Brain volume in bipolar disorder increases during depression and shrinks during remission

A longitudinal neuroimaging study comparing individuals with bipolar disorder and healthy participants found that bipolar disorder patients with a higher number of depressive episodes tended to show increases in gray matter volume of the right exterior cerebellum. The paper was published in the journal Neuropsychopharmacology.

Bipolar disorder is a mental health condition characterized by extreme shifts in mood, energy, and activity levels. People with bipolar disorder experience episodes of mania or hypomania, which involve elevated or irritable mood, increased energy, and reduced need for sleep. These episodes alternate with depressive episodes, marked by sadness, loss of interest, fatigue, and feelings of hopelessness.

Research suggests that differences in brain structure, neurotransmitter systems, and emotional regulation networks may play a role in the development of bipolar disorder. This disorder typically begins in late adolescence or early adulthood, although it can appear earlier or later in life.

Study author Florian Thomas-Odenthal and his colleagues wanted to explore changes in gray matter volume of the brain in individuals suffering from bipolar disorder with and without recurring depressive or manic episodes during a 2-year follow-up and compare them to healthy participants.

The authors hypothesized that patients with bipolar disorder who experience a new depressive or manic episode during the follow-up period would show decreases in gray matter volume associated with manic episodes and increases in gray matter volume associated with depressive episodes. Gray matter is the part of the central nervous system that consists mainly of neuronal cell bodies, dendrites, and synapses.

Study participants were 124 individuals participating in the ongoing Marburg–Münster Affective Disorder Cohort Study (MACS), investigating the neurobiology of major psychiatric disorders. Sixty-two of the participants suffered from bipolar disorder, while the other 62 were healthy individuals, included as control participants.

All participants completed magnetic resonance imaging at two time points approximately two years apart (2.18 years, on average). Aside from this, study participants completed semi-structured clinical interviews at those two time points in which they reported on the course of their illness, whether they were currently experiencing symptoms of the disorder (remission status), and current medication use.

They also completed assessments of psychopathology, global psycho-social functioning, and familial risk. Their body mass index was calculated. Study authors further divided participants with bipolar disorder into those who experienced a new manic or depressive episode during the follow-up period and those who did not.

Results indicated that patients with bipolar disorder who did not experience a new manic or depressive episode during the follow-up period tended to show significant decreases in the gray matter volume of the right exterior cerebellum. Patients with bipolar disorder who experienced a depressive or manic episode during the follow-up period showed a non-significant increase in gray matter volume. Gray matter volume in this region did not change in healthy participants.

A higher number of depressive, but not manic, episodes during the follow-up period was moderately associated with higher increases in gray matter volume of the mentioned brain area. In bipolar disorder patients who did not experience a new manic or depressive episode during the follow-up, longer durations of manic episodes prior to the baseline assessment were associated with decreases in gray matter volume in the right exterior cerebellum during the follow-up period.

“Our findings underscore the dynamic nature of brain changes in BD [bipolar disorder]. GMV [gray matter volume] increases in BD patients with recurrence may be due to acute neuroinflammatory mechanisms including glial cell proliferation, whereas GMV reductions in BD patients without recurrence may result from abnormal synaptic refinement or pruning, as a consequence of past neuroinflammation during BD episodes,” the study authors concluded.

The study sheds light on the structural brain changes associated with bipolar disorder. However, it should be noted that the design of the study does not allow any definitive causal inferences to be derived from the results.

The paper “Differential impact of manic versus depressive episode recurrence on longitudinal gray matter volume changes in bipolar disorder” was authored by Florian Thomas-Odenthal, Lea Teutenberg, Frederike Stein, Nina Alexander, Linda M. Bonnekoh, Katharina Brosch, Kira Flinkenflügel, Janik Goltermann, Dominik Grotegerd, Tim Hahn, Andreas Jansen, Elisabeth J. Leehr, Susanne Meinert, Julia-Katharina Pfarr, Harald Renz, Kai Ringwald, Navid Schürmeyer, Thomas Stief, Benjamin Straube, Katharina Thiel, Paula Usemann, Axel Krug, Igor Nenadić, Udo Dannlowski, and Tilo Kircher.