Large-scale fine mapping of brain morphometry in bipolar disorder and major depression

University Of Southern California, Los Angeles CA

Investigators

Abstract

ABSTRACT Bipolar disorder (BD) is a chronic illness in which nearly half of all patients attempt suicide and no biological measures exist to reliably guide diagnosis or treatment. This project builds off 15 years of successful team science, reviving existing and independently collected neuroimaging and clinical data from around the world to create the largest studies of BD and the brain. In this new initiative from the Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) Consortium Bipolar Disorder Working Group (ENIGMA-BD), we will apply a recently standardized method for large-scale voxel-wise brain mapping to improve replication and generalizability BD-related brain signatures, its clinical factors, and transdiagnostic comparisons to major depressive disorder (MDD). The ENIGMA-VBM (Voxel-wise Based Morphometry) Pipeline includes built-in voxel-wise processing, quality control, and analysis tools for both pooled mega- and federated meta-analysis. Whereas most prior ENIGMA studies have used region of interest measures in which local brain variations are averaged across parcels of the brain defined by anatomical atlas, ENIGMA-VBM quantifies whole-brain, atlas-free variations at the voxel level. This new direction allows for focal mapping across the entire brain, including frequently omitted structures such as the cerebellum. Aim 1 will compute ENIGMA-VBM measures across a target sample of 3,500 BD and 8,500 healthy controls, and analyze focal morphometric patterns associated with BD diagnostic subtypes, illness severity, polypharmaceutical treatment effects, and other important clinical factors such as age, sex, age of onset, and comorbid substance abuse. Aim 2 will derive VBM features from the ENIGMA-Major Depressive Disorder Working Group (ENIGMA-MDD) and identify overlapping and distinct voxel-wise patterns across the largest samples of BD and MDD ever studied (N=22,500). Interactions between transdiagnostic brain variations and key clinical factors such as age of onset, duration/severity of illness, number of overlapping/distinct mood episodes, and pharmaceutical treatment will be assessed. The project represents a new phase of the ENIGMA Consortium and will create a novel set of atlas-free brain phenotypes to empower the largest transdiagnostic neuroimaging studies of BD, MDD and beyond.