Attention Deficit Hyperactivity Disorder Symptoms and Brain Morphology: Examining Confounding Bias

Abstract

ABSTRACTBackgroundAssociations between attention-deficit/hyperactivity disorder (ADHD) and brain morphology have been reported, although with several inconsistencies. These may partly stem from confounding bias, which could distort associations and limit generalizability. We examined how associations between brain morphology and ADHD symptoms change with adjustments for potential confounders typically overlooked in the literature (aim 1), and for IQ, which is typically corrected for but plays an unclear role (aim 2).MethodsParticipants were 10-year-old children from the Adolescent Brain Cognitive Development (N=7,961) and Generation R (N=2,531) studies. Cortical area and volume were measured with MRI and ADHD symptoms with the Child Behavior Checklist. Surface-based cross-sectional analyses were run.ResultsADHD symptoms related to widespread cortical regions when solely adjusting for demographic factors. Additional adjustments for socioeconomic and maternal behavioral confounders (aim 1) generally attenuated associations, as cluster sizes halved and effect sizes substantially reduced. Cluster sizes were further reduced when including IQ (aim 2), however, we argue that adjustments could have introduced bias (e.g., by conditioning on a collider).ConclusionsCareful confounder selection and control can help identify more robust and specific regions of associations for ADHD symptoms, across two cohorts. We provided guidance to minimizing confounding bias in psychiatric neuroimaging.FundingAuthors are supported by an NWO-VICI grant (NWO-ZonMW: 016.VICI.170.200 to HT) for HT, LDA, SL, and the Sophia Foundation S18-20, and Erasmus University and Erasmus MC Fellowship for RLM.