Summary: Over time, cortical thinning was linked to bipolar disorder patients who experienced more manic episodes. These changes were most pronounced in the prefrontal cortex, a region involved in emotional regulation and executive function.
Source: Elsevier
Bipolar disorder (BD) is a severe psychiatric condition marked by alternating episodes of depression and mania. While prior small cross-sectional brain imaging studies hinted at structural and functional brain abnormalities in BD, single timepoint data offer limited insight into how the brain changes over time.
A new large, multi-center longitudinal study now provides clearer evidence of progressive brain changes in people with BD, linking some of those changes specifically to the frequency of manic episodes.
The findings are reported in Biological Psychiatry and come from a coordinated effort by more than 70 researchers in the ENIGMA Bipolar Disorder Working Group.
“The ENIGMA Bipolar Disorder Working Group report illustrates the power of large-scale multi-center collaboration,” said John Krystal, MD, Editor of Biological Psychiatry. “Longitudinal neuroimaging studies are extremely challenging to conduct. By combining data from 14 sites, we get one of the clearest pictures we have of the potential neurotoxic impact of bipolar disorder, particularly manic episodes.”
The research team pooled magnetic resonance imaging (MRI) and clinical data from 307 individuals diagnosed with BD and 925 healthy control participants from 14 international clinical sites. Each participant underwent MRI scanning at two timepoints, with intervals ranging from six months up to nine years.
The most notable result was that the cerebral cortex—the brain’s outer layer—showed greater thinning over time in people who experienced more manic or hypomanic episodes between scans. In contrast, participants with BD who had few or no manic episodes displayed little cortical thinning and, in some regions, slight cortical thickening. The most pronounced thinning associated with manic episodes occurred in the prefrontal cortex (PFC), a critical region for emotion regulation, decision-making, and executive control.
“The fact that cortical thinning in patients related to manic episodes stresses the importance of treatment to prevent mood episodes and is important information for psychiatrists,” said senior author Mikael Landén, MD, PhD, Professor and Chief Physician at the Institute of Neuroscience and Physiology, University of Gothenburg, Sweden. He emphasized the need for further study into the mechanisms that drive progressive brain changes in BD to improve long-term treatment strategies.
In addition to cortical findings, the study found that people with BD experienced faster enlargement of the brain’s ventricles—fluid-filled cavities—compared with healthy controls. Interestingly, outside of the prefrontal regions, some cortical areas in BD patients exhibited slower thinning than controls; the authors suggest that this pattern could reflect heterogeneous influences, including potential neuroprotective effects of certain medications.
Lead author Christoph Abé, PhD, Assistant Professor at Karolinska Institutet, noted: “The abnormal ventricle enlargements and the associations between cortical thinning and manic symptoms indicate that bipolar disorder may in fact be a neuroprogressive disorder, which could help explain clinical worsening in some patients.”
The investigators also discussed lithium, a common mood stabilizer for BD, which has documented neuroprotective properties and may help maintain or increase cortical thickness in some individuals. While medication effects were considered, the study primarily highlights structural brain changes that correlate with illness course, especially the number of manic episodes.
About this bipolar disorder research news
Author: Rhiannon Bugno
Source: Elsevier
Contact: Rhiannon Bugno – Elsevier
Image: The image is in the public domain
Original Research: Open access.
“Longitudinal structural brain changes in bipolar disorder: A multicenter neuroimaging study of 1,232 individuals by the ENIGMA Bipolar Disorder Working Group” by Mikael Landén et al. Biological Psychiatry. DOI: 10.1016/j.biopsych.2021.09.008
Abstract
Longitudinal structural brain changes in bipolar disorder: A multicenter neuroimaging study of 1,232 individuals by the ENIGMA Bipolar Disorder Working Group
Background
Bipolar disorder has been associated with structural differences in cortical and subcortical brain regions. Until now, it remained unclear whether these alterations change progressively over time and how they relate to the number of mood episodes a person experiences. To address these questions, the ENIGMA-BD Working Group analyzed a large, diverse international sample with longitudinal MRI and clinical follow-up to identify structural brain changes linked to bipolar disorder.
Methods
The study combined longitudinal structural MRI and clinical data from 14 sites, including 307 patients with bipolar disorder and 925 healthy controls, for a total sample of 1,232 individuals. Participants (male and female) had a mean age of approximately 40 years (±17) and underwent MRI at two distinct timepoints. Using FreeSurfer, investigators measured cortical thickness, surface area, and subcortical volumes, then calculated annualized change rates for each imaging measure. They compared change rates between BD and control groups and examined associations between brain change rates and the number of mood episodes occurring between scans, while accounting for demographic and clinical variables.
Results
Compared with healthy controls, individuals with bipolar disorder exhibited faster enlargement of ventricular volumes. In cortical analyses, BD patients showed slower thinning in fusiform and parahippocampal regions (effect sizes 0.18 < d < 0.22). Crucially, a higher number of manic or hypomanic episodes between scans was associated with accelerated cortical thinning, predominantly in prefrontal cortical regions involved in emotion regulation and executive function.
Conclusion
In this largest-to-date longitudinal MRI study of bipolar disorder, researchers did not find widespread accelerated cortical thinning across all regions but did observe faster ventricular enlargement in BD. Importantly, frequent manic episodes were linked to abnormal fronto-cortical thinning, suggesting a disease-related progression in specific brain areas. These results underscore the importance of preventing manic episodes as part of long-term treatment strategies for bipolar disorder and motivate further research into the biological mechanisms that drive neuroprogression in BD.