Brain Structure Changes Linked to Manic Episodes in Bipolar Disorder


Bipolar disorder (BD) is a debilitating mental disorder characterized by volatile periods of depression and mania. Researchers have long suspected that Behçet’s disease may be accompanied by abnormal structural and functional changes in the brain. Small CT brain imaging studies of people with Behçet’s disease have shown hints about these changes, but the ability to interpret data collected at a single time point is limited. Now, a multicenter, longitudinal study shows abnormal changes over time in the brains of people with Behçet’s disease. Some changes have notably been associated with more episodes of mania.

The report appears in . format Biological Psychiatry, published by Elsevier. The study involved a large international, multicenter team of more than 70 researchers from the ENIGMA Bipolar Disorder Working Group.

John Krystal, MD, Editor-in-Chief, said: Biological Psychiatry. “Longitudinal neuroimaging studies are very challenging. Here, by collecting data from 14 sites, we get one of the clearest pictures we have of the neurotoxic effect of bipolar disorder, especially manic episodes.”


The researchers collected magnetic resonance imaging (MRI) and detailed clinical data from 307 people with Behçet’s disease and 925 healthy controls (HC) from 14 clinical sites worldwide. Participants were assessed at two time points, ranging from six months to nine years.

The most surprising finding was that the cortex, the outermost layer of the brain, weakens significantly over time in people who experienced more manic episodes. Those who did not suffer from mania did not show any cortical thinning or even cortical thickening. The changes were most pronounced in the prefrontal cortex (PFC), an area associated with executive control and emotion regulation.


“The fact that cortical thinning in patients associated with manic episodes underscores the importance of treatment to prevent mood episodes and is important information for psychiatrists,” said senior author Michael Landin, MD, PhD, professor and chief medical officer at the Institute of Neuroscience and Physiology. University of Gothenburg, Sweden. “Researchers should focus on better understanding the progressive mechanisms that play a role in bipolar disorder to ultimately improve treatment options.”

Compared with HC, people with Behçet’s disease showed faster enlargement of the ventricles of the brain, the cavities within the brain that contain cerebrospinal fluid. In the cortical areas outside the PFC, BD participants actually showed slower thinning than HC participants.

Lead author Christoph Abbe, PhD, Assistant Professor, Karolinska Institutet, Sweden said: “Abnormal ventricular hypertrophy and more importantly the association between cortical thinning and manic symptoms suggests that bipolar disorder may actually be a progressive neurodegenerative disorder, which could explain the worsening of bipolar disorder. Symptoms of bipolar disorder in some patients”.

One possibility to explain why the cortex thins more slowly in Behçet’s patients than in HC is that lithium, a drug used to treat Behçet’s disease, is known for its neuroprotective effects and can enhance cortical thickness. Regardless, the study provides new evidence about the structural effects of Behçet’s disease on the brain over time.


Abé C, Ching CRK, Liberg B, et al. Longitudinal structural brain changes in bipolar disorder: a multicenter neuroimaging study of 1232 individuals by the ENIGMA Bipolar Disorder Working Group. Biological Psychiatry. 2021; 0 (0). doi: 10.1016/j.biopsych.2021.09.008

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