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Mol Psychiatry. 2019 Jun 21. doi: 10.1038/s41380-019-0444-y. [Epub ahead of print]

Do ADHD-impulsivity and BMI have shared polygenic and neural correlates?

Author information

1
Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. ted.barker@kcl.ac.uk.
2
Centre for Population Neuroscience and Stratified Medicine (PONS), MRC Social, Genetic and Developmental Psychiatry (SGDP) Centre, London, UK. ted.barker@kcl.ac.uk.
3
Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
4
Centre for Population Neuroscience and Stratified Medicine (PONS), MRC Social, Genetic and Developmental Psychiatry (SGDP) Centre, London, UK.
5
Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, China.
6
Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence, Ministry of Education, Fudan University, Shanghai, China.
7
Division of Psychology & Language Sciences, University College London, London, UK.
8
Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Square J5, 68159, Mannheim, Germany.
9
Discipline of Psychiatry, School of Medicine and Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland.
10
University Medical Centre Hamburg-Eppendorf, House W34, 3.OG, Martinistr. 52, 20246, Hamburg, Germany.
11
School of Health Science, Merrimack College, 315 Turnpike Street North Andover, North Andover, MA, 01845, USA.
12
Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Square J5, Mannheim, Germany.
13
Department of Psychology, School of Social Sciences, University of Mannheim, 68131, Mannheim, Germany.
14
NeuroSpin, CEA, Université Paris-Saclay, F-91191, Gif-sur-Yvette, France.
15
Departments of Psychiatry and Psychology, University of Vermont, 05405, Burlington, VT, USA.
16
Sir Peter Mansfield Imaging Centre School of Physics and Astronomy, University of Nottingham, University Park, Nottingham, UK.
17
Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charitéplatz 1, Berlin, Germany.
18
Physikalisch-Technische Bundesanstalt (PTB), Abbestr. 2 - 12, Berlin, Germany.
19
Institut National de la Santé et de la Recherche Médicale, INSERM Unit 1000 "Neuroimaging & Psychiatry", University Paris Sud, University Paris Descartes - Sorbonne Paris Cité; and Maison de Solenn, Paris, France.
20
Institut National de la Santé et de la Recherche Médicale, INSERM Unit 1000 "Neuroimaging & Psychiatry", University Paris Sud, University Paris Descartes; Sorbonne Université; and AP-HP, Department of Child and Adolescent Psychiatry, Pitié-Salpêtrière Hospital, Paris, France.
21
Department of Child and Adolescent Psychiatry and Psychotherapy, University Medical Centre Göttingen, von-Siebold-Str. 5, 37075, Göttingen, Germany.
22
Department of Psychiatry and Neuroimaging Center, Technische Universität Dresden, Dresden, Germany.
23
Department of Psychiatry and Psychotherapy, Technische Universität Dresden, Dresden, Germany.
24
School of Psychology and Global Brain Health Institute, Trinity College Dublin, Dublin, Ireland.

Abstract

There is an extensive body of literature linking ADHD to overweight and obesity. Research indicates that impulsivity features of ADHD account for a degree of this overlap. The neural and polygenic correlates of this association have not been thoroughly examined. In participants of the IMAGEN study, we found that impulsivity symptoms and body mass index (BMI) were associated (r = 0.10, n = 874, p = 0.014 FWE corrected), as were their respective polygenic risk scores (PRS) (r = 0.17, n = 874, p = 6.5 × 10-6 FWE corrected). We then examined whether the phenotypes of impulsivity and BMI, and the PRS scores of ADHD and BMI, shared common associations with whole-brain grey matter and the Monetary Incentive Delay fMRI task, which associates with reward-related impulsivity. A sparse partial least squared analysis (sPLS) revealed a shared neural substrate that associated with both the phenotypes and PRS scores. In a last step, we conducted a bias corrected bootstrapped mediation analysis with the neural substrate score from the sPLS as the mediator. The ADHD PRS associated with impulsivity symptoms (b = 0.006, 90% CIs = 0.001, 0.019) and BMI (b = 0.009, 90% CIs = 0.001, 0.025) via the neuroimaging substrate. The BMI PRS associated with BMI (b = 0.014, 95% CIs = 0.003, 0.033) and impulsivity symptoms (b = 0.009, 90% CIs = 0.001, 0.025) via the neuroimaging substrate. A common neural substrate may (in part) underpin shared genetic liability for ADHD and BMI and the manifestation of their (observable) phenotypic association.

PMID:
31227801
DOI:
10.1038/s41380-019-0444-y

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