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

Edward D Barker ,Penny Gowland,Sylvane Desrivières,Christian Büchel,Jean‐Baptiste Pingault ,Andreas Heinz,Michael N Smolka ,Alex Ing,Robert Whelan,Frauke Nees,Yuning Zhang,Arun L.w Bokde ,Barbara Ruggeri,Vincent Frouin,Philip Asherson,Hugh Garavan,Henrik Walter,Marie‐Laure Paillère Martinot ,Tobias Banaschewski,Jean‐Luc Martinot ,Sarah Hohmann,Bernd Ittermann,Ebba Du Rietz,Dimitri Papadopoulos‐Orfanos ,Luise Poustka,Nora C Vetter,Tianye Jia,Herta Flor,Erin Burke Quinlan,April Bowling ,Edmund Sounga-Barke,Francesca Biondo,Uli Bromberg,Gunter Schümann

doi:10.1038/s41380-019-0444-y

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.

Highlights

Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder with a typical onset during childhood, and shows mixed patterns of continuity and remittance, along with an adulthood onset [1]
The body mass index (BMI) polygenic risk scores (PRS) score was significantly associated with BMI (r = 0.23, n = 874, p = 2.2 × 10−11 FWE corrected) and the PRS score for ADHD was significantly associated with impulsivity symptoms (r = 0.10, n = 874, p = 0.014 FWE corrected)
Using sparse partial least squared analysis (sPLS), we found that both the ADHD and BMI phenotypes, and their respective polygenic risk scores, are significantly associated with a common neural substrate, constructed from T1 and fMRI data, which we term the ‘neural endophenotype’

Summary

Introduction

Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder with a typical onset during childhood, and shows mixed patterns of continuity and remittance, along with an adulthood onset [1]. Research has identified factors contributing to the comorbidity between ADHD and obesity, including fetal programming, psychosocial stress, and factors directly related to energy balance, reduced physical exercise and sleep patterns alterations [6]. Neural and genetic liabilities may be important components underlying the phenotypic association between ADHD and overweight/obesity [6]

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