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Attention as neurocognitive endophenotype of ADHD across the life span: a family study

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Abstract

Endophenotypes mediate pathways between genetic variations and the psychiatric phenotype, or share genetic risk with the psychiatric phenotype. Identifying endophenotypes is an important step to unravel disease pathways underlying complex psychiatric phenotypes such as ADHD. Potential viable endophenotypes for ADHD across the lifespan are neurocognitive measures of basic attention functions, such as sustained attention, and executive attention functions (EF), such as inhibition. The present study evaluated the endophenotype criteria of familiality and state-independency for measures of basic attention and EF in affected- and unaffected parents of children with ADHD (N = 139), and typically developing children (N = 60). In addition, the added value of neurocognitive measures relative to questionnaire data in genetically informed designs was explored by comparing the intergenerational transmission of neurocognitive measures to those of ADHD symptom scores. Results revealed small-to-medium-sized familial effects of ADHD for reaction time measures of EF components and state-independency given familial effects. Parent–child correlations as estimates of intergenerational transmission of those neurocognitive measures were not higher than those of behavioral ADHD symptom ratings. Taken together, our results argue against neurocognitive measures as pivotal endophenotypes for ADHD across the lifespan. If studied as neurocognitive endophenotypes of ADHD in adults, reaction time measures of executive—rather than basic attention function—seem to be more sensitive.

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Acknowledgements

We gratefully thank all children and their families for their participation in our study. Data collection was supported by grants of the German Research Foundation DFG to Christine M. Freitag and Jobst Meyer (Grants ME 1923/5-1, ME 1923/5-3), the German Federal Ministry of Education and Research (BMBF) Grant 01GV0605, and the BMBF/EC ERA-Net grant 01EW1105 to Christine M. Freitag.

Funding

Data analysis and writing was supported by the EU funded International Training Network MiND to CMF (Grant Number 82600321). CMF receives royalties for books on Attention Deficit/Hyperactivity Disorder and Autism Spectrum Disorder. She has served as consultant to Desitin and Roche. None of the other authors has to report any conflict of interests.

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  1. Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital Frankfurt, Goethe University Frankfurt am Main, Deutschordenstr. 50, 60528, Frankfurt am Main, Germany

    Sara Boxhoorn, Eva Lopez, Catharina Schmidt, Diana Schulze, Hannah Cholemkery & Christine M. Freitag

  2. Department of Child and Adolescent Psychiatry and Psychotherapy, Saarland University Hospital, Homburg, Germany

    Susann Hänig

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  7. Christine M. Freitag
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Correspondence to Christine M. Freitag.

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Boxhoorn, S., Lopez, E., Schmidt, C. et al. Attention as neurocognitive endophenotype of ADHD across the life span: a family study. Eur Arch Psychiatry Clin Neurosci 269, 627–644 (2019). https://doi.org/10.1007/s00406-019-00993-3

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