Abstract
BackgroundBipolar disorder (BD) is associated with cortical and subcortical structural brain abnormalities. It is unclear whether such alterations progressively change over time, and how this is related to the number of mood episodes. To address this question, we analyzed a large and diverse international sample with longitudinal magnetic resonance imaging (MRI) and clinical data to examine structural brain changes over time in BD. MethodsLongitudinal structural MRI and clinical data from the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) BD Working Group, including 307 patients with BD and 925 healthy control subjects, were collected from 14 sites worldwide. Male and female participants, aged 40 ± 17 years, underwent MRI at 2 time points. Cortical thickness, surface area, and subcortical volumes were estimated using FreeSurfer. Annualized change rates for each imaging phenotype were compared between patients with BD and healthy control subjects. Within patients, we related brain change rates to the number of mood episodes between time points and tested for effects of demographic and clinical variables. ResultsCompared with healthy control subjects, patients with BD showed faster enlargement of ventricular volumes and slower thinning of the fusiform and parahippocampal cortex (0.18 <d < 0.22). More (hypo)manic episodes were associated with faster cortical thinning, primarily in the prefrontal cortex. ConclusionsIn the hitherto largest longitudinal MRI study on BD, we did not detect accelerated cortical thinning but noted faster ventricular enlargements in BD. However, abnormal frontocortical thinning was observed in association with frequent manic episodes. Our study yields insights into disease progression in BD and highlights the importance of mania prevention in BD treatment.
Highlights
Bipolar disorder (BD) is a heritable [1, 2] psychiatric disorder characterized by recurrent episodes ofmania and depression [3, 4]
The BD group differed from healthy controls (HC) in educational level, had higher BMI, and was more likely to smoke than HC
A few HC (4%) reported alcohol abuse, one control subject had generalized anxiety disorder (GAD), and one control reported a history of psychotic symptoms
Summary
Bipolar disorder (BD) is a heritable [1, 2] psychiatric disorder characterized by recurrent episodes of (hypo)mania and depression [3, 4]. These single-center studies and recent reviews [29] suggest progressive features in prefrontal and temporal cortices associated with BD These brain changes could be part of the natural course of BD, but could reflect cortical changes influenced by medication [30, 31], genetic factors [25], and by the occurrence of mood episodes [24,25,26,27]. Bipolar disorder (BD) is associated with cortical and subcortical structural brain abnormalities It is unclear whether such alterations progressively change over time, and how this is related to the number of mood episodes. Journal Pre-proof sample with longitudinal magnetic resonance imaging (MRI) and clinical data to examine structural brain changes over time in BD
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