Longitudinal Cortical Thickness Changes in Bipolar Disorder and the Relationship to Genetic Risk, Mania, and Lithium Use
Christoph Abé, Benny Liberg, Jie Song, Sarah E Bergen, Predrag Petrovic, Carl Johan Ekman, Carl M Sellgren, Martin Ingvar, Mikael Landén, Christoph Abé, Benny Liberg, Jie Song, Sarah E Bergen, Predrag Petrovic, Carl Johan Ekman, Carl M Sellgren, Martin Ingvar, Mikael Landén
Abstract
Background: Bipolar disorder (BD) is a highly heritable psychiatric disorder characterized by episodes of manic and depressed mood states and associated with cortical brain abnormalities. Although the course of BD is often progressive, longitudinal brain imaging studies are scarce. It remains unknown whether brain abnormalities are static traits of BD or result from pathological changes over time. Moreover, the genetic effect on implicated brain regions remains unknown.
Methods: Patients with BD and healthy control (HC) subjects underwent structural magnetic resonance imaging at baseline (123 patients, 83 HC subjects) and after 6 years (90 patients, 61 HC subjects). Cortical thickness maps were generated using FreeSurfer. Using linear mixed effects models, we compared longitudinal changes in cortical thickness between patients with BD and HC subjects across the whole brain. We related our findings to genetic risk for BD and tested for effects of demographic and clinical variables.
Results: Patients showed abnormal cortical thinning of temporal cortices and thickness increases in visual/somatosensory brain areas. Thickness increases were related to genetic risk and lithium use. Patients who experienced hypomanic or manic episodes between time points showed abnormal thinning in inferior frontal cortices. Cortical changes did not differ between diagnostic BD subtypes I and II.
Conclusions: In the largest longitudinal BD study to date, we detected abnormal cortical changes with high anatomical resolution. We delineated regional effects of clinical symptoms, genetic factors, and medication that may explain progressive brain changes in BD. Our study yields important insights into disease mechanisms and suggests that neuroprogression plays a role in BD.
Keywords: Bipolar disorder; Cortical thickness; Lithium; Longitudinal study; Mania; Polygenic risk score.
Copyright © 2019 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
Source: PubMed