What we learn about bipolar disorder from large-scaleneuroimaging: Findings and future directions from theENIGMA Bipolar Disorder Working Group

Abstract

MRI-derived brain measures offer a link between genes, the environment and behav-ior and have been widely studied in bipolar disorder (BD). However, many neuroimag-ing studies of BD have been underpowered, leading to varied results and uncertaintyregarding effects. The Enhancing Neuro Imaging Genetics through Meta-Analysis(ENIGMA) Bipolar Disorder Working Group was formed in 2012 to empower discov-eries, generate consensus findings and inform future hypothesis-driven studies ofBD. Through this effort, over 150 researchers from 20 countries and 55 institutionspool data and resources to produce the largest neuroimaging studies of BD ever con-ducted. The ENIGMA Bipolar Disorder Working Group applies standardized4CHINGET AL. processing and analysis techniques to empower large-scale meta- and mega-analysesof multimodal brain MRI and improve the replicability of studies relating brain varia-tion to clinical and genetic data. Initial BD Working Group studies reveal widespreadpatterns of lower cortical thickness, subcortical volume and disrupted white matterintegrity associated with BD. Findings also include mapping brain alterations of com-mon medications like lithium, symptom patterns and clinical risk profiles and haveprovided further insights into the pathophysiological mechanisms of BD. Here we dis-cuss key findings from the BD working group, its ongoing projects and future direc-tions for large-scale, collaborative studies of mental illness.