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Why is there selective subcortical vulnerability in ADHD? Clues from postmortem brain gene expression data

Molecular Psychiatry volume 23, pages 1787–1793 (2018)Cite this article

Abstract

Sub-cortical volumetric differences were associated with attention-deficit/hyperactivity disorder (ADHD) in a recent multi-site, mega-analysis of 1713 ADHD persons and 1529 controls. As there was a wide range of effect sizes among the sub-cortical volumes, it is possible that selective neuronal vulnerability has a role in these volumetric losses. To address this possibility, we used data from Allen Brain Atlas to investigate variability in gene expression profiles between subcortical regions of typically developing brains. We tested the hypothesis that the expression of genes in a set of curated ADHD candidate genes and five a priori selected, biological pathways would be associated with the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) findings. Across the subcortical regions studied by ENIGMA, gene expression profiles for three pathways were significantly correlated with ADHD-associated volumetric reductions: apoptosis, oxidative stress and autophagy. These correlations were strong and significant for children with ADHD, but not for adults. Although preliminary, these data suggest that variability of structural brain anomalies in ADHD can be explained, in part, by the differential vulnerability of these regions to mechanisms mediating apoptosis, oxidative stress and autophagy.

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Acknowledgments

Dr Faraone is supported by the K.G. Jebsen Centre for Research on Neuropsychiatric Disorders, University of Bergen, Bergen, Norway, the European Union’s Seventh Framework Programme for research, technological development and demonstration under grant agreement number 602805, the European Union’s Horizon 2020 research and innovation programme under grant agreement number 667302 and NIMH grants 5R01MH101519 and U01 MH109536-01. Dr Akutagava-Martins’ contribution was supported by the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Brazil.

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Authors and Affiliations

  1. Department of Psychiatry and Behavioral Sciences, SUNY Upstate Medical University, Syracuse, NY, USA

    J L Hess, G C Akutagava-Martins, S J Glatt & S V Faraone

  2. Department of Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, NY, USA

    J D Patak, S J Glatt & S V Faraone

  3. K.G. Jebsen Centre for Research on Neuropsychiatric Disorders, University of Bergen, Bergen, Norway

    S V Faraone

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Correspondence to S V Faraone.

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Conflict of Interest

In the past year, Dr Faraone received income, potential income, travel expenses continuing education support and/or research support from Lundbeck, Rhodes, Arbor, KenPharm, Ironshore, Shire, Akili Interactive Labs, CogCubed, Alcobra, VAYA, Sunovion, Genomind and Neurolifesciences. With his institution, he has US patent US20130217707 A1 for the use of sodium-hydrogen exchange inhibitors in the treatment of ADHD. In previous years, he received support from: Shire, Neurovance, Alcobra, Otsuka, McNeil, Janssen, Novartis, Pfizer and Eli Lilly. Dr Faraone receives royalties from books published by Guilford Press: Straight Talk about Your Child’s Mental Health, Oxford University Press: Schizophrenia: The Facts and Elsevier: ADHD: Non-Pharmacologic Interventions. He is principal investigator of www.adhdinadults.com. All other authors declare no conflict of interest.

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Hess, J.L., Akutagava-Martins, G.C., Patak, J.D. et al. Why is there selective subcortical vulnerability in ADHD? Clues from postmortem brain gene expression data. Mol Psychiatry 23, 1787–1793 (2018). https://doi.org/10.1038/mp.2017.242

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