show abstract

Section: Association Analysismentioning

confidence: 99%

Common genetic variation and performance on standardized cognitive tests

et al. 2010

View full text Add to dashboard Cite

show abstract

“…36 Individuals with ADHD have an IQ that is generally about 10 points lower than in healthy participants, 37 which could argue in favour of including IQ as a covariate. However, IQ might share meaningful variance with ADHD, 19 at least partially, and therefore covarying for IQ might lead to an overcorrection. In the present study, both analyses are provided.…”

Section: J Psychiatry Neurosci 2016;41(4)mentioning

confidence: 99%

“…As the present study consisted of a large naturalistic group of participants with ADHD and controls, differences in IQ and sex were present in our sample, which is frequently the case in studies of ADHD. 15,19 Similarly, most of the participants with ADHD had used medication. An alternative approach to the sensitivity analyses presented would have been to specify groups before analysis (e.g., by investigating only medication-naive participants with ADHD matched to controls by age, sex, IQ and psychiatric comorbidity), 31 but the trade-off would have been a smaller sample size consisting of atypical ADHD cases.…”

Section: Limitationsmentioning

confidence: 99%

“…We investigated the potentially confounding role of medication use, age, sex and IQ on brain volume differences between participants with ADHD and controls. 19 In short, ADHD families with at least 1 child with ADHD and at least 1 biological sibling (regardless of ADHD diagnosis) were recruited, as were control families with at least 1 child and 1 biological sibling with no formal or suspected ADHD diagnosis in any of the first-degree family members. For references and a detailed description of the NeuroIMAGE project and study procedures, see the study by von Rhein and colleagues.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Voxel-based morphometry analysis reveals frontal brain differences in participants with ADHD and their unaffected siblings

Bralten

Greven

Franke

et al. 2016

jpn

View full text Add to dashboard Cite

IntroductionAttention-deficit/hyperactivity disorder (ADHD) is a common neuropsychiatric disorder characterized by developmentally inappropriate impulsive, hyperactive and/or inattentive symptoms.1 Previous MRI studies have reported smaller total brain volumes in participants with ADHD than in controls.2,3 Metaanalyses of regions of interest (ROI) studies have shown significantly smaller volume in total and right cerebral volume, frontal brain areas, the right caudate and cerebellar regions in participants with ADHD than in controls.3 Volumetric ROI studies, however, are restricted to a small number of a priori selected regions, which could give rise to selection bias.A method that circumvents this potential bias and allows a whole brain, hypothesis-free analysis is voxel-based morphometry (VBM), 4 an MRI analysis technique that assesses differences between groups in voxelwise grey matter volume. Three meta-analyses of VBM studies reporting on partly the same samples have investigated the most prominent volumetric differences between participants with ADHD and controls. [5][6][7] The first meta-analysis (114 children with ADHD and 143 controls) reported smaller grey matter volume in the right putamen and globus pallidus in children with ADHD than in controls.5 A more recent meta-analysis (202 children and adolescents and 176 adults with ADHD and 344 controls) confirmed the reduced localized subcortical grey matter findings Background: Data on structural brain alterations in patients with attention-deficit/hyperactivity disorder (ADHD) have been inconsistent. Both ADHD and brain volumes have a strong genetic loading, but whether brain alterations in patients with ADHD are familial has been underexplored. We aimed to detect structural brain alterations in adolescents and young adults with ADHD compared with healthy controls. We examined whether these alterations were also found in their unaffected siblings, using a uniquely large sample. Methods: We performed voxelbased morphometry analyses on MRI scans of patients with ADHD, their unaffected siblings and typically developing controls. We identified brain areas that differed between participants with ADHD and controls and investigated whether these areas were different in unaffected siblings. Influences of medication use, age, sex and IQ were considered. Results: Our sample included 307 patients with ADHD, 169 unaffected siblings and 196 typically developing controls (mean age 17.2 [range 8-30] yr). Compared with controls, participants with ADHD had significantly smaller grey matter volume in 5 clusters located in the precentral gyrus, medial and orbitofrontal cortex, and (para)cingulate cortices. Unaffected siblings showed intermediate volumes significantly different from controls in 4 of these clusters (all except the precentral gyrus). Medication use, age, sex and IQ did not have an undue influence on the results. Limitations: Our sample was heterogeneous, most participants with ADHD were taking medication, and the comparison was cross-sectional. Conclusion: Br...

show abstract

“…This view of IQ and EF as independent of one another is also supported by data from Rommelse, Altink, et al [16] whose large study of children with ADHD vs. controls found that group differences on EF were not explained by group differences on IQ and vice versa. In principal components analysis that study also demonstrated that EF and IQ are relatively independent of each other in the same child.…”

Section: Introductionmentioning

confidence: 54%

Executive function impairments in high IQ children and adolescents with ADHD

Brown¹,

Reichel²,

Quinlan³

2011

OJPsych

View full text Add to dashboard Cite

Objective: To demonstrate that high IQ children and adolescents diagnosed with ADHD tend to suffer from executive function (EF) impairments that: a) can be identified with a combination of standardized measures and normed self-report data; and b) occur more frequently in this group than in the general population. Method: From charts of 117 children and adolescents aged 6 to 17 years with high IQ ( ≥ 120) who fully met DSM-IV diagnostic criteria for ADHD, data on 8 normed measures of executive function (EF) were extracted: IQ index scores for working memory and processing speed, a standardized measure of auditory verbal memory, and 5 clusters of the Brown ADD Scale, a normed, age-graded rating scale for ADHD-related executive function impairments in daily life. Significant impairment was computed for each individual relative to age-appropriate norms for each measure and comparisons were made to base-line rates in the general population. Results: Sixty-two percent of participants were significantly impaired on at least 5 of these 8 markers of EF. Chi-square comparisons of scores from these high IQ participants were significantly different (p < 0.001) from standardization norms for each of the eight EF measures. Conclusions: High IQ children and adolescents with ADHD, despite their cognitive strengths, tend to suffer from significant impairments of executive functions that can be assessed with these measures; incidence of these impairments is significantly greater than in the general population. These results are fully consistent with data on high IQ adults diagnosed with ADHD.

show abstract

Support for an independent familial segregation of executive and intelligence endophenotypes in ADHD families

Cited by 102 publications

References 67 publications

Common genetic variation and performance on standardized cognitive tests

Common genetic variation and performance on standardized cognitive tests

Voxel-based morphometry analysis reveals frontal brain differences in participants with ADHD and their unaffected siblings

Executive function impairments in high IQ children and adolescents with ADHD

Contact Info

Product

Resources

About