Structural magnetic resonance imaging of bipolar disorder

Bipolar disorders are illnesses with recurring episodes of elevated or depressed mood. Although most affected individuals have periods when they are free of symptoms, they carry a life-long risk of relapse. The cause of the illness has not yet been established. During the last three decades, a growing number of brain imaging studies have shown differences in brain morphology between persons with a bipolar disorder and healthy controls, though the affected brain regions have varied greatly across studies. Too small sample sizes are likely one explanation of this variability. The aims of this thesis were to investigate i) differences in brain morphology between bipolar patients and healthy controls, ii) differences between subgroups of bipolar disorder, and iii) changes in brain morphology associated with illness progression. To these ends, we collected a large sample of bipolar disorder patients and examined their brains using magnetic resonance imaging. We then made analyses on group level.

In Study 1, we analyzed differences in gray matter volume between persons with bipolar disorder and healthy controls. We found lower volume in the bilateral insula and medial prefrontal cortex in the bipolar group. We also found that these two regions covary in size.

In Study 2, we examined if cortical volume, thickness, and surface area differ between patients with bipolar disorder I and II. We found that bipolar I subjects had thinner rostral temporal cortex than bipolar II subjects.

Many patients with bipolar disorder experience psychotic symptoms during an illness episode. In Study 3, we investigated if gray matter volume differs between patients with a history of psychosis and those without. We found lower volume in the fusiform gyrus, dorsolateral prefrontal cortex, and inferior frontal cortex in the group of patients with previous psychosis.

In Study 4, we analyzed if gray matter volume was associated with the lifetime number of manic or depressive episodes, or the duration of the illness in a group of patients with bipolar I disorder without comorbidity. We found a linear negative correlation between the volume of the dorsolateral prefrontal cortex and the lifetime number of manic episodes. This cross sectional analysis could, however, not establish if the volume reduction predates the manic episodes or is an effect of manic episodes. Therefore, we re-scanned the patients after six years. In study 5, we then compared those patients who had had at least one manic episode between baseline and follow-up with those who did not. We found that the volume in the dorsolateral and inferior frontal cortex decreased in the group who had had a manic episode.

In summary, the studies suggest that bipolar disorder is associated with reduced gray matter volume in brain areas responsible for emotional regulation. We also found that the brain morphology differs between subgroups of bipolar disorder. Finally, our results suggest that manic episodes cause gray matter volume reduction in regions coupled to cognitive functions that tend to be impaired in bipolar disorder.

List of scientific papers

I. CARL JOHAN EKMAN, Predrag Petrovic, Christoph AbŽ, Eleonore RydŽn, Martin Ingvar, Mikael LandŽn. Altered prefrontal - insular network in bipolar disorder. [Submitted]

II. Christoph AbŽ, CARL JOHAN EKMAN,Carl Sellgren,Predrag Petrovic, Martin Ingvar, Mikael LandŽn. Cortical thickness, volume and surface area in patients with bipolar disorder types I and II. Psychiatry Neurosci. 2016 Jun;41(4):240-50.
https://doi.org/10.1503/jpn.150093

III. CARL JOHAN EKMAN, Predrag Petrovic, Anette Johansson, Carl Sellgren, Martin Ingvar, Mikael LandŽn. A history of psychosis in bipolar disorder is associated with gray matter volume reduction. [Accepted]
https://doi.org/10.1093/schbul/sbw080

IV. CARL JOHAN EKMAN, Johanna Lind, Eleonore RydŽn, Martin Ingvar, Mikael LandŽn. Manic episodes are associated with grey matter volume reduction : a voxel-based morphometry brain analysis. Acta Psychiatr Scand. 2010 Dec;122(6):507-15.
https://doi.org/10.1111/j.1600-0447.2010.01586.x

V. Christoph AbŽ, CARL JOHAN EKMAN, Carl Sellgren, Predrag Petrovic, Martin Ingvar, Mikael LandŽn. Manic episodes are related to changes in frontal cortex : a longitudinal neuroimaging study of bipolar disorder 1. Brain. 2015 Nov;138(Pt 11):3440-8.
https://doi.org/0.1093/brain/awv266