How bipolar disorder changes the brain over time

Researchers have long suspected that bipolar disorder (BD) — a debilitating psychiatric disorder characterised by fluctuating periods of depression and mania — may be accompanied by abnormal structural and functional changes in the brain, but the ability to interpret data from cross-sectional brain imaging has so far been limited. Now, a multicentre longitudinal study has confirmed aberrant changes over time in the brains of people with BD — with some changes specifically associated with more episodes of mania.

The study involved an international multicentre team of more than 70 researchers from the ENIGMA Bipolar Disorder Working Group. The researchers gathered magnetic resonance imaging (MRI) and detailed clinical data from 307 people with BD and from 925 healthy controls (HC) from 14 clinical sites worldwide. Participants were assessed at two timepoints, ranging from six months to nine years apart, with the results published in the journal Biological Psychiatry.

The most striking finding was that the cortex, the brain’s outermost layer, thinned over time to a greater extent in people who experienced more manic episodes. Those who did not have mania showed no cortical thinning or even cortical thickening. The changes were most evident in the prefrontal cortex (PFC), an area associated with executive control and emotion regulation.

“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, Professor and Chief Physician at the Institute of Neuroscience and Physiology, University of Gothenburg. “Researchers should focus on better understanding the progressive mechanisms at play in bipolar disorder to ultimately improve treatment options.”

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

“The abnormal ventricle enlargements and importantly the associations between cortical thinning and manic symptoms indicate that bipolar disorder may in fact be a neuroprogressive disorder, which could explain the worsening of bipolar symptoms in some patients,” said lead author Christoph Abé, Assistant Professor at Sweden’s Karolinska Institutet.

One possibility to explain why BD patients may have slower thinning of the cortex compared to HC is that lithium, a medication used to treat BD, is known to have neuroprotective effects and could bolster cortical thickness. Regardless, the study provides new clues about the structural effects of BD on the brain over time.

“The ENIGMA Bipolar Disorder Working Group report illustrates the power of large-scale multicentre collaboration,” concluded Dr John Krystal, Editor of Biological Psychiatry. “Here, by combining data from 14 sites, we get one of the clearest pictures we have of the neurotoxic impact of bipolar disorder, particularly manic episodes.”

Image credit: ©stock.adobe.com/au/vege

Please follow us and share on Twitter and Facebook. You can also subscribe for FREE to our weekly newsletters and bimonthly magazine.